Biomedical subjects
R A Clark
Publications and source records attributed to R A Clark.
Perimenopausal symptomatology among HIV-infected women at least 40 years of age.
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Factors associated with the decline in sexually transmitted infections among HIV-positive women.
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Melanoma lymphoscintigraphy and lymphatic mapping.
Lymphoscintigraphy in melanoma has proven to be a reliable method to identify regional lymph nodes at risk for metastases. The first lymph node to drain a cutaneous lesion, the sentinel lymph node (SLN), is predictive of the metastatic status of the regional lymph node group. Lymphatic mapping allows for the identification of the SLN and for selective lymph node sampling. Selective lymph node sampling is less invasive and because only a small quantity of high-risk tissue is submitted for pathological examination, it allows for a more complete and comprehensive pathological examination, which identifies melanoma with up to 100 times the sensitivity of conventional examinations.
Adult-onset recalcitrant eczema: a marker of noncutaneous lymphoma or leukemia.
BACKGROUND: Generalized eczema or erythroderma may be the presenting sign of cutaneous T-cell lymphoma. Additionally, intractable pruritus has been associated with Hodgkin's lymphoma. However, reports of adult-onset eczematous dermatitis has rarely been linked to noncutaneous lymphoproliferative disorders. OBSERVATIONS: We observed one patient in 1993 who had the onset of intractable dermatitis characterized by prurigo nodularis-like lesions and widespread erythematous plaques. After 18 months of cutaneous symptoms he experienced dyspnea. At this time Hodgkin's disease was diagnosed. This observation prompted us to evaluate subsequent patients with adult-onset eczema who were poorly responsive to therapy and in whom an obvious cause could not be determined. Over the next 24 months we identified an additional 2 patients with lymphoma who met this criteria. CONCLUSION: Unexplained eczema of adult onset may be associated with an underlying lymphoproliferative malignancy. When a readily identifiable cause (eg, contactants, drugs, or atopy) is not found, a systematic evaluation should be pursued. Patients should be evaluated with a careful physical examination, complete blood cell counts, peripheral blood smears, chest roentgenography, computed tomography of the chest and abdomen, and serum protein electrophoresis.
Facial asymmetry in superior oblique muscle palsy and pulley heterotopy.
INTRODUCTION: Some observers have considered facial asymmetry as characteristic of congenital superior oblique muscle (SO) palsy. However, recent orbital imaging studies have determined that incomitant vertical strabismus resembling SO palsy can be caused by heterotopic rectus muscle pulleys. This finding suggests that facial asymmetry may predict the presence of abnormal orbital anatomy rather than be secondary to ocular torticollis. METHODS: Subjects who underwent orbital computed tomography or magnetic resonance imaging were divided into 5 groups based on clinical evaluation and previously established imaging criteria: (1) congenital SO palsy; (2) acquired SO palsy; (3) strabismus with pulley heterotopy; (4) strabismus without SO palsy or pulley heterotopy; and (5) orthotropic subjects. Frontal photographs were digitized and the following 3 facial morphometric features recorded: (1) angle of inclination of each orbit; (2) relative facial size; and (3) facial angle. RESULTS: The 79 subjects who underwent imaging were divided into the 5 groups as follows: 6 with congenital SO palsy; 7 with acquired SO palsy; 20 with pulley heterotopy; 26 with strabismus without SO palsy or pulley heterotopy; and 20 control subjects. All subjects with either congenital or acquired SO palsy had torticollis. Multivariate analysis demonstrated no significant differences in any of the 3 facial morphometric features among any of the groups. CONCLUSION: Facial asymmetry as assessed by these 3 morphometric features is not useful in distinguishing between congenital SO palsy or pulley heterotopy and other acquired forms of strabismus. This finding casts doubt on the relationship between ocular torticollis and facial asymmetry.
Positron emission tomography in initial staging and diagnosis of persistent or recurrent disease.
