Janice M. Pogoda

Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin.

BACKGROUNDThe Monitored Atherosclerosis Regression Study, a randomized, double-blind, placebo-controlled, 2-year trial of lovastatin monotherapy, found that coronary lesions or = 50% S at baseline had different responses to therapy. We now report on clinical, lipid, and nonlipid risk factors of treatment response in these lesion subsets.METHODS AND RESULTSTwo hundred seventy subjects, 37 to 67 years old, with plasma total cholesterol (TC) 190 to 295 mg/dL (4.91 to 7.63 mmol/L) and total triglyceride or = 50% S) lesions in 220 angiogram pairs analyzed by computer quantitative coronary angiography. In the placebo group, risk factors (P < .05) for the progression of mild/moderate lesions were trig...

Botulinum toxin type A (BOTOX) for treatment of migraine headaches: An open-label study

ABSTRACT OBJECTIVE: The object of this clinical experience was to evaluate the correlation between pericranial botulinum toxin type A (BOTOX, Allergan Corp, Irvine, CA) administration and alleviation of migraine headache symptoms. STUDY DESIGN AND SETTING: A nonrandomized, open-label study was performed at 4 different test sites. The subjects consisted of 106 patients, predominantly female, who either (1) initially sought BOTOX treatment for hyperfunctional facial lines or other dystonias with concomitant headache disorders, or (2) were candidates for BOTOX treatment specifically for headaches. Headaches were classified as true migraine, possible migraine, or nonmi-graine, based on baseline headache characteristics and International Headache Society criteria. BOTOX was injected into the glabellar, temporal, frontal, and/or suboccipital regions of the head and neck. Main outcome measures were determined by severity and duration of response. The degrees of response were classified as: (1) complete (symptom elimination), (2) partial (≥50% reduction in headache frequency or severity), and (3) no response [neither (1) nor (2)]. Duration of response was measured in months for the prophylactic group. RESULTS: Among 77 true migraine subjects treated prophylactically, 51% (95% confidence interval, 39% to 62%) reported complete response with a mean (SD) response duration of 4.1 (2.6) months; 38% reported partial response with a mean (SD) response duration of 2.7 (1.2) months. Overall improvement was independent of baseline headache characteristics. Seventy percent (95% confidence interval, 35% to 93%) of 10 true migraine patients treated acutely reported complete response with improvement 1 to 2 hours after treatment. No adverse effects were reported. CONCLUSIONS: BOTOX was found to be a safe and effective therapy for both acute and prophylactic treatment of migraine headaches. Further research is needed to explore and develop the complete potential for the neuroinhibitory effects of botulinum toxin.

Effects of estrogen replacement therapy on response to tacrine in patients with Alzheimer's disease

Objective: To examine whether estrogen replacement therapy (ERT) affects clinical and cognitive responses to tacrine in women with Alzheimers disease (AD). Design: A 30-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial of tacrine in which a subgroup of women were receiving ERT prior to randomization. Patients: Women with mild to moderate-stage AD, at least 50 years of age, who were enrolled in the previously reported trial. Interventions: Randomized assignment to placebo or to one of three ascending-dosage regimens of tacrine: maximum dosages of 80 mg/d, 120 mg/d, or 160 mg/d. Outcome measures: Alzheimers Disease Assessment Scale--Cognitive Scale (ADASc), Clinician Interview-Based Impression of change (CIBI), Mini-Mental State Examination (MMSE), Caregivers Impression of Change (CIC). Results: Of 318 women with evaluable data 14.5% were receiving ERT. Women completing the trial taking ERT and tacrine improved more than women not receiving ERT who were randomly assigned to tacrine or to placebo as assessed by the ADASc (p < 0.01), the CIBI (p = 0.02), the CIC (p = 0.006), and the MMSE (p = 0.07). They improved significantly on the ADASc (p = 0.01) using an intent-to-treat analysis. Conclusions: Prior and continuing ERT may enhance response to tacrine in women with AD. Randomized trials are needed. NEUROLOGY 1996;46: 1580-1584

Exposure Stratified Case-Cohort Designs

A variant of the case-cohort design is proposed for the situation in which a correlate of the exposure (or prognostic factor) of interest is available for all cohort members, and exposure information is to be collected for a case-cohort sample. The cohort is stratified according to the correlate, and the subcohort is selected by stratified random sampling. A number of possible methods for the analysis of such exposure stratified case-cohort samples are presented, some of their statistical properties developed, and approximate relative efficiency and optimal allocation to the strata discussed. The methods are compared to each other, and to randomly sampled case-cohort studies, in a limited computer simulation study. We found that all of the proposed analysis methods performed well and were more efficient than a randomly sampled case-cohort study.

