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Biomedical subjects

D Plotkin

Publications and source records attributed to D Plotkin.

At least 19 recordsLinked to original sources
PubMed2000

Effect of cholesterol-lowering therapy on coronary endothelial vasomotor function in patients with coronary artery disease.

BACKGROUND: Improved endothelial function may contribute to the beneficial effects of cholesterol-lowering therapy. METHODS AND RESULTS: In this randomized, double-blind study, we compared the effect of 6 months of simvastatin (40 mg/d) treatment with that of placebo on coronary endothelial vasomotor function in 60 patients with coronary artery disease. Simvastatin lowered LDL-cholesterol by 40+/-12% from 130+/-28 mg/dL (P<0.001). Peak intracoronary acetylcholine infusion produced epicardial coronary constriction at baseline in both the simvastatin (-17+/-13%) and placebo (-24+/-16%) groups. After treatment, acetylcholine produced less constriction in both groups (-12+/-19% and -15+/-14%, respectively, P=0.97). The increase in coronary blood flow during infusion of the peak dose of substance P was blunted at baseline in both the simvastatin (42+/-50%) and placebo (55+/-71%) groups, reflecting impaired endothelium-dependent dilation of coronary microvessels. After treatment, the flow increase was 82+/-81% in the simvastatin group and 63+/-53% in the placebo group (P=0.16). CONCLUSIONS: Six months of cholesterol-lowering therapy has no significant effect on coronary endothelial vasomotor function in the study population of patients with coronary artery disease and mildly elevated cholesterol levels. These findings suggest that the effects of cholesterol lowering on endothelial function are more complex than previously thought.

Adult↗
PubMed2000

Effects of simvastatin (40 and 80 mg/day) in patients with mixed hyperlipidemia.

Mixed hyperlipidemia is characterized by both elevated total cholesterol and triglycerides. It is estimated to account for 10% to 20% of patients with dyslipidemia. This study assessed the lipid-altering efficacy and tolerability of simvastatin 40 and 80 mg/day as monotherapy. One hundred thirty patients (62 women [48%], 24 [16%] with type 2 diabetes mellitus, mean age 53 years) with mixed hyperlipidemia (baseline low-density lipoprotein [LDL] cholesterol 156 mg/dl [mean], and triglycerides 391 mg/dl [median) were randomized in a multicenter, double-masked, placebo-controlled, 3-period, 22-week, balanced crossover study, and received placebo, and simvastatin 40 and 80 mg/day each for 6 weeks. Compared with placebo, simvastatin produced significant (p <0.01) and dose-dependent changes in all lipid and lipoprotein parameters (LDL cholesterol 2.1%, -28.9%, and -35.5%; triglycerides -3.5%, -27.8%, and -33.0%; high-density lipoprotein cholesterol 3.3%, 13.1%, and 15. 7%; apolipoprotein B 3.8%, -23.1%, and -30.6%; and apolipoprotein A-I 4.0%, 8.2%, and 10.5% with placebo, and simvastatin 40 and 80 mg/day, respectively). The changes were consistent in patients with diabetes mellitus. One patient taking simvastatin 80 mg/day had an asymptomatic and reversible increase in hepatic transaminases 3 times above the upper limit of normal. Simvastatin 40 and 80 mg/day is effective in patients with mixed hyperlipidemia across the entire lipid and lipoprotein profile. The reductions in LDL cholesterol and triglycerides are large, significant, and dose dependent. The increase in high-density lipoprotein cholesterol was greater than that observed in patients with hypercholesterolemia, and appears dose dependent.

Adult↗
PubMed1999

Declarative and procedural memory functioning in abstinent cocaine abusers.

BACKGROUND: We determined the nature and recovery of procedural and declarative memory functioning in a cocaine-abusing cohort in the 45-day period following use. METHODS: Thirty-seven cocaine abusers and 27 control subjects were administered the following memory and mood measures: California Verbal Learning Test, recall of the Rey-Osterrieth Complex Figure Test, Pursuit Rotor Task, and Profile of Mood States at 4 visits (within 72 hours of admission and at 10, 21, and 45 days following abstinence). RESULTS: Analysis of performance on the Rey-Osterrieth Complex Figure Test revealed that both groups improved in their recall over repeated administrations, though the control group recalled significantly more of the information than cocaine subjects during the 45-day interval. Results for the California Verbal Learning Test indicated improved learning for both subject groups over time, but no group x time interaction. On the Pursuit Rotor Task, cocaine abusers improved their performance at a faster rate than controls at visit 1. At day 45 (visit 4), cocaine abusers again showed improvement on the Pursuit Rotor Task, whereas controls demonstrated a relative plateau in rate of learning. CONCLUSIONS: This study documented a lasting detrimental effect on a sensitive nonverbal declarative memory task in cocaine-dependent subjects following abstinence of 45 days. In contrast, abstinence from cocaine during this 45-day period was associated with sustained improvement on a motor learning test in the cocaine abusers relative to controls.

