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continued from previous page muscles. In fact, these drugs appear to have only minimal side effects. Says Krikler, "The lack of long-term noxious effects with verapamil over ten years of therapy is most impressive. Even large doses produce little more than constipation." Schroeder estimates that diltiazem has one of the lowest rates of undesirable effects, about 2%. This compares with about 10% for verapamil and 30% for nifedipine, a sign of the latter two drugs' "stronger peripheral vasodilatory effect," he says. The strong vasodilatory effect of nifedipine is verified by Michael Klein, who has found some patients with ankle swelling and a few with paresthesias-necessitating withdrawal of the drug in a few cases.The most likely reason why the expected peripheral skeletal muscle effects have not appeared is the difference in calcium function between cardiac and vascular smooth muscle on the one hand and skeletal muscle on the other. Explains Zelis, "Skeletal muscle contains a large pool of intracellular calcium, allowing repeated cycles of contraction and relaxation even in the absence of significant calcium influx.Cardiac muscle and vascular smooth muscle contain much less intracellular calcium and depend on cal¬ cium transport into the cell to maintain activity, so they are more vulnerable to inhibitors." Some investigators have raised the possibility that heart failure could occur if verapamil is combined with /3-blockers, since both classes of drugs have a negative inotropic effect. The combination is only now being tested and with great caution, but preliminary results are reassuring. Says Rosing, "When we did a systematic study of the two drugs together in patients with coronary disease, we found no more problems than with other drugs combined with propranolol." Left ventricular function was only mildly suppressed and the ejection fraction was not altered beyond the mild decreases seen with verapamil alone. (Patients were chosen on the basis of having an ejection fraction of at least 30% and no evidence of severe heart block.) Robert Myerburg, MD, director of the cardiology division at the University of Miami School of Medi¬ cine, and colleagues came to the same conclusion as a result of hemodynamic studies. "The combined nega¬ tive inotropic effects of verapamil and propranolol are of negligible importance in patients with mild or moderate left ventricular dysfunction," they stated.In addition to the existing clinical uses for calcium influx inhibitors and the exciting applications that are still being explored, understanding of cardiac function is being enhanced by these drugs. Says Zelis, "Calcium influx inhibitors have spurred research into what causes angina and how calcium is used in the heart and blood vessels."-by William A. Check

Objective: To conduct a systematic literature search to identify and determine the prevalence, signs and symptoms, and clinical management of vulvar and vaginal graft versus host disease (GVHD).Methods: A systematic literature search of articles from 1993 to August 2022 was performed. Studies were included if full text was available in the English language and provided reports on female subjects with more than four patients. Review articles, conference abstracts, case reports, and case series of less than 5 patients were excluded. Included studies had their reference list searched for further manuscripts. Two authors reviewed the search results and independently identified studies that met the selection criteria and summarized available data.Results: There were 29 studies available in the literature that met the inclusion criteria. There was a high risk of bias within the available literature. The prevalence of vulval and vaginal GVHD varied between 27% and 66% of women after allogeneic stem cell transplant. Other organ GVHD, most commonly the skin, mouth, and eyes, may be present concurrently in these patients, or they may be asymptomatic. Specialist gynecology review, topical estrogen, topical steroids, topical immunosuppression, and vaginal dilatation led to a reduction in complications associated with the condition, and surgery was helpful in some severe refractory cases. These patients remain at higher risk of developing cervical dysplasia, and regular human papillomavirus screening is recommended.Conclusions: Female genital GVHD is a rare phenomenon. Early, coordinated, and regular gynecological reviews after stem cell transplant are essential to reduce the long-term complications.

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