Relationship of medical status, medications, and salivary flow rates in adults of different ages

Multiple systemic disorders and medications have been reported to cause xerostomia or salivary gland hypofunction. The purpose of this study was to evaluate the relationship among systemic disorders, medications, and salivary flow rates. Sixty-three ambulatory dental patients aged 23 to 82 years were randomly selected. The nature, duration, and number of systemic disorders and medications were documented. Repeated measurements of unstimulated whole, chewing-stimulated whole, acid-stimulated parotid, and candy-stimulated parotid salivary flow rates were obtained. Data were analyzed with the Wilcoxon rank-sum test, nonparametric multivariate analysis of variance, and Fishers exact test. For persons with systemic disorders who were taking medication, all salivary flow rates were significantly (p = 0.03 - 0.001) lower than the flow rates in healthy persons. Among persons with at least one systemic disorder who were taking medication, those who had been taking medication for longer than 2 years had significantly lower unstimulated whole saliva (p = 0.002), chewing-stimulated whole saliva (p = 0.0004), and candy-stimulated parotid saliva (p = 0.02) flow rates than those who had been taking medication for 1 to 2 years. The number of systemic disorders significantly (p = 0.02) and negatively affected the acid-stimulated parotid salivary rates. The prevalence of salivary hypofunction determined on the basis of unstimulated whole saliva and acid-stimulated parotid saliva was significantly higher (p = < 0.001, p = 0.007) in the those persons with systemic disorders and taking medications. The results suggest that salivary secretion is affected by the number of systemic disorders and duration of the potentially xerogenic medications.

A review: dietary and endogenously formed N-nitroso compounds and risk of childhood brain tumors.

Maternal dietary exposure to N-nitroso compounds (NOC) or to their precursors during pregnancy has been associated with risk of childhood brain tumors. Cured meat is one source of exposure to dietary NOC and their precursors. Most epidemiological studies that have examined the role of maternal consumption of cured meats during pregnancy have found a significant positive association between maternal intake of cured meat and the risk of childhood brain tumor (CBT). NOC consist of two main groups, N-nitrosamines and N-nitrosamides. The carcinogenicity profiles of NOC suggest that N-nitrosamides rather than N-nitrosamines are the compounds that may be associated with CBT and that they should be investigated more closely in epidemiological studies. We present a review of the chemical and carcinogenic properties of NOC in connection with the findings of case–control studies. This approach may be helpful in determining the essential information that must be collected in future epidemiological studies on CBT.

Solar radiation, lip protection, and lip cancer risk in Los Angeles County women (California, United States).

A population-based case-control study of 74 women with lip cancer diagnosed from 1978 to 1985 in Los Angeles County (California, United States) and frequency matched to 105 controls investigated the risk of solar radiation and protection from lip sunscreening agents to explore the hypothesis that excess incidence of lip cancer seen in men is due partly to lower rates in women, conferred by frequent use of lip protection. We confirm the importance in women of risk factors similar to those found in men, i.e., fair complexion, sun exposure, and smoking. Risk was related strongly to lifetime solar radiation (odds ratio [OR]=13.5 for highest quartile of exposure, 95 percent confidence interval [CI]=4.5–40.6, P trend <0.0001) and time spent outdoors (OR=4.7 for highest quartile of average yearly hours, CI=1.9–12.1, P trend=0.01). Further, among women with high lifetime solar-radiation exposure, those who used lip protection once a day or less had twice the risk of lip cancer than women who used lip protection more than once a day (OR=7.3, CI=1.9–27.2 cf OR=3.2, CI=1.1–9.2). These findings show that solar radiation is a major risk factor for lip cancer and suggest that lip sunscreening is protective, thereby supporting the hypothesis that use of lipstick and other sunscreening agents by women has contributed to their lower incidence of this disease.

Prenatal vitamin supplementation and risk of childhood brain tumors.

An international case‐control study of primary pediatric brain tumors included interviews with mothers of cases diagnosed from 1976 to 1994 and mothers of population controls. Data are available on maternal vitamin use during pregnancy for 1,051 cases and for 1,919 controls from 8 geographic areas in North America, Europe and Israel. While risk estimates varied by study center, combined results suggest that maternal supplementation for 2 trimesters decreased risk of brain tumor [odds ratio (OR) = 0.7; 95% confidence interval (CI) = 0.5, 0.9], with a trend of less risk with longer duration of use (p trend = 0.0007). The greatest risk reduction was among children diagnosed under 5 years of age whose mothers used supplements during all 3 trimesters (OR = 0.5; CI = 0.3, 0.8). This effect did not vary by histology and was seen for supplementation during pregnancy rather than during the month before pregnancy or while breast‐feeding. Our findings are largely driven by data from the United States, where most mothers took vitamins. The proportion of control mothers who took vitamins during pregnancy varied markedly from 3% in Israel and in France, 21% in Italy, 33% in Canada and 52% in Spain to 86–92% at the 3 U.S. centers. The composition of the various multivitamin compounds taken also varied: daily dose of vitamin C ranged from 0 to 600 mg; vitamin E from 0 to 70 mg; vitamin A from 0 to 30,000 IU; and folate from 0 to 2,000 μg. Mothers also took individual micronutrient supplements (e.g., vitamin C tablets), but most mothers who took these also took multivitamins, making it impossible to determine the potential independent effects of these micronutrients. Int. J. Cancer Supplement 11:17–22, 1998.

