The prevalence of overmedication with levothyroxine in ambulatory elderly patients

Objective To estimate the prevalence of overmedication with levothyroxine in ambulatory elderly patients and to determine if this older patient population is inherently more likely to have suppressed serum TSH concentration. Research design and methods The medical records of 180 elderly men above the age of 60 years who were on levothyroxine therapy were reviewed. The prevalence of suppressed TSH as measured by a supersensitive assay in 935 ambulatory patients in a Department of Veterans Affairs Medical Center and 214 unselected elderly subjects presenting to a health fair was also evaluated. Concomitant free T₄ measurements done with a competitive binding assay kit were available in 381 patients. Results The overall prevalence of low serum TSH levels among patients on levothyroxine therapy followed up in an academic center is 13,3%. Patients seen in general medicine (8.7%) and geriatric clinic (7.7%) had the lowest rates of overreplacement with thyroid hormone compared to other medical subspecialty clinics (16.7%). There was a significant correlation between levothyroxine dose used and serum free T₄, TSH or log TSH values. The prevalence of low TSH in elderly subjects without known history of thyroid disease was 1.7% in the community and 3.1% in patients seen in clinics. The sensitivity of the pituitary thyrotrophs to thyroid hormone was not increased in elderly patients. Conclusions The prevalence of overmedication with levothyroxine in elderly patients is high, especially in those seen in community clinics. The suppressed serum TSH levels in elderly patients on levothyroxine is the result of overdosage rather than secondary to increased pituitary gland sensitivity to thyroid hormone.     

Abdominal visceral findings in patients with Marfan syndrome.

PURPOSE: Marfan syndrome is an autosomal dominant disorder historically defined by well-characterized features in the cardiovascular, ocular, and skeletal systems. To date, there have been no reports concerning abdominal visceral findings in this disorder. The purpose of this study was to determine the prevalence of abdominal visceral findings in patients with Marfan syndrome. METHODS: Computed tomography or magnetic resonance studies of 69 patients with Marfan syndrome and an age- and sex-matched cohort of control subjects were reviewed. The presence of abdominal visceral findings was noted. Chi-square and Student t tests were used to determine significance of differences between the patient and control groups. This retrospective study was approved by the local institutional review board and determined to be exempt from Health Insurance Portability and Accountability Act reporting requirements. RESULTS: Renal cysts were present in 41 Marfan patients (59.4%) versus 21 control subjects (30.4%), P=0.001. The average number of renal cysts was greater in Marfan patients than controls (2.4 vs. 0.9, P=0.005). Hepatic cysts were present in 24 Marfan patients (34.8%) versus 12 control patients (17.3%), P=0.02. The average number of hepatic cysts was also greater in Marfan patients than controls (0.9 vs. 0.3, P=0.027). Cholelithiasis was present in 12 Marfan patients (18.1%) versus one control patient (1.5%), P<0.001. CONCLUSIONS: Marfan syndrome patients have liver and renal cysts more often, in increased number, and at an earlier age than controls, in addition to an increased prevalence of cholelithiasis. Further study will be needed to relate these findings to recent developments concerning the underlying molecular genetics of this disorder.     

Matrix metalloproteinase activity and immunohistochemical profile of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 during human dermal wound healing

Proteolytic activity is required for the turnover of the extracellular matrix during wound healing. Matrix metalloproteinases can collectively cleave all components of the extracellular matrix, with the endogenous tissue inhibitor of metalloproteinase-1 regulating their activity. Breast tissue taken at varying postoperative times (n= 92) or during surgery (controls, n= 17), was used to investigate the temporal and spatial activity of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 during human wound healing. Matrix metalloproteinase activity, determined using a quenched fluorescence substrate assay, increased during early healing (3-8 weeks) compared to controls, and then decreased between 24 and 36 weeks after surgery (p < 0.05 until 24 weeks, Mann-Whitney U-test). Immunohistochemistry scores for matrix metalloproteinase-9 expression were significantly elevated compared to controls in scar endothelial cells and fibroblasts from 2 until 12 and 20 weeks, respectively. Matrix metalloproteinase-2 staining was observed exclusively in fibroblasts, reaching maximum levels 8-12 weeks after surgery, decreasing by 1.5 years but remaining significantly increased. Tissue inhibitor of metalloproteinase-1 staining was relatively sparse but was significantly increased until 8 weeks after surgery. These results show that matrix metalloproteinases are present at elevated levels during early wound healing, when angiogenesis occurs, and suggest that matrix metalloproteinase-9 may play a significant role. The later expression of matrix metalloproteinase-2 and -9 in fibroblasts suggests a role in extracellular matrix remodeling.     

Prognostic Validity of Short-Term Abstinence in Alcoholism

A demonstrated period of abstinence is often viewed as a good prognostic sign in alcoholism. For example, short-term abstinence one factor often considered important as a selection criteria for alcoholics who are being evaluated as liver transplant candidates. However, the prognostic validity of short-term abstinence is unclear. We evaluated the effects of 3 and 6 months of abstinence on readmission rates in a series of 299 alcoholics following discharge from inpatient treatment. Readmission rates were stratified using 3-factor model of alcoholism severity. This 3-factor model defined groups with 1-year readmission rates, ranging from 15.8% to 62.7%. Short-term abstinence did not have strong effects on readmission rates for the most severe alcoholics, nor did short-term abstinence produce clinically significant reduction for readmission rates for the least severe alcoholics. We conclude that short-term abstinence has minimal effect on prognosis for alcoholics with various levels of baseline severity.     

