The roles of plasma binding and receptor specificity in the mineralocorticoid action of aldosterone.
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Biomedical subjects
Publications and source records attributed to D Feldman.
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Methods for the elimination of salmonellae from selected powdered pharmaceuticals of animal glandular origin were studied. Terminal heat treatment under carefully controlled conditions was effective for pancreatin-a powder containing proteolytic, amylolytic, and lipolytic enzymes prepared from hog pancreas glands. Use of this method resulted in a significant reduction in the number of salmonella-positive batches and also reduced the testing procedures required to confirm the absence of viable salmonellae among the majority of samples tested. Powders such as stomach substance and thyroid, in which the biological activity is not enzyme in nature, were treated successfully with acidified organic solvents. Other methods were investigated but were not suitable because of a deleterious effect on the biological activity or physical properties of the product or an inability to effect salmonella elimination.
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Prostate cancer is the second leading cause of cancer deaths in men in the United States. Developing new treatment strategies is critical to improving the health of men. This article will be a general review of the field with a focus on research from our laboratory. Our research has focused on four areas in which we have pursued the possible use of 1alpha,25(OH)(2)D(3) and its analogs to treat prostate cancer: 1) The ability of 1alpha,25(OH)(2)D(3) to up-regulate androgen receptors in LNCaP human prostate cancer cells. The implications of this finding on 1alpha,25(OH)(2)D(3)'s ability to inhibit cell growth in vivo are unclear at present.2) The reasons for an inability of 1alpha,25(OH)(2)D(3) to inhibit DU 145 prostate cancer cell growth were explored. We found that combination of an imidazole drug, Liarozole, with 1alpha,25(OH)(2)D(3) was capable of inhibiting DU 145 cell growth.3) A number of low-calcemic vitamin D analogs exhibit potent anti-proliferative activity on prostate cancer cells. We have developed a novel approach using the yeast two-hybrid system to screen for potent analogs.4) The results of a clinical trial of 1alpha,25(OH)(2)D(3) treatment of patients with early recurrent prostate cancer. We provide preliminary evidence that 1alpha,25(OH)(2)D(3) may be effective in slowing the rate of PSA rise in selected cases of prostate cancer. In conclusion, we believe that 1alpha,25(OH)(2)D(3) has a role in the treatment and/or prevention strategies being developed for prostate cancer. However, to increase antiproliferative potency without increasing side-effects, the use of less calcemic analogs appears to be the most reasonable approach.
Stress fractures frequently occur from overtraining. When stress fractures recur, underlying metabolic abnormalities should be ruled out. We report a middle-aged woman in whom such an evaluation demonstrated previously undiagnosed hypophosphatemic rickets after she presented with recurring stress fractures in her feet. Treatment with phosphate and calcitriol was associated with clinical improvement that would likely not have occurred without this intervention. Any patient with recurring stress fractures should be evaluated with several screening laboratory tests, metabolic bone x-rays, and a measurement of bone mineral density.
In this preliminary study, the wound healing response of full-thickness skin defects to transforming growth factor beta (TGF-beta) incorporated in a collagen scaffold was evaluated. The objectives of this study were (1) to compare the effects of TGF-beta on the cellular and tissue response and mechanical properties and (2) to determine the effects of a collagen scaffold on wound healing when compared to control. Three 3 x 3 cm, full-thickness defects were created on the dorsi of 15 New Zealand White rabbits. Each rabbit had a control (no treatment), collagen scaffold, and collagen scaffold with TGF-beta (2 microg/cm2). All the wounds were covered with a transparent polyurethane dressing. There were three periods of study (1, 2, and 3 weeks) with five rabbits in each period. The volume fraction of the tissue and cells was histomorphometrically determined for each wound. A greater inflammatory response was found in the collagen scaffold-treated group, but the fastest epithelialization and contraction rates were associated with TGF-beta and collagen. No significant differences in the mechanical strength between the different treatment groups were seen. Overall, TGF-beta delivered through a collagen scaffold enhanced the healing process and showed promise for future clinical applications.
