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8042257 | Inflatable cavernosal body device: feasibility and acute safety study in the canine model. | To determine the feasibility, safety, and acute mechanical reliability of a two-piece, implantable, inflatable cavernosal body compression device in the canine model. Six large male dogs underwent implantation of an inflatable cavernosal compression device consisting of an inflatable cuff and a pump reservoir. The device was implanted around the corpora cavernosa excluding the corpus spongiosum near the crura. All devices were cycled three times a week for 2 months and radiographic evaluation found them to be mechanically reliable. Infusion cavernosometry with inflation of the device demonstrated greater than a 100% increase of intracorporeal pressure from baseline levels. Histologic assessment showed no adverse tissue effects on the penile tissue underlying the cuff or remote from the cuff in the penis and there was no development of distant thromboembolism. The results from this study will form the basis of long-term canine studies to investigate physiologic changes on the canine erection and chronic safety and reliability of the device. |
8042256 | Use of biodegradable mesh as a transport for a cultured uroepithelial graft: an improved method using collagen gel. | To create an improved delivery vehicle for cultured uroepithelial cells using biodegradable mesh and collagen gel. Twenty uroepithelial grafts were prepared by seeding cultured urothelial cells onto previously prepared collagen gel-polyglactin mesh. As a control, cells were seeded onto 20 plain polyglactin mesh (without gel) squares in the same fashion. The presence of urothelial cells was confirmed in all cultures by immunohistochemistry testing with anticytokeratin antibody. After 5 to 7 days, a confluent monolayer of cells covered 90% to 100% of the surface of all 20 collagen gel-mesh grafts. A confluent monolayer of cells did not form on any control graft (plain mesh). After 3 weeks, the cells had formed a sporadic, multiple cell layer confluence over 10% to 50% of the control graft surface; however, the mesh became friable and fell apart. By combining collagen gel with a biodegradable mesh scaffold, we created a surgically implantable cultured uroepithelial graft. The production of the collagen gel-mesh vehicle is simple and inexpensive. With this technique, the use of cultured urothelium for reconstructive urologic surgery can be investigated in greater detail. |
8042255 | Primary leiomyosarcoma of the seminal vesicle. | A case of leiomyosarcoma of the seminal vesicle is described in a 68-year-old man. Digital rectal examination and pelvic computed tomography (CT) scan disclosed a large pelvic mass in the region of the prostate, whereas magnetic resonance imaging (MRI) suggested that the mass arose from the right seminal vesicle. Biopsy of the mass revealed a high-grade malignancy, thus a radical cystoprostatectomy was performed. Pathologic examination revealed a leiomyosarcoma arising from the right seminal vesicle. The patient is well and free of recurrent disease 13 months following surgery. |
8042254 | Closure of large postradiation vesicovaginal fistula with rectus abdominis myofascial flap. | We report the case of a patient who developed a large radiation-induced vesicovaginal fistula. She also had a paucity of the omentum due to previous laparotomy and adhesions. We were able to treat this patient successfully with a pedicled myofascial rectus abdominis flap. |
8042253 | Primitive neuroectodermal tumor of the retroperitoneal cavity. | We report a case of primitive neuroectodermal tumor (PNET) arising from the retroperitoneal cavity. Because of infiltration, the tumor was excised en bloc with the left kidney. Despite postoperative adjuvant chemotherapy and local radiation therapy, the tumor recurred and the patient died of the disease 3 months postoperatively. Serum levels of neuron-specific enolase (NSE) correlated with those of lactate dehydrogenase (LDH), and it is suggested that monitoring NSE and LDH is useful in evaluating tumor recurrence. The clinical course and the treatment of this aggressive tumor are reviewed. |
8042252 | Laparoscopic surgical correction of circumcaval ureter. | Laparoscopic transposition and reanastomosis of a circumcaval ureter were performed in a 52-year-old man with right flank pain. A preoperative perfusion pressure study revealed abnormally high intrapelvic pressure. Under laparoscopy, the renal pelvis was divided above the ureteropelvic junction and the ureter was relocated from behind the vena cava. A 5 cm segment of redundant ureter containing the postcaval segment was resected and the ureteral end and renal pelvis were reapproximated with interrupted sutures by intracorporeal knot typing. The postoperative convalescence was uneventful, not necessitating the administration of analgesics. The patient resumed full activities 3 weeks later. The intravenous urogram and renogram obtained 2 months after the operation revealed remarkable improvement in the ureteral obstruction. |
8042251 | Medullary renal dysplasia mimicking renal tumor in the Beckwith-Wiedemann syndrome. | The known association of Wilms' tumor with the Beckwith-Wiedemann syndrome has prompted a surveillance regimen for children with this problem. Herein we report a case of medullary renal dysplasia that was a new onset by documented ultrasound. The association of medullary renal dysplasia with Beckwith-Wiedemann syndrome is discussed as well as the management of this problem. |
8042250 | Simplified technique for improving exposure of the apical prostate during radical retropubic prostatectomy. | We describe a rapid and easily learned technique that greatly assists in exposure of the apical prostate during radical retropubic prostatectomy. The technique is a modification of the previously reported "bunching" maneuver. A curved Kocher clamp is used to compress the dorsal vein complex and surrounding fascia into a tight midline bundle. Once transected, dissection of the prostatomembranous urethra, neurovascular bundles, and apical prostate is markedly facilitated. |
8042249 | Bladder autoaugmentation by vesicomyotomy in the pediatric neurogenic bladder. | The authors describe the procedure of bladder autoaugmentation by vesicomyotomy in 12 pediatric patients with neurogenic bladders. Indications for augmentation included low-capacity, high-pressure bladders with incontinence despite maximal anticholinergic therapy. Clean intermittent catheterization was successfully reinstituted postoperatively and no patient has subsequently required enterocystoplasty. There were no major complications and eight patients underwent concurrent procedures on the bladder. Urodynamic studies revealed a mean increase in capacity of 40% and a mean decrease in leak point pressure of 33% compared with preoperative values. Early clinical experience would suggest that vesicomyectomy (excision of released detrusor) offers no advantages over vesicomyotomy in pediatric patients. Vesicomyotomy (simple incision into detrusor) proved to be a simple technique that could be safely performed in pediatric patients. |
8042248 | Genitourinary polyps in children. | This study was undertaken to review the presenting complaints, diagnostic evaluation, treatment, and natural history of children with genitourinary polyps seen at the Mayo Clinic during the past 35 years. We retrospectively reviewed the charts of all children less than 16 years of age with symptomatic genitourinary polyps who were seen at the Mayo Clinic between 1957 and 1992. The age of each patient, clinical presentation, anatomic location of the polyp, diagnostic evaluation, and treatment were reviewed. Long-term follow-up data, including complications, were recorded, and the literature was reviewed. The most common presenting symptoms were hematuria in 9 patients, (gross 7, microscopic 2) and urinary tract obstruction in 9 patients (upper tract 3, lower tract 6). Four children had ureteral polyps. Excretory urography showed hydronephrosis and filling defects in 3 patients and a filling defect without hydronephrosis in 1 child. Two patients underwent segmental ureterectomy, 1 had open excision of the polyp, and 1 had ureteroscopic excision. Urethral polyps were identified in 12 children, most often as a filling defect of the posterior urethra on voiding cystourethrography (5 patients) or during cystourethroscopy (7 patients). All 12 patients were managed successfully by transurethral resection. Genitourinary polyps in children require a high degree of alertness and can be diagnosed with excretory urography, with voiding cystourethrography, or endoscopically. The biologic activity of these polyps is uniformly benign, and there have been no recurrences following complete excision. |
8042247 | Endoscopic urethroplasty of posterior urethral avulsion. | Traumatic avulsion of the posterior urethra represents a challenging reconstructive problem that traditionally has been managed by the transpubic or transperineal approach. We report the advantages of endourologic techniques to reconstruct short posterior urethral disruptions based on the principles of establishing proximal urethral control and balloon dilation of the newly constructed urethra. Endourologic urethroplasty consists of: (1) antegrade flexible cystoscopy or antegrade passage of a Goodwin sound, (2) retrograde urethrotomy to light or to tip of Goodwin sound, facilitated by C-arm fluoroscopy, (3) establishment of urethral continuity by passage of a guide wire, (4) balloon dilation of the newly established urethra to 24 to 30 F over a length of 4 cm, and (5) long-term urethral stenting (4 to 8 weeks) with a silicone Foley catheter. In four men initially managed by suprapubic cystostomy, endourologic reconstruction was performed. The mean blood loss was 250 mL, and mean length of hospitalization was 5.4 days. All patients were continent and three were potent over a mean follow-up of 10.5 months. Uroflowmetric monitoring showed satisfactory voiding patterns with subsequent minor endoscopic revisions required in three patients. The technical advantages of this method include stabilization and identification of the proximal urethra, intraoperative shortening of the urethral gap to facilitate the urethrotomy, and radial distention of the urethra by balloon dilation. We conclude that endourologic methods provide a safe and effective initial treatment of urethral avulsion. |
8042241 | Diminished cytotoxic gene expression in rat cardiac transplants with low-dose cyclosporine/methotrexate combination therapy. | We have previously shown that administration of a combination low-dose cyclosporine (CsA) (1.0 mg/kg/day)/methotrexate (MTX) (450 micrograms/kg/wk) treatment significantly increases the survival of rat cardiac allografts, and may therefore potentially serve as an alternative immunosuppressive therapy designed to promote transplant survival while minimizing high-dose CsA side effects. In contrast to high-dose CsA, low-dose CsA/MTX treatment does not appear to alter IL-2 gene expression, since similar patterns of IL-2 gene transcripts were found in both low-dose CsA/MTX-treated and untreated control allografts on days 1 through 8 posttransplantation (post-tx). The mechanism(s) by which low dose CsA/MTX therapy increases the time of allograft survival remains to be elucidated. The aim of the present study was to determine the effects of low-dose CsA/MTX on the expression of the cytotoxic cytokines, TNF alpha, TNF beta, or lymphotoxin (LT), and the serine proteases HF and C11 (granzymes A and B, respectively) in rat cardiac allografts during rejection. RNA blot analysis showed significant suppression of TNF alpha, LT, HF, and C11 gene expression on days 1 through 8 post-tx in cardiac allografts from low-dose CsA/MTX-treated recipients compared with untreated allograft controls. TNF protein levels in cardiac allografts from low-dose CsA/MTX-treated recipients were also found to be significantly reduced on days 1 through 8 post-tx when compared with time-matched untreated allograft controls (P < or = 0.001). We conclude that low-dose CsA/MTX treatment, while effective in prolonging cardiac transplant survival, appears to act at the mRNA level to downregulate cytotoxic cytokine gene expression. Such trials aimed at evaluating low-dose combination therapy may afford new insight into mechanisms underlying improvement in immunosuppressive treatment. |
8042240 | Interstitial pneumonitis and lymphocytic bronchiolitis/bronchitis as a direct result of acute lethal graft-versus-host disease duplicate the histopathology of lung allograft rejection. | Pulmonary complications are often lethal components of acute graft-vs.-host disease (GVHD). Although interstitial pneumonitis and lymphocytic bronchitis have been implicated as elements of acute GVHD, previous studies have not determined a correlation between the onset of these histopathologies or their contribution to a pulmonary syndrome that may occur as a direct result of acute GVHD. The present study used the adult, nonirradiated (DA x LEW) F1 hybrid rat in the absence of chemotherapy, immunosuppressive drugs, or overt infection to study these aspects of pulmonary pathology during acute GVHD. F1 animals were intravenously injected with 1 x 10(6) DA parental lymphoid cells/g body weight, which produced 100% morbidity and mortality by day 21. Neither syngeneically injected nor noninjected F1 control animals contained any observable or measurable histopathology. In addition, GVHD and control tissues did not contain bacterial, fungal, or CMV contamination as determined by specific tissue and immunohistochemical staining. GVHD animals were killed on days 3, 7, 10, 14, and 15-21 following injection. Whole-lobe tissue sections (4 mu) were stained with H&E, and histologic alterations within predetermined tissue sites were quantified using light-microscopic image analysis. Alveolar septal widths and perivascular infiltrate volume densities were increased significantly above controls by day 7, and reached 2.4- and 2.6-fold increases, respectively, by day 21. These data corroborated the development of an interstitial pneumonitis and lymphocytic bronchiolitis/bronchitis that duplicated the histopathology of lung allograft rejection. The discovery of pulmonary pathology corresponding to lung allograft rejection during acute GVHD in the adult F1 rat implicates the lung as a potential target organ. |
8042239 | UHG crossmatching. A comparison with PCR-SSO typing in the selection of HLA-DPB1-compatible bone marrow donors. | The technique of universal heteroduplex generator (UHG) crossmatching has been developed to permit comparison of HLA-DPB1 alleles between two or more individuals. It offers a rapid and simple method of screening prospective bone marrow donors for HLA-DPB1 compatibility with the recipient. We present the nucleotide sequence and describe the method of construction of the DPB1 UHG. To test its effectiveness, 56 patient-bone marrow donor pairs previously HLA-DPB1-typed by PCR-SSO probing, were tested by UHG crossmatching. In 52/56 (93%) pairs there was concordance between PCR-SSO typing and UHG crossmatching. All 32 pairs that were defined as mismatched by PCR-SSO typing were also mismatched by UHG crossmatching. We conclude that UHG crossmatching is a simple, sensitive, and cost effective method of HLA-DPB1 matching for the rapid selection of compatible bone marrow donors. |
8042238 | A pilot study of indocyanine green clearance as an early predictor of graft function. | Primary graft dysfunction occurs in up to 10% of liver transplant recipients and is the major reason for early mortality and retransplantation. The conventionally used markers of early graft function--i.e., correction of acidosis, glucose requirement, consumption of potassium, serum alanine transaminase (ALT), prothrombin time (PT), bile flow, resolution of encephalopathy and haemodynamic instability can be very misleading as they are dependent on numerous other factors. The aim of this study was to assess the use of indocyanine green clearance (ICG) as a measure of graft function. Peripheral ICG clearance was measured 18-24 hr after liver transplantation in twenty-three consecutive patients (24 transplants). Doppler ultrasonography confirmed normal hepatic arterial blood flow. Correlations between ICG clearance and other markers of graft function and outcome were sought. The mean ICG clearance was 406 mls/min (SD 137.5). A threshold value of 200 ml/min reliably predicted outcome. Significant correlations were found between ICG clearance and times to normalization of PT (P < 0.02) and to the correction of acidosis (P < 0.05). No correlation was found with ALT, PT, bile flow, glucose requirement, or consumption of potassium. ICG clearance measured on the day after liver transplantation accurately reflects graft function and may be used to predict graft survival and final outcome. |
