A prospective comparative study on IVF outcomes with either purified FSH or human menopausal gonadotrophin in downregulated normogonadotrophic women

OBJECTIVE: In compare the use of purified follicle-stimulating hormone with that of a preparation containing follicle-stimulating hormone and luteinizing hormone in infertile females undergoing IVF. DESIGN: Open-labelled prospective controlled single-center study. SETTING: Nile Badrawy IVF unit. PARTICIPANTS: 153 infertile females undergoing their first cycle of IVF divided into 2 groups. Interventions: Ovarian stimulation was done with either highly purified FSH for group 1 (n = 75) or human menopausal gonadotrophin group 2 (n = 78) after pituitary desensitization commenced in the midluteal phase of the preceding cycle. Monitoring was performed by ultrasound transvaginal oocyte retrieval followed by IVF and transfer of three embryos. OUTCOMES: Number of oocytes >18 mm at day of hCG, fertilization rate, embryo transfer rate, clinical pregnancy rate and incidence of ovarian hyperstimulation syndrome. RESULTS: The response to ovarian hyperstimulation was similar in both groups. The number of follicles >18 mm achieved at day of hCG was 12.3 +/- 0.9 (mean +/- SEM) following stimulation with 38.3 +/- 0.9 ampoules of Fostimon The Menogon-treated group needed 39.1 +/- 0.8 ampoules to produce 11.6 +/- 0.7 follicles. Fertilization rate (2PN/cell) was 58.6 vs. 64.2% in the Fostimon and Menogon group, respectively (p > 0.05). The number of embryos transferred per woman was 3.1 +/- 0.1 in the Fostimon group and 3.6 +/- 0.1 in the Menogon group. The pregnancy rate per woman was 33.3 vs. 25.6% in the Fostimon- and Menogon-treated groups, respectively (p > 0.05). Miscarriage rate was 16 vs 20%, respectively. However, the incidence of multiple pregnancies was significantly higher in the Fostimon-treated group (32%) vs. 10% only in the Menogon-treated group (p < 0.01). CONCLUSION: Purified FSH yields similar clinical outcome to hMG in terms of oocytes retrieved and clinical pregnancies in a standard IVF regimen.     

Idiopathic nodular glomerulosclerosis is a distinct clinicopathologic entity linked to hypertension and smoking

Idiopathic nodular glomerulosclerosis (ING) is an enigmatic condition that resembles nodular diabetic glomerulosclerosis but occurs in nondiabetic patients. We reviewed clinicopathologic features, immunohistochemical profiles, and outcomes in 23 patients with ING diagnosed from among 5,073 native renal biopsy samples (0.45%) at Columbia University from January 1996 to March 2001. This cohort, in which diabetes mellitus was excluded, consisted predominantly of older (mean age, 68.2 years) white (73.9%) men (78.3%). Clinical findings at presentation included renal insufficiency in 82.6% (mean serum creatinine = 2.4 mg/dL), proteinuria (> 3 g/d in 69.6%; mean 24-hour urine protein = 4.7 g/d), and-less frequently-full nephrotic syndrome (21.7%). There was a high prevalence of hypertension (95.7%; mean = 15.1 +/- 3.4 years), smoking (91.3%; mean = 52.9 +/- 6.9 pack-years), hypercholesterolemia (90%), and extrarenal vascular disease (43.5%). All 23 patients had prominent diffuse and nodular mesangial sclerosis, glomerular basement membrane thickening, arteriosclerosis, and arteriolosclerosis. Immunohistochemical staining for CD34, a marker of endothelial cells, showed an increased number of vascular channels within ING glomeruli compared with normal controls. Follow-up data were available for 17 patients, 6 of whom reached end-stage renal disease (ESRD) (35.3%). By Kaplan-Meier estimates, the median time after biopsy to ESRD was 26 months. Predictors of progression to ESRD included continuation of smoking (P =.0165), lack of angiotensin II blockade (P =.0007), degree of tubular atrophy and interstitial fibrosis (P =.0517), and degree of arteriosclerosis (P =.0096). In conclusion, ING is a progressive vasculopathic lesion linked to hypertension and cigarette smoking.     