Positron emission tomography (PET) constitutes a major advance in the diagnosis, staging, prognostic assessment, and follow-up of lung cancer. However, it is not a magic bullet that can solve all of the uncertainties that beguile the imaging of this disease. Small lesions, particularly those in the brain, may often be missed with PET, and three-dimensional localization of suspected sites may also be unreliable. We are still learning how best to apply this new technology in an environment that demands the efficient use of medical resources. PET will probably be used most enthusiastically in the prethoracotomy staging of patients who are considered operable or probably operable on the basis of computed tomography and in the assessment of treatment response and disease recurrence when clinical management will be determined by prompt recognition of these events.
Incidence and predictors of reinfection with Trichomonas vaginalis in HIV-infected women.
BACKGROUND AND OBJECTIVES: The presence of sexually transmitted infections (STIs) may facilitate transmission of HIV to uninfected partners. GOAL: To describe the incidence of reinfection with Trichomonas vaginalis in HIV-infected women and to assess predictors of reinfection. STUDY DESIGN: A retrospective cohort study using data abstracted from medical records of HIV-infected women with at least one diagnosis of trichomoniasis. RESULTS: Approximately one third (36%) of the study population was reinfected with T vaginalis during the follow-up period, with an incidence of 16.4 reinfections per 100 person years. Significant predictors of reinfection included history of another STI (hazard ratio, 1.52; 95% CI, 1.08-2.14) and becoming pregnant during the follow-up period (hazard ratio, 0.59; 95% CI, 0.39-0.87). CONCLUSIONS: There is a high rate of reinfection with T vaginalis in HIV-infected women. Further research that includes information on sexual partners should be conducted to better describe the reinfection patterns of trichomoniasis.
Deep venous thrombosis: detection by using indirect CT venography. The Pulmonary Angiography-Indirect CT Venography Cooperative Group.
PURPOSE: To assess the clinical benefits of performing indirect computed tomographic (CT) venography after pulmonary CT angiography to detect deep venous thrombosis (DVT) in patients suspected of having a pulmonary embolism. MATERIALS AND METHODS: The authors prospectively enrolled 541 consecutive patients who underwent pulmonary CT angiography for suspected pulmonary embolism at seven institutions. Using a protocol that optimizes venous enhancement without additional contrast material injection, the authors obtained contiguous images from the pelvis to the popliteal fossa. Ultrasonography (US) also was performed in 116 patients. RESULTS: DVT was found at indirect CT venography in 45 (8%), and pulmonary embolism was found at pulmonary CT angiography in 91 (17%) of 541 patients. Among the 45 patients with DVT, DVT occurred in 16 patients who had no pulmonary embolism at pulmonary CT angiography, which increased the diagnosis of thromboembolic disease by 18%. Among 116 patients who underwent US and indirect CT venography, 15 had DVT at US, and in all 15, DVT also was seen at indirect CT venography. In four additional cases, DVT was seen at only indirect CT venography. CONCLUSION: Among patients suspected to have pulmonary embolism, a substantial number had DVT in the absence of pulmonary embolism. Combined pulmonary CT angiography-indirect CT venography can depict these cases with accuracy comparable to that of US and thus could have a significant effect on patient care.
Grand rounds #58: a case of a lost medial rectus in the fixing eye of a patient with a face turn secondary to nystagmus.
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Critical flanking sequences of PU.1 binding sites in myeloid-specific promoters.