8042237 | The beneficial effect of dietary antioxidant supplementation on platelet aggregation and cyclosporine treatment in heart transplant recipients. | To determine whether dietary antioxidant supplementation can reduce platelet reactivity in heart transplant recipients, 20 patients were prospectively randomized to receive either 500 IU vitamin E orally per day in the form of acetate for 2 months or no vitamin E. Blood creatinine (P = 0.01) and lymphocyte count (P = 0.009) significantly decreased only in supplemented patients, whereas the cyclosporine blood level was not modified. Platelet aggregation was stable in control patients but significantly decreased in supplemented patients in response to either thrombin (from 8.3 +/- 0.9% of maximum aggregation to 3.7 +/- 0.7, P = 0.001) or ADP (secondary wave: from 44.7 +/- 5.9% to 33.2 +/- 7.0, P = 0.02). Thus antioxidant supplementation tended to improve immunosuppression (by reducing lymphocyte count), to reduce cyclosporine nephrotoxicity, and to decrease the high thrombotic risk associated with heart transplantation. |
8042236 | Prostaglandin E in the treatment of recurrent hepatitis B infection after orthotopic liver transplantation. | While orthotopic liver transplantation (OLT) has become the treatment of choice for most irreversible end-stage liver diseases, its role in patients with hepatitis B (HBV) infection is controversial. A high risk of reinfection of the transplanted graft, associated with significant morbidity and mortality, has been reported. Although passive and active immunization can delay reappearance of the virus in the allograft, there is not yet an effective therapy for recurrent HBV infection in liver transplant recipients. Between October 1985 and March 25, 1991, 28 OLT in 25 patients with acute and chronic HBV infections were performed. Twelve of the patients were HBV DNA-negative, six were HBV DNA-positive, and seven were not tested prior to transplantation. Only the 19 patients surviving more than 100 days after transplantation were considered to have sufficient duration of follow-up (mean 734 days; range 500-1545) to include in analysis of recurrence. Five (26%) were free of recurrent disease at the time of last follow-up (mean 1031 days, range 526 to 1770 days. Recurrent HBV in the allograft, as defined by positive immunoperoxidase stains of biopsy sections for viral antigens, was detected in 74% (13 male, 1 female; 7 Asian, 7 white) at a mean of 134 days posttransplantation. Histological changes of viral hepatitis, first appearing an average of 157 days (range 95-326) posttransplantation, were evident in 13 of 14 with positive immunostaining. Twelve of the 14 patients were treated, on an open trial basis, with intravenous and oral prostaglandin E (PGE) because of deteriorating clinical condition. Eleven of the twelve responded to PGE with an initial drop in serum transaminases, improvement in coagulopathy and resolution of encephalopathy. One patient failed to respond and died of a myocardial infarction within 9 days of institution of therapy. Three of the eleven patients with an initial response relapsed and died in liver failure as a direct result of recurrent HBV after 13, 16, and 37 days of treatment in association with generalized sepsis. Eight of the 12 patients (67%) had a sustained favorable response to PGE therapy (mean follow-up 737 days, range 403-1545). All patients with a sustained response had accompanying improvement in histology and reduction in viral antigen staining in hepatocytes. Treatment with PGE appeared to be of benefit in recurrent HBV infection of the transplanted liver with an initial response rate of 92% and a sustained response rate of 67%. |
8042235 | Transhepatic metabolism of TNF-alpha, IL-6, and endotoxin in the early hepatic reperfusion period after human liver transplantation. | Several studies have shown that the postoperative course of cytokines such as TNF-alpha or IL-6 is predictive of rejection and infection after human orthotopic liver transplantation (OLT). The aim of this prospective clinical trial was to evaluate the impact of transhepatic metabolism of endotoxin (ET), tumor necrosis-factor-alpha (TNF-alpha), and interleukin-6 (IL-6) after hepatic ischemia/reperfusion on the postoperative graft function. In 13 consecutive elective adult OLT patients with primary grafts, we determined concentrations of ET, TNF-alpha, and IL-6 in the radial artery, portal vein, and right hepatic vein at 1, 4, 7, 10, and 13 min after reperfusion. Of the 13 patients, four had ET levels below the detection limit (< 10 ng/L), and one patient had extremely high ET concentrations (151 ng/L in the hepatic vein). In the remaining patients the mean ET levels were 26 +/- 14, 26 +/- 15, and 24 +/- 14 ng/L in the portal vein, hepatic vein, and in the radial artery, respectively. These values indicate that in patients with a moderately elevated ET level, no transhepatic concentration differences of ET exist. However, in the patient with severe endotoxemia, the liver was apparently an ET-producing organ (HV-P: 29 +/- 13 ng/L). TNF-alpha levels were not measurable in four patients, and varied between 15 and 72 pg/ml (portal vein) in the remaining patients. The transhepatic concentration differences (HV-P and HV-A, respectively) of patients with PNF or dysfunction were higher than in those with "good" or "excellent" graft function (HV-P: 160 +/- 122 pg/ml vs. 7.3 +/- 9.7 pg/ml; P < 0.01 and HV-A: 137 +/- 101 pg/ml vs. 3.9 +/- 12 pg/ml; P < 0.01, respectively). Arterial IL-6 levels were below 88 pg/ml (mean value: 31 +/- 20 pg/ml) at the beginning of the operation, and increased considerably in three patients during the anhepatic phase and after reperfusion. No clinical correlation was found with the transhepatic concentration differences of IL-6. We conclude that in OLT patients without infection no transhepatic ET exchange was documented. However, a stimulated hepatic TNF-alpha release seems to be predictive of the beginning of liver dysfunction. |
8042234 | A randomized trial comparing triple-drug and double-drug therapy in renal transplantation. Analysis at 7 years. | This is the 7-year update of a randomized trial comparing triple (TT) and double (DT) immunosuppressive therapy in renal transplantation. At 7 years, patient survival rate was 85% in DT vs. 87% in TT (P = NS); graft survival rate was 73% in DT and 68% in TT (P = NS); pure graft survival was 86% in DT vs. 77% in TT (P = 0.096). The 7-year graft survival rate was 67% for cadaver graft recipients vs. 92% for living-related graft recipients (P = 0.044). No difference in the slopes of plasma creatinine between the two groups was observed. Ten DT and 13 TT patients changed their original therapy: statistical analysis, however, was carried out according to intention to treat. Both CsA levels and doses were significantly higher in DT than in TT group (P < 0.001) at any time point up to the 7th year. At univariate analysis, a living-related donor kidney (P = 0.044) and immediate recovery of renal function (P < 0.001) were the only two parameters associated with graft survival at 7 years. At multivariate analysis, only early graft function recovery was correlated with late graft survival (RR = 10.480). Thus, even in the longterm, there is no difference between DT and TT, either in patient or in graft survival: at the doses we used, TT had a lower prevalence of late side effects than DT, however, long-term pure graft survival was better, although not significantly, in DT than in TT. The possibility of a safe shift from one regimen to the other one makes the two treatments complementary rather than alternatives. |
8042233 | The role of endothelin in the pathophysiology of renal impairment during acute liver rejection. | We assessed the role of endothelin in the development of renal dysfunction during acute rejection by examining the effect of a selective endothelin A (ETA) receptor antagonist BQ-123 in rats with acute liver rejection. Serum endothelin levels and endogenous creatinine clearance (Ccr) were monitored on days 1, 3, 5, 7, and 9 postoperatively. As indicators of renal hemodynamics, the estimated hemoglobin concentration of renal tissue (IHb) and the oxygen saturation of hemoglobin in renal blood (ISO2) were determined by reflectance spectrophotometry. In addition, the clearance of inulin and P-aminohippurate were determined, and the renal tissue blood flow was estimated by laser-Doppler flowmetry (LDF). As a model of allograft rejection, Lewis rats were transplanted orthotopically with DA rat livers. The serum endothelin level of allografted rejectors was significantly (P < 0.05) higher than that of isografted controls (Lewis rats with Lewis livers) on postoperative day 5, and it increased to a maximum of 5.38 +/- 0.95 pg/ml on day 9 (versus 1.23 +/- 0.18 pg/ml preoperatively). The values of Ccr, IHb, and ISO2 were all significantly (P < 0.05) lower in allografted rejectors than in isografted controls on day 5, and subsequently declined to a minimum on day 9 (P < 0.01). Treatment of allografted rejectors with BQ-123 markedly improved the renal parameters to levels similar to those in the isografted controls. These results strongly suggest that endogenous endothelin may play an important role in the development of renal impairment during acute liver rejection by reducing renal blood flow through binding with ETA receptor. |
8042232 | The impact of arterialization on prostanoid generation after liver transplantation in the rat. | Arterial reconstruction is not applied in most studies of hepatic transplantation. Differences in some parameters related to the microcirculatory status, depending on whether the graft has been subjected to both arterial and venous or only venous reconstruction have been demonstrated. We have evaluated whether arterialization has an effect on the production of inflammatory event-related mediators such as eicosanoids and oxygen free radicals. For this purpose, we have measured tissue eicosanoid levels, lipid peroxidation, and superoxide dismutase activity in livers subjected to arterial and venous or only venous reconstruction. No changes were observed in lipid peroxidation or superoxide dismutase activity when single and double revascularization were compared. Prostacyclin and thromboxane metabolites showed increased levels after 24-hr preservation when only venous reconstruction was carried out. In contrast, these metabolites remained unaltered when double revascularization was performed. This result suggests that eicosanoid metabolism is altered only when venous reconstruction was employed, and this fact can help explain microcirculatory changes reported in this experimental model of liver transplantation. |
8042231 | Induction of operational tolerance by random blood transfusion combined with anti-CD4 antibody therapy. A protocol with significant clinical potential. | Previous work from this laboratory has shown that donor-specific tolerance can be achieved in a mouse heart model if recipients are pretreated with a donor-specific blood transfusion (DST) in combination with a depleting anti-CD4 antibody. The advantage of this approach instead of simply using the antibody alone at the time of transplantation is that the nonspecific immunosuppressive effects of the antibody have largely decayed by the time of transplant such that donor-specific, rather than total, unresponsiveness results. However, this approach would not be applicable to clinical cadaveric transplantation since donor-specific transfusion at a specified time before transplant would not be possible. In an attempt to address these problems we have sought to determine (A) whether the state of unresponsiveness established by the anti-CD4/DST protocol could be maintained by repeated exposure only to the tolerizing antigen; (B) whether unrelated or random transfusion (RT) could substitute for DST in the anti-CD4/antigen pretreatment protocol, and (C) whether these two approaches could be successfully combined to provide an "umbrella unresponsiveness" that could be maintained until the time of transplant. Our data show, first, that antigen rechallenge without further antibody treatment can maintain a state of unresponsiveness to alloantigen; second, that random blood transfusion given under the cover of anti-CD4 monoclonal antibody leads to indefinite allograft survival and true tolerance in the long-term; and third, that once established by random transfusion under anti-CD4 cover, unresponsiveness can be maintained for an extended period by random transfusion alone. These results suggest that random blood transfusion combined with anti-CD4 monoclonal antibody therapy might be considered as a possible approach to the induction of specific unresponsiveness in clinical transplantation. |
8042230 | Mechanisms of acquired thymic unresponsiveness to renal allografts. Thymic recognition of immunodominant allo-MHC peptides induces peripheral T cell anergy. | We have recently shown that a single intrathymic injection of synthetic 25mer peptides, representing full sequences of the hypervariable domain of RT1.BuB (4 peptides) and RT1.Du beta (4 peptides) WF class II MHC molecules, 48 hr before transplantation induces donor-specific unresponsiveness to WF rat renal allografts in adult LEW recipients. The induction of unresponsiveness was abrogated by the recipient's thymectomy within the first week after intrathymic injection. Peripheral T cells of long-term survivors exhibited antigen-specific hyporesponsiveness in the LEW x WF MLR. Studies on the mechanisms of induction of acquired thymic unresponsiveness to alloantigen in vivo and in vitro are now reported. First, since we have previously demonstrated in LEW responders that only 4 of the 8 synthetic 25mer peptides, 2 RT1.Du beta and 2 RT1.Bu beta sequences, were immunogenic in vitro and in vivo, we compared the tolerogenicity of the immunogenic versus the nonimmunogenic peptides. While LEW rats intrathymically injected with the nonimmunogenic peptides acutely rejected their renal allografts within 6-10 days, animals injected with the immunogenic peptides did not reject their grafts and are surviving > 100 days with normal allograft function. In vitro studies established that peripheral T cells from intrathymically tolerized animals exhibited antigen-specific hyporesponsiveness in the LEW x WF MLR starting as early as 1 week posttransplant. Immunohistological evaluation of renal allografts from intrathymically tolerized animals 1 week postengraftment showed marked reduction in mononuclear cell infiltrates with no evidence of tubulitis, and marked reduction in intragraft staining for activation and inflammatory cytokines and alloantibodies, as compared with acutely rejecting controls. Systemic administration of 1000 U of rIL-2 daily for 5 days starting on the day of transplantation abrogated the tolerogenic effect of intrathymic MHC allopeptides. Injection of 100 micrograms of a single immunogenic peptide, RT1.Du beta 2 (residues 20-44), into the thymus of responder LEW rats 48 hrs before immunization with RT1.Du beta 2 effected significant reduction of in vitro proliferation of primed lymphocytes to RT1.Du beta 2, an effect that was abrogated by addition of rIL-2 in vitro. In contrast, thymectomy beyond 2 weeks and administration of rIL-2 at 4-6 weeks after transplantation failed to cause rejection. These observations indicate that thymic recognition of immunodominant class II MHC allopeptides leads to peripheral T cell anergy that mediates the induction phase of systemic unresponsiveness to renal allografts. The maintenance phase appears to be mediated by dense anergy or clonal deletion.(ABSTRACT TRUNCATED AT 400 WORDS) |
8042223 | Cerebrospinal fluid and therapy of isolated angiitis of the central nervous system. | Serial cerebral angiograms, computed tomography, and magnetic resonance imaging are among the proposed methods for monitoring disease activity and response to therapy in isolated angiitis of the central nervous system. Cerebrospinal fluid has not proved to be useful in monitoring clinical course. We describe a 45-year-old man with histological diagnosis of isolated angiitis of the central nervous system that was treated with prednisone plus azathioprine and monitored for 2 years. Samples of the cerebrospinal fluid were obtained for cytological and routine chemical examination, as well as albumin and immunoglobulin content. Before treatment, cerebrospinal fluid showed marked plasmatic transudation of albumin and intrathecal synthesis of immunoglobulins. During the first year of immunosuppression no events were noticed, and the previously abnormal aspects of the cerebrospinal fluid showed improvement. During the weaning of azathioprine, a new stroke occurred in conjunction with a marked deterioration of cerebrospinal fluid parameters. Immunosuppression was resumed at previous levels, and during the following year no further events occurred. Once again, abnormal cerebrospinal fluid values improved significantly. We report a case of isolated angiitis of the central nervous system in which the serial cerebrospinal fluid examinations (albumin and immunoglobulin content) showed a close correlation with clinical course. This method may be useful in monitoring response to therapy. |
