The effects of illicit drug use and HIV infection on sex hormone levels in women.

Drug use and HIV infection may affect sex hormone levels in women. One hundred and ninety-six women with and without a history of illicit drug use (50 HIV-negative and 148 HIV-infected), with regular menses, who never used antiretrovirals, were evaluated. Luteinizing hormone levels were significantly higher in women with a CD4 cell count <200/microl (p < 0.002). Current methadone use was associated with lower levels of total testosterone (p = 0.03) and higher levels of prolactin (p = 0.002); mean estradiol levels were 43% lower in women who used intravenous drugs (p < 0.001). Alcohol and crack cocaine use was not associated with sex hormone levels. Age, race, body mass index and degree of HIV immunosuppression were also associated with differences in sex hormone levels.     

Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.     

Glutathione S-transferases in human testicular germ cell tumors: changes of expression and activity.

Glutathione S-transferases are involved in the detoxification of carcinogens and xenobiotics and are potentially associated with the development of drug-resistance. Forty-six testicular germ cell tumors and 33 adjacent normal testicular tissue specimens were analyzed at the RNA level for the expression of glutathione S-transferase alpha and pi. Glutathione S-transferase alpha was expressed in 31 of the 33 normal testicular tissues (94%) but in only three of the 46 germ cell tumors (7%). Glutathione S-transferase pi mRNA was detected in all normal and malignant testicular tissue samples. Thirteen testicular germ cell tumors and eight normal testicular tissue samples were analyzed at the protein level. The mean specific activity of total cytosolic glutathione S-transferase in tumor tissue was decreased by about 80% as compared to normal testicular tissue. Protein analysis of the glutathione S-transferase subunits of normal testicular tissue demonstrated the presence of the glutathione S-transferase classes alpha, mu and pi, with a predominance of the mu class. In testicular germ cell tumors the glutathione S-transferase subunit pattern showed a predominance of glutathione S-transferase pi representing 88% +/- 3% of total glutathione S-transferase. Since all three glutathione S-transferase isoenzyme classes contribute to the resistance to antineoplastic drugs, the altered glutathione S-transferase isoenzyme pattern and the decrease of glutathione S-transferase activity may play a role in the high inherent drug sensitivity of human testicular germ cell tumors.     

Gallstone pancreatitis: a prospective randomized trial of the timing of surgery

The correct timing of surgery in cases of gallstone pancreatitis is debatable. To delineate more clearly the influence of the timing of surgery in the treatment of the disease, a prospective randomized clinical study of early surgery (less than 48 hours after admission) and delayed surgery (more than 48 hours after admission) was conducted in 165 patients. Ranson's prognostic signs of severity of disease were used to classify the patients into two risk groups: mild pancreatitis (three or fewer positive signs) and severe pancreatitis (more than three positive signs). In patients with three or fewer positive Ranson's signs, the time of surgery appeared to have little effect on the outcome, whereas in patients with more than three positive signs, early surgery resulted in a significant increase in rates of morbidity and mortality. Controlled randomization showed that in patients with gallstone pancreatitis, edematous or hemorrhagic necrotizing pancreatitis can develop, with or without impacted stones, early or late in the progression of the disease, during early or delayed surgery. These findings suggest that (1) although a gallstone initiates a bout of pancreatitis, it does not cause the progression of the disease; (2) the fate of the progression of pancreatitis is decided early by the amount of digestive enzymes being activated; (3) early removal of an impacted stone does not ameliorate the progression of pancreatitis; and (4) surgery should be performed during the initial hospital admission after the pancreatitis has subsided.     

Becoming a Father: First-Time Fathers' Experience of Labor and Delivery

In this study, ethnographic interviews were used to identify first-time fathers' experiences of the birth of their first child. Fourteen fathers were interviewed, and prenatal expectations of the experience are compared with the fathers' perceptions after the birth. Although the fathers expected to be treated as part of a laboring couple, they found that they were relegated to a supporting role. Initially the fathers were confident of their ability to support their wives, but they found that labor was more work than they had anticipated. They became fearful of the outcome, but hid these fears from their partners. Later, they found that their focus moved from their wives to their babies at the time of birth. The men all completed the experience with an enhanced respect for their wives. Fathers should be included in labor management plans and need support for their role as coach, particularly when their wives experience pain. They also need to be encouraged to eat and take a break from their wives' labor when appropriate.     