The myeloid-specific transcription factor PU.1 is essential for expression of p47(phox), a component of the superoxide-forming phagocyte NADPH oxidase. The consensus PU.1 binding sequence (GAGGAA) is located on the non-coding strand from position -40 to -45 relative to the transcriptional start site of the p47phox promoter. A promoter construct extending to -46 was sufficient to drive tissue-specific expression of the luciferase reporter gene, but extension of the promoter from -46 to -48 resulted in a significant increase in reporter expression. Mutations of the nucleotides G at -46 and/or T at -47 reduced both reporter expression and PU.1 binding, whereas mutations at -48 had no effect. The PU.1 binding avidity of these sequences correlated closely with their capacity to dictate reporter gene transcription. In parallel studies on the functional PU.1 site in the promoter of CD18, mutations of nucleotides G and T at positions -76 and -77 (corresponding to -46 and -47, respectively, of the p47phox promoter) reduced PU.1 binding and nearly abolished the contribution of this element to promoter activity. We conclude that the immediate flanking nucleotides of the PU.1 consensus motif have significant effects on PU.1 binding avidity and activity and that this region is the dominant cis element regulating p47phox expression.
Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes.
Genetic variation in CC chemokine receptor 5 (CCR5), the major HIV-1 coreceptor, has been shown to influence HIV-1 transmission and disease progression. However, it is generally assumed that the same CCR5 genotype (or haplotype) has similar phenotypic effects in different populations. To test this assumption, we used an evolutionary-based classification of CCR5 haplotypes to determine their associated HIV-1 disease-modifying effects in a large well-characterized racially mixed cohort of HIV-1-seropositive individuals. We demonstrate that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians. Also, we show that there is a strong interactive effect between CCR5 haplotypes with different evolutionary histories. The striking population-specific phenotypic effects associated with CCR5 haplotypes emphasize the importance of understanding the evolutionary context in which disease susceptibility genes are expressed.
Predictive markers of HIV-related weight loss and determination of differences between populations with weight loss stratified by opportunistic processes.
OBJECTIVE: To describe factors predictive of >10% weight loss among enrolled participants in clinical trials of the AIDS Clinical Trial Group (ACTG). DESIGN: A retrospective analysis of data from selected ACTG antiretroviral clinical trials completed prior to 1996 (ACTG 116, 117, 155, 175, and 241), which did not include protease inhibitors. METHODS: Data were analyzed in Cox proportional hazards models to determine significant predictors for >10% weight loss while on study. Weight loss occurring within 30 days before or after an opportunistic infection (OI) was defined as "OI-associated." Both univariate and multivariate models were considered; gender-specific models were also analyzed to provide insight into potential gender differences in predictors of weight loss. RESULTS: We found that substantial weight loss is a frequent occurrence among those enrolled in clinical trials of antiretroviral agents; approximately 15% of subjects in the studies considered experienced >10% weight loss. CD4 cell count and HIV-1 RNA at week 8, Karnofsky score, and injection drug use status were significant multivariate predictive markers for weight loss associated with an OI; baseline weight, hemoglobin, triglycerides, and gender were additional predictors for weight loss not associated with an OI. CONCLUSIONS: This is the first study to characterize the association between baseline viral load and future weight loss. Baseline and week 8 immunologic parameters as well as measures of baseline symptomatology were significant predictors of weight loss associated and not associated with an OI.
Cutaneous wound healing.
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Advising parents of asthmatic children on passive smoking: randomised controlled trial.
OBJECTIVE: To investigate whether parents of asthmatic children would stop smoking or alter their smoking habits to protect their children from environmental tobacco smoke. DESIGN: Randomised controlled trial. SETTING: Tayside and Fife, Scotland. PARTICIPANTS: 501 families with an asthmatic child aged 2-12 years living with a parent who smoked. INTERVENTION: Parents were told about the impact of passive smoking on asthma and were advised to stop smoking or change their smoking habits to protect their child's health. MAIN OUTCOME MEASURES: Salivary cotinine concentrations in children, and changes in reported smoking habits of the parents 1 year after the intervention. RESULTS: At the second visit, about 1 year after the baseline visit, a small decrease in salivary cotinine concentrations was found in both groups of children: the mean decrease in the intervention group (0.70 ng/ml) was slightly smaller than that of the control group (0.88 ng/ml), but the net difference of 0.19 ng/ml had a wide 95% confidence interval (-0.86 to 0.48). Overall, 98% of parents in both groups still smoked at follow up. However, there was a non-significant tendency for parents in the intervention group to report smoking more at follow up and to having a reduced desire to stop smoking. CONCLUSIONS: A brief intervention to advise parents of asthmatic children about the risks from passive smoking was ineffective in reducing their children's exposure to environmental tobacco smoke. The intervention may have made some parents less inclined to stop smoking. If a clinician believes that a child's health is being affected by parental smoking, the parent's smoking needs to be addressed as a separate issue from the child's health.