8042222 | Effects of total hemoglobin and hemoglobin S concentration on cerebral blood flow during transfusion therapy to prevent stroke in sickle cell disease. | The standard treatment of stroke in sickle cell disease is chronic transfusion to maintain the fraction of abnormal hemoglobin (hemoglobin S [HbS]) below 20%. Risks associated with such transfusion can be reduced by allowing higher HbS levels, but the physiological consequences of this modification are unknown. Cerebral blood flow is elevated in sickle cell disease proportionate to the degree of anemia and is reduced by transfusion. We tested the effects of various HbS levels on cerebral blood flow during the course of transfusion therapy. We monitored cerebral blood flow (by the 133Xe inhalation method) in three patients whose chronic transfusion program was changed from a traditional regimen (HbS < 20%) to a moderate one, allowing HbS to rise to 45% to 50% between treatments. As expected, cerebral blood flow was higher with lower hemoglobin and higher HbS concentration. However, the HbS fraction appeared to exert a separate influence on the hyperemia, independent of total hemoglobin concentration. Furthermore, cerebral blood flow was higher during the modified regimen, despite equivalent anemia. These results suggest caution in adapting the modified transfusion regimen. Although HbS concentrations of 50% did not cause any frank neurological sequelae, the possible consequences of the associated hyperemia over time are unknown. We conclude that larger clinical and physiological studies of moderate transfusion regimens (allowing higher concentration of HbS) are necessary before it can become standard therapy. |
8042221 | Primary medullary hemorrhage. Report of four cases and review of the literature. | Primary medullary hemorrhage is uncommon. Its clinical profile and prognosis are not well known. We report four cases of medullary hemorrhage and a review of the English and French literature since 1964 to analyze the clinical presentation and prognosis. Of sixteen case reports of medullary hemorrhage reviewed from the literature, sixteen contained sufficient information for review and are included in this report. The age distribution of the patients was between 13 and 72 years, and 10 of these patients were men. The most frequent symptoms at onset were vertigo, sensory symptoms, and dysphagia. Presenting signs included palatal weakness, nystagmus, hypoglossal palsy, cerebellar ataxia, and limb weakness. The diagnosis was made at autopsy in 3 patients, at surgery in 3, by computed tomography in 4, and more recently by magnetic resonance imaging in 6. In nine instances the etiology of hemorrhage was undetermined; a ruptured vascular malformation was the cause in 3 patients, 1 was attributed to the use of anticoagulants, and hypertension was the suspected cause in the other 3 patients. Mortality rate was 19%; however, survivors generally had nonincapacitating sequelaes. These findings indicate that primary medullary hemorrhage presents with a characteristic syndrome of sudden onset of headache and vertigo with neurological signs that correspond to various combinations of medial and lateral medullary involvement. In those patients who survive, prognosis usually is good. |
8042220 | Cerebral vasodilation during hypercapnia. Role of glibenclamide-sensitive potassium channels and nitric oxide. | The purpose of these experiments was to examine mechanisms by which hypercapnia produces vasodilatation in brain. We examined the hypothesis that dilatation of cerebral arterioles during hypercapnia is dependent on activation of ATP-sensitive potassium channels and formation of nitric oxide. Diameters of cerebral arterioles were measured using a closed cranial window in anesthetized rabbits. Changes in diameter of arterioles were measured in response to topical application of acetylcholine and sodium nitroprusside and during two levels of systemic hypercapnia. Increasing arterial PCO2 from 32 +/- 1 mm Hg (mean +/- SE) to 54 +/- 1 and 66 +/- 1 mm Hg dilated cerebral arterioles by 25 +/- 3% and 38 +/- 5%, respectively, from a control diameter of 93 +/- 3 microns. The response to the low level of hypercapnia was attenuated (25 +/- 3% versus 16 +/- 4%, P < .05) by glibenclamide (1 mumol/L), an inhibitor of ATP-sensitive potassium channels. Vasodilatation in response to the high level of hypercapnia was not affected by glibenclamide. Increases in arteriolar diameter in response to sodium nitroprusside were not inhibited by glibenclamide. NG-nitro-L-arginine (300 mumol/L), an inhibitor of nitric oxide synthase, completely inhibited dilatation of cerebral arterioles in response to the low level of hypercapnia and inhibited vasodilatation during the high level of hypercapnia by 66%. Thus, activation of glibenclamide-sensitive potassium channels may contribute to dilatation of cerebral arterioles during hypercapnia. Cerebral vasodilatation during hypercapnia is dependent in large part on production of nitric oxide. |
8042219 | Reperfusion-induced injury to the blood-brain barrier after middle cerebral artery occlusion in rats. | The integrity of the blood-brain barrier may play an important pathophysiological role during postischemic reperfusion. To determine the factors that lead to exacerbation of brain injury by reperfusion, we investigated changes in cerebral blood flow, blood-brain barrier permeability, edema formation, and infarction in permanent or temporary middle cerebral artery occlusion in rats and studied the relation between local cerebral blood flow and blood-brain barrier disruption. Middle cerebral artery occlusion was performed with the rat suture model, allowing either permanent (6 hours) or temporary occlusion (3 hours of occlusion and 3 hours of reperfusion). We measured brain water, ion contents, and infarct volumes and determined cerebral blood flow using laser Doppler flowmetry and blood-brain barrier permeability with [3H] alpha-aminoisobutyric acid. During occlusion, cerebral blood flow was reduced to 7% to 15% (permanent) and 10% to 17% (temporary) of the baseline. During 3 hours of reperfusion, it returned to 47% to 80% (lateral cortex) and 78% to 98% (medial cortex) of the baseline. Compared with the contralateral hemisphere, the water content in the ischemic area increased in both permanent and temporary groups (P < .05, P < .01). Both infarct volume and blood-brain barrier disruption were greater in the reperfusion group compared with the permanent occlusion group (P < .05). Blood-brain barrier disruption correlated with cerebral blood flow during reperfusion (P < .05). These findings demonstrate that brain infarct and blood-brain barrier disruption are exacerbated after reperfusion in this model of focal ischemia. Blood-brain barrier disruption may relate to the degree of cerebral blood flow recovery. Thus, although early reperfusion in focal ischemia may preserve penumbra tissue, late reperfusion may increase the tissue injury. |
8042218 | Mechanisms of vasodilation of cerebral vessels induced by the potassium channel opener nicorandil in canine in vivo experiments. | Nicorandil, a potent antianginal agent characterized as a potassium channel opener, could produce cerebrovascular dilation in in vitro studies. Our aim was to investigate the pharmacologic response to the topical application of nicorandil on the vasomotor tone of pial vessels in vivo. To elucidate its mechanism, we also studied the inhibitory action of methylene blue and glibenclamide against nicorandil-induced vasodilation. In 14 dogs prepared with a parietal cranial window, we administered five different concentrations of nicorandil solution (10(-7), 10(-6), 10(-5), 10(-4), and 10(-3) mol/L) under the window and measured pial arterial and venular diameters. After pretreating pial vessels with either 10(-5) mol/L methylene blue or 10(-5) mol/L glibenclamide, we examined inhibitory action after the application of 10(-5) mol/L nicorandil. In additional experiments with 9 dogs, we evaluated the effects of nitroglycerin and cromakalim on pial vessels in the absence or presence of 10(-5) mol/L methylene blue and 10(-5) mol/L glibenclamide, respectively. Nicorandil produced significant, concentration-dependent dilation of pial vessels (P < .05). Methylene blue blocked nicorandil-induced dilation, whereas glibenclamide only attenuated such action of nicorandil. Nitroglycerin and cromakalim also produced a concentration-dependent increase in pial arteriolar and venular diameters (P < .05), and those effects were blocked in the presence of methylene blue or glibenclamide, respectively. Our in vivo study demonstrates that topical application of nicorandil dilates both pial arterioles and venules in a concentration-dependent manner and suggests that the mechanisms of such actions are most likely due to both cyclic GMP-mediated vascular smooth muscle dilation and the regulation of K+ flux. |
8042217 | Therapeutic time window and dose response of the beneficial effects of ketamine in experimental head injury. | The aim of this study was to determine the time and dose response of the therapeutic effects of the N-methyl-D-aspartate receptor antagonist ketamine in experimental head injury. Sixty-six male Sprague-Dawley rats were divided into eight groups. Groups A, B, and C were surgically prepared but received no trauma. Groups D through H received a nonpenetrating impact to the left cranium. Group A (n = 7) received no treatment. Groups B (n = 4) and C (n = 5) received 60 and 120 mg/kg IP ketamine, respectively. Group D (n = 8) received no treatment. Groups E (n = 8) and F (n = 7) received 120 and 180 mg/kg IP ketamine, respectively, 1 hour after head trauma. Groups G (n = 7) and H (n = 9) were treated with 180 mg/kg IP ketamine 2 and 4 hours after head trauma, respectively. Neurological severity score (NSS, 0 through 25 from no injury to severe injury) was determined at 1, 24, and 48 hours after head trauma. After death at 48 hours, cortical slices were taken adjacent to the lesion on the traumatized hemisphere and from comparable sites in the contralateral hemisphere for determination of tissue specific gravity and water content. Brains were then placed in 4% formaldehyde, and the volume of hemorrhagic necrosis was measured 4 days later. NSS was compared within and between groups using the Kruskal-Wallis test for repeated measurements and Mann-Whitney U test for post hoc testing. Water content, specific gravity, and hemorrhagic necrosis were compared within and between groups using two-way ANOVA followed by Fisher's protected least significant difference procedure. A value of P < .05 was considered statistically significant. Head trauma alone increased NSS, decreased specific gravity, increased water content, and caused cerebral infarction in the injured hemisphere. Ketamine given in two time-dose regimens, 180 mg/kg IP at 2 hours (group G) and 120 mg/kg IP at 1 hour (group F) after trauma, improved NSS from 11.6 +/- 1.7 and 14.4 +/- 0.8 at 1 hour to 4.4 +/- 1.3 and 8.0 +/- 1.4 (mean +/- SEM) at 48 hours, respectively (P < .03). Compared with the untreated group (group D), 180 mg/kg IP ketamine given at 2 and 4 hours after head trauma decreased the volume of hemorrhagic necrosis from 37.1 +/- 9.5 mm3 to 10.1 +/- 3.8 and 15.3 +/- 3.6 mm3, respectively (P < .05). Brain tissue specific gravity and water content at 48 hours were not significantly different between treated and untreated groups. There was no difference in rectal and temporalis muscle temperature between groups. We conclude that 180 mg/kg IP ketamine was effective in ameliorating neurological dysfunction after head trauma in rats when the administration time was delayed for 1 hour to 2 hours but not after 4 hours. When given at 1 hour after head trauma, ketamine at 120 mg/kg but not 60 mg/kg is effective in reducing neurological damage after head trauma. |
8042216 | Fibrin content of carotid thrombi alters the production of embolic stroke in the rat. | Mechanical denudation of the endothelium of the carotid artery in animals produces a nonocclusive thrombus, but the brains of these animals have not been examined for the presence of embolic stroke. The endothelium of the right carotid artery of 16 Wistar rats was denuded using a balloon catheter. Phosphotungstic acid hematoxylin (PTAH) staining and scanning electron micrographs of the nonocclusive thrombi in the carotid arteries were compared with those produced by photochemical methods, and brains were examined for infarcts. Although nonocclusive thrombi were present in the carotid arteries of 4 of 4 rats killed at 4 hours and in 8 of 12 killed at 24 hours, neither cerebral infarcts nor emboli were seen in the 14 brains evaluated by light microscopy. PTAH demonstrated a high fibrin content in the thrombus produced by the endothelial denudation, with almost no fibrin seen in photochemically induced thrombi. Scanning electron microscopy confirmed dense networks of fibrin in the thrombi produced by balloon denudation. The composition of a nonocclusive thrombus may determine the embolic potential of this thrombus. A low fibrin content in a nonocclusive platelet thrombus may enhance the embolic potential. This suggests that platelet inhibition may also be indicated in patients with carotid artery disease who are being treated with anticoagulant. |
8042215 | Cost of acute stroke care in Toronto, Canada. | Stroke cost consumes a large proportion of the gross domestic product in all developed countries, and while health care costs are rising, the ability to contain them is diminishing. We calculated the cost of acute stroke care for all first admissions to a teaching hospital in Toronto, Canada, in 1991 through 1992 for 285 consecutive patients. The average cost per patient was $27,500 Canadian, and strokes in men cost less than in women ($23,000 versus $32,000 Canadian), for a total cost of $8 million Canadian over 2 years. More women died than men (34% versus 17%, P < .02), mainly from systemic complications of stroke, but because women stayed hospitalized longer, they cost more in the long term. The major factor determining cost was social support, and more men than women went home or to rehabilitation units (P < .02). Family support was greater for men (82%) than women (39%, P < .0002). Significant cost reductions are more likely to be achieved by altering discharge policies and improving social conditions for early return to the home than by reducing laboratory or medical personnel costs. |
8042214 | Definition of initial grading, specific events, and overall outcome in patients with aneurysmal subarachnoid hemorrhage. A survey. | Scientific communication in medicine can be effective only if reports are based on unequivocal criteria for clinical conditions or specific diagnoses. We reviewed all articles about subarachnoid hemorrhage published in nine neurosurgical or neurological journals from 1985 through 1992 and assessed the presence and the precision of definitions used for reporting the initial grade, the specific complications of rebleeding, delayed cerebral ischemia, and hydrocephalus, and the overall outcome. We identified 184 articles reporting direct observations in at least 10 patients on one or more of these conditions. Of 161 articles reporting the initial condition, only 19% used an unequivocal grading system (World Federation of Neurological Surgeons Scale or Glasgow Coma Scale); this proportion did not increase after 1988, when the World Federation of Neurological Surgeons Scale was introduced. The specific outcome events of rebleeding, ischemia, and hydrocephalus (283 instances) were sufficiently defined in only 31% of instances, incompletely in 22%, and not at all in 47%. The proportions were similar when the results were analyzed according to the type of complication, the year of publication, or per study. The four exclusively neurosurgical journals featured suitable definitions for any of the three outcome events in 20% of 209 instances, whereas the five mainly neurological journals published fewer articles about subarachnoid hemorrhage (74 instances of outcome events) but more often with precise criteria (65%). Overall outcome was adequately reported in 63% of all articles, with an increase over the years (54% in 1985 through 1988, 71% in 1989 through 1992). Reports about subarachnoid hemorrhage require closer scrutiny before publication to ascertain whether the conclusions about specific outcome events are based on unequivocal criteria. |
