Male Contraception,IV: Hypotonic-Like Effect from Echeveria gibbiflora on Human Sperm

At present there is no accepted method for the regulation of male fertility. The most appropriate form of contraception would undoubtedly be to develop from traditional plant-derived folk drugs a contraceptive male method. Hypoosmotic shock is used for validate plasma membrane function and its fertilizing capacity of human sperm. Such effect is induced in human sperm in the presence of a purified fraction from Echeveria gibbiflora (PFEG) aqueous crude extract. The hypotonic-like effect included a distension of the plasma membrane over the acrosome region and in some occasions around the sperm middle piece. An enhanced activity of the immobilizing and agglutination effects was induced instantaneously after the addition of PEFG versus aqueous crude extract activity (OBACE). Using electron microscopy it was possible to observe a deposit of a ''sticky'' dense material intercalated along the plasma membrane. The membrane was sealed making it impossible to measure the viability or metabolic activity of the treated sperm by the fluorescence (FDA-IP) technique. It was also possible to corroborate the dispersion of the acrosomal content and the disappearance of the acrosomal and nuclear membrane. Results that makes PFEG hypotonic-like effect a serious candidate to conduct a study to determine the predicting capacity of this compound in human infertility and suggest that the plant may yield a compound suitable for use as male contraceptive agent.     

Histopathological lesions of the liver in hairy cell leukemia: a report of 14 cases

Pathological lesions of the liver were studied in 14 cases of hairy cell leukemia, a rare hematologic neoplasm involving numerous organs. Tumor infiltration of hepatic parenchyma was observed in all cases. Tumor cells were easily recognized by their cytological features, namely their "halo" appearance consisting of a clear rim of abundant cytoplasm surrounding uniform round or slightly indented nuclei. Portal infiltration was observed in all cases, associated with sinusoidal infiltration in 12 cases. A peculiar change of the sinusoids, i.e., the angiomatous lesions, was noted in 9 of 14 patients. Angiomatous lesions consisted of intralobular cavities without zonal predominance which were lined by tumor cells which replaced the normal sinusoidal wall and were filled with red blood cells and tumor cells. This pattern of involvement is different from hepatic localization of other blood malignancies and is highly suggestive of hairy, cell leukemia. It might reflect the unique phenotype of the tumor cells, which express lymphocytic and monocytic features. The angiomatous lesion strongly mimics peliosis hepatis and could be, as well as in peliosis, the consequence of modification of the sinusoidal barrier. In hairy cell leukemia, sinusoidal wall abnormalities might be secondary to infiltration of the sinusoids by tumor cells.     

Allergic Conjunctivitis Renders CD4+ T Cells Resistant to T Regulatory Cells and Exacerbates Corneal Allograft Rejection

Allergic diseases rob corneal allografts of immune privilege and increase immune rejection. Corneal allograft rejection in BALB/c allergic hosts was analyzed using a short ragweed (SWR) pollen model of allergic conjunctivitis. Allergic conjunctivitis did not induce exaggerated T‐cell responses to donor C57BL/6 (B6) alloantigens or stimulate cytotoxic T lymphocyte (CTL) responses. Allergic conjunctivitis did affect T regulatory cells (Tregs) that support graft survival. Exogenous IL‐4, but not IL‐5 or IL‐13, prevented Treg suppression of CD4⁺ effector T cells isolated from naïve mice. However, mice with allergic conjunctivitis developed Tregs that suppressed CD4⁺ effector T‐cell proliferation. In addition, IL‐4 did not inhibit Treg suppression of IL‐4Rα^?/? CD4⁺ T‐cell responses, suggesting that IL‐4 rendered effector T cells resistant to Tregs. SRW‐sensitized IL‐4Rα^?/? mice displayed the same 50% graft survival as nonallergic WT mice, that was significantly less than the 100% rejection that occurred in allergic WT hosts, supporting the role of IL‐4 in the abrogation of immune privilege. Moreover, exacerbation of corneal allograft rejection in allergic mice was reversed by administering anti‐IL‐4 antibody. Thus, allergy‐induced exacerbation of corneal graft rejection is due to the production of IL‐4, which renders effector T cells resistant to Treg suppression of alloimmune responses.     