Cell cycle analysis of p26-BCL-2 protein levels in proliferating lymphoma and leukemia cell lines.

The BCL-2 (B-cell lymphoma/leukemia-2) gene is frequently involved in t(14;18) translocations in non-Hodgkin's lymphomas and encodes a 26-kDa intracellular, membrane-associated protein. Expression of the BCL-2 gene has previously been correlated with cellular proliferation in normal and neoplastic lymphoid cells under a variety of experimental conditions. To examine the regulation of p26-BCL-2 protein levels during the cell cycle, we utilized the method of counterflow centrifugal elutriation to enrich for cells in various phases of the cell cycle. Relative levels of p26-BCL-2 protein were measured by immunoblotting, and comparisons were made with a cell cycle-regulated protein, p62-CYCLIN-A, and a protein whose levels are constant throughout the cell cycle, p36-PCNA (DNA polymerase-delta auxiliary factor). Relative levels of p26-BCL-2 and p36-PCNA did not vary among cell fractions enriched for specific phases of the cell cycle, whereas p62-CYCLIN-A was elevated in late S- and G2/M-phase cells. Similar results were obtained with lymphoma and leukemia cell lines that have either normal or translocated BCL-2 genes. These results obtained by elutriation were confirmed by pharmacologically inducing cell cycle arrest in proliferating lymphoid cell lines with hydroxyurea, quercetin, and nocodazole which blocked cells at S, G2, and M phases, respectively. Taken together, the data indicate that p26-BCL-2 is not a true cell cycle-regulated protein, although its levels can fluctuate in connection with changes in rates of cellular proliferation under some circumstances.     

Evaluation of a latex agglutination test for the identification of Candida species in vaginal discharge.

BACKGROUND: The diagnosis of Candida vulvovaginitis using historical symptoms, pelvic examination findings, and results of traditional in-office laboratory tests is often inaccurate. Although Candida cultures can verify the diagnosis, they are not routinely used. METHODS: We prospectively compared the accuracy of a commercially available, in-office, rapid, latex agglutination test (CandidaSure) for the identification of Candida species with results from Candida culture. RESULTS: The sensitivity of the latex agglutination test was 66 percent and the specificity was 63 percent when compared with Candida culture results in patients with vaginal symptoms. When compared with a microscopic evaluation using potassium hydroxide (KOH), the CandidaSure test had greater sensitivity but a lower specificity. In 74 percent of cases with a positive KOH preparation, yeast forms were present on culture, and little was gained by adding the CandidaSure test in this situation. The addition of the CandidaSure test in those cases with a negative KOH preparation resulted in increased sensitivity but also increased the number of false-positive diagnoses. CONCLUSIONS: The CandidaSure test has greater sensitivity than the KOH preparation, but it is less predictive of a positive culture. Because of this limitation, Candida should be documented by culture for any patient who has recurrent or persistent disease and a negative KOH slide.     

Tumor-associated macrophages share in vitro growth characteristics with resident but not elicited macrophages

Recent studies have shown that tissue macrophages are capable of proliferation and that this capability is enhanced by various cytokines, including macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Tumor-associated macrophages (TAM) have been demonstrated to proliferate in vitro, but no information is currently available on the ability of M-CSF and GM-CSF to enhance this response. To address this problem, limiting dilution analysis was utilized to examine the proliferative ability of macrophages isolated from two murine tumors of distinct origin following growth in secondary hosts. As a means of comparison, resident peritoneal macrophages (RPM) and thioglycolate-elicited macrophages (TEM) were also analyzed. Results indicate that a rare subset of TAM and RPM is capable of proliferation and that M-CSF and GM-CSF enhance the frequency of TAM and RPM which proliferate, but do not enhance the growth of TEM.     

Do coronary heart disease risk factors measured in the elderly have the same predictive roles as in the middle aged. Comparisons of relative and attributable risks.

Risk factors for the 12-year incidence of definite coronary heart disease (CHD) among 3440 men who were middle-aged (51 to 59 years old) and 1419 men who were elderly (65 to 74 years old) at baseline examination were examined for differences in predictive values in terms of both relative risk and attributable (excess) risk of the highest versus the lowest quartile or appropriate categories. In multivariate models using Cox life-table regression procedures, serum cholesterol level, cigarette smoking, systolic blood pressure, and history of treatment for diabetes were significant predictors of incident CHD for both age groups. Alcohol consumption when modeled as drinker versus nondrinker showed a protective effect in both younger and older men. There was no dose relationship, however, among elderly drinkers. While the relative risks for the variables studied were similar between the two age groups, the excess risk was typically between 1.5 to 2.0 times higher for the older than the middle-aged men. In contrast, the detrimental effect of adiposity as measured by body mass index appeared to decline after age 65 for both measures of risk. This may partly be attributed to diminished adiposity overall in the older age group. The implications of these results are that serum cholesterol level, smoking, hypertension, diabetes, and possibly alcohol consumption continue to be important predictors for CHD when measured after age 65, and that the public health impact of these risk factors, in terms of excess risk, may be more important in the elderly.