8042213 | Trends in survival after stroke among Medicare beneficiaries. | Most strokes occur among people aged 65 years and older. The increasing proportion of persons who are in this age group underlines the importance for health-care providers to be aware of trends in poststroke survival. We investigated poststroke survival trends from 1985 to 1989 among Medicare beneficiaries. Medicare hospital claim records and enrollment data were obtained on 1 901 439 Medicare patients with a principal diagnosis of stroke occurring during the years 1985 through 1989. Cox proportional hazard techniques were used to compare the 2-year poststroke survival for strokes occurring in 1986, 1987, 1988, and 1989 relative to strokes occurring in 1985. Poststroke survival trends were examined among groups defined by age, race, region, type of stroke, and, for a 20% subset, history of stroke. We observed a modest improvement in poststroke survival from 1985 to 1989 (1989:1985 hazard ratio, 0.96; P < .05). Trends for persons with hemorrhagic stroke showed more improvement (hazard ratio, 0.88; P < .05) than those for persons with ischemic stroke (hazard ratio, 0.98; P < .05). Improvement was also greater among persons without known prior hospitalization for stroke (hazard ratio, 0.94; P < .05) and during periods of follow-up shorter than 2 years. The variations in poststroke survival among subgroups of the population have important implications for the quality of life of stroke survivors and for the future medical and nursing needs of these populations. |
8042211 | Hypertension and risk of stroke recurrence. | Hypertension is a risk factor for initial stroke, but its relation to stroke recurrence is unclear. Therefore, we sought to analyze the effect of hypertension and its control on risk of stroke recurrence. Within 1 month of onset, a population-based cohort of 662 patients from the Lehigh Valley with an initial stroke were enrolled. Hypertension was determined at enrollment by history. Blood pressure was also measured at enrollment and at each follow-up at 4- to 6-month intervals for up to 48 months (mean, 24 months). Stroke recurrence was verified by history, examination, and review of medical reports. Various criteria for control of blood pressure were defined. History of hypertension, measured blood pressure, and its control were analyzed in relation to stroke recurrence frequency using Kaplan-Meier and univariate, multivariate, and time-dependent Cox proportional hazards models. At enrollment, 59.4% of the cohort had a history of hypertension and 81 patients had a second stroke. Those with a history of hypertension had a significantly higher stroke recurrence rate than those without such a history (P = .01). Among those with measured diastolic blood pressure at enrollment > or = 95 mm Hg, 43% had a stroke recurrence by the end of the study compared with only 19% below this cutoff (P = .005). Recurrence risk was reduced in a multivariate analysis as quality of diastolic blood pressure control increased (relative risk = 8.4, 3.9, and 2.0 among those with poor, fair, and good control, respectively, compared with nonhypertensive subjects). Systolic blood pressure and its control appeared less or not significantly associated with stroke recurrence. History of hypertension and elevated measured diastolic pressure after the initial stroke were associated with an increased risk of second stroke. Controlling diastolic pressure substantially reduced this risk. |
8042212 | Prognosis after transient ischemic attack and ischemic stroke in young adults. | We undertook this study to describe the risk of stroke recurrence and functional and occupational status in the long-term follow-up of young adults with ischemic strokes and to identify possible predictors for stroke recurrence, disability, and working status. A cohort of 215 patients aged < or = 45 years with ischemic cerebral events (43 transient ischemic attacks, 135 minor strokes, 37 major strokes), evaluated at our institution from May 1985 through March 1992, was followed for a mean of 43.1 months (SD, 39.7 months; range, 1 to 228 months). Information on death and recurrent cerebral vascular events, functional disability (Rankin Scale), retirement, and working status was obtained from direct observation, mail questionnaire, and telephone interviews. Four patients (2%) with major strokes died acutely. Information on stroke recurrence and disability was available for 184 (87%) of the survivors and on retirement and working status for 140 (67%) of the patients. Two patients died from cancer. Seven transient ischemic attacks and eight strokes (two hemorrhagic) occurred during follow-up. Patients with strokes of unknown cause experienced no recurrent strokes, contrasting with two deaths and eight strokes in those whose stroke cause was identified (difference between proportions: 8%; 95% confidence interval, 3 to 13). Eighty-eight patients had a complete recovery, and only 21 were disabled (Rankin grades 4 or 5). Logistic regression analysis identified the severity of the initial stroke (Rankin grade > 3) as the only significant predictor of disability (odds ratio, 10.7; 95% confidence interval, 3.7 to 30.6). Of the survivors, 73% were working, and only 18% were retired. Disability at follow-up was the best (but nonsignificant) predictor of retirement (odds ratio, 1.6; 95% confidence interval, 0.8 to 3.4). Ischemic stroke in young adults has a low acute mortality and few recurrences, more so if the cause is not identified. The majority of patients return to an active professional life. Severity of the initial stroke is the major predictor of independence. The relation between disability and return to work or retirement is less clear. |
8042210 | The importance of family history in cerebrovascular disease. | The role of genetics in cerebrovascular disease remains controversial. The purpose of this study was to assess the influence of family history on atherothrombotic infarction or transient ischemic attack. Ninety patients with stroke or transient ischemic attack and 90 age- and sex-matched community control subjects were studied prospectively. Medical and family histories were obtained from all subjects, and a complete physical examination was performed. Eighty-five patients and 86 control subjects knew their family history for ischemic heart disease and stroke. A positive history for ischemic heart disease was present in 62 (73%) of the patients and 46 (53%) of the control subjects (P = .019), and a positive family history for stroke was present in 38 (47%) of the patients and 21 (24%) of the control subjects (P = .014). Although a positive vascular family history was not an independent risk factor in a multivariate analysis, it was an excellent marker of the presence of other established vascular risk factors. Personal histories of ischemic heart disease, hypertension, and hyperlipidemia were found to be significant independent risk factors for stroke. |
8042209 | Alcohol consumption and carotid atherosclerosis: evidence of dose-dependent atherogenic and antiatherogenic effects. Results from the Bruneck Study. | Although a variety of epidemiological studies have suggested a U-shaped association between alcohol and cardiovascular disease, controversy still surrounds the role of atherogenesis in the mediation of alcohol effects. Carotid atherosclerosis was measured with a sensitive and reproducible B-mode score in a random sample of 460 men drawn from the Bruneck Study (baseline examination in 1990). The age-adjusted relation between alcohol and carotid artery disease was U shaped, with light drinkers facing a lower atherosclerosis risk (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.85; P = .01) than either abstainers (odds ratio, 1.00) or heavy drinkers (odds ratio, 2.78; 95% confidence interval, 1.32 to 5.84; P < .01). The association was not explained by the lifestyle of alcohol consumers (smoking) or inclusion of former (heavy) drinkers in the reference group. The effect of alcohol was modified by drinking behavior (type of beverage). Approximately a quarter of the atherosclerosis risk caused by severe alcohol consumption was mediated by the risk profile associated with drinking, whereas the apparent beneficial effect of low alcohol intake emerged independent of conventional risk attributes. Our results support the hypothesis that adverse and beneficial effects of alcohol on cerebrovascular disease are mediated in part by analogous atherogenic and antiatherogenic properties. |
8042208 | Common carotid intima-media thickness measurement. A method to improve accuracy and precision. | High-resolution ultrasonographic imaging is a noninvasive method that allows estimation of the thickness of the intima-media complex in human carotid arteries. The determination of intima-media thickness involves several steps, each of which may introduce an error that influences the reproducibility of the method. In the present study, apart from the general reproducibility of the determination of intima-media thickness, the error introduced by each step was evaluated. B-mode scans were performed on 14 randomly selected patients. The common carotid arteries were examined in anterior, lateral, and posterior planes, with a standard methodology and by a new method, making use of external reference points. The error in general reproducibility in determination of the subject's mean intima-media thickness was 5.9%. This parameter was also evaluated in a paired manner after dividing the whole artery into sectors; with this protocol, the percent error in general reproducibility was 15%. The main source of variability in the evaluation of common carotid intima-media thickness was found to lie in the operator's subjectivity in the choice of the carotid sector to be processed (percent error, 10.27%). A method was therefore designed that used external reference points, resulting in reduction of this error by 38.2%. While the mean intima-media thickness might be considered a reproducible parameter to evaluate differences between populations exposed to diverse risk factors, evolutional or therapy-induced changes in the individual may be better monitored on defined carotid sectors. This may be achieved with a high reproducibility by use of the proposed method based on external reference points. |
8042207 | Relations of intimal-medial thickness among sites within the carotid artery as evaluated by B-mode ultrasound. ARIC Investigators. Atherosclerosis Risk in Communities. | B-mode ultrasound is a widely used technique for the clinical and epidemiological assessment of carotid atherosclerosis. This article describes the relation between arterial intimal-medial thickness (IMT) at different sites within the extracranial carotid artery. IMT was measured by B-mode real-time ultrasound as an index of atherosclerotic involvement in the extracranial carotid arteries as part of the population-based Atherosclerosis Risk in Communities (ARIC) study. The relation between IMT at different sites was described by correlation coefficients and percentile regression techniques based on between 4034 and 9386 pairs of measurements (variation in sample size depending on the paired sites). Increased IMT at one site was associated with increased IMT at other sites. The correlation between right and left IMT at the same anatomic location in the carotid artery ranged from .34 to .49; the correlation at different anatomic locations in the carotid artery on the same side ranged from .25 to .43. The distribution of IMT, described by the percentiles of IMT at the inference site as a function of IMT at the index site, showed constricted percentiles of IMT at the inference site for small IMT at the index site and an increase in the spread of percentiles with increasing IMT. Although increased carotid IMT at one site is positively associated with thickened walls at other carotid sites, the ability to accurately predict wall thickness at a site given the wall thickness at other sites is modest. The general association between sites supports the systemic nature of atherosclerosis, while the lack of tight agreement between sites supports the focal nature of the atherosclerotic process. |
8042206 | Early treatment of stroke with monosialoganglioside GM-1. Efficacy and safety results of the Early Stroke Trial. | The Early Stroke Trial (EST) is a randomized, double-blind, placebo-controlled trial to assess the effect of monosialoganglioside GM-1 in improving recovery in patients who experienced an ischemic supratentorial stroke. Sixteen clinical centers recruited 805 patients, of whom 792 were confirmed to be eligible. Treatment, consisting of a first dose of either 200 mg GM-1 or placebo, was initiated within 5 hours of the onset of stroke; a second dose of either 100 mg GM-1 or placebo was administered 12 hours later. Thereafter, patients received a daily injection of 100 mg GM-1 or placebo intravenously from day 2 through 10 and intramuscularly from day 11 through 21. Patients were followed up for a total of 4 months. Survival was similar in the two treatment groups. Improvement in neurological status, as measured by the change in Canadian Neurological Scale score between baseline and 4-month assessments, was greater in the group receiving GM-1; the observed difference between treatment groups was 0.22 (P = .06). A post hoc analysis in the subgroup of patients treated within 4 hours showed a statistically significant difference, with Canadian Neurological Scale mean improvement of 0.41 (P = .016). GM-1 use was not associated with differences in frequency, nature, or severity of adverse experiences. These findings suggest that GM-1 is safe in the dose and treatment schedule used and that its efficacy in ischemic stroke is greater when given soon after onset of stroke. |
8042205 | Shear-induced platelet aggregation in cerebral ischemia. | Recent evidence has suggested that shear-induced platelet aggregation is an important mechanism of thrombosis at arterial bifurcations or stenoses. We measured shear-induced platelet aggregation with a new apparatus in patients with cerebral ischemia and also studied correlations with other hemostatic parameters as well as the effect of antiplatelet agents. The subjects were 75 patients with cerebral ischemia and 26 control subjects. Platelet aggregation was induced in citrated platelet-rich plasma by a high shear stress (108 dynes/cm2) that was applied by means of a cone-plate streaming chamber based on turbidimetry. We studied the correlation of test results with hemostatic parameters and also the effects of antiplatelet agents. Compared with the control subjects, an increase of shear-induced platelet aggregation was observed in 21 patients with atherothrombotic stroke and 12 with transient ischemic attacks, but not in 11 with cardioembolic stroke or 31 with lacunar stroke. There was no significant correlation of shear-induced platelet aggregation with platelet count, agonist-induced platelet aggregation, fibrinogen level, or beta-thromboglobulin level. The extent of shear-induced aggregation was not correlated with von Willebrand factor antigen levels but was significantly correlated with the amounts of larger von Willebrand factor multimers. Oral aspirin (81 mg/d) did not inhibit shear-induced platelet aggregation, whereas oral ticlopidine (200 mg/d) significantly inhibited it. These results indicate that shear-induced platelet aggregation is increased in patients with atherothrombotic stroke and transient ischemic attacks, is correlated with the increase of larger von Willebrand factor multimers, and is corrected by ticlopidine but not by low-dose aspirin. |
8042204 | Iron-related damage in acute ischemic stroke. | Although iron-mediated mechanisms are important in experimental brain injury after carotid occlusion, their clinical role in acute ischemic stroke has not been determined. We evaluated the influence of iron stores, measured as serum ferritin, on the outcome of acute cerebral infarct. Admission and fasting glycemia, glycosylated hemoglobin, serum cortisol, serum ferritin, and 24-hour urinary free cortisol levels were measured on the first day of hospitalization in 67 patients admitted with an acute ischemic stroke of less than 24 hours' duration. Patients were classified into two groups according to their Canadian Stroke Scale (CSS) score on day 30: good outcome group (alive and CSS score > 7 points) and poor outcome group (dead or CSS score < or = 7 points). Thirty-three patients (49%) had good outcome and 34 (51%) poor outcome. Fasting glycemia (P = .001), serum cortisol (P < .001), and urinary free cortisol (P = .001) but not admission glycemia and glycosylated hemoglobin had higher levels in patients with poor outcome. Serum ferritin values were greater in the poor outcome group (218 +/- 156 micrograms/L versus 133 +/- 125 micrograms/L; P = .004), and a correlation between ferritin values and degree of worsening or improvement of the CSS score on day 30 was found (P = .002). Serum cortisol (odds ratio [OR], 6.7; 95% confidence interval [CI], 1.7 to 26), fasting glycemia (OR, 5.4; 95% CI, 1.2 to 24), and serum ferritin (OR, 4.6; 95% CI, 1.1 to 19) were independently related to poor outcome in a logistic regression analysis. High serum ferritin levels within the first 24 hours of hospitalization for an acute ischemic stroke are related to a poor prognosis, independent of the stress response. More research is needed to determine the origin of increased serum ferritin levels and the therapeutic implications. |