Neuropathy associated with “benign” anti-myelin-associated glycoprotein IgM gammopathy: Clinical,immunological, neurophysiological pathological findings and response to treatment in 33 cases

We studied 33 patients presenting with a peripheral neuropathy associated with non-malignant anti-myelin-associated glycoprotein (MAG) IgM monoclonal gammopathy (MG) in an attempt to delineate their clinical, immunological, electrophysiological and pathological characteristics; we also reviewed our experience concerning long-term follow-up and therapy. Peripheral neuropathy associated with non-malignant anti-MAG IgM MG was observed mostly in males (sex ratio 7.2), and mean age at onset was 67 years (range 46–81). A predominantly sensory pattern was noted in more than 80% of cases, although some patients were affected by a predominantly motor peripheral neuropathy. Although disease progression was slow in most cases, 45% of patients suffered severe disability, and in 2 cases, the patient's death appeared to stem directly from the neuropathy. The electrophysiological findings were indicative of a demyelinating process in 90% of cases, and electron microscopic examination of nerve biopsy specimens demonstrated widening of the myelin lamellae in more than 95% of cases. Most of our patients showed a disappointing response to steroids and chemotherapy or plasma exchanges. Intravenous immune globulin, evaluated in 17 patients, had a transient, mostly subjective effect in 35% and led to a clear-cut improvement in 24% of cases. We did not observe any correlation between the severity of the clinical picture and the anti-sulphoglucuronyl paragloboside antibody titre; in individual cases, clinical improvement occurred without lowering of IgM levels. Although the severity and the rate of progression may greatly vary from patient to patient, the combination of clinical, electrophysiological and pathological features delineates a characteristic pattern in peripheral neuropathy associated with non-malignant anti-MAG IgM MG.     

Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles

Electromyographic (EMG) recordings were obtained by concentric needle electrodes from the bulbocavernosus (BC) and ischiocavernosus (IC) muscles in 7 human volunteers during excitement to erection and subsequent ejaculation. Simultaneous registration of the time course and volume of each expressed spurt of semen was obtained using an aluminium pan suspended in front of the subject's penis on a force transducer the output of which was charted with the EMG activity. The BC and IC muscles showed no EMG activity during erection and detumescence cycles induced by visual sex stimulation. In 5 of 7 subjects, the first EMG burst of the BC in ejaculations induced by masturbation was not correlated with an expelled spurt of semen as were subsequent bursts. However, only 26 to 60% of the total number of EMG bursts were accompanied by expulsion of a spurt of semen. There thus appears to be a large safety factor in the striated muscle expulsive mechanism. Oral phenoxybenzamine treatment in 2 subjects did not significantly affect either the number of EMG bursts of the BC or the subjective pleasure of the orgasm but did significantly reduce the volume of semen expelled. Semen volume does not appear to be a unique determinant of the pleasure felt or the trigger for ejaculation.     

Translocation of BCR to chromosome 9: A new cytogenetic variant detected by FISH in two Ph-negative,BCR-positive patients with chronic myeloid leukemia

Leukemic cells from two patients with Philadelphia-negative chronic myeloid leukemia (CML) were investigated: I) Cytogenetics showed a normal 46.XY karyotype in both cases, 2) molecular studies revealed rearrangement of the M-BCR region and formation of BCR-ABL fusion mRNA with b2a2 (patient I) or b3a2 (patient 2) configuration, and 3) fluorescence in situ hybridization (FISH) demonstrated relocation of the 5′ BCR sequences from one chromosome 22 to one chromosome 9. The ABL probe hybridized to both chromosomes 9 at band q34, while two other probes which map centromeric and telomeric of BCR on 22q 11 hybridized solely with chromosome 22. For the first time, a BCR-ABL rearrangement is shown to take place on 9q34 instead of in the usual location on 22q 11. A rearrangement in the latter site is found in all Ph-positive CML and in almost all investigated CML with variant Ph or Ph-negative, BCR-positive cases. The few aberrant chromosomal localizations of BCR-ABL recombinant genes found previously were apparently the result of complex and successive changes. Furthermore in patient 2, both chromosomes 9 showed positive FISH signals with both ABL and BCR probes. Restriction fragment length polymorphism (RFLP) analysis indicated that mitotic recombination had occurred on the long arm of chromosome 9 and that the rearranged chromosome 9 was of paternal origin. The leukemic cells of this patient showed a duplication of the BCR-ABL gene, analogous to duplication of the Ph chromosome in classic CML. In addition they had lost the maternal alleles of the 9q34 chromosomal region. The lymphocytes of patient 2 carried the maternal chromosome 9 alleles and were Ph-negative as evidenced by RFLP and FISH analyses, respectively. © 1993 Wiley-Liss, Inc.