Adult↗
PubMed1999

Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. The MK-677 Study Group.

Growth hormone (GH) stimulates osteoblasts in vitro and increases bone turnover and stimulates osteoblast activity when given to elderly subjects. Probably a major effect of GH on bone is mediated through stimulation of either circulating or locally produced insulin-like growth factor I (IGF-I). We determined the effect of chronic administration of the GH secretagogue, MK-677, on serum IGF-I and markers of bone turnover in 187 elderly adults (65 years or older) enrolled in three randomized, double-blind, placebo-controlled clinical studies lasting 2-9 weeks. Urine was collected for determination of N-telopeptide cross-links (NTXs), a marker of bone resorption, and blood was collected for determination of serum osteocalcin and bone-specific alkaline phosphatase (BSAP), as bone formation markers, and serum IGF-I levels pre- and post-treatment. Dose response data were initially obtained in healthy elderly subjects who received oral doses of 10 mg or 25 mg of MK-677 or placebo for 2 weeks (n = 10-12/group). Treatment with 10 mg and 25 mg of MK-677 for 2 weeks increased mean urine NTXs 10% and 17%, respectively (p < 0.05 vs. placebo). Additionally, 50 healthy elderly subjects received either placebo (n = 20) for 4 weeks or 25 mg of MK-677 (n = 30) daily for 2 weeks followed by 50 mg daily for 2 weeks. MK-677 increased mean serum osteocalcin by 8% (p < 0.05 vs. placebo). In both studies, MK-677 increased serum IGF-I levels significantly (55-94%). Subsequently, the biological effects of MK-677 were studied in 105 elderly subjects who met objective criteria for functional impairment. Subjects were randomized to receive oral doses of placebo for 9 weeks or either 5, 10, or 25 mg of MK-677 daily for an initial 2 weeks followed by 25 mg of MK-677 daily for the next 7 weeks(n = 63 on MK-677 and n = 28 on placebo completed 9 weeks of therapy). Treatment with MK-677 (all MK-677 groups combined) for 9 weeks increased mean serum osteocalcin by 29.4% and BSAP by 10.4% (p < 0.001 vs. placebo) and mean urinary NTX excretion by 22.6% (p < 0.05 vs. placebo). The change from baseline serum osteocalcin correlated with the change from baseline serum IGF-I in the MK-677 group (r = 0.37; p < 0.01). In conclusion, once daily dosing with MK-677, an orally active GH secretagogue, stimulates bone turnover in elderly subjects based on elevations in biochemical markers of bone resorption and formation.

Aged↗
PubMed1998

Determining the potential need for a bereavement follow-up program: how well are family and health care workers' needs currently being met?

The purpose of the study was to determine the need for a bereavement follow-up program for either the families of patients dying in a critical care unit or the health care workers who care for these patients. Two questionnaires, the first a telephone administered questionnaire to all consenting family members of patients dying in the critical care unit, and the second a self-administered questionnaire administered to all health care workers in the critical care unit, were developed and piloted for content validity and clarity. The data was analyzed using descriptive statistics. Family members of 42 patients who died in the critical care unit were interviewed (54% response rate). During the critical care unit stay most family members obtained support from family and friends. While 70% listed health care workers as a source of support, 50% were satisfied with the support from staff. After a family member had died, 40% of those interviewed did not identify a specific source for support and 48% were interested in obtaining information on community resources available for aid in the bereavement process. The results from 117 (79% response rate) health care workers revealed that 30% were either uncomfortable or only somewhat comfortable with the dying process and the support available for them to deal with the death of their patients. The authors identified a need for bereavement follow-up programs for both the families of patients who die in the critical care unit and for the health care workers who care for these patients.

Adult↗
PubMed1991

Breast cancer--biology and malpractice.

Cure of breast cancer, strictly defined, is the elimination of hazard for death due to breast cancer. Five-year survival is often incorrectly equated with cure. A review of the literature reveals (a) the relative survival for breast cancer maintains a negative slope for up to 30+ years, a sign of incurability; (b) no more than 20% of women diagnosed with breast cancer survive their disease and die of other causes (personal cures). The incidence of breast cancer has been rising for over 50 years; a rise in breast cancer mortality is possibly beginning. Modest evidence for cure of breast cancer is largely based on the results of the Health Insurance Plan study. Important methodologic problems of the study warrant cautions interpretation. When treatment expectations are maintained at a high level and there is no improvement and perhaps a worsening of mortality, the stage is set for a distressingly large volume of medical malpractice actions.

Aged↗
PubMed1986

Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial.