8042203 | Chronic oral administration of methylcyclopentadienyl manganese tricarbonyl altered brain biogenic amines in the mouse: comparison with inorganic manganese. | This study was conducted to investigate the effects associated with high dose administration of organic manganese to mice and to compare these effects with those of inorganic manganese. The disposition and toxicity of methylcyclopentadienyl manganese tricarbonyl (MMT; a potential substitute for lead in gasoline) in the brains of ddY mice was studied after 12-months administration (at 0.5 g/kg of MMT) in food. Mice exposed to inorganic manganese received 2.0 g/kg of MnCl2 in food for the same period. There was no significant difference in food intake between the control mice and the MMT-exposed mice or MnCl2-exposed mice. Normetanephrine level in the cerebellum of the MMT-exposed group was significantly increased compared with the control, and correlated with the manganese concentration. The manganese concentration was significantly increased in the cerebellum of the MMT-exposed group compared with the control and MnCl2-exposed groups. On the whole, methoxylation from the 3-hydroxyl of catecholamine tended to be promoted by manganese. |
8042202 | Alteration of femoral structure in later life by chronically feeding caffeine during rapid growing period in newborn female rats. | The effects of caffeine intake in early life on bone structure later in life were studied in rats. At day 9 of gestation, dams were divided into 2 groups. Group 1 (control) received a 20% protein diet; group 2 received the 20% protein diet supplemented with caffeine (2 mg/100 g body weight). After birth pups were continuously fed their respective diets until day 93, when the diet of group 2 was replaced with a noncaffeine 20% protein diet. On day 388 animals from both groups were weighed, killed, and femora and mandibles were removed. Calcium, phosphorus, magnesium, zinc, hydroxyproline, and hexosamine concentrations were measured. Radiographs of some femora were taken and paraffin cross sections were made at the midshaft of others. Femora in the caffeine group were wider, periosteal bone area/total bone area was greater, the cross sectional area of femoral bone was smaller, and there were fewer osteocytes/bone area than in controls. Calcium, phosphorus, zinc, and hydroxyproline concentrations in the caffeine group were less in both bones of the caffeine group. These results indicate that if animals are exposed to caffeine during the rapidly growing period, changes occur in femoral bone which are similar to those that occur with aging. |
8042201 | Differential regulation of muscarinic receptor subtypes in rat brain regions by repeated injections of parathion. | Repeated injections with increasing moderate doses of parathion into adult male rats for 21 days resulted in 84-90% inhibition of acetylcholinesterase in the brain without overt signs of toxicity. Muscarinic acetylcholine receptor (mAChR) affinities for ligands were unaffected, but there was significant down-regulation of the m4 receptor subtype gene product, m1 mRNA and m3 mRNA in the frontal cortex as well as the m4 subtype and m4 mRNA in the striatum. However, in the hippocampus, there were no significant reductions in either the m1 receptor subtype nor its mRNA. The data suggest that the receptor subtype down-regulations in the cortex and striatum are due to reductions in mRNA expression. Since the degrees of inhibition of acetylcholinesterase were similar in the 3 brain regions, it is suggested that the in situ concentrations of paraoxon were also similar. Accordingly, the absence of down-regulation of the m1 receptor in the hippocampus is not due to a lower concentration of paraoxon than in the cortex or striatum. It is possible that injections of higher parathion doses would produce down-regulation of mAChRs in the hippocampus, and that the hippocampus may have differences in the feed-back mechanisms for receptor regulation from those in the frontal cortex and the striatum. |
8042200 | Methylglyoxal toxicity in mammals. | Although the interest is growing towards glyoxalases and methylglyoxal, their role in metabolism is still an enigma. In this paper, the effects of methylglyoxal in both in vivo and in vitro mammalian systems are reviewed and correlated with its interaction with macromolecules (nucleic acids, proteins). The theories on the role of methylglyoxal and glyoxalases are also discussed. Recently, data obtained have focused attention on the possible role of disturbed methylglyoxal metabolism in the development of diabetic complications and it is hoped that the contribution of methylglyoxal to pathological events can be ascertained in the near future. |
8042199 | Thirteen-week oral toxicity study of magnesium chloride in B6C3F1 mice. | Magnesium chloride (MgCl2.6H2O) was administered at dietary levels of 0 (control), 0.3, 0.6, 1.25, 2.5 or 5% to groups of 10 male and 10 female B6C3F1 mice for 13 weeks. In both sexes of the 5% treatment group a decrease in body weight was observed. While clinical signs and hematological or blood biochemistry parameters showed no treatment-related effects, histopathologically, vacuolation of kidney tubular cells was apparent in males of the 2.5 and 5% concentration groups. Thus, the study demonstrated that diet containing over 2.5% MgCl2.6H2O exerts toxic effects in B6C3F1 mice. We therefore conclude that a 2.5% level of MgCl2.6H2O in the diet is the minimal toxic dose. |
8042196 | Functional morphological alterations of human blood platelets induced by oxidized low density lipoprotein. | The effect of oxidized low density lipoprotein (LDL) on the functional morphology of human platelets in vitro was studied by means of transmission electron microscopy. The washed platelets, stimulated by oxidized LDL (50-300 micrograms protein/ml), showed disc-sphere transformation, centralization of granules and complete degranulation in a dose- and time-dependent manner. A cytodamage in platelet membrane was induced by oxidized LDL leading to a lower electron density of cytoplasm compared to control. The morphological observations were supported by an analysis of the platelet shape-change parameter. Since the shape change, induced by oxidized LDL (50 micrograms/ml), was inhibited by a preincubation of platelets with staurosporine (10 nM), the protein kinase C was probably involved in the platelet activation initiated by oxidized LDL. The present results suggest that oxidized LDL could contribute to pathological thrombosis and atherogenesis by activating platelets. |
8042195 | A simple quantitative assay for ristocetin cofactor activity using microtiter plate and ELISA plate reader. | Ristocetin cofactor activity is the test of choice for diagnosing von Willebrand disease. There is however no simple and precise quantitative method for its rapid determination in the clinical laboratory. We describe here a new approach for measuring ristocetin cofactor activity using an ELISA plate reader. Paraformaldehyde-fixed platelets, diluted plasma samples and ristocetin were mixed and incubated in the wells of a microtiter plate. Platelet agglutination was measured by light absorbance at 405 nm. Measurements of platelet agglutination at 1x to 64x dilution of a normal pooled plasma were used to construct a standard curve. Further characterization showed a significant linear correlation between results determined by the new method and by an aggregometer assay (p < 0.0001), and that the intra- and inter-assay variations were 6% and 17%, respectively. Therefore, the newly developed assay provides a simple and rapid way for precise quantitation of plasma ristocetin cofactor activity. |
8042194 | Platelet adhesion to collagen under flow conditions in diabetes mellitus. | Since vascular complications in diabetes mellitus are attributed in part to blood platelets, our study tested the hypothesis that adhesion of platelets to collagen is enhanced in diabetic subjects. Platelet adhesion kinetics to type I collagen in the presence of plasma were evaluated by a new continuous-flow, micro-adhesion assay combined with resistive-particle counting to detect the loss of single platelets between 0.3 and 2.3 sec. Adhesion was also studied in a magnesium-containing Krebs-Ringer buffer to help assess whether the platelets themselves might be abnormal. We did not observe any differences in adhesion kinetics to collagen between the insulin-dependent (type I), the non-insulin dependent (type II) diabetics and the control subjects for platelets suspended in plasma or in washed platelets (p > 0.05). These findings suggest that platelet adhesiveness to type I collagen is not enhanced in diabetic subjects and is unlikely to contribute to the development of vascular complications. |
8042193 | Platelet release reaction during EDTA-induced platelet agglutinations and inhibition of EDTA-induced platelet agglutination by anti-glycoprotein II b/III a complex monoclonal antibody. | To characterize the nature of EDTA-induced platelet agglutination, the spontaneous release of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) was examined during EDTA-induced platelet agglutinations. A slight release of beta-TG and PF4 was observed when EDTA-anticoagulated whole blood from cases with EDTA-induced platelet agglutination was kept for 60 minutes, whereas a high spontaneous release of these proteins was found from normal blood anticoagulated with EDTA. These findings imply that EDTA-dependent platelet agglutinin may stabilize the platelet membrane surfaces. Secondly, we found that pretreatment of fresh blood with anti-glycoprotein (GP) II b/III a complex monoclonal antibody dramatically reduced EDTA-induced platelet agglutinations. This study indicated that the binding sites of EDTA-dependent antibody might be GP II b/III a complex. The use of an anti-GP II b/III a complex monoclonal antibody may be useful in avoiding analytical errors in some cases with EDTA-induced pseudothrombocytopenia. |
8042192 | Influence of co-incubation and cell number of platelets and polymorphonuclear leukocytes in cellular inhibition and activation phenomena. | Evidence indicates that complex interactions occur between blood platelets and polymorphonuclear leukocytes (PMN) referring to both activation and inhibition phenomena. We studied the influence of co-incubating activated PMN and platelets at varying cell counts in the production of two active metabolites, thromboxane A2 (TxA2) measured as thromboxane B2 (TxB2) and platelet activating factor (PAF). The decrease observed in the quantity of TxA2 synthesized by 2 x 10(8) platelets/ml in the presence of physiological PMN counts clearly indicates an inhibitory effect of PMN in AA-derived metabolites. This suggests there is an influence of PMN-released products on activated platelets, decreasing their capacity to synthesize TxA2. Moreover, we found that the addition of platelets, which do not make measurable quantities of PAF, to PMN suspensions significantly decreased the capacity of PMN to synthesize this mediator. Together with this inhibiting action we also observed an activating effect, in such a way that the more PMN were added to platelet suspensions the more TxA2 was produced. Conversely, the maximal amounts of PAF were synthesized when the highest platelet count suspensions were added to PMN. In summary, the results we present here clearly show cellular interactions between platelets and PMN that directly influence the amounts of metabolites synthesized by both cells. |
8042191 | In vitro studies on the effect of thromboxane receptor blockade on platelet deposition on vascular surfaces. | The efficacy of platelet inhibition by a thromboxane receptor antagonist (Bay U3405) and acetylsalicylic acid was investigated in vitro using a new perfusion system. Rabbit 51Cr-labeled platelets were suspended in saline as perfusate. Vascular grafts, PTFE or Dacron (precoated with blood or uncoated) as well as native aorta were perfused in vitro. Three sets of grafts (vessels) were perfused simultaneously with either acetylsalicylic acid (10(-5) M), Bay U3405 (10(-6) M) treated or untreated (control) labeled platelets. Platelet deposition on the grafts (vessels) was measured in a gamma counter. Values were normalised to graft weight or vessel surface area respectively and to the platelet concentration of perfusate. The results of these experiments indicated that thromboxane receptor inhibition was superior to cyclooxygenase blockade in preventing platelet deposition on synthetic grafts and native aorta vessels in vitro. Whether this is valid in vivo has to be confirmed. |
8042190 | Sulfhydryl compounds influence immunoreactivity, structure and functional aspects of lipoprotein(a). | Human plasma Lp(a) is susceptible to various sulfhydryl compounds. In this study we present evidence indicating that after treatment of Lp(a) with sulfhydryl compounds, immunoreactivity is changed, structural changes occur and functional characteristics regarding the numerous kringle structures in apo(a) disappear. Purified Lp(a) was subjected to variable concentrations (0.01-10 mM) of various sulfhydryl compounds: DTT, 2-mercapto-ethanol (BME), N-acetylcysteine (NAC) and homocysteine (HCys). Free SH groups were blocked by iodoacetamide. Reduced and alkylated Lp(a) was tested in two ELISAs, one detecting apo(a) alone and one detecting apo(a)-apoB complexes. In both ELISAs polyclonal antibodies were used. For comparison a commercial apo(a) IRMA utilizing two monoclonal antibodies was used. The results indicate that a similar decrease in response of both ELISAs is observed, whereas the IRMA response is less affected. Western blotting of "DTT treated" Lp(a) after SDS-PAGE under nonreducing conditions showed that separate apo(a) and apoB-100 bands became detectable at 1 mM DTT. Native PAGE (2.5-16%) indicated structural changes of Lp(a) beginning to occur at 0.03 mM DTT. Epsilon-aminocaproic acid-inhibitable binding of "DTT-treated" Lp(a) to Desafib-X decreased with increasing DTT concentrations in concert with a loss of the capacity of Lp(a) to inhibit plasminogen activation upon treatment with DTT. The observed immunological and functional changes of Lp(a) indicate that apo(a) kringle function is severely affected by sulfhydryl compounds. |
8042189 | Growth factors for human pleural mesothelial cells in soluble products from formed clots. | Fibrin deposition within the pleural space may influence repair following pleural injury. Although the mesothelial surface can organize fibrin, the contribution of pleural mesothelial cells to pleural repair is unknown. During coagulation thrombin cleaves Fibrinopeptide A (FPA, A alpha 1-16) and fibrinopeptide B (FPB) from the A alpha and B beta chains of fibrinogen to generate fibrin monomer. Since these peptides are mitogenic for human fibroblasts, we considered that they might stimulate replication of human pleural mesothelial cells (HPMC). Application of fluid expressed from fibrin clots significantly increased cell number and stimulated uptake of 3H-thymidine by HPMC compared with untreated cells. The mitogenic response of subconfluent HPMC to dilutions of clot fluid (30-150 micrograms/ml protein) was comparable to that of 0.1 nM TGF-beta. Fibrinopeptide A (7.5-30 microM) stimulated 3H-thymidine uptake in HPMC, but FPB had only a slight effect at 30 microM. Antibody to FPA antibody significantly attenuated the mitogenic effect of clot fluid, indicating that a major component is FPA. Our study suggests that fibrinopeptides released during fibrin formation in vivo may stimulate local mesothelial regeneration following pleural injury. |