Is adjuvant chemotherapy for bladder cancer safer in patients with an ileal conduit than a neobladder?

OBJECTIVE: To assess the safety of adjuvant chemotherapy in patients with neobladder reconstruction in comparison to ileal conduit, as radical cystectomy and urinary diversion is an effective curative surgical treatment for muscle-invasive and high-risk superficial bladder cancer, and adjuvant chemotherapy is usually considered for patients with clinical stage > T2 and nodal metastasis. PATIENTS AND METHODS: We analysed retrospectively patients who had had a radical cystectomy and urinary diversion between 1992 and 2004. Patients with high-risk disease who had adjuvant chemotherapy were identified and stratified based on the type of urinary diversion (ileal conduit or neobladder). The chemotherapy regimen, complications from the adjuvant chemotherapy and other relevant data were analysed. RESULTS: Overall, 343 patients had radical cystectomy, 40 had adjuvant chemotherapy; 25 had an ileal conduit and 15 had a neobladder. Patient characteristics including age, stage and follow-up were similar. In all, 55% of patients had grade 1 toxicity, 23% grade 2, 18% grade 3, and 13% grade 4. No patients had serious organ toxicity and none died. There were no significant differences in the toxicity among the two groups. CONCLUSIONS: Adjuvant chemotherapy appears to be safe in patients with a neobladder and equally safe in patients with an ileal conduit. Hence neobladder reconstruction should not be denied to patients with bladder cancer who are at high risk of recurrence and who might require adjuvant chemotherapy.     

Tracheoesophageal fistula in an intubated patient. Treatment through exclusion and esophageal patch

Currently, acquired benign tracheoesophageal fistulas are mainly iatrogenic lesions produced by prolonged tracheal intubation. Their occurrence in intubated patients is infrequent but devastating and their therapeutic resolution is highly complex. We present the case of a patient with an extensive tracheoesophageal fistula following tracheal intubation that was surgically treated through esophageal exclusion (cervical esophagostomy and suture-stapling of the distal esophagus) and closure of the tracheal defect using the posterior esophageal wall.     

The absence of chronic rejection in pediatric primary liver transplant patients who are maintained on tacrolimus-based immunosuppression: a long-term analysis

BACKGROUND: Although the outcome of liver transplantation has improved significantly during the past two decades, graft loss caused by chronic rejection after liver transplantation still occurs in 2% to 20% of recipients. The overall incidence of chronic rejection is also reported to be low in adult recipients, and risk factors have been identified. Chronic rejection is associated with the inability to maintain baseline immunosuppression. Additionally, the diagnoses of primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, hepatitis B virus, and hepatitis C virus, common indications for liver transplantation in adults, are associated with a higher incidence of chronic rejection. Fortunately, these diagnoses are rarely seen in children. Little is known about chronic rejection in long-term pediatric liver transplant survivors. The purpose of this longitudinal study was to examine the incidence of biopsy-proven chronic rejection in long-term survivors of primary pediatric liver transplantation under tacrolimus-based immunosuppression. METHODS: From October 1989 to December 1992, 166 children (boys=95, girls=71; mean age=5.0+/-2.9 years) received a primary liver transplant. These patients were followed until March 2000 with a mean follow-up of 9+/-0.8 (range, 7.4-10.4) years. All liver biopsy specimens and explanted grafts were evaluated for evidence of chronic rejection using the International Banff Criteria. RESULTS: The mortality rate during the follow-up period was 15% (n=25). Retransplantation was required in 11% (n=18) of recipients. Actuarial patient and graft survival rates at 10 years were 84.9% and 80.1%, respectively. There were 535 liver biopsy samples available for evaluation, including the 18 explanted allografts. Biopsy specimens of three other functioning allografts showed evidence of chronic rejection. Immunosuppression had been discontinued or drastically reduced in these recipients because of life-threatening infections, noncompliance, or both. On restoring baseline immunosuppression, all three children had normalized liver function and the allografts were maintained; the liver transplant patients who are alive currently have normal liver functions. CONCLUSION: The findings of this study suggest that chronic rejection does not occur in pediatric liver transplant recipients receiving tacrolimus-based immunosuppression, provided baseline immunosuppression is maintained.     

