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Biomedical subjects

C Best

Publications and source records attributed to C Best.

At least 19 recordsLinked to original sources

Four cases of tendinopathy in patients on statin therapy.

During the last decade, statins have been widely prescribed as lipid-lowering drugs. Their overall safety profile is good. The main musculoskeletal side effects have consisted of muscle pain and weakness, peripheral neuropathy, and a few cases of drug-induced lupus. We report the first four cases of tendinopathy in patients receiving statin therapy. There were three men and one woman. The diagnoses were extensortenosynovitis at the hands (case 1), tenosynovitis of the tibialis anterior tendon (case 2), and Achilles tendinopathy (cases 3 and 4). Two patients were on simvastatin and two on atorvastatin. The tendinopathy developed 1 to 2 months after treatment initiation. The outcome was consistently favorable within 1 to 2 months after discontinuation of the drug. Similar cases have been reported to French pharmacovigilance centers. This report of four cases of tendinopathy draws attention to a possible and heretofore unrecognized side effect of a drug class that is becoming increasingly popular. Statins are effective in lowering high cholesterol levels in patients with type IIa or IIb hypercholesterolemia. They have been widely used for the last decade, particularly in the secondary and primary prevention of major coronary events. Statins act by inhibiting the enzyme hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Although most patients tolerate statins extremely well, a few experience side effects requiring treatment discontinuation. Reported musculoskeletal side effects include myalgia and a few cases of rhabdomyolysis and polymyositis. Induced lupus and peripheral neuropathy are exceedingly rare.

Acute Disease↗

Rape and physical violence: comparison of assault characteristics in older and younger adults in the National Women's Study.

This study compared characteristics of recently occurring assaults against younger adults (age 18-34 years) with those of distant-past assaults against older adults (age 55-89 years) when they were younger. Responses of a subset of participants in the National Women's Study were the source of data for this study. With the exception of perceived life threat during assault (more prevalent in younger women), assault characteristics did not vary greatly by age in terms of proportions reporting that they had seen the perpetrator before; the event was one in a series; they or the perpetrator were under the influence of a substance; they actually experienced injury; and they reported the assault to authorities. Consistent with previous research, younger women reported greater prevalences of assault than older women.

Adolescent↗

Assault, PTSD, family substance use, and depression as risk factors for cigarette use in youth: findings from the National Survey of Adolescents.

A national household probability sample of 4,023 adolescents aged 12 to 17 years was surveyed by telephone via structured clinical interview to determine the impact of familial substance use, sexual and physical assault, witnessed violence, depression and posttraumatic stress disorder (PTSD) on risk of smoking. Results indicated that familial substance use increased risk of smoking only for boys and sexual assault or depression increased risk of smoking only for girls. Age, Caucasian ethnicity, and experiencing physical assault or witnessing violence elevated risk of current cigarette use for both genders. By contrast, PTSD per se was not associated with increased risk of smoking, after the effects of other variables were controlled.

Adolescent↗

A case of hand ulceration in the diabetic foot clinic--a reminder of hand neuropathy in 'at risk' patients.

BACKGROUND: A case of hand ulceration in a diabetic patient with known lower extremity complications is presented. Although often asymptomatic, quantitative testing in patients indicates reduced hand sensation in patients with lower extremity neuropathy. Hand neuropathy may occasionally lead to anaesthetic injuries, particularly in certain 'manual' occupations, as seen in our patient. CONCLUSIONS: Education on hand care is virtually nonexistent in most clinic settings, and our case highlights the need for more awareness on this potentially troublesome complication.

Diabetes Mellitus, Type 1↗

Factors related to the reporting of childhood rape.