8042188 | Fibrinolytic compromise by simultaneous administration of site-directed inhibitors of thrombin. | Newly developed synthetic and recombinant thrombin inhibitors possess strong anticoagulant effects. Despite these effects, interactions of these agents with enzymes in the fibrinolytic network result in the modulation of such proteases as t-PA, u-PA and streptokinase. The inhibitory spectrum of several thrombin inhibitors [D-Phe-Pro-Arg-H(GYKI 14166), D-MePhe-Pro-Arg-H(GYKI 14766), Boc-D-Phe-Pro-Arg-H (GYKI 14451), Ac-D-Phe-Pro-boroArg-OH (DuP 714), recombinant hirudin (r-Hir) and unfractionated porcine mucosal heparin complexed with antithrombin III (Heparin/AT-III)] was studied towards various serine proteases such as tissue plasminogen activator (t-PA), plasmin, plasminogen/streptokinase complex, urokinase and kallikrein. Aprotinin was also studied in the same systems as the thrombin inhibitors. All four tripeptide derivatives were found to inhibit t-PA, plasmin and plasminogen/streptokinase complex at micromolar concentrations (IC50: 0.57 mM-3.3 microM). Boc-D-Phe-Pro-Arg-H and Ac-D-Phe-Pro-boroArg-OH also inhibited urokinase, while Ac-D-Phe-Pro-boroArg-OH inhibited kallikrein as well (IC50: 0.15 mM-16 microM). In contrast, r-Hir and Heparin/AT-III did not inhibit any of these enzymes at millimolar concentrations (IC50 > or = 1 mM). Aprotinin inhibited plasmin, plasminogen/streptokinase complex and kallikrein at micromolar concentrations (IC50: 3.1-0.85 microM). In a rabbit thrombolysis model, where pre-formed clots are lysed by streptokinase, simultaneous administration of D-MePhe-Pro-Arg-H or Ac-D-Phe-Pro-boroArg-OH, at concentrations approximately 1 mumol/kg, i.v. resulted in complete inhibition of the fibrinolytic process. Aprotinin at 0.1 mumol/kg, i.v. produced similar inhibition. These results demonstrate that thrombin inhibitors may exert significant antiprotease actions against various fibrinolytic enzymes. |
8042187 | Inhibition of factor Xa-induced platelet aggregation by a selective thrombin inhibitor, argatroban. | In the present study, a direct selective thrombin inhibitor, argatroban, and an indirect non-selective inhibitor, heparin, were examined for the inhibitory effect on factor Xa-induced platelet aggregation. Platelet aggregation was induced by thrombin or factor Xa+prothrombin in the presence of Ca++ using rabbit gel-filtered platelets. IC50 of argatroban on factor Xa-induced aggregation was 5-7 times higher than that on thrombin-induced aggregation, while IC50 of heparin in the presence of antithrombin III on factor Xa-induced aggregation was 90-200 times higher than that on thrombin-induced aggregation. This finding suggests that argatroban inhibits thrombin generating on the platelet surface more efficiently than heparin, and this may be one of the reasons for the higher efficacy of argatroban in arterial thrombosis as compared with heparin. |
8042186 | Isradipine decreases arterial thrombogenicity in rabbits. A morphometric and radioisotopic study. | The effect of isradipine, a calcium antagonist, on aortic and iliac wall thrombogenicity was examined in rabbits. After one week of dosing, the abdominal aortic and iliac artery endothelium was abraded using a Fogarthy catheter. One group of animals (n = 8) was dosed for one week with isradipine 0.3 mg/kg. A second group of animals received 10 mg acetylsalicylic acid (ASA)/kg daily in addition, while a third group received the vehicle only. Finally, a fourth group of animals (n = 8) was treated with ASA only. The percentage denuded surface covered with contact (unspread) platelets decreased significantly (p < 0.01) from 14.7 +/- 2.0 to 9.3 +/- 2.1 (6.2 +/- 0.8 to 3.7 +/- 0.4). The amount of contact and spread platelets was diminished from 84.9 +/- 5.6 to 71.4 +/- 4.4 (91.8 +/- 5.3 to 75.2 +/- 4.6). Platelet thrombi decreased from 7.4 +/- 0.9 to 4.6 +/- 1.4 (9.4 +/- 1.9 to 5.2 +/- 0.7) in the aortic and the iliac artery, respectively. In-platelet deposition decreased by 39.9 and 41.9%. Concomitant ASA therapy not only abolished the effect of isradipine but enhanced thrombogenicity, probably as a result of almost complete blockade of vascular PGI2-production. |
8042146 | Receptor-receptor link in membranes revealed by ligand competition: example for dopamine D1 and D2 receptors. | An interaction or link between dopamine D1 receptors and dopamine D2 receptors was found by a ligand competition method, using [3H]raclopride to label dopamine D2 receptors and SCH 23390 to block dopamine D1 receptors. In the presence of endogenous or exogenous dopamine, SCH 23390 increased the binding of [3H]raclopride in post-mortem human striata homogenates or in tissue culture cells containing human dopamine D1 and D2 receptors. In order to reveal such intramembrane receptor-receptor interactions in general, therefore, it appears essential to add two agonists, one for each receptor, and then to block one of the receptors when measuring the binding of a ligand to the second receptor. |
8042145 | Loss of paired-pulse facilitation at the corticostriatal synapse of the aged rat. | Changes in calcium (Ca2+) homeostasis have been proposed to contribute to the aging process. Paired-pulse facilitation, a form of synaptic enhancement that relies upon an accumulation of Ca2+ in the presynaptic terminal, was used to examine the effect of aging at the corticostriatal synapse. Intracellular recordings in striatal neurons from young rats demonstrated a consistent enhancement in the second of two synaptic responses evoked by stimulation of the corpus callosum. In contrast, neurons from aged rats showed a consistent depression of the second synaptic response at identical pairing intervals. These differences were not explained by an age-dependent increase in synaptic depression and demonstrate an alteration in the Ca(2+)-mediated process of presynaptic facilitation. |
8042144 | The effects of chronic haloperidol administration on GABA-immunoreactive axon terminals in rat medial prefrontal cortex. | Several reports have suggested that chronic haloperidol (HAL) treatment induces ultrastructural changes in synapses of substantia nigra, corpus striatum, and medial prefrontal cortex (mPFC) of rat brain. The effects of HAL on specific cortical transmitter systems, however, are not well characterized. Recent studies have indicated that there may be a loss of gamma-aminobutyric acid (GABA)ergic cells in anterior cingulate cortex of schizophrenic subjects and this hypothesis has prompted interest in the question of whether dopamine receptor antagonists, such as HAL, may influence the activity of this transmitter system. This current report describes a quantitative light microscopic analysis of GABA-immunolabeled axosomatic terminals in mPFC of rats treated with HAL decanoate (0.5 mg/kg/day, i.m.) for a period of 4 months. GABA-containing terminals were visualized with an avidin-biotin immunoperoxidase method for localizing anti-GABA antibodies. Computer-assisted image processing was employed to determine the total number of pixels representing GABA-immunoreaction product in axon terminals that were in direct apposition to pyramidal cell bodies. Drug-treated animals showed a significant increase in the number of pixels representing GABA-immunoreaction product in axosomatic terminals of layers II, III, VI, and VI (93%, 63%, 31%, and 43%, respectively). These data are consistent with the idea that chronic HAL administration may be associated with a significant increase in the amount of GABA present in terminals surrounding pyramidal neurons of rat mPFC. The fact that GABA-containing terminals showed the greatest increase in layer II is not consistent with the known distribution of dopamine afferents to this region which is lowest in superficial laminae. Based on the laminar distribution of non-dopaminergic receptor types that have a high affinity for HAL, the effect of this drug on GABAergic transmission could potentially involve changes that are mediated through mechanisms in which 5-HT2 or sigma opiate receptors play a role. |
8042143 | Relationship between asymmetries in striatal dopamine release and the direction of amphetamine-induced rotation during the first week following a unilateral 6-OHDA lesion of the substantia nigra. | In animals with a large unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal dopamine (DA) system the traditional "rotational behavior model" states that amphetamine will induce circling behavior towards the denervated striatum (ipsiversive), that is, away from the side where there is greater amphetamine-stimulated DA release and greater DA receptor stimulation. It is puzzling, therefore, why amphetamine induces contraversive rotation in rats tested 4 days after a unilateral 6-OHDA lesion, despite a 90-95% loss of the dopaminergic input to the striatum by this time. Rats reverse their direction of amphetamine-induced rotation by 8 days post-lesion and turn in the ipsiversive direction thereafter. To try and resolve this paradox, bilateral striatal microdialysis was used to estimate the effects of amphetamine on DA neurotransmission on Day 4 and Day 8 following a large unilateral 6-OHDA lesion of the substantia nigra. On Day 4 post-lesion, amphetamine produced a moderate (around 50% of control) increase in the extracellular concentration of DA in the denervated striatum. This amphetamine-releasable pool of DA was exhausted by a single amphetamine-challenge, because a second injection of amphetamine given 3 h after the first did not produce a comparable increase in DA. It is suggested that on Day 4 post-lesion the amount of DA released by amphetamine in the denervated striatum is sufficient to produce greater DA receptor stimulation on that side, because of DA receptor supersensitivity, and this leads to contraversive rotation. On Day 8 post-lesion, amphetamine induced DA release in the intact striatum but had no effect on extracellular DA in the denervated striatum (DA was nondetectable). On Day 8, therefore, DA receptor stimulation would be greatest in the intact striatum, leading to ipsiversive rotation. In conclusion, it is suggested that the seemingly paradoxical reversal in the direction of amphetamine-induced rotation that occurs over the first week following a unilateral 6-OHDA lesion is consistent with the traditional rotational model, and is due to time-dependent changes in the ability of amphetamine to release DA in the denervated striatum. |
8042142 | Quantitative autoradiography of the serotonin transporter to assess the distribution of serotonergic projections from the dorsal raphe nucleus. | The binding of 3H-CN-IMI to 5-HT uptake sites, as measured by quantitative autoradiography, was used as a marker of serotonergic neurons. Within the dorsal raphe nucleus the binding of 3H-CN-IMI was compared in adjacent coronal sections of rat brain to the binding of 3H-DPAT to 5-HT1A receptors, which have a known somatodendritic localization. The heterogeneous pattern of binding of these two radioligands within the dorsal raphe nucleus was similar and corresponded to the distribution of serotonergic cell bodies as visualized by 5-HT immunohistochemistry. Intracerebroventricular administration of 5,7-dihydroxytryptamine (5,7-DHT), which caused a dramatic loss of 5-HT immunoreactivity and 3H-DPAT binding to 5-HT1A receptors, resulted in a marked reduction of 3H-CN-IMI binding in this nucleus. Treatment of rats with a dose of para-chloroamphetamine (PCA) which has been reported to selectively lesion serotonergic processes arising from the dorsal raphe nucleus, while sparing serotonergic cell bodies and projections from the median raphe nucleus, did not alter the binding of 3H-DPAT or 3H-CN-IMI in the dorsal raphe nucleus; serotonergic cell bodies appeared morphologically unaffected. The lack of effect of PCA treatment on the binding of 3H-DPAT and 3H-CN-IMI is consistent with a somatodendritic localization of the 5-HT transporter in the dorsal raphe nucleus. PCA treatment appeared to produce a moderate loss of serotonergic innervation in serotonergic terminal field areas as visualized by serotonin immunohistochemistry. The reductions in 3H-CN-IMI binding observed in terminal field areas (24 to 69%) following treatment of rats with PCA did not reflect a marked differential innervation of forebrain areas by the dorsal and medial raphe nuclei as expected from previous biochemical studies, and were not entirely consistent with the findings of neuroanatomical studies using histochemical techniques. Site-specific injection of 5,7-DHT into the dorsal raphe nucleus produced an 80 +/- 11% reduction in the binding of 3H-CN-IMI in this nucleus, whereas the binding of 3H-CN-IMI in the median raphe nucleus was not reduced.(ABSTRACT TRUNCATED AT 400 WORDS) |
8042141 | Periodontal conditions in medically compromised elderly subjects: assessments of treatment needs. | Periodontal conditions were studied in 42 dentate elderly subjects (mean age, 84.1 +/- 8.0 years). None of them had received recent dental care or was routinely seen by a dentist. Overall, they had 20.2 +/- 7.1 teeth (range, 6-32). The CPITN was used to assess periodontal status. Twenty-nine percent of all sextants were either edentulous or had only one remaining tooth. The overall oral hygiene was poor (Plaque Index, 1.8 +/- 0.5) and gingival inflammation severe (Gingival Index, 1.9 +/- 0.8). Significant correlations were found between: Gingival and Plaque Indices (r = 0.82, p < 0.001), and pocket depth and Gingival Index (r = 0.38, p < 0.05). Plaque Index was negatively correlated to the number of remaining teeth (r = -0.43, p < 0.050). Age and remaining teeth were negatively correlated (r = -0.38, p < 0.05). Thirty percent of the posterior sextants had a CPITN score of "4," and 75% of the posterior sextants had at least one site with a pocket depth 4 mm. Only 2.9% of all sites demonstrated pocket depth 6 mm and these sites were distributed among 67% of the subjects. The CPITN index was correlated to the mean pocket depth for the various sextants, the correlation varying between r = 0.67, p < 0.001 (upper right posterior) and 0.36, p < 0.05 (upper left posterior) sextants. The total manpower estimated to complete initial therapy for 42 patients was approximately 63 hours by a dentist and 85 hours by a dental hygienist. |
8042139 | Appliance therapy for chronic drooling in a patient with mental retardation. | Multiple physical impairments are associated with chronic drooling. This case illustrates the use of a simple appliance to align the patient's lip to provide opportunity for a lip seal when swallowing or at rest in a patient with a Class II malocclusion. The appliance resulted in a significant decrease in drooling in this patient. |
8042138 | Bond strength of double-sided adhesive tapes used for facial prostheses. | This study evaluated the tensile bond strengths of five silicone facial elastomers to human skin by use of five different double-sided adhesive tapes. Discs of silicone elastomers were fixed in circular metal holders and glued to the inner aspect of a forearm with the various adhesive tapes. The specimens were pulled off 20 seconds after fixation by means of a universal testing machine at a cross-head speed of 1 mm/min. Eight specimens of each silicone/tape combination were tested. Significant differences were observed among the various silicone/tape combinations. MDX4-4210 and Cosmesil facial elastomers had the strongest bond to skin with the majority of adhesive tapes, whereas Silskin II, Cosmesil HC2, and RS 330T-RTV were the weakest. After the bond failure, tapes remained adhered to the skin and not to the silicone specimens. |
8042137 | Fragile X (Martin-Bell) syndrome. | Fragile X syndrome is a common condition resulting from a cytogenetic abnormality in the X chromosome. Mental retardation, characteristic facies, and large testes are some of the most important characteristics of the condition. The relatively high incidence of the syndrome--approximately one per thousand--the high incidence of cardiac anomalies in these individuals, the oral and facial features associated with the condition, and the paucity of reported cases in the dental literature make it particularly interesting to dentistry. Here we report the case of a 12-year-old male, including the cytogenetic and cephalometric analyses, presenting with some of the classic features and some features not commonly reported. |
8042136 | Factors related to acceptance of dental treatment services in a nursing home population. | This study reports on factors related to acceptance of restorative, oral surgery, and prosthodontic dental treatment services by a population of nursing home residents. Lower cost treatment plans and eligibility for Medicaid benefits were associated with acceptance of all treatment, and for the categories of oral surgery and prosthodontic services. Acceptance of routine restorative procedures was more strongly associated with female residents. It is concluded that financial concerns appear to pose the greatest barrier in providing dental treatment services to nursing home residents. |