In this National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial, 1,891 women with primary operable breast cancer and positive axillary nodes were randomized between Jan, 1977 and May 1980 to receive L-phenylalanine mustard (L-PAM) and 5-fluorouracil (5-FU) either with or without tamoxifen (TAM)-PFT. This report presents life table probabilities, cumulative odds ratios, and P values for disease-free survival (DFS) and survival at yearly intervals through 5 years of observation (mean time on study, 72 months). When patients were examined overall without regard for any discriminant associated with outcome, ie, age, number of positive nodes, or tumor receptor status, there was a significant prolongation of DFS (P = .002), but not survival through the fifth postoperative year. The benefit was almost entirely restricted to those greater than or equal to 50 years with greater than or equal to 4 positive nodes. In that group there was a 66% greater chance of remaining disease free if PFT was received (P less than .001), and there was also a significant survival benefit (P = .02). The advantage from PFT was found to be associated with tumor estrogen receptor (ER) and progesterone receptor (PR) as well as patient age and nodal status. Overall there was a significant improvement in DFS from PFT in those having tumors with an ER or PR level greater than or equal to 10 femtomole (fmol) (P = .01 and .009, respectively). No significant benefit in DFS or survival has been observed in patients less than or equal to 49 years old related either to nodes or tumor receptor status. Survival continues to be adversely affected by TAM in those patients (less than or equal to 49 years old), particularly when their tumors have a PR of 0 to 9 fmol (P = .007). In patients greater than or equal to 50 years old with four or more positive nodes, a significant DFS benefit persisted through the fifth year of observation in those having tumor ER or PR levels greater than 10 fmol (P less than .001 and .002). The advantage was observed in patients 50 to 59 years old as well as those 60 to 70. Women in the older decade demonstrated some advantage from PFT when their tumor ER or PR was 0 to 9 fmol. The most likely explanation for this finding is analytical error in receptor analyses.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1985

A randomized multicenter trial of cyclophosphamide, Novantrone and 5-fluorouracil (CNF) versus cyclophosphamide, Adriamycin and 5-fluorouracil (CAF) in patients with metastatic breast cancer.

As of August 1984, 115 women with advanced breast cancer have been randomized to receive a combination of either cyclophosphamide, Novantrone (mitoxantrone) and 5-fluorouracil (CNF) or cyclophosphamide, Adriamycin (doxorubicin) and 5-fluorouracil (CAF). Seventy-one percent of all patients were post-menopausal and 44% of CNF patients and 57% of CAF patients were estrogen receptor (ER) negative. Slightly over 30% of all patients had received hormonal therapy or chemotherapy in an adjuvant setting. Hematologic toxicity was similar in regard to platelet counts but slightly lower nadirs were experienced with CNF therapy than with CAF. However, there were fewer dosage decreases with CNF. Significantly less nausea and vomiting were observed with the CNF regimen compared to CAF. Moreover, alopecia was reduced appreciably in patients who received CNF. The response rate to CNF for the first 38 eligible and evaluable patients was 42%, and for 53 eligible and evaluable patients who received CAF the response rate was 45%, a non-significant difference. Median response durations were similar also, 140 days for CNF and 168 days for the CAF regimen. Time to treatment failure was similar for both regimens. CNF is an effective regimen for patients with advanced breast cancer, with less toxicity than CAF.

Adult↗
PubMed1985

Adaptive abilities in nonclinical second-generation Holocaust survivors and controls: a comparison.

A nonclinical second-generation Holocaust survivor group of young adults is contrasted with a comparable North American Jewish control group. A discriminate analysis of questionnaire responses indicates specific differences between the functioning second generation (N = 68) and the control group (N = 51). Focus was on growth-producing rather than pathogenic factors. Sample characteristics, interview data, techniques of data analyses and results are presented and discussed; some literature and work in progress is noted. Recommendations regarding further research efforts are made.

Adaptation, Psychological↗
PubMed1985

Staphylococcal Protein A column: correlation of mitogenicity of perfused plasma with clinical response.

Eleven patients with advanced breast cancer and four with astrocytoma were treated with plasma perfused over columns containing staphylococcal Protein A (SPA). Doses of 5 to 20 mg of SPA were bound to collodion charcoal particles, and this treatment resulted in partial remissions in one patient with astrocytoma and in two patients with breast cancer. Remission duration was 6 wk to 6 mo. Resolution of lymphadenopathy and a decrease in carcinoembryonic antigen were noted in an additional two breast cancer patients. Systemic reactions to infused plasma consisted of fever, chills, and rigors. In brain cancer patients, increased intracranial pressure was also noted. A mitogenic substance was generated in plasma of 11 patients after it was perfused over the SPA charcoal matrix. The mitogenic material induced lymphoproliferation comparable to concanavalin A and required the presence of SPA on the collodion charcoal but was not due to leakage of SPA from the column during plasma perfusion. Of considerable significance was that only patients whose column perfused plasma contained this mitogenic activity exhibited systemic reactions, and five of these patients obtained antitumor responses. This striking correlation implies that the mitogenic factor is an active component of SPA therapy. The ability to demonstrate mitogenicity in column perfused plasma might also be useful for selecting patients amenable to SPA therapy. These findings attest to the therapeutic value of this mode of treatment and provide an initial definition of a mediator of SPA antitumor activity.

