The New England Journal of Medicine

Green, Daniel M.; Zevon, Michael A.; Lowrie, Geoffrey; Seigelstein, Nina; Hall, Brenda

doi: 10.1056/NEJM199107183250301pmid: 2052058

AbstractBackground.Many patients who have been treated successfully for childhood cancer with regimens that contain one or more mutagenic chemotherapeutic agents are concerned that their own treatment during childhood or adolescence may adversely affect their children.Methods.To determine the effect of chemotherapy for cancer during childhood and adolescence on the outcome of subsequent pregnancies, we reviewed the records of 306 men and women who had been treated for pediatric cancer and who responded to our questionnaire. One hundred of the 306 patients reported 202 pregnancies. Among the patients who had received chemotherapy as part of their treatment for cancer, 60 patients or wives of patients had had one or more pregnancies of 20 or more weeks' gestation. The 60 former patients had a total of 100 live-born and 2 stillborn children.Results.The frequency of congenital anomalies was 8.1 percent (5 of 62) among the live-born children of the women and 7.9 percent (3 of 38) among the live-born children of the men. Structural congenital cardiac defects were identified in 10.0 percent (2 of 20) of the children of women who had been treated with dactinomycin, as compared with 0.6 percent (144 of 24,153) among the children in a multicenter survey of fetal anomalies (P = 0.0126). We found no relation between the number of mutagens received or the cumulative dose of any agent received and the frequency of congenital anomalies in the children.Conclusions.These data suggest that treatment of children and adolescents with mutagenic chemotherapeutic agents, in the dose ranges we examined, does not increase the frequency of congenital anomalies in the children subsequently born to the former patients. However, the possible adverse effect of dactinomycin on the children of such patients requires further study. (N Engl J Med 1991;325:141–6.)

Helmrich, Susan P.; Ragland, David R.; Leung, Rita W.; Paffenbarger, Ralph S.

doi: 10.1056/NEJM199107183250302pmid: 2052059

Background.Physical activity is recommended by physicians to patients with non-insulin-dependent diabetes mellitus (NIDDM), because it increases sensitivity to insulin. Whether physical activity is effective in preventing this disease is not known.Methods.We used questionnaires to examine patterns of physical activity and other personal characteristics in relation to the subsequent development of NIDDM in 5990 male alumni of the University of Pennsylvania. The disease developed in a total of 202 men during 98,524 man-years of follow-up from 1962 to 1976.Results.Leisure-time physical activity, expressed in kilocalories expended per week in walking, stair climbing, and sports, was inversely related to the development of NIDDM. The incidence rates declined as energy expenditure increased from less than 500 kcal to 3500 kcal. For each 500-kcal increment in energy expenditure, the age-adjusted risk of NIDDM was reduced by 6 percent (relative risk, 0.94; 95 percent confidence interval, 0.90 to 0.98). This association remained the same when the data were adjusted for obesity, hypertension, and a parental history of diabetes. The association was weaker when we considered weight gain between the time of college attendance and 1962 (relative risk, 0.95; 95 percent confidence interval, 0.90 to 1.00). The protective effect of physical activity was strongest in persons at highest risk for NIDDM, defined as those with a high body-mass index, a history of hypertension, or a parental history of diabetes. These factors, in addition to weight gain since college, were also independent predictors of the disease.Conclusions.Increased physical activity is effective in preventing NIDDM, and the protective benefit is especially pronounced in persons at the highest risk for the disease. (N Engl J Med 1991; 325:147–52.)

Asakai, Rei; Chung, Dominic W.; Davie, Earl W.; Seligsohn, Uri

doi: 10.1056/NEJM199107183250303pmid: 2052060

AbstractBackground and Methods.Severe factor XI deficiency, which is relatively common among Ashkenazi Jews, is associated with injury-related bleeding of considerable severity. Three point mutations — a splice-junction abnormality (Type I), Glu117→Stop (Type II), and Phe283→Leu (Type III) — have been described in six patients with factor XI deficiency. Clinical correlations with these mutations have not been carried out. We determined the relative frequency of the mutations and their association with plasma levels of factor XI clotting activity and bleeding, analyzing the mutations with the polymerase chain reaction and restriction-enzyme digestion.Results.The Type II and Type III mutations had similar frequencies among 43 Ashkenazi Jewish probands with severe factor XI deficiency; these two mutations accounted for 49 percent and 47 percent, respectively, of a total of 86 analyzed alleles. Among 40 of the probands and 12 of their relatives with severe factor XI deficiency, patients homozygous for Type III mutation had a significantly higher level of factor XI clotting activity (mean [±SD] percentage of normal values, 9.7±3.8 percent; n = 13) than those homozygous for Type II mutation (1.2±0.5 percent, n = 16) or compound heterozygotes with Type II/III mutation (3.3±1.6 percent, n = 23), as well as significantly fewer episodes of injury-related bleeding. Each of these three groups had a similarly increased proportion of episodes of bleeding complications after surgery at sites with enhanced local fibrinolysis, such as the urinary tract, or during tooth extraction.Conclusions.Type II and Type III mutations are the predominant causes of factor XI deficiency among Ashkenazi Jews. Genotypic analysis, assay for factor XI, and consideration of the type and location of surgery can be helpful in planning operations in patients with this disorder. (N Engl J Med 1991; 325:153–8.)