OBJECTIVE: To detect chlamydial DNA on archived Papanicolaou-stained (Pap) smears using the polymerase chain reaction (PCR) technique. STUDY DESIGN: A PCR assay was designed to identify chlamydial DNA using consensus sequences unique to the genus Chlamydia in the 16S rRNA gene. This assay produced a 109 base pair product containing a single Pvu II restriction site. One hundred cervicovaginal Pap smears from a teen clinic population were processed for DNA isolation and PCR. Amplifiable DNA was isolated from 93 of the 100 cases as determined by a human growth hormone gene. These specimens were subjected to chlamydial PCR. RESULTS: PCR analysis of the 93 samples yielded 6 that were positive for the chlamydial 16S rRNA sequence. The six positive chlamydial amplicons were purified and subjected to Pvu II restriction enzyme analysis to validate their identity. The analysis confirmed the identity of the products, as a single Pvu II restriction site resulted in 41 base pair and 68 base pair products, as predicted. CONCLUSION: PCR testing for Chlamydia trachomatis can be performed on DNA isolated from archival Pap smears. Using this methodology, 6.5% of young women in our teen clinic population were positive for chlamydial DNA.
Although dental implants continue to provide consistent and predictable treatment options for most patients, some people with uncontrolled systemic disease may be denied implant treatment. Diabetes is one such disease. According to the U.S. Centers for Disease Control and Prevention, diabetes is a leading cause of blindness, kidney failure, and amputations of the lower extremities. These complications result from microvascular disturbances associated with diabetes. The effect of diabetes on the healing of titanium implants has not been well established. In this study of 32 rats, diabetes was induced in 16 animals by injection of streptozotocin (65 mg/kg); the remaining 16 animals served as controls. Titanium alloy implants were placed in the tibiae of all 32 rats using standard surgical techniques. Implants healed for 14 days. Blood samples were obtained for serum glucose, osteocalcin, and alkaline phosphatase analyses. Implants were retrieved and processed for histomorphometric analyses. Three quantities were measured using light microscopy, video capture, and computer analysis: percent osseointegration (i.e., linear bone interface), associated bone volume percent, and contact frequency. Diabetic animals demonstrated significantly less osseointegration than controls. However, bone volume percent in diabetic animals was about 4 times greater than controls. Biochemical analyses were mixed; diabetic animals demonstrated increased serum osteocalcin levels compared to controls but decreased alkaline phosphatase. Based on the results of this study, it was concluded that the bone response associated with titanium alloy implants in the tibiae of diabetic rats is uniquely different from controls.
OBJECTIVE: To study the efficacy and tolerability of amitriptyline and nortriptyline in a Brazilian population with fibromyalgia and to evaluate the instruments used to measure the efficacy of the treatment. METHODS: A total of 118 fibromyalgia patients were randomly assigned to 3 groups: amitriptyline (AM, n = 40), nortriptyline (NOR, n =38) and placebo (PL, n = 40), and were blindly given 25 mg at bedtime of the assigned treatment for 8 weeks. Clinical evaluation before and at the end of the study included the number of tender points (NTP), FIQ score (FIQ), and global improvement as reported by the patients on a verbal scale (VSGI). RESULTS: The 3 groups were comparable at baseline for all the parameters studied. After 8 weeks, the 3 groups improved in all parameters: (36.5% AM, 26.7% NOR and 24% PL patients improved on FIQ; 13.9% AM, 19.5% NOR and 8.57% PL patients improved on NTP; 86.5% AM, 72.2% NOR and 57.6% PL patients improved on VSGI). Only the AM group differed from the PL group on VSGI. Side effects were noted among the groups, but none were serious (16 in the AM group, 31 in the NOR group, and 25 in the PL group). CONCLUSION: All three groups improved after treatment. Only the patient's subjective global assessment of improvement differed between the AM patients and the PL group (p < or = 0.03). In fibromyalgia, placebo groups are important in drug trials. Different measures of therapeutic effect are not better than the patient's self assessment.
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