Prevalence of anal intraepithelial neoplasia defined by anal cytology screening and high-resolution anoscopy in a primary care population of HIV-infected men and women.

BACKGROUND: Prevalence of high-grade anal intraepithelial neoplasia, the human papillomavirus-associated putative anal cancer precursor, is high in HIV-infected men who have sex with men, but less is known about its prevalence in other HIV-infected subgroups. Similarly, the prevalence of abnormal cytology, used as a screen, is not well-defined in these subgroups. OBJECTIVE: This study aimed to estimate the prevalence of abnormal cytology and anal intraepithelial neoplasia in a primary care HIV-infected population. DESIGN: This investigation was designed as a cross-sectional study. SETTING: This study took place at a Ryan White–funded clinic. PATIENTS: Included in the study were all (n = 779) HIV-infected patients receiving primary care services between March 2006 and March 2008. MAIN OUTCOME MEASURES: The main outcome measures were anal cytology and high-resolution anoscopy results. RESULTS: The prevalence of abnormal cytology was 43%: 62% in men who reported receptive anal intercourse, 39% in women who reported receptive anal intercourse, and 25% in all others (P trend <.0001). High-grade anal intraepithelial neoplasia prevalence was 27%: 44% in men who reported receptive anal intercourse, 26% in women who reported receptive anal intercourse, and 10% in all others (P trend <.0001). Two patients had squamous-cell cancer. Independent predictors of dysplasia were CD4 at screening, receptive anal intercourse, sexual orientation, and history of human papillomavirus disease. Anal cytology and histology findings were not well correlated. LIMITATIONS: The study population may not be representative of the general HIV-infected population, there were differences between screened and unscreened patients and between patients with abnormal cytology who had high-resolution anoscopy and those who did not, only patients with abnormal cytology had high-resolution anoscopy, and there were possible misclassification errors and uncontrolled possible confounders. CONCLUSIONS: High-grade anal intraepithelial neoplasia is relatively common in HIV-infected patients regardless of sexual practice. Although risk increases with receptive anal intercourse, patient-provided information on this sexual practice should not be used as a determining factor for screening. Strategies to prevent anal cancer are necessary for all HIV-infected patients.

Evaluation of microfocused ultrasound with visualization for lifting, tightening, and wrinkle reduction of the decolletage

BACKGROUND Laxity and rhytides are manifestations of photodamage on the chest. OBJECTIVE We sought to evaluate efficacy and safety of microfocused ultrasound with visualization treatment of décolletage laxity and rhytides. METHODS In all, 24 subjects with moderate to severe rhytides, as measured by a validated 5-point photonumeric scale (Fabi/Bolton Chest Wrinkle Scale), received microfocused ultrasound with visualization treatment. Efficacy was measured at 90 and 180 days by the Fabi/Bolton Chest Wrinkle Scale, mid-clavicular to nipple distance, masked assessment, Physician and Subject Global Aesthetic Improvement Scales, and patient satisfaction. Adverse events were recorded. RESULTS Rhytides improved over time (P < .0001), with 46% and 62% of subjects showing a 1- to 2-point improvement at days 90 and 180, respectively. Mean (SD) mid-clavicular to nipple distance decreased (P < .0001), from 20.9 (1.57) cm to 19.8 (1.50) cm and 19.5 (1.59) cm, at days 90 and 180, respectively. At day 90, 100% were improved by Subject Global Aesthetic Improvement Scale score (P < .0001) and 96% were improved by Physician Global Aesthetic Improvement Scale score (P < .0001), with similar findings at day 180. All subjects were satisfied or very satisfied at day 90, with similar results at day 180. Improvement by masked assessment at day 90 was 71%. LIMITATIONS Single-center study, small sample size, and only Fitzpatrick skin types I and II enrolled were limitations. CONCLUSION There was appreciable efficacy and patient satisfaction after a single microfocused ultrasound with visualization treatment in wrinkle reduction and lifting of the décolletage.