Szer, Ilona S.; Taylor, Elise; Steere, Allen C.

doi: 10.1056/NEJM199107183250304pmid: 2052061

AbstractBackground and Methods.The natural history of Lyme disease is not completely known. We studied the long-term course of Lyme arthritis in 46 children in whom the onset of the disease occurred between 1976 and 1979 and who received no antibiotic therapy for at least the first four years of the illness.Results.Of the 46 children (age range, 2 to 15 years), 33 (72 percent) initially had erythema migrans, 7 (15 percent) had influenza-like symptoms, and 6 (13 percent) had migratory joint pain. These manifestations were followed by brief attacks of arthritis, particularly affecting the knee. The percentage of children with recurrent episodes of arthritis declined each year. By year 4, only 10 children still had a mean of two episodes of arthritis per year; the duration of arthritis was generally longer in older children (P<0.05). During the sixth year of illness, two children (4 percent) had keratitis, and more than 10 years after the onset of disease, a subtle encephalopathy developed in two other children. Of the 39 children whom we were able to contact in 1988–1989, 12 (31 percent) still had occasional brief episodes of joint pain and 1 (3 percent) had marked fatigue. All 46 children had positive IgG antibody responses to Borrelia burgdorferi throughout the illness and on long-term follow-up. As compared with those who became asymptomatic, the children with recurrent symptoms more often had IgM responses to the spirochete and had significantly higher IgG titers (P<0.05).Conclusions.The course of initially untreated Lyme disease in children may include acute infection followed by attacks of arthritis and then by keratitis, subtle joint pain, or chronic encephalopathy. (N Engl J Med 1991; 325:159–63.)

Crawford, Jeffrey; Ozer, Howard; Stoller, Ronald; Johnson, David; Lyman, Gary; Tabbara, Imad; Kris, Mark; Grous, John; Picozzi, Vincent; Rausch, Gregory; Smith, Roy; Gradishar, William; Yahanda, Anne; Vincent, Martha; Stewart, Morgan;

Koh, Howard K.

doi: 10.1056/NEJM199107183250306pmid: 1805813

CUTANEOUS melanoma has become a common form of cancer.1 Decades of steady increases in the incidence and mortality rates of cutaneous malignant melanoma have sparked global interest in the nature of this cancer.2 3 4 5 6 Recent research has advanced our understanding of cutaneous melanoma and its biology, natural history, and treatment.7 This article reviews the current state of knowledge of melanoma and outlines approaches to treatment and control. Epidemiology The incidence of melanoma continues to rise throughout the world (Table 1). In the United States, the incidence of melanoma has almost tripled in the past four decades, growing faster than that of . . .

Kirkman, Robert L.; Ferry, Judith A.

doi: 10.1056/NEJM199107183250307pmid: 1646963

Presentation of Case A 56-year-old woman was admitted to the hospital because of recurrent intermittent fever after renal transplantation. There was a history of interstitial nephritis that led to chronic renal failure six years earlier. Extracorporeal hemodialysis was begun. Three months before entry a cadaveric renal-transplantation procedure was performed. The patient's postoperative course was complicated by fever, with the temperature rising as high as 38.9°C on the seventh postoperative day. A diagnosis of acute rejection was made. Management of her care included three 500-mg boluses of methylprednisolone by vein and a 12-day course of OKT3 monoclonal antibodies; ganciclovir was administered . . .

Horton, Edward S.

doi: 10.1056/NEJM199107183250308pmid: 2052062

Although the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) is not fully understood, it is clear that at least three factors are important: a genetic predisposition to the disease; a decrease in the action of insulin in insulin-sensitive tissues, including adipose tissue, skeletal muscle, and the liver; and a defect in pancreatic β-cell function.1 Conditions associated with the development of insulin resistance increase the risk of NIDDM greatly. Chief among these are obesity and advancing age. More recently, it has been recognized that hypertension may be associated with resistance to insulin and hyperinsulinemia.2 So, too, may be the increase in plasma . . .

Blumenthal, David

doi: 10.1056/NEJM199107183250309pmid: 2052063

The conventional wisdom among health policy makers now holds (as it did 20 years ago) that major federal reform in our health system is just a matter of time. This view originates in the extraordinary economic, social, and ethical tensions created by a system that consumes 12 percent of our gross national product while failing to provide any insurance coverage to 31 million citizens.1 Business, it is argued, will soon rebel against the cost of health care. The public at large, scandalized by the plight of the uninsured and insecure about eroding private health care coverage, will support a guaranteed . . .

Kessler, David A.

doi: 10.1056/NEJM199107183250310pmid: 2052064

Conventional methods of drug promotion — such as print advertising, direct marketing by salespeople, and the distribution of written materials at meetings — have increasingly been supplemented by nontraditional approaches that rely heavily on the involvement of researchers and other medical experts. To the extent that these activities are represented as independent educational efforts when they are in fact promotional, they can undermine the unbiased exchange of scientific information, raise questions of professional ethics, and violate the standards set by the Food and Drug Administration. Physicians who have been conducting studies in a particular field or of a certain drug . . .