8042135 | Preanesthesia transfusion and sickle cell anemia patients: case report and controversies. | Preoperative transfusion of sickle cell anemia (SCA) patients prior to general anesthesia is considered a routine procedure to ensure adequate levels of normal adult hemoglobin A to prevent a sickle cell crisis. Blood transfusion risks have led some clinicians to question this procedure. A case report is presented in which a SCA patient developed a delayed hemolytic reaction from a transfusion given prior to dental treatment under general anesthesia. The controversy of transfusion in this patient group is presented. |
8042134 | Dental management of the geriatric patient with major depression. | Major depression is a psychiatric disorder in which mood, thought content, and behavioral patterns are impaired, often for an extended period of time. The condition is encountered among elderly persons admitted to the hospital and those residing in nursing homes. Major depression is predominantly biologic in origin and may arise from dysfunction of the limbic-hypothalamic-pituitary-adrenal axis. It is associated with personal neglect, including a disinterest in performing appropriate preventive oral hygiene techniques. The majority of antidepressant medications cause xerostomia and magnify the incidence of dental disease. Appropriate dental management of patients with the disorder necessitates the use of anti-caries agents containing fluoride, saliva substitutes, and special precautions when analgesics and local anesthetics are being prescribed or administered. Dental treatment helps to improve the patient's self-image and quality of life. |
8042133 | Elderly nonrespondents to a mail survey: a telephone follow-up. | The most frequently used method to request and collect health-related information has been the mail questionnaire. While self-administered surveys offer a relatively low-cost and convenient method for collecting health data, they have been unpopular among researchers because of concerns about low response rates and nonresponse bias. This study examines differences in demographic and health characteristics between mail survey respondents and nonrespondents who were subsequently interviewed by telephone. Subjects for this study had at least one health care encounter in 1990 from a Medicare-waiver program. The telephone survey was conducted approximately two months after the last wave of a three-wave mailing survey of this urban elderly population. No significant differences were found between telephone and mail respondents for demographic, socioeconomic, quality of life, or perceived oral health characteristics. However, mail respondents were more likely to be dentate and report better perceived general health than were the telephone respondents. |
8042132 | Dental management of long-term amyotrophic lateral sclerosis: case report. | Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease. Methods of dental treatment of a young male patient with ALS are presented. This case is unusual in several respects: the early age of onset, the long survival time, and the period of time in which the case was followed in our dental clinic. Aspects of ALS which are of concern to dentistry, as related to clinical care and strategies for effective oral health delivery, are presented. |
8042131 | Periodontal pocketing in HIV-associated periodontitis. | Gingival and periodontal involvement has been described in individuals with Human Immunodeficiency Virus (HIV) infection. The manifestations often include erythematous gingivitis, necrotizing gingivitis, and periodontal involvement characterized by rampant loss of bone and soft tissue, resulting in recession without the formation of periodontal pockets. We present cases of HIV-associated periodontitis (HIV-P) in which advanced periodontal pocket formation was present. Periodontal disease may show a broad range of severity in patients with various T4 helper cell counts. |
8042130 | A comparison of oral health in spinal cord injury and other disability groups. | A controlled pilot study determined oral health in persons with quadriplegia due to spinal cord injury, and compared dental disease rates in spinal cord injury and other disability groups. Seventeen adults with spinal cord injury and 17 controls were assessed for dental/medical/social history; manual function; head, neck, and oral lesions; salivary flow; DMFS; and gingivitis, periodontal pockets, plaque, and calculus. Findings were compared with those from prior studies according to the same protocol, for groups of similar age with mental retardation, cerebral palsy, traumatic brain injury, and chronic mental illness. No significant differences between spinal cord injury and control subjects were noted, except that fewer spinal cord injury subjects brushed daily or flossed (p < 0.05); dependent subjects tended to have more plaque and gingivitis than those brushing independently. Subjects with spinal cord injury and mental illness had less gingivitis than those with mental retardation and cerebral palsy (p < 0.001); on calculus, subjects with spinal cord injury ranked lower than subjects with mental illness (p < 0.05). On DFS, mentally ill subjects and those with traumatic brain injury ranked higher than mentally retarded and cerebral palsy groups, with spinal cord injury subjects intermediate. Mentally retarded and traumatic-brain-injured subjects had fewer teeth than other groups (p < 0.05). The findings suggest differences in oral health status and oral care for various disabled populations. |
8042129 | Development of sexually transmitted diseases treatment guidelines, 1993. New methods, recommendations, and research priorities. STD Treatment Guidelines Project Team and Consultants. | To develop the 1993 Sexually Transmitted Diseases Treatment Guidelines, experts from the Centers for Disease Control and Prevention reviewed the literature on sexually transmitted disease treatment, assembled tables of evidence, and listed key questions on therapeutic outcome: microbiologic cure, alleviation of symptoms, and prevention of sequelae and transmission. At a meeting with external experts, evidence was systematically assessed and guidelines developed. Quality of evidence for microbiologic cure was generally good for gonorrhea and chlamydia, poor for syphilis, and fair for most other diseases. Evidence on preventing sequelae and transmission was limited. The Guidelines include new recommendations for single-dose oral therapy of gonorrhea (cefixime, ciprofloxacin, and ofloxacin), chlamydia (azithromycin), and chancroid (azithromycin); outpatient therapy of pelvic inflammatory disease (ofloxacin and either clindamycin or metronidazole); and patient-applied therapy of genital warts (podofilox). Syphilis therapy did not change substantially. Several global issues that emerged during the development of the World Health Organization Recommendations for the Management of Sexually Transmitted Diseases also are discussed. This evidence-based approach clarified important treatment issues and the rationale for recommendations, and identified research priorities. |
8042127 | Notes on currently used public health measures for sexually transmitted diseases. | Traditional public health measures for sexually transmitted diseases (STDs) have been to create laws that allow the society to investigate and treat assumed cases of STD. Such laws often include STD that in many communities are rare, but left out very common ones, e.g., genital chlamydial and human papillomavirus infection. However, such laws do not often stress the rights of infected persons to receive counseling, confidentiality, and help to notify the partner(s) if asked for. Although, free health care may be provided at venereal (STD) clinics, this is not true for many other types of clinics or at private clinicians, thereby restricting the choice of physician. In spite of partner notification being a must to successfully combat any STD epidemic of treatable STD, this measure is far from regularly undertaken. The introduction of DNA-based tests have provided new sensitive means for detection STD-infections by testing urine. Screening such samples for STD agents has proven cost beneficial in most societies. Treatment recommendations for STD ought to be accompanied by making suitable drugs available at prices that can be paid by affected persons or being free of charge (which may be important for teenagers and others without income). It is important that health authorities constantly update treatment recommendations. |
8042126 | Human papillomavirus in genital carcinogenesis. | Human papillomavirus (HPV) is known to induce three different manifestations: clinical, subclinical, and latent infection. Clinical infections (exophytic, endophytic, or flat condylomas) frequently are associated with intraepithelial neoplasia and invasive squamous cell cancer. Colposcopy, cytology, and histopathology play a central role in diagnosis of clinical HPV infections, whereas DNA hybridization techniques and DNA amplification with polymerase chain reaction (PCR) are needed to detect the subclinical and latent HPV infections. The biologic behavior of genital HPV infections is a complex one: regression, persistence, progression, and fluctuation are recognized disease patterns. In young women, the prevalence of HPV infections in Papanicolaou smears is 3%, and the annual incidence approximately 8%. The lifetime risk approaches 80% for women between 20 and 80 years of age. The number of sexual partners during the past 2 years (relative risk [RR] > 9.0) and current smoking (RR > 5.0) proved to be the two most significant risk factors for clinical HPV infection in a recent case-control study. In the author's prospective follow-up study, clinical progression was significantly related to the grade of HPV lesion (P < 0.0001), and to HPV type, with the progression rate of HPV 16 lesions being more than five times greater than that of HPV 6 or 11 lesions. The detection rate of HPV in men is significantly lower (approximately 30%) than in women, and the concordance of HPV types in the couples having sexual relations is surprisingly low (5% to 10%).(ABSTRACT TRUNCATED AT 250 WORDS) |
8042125 | Rapid sexually transmitted disease assessment in two developing countries. | Two rapid assessment studies of the magnitude of sexually transmitted disease (STD) were performed in Senegal and Uganda in 1989 and 1990. The study objectives were: to develop and validate STD indicators for the "rapid" assessment of the frequency of STD in populations; and to develop a standardized survey methodology to assess STD prevalence using these indicators. The World Bank, World Health Organization (WHO), and Senegal and Ugandan government officials desired a product similar to the WHO/UNICEF immunization coverage survey instrument, which is an accepted and proven methodology, implemented by national programs and donors worldwide. Three indicators were used: 1) past or present signs of selected STD; 2) symptoms as noted by a clinician; and 3) simple laboratory tests performed and results obtained at examination. Each indicator was validated against a confirmatory laboratory test considered the gold standard in indicating the presence or absence of an STD. Male military members, women seeking prenatal care, and female prostitutes were the three population groups chosen. With the exception of the rapid plasma reagin (RPR) test for syphilis, symptoms, signs, and simple laboratory tests failed to accurately predict STD in individuals in all three of these population groups. Indicators for the major STD other than syphilis among populations not seeking STD care will have to be the "gold standard laboratory tests" until easy-to-perform and low-cost alternatives are found. |
8042124 | Epidemiology of sexually transmitted diseases. What does it tell us? | Incidence numbers of Neisseria gonorrhoeae, Treponema pallidum and Chlamydia trachomatis differ substantially in different countries at different times. In European countries, the incidence of gonorrhea and of primary and secondary syphilis currently is extremely low. In North American countries gonorrhea incidence declined at a very slow annual rate and syphilis incidence increased. Chlamydial infections show a profile that seems to be delayed by two decades from infections with Neisseria gonorrhoeae. Our efforts in the future should be directed to prevent the resurgence of gonorrhea and syphilis and to achieve the same success with chlamydial infections. Poor populations in developed and developing countries, which have similar demographic, social and economic characteristics, represent one important target group for control programs. Education of young and poor people represent the challenge of the future for sexually transmitted diseases control strategies. Combined strategies also will have an effect on incurable viral STD. |
8042123 | Recent changes in the epidemiology of genital ulcer disease in the United States. The crack cocaine connection. | The incidence of syphilis and chancroid began to increase in the United States among heterosexuals in the mid-1980s, with most cases reported among minorities living in Eastern cities and in the South. A number of studies have established a link between increasing syphilis incidence rates and cocaine use, specifically the smoked form of the drug, which is known as "crack." A similar link was hypothesized for chancroid, but supporting data became available only recently. In New Orleans, we showed that Haemophilus ducreyi infection in male patients was strongly associated with crack cocaine use. However, our studies also demonstrated that drug use by the patient actually was a marker for a more important risk factor: sexual exposure to a cocaine-using woman. Thus, although the details of the relationships among crack, sexual behavior, and the size and nature of core transmitter groups are not known, it is clear that crack cocaine abuse is the driving force behind the recent syphilis and chancroid epidemics in the United States. Although it is not possible to predict the effects of these events on human immunodeficiency virus (HIV) transmission, the potential for significant synergism between them exists. New approaches to HIV surveillance should be developed taking this possibility into account. During the last 3 to 4 years, incidence rates of syphilis and chancroid have fallen in the United States, despite continued problems throughout the country with crack cocaine abuse. However, our studies and those of others have shown how difficult it is to recognize chancroid clinically, suggesting that the disease may be grossly underreported.(ABSTRACT TRUNCATED AT 250 WORDS) |
8042122 | Sexually transmitted disease prevention approaches that work. Interventions to reduce risk behavior among individuals, groups, and communities. | Behavior change remains the only available means to curtail new HIV infections. Although much remains to be learned about the effectiveness of different prevention strategies, there has already been evidence that both face-to-face interventions focused on individuals and community-level interventions focused on vulnerable communities can produce substantial reductions in high-risk sexual behavior. This article briefly describes the results of controlled outcome studies that have employed cognitive-behavioral and norm change elements to reduce HIV risk behaviors in face-to-face and community-level trials with both inner-city women and homosexual men. |
8042121 | Sexually transmitted diseases in the 1990s. Global epidemiology and challenges for control. | Epidemiologic trends of STD are strikingly different in various parts of the world. In Northern and Western Europe there has been a spectacular decline in the incidence of STD, particularly gonorrhea and syphilis. It is probably due to a combination of an early initiation of sex education at school, behavior change, condom promotion, and the wide availability of STD treatment. The situation in North America is far more complex, with geographic areas and large population groups having low levels of STD and others continuing to experience an epidemic of STD, particularly inner-city minority populations in the United States. In developing countries both the prevalence and incidence of STD are still very high and STDs are a major public health problem making up the second cause of healthy life lost in women of 15 and 45 years of age after maternal morbidity and mortality. "Business as usual" is clearly not acceptable any longer. A better understanding of the determinants of STD epidemiology is essential for a more effective approach to STD control as well as recognizing the limitations of each single intervention, be it medical or behavioral. The major challenges are to mobilize political commitment and funds, and to transfer small scale interventions into large scale public health programs, and to apply the right mix of approaches, including medical, behavioral, societal interventions. |
