Biomedical subjects

Myles Wolf

Publications and source records attributed to Myles Wolf.

23 records · Page 2Linked to original sources

PubMed2002

Patients with Fabry disease on dialysis in the United States.

BACKGROUND: : Fabry disease results from an X-linked deficiency of lysosomal alpha-galactosidase A and is a rare cause of end-stage renal disease. Little is known about the characteristics of patients with Fabry disease that initiate dialysis in the United States, although data from Europe suggests these individuals have a poor survival. METHODS: : Using the United States Renal Disease System database, we first studied in detail 42 Fabry patients who initiated dialysis between April 1995 (following the introduction of the new detailed HCFA 2728 form) and July 1998. To examine crude survival in a larger cohort, 95 Fabry patients were studied who initiated dialysis between 1985 and 1993, similar to the European Registry. Diabetic and non-diabetic controls matched by age, gender, race, year of dialysis initiation, and initial dialysis modality were examined for comparison. RESULTS: : During the years 1995 to 1998, the mean age of Fabry patients that initiated dialysis was 42 years, 83% were Caucasian, and 10% were African American. Despite the X-linked inheritance of Fabry disease, 12% of Fabry patients on dialysis were female. At initiation of dialysis mean serum albumin and creatinine were significantly higher and mean body mass index was significantly lower among Fabry patients, but mean glomerular filtration rate was similar to controls. Fabry patients tended to have a lower three-year survival compared to non-diabetic controls, but the results were not significantly different. In a larger cohort of Fabry patients who initiated dialysis between 1985 and 1993, the three-year survival of Fabry patients was significantly lower than non-diabetic controls: 63% (95% CI, 50 to 75%) versus 74% (95% CI, 67 to 80%; P=0.03). CONCLUSION: : End-stage renal disease is associated with significant morbidity and mortality among patients with Fabry disease. Recent evidence that progression of Fabry disease may be attenuated by enzyme replacement therapy necessitates increased awareness of Fabry disease and its comorbidities.

Adult↗

PubMed2002

Clinical research career development: the individual perspective.

The process of integrating medical scientific breakthroughs into improved clinical practice requires talented and dedicated clinical investigators. Unfortunately, substantial impediments deter gifted physicians from clinical research. The experience of "Dr. Ross," an aspiring (fictional) clinical investigator, is presented in this report. The factors that ultimately contribute to Dr. Ross' choice to abandon an academic clinical research career are explored. Issues relating to research training, mentoring, funding, and academic promotion standards are analyzed from his individual perspective. Special emphasis is given to the intense financial pressure trainees face. Finally, potential solutions are presented. These include a description of the National Institutes of Health K23, K24, and K30 programs and its new extramural Loan Repayment Program for clinical researchers. These important advances provide much-needed support, but additional work must be done. In the absence of further reform, academic medicine's mission to train tomorrow's clinical investigators will erode further.

Adult↗

PubMed2002

Insulin resistance but not inflammation is associated with gestational hypertension.

Hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are leading causes of pregnancy-associated morbidity. Although insulin resistance and inflammation contribute to preeclampsia, prospective data regarding mechanisms of gestational hypertension are sparse. We conducted a prospective, nested case-control study to test the hypotheses that insulin resistance, marked by reduced sex hormone-binding globulin (SHBG) levels, and inflammation, marked by increased C-reactive protein levels, are similarly associated with gestational hypertension. We measured first-trimester C-reactive protein and SHBG levels in 51 women who subsequently developed gestational hypertension and 102 randomly selected normotensive pregnant controls. Compared with controls, first-trimester SHBG levels were significantly reduced among women who later developed gestational hypertension (176+/-73 versus 203+/-79 nmol/L; P=0.03), but there was no difference in C-reactive protein levels. There was statistically significant interaction among nulliparity, first-trimester SHBG levels, and risk of gestational hypertension, such that increasing SHBG levels were associated with significantly reduced risk of gestational hypertension among nulliparous women (odds ratio, 0.64 per 50-nmol/L increase; 95% confidence interval, 0.46, 0.90; P<0.01) but not among multiparous women. This association remained significant after adjusting for potential confounders (odds ratio, 0.55; 95% confidence interval, 0.31, 0.98; P=0.04). We conclude that insulin resistance, but not inflammation, is an independent risk factor for gestational hypertension among nulliparous women. Furthermore, important mechanistic differences exist in the pathogenesis of gestational hypertension comparing nulliparous and multiparous women.

