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Biomedical subjects

Gary D Friedman

Publications and source records attributed to Gary D Friedman.

At least 19 recordsLinked to original sources

Sequelae of systemic hypertension in alcohol abstainers, light drinkers, and heavy drinkers.

A link exists between alcohol intake and increased blood pressure (BP), with many studies showing increased hypertension prevalence in heavy drinkers. The harmful and beneficial effects of alcohol can confound the study of the long-term risks of alcohol-related hypertension. We therefore studied cardiovascular sequelae separately in heavy drinkers, light drinkers, and abstainers among 127,212 subjects with BP and alcohol intake ascertained at 1978 to 1985 health examinations. Subsequent cardiovascular end points included mortality risk, hospitalization risk, and outpatient diagnosis of hypertension. Analyses were performed for all subjects and stratified by 5 alcohol-drinking categories (from never drinkers to >or=3 drinks/day). With <120/80 mm Hg as the referent, Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals for 3 higher BP categories (120 to 129/80 to 84, 130 to 139/85 to 89, and >or=140/90 mm Hg). The covariates were age, gender, race, body mass index, education, and smoking. The risk of all outcomes was progressively higher for increasing BP categories, with a similarly increased risk for abstainers, light drinkers, and heavy drinkers. The interaction tests for alcohol and BP were not statistically significant for the mortality and hospitalization outcomes. Interpretation was limited by an inability to separate subjects with increased BP from alcohol consumption from those with other etiologies. In conclusion, the data indicate that the risks of hypertension are similar regardless of the amount of alcohol consumption.

Adult↗

Coffee, cirrhosis, and transaminase enzymes.

BACKGROUND: A minority of persons at risk develop liver cirrhosis, but knowledge of risk modulators is sparse. Several reports suggest that coffee drinking is associated with lower cirrhosis risk. METHODS: We studied 125,580 multiethnic members of a comprehensive prepaid health care plan without known liver disease who supplied baseline data at voluntary health examinations from 1978 to 1985. Subsequently, through 2001, 330 of them were diagnosed with liver cirrhosis. Review of medical records confirmed the diagnosis of cirrhosis and ascertained probable etiology. The association of coffee drinking with cirrhosis was estimated by Cox proportional hazards models with 7 covariates. We also did a cross-sectional analysis of baseline aspartate aminotransferase and alanine aminotransferase levels, studied by logistic regression. RESULTS: In the cohort study, relative risks of alcoholic cirrhosis (199 subjects) for coffee drinking (vs none) were less than 1 cup per day, 0.7 (95% confidence interval [CI], 0.4-1.1); 1 to 3 cups, 0.6 (95% CI, 0.4-0.8; P<.001); and 4 or more cups, 0.2 (95% CI, 0.1-0.4; P<.001). For 131 subjects with nonalcoholic cirrhosis, relative risks were less than 1 cup, 1.2 (95% CI, 0.6-2.2); 1 to 3 cups, 1.3 (95% CI, 0.8-2.1); and 4 or more cups, 0.7 (95% CI, 0.4-1.3). These relative risks for coffee drinking were consistent in subsets. Tea drinking was unrelated to alcoholic or nonalcoholic cirrhosis. In the cross-sectional analyses, coffee drinking was related to lower prevalence of high aspartate aminotransferase and alanine aminotransferase levels; for example, the odds ratio of 4 or more cups per day (vs none) for a high aspartate aminotransferase level was 0.5 (95% CI, 0.4-0.6; P<.001) and for a high alanine aminotransferase level, 0.6 (95% CI, 0.6-0.7; P<.001), with stronger inverse relations in those who drink large quantities of alcohol. CONCLUSION: These data support the hypothesis that there is an ingredient in coffee that protects against cirrhosis, especially alcoholic cirrhosis.

Alanine Transaminase↗

Antibiotics and risk of breast cancer: up to 9 years of follow-up of 2.1 million women.

Antibiotic use has been associated with risk of breast cancer in previous reports. Using Cox proportional hazards analysis, we evaluated this association in 2,130,829 adult female subscribers of a health care program according to their receipt of prescriptions of antibiotics from outpatient pharmacies. Hormone use was taken into account. Altogether, 18,521 women developed breast cancer in up to 9.4 years of follow-up. Use of any antibiotic was associated with slightly increased risk [hazard ratio (HR), 1.14; 95% confidence interval (95% CI), 1.10-1.18] but there was little, if any, evidence of dose response, with HR of 1.17 (95% CI, 0.97-1.42) for >1,000 days of use compared with no use. The only two weakly associated antibiotic groups (HR >1.10 for >100 days of use) were tetracyclines and macrolides with HRs (95% CI) of 1.23 (1.11-1.36) and 1.16 (0.98-1.36), respectively. An association of lincosamides with breast cancer in an earlier, smaller database was not confirmed, but follow-up was too short in the present data for adequate evaluation. Medical record review suggested that acne and/or rosacea could be the underlying factor, associated with long-term antibiotic therapy and found by others to be associated with risk of breast cancer. Although causality cannot be ruled out, the observed associations of antibiotics overall, tetracyclines, and macrolides with breast cancer were weak and could be explained by uncontrolled confounding by the diseases being treated or by other factors.

Acne Vulgaris↗

Higher prevalence of systemic hypertension among moderate alcohol drinkers: an exploration of the role of underreporting.

OBJECTIVE: Heavy alcohol drinking is associated with increased prevalence of systemic hypertension (HTN), but the relationship between moderate drinking and HTN remains unclear. We explored the possible role of underreporting among moderate drinkers. METHOD: In a cross-sectional analysis of 105,378 persons, we defined a subset among persons reporting three or fewer drinks per day that was likely to include a disproportionate number of underreporters. This subset included persons who, on another occasion, indicated intake of three or more drinks per day or who ever had a diagnosis of an alcohol-related condition; these persons are called "positive." Persons who never reported three or more drinks per day and who had no alcohol-related diagnosis were called "negative." Logistic regression models estimated the odds ratios (ORs) for prevalent HTN (140/90 mm Hg or greater) in the positive and negative subgroups, compared with lifelong abstainers as referent. All persons and four race-gender groups were studied, and they were controlled for age, education, smoking, and body mass index. We also studied the relationship of blood liver transaminase enzyme levels in the positive and negative subgroups at specific alcohol intake strata. RESULTS: For persons reporting one to two drinks per day, the OR (95% confidence interval) of HTN was 1.32 (1.21-1.43) for positive persons and 1.16 (1.09-1.25) for negative persons. For those reporting less than one drink per day, the ORs were 0.97 (0.89-1.06) for positives and 0.92 (0.87-0.98) for negatives. For those reporting one to two drinks per day, positive/negative comparisons showed approximately a 75% increased prevalence of high liver transaminase enzymes. For those reporting less than one drink per day, the positive/negative difference was approximately 30%. CONCLUSION: In these data, increased prevalence of HTN among persons reporting one to two drinks per day appears to be partially due to underreporting of alcohol intake.

Adult↗

Short-term chloral hydrate administration and cancer in humans.

OBJECTIVE: Chloral hydrate, used as a hypnosedative in adults and children, has been shown to be genotoxic and carcinogenic in animal studies. We investigated the potential causal association