OBJECTIVE: The aim of this study was to examine whether there would be differences in reported versus unreported cases of childhood rape on incident characteristics including life threat, physical injury, identity of the perpetrator, frequency of assault(s), and rates of posttraumatic stress disorder or major depression. METHOD: In a telephone interview, a national probability sample of 4,008 (weighted) adult women was screened for a history of completed rape in childhood. Respondents were also assessed for DSM-III-R diagnoses of major depressive episode and/or posttraumatic stress disorder (PTSD). Three hundred forty-one (8.5%) of these women were victims of at least one rape prior to the age of 18, for a total of 437 completed rapes. Of these 437 rape incidents, 52 (11.9%) were reported to the police or other authorities. RESULTS: Significant differences were obtained between reported versus nonreported cases on incident characteristics, including life threat, physical injury, identity of the perpetrator. Reported cases were more likely to involve life threat and/or physical injury, and were more likely to have been committed by a stranger than nonreported cases. No significant differences between reported and nonreported cases were found concerning whether the rape involved a single incident versus series of events, or rates of PTSD or major depression. CONCLUSIONS: Findings suggest that different characteristics are associated with reported versus unreported cases of childhood rape. Since few cases of childhood rape are actually reported to the authorities, it appears that we may be missing valuable information. Implications for research and clinical intervention are discussed.

Adolescent↗

Endoscopic management of upper tract urothelial tumors.

We evaluated renal-preserving endourology in the diagnosis and management of upper tract urothelial tumors. Referral patients were identified for the endourologic management of upper urinary tract tumors between January 1990 and May 1996 at two tertiary care referral centers. Chart reviews, indications for intervention, and treatment outcomes were assessed. Twenty patients (mean age 66 years; range 32-89; males 14; females 6) underwent endourologic diagnosis and/or management of upper tract urothelial neoplasms. Mean follow-up was 25 months. The diagnosis of transitional cell carcinoma (TCC) was endoscopically confirmed in all cases. Twenty-one biopsies were performed for pathological diagnoses; one identified pathological muscle that assisted in clinical staging. Percutaneous approaches were required in four patients (six kidneys) as a result of inadequate retrograde access or excessive tumor burden. Four (44%) renal pelvic tumors recurred after long-term follow-up; ureteral recurrences occurred in 4 (80%) of 5 patients. Open surgery was required in six patients for excessive tumor burden/concurrent muscle invasive bladder tumors. No endoscopically managed patient developed metastatic disease. No patient died as a result of TCC. Endourologic biopsies are small, yet sufficient for pathological diagnoses of upper tract tumors; most biopsies lack muscle to evaluate staging. Recurrent upper tract tumors are common and may require multiple staged endoscopic interventions. Successful endoscopic management of upper urinary tract neoplasms is primarily related to tumor burden and pathological grade. Minimally invasive endourologic management of upper tract tumors should be considered in select patients. Open surgical management does not equate with failure.

Adult↗

D-3 phosphoinositide metabolism in cells treated with platelet-derived growth factor.

Despite extensive analysis of phosphoinositide 3-hydroxykinases (PI 3-kinases) at the molecular level, comparatively little is known about the mechanisms by which products of these enzymes exert their expected second-messenger functions. This study examines the metabolism of D-3 phosphoinositides in mouse Ph-N2 fibroblasts lacking the platelet-derived growth factor (PDGF) alpha-receptor. Treatment of these cultures with BB PDGF, but not AA PDGF, resulted in transient activation of PI 3-kinase activity measured in vitro. Treatment of myo-[3H]inositol-labelled Ph-N2 cells with BB PDGF resulted in the rapid induction of PtdIns(3,4)P2 and PtdIns(3,4,5)P3 and, to a smaller extent, PtdIns3P. The appearance of PtdIns(3,4,5)P3 preceded that of PtdIns(3,4)P2 and PtdIns3P after the addition of PDGF, suggesting that PtdIns(4,5)P2 is the preferred substrate of the agoniststimulated PI 3-kinase in intact cells. Treatment of both resting and PDGF-stimulated cells with the fungal metabolite wortmannin resulted in pronounced, selective effects on the levels of all D-3 phosphoinositides. Kinetic studies with this PI 3-kinase inhibitor revealed the presence of at least two independent routes for the biosynthesis of D-3 phosphoinositides in PDGF-treated cells.

