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Biomedical subjects

N Shulman

Publications and source records attributed to N Shulman.

9 recordsLinked to original sources

Differences in the susceptibility of herpes simplex virus types 1 and 2 to modified heparin compounds suggest serotype differences in viral entry.

Although heparan sulfate (HS) serves as an initial receptor for the binding of both herpes simplex virus type 1 (HSV-1) and HSV-2 to cell surfaces, the two serotypes differ in epidemiology, cell tropism, and ability to compete for viral receptors in vitro. These observations are not necessarily contradictory and can be explained if the two serotypes recognize different structural features of HS. To compare the specific features of HS important for the binding and infection of HSV-1 and HSV-2, we took advantage of structural similarities between heparin and cell surface HS and compared the abilities of chemically modified heparin compounds to inhibit plaque formation. We found that the antiviral activity of heparin for both serotypes was independent of anticoagulant activity. Moreover, specific negatively charged regions of the polysaccharide, including N sulfations and the carboxyl groups, are key structural features for interactions of both HSV-1 and HSV-2 with cell surfaces since N desulfation or carboxyl reduction abolished heparin's antiviral activity. In contrast, 6-O sulfations and 2-,3-O sulfations are important determinants primarily for HSV- 1 infection. The O-desulfated heparins had little or no inhibitory effect on HSV-1 infection but inhibited HSV-2 infection. Using a series of intertypic recombinant mutant viruses, we found that susceptibility to O-desulfated heparins can be transferred to HSV-1 by the gene for glycoprotein C of HSV-2 (gC-2). This supports the notion that the envelope glycoproteins of HSV-1 and HSV-2 interact with different affinities for different structural features of heparin. To determine if the modified heparin compounds inhibited plaque formation by competing with cell surface HS for viral attachment, binding studies were also performed. As anticipated, most compounds inhibited binding and plaque formation in parallel. However, several compounds inhibited the binding of HSV-1 to cells during the initial attachment period at 4 degrees C; this inhibitory effect was reversed when the cells and inoculum were shifted to 37 degrees C. This temperature-dependent differential response to modified heparin compounds was evident primarily when glycoprotein C of HSV-1 (gC-1) was present in the virion envelope. Minimal temperature-dependent differences were seen for HSV-1 with gC-1 deleted and for HSV-2. These results suggest differences in the interactions of HSV-1 and HSV-2 with cell surface HS that may influence cell tropism.

Animals

Ultrasonic assessment of the endometrium as a predictor of oestrogen status in amenorrhoeic patients.

Thirty consecutive amenorrhoeic patients were assessed with regard to the following: medical history, physical examination, pelvic ultrasonography, serum levels of 17-beta oestradiol (E2), other relevant serum hormones and the response to a progesterone challenge test. The results showed a correlation coefficient of 71% (P = 0.001) between the E2 levels and the endometrial width and of 52% (P = 0.03) between the testosterone levels and the E2 levels. Linear regression of endometrial width against E2 levels showed beta = 0.018 (R2 = 22%, P = 0.02). Patients with an endometrial width of 4 mm or less reported no bleeding or only scanty bleeding following progesterone and all the patients with an endometrial width of greater than 5 mm responded to progesterone with normal menstrual bleeding.

Adolescent

Antihypertensive drug side effects in the Hypertension Detection and Follow-up Program.

The 5485 participants in the Hypertension Detection and Follow-up Program, Stepped-Care group form one of the largest groups to date on which detailed surveillance of long-term antihypertensive therapy and drug side effects has been reported. During a 5-year period, among all hypertensive persons (mild, moderate, and severe combined) who were not taking antihypertensive medications at the beginning of the study and who attended the clinic at least once during the 5-year trial, a total of 9.3% had definite or probable side effects severe enough to cause discontinuation of the drug treatment in question. Less than 1% of active participants required hospitalization for side effects. No death that could be attributed to side effects was detected. Thus, the Hypertension Detection and Follow-up Program data, which have previously demonstrated the beneficial effects of antihypertensive therapy, confirm the relative safety of such therapy.

Adult

Antacid versus sucralfate in preventing acute gastrointestinal bleeding. A randomized trial in 100 critically ill patients.

A randomized, controlled trial of sucralfate versus antacid as prophylaxis against upper gastrointestinal bleeding was carried out in 100 critically ill intensive care unit patients. Both groups were comparable with regard to sex, age, duration of prophylaxis, and the number of risk factors per patient. There was no gross bleeding in any of the patients. Three of the 48 sucralfate patients and 2 of the 52 antacid patients showed strongly positive results of Gastroccult tests of three successive hourly samples of gastric aspirate and were considered treatment failures. We conclude that sucralfate therapy is as effective as an antacid regimen in the prevention of gastrointestinal bleeding in critically ill patients. In view of a considerable savings in nursing time, it offers the opportunity for considerable reduction in the cost of intensive care while providing effective protection.

Aluminum

Correlates of attendance and compliance in the hypertension detection and follow-up program.

The Hypertension Detection and Follow-Up Program (HDFP) screened 159,000 individuals aged 30-69 years in 14 communities. Using a two-stage process, 10,940 hypertensives were randomized into two treatment groups. The first group was referred to community sources for care (RC), and the second received free Stepped Care (SC) treatment with extensive efforts to reduce the barriers to care. One year after enrollment, attendance showed 85% of SC participants active (white males 88%, white females 84%, black males 83%, and black females 84%). One year attendance rates ranged from a low of 84% for those with baseline DBP 90-104 mm Hg to a high of 90% for those with baseline DBP greater than or equal to 115 mm Hg. There was no apparent association with age, however, attendance exhibited a positive relationship with education, ranging from 83% for those completing less than high school to 94% for those with degrees beyond college. Life tables analyses demonstrated that race, sex, and blood pressure level compliance differences manifest themselves at the early stages of enrollment with little variation among participants once in the program. Pill counts correlated with percent with controlled blood pressure as well as serum potassium and calcium levels. Educational level was also a major predictor of drug adherence ranging from 74.7% to 89.7% (from under 7th grade to above college) having taken greater than or equal to 80% of their pills.

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