8042120 | Sex and disease. Playing the odds in the 1990s. | Selected results from a recent study on sexual behavior in the United States are presented, focusing on the association between sexual behavior, disease prevention, and STD outcome. The data are from national household samples of adult men and women. The results show that a sizeable proportion of the U.S. adult population engage in sexual behaviors that expose them to the risk of acquiring STD. These behaviors tend to cluster so that the likelihood of engaging in one high-risk sexual activity is highly correlated with the likelihood of engaging in the other high-risk behaviors thereby increasing the risk of STD acquisition for these core groups. Although preventive behavior is relatively more prevalent in core groups, it is nowhere near the desired level, nor is it uniform across the risk groups. High-risk sexual behaviors are strongly correlated with the likelihood of self-reported STD experience, and prior STD history is strongly associated with subsequent preventive behavior. |
8042119 | Sexual behavior in sexually transmitted disease research. An overview. | Determinants of sexually transmitted disease (STD) incidence have been described at the individual and the population level of analysis. Some issues of measurement remain unresolved in the assessment of risk and preventive behaviors. In general, risk behaviors (sexual, substance abuse, health) and contextual determinants of risk tend to occur together. Population prevalence of many STD risk behaviors is higher among minority populations of lower socioeconomic status. The major issues related to the choice of target groups involve lack of adequate data. Different behavioral interventions may be more appropriate for specific STD. The most important unresolved issue in the context of intervention research may be that interventions to change sexual behaviors are not supported by conclusive empirical evidence. In the past, in most countries, policy instruments have not been used effectively to achieve risk-reducing changes in sexual behavior. Elaboration of these points provides a description of the state of behavioral issues in STD research. |
8042118 | Sexually transmitted diseases and reproductive health. | Sexually transmitted diseases (STD) are a major health problem, particularly for women in developing countries. Serious sequelae include ascending infections leading to chronic discomfort, ectopic pregnancy and infertility, cervical cancer, and adverse pregnancy outcomes. Primary prevention involves sexual behavior modifications and condom use, and secondary prevention targets early and appropriate management of STD and reproductive tract infections (RTI). There is an urgent need for comprehensive preventive and curative reproductive health services, as well as for inexpensive, simple, rapid, and convenient STD diagnostics and treatment regimens. Female controlled barrier methods are a priority in the field of applied research. In additions, women's voices have to be heard in health and development programs. |
8042117 | Sexually transmitted disease and human immunodeficiency virus. Is everyone at risk and does everyone have to pay? | The pattern of disease within populations depends on the complex interaction between individuals. For example, the linking of individuals to form social and sexual networks affects disease incidence and prevalence. As described by Potterat, the formation of these networks results in various patterns of disease spread. However, phenomena that occur among individuals do not necessarily mirror those observed in groups or populations. The interactions that characterize the relationship between individual and group level phenomena were considered during this session of the Tenth International Meeting of the International Society for STD Research. By examining these interactions we hoped to address the following two questions: Are all individuals equally at risk for sexually transmitted diseases (STD) and infection with human immunodeficiency virus (HIV)? and Must the costs and benefits of interventions designed to prevent these outcomes be divided equally among all individuals to ensure the success of such interventions? |
8042116 | Epidemiology of sexually transmitted diseases. | The epidemiologic patterns of sexually transmitted diseases (STD) in developed countries are changing, but the picture is different in Europe and the United States. General trends are summarized. |
8042115 | Epidemiology and control of sexually transmitted diseases in developing countries. | The knowledge of the epidemiology of STD in the developing world had increased considerably during the last decade. This better understanding combined with the emergence of the epidemic of a new fatal STD (HIV) encouraged health planners to define appropriate effective and feasible STD control strategies. Major progress has been made with regard to the primary prevention and optimal case management of STD, both in terms of strategies and feasibility of implementation in field conditions. |
8042114 | The current trend in genital herpes. Progress in prevention. | Recent serosurveys indicate that the prevalence of genital herpes has continued to increase even during the decade of HIV. Much of this continued transmission is due to the difficulty of identifying the subclinical carrier of HSV-2. The development of serologic assays that accurately distinguish HSV-1 from HSV-2 infection now allow such persons to be identified, and recent studies indicate almost all HSV-2 seropositives have symptoms and signs of reactivation HSV-2. Moreover, over 50% will shed virus subclinically in the genital tract. This underestimation of this reactivation rate appears to be another factor in the continued spread of the virus throughout the population. The development of an HSV vaccine is imperative if we are to control this rapidly increasing infection. |
8042113 | Sexually transmitted diseases and infertility. | In both men and women, STD-associated genital infections may cause permanent damage to the reproductive tract resulting in sub- or infertility. In men, the wide zone between sterility and normal fertility makes it difficult to demarcate the precise role of infection on post-infection fecundity, but it seems less important than in women. The reproductive events were studied in a cohort of 1,309 pregnancy-seeking women, < or = 35 years of age, after laparoscopically verified acute salpingitis, and 451 women with normal laparoscopy. Tubal factor infertility (TFI) was diagnosed in 12.1% of the patients and 0.9% of the controls, and the first pregnancy was ectopic in 7.8% and 1.3%, respectively. Of independent importance for infertility, ectopic pregnancy, and time between PID and first intrauterine pregnancy were number of infections, severity of the infections, contraception at the index laparoscopy, age, and delayed treatment. STD-associated in-subfertility is acquired and, hence, preventable. |
8042112 | Human immunodeficiency virus infection and pregnancy. | Vertical transmission from mother-to-child is the main mode of acquisition of HIV infection in children. Infection may be acquired before, during, or after birth, but the relative contribution of each of these routes remains unknown. Estimates of the rate of vertical transmission range from 15% to 39%, and the rate is lower in European studies than in African studies. This variation reflects differences in distribution of risk factors associated with vertical transmission, including maternal clinical and immunological HIV status, and breastfeeding. There is some suggestion that mode of delivery may also be associated with the likelihood of transmission. About 25% of infected children develop AIDS in the first year of life; the prognosis for the remainder is less clear. Increasingly, attention is being given to approaches that aim to reduce vertical transmission, such as avoidance of breastfeeding, cleansing of the birth canal, antiretroviral therapy and passive or active immunization. |
8042111 | Recent advances in diagnosis of sexually transmitted diseases. | In an effort to better diagnose, treat, and control sexually transmitted diseases (STD), a number of new diagnostic assays using molecular techniques have been developed. By incorporating molecular amplification, the sensitivity for detecting sexually transmitted infections has become markedly enhanced, and organisms that were difficult or impossible to cultivate, such as human papillomavirus (HPV) or Treponema pallidum can now be detected and monitored. By using polymerase chain reaction (PCR) or ligase chain reaction (LCR), the sensitivity of detecting some pathogens is comparable to, or in some cases better than, direct in vitro cultivation of the agent. DNA fingerprint analysis of amplified microbial DNA also has been effectively used for detailed study of the epidemiology and pathophysiology of sexually transmitted infections. In addition to direct detection, molecular techniques have been used to enhance serologic techniques by use of cloned proteins and recombinant antigens. These techniques have enabled investigators to differentiate infection caused by closely related pathogens, such as human immunodeficiency virus type 1 (HIV-1) and HIV-2 and human T-cell lymphotrophic virus type 1 (HTLV-1) and HTLV-2. As a consequence of these molecular tools, the diagnostic repertoire of the clinical laboratory for the diagnosis of STD will expand significantly, allowing investigators to better diagnose and more effectively control the spread of STD. However, with such new technology, new problems and challenges have arisen, such as the risk of sample contamination resulting in false-positive results, and the presence of inhibitors resulting in false-negative results.(ABSTRACT TRUNCATED AT 250 WORDS) |
8042110 | Trends in sexual behavior. Analyse des Comportements Sexuels en France Investigators. | The definition of strategies for preventing STD and AIDS requires a better knowledge of sexual behavior in the general population and in specific subgroups of the population. Surveys have been undertaken in different countries to provide such information, and they allow to draw some general conclusions. Even if there exist a very important variability of sexual behaviors between individuals and within individuals in different situations, the primary characteristics of sexual behavior in different developed countries appear to be quite similar. All prevention efforts need to be directed toward everybody in the population, but they must in the same time be made age specific, gender specific, and culture specific. The repertoire of available methods must be expanded to offer different choices, taking into account important psychological and sociologic determinants of sexual behavior. The development of methods under women's control would permit to combine the goals of contraception and of STD prevention. |
8042108 | Inequalities in South African health care. Part II. Setting the record straight. | While Part I of this article analysed the problem of structural inequalities in South African health care, this follow-up explores feasible and socially accountable principles as well as a policy strategy to equalize existing discrepancies and disparities. In addition, the prospects of equalizing the disparities and discrepancies are weighed against prevailing realities. for the foreseeable future the chances for equality in South African health care appear to be rather slim; a myriad interest groups with vested interests in the status quo are at play, opposing any fundamental reform to ensure greater equality. However, what is more important than the acceptance of this fate is our sincere endeavours to minimise these inequalities. |
8042107 | Inequalities in South African health care. Part I. The problem--manifestations and origins. | This exposition analyses and contextualizes the complex problem of structural inequality in South African health care. Socio-economic conditions, racial divisions and geographical location are isolated as the main determinants of inequality in the provision, allocation and distribution of health care; the prevailing inequalities are attributed to a wide range of underlying causes, including the absence of a central, binding health policy, the prominent role of apartheid and white domination, the free market and the medical profession, as well as the unique sociocultural set-up of the country. The urgent need for deliberate strategies to equalize the prevailing disparities and discrepancies is posed. |
8042106 | A national sentinel surveillance network for the measurement of ill-health in South Africa. A prerequisite for epidemiological research and health planning. | Data on births, on deaths by cause and on morbidity are essential in planning appropriate health interventions, but the scarcity of these data in South Africa is striking. Some of the limitations of national mortality and morbidity data collection systems are reviewed. In order to improve the usefulness of vital statistical information, it is proposed that active disease monitoring be introduced in a number of surveillance sites where the population has been properly enumerated. A network of these sites would routinely gather information on births and deaths by cause and on a list of conditions that are: (i) easy to identify clinically; (ii) would bring most people to the attention of health personnel; and (iii) would indicate failure of health service provision, environmental control or resource allocation. The measurement of the geographical variation of a number of conditions, coupled with geographical information on health care indicators and risk and health promotive factors in each site, would facilitate the planning of interventions in a rational manner. |
8042105 | Current thoughts on total hip replacement. | Opinion leaders in the field of total hip arthroplasty express antipodal views with bewildering frequency. New trends notwithstanding, Charnley low-friction arthroplasty has a record of outstanding success, and we should attempt to identify specific problems, and address these accordingly. Biological and biomechanical matching remain important and increased attention to meticulous cement technique should favourably improve the long-term performance of cemented implants. The concept of cementless replacement should not, however, be summarily discarded, particularly for the younger patient. The discovery of existing design limitations should lead to further development based on sound scientific research. In an era of exploding technology, cost-containment must remain a pragmatic reality in the provision of a health-care service to the community. At this stage we would recommend a cementless hip replacement for the very young, hybrid replacement (cemented stem, uncemented cup) for the middle-aged and a fully cemented replacement for the elderly. |
8042104 | Incidence of heat-labile enterotoxin-producing Escherichia coli detected by means of polymerase chain reaction amplification. | Diarrhoea can be caused by many different organisms, some of which are notoriously difficult to identify. One of these is enterotoxin-producing Escherichia coli. Recently a new diagnostic technique that uses polymerase chain reaction DNA amplification was developed for detection of the 'A' subunit of the labile enterotoxin-producing E. coli gene. This technique was used to evaluate the incidence of heat-labile (LT+) enterotoxin-producing E. coli in the causation of diarrhoea. The results from this study showed that LT+ E. coli is a cause of diarrhoea in the western Cape and that 5.3% of non-diagnosed diarrhoea patients in Tygerberg Hospital were infected with this pathogen. This represented less than 1% of the total number of cases of diarrhoea investigated in this hospital. The peak coincides with the wetter months in this locality and the infection rate is lower than that reported in most other countries. Given the low incidence of occurrence of this organism we do not recommend routine implementation of the diagnostic procedure. However, this test may be useful at times, e.g. to ascertain the source of a diarrhoea epidemic. |
8042103 | Haemorrhage--the main presenting feature of diverticular disease of the colon in blacks. | Haemorrhage is one of the less common presentations of diverticular disease. This retrospective 5-year study of 23 patients has identified it as the main presentation (74%) among South African blacks in whom the disease is uncommon, but emerging as a clinical problem. Women constituted a statistically significant majority of patients with bleeding (76%); this was in excess of their overall proportion among patients with diverticular disease (61%) (P = 0.018). |
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