Androstadienes↗

Characterization of human T cell clones specific for coronavirus 229E.

Coronaviruses (CV) are pleomorphic enveloped RNA viruses that are ubiquitous in nature, causing a variety of diseases in both man and domestic animals. In man, CV are generally associated with upper respiratory tract infections. The two prototype strains that are the best studied human CV isolates and which are thought to be responsible for most of the respiratory infections caused by CV are called 229E and OC43. Humoral responses consisting of neutralizing antibodies to CV are present in most individuals by six years of age. Although the cellular immune response to CV in man has not been characterized at all, it is known that the spike (S) and nucleocapsid (N) proteins elicit the major cell mediated immune responses in the mouse. This report describes the production and characterization of eleven independently isolated T cell clones that are specific for the human CV(HCV) 229E. The T cell clones are CD4+ and presumably recognize a processed viral peptide presented by class II molecules on the surface of antigen presenting cells. Of six 229E-specific T cell clones tested against purified viral proteins, three recognize the 180 kD spike glycoprotein while the other three recognize the 55 kD nucleocapsid phosphoprotein. Analysis of the human T cell mediated response to HCV will provide information regarding which viral proteins elicit the immunodominant response, what the fine specificity of these T cell clones are (immuno-dominant peptides), and what the T cell receptor (TCR) and cytokine usage is of these virus specific clones.

Capsid↗

The Fc epsilon RII/CD23 gene is actively transcribed during all stages of murine B-lymphocyte development.

It is generally accepted that the expression of Fc epsilon RII/CD23 on the surface of the B-lineage cells is restricted to the stage of the resting, mature (sIgM+/sIgD+) B-lymphocyte. However, it is unknown whether activation of the Fc epsilon RII/CD23 gene is also restricted to the stage of the mature B-lymphocyte. To address this question we investigated a panel of B-lineage cell lines for the presence of transcripts encoding Fc epsilon RII/CD23. We detected transcripts in 16 of 26 B-lineage cell lines representing the entire spectrum of B-cell development. In most cases (13 of 16) active transcription of the murine Fc epsilon RII/CD23 gene was not coupled with the expression of cell surface Fc epsilon RII/CD23 expression did not hold for all murine B-cell lines. One post-switch B-cell line (sIgM-/sIgG+) expressed Fc epsilon RII/CD23 on the cell surface and another could be induced with IL-4 and LPS to express surface Fc epsilon RII/CD23. Transcription of the murine CD23 gene in the absence of cell surface expression of Fc epsilon RII/CD23 does not appear to simply be an aberrant feature of transformed B-cells since we found transcripts, but not surface expression, in some normal splenic and peritoneal B-lymphocytes. Our findings suggest that the potential for expression of Fc epsilon RII/CD23 may occur over a much broader development window of the B-lineage than previously suspected. Transcription of the Fc epsilon RII/CD23 gene, in the absence of detectable cell surface protein expression in B-lineage cell lines, and in sort-purified B-lymphocyte subpopulations, implies that in addition to regulatory mechanisms already known, murine CD23 is also regulated through post-transcriptional mechanisms that have not yet been characterized.

Animals↗

The azaspirane SKF 105685 ameliorates renal allograft rejection in rats.