An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis.
OBJECTIVE: To critically review the body of clinical trials that refute or support the efficacy of antihistamines in relieving pruritus in patients with atopic dermatitis. DESIGN: Review of MEDLINE from 1966 through March 1999, the Cochrane Database of Systematic Reviews, and Best Evidence to identify therapeutic trials of antihistamines in patients with atopic dermatitis. MAIN OUTCOME MEASURES: All randomized controlled trials or clinical trials of antihistamines used in the treatment of atopic dermatitis. We found 16 studies throughout the literature. RESULTS: Large, randomized, double-blind, placebo-controlled clinical trials with definitive conclusions (grade A trials) have not been performed. Two grade B trials (small, rigorous, randomized trials with uncertain results due to moderate to high alpha or beta error) refuted the use of antihistamines in relieving pruritus. One grade B trial supported the efficacy of antihistamines in relieving pruritus. All remaining trials (grade C) lacked placebo controls or randomization, or contained fewer than 20 patients in each treatment group. CONCLUSIONS: Although antihistamines are often used in the treatment of atopic dermatitis, little objective evidence exists to demonstrate relief of pruritus. The majority of trials are flawed in terms of the sample size or study design. Based on the literature alone, the efficacy of antihistamines remains to be adequately investigated. Anecdotally, sedating antihistamines have sometimes been useful by virtue of their soporific effect and bedtime use may be warranted. There is no evidence to support the effectiveness of expensive nonsedating agents.
Ethnic differences in body image attitudes and perceptions among women infected with human immunodeficiency virus.
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Posterior fixation sutures: a revised mechanical explanation for the fadenoperation based on rectus extraocular muscle pulleys.
PURPOSE: To determine the effect of the rectus extraocular muscle pulleys on the fadenoperation, an operation designed to fixate the posterior muscle belly to the underlying retroequatorial sclera. METHODS: First, duction into the field of action of the operated-on muscle was quantified retrospectively after fadenoperation. Magnetic resonance imaging was then performed prospectively after surgery to verify anatomic changes. Forced duction testing was performed prospectively during surgery before and after faden placement. Finally, computed tomography in a cadaver containing radiographic markers was performed prospectively to determine the effect of fadenoperation on the position of the medial rectus insertion relative to its pulley. RESULTS: Mean maximum adduction after medial rectus fadenoperation was 18 degrees (range, 10 to 25 degrees; 13 eyes). Fadenoperations combined with large medial rectus recessions restricted adduction more than fadenoperations combined with smaller recessions (P = .019), but even fadenoperations without recessions substantially restricted adduction. Mean maximum abduction after lateral rectus fadenoperation was 40 degrees (range, 25 to 45 degrees; four eyes). Axial magnetic resonance imaging in two eyes demonstrated a smaller loss of muscle tangency to the globe during contraction than predicted by geometric models. Forced ductions in nine patients performed immediately after faden placement demonstrated a new mechanical restriction to duction toward the operated-on muscle. Cadaveric computed tomographic scans demonstrated posterior displacement of the medial rectus pulley during adduction after fadenoperation. CONCLUSIONS: Posterior fixation sutures do not significantly decrease muscle torque during contraction. Because posterior fixation sutures posteriorly displace the pulley sleeve during duction toward the operated-on muscle, the mechanical restriction after surgery probably represents the force deforming the pulley. This mechanical restriction may account for the limitation in duction seen after fadenoperation.