The value of frozen section Pipelle endometrial biopsy as an outpatient procedure in the diagnosis of ectopic pregnancy.

This is a prospective study evaluating 28 patients who were suspected to have ectopic pregnancy. Frozen section Pipelle endometrial biopsy was performed as an outpatient procedure to look for the presence of chorionic villi in the specimen. The sensitivity of the frozen section endometrial biopsy in detecting the presence of chorionic villi was 13.3% and the specificity was 100%. The positive predictive value was 100% and the negative predictive value was 50%. We concluded that frozen section endometrial biopsy was not helpful in predicting intrauterine gestational process; therefore, it has a limited application in patients suspected to have ectopic pregnancy.     

Expression of fibrinogen receptors during activation and subsequent desensitization of human platelets by epinephrine

Epinephrine causes platelet aggregation and secretion by interacting with alpha 2-adrenergic receptors on the platelet surface. Platelet aggregation requires the binding of fibrinogen to a specific receptor on the membrane glycoprotein IIb-IIIa complex. Although the IIb-IIIa complex is identifiable on the surface of resting platelets, the fibrinogen receptor is expressed only after platelet activation. The current studies were designed to examine the effect of occupancy of platelet alpha 2-adrenergic receptors by epinephrine on the expression of fibrinogen receptors and on the aggregation of platelets. The ability of epinephrine to induce the expression of fibrinogen receptors was studied under two different conditions: acute stimulation (less than 1 min) and prolonged stimulation (50 to 90 min), the latter of which is associated with a reduction or "desensitization" of the platelet aggregation response. Expression of the fibrinogen receptor was monitored with 125I-fibrinogen as well as with 125I-PAC-1 (PAC-1), a monoclonal antibody that binds to the glycoprotein IIb-IIIa complex only after platelets are activated. Epinephrine caused an immediate increase in PAC-1 and fibrinogen binding that was dependent on occupancy of the alpha 2-receptor by epinephrine and on the presence of extracellular free Ca (KCa = 30 mumol/L). By itself, 1 mmol/L Mg was unable to support induction of the fibrinogen receptor by epinephrine. However, it did decrease the Ca requirement by about two orders of magnitude. Prolonged stimulation of unstirred platelets by epinephrine led to a 70% decrease in the aggregation response when the platelets were subsequently stirred. Despite their decreased aggregation response, desensitized platelets bound PAC-1 and fibrinogen normally, indicating that the loss of aggregation was not due simply to a decrease in fibrinogen receptor expression. Although desensitization was not affected by pretreatment of the platelets with aspirin, it was partially prevented when extracellular Ca was chelated by EDTA during the long incubation with epinephrine. These studies demonstrate that once platelet alpha 2-adrenergic receptors are occupied by epinephrine, extracellular Ca is involved in initiating the aggregation response by supporting the induction of the fibrinogen receptor and the binding of fibrinogen. Furthermore. Ca-dependent reactions subsequent to fibrinogen binding may be necessary for maximal platelet aggregation and are impaired when platelets become desensitized to epinephrine.     

Detection of Toxoplasma gondii DNA and specific antibodies in high-risk pregnant women

Primary maternal infection with toxoplasmosis during pregnancy is frequently associated with transplacental transmission to the fetus. This study was conducted to test the utility of a polymerase chain reaction (PCR) assay to detect recent infections with Toxoplasma in pregnant women. One hundred forty-eight women with high-risk pregnancies who had abnormal pregnancy outcomes (cases) and 100 with normal pregnancies (controls) were tested for the presence of Toxoplasma DNA in their blood by a nested PCR and specific antibodies to Toxoplasma by an enzyme-linked immunosorbent assay. The IgG results of the cases differed significantly from those of the controls (54% and 12%, respectively; P < 0.02). Four (2.7%) of the cases were IgM positive, but none of the controls were positive. Detection of Toxoplasma DNA in 20 (8.1%) of the IgG-positive cases suggests a recent infection. The risk factors associated with the infection were eating raw meat and contact with soil. The diagnostic serology of recent infection in early pregnancy could be confirmed by a positive Toxoplasma-specific PCR result in blood samples collected in the first half of pregnancy, even in the presence of serologic results difficult to interpret due to the lack of sequential follow-up during pregnancy.     

Chlorambucil therapy in hairy cell leukemia: effects on lipid composition and lymphocyte subpopulations

Two patients with progressive hairy cell leukemia following splenectomy were treated with low-dose daily chlorambucil. Both had an objective hematologic response as determined by a return to normal hematocrit and platelet count. This was also reflected in the mononuclear cell fraction by the normalization of cholesterol content, cholesterol/phospholipid ratio, and the lymphocyte subpopulations. This article confirms previous reports on the efficacy of chlorambucil in this setting and describes some morphological, and biochemical concomitant events.     

Trastuzumab-induced cardiotoxicity in elderly women with HER-2-positive breast cancer: a meta-analysis of real-world data

Background: We conducted a meta-analysis to assess the overall risk of cardiac toxicity associated with trastuzumab treatment in elderly breast cancer patients.

Methods: We searched databases from PubMed, EMBASE and Cochrane Central Registry of Controlled Trials to identify relevant studies. Statistical analyses were conducted to calculate the incidence rate, overall hazard ratio (HR) and 95% CIs using a fixed effects model.

Results: A total of 116,342 and 360 elderly patients from five cohort studies and two randomized clinical trials (RCTs) were included for analysis. The pooled incidences of symptomatic congestive heart failure (CHF) and CHF/HF/CM were 6.4% (95% CI 4.1% – 9.4) and 16.4% (95% CI 16.19% – 16.61) in patients with median age of 67.5 years from two RCTs and in patients with median age of 67.5 (60 – 75), 71 (66 – 80+), 74.5 (65 – 89), 75 (66 – 81+) and 79.5 (60 – 99) from five cohort studies, respectively. Trastuzumab was significantly correlated with an increased risk of defined cardiac toxicities in five cohort studies (HR = 1.89, 95% CI 1.72 – 2.07, p < 0.00001) and two RCTs (HR = 3.00, 95% CI 1.71, 5.26, p < 0.00001). Sub-group analysis showed that the anthracycline-based chemotherapy increased the risk of CHF/HF and CM in patients among five cohort studies (HR = 2.16, 95% CI: 1.8 – 1.87, p < 0.00001).

Conclusion: Trastuzumab is likely associated with an increased risk of cardiac toxicity in elderly patients with HER-2-positive breast cancer. Carefully monitoring cardiac function in elderly patients receiving trastuzumab, particularly with concurrent use of anthracycline, is warranted.     

Glibenclamide treatment in permanent neonatal diabetes mellitus due to an activating mutation in Kir6.2

Permanent neonatal diabetes mellitus (PNDM) is a rare form of diabetes characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Recently, activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 were identified in 10 PNDM patients. Tolbutamide-stimulated insulin secretion, demonstrated in 3 of these patients suggested that some PNDM patients may respond to oral sulfonylurea treatment. In this report, we describe an infant with PNDM due to an arginine-to-histidine substitution at position 201 (R201H) of the gene encoding Kir6.2. After insulin pump therapy for six months, he was shifted to oral glybenclamide therapy at a daily dose of 0.8 mg/kg. Basal c-peptide level increased by two fold during glybenclamide treatment, but no further elevation was observed following intravenous glucose administration. Outpatient, continuous glucose monitoring while on a normal infant diet demonstrated a marked improvement in glycemic control. This study demonstrates the feasibility of oral sulfonylurea treatment in PNDM patients with Kir6.2 mutations even during infancy, and the superiority of this approach over insulin administration.