Infrainguinal Bypass Graft Patency and Limb Salvage Rates in Critical Limb Ischemia: Influence of the Mode of Presentation

Rest pain, ulceration, and gangrene are often considered together in studies describing outcomes in patients with critical limb ischemia. A retrospective analysis of prospectively collected data of 152 infrainguinal bypass grafts performed on 128 patients with chronic critical limb ischemia over a 6-year period was carried out. Grafts were classified according to the mode of presentation and were followed up by regular clinical and duplex examinations. Mean follow-up period was 29 months (range 12 to 60 months). Patients' demographics, risk factors, and graft characteristics were not statistically different between the groups. The 5-year cumulative primary patency rates were 33%, 52%, and 51% for gangrene, ulceration, and rest pain, respectively (p = 0.04). The 5-year cumulative primary assisted patency rates were 46%, 70%, and 72% for gangrene, ulceration, and rest pain, respectively (p = 0.01). The 5-year cumulative secondary patency rates were 48%, 76%, and 75% for gangrene, ulceration, and rest pain, respectively (p = 0.003). The 5-year cumulative limb salvage rates were 59%, 87%, and 83%, for gangrene, ulceration, and rest pain, respectively (p = 0.01). Gangrene is a distinct subcategory of critical limb ischemia with a worse prognosis than ulceration and rest pain and should be classified as such when reporting results of infrainguinal bypass grafts.     

Prevalence of hepatitis C virus isolate genotypes from chronically infected Lebanese patients: a hospital-based study

To assess percentages of hepatitis C virus (HCV) genotypes in infected Lebanese patients referred to St. George Hospital, Beirut, Lebanon, 77 infected cases were studied. Of those, 27 were hemodialysis patients. Genotyping was performed by nested PCR of the HCV core-region with specific primers, followed by DNA enzyme-immunoassay using HCV type and subtype-specific probes. Single genotype infections were detected in 52 patients (67.5%). In these cases, types 1, 2, 3 and 4 were detected in 19.5%, 32.5%, 5.1% and 10.4% of the cases respectively. Twenty-five (32.5%) samples showed mixed genotype infections. Single genotype distribution was significantly different among dialysis and non-dialysis patients. In the dialysis group, genotype 2 was predominant (80%, p < 0.001). In single HCV genotype-infected patients, subtype 1b was frequently detected in nondialysis cases (34.4%) whereas this genotype was found in only 5% of dialysis cases. Genotypes 5 and 6 were not detected in any of the cases studied. This pilot hospital-based study provides evidence for the diversity of HCV genotypes in the Lebanese population and establishes differences in distribution depending on the risk group.     

Kawasaki disease: an update

Kawasaki disease is one of the commonest vasculitides seen in children. It presents with prolonged fever and a polymorphic exanthem. It is a major cause of acquired heart disease in western society. Its exact cause is not known, but exposure to a superantigen has been suggested as a possible aetiological factor. Diagnosis of Kawasaki disease still relies on clinical criteria (Table 1) and investigations are done mainly to exclude other diseases and to detect early or established cardiac complications. Coronary complications can be reduced significantly by the use of intravenous immunoglobulin therapy combined with oral aspirin. The serious consequences of Kawasaki disease require a heightened awareness of this condition when dealing with childhood exanthems.     

Deletions and losses in chromosomes 5 or 7 in adult acute lymphocytic leukemia: incidence, associations and implications.

