Localisation and Function of the Endocannabinoid System in the Human Ovary

Although anandamide (AEA) had been measured in human follicular fluid and is suggested to play a role in ovarian follicle and oocyte maturity, its exact source and role in the human ovary remains unclear.Immunohistochemical examination of normal human ovaries indicated that the endocannabinoid system was present and widely expressed in the ovarian medulla and cortex with more intense cannabinoid receptor 2 (CB2) than CB1 immunoreactivity in the granulosa cells of primordial, primary, secondary, tertiary follicles, corpus luteum and corpus albicans. The enzymes, fatty acid amide hydrolase (FAAH) and N-acyclphosphatidylethanolamine-phospholipase D (NAPE-PLD), were only found in growing secondary and tertiary follicles and corpora lutea and albicantes. The follicular fluid (FF) AEA concentrations of 260 FF samples, taken from 37 infertile women undergoing controlled ovarian hyperstimulation for in vitro fertilisation and intracytoplasmic sperm injection with embryo transfer, were correlated with ovarian follicle size (P = 0.03). Significantly higher FF AEA concentrations were also observed in mature follicles (1.43+/-0.04 nM; mean+/-SEM) compared to immature follicles (1.26+/-0.06 nM), P = 0.0142 and from follicles containing morphologically assessed mature oocytes (1.56+/-0.11 nM) compared to that containing immature oocytes (0.99+/-0.09 nM), P = 0.0011. ROC analysis indicated that a FF AEA level of 1.09 nM could discriminate between mature and immature oocytes with 72.2% sensitivity and 77.14% specificity, whilst plasma AEA levels and FF AEA levels on oocyte retrieval day were not significantly different (P = 0.23).These data suggest that AEA is produced in the ovary, is under hormonal control and plays a role in folliculogenesis, preovulatory follicle maturation, oocyte maturity and ovulation

Comparison of clinical and neuropathologic diagnoses of Alzheimer’s disease in 3 epidemiologic samples

Background: Studies of dementia in populations avoid many of the selection biases in clinical samples but require special evaluation and diagnostic methods to obtain high participation rates. To address this issue, we developed a unique in-home dementia assessment. We assessed validity of these assessments using neuropathologic confirmation of the clinical diagnosis in 3 epidemiologic samples. Methods: Subjects were 175 participants in 3 ongoing studies of dementia. Two were population based and identified dementia by cognitive screening. The third study sought volunteers via advertisements. Dementia evaluations were then conducted at the participants’ residences by specially trained nurses and psychometricians. Evaluation results were interpreted, and preliminary diagnoses were assigned by a geropsychiatrist or neurologist and a psychologist. Final diagnoses were assigned by a consensus panel of neurologists, geropsychiatrists, and psychologists. We compared the clinical diagnoses with the gold-standard neuropathologic diagnoses for those participants who subsequently underwent autopsy. Results: Among the demented, the sensitivity of a clinical diagnosis of probable or possible Alzheimer’s disease (AD) was 93% across the 3 studies. The rate of overall diagnostic agreement was 81%. Measures of agreement did not differ meaningfully across varying levels of dementia severity. Conclusions: Rates of neuropathologic confirmation for clinical AD diagnoses in these studies were similar to those reported from clinic-based samples. These results support the validity of clinical diagnoses of AD from a structured in-home assessment of community dwelling and institutionalized individuals using relatively economical methods of dementia screening and assessment

Frequent false positive beta human chorionic gonadotropin tests in immunoglobulin A deficiency

A patient with IgA deficiency had a series of positive serum pregnancy tests which led to medical and surgical procedures for suspected molar pregnancy. These tests were found to be falsely positive due to heterophile antibody. The aim of this study was to determine the frequency of false positive βhCG assays in sera of IgA deficient patients. Sera from a panel of IgA deficient (IgA < 7 mg/dl) patients were tested for the presence of βHCG using three different assays, and also for IgG anti-goat and anti-mouse antibodies. Patients were seen at Mount Sinai Medical Center and included 54 patients (ages 1–80 years, 32 females, 22 males) with IgA deficiency. Thirty percent of 54 IgA deficient patient sera yielded positive pregnancy tests by one or more of the three βhCG assays, however, none of the patients were pregnant. In comparison to sera of normal controls, 39% of the patient sera contained significant amounts of anti-goat antibody and 18% contained significant amounts of anti-mouse antibody. While heterophile antibodies are common in IgA deficient serum, false positive assays for βhCG in IgA deficient serum have not been previously reported. The possibility of false positive test results should be considered prior to invasive procedures in IgA deficient patients