Adult↗

PubMed2002

First trimester insulin resistance and subsequent preeclampsia: a prospective study.

Insulin resistance is implicated in the pathogenesis of preeclampsia, but prospective data are limited. SHBG, a marker of insulin resistance among nonpregnant individuals, has not been studied in detail during pregnancy. We conducted a prospective, nested, case-control study to test the hypothesis that increased insulin resistance, marked by reduced first trimester SHBG levels, is associated with increased risk of subsequent preeclampsia. First trimester SHBG levels were measured in 45 nulliparous women who subsequently developed preeclampsia (blood pressure, > or =140/90 mm Hg; proteinuria, either > or =2+ by dipstick or > or =300 mg/24 h, after 20 wk gestation) and in 90 randomly selected normotensive nulliparous controls. Compared with controls, women who developed preeclampsia had significantly reduced first trimester SHBG levels (302 +/- 130 vs. 396 +/- 186 nmol/liter; P < 0.01). Every 100 nmol/liter increase in SHBG was associated with a 31% reduced risk of preeclampsia [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.55, 0.88; P < 0.01]. After adjusting for covariates in a multiple logistic regression model, the association between first trimester SHBG and preeclampsia remained significant (per 100 nmol/liter increase; OR, 0.66; 95% CI, 0.47, 0.92; P = 0.01). When subjects were stratified by body mass index (lean: body mass index, < 25 kg/m(2); overweight: body mass index, > or =25 kg/m(2)), overweight women had lower SHBG levels than lean women (286 +/- 156 vs. 410 +/- 166 nmol/liter; P < 0.01), and within each stratum, women with preeclampsia had lower SHBG levels than their respective controls. In a multivariable analysis, the association between SHBG and preeclampsia strengthened among lean women, such that every 100 nmol/liter increase in serum SHBG was associated with a 55% reduction in the risk of preeclampsia (OR, 0.45; 95% CI, 0.27, 0.77; P < 0.01), whereas in overweight women, the association was mitigated (OR, 1.02; 95% CI, 0.62, 1.69; P = 0.9). We conclude that increased early pregnancy insulin resistance is independently associated with subsequent preeclampsia. First trimester SHBG levels may be a useful biomarker for preeclampsia, especially among lean women who otherwise would be perceived to be at low risk.

Adult↗

PubMedDate not supplied

Beyond minerals and parathyroid hormone: role of active vitamin D in end-stage renal disease.

Secondary hyperparathyroidism is a common complication of end-stage renal disease (ESRD) that is often treated with activated forms of intravenous vitamin D. The natural course and treatment of secondary hyperparathyroidism in hemodialysis patients is punctuated by episodes of hypercalcemia, hyperphosphatemia, and increased calcium-phosphate product, which in previous studies were linked to increased mortality. Historically these episodes have been attributed to vitamin D, leading some authorities to favor decreased vitamin D use. However, the studies that examined the impact of mineral levels and parathyroid hormone (PTH) on survival did not consistently account for vitamin D therapy itself on hemodialysis patient survival. The current review examines in detail two recent large-scale studies of hemodialysis patients: one that demonstrated a survival advantage of paricalcitol over calcitriol and a second that demonstrated a significant survival advantage of any intravenous vitamin D formulation versus none. In both studies, the effects were independent of mineral and PTH levels, suggesting "nontraditional" actions of vitamin D contributed to the observed survival advantage. Several of these nontraditional actions are reviewed with an emphasis on those that might impact hemodialysis outcomes.

Clinical Trials as Topic↗