Deletions or losses in chromosomes 5 or 7 are recurrent non-random abnormalities in acute myeloid leukemia (AML), and are associated with prior exposure to carcinogens or leukemogenic agents, and with poor prognosis. Their occurrence and significance in adult acute lymphocytic leukemia (ALL) is not well described. The aim of the study was to evaluate the incidence, associations and implications of chromosome 5 or 7 abnormalities in adult ALL. Patients with newly diagnosed ALL referred to MD Anderson Cancer Center between 1980 and 1996 were analyzed. Characteristics and outcome of patients with or without chromosome 5 or 7 abnormalities were compared by standard statistical methods. Thirty-one of 468 patients (6.6%) had chromosome 5 or 7 abnormalities. Loss of chromosome 5 occurred in six cases, three of them had both chromosome 5 and 7 abnormalities. Deletion or loss of chromosome 7 occurred as a single abnormality in three patients; in 28 patients it was associated with other abnormalities. The most significant cytogenetic association was with the Philadelphia chromosome (Ph) abnormality occurring in nine patients (29%). Compared with patients without the abnormalities, patients with chromosome 5 or 7 abnormalities tended to express CD34 more frequently (74% vs 54% P = 0.07), to be older (age >60 years 29% vs 18% P = 0.14), and to be associated with Ph (29% vs 11% P = 0.004). With therapy, the complete response (CR) rate with chromosome 5 or 7 abnormalities was lower (64% vs 79% P = 0.038) but the survival rate was similar (3-year survival rate 32% vs 36% P = 0.14). When the 22 patients without Ph were considered separately, the CR and survival rates were similar among patients with or without chromosome 5 or 7 abnormalities. Abnormalities in chromosome 5 or 7 are not specific for AML, and may occur in ALL. Unlike in AML, chromosome 5 or 7 abnormalities in ALL were not predictive of worse prognosis, which is accounted for mostly by the association with Ph.     

Absence of mood switch with and tolerance to modafinil: a replication study from a large private practice

BACKGROUND: Fatigue is a common symptom of depression, especially the bipolar type. Modafinil is a wake-promoting agent that can alleviate fatigue in depressed patients. Many stimulants used to treat fatigue carry the risk of a switch into mania or hypomania in bipolar patients as well as the risk for tolerance or abuse. METHOD: A retrospective chart review was performed on all patients currently being seen in a large outpatient practice who received modafinil at some point during their treatment. Data collected included patient demographics, MiniSCID diagnoses, clinical diagnoses including history of substance abuse, and length and dosage of treatment with modafinil. RESULTS: Of the 191 patients who were given modafinil at some point during their treatment, 105 patients remained on it for 2 months or more and 37% of these patients were bipolar (18 BPI and 21 BPII). In addition, 86 patients were on modafinil for less than 2 months and 31% of these patients were bipolar(16% BPI and 15% BPII). No patients in any group demonstrated a switch into mania or hypomania while on modafinil. There was also no significant difference in final modafinil dosage between patients who had a positive history of chemical abuse/dependence (290 mg/day) and those who did not (258 mg/day). LIMITATIONS: Retrospective chart review. CONCLUSIONS: Adult affective disorder patients, whether unipolar or bipolar, can use modafinil to relieve symptoms of depression, including fatigue and sleepiness, without risking a switch in their mood or developing tolerance or abuse of this medication.     

Role of glutathione S-transferases polymorphisms and monocyte CD64 expression in Egyptian patients with systemic lupus erythematosus

Aim of work

To study the genetic variants of glutathione S-transferases and monocyte CD64 expression in systemic lupus erythematosus patients and to evaluate their role in disease susceptibility, activity and damage.

Arsenic-interferon-alpha-triggered apoptosis in HTLV-I transformed cells is associated with tax down-regulation and reversal of NF-kappa B activation

Human T-cell lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature activated T cells resistant to conventional chemotherapy. The viral transactivator protein Tax plays a critical role in HTLV-I-induced transformation and apoptosis resistance by inducing I kappa B-alpha degradation, resulting in the activation of the NF-kappa Bpathway. In these HTLV-I-transformed cells, arsenic trioxide (As) and interferon (IFN)-alpha synergize to induce cell cycle arrest and apoptosis. We demonstrate that cell death induction is only partly dependent upon caspase activation and is not associated with modulation of bcl-2, bax, or p53 expression. However, combined As and IFN induce the degradation of Tax, associated with an up-regulation of I kappa B-alpha resulting in a sharp decrease in RelA DNA binding nuclear factor (NF)-kappa B complexes because of the cytoplasmic retention of RelA. Taken the role of Tax in HTLV-I-induced transformation, its down-regulation probably accounts for cell death induction through inactivation of the NF-kappa B pathway. Such specific targeting of the viral oncoprotein by As-IFN treatment, reminiscent of As targeting of promyelocytic leukemia/retinoic acid receptor-alpha in acute promyelocytic leukemia, provides strong rational for combined As-IFN therapy in ATL patients. (Blood. 2000;96:2849-2855)