Adult↗
PubMed1983

Relation of estrogen and/or progesterone receptor content of breast cancer to patient outcome following adjuvant chemotherapy.

In 1977 the National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a prospectively randomized clinical trial to evaluate the relative merits of 1-phenylalanine mustard and 5-fluorouracil (PF) with and without tamoxifen (T) as adjuvant therapy for patients with primary breast cancer and positive axillary nodes. A previous presentation of findings noted that there was a strong relationship between the outcome of those receiving PFT and the estrogen receptor (ER) and progesterone receptor (PR) content of their tumors. This report relates the outcome of the PF-treated patients in that trial with these tumor receptors. It indicates that the results observed following nonhormonal therapy (PF) are also related to tumor receptors. Both the disease-free survival (DFS) and survival (S) of women following PF therapy were influenced by the ER and PR content of their tumors. Subsequent to adjustment for other prognostic variables, the predictive influence of tumor ER persisted. Both the DFS (p = 0.0003) and the S (p = 0.00003) were significantly higher in those with greater than or equal to 10 fmol tumor ER than in those with less than 10 fmol ER. The PR significantly added to the predictive value of ER. Thus, this analysis is the first to demonstrate that having information on both ER and PR is important for predicting outcome of patients receiving adjuvant chemotherapy. The study does not provide information which correlates receptor status with the response of patients to adjuvant chemotherapy since there is no similar nonchemotherapy-treated group of patients in the trial. The findings continue to emphasize that there is a heterogeneity in outcome of breast cancer patients to adjuvant chemotherapy which is related to an increasing number of host and tumor variables. For proper assessment of overall results, it is essential that analyses employ tests for interaction to indicate homogeneity or heterogeneity of patient subsets and that adjustments be made for imbalances in tumor ER and PR as well as in other prognostic factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Hypothesis: discontinuous chemotherapy for advanced breast cancer.

At present, advanced breast cancer is traditionally managed as if cure were a possibility. In order to preserve the quality of remaining life of such patients and permit the possibility of useful secondary or tertiary therapies, the consideration of discontinuous chemotherapy for recurrent breast malignancy seems warranted.

Antineoplastic Agents↗
PubMed1982

Biological studies in adult attention deficit disorder: case report.

The authors describe the case of a patient diagnosed as suffering from attention deficit disorder, adult type. The case is noteworthy because of its presentation as manic disorder and the accompanying neurologic deficits. Biochemical and behavioral observations suggested an abnormality in noradrenergic transmission.

Adult↗
PubMed1981

Treatment of primary breast cancer with chemotherapy and tamoxifen.

We studied the possibility that the addition of tamoxifen to L-phenylalanine mustard combined with 5-fluorouracil enhances the benefit from the latter two drugs that has been observed in women with primary breast cancer and positive axillary nodes. Recurrence of disease was reduced at two years in patients given the three-drug regimen whose tumor estrogen-receptor levels were greater than or equal to 10 fmol. Among patients greater than or equal to 50 years old treatment failure was significantly reduced (P less than 0.001): by 51 per cent in those with one to three positive nodes and by 64 per cent in those with four or more. Higher receptor levels were associated with a greater probability of disease-free survival. Patients less than or equal to 49 years old were less responsive: those with one to three positive nodes received no benefit from tamoxifen at any receptor level, whereas those with four or more appeared to have reduced treatment failure associated with higher receptor levels. This adjuvant chemotherapy is not indicated in patients less than or equal to 49 years old whose tumor receptor levels are below 10 fmol; there is a suggestion of benefit in patients greater than or equal to 50 years old whose levels are low.

Age Factors↗
PubMed1978

Tamoxifen flare in advanced breast cancer.

The antiestrogen tamoxifen citrate is an effective antitumor agent in postmenopausal women with advanced breast cancer. The drug has produced relatively few and generally mild side effects. However, a not uncommon clinical phenomenon that may falsely suggest premature discontinuation of tamoxifen therapy has become evident to us and has not yet been sufficiently emphasized in the literature. We have designated this phenomenon as the tamoxifen flare. It consists of transient, at times severe, increase in pain with an apparent worsening of the patient's clinical status occurring within the first few weeks of therapy. In each of six patients experiencing this flare (45 patients treated) pain subsided despite continuation of tamoxifen therapy, followed by a partial remission lasting from six to 20 months.

Adult↗