Pancreatitis after liver transplantation in children: a single-center experience

BACKGROUND AND METHOD: Posttransplantation acute pancreatitis (PTAP) is a rare but serious complication after pediatric liver transplantation (LTx). We performed a retrospective review in a large cohort of pediatric liver transplant recipients at a single institution to define the impact of this problem in children. RESULTS: Between January 1986 and December 1999, 634 pediatric LTx were performed. Twenty-six patients developed serious acute pancreatitis. The mean age at transplantation was 7.7 years (9 months to 19 years), and the indications for transplantation were biliary atresia in seven, fulminant hepatic failure in six, chronic rejection in seven, and other etiologies in six patients. PTAP was more likely to occur early after LTx (61% within the first week), was associated with the presence of an infrarenal aortic graft in 14 (54%) of 26 patients, was more likely to occur after retransplantation (11/26 patients), and was associated with blood loss and prolonged surgery in four cases. Acute renal failure occurred in 15 (58%) of 26 patients. Mortality was 42% (11/26); causes of death were sepsis or multiple organ failure in nine and hemorrhage in two patients. Management of PTAP included antibiotics, sphincterotomy, debridement with drainage, hepatic arterial revascularization, and arterial ligation. Of the 14 patients with complicated pancreatitis, 5 were treated conservatively and died. Nine patients had extensive operative interventions and four survived (45%). CONCLUSIONS: Several risk factors such as retransplantation, extensive dissection at the time of LTx, and use of infrarenal arterial graft contribute to development of PTAP in children. Early exploration and debridement in patients with complicated pancreatitis may result in a better outcome. Retransplantation in the presence of clinical pancreatitis has a high failure rate.     

Comparison of 64-slice cardiac computed tomography with myocardial perfusion scintigraphy for assessment of global and regional myocardial function and infarction in patients with low to intermediate likelihood of coronary artery disease

Background. Cardiac computed tomography (CCT) has the potential to assess both coronary anatomy and ventricular function in a single study. We examined the agreement between CCT and myocardial perfusion scintigraphy (MPS) for the assessment of global and regional ventricular function. Methods and Results. Research CCT was performed in 52 patients with a low to intermediate likelihood of coronary artery disease referred for MPS. Left ventricular enddiastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction (LVEF), and myocardial wall motion and thickening were compared between techniques. In addition, myocardial contrast attenuation on CCT was compared with radiotracer uptake on MPS. LVEF values agreed well (mean difference, 4.1%; SD, 15.13%), but CCT left ventricular end-diastolic volume was greater compared with MPS (mean difference, 46.0 mL; SD, 33.34 mL) (P<.001). There was moderate agreement for segmental myocardial motion and thickening, with κ values of 0.57 (95% confidence interval, 0.51–0.63) and 0.47 (95% confidence interval, 0.41–0.53), respectively. Seventeen patients had hypoattenuation in at least 1 myocardial segment on CCT. Three of four patients with concomitant abnormalities of wall motion and thickening on CCT had infarction in the same territory on MPS. Conclusions. There was good agreement for LVEF between CCT and MPS but myocardial volumes differed, and these modalities cannot be used interchangeably. Mild abnormalities of regional function are detected more commonly by CCT than by MPS. Myocardial hypoattenuation on CCT is highly specific for myocardial infarction when associated with reduction of systolic wall thickening and regional wall motion abnormality. Dr Nicol received a grant from the Defence Postgraduate Medical Deanery.