The azaspirane SKF 105685 (N,N-dimethyl-8, 8-dipropyl-2-azaspiro (4.5) decane-2-propanamine dihydrochloride) has been shown to attenuate or reverse the course of immunologic disease in several animal models, possibly through the induction of nonspecific suppressor activity. To investigate its effects on immune-mediated renal disease, SKF 105685 was administered by gavage to rats with kidney allografts. Six days after transplantation, GFR (inulin clearance, 1.46 +/- 0.27 versus 0.41 +/- 0.15 mL/min per kg; P < 0.005) and RPF (p-aminohippurate clearance, 5.48 +/- 0.98 versus 1.99 +/- 0.72 mL/min per kg; P < 0.01) were significantly higher in SKF 105685-treated rats compared with vehicle-treated control rats. In addition, mononuclear inflammatory cell infiltrates were significantly reduced in SKF 105685-treated animals compared with controls. Treatment also reduced renal production of thromboxane B2 (81 +/- 22 versus 424 +/- 76 pg/min per mg of protein; P < 0.0005), prostaglandin E2 (612 +/- 165 versus 2,059 +/- 351 pg/min per mg of protein; P < 0.005), and 6-keto prostaglandin F1 alpha (217 +/- 56 versus 943 +/- 186 pg/min per mg of protein; P < 0.005), but interleukin-1 beta mRNA levels within kidney allografts were not affected by treatment. Thus, the azaspirane SKF 105685 is a novel immunosuppressive agent that substantially ameliorates renal allograft rejection in the rat. Although the mechanism of action is unknown, the beneficial effects of SKF 105685 in rejection may relate to its ability to induce suppressor activity and/or its effects on eicosanoid production.

Animals↗

Post-transplant hypertension in the rat: effects of captopril and native nephrectomy.

In patients with well-functioning renal allografts, the presence of diseased native kidneys appears to be a common cause of elevated blood pressure. We evaluated the role of native kidneys in post-transplant hypertension using a rat model in which the confounding variables of rejection and immunosuppression could be eliminated. To produce disease in native kidneys. PVG rats were subjected to 5/6 nephrectomy. Four weeks following renal ablation, these hypertensive animals were transplanted with kidneys from syngeneic PVG donors. Four weeks later, the effects of captopril and native nephrectomy on blood pressure and renal hemodynamics were examined. Animals with remnant native kidneys which received non-rejecting renal isografts had sustained hypertension, elevated plasma renin levels and reduced transplant function. In these animals, administration of captopril reduced systemic blood pressure. Despite the reduction in blood pressure, PAH clearance by the transplanted kidney increased markedly while GFR rose modestly. Removal of the remnant native kidney also acutely lowered blood pressure. However, compared to captopril, native nephrectomy produced a more marked increase in GFR without significantly affecting renal blood flow. In this model of post-transplant hypertension in the rat, elevated blood pressure and reduced isograft function are mediated by the diseased native kidney, in part through the effects of angiotensin II. These data suggest that ACE inhibitors and native nephrectomy may have beneficial hemodynamic effects in patients with post-transplant hypertension caused by native kidneys.

Aminohippuric Acids↗

Ischemic heart disease risk factors in middle-aged Seventh-day Adventist men and their neighbors.

Seventh-day Adventists in California have much lower mortality from ischemic heart disease than do other Californians, but the risk factors have not been well documented previously for a representative sample. This study, conducted in 1982, chose a random sample of 160 Californian non-Hispanic white middle-aged Adventist men, 160 of their similar-aged male neighbors, and documented traditional ischemic heart disease risk factors. Results show major dietary differences between the two groups as expected, this being reflected in significant differences in consumption of total fat, saturated fat, dietary cholesterol, and crude fiber. Questionnaire data suggested that the Adventists also exercised 50% more, rarely smoked, but had identical Framingham Type A/B scores. There were no differences in obesity or blood pressure levels, but serum total cholesterol was significantly lower in the Adventists (190.1 vs. 203.5 mg/dl, p less than 0.001), as was low density lipoprotein cholesterol (125 vs. 134.0 mg/dl, p less than 0.03) and high density lipoprotein (HDL) cholesterol (42.3 vs. 46.0 mg/dl, p less than 0.005). Consequently, the ratio of total cholesterol/HDL cholesterol was virtually identical between the two groups. Possible explanations for some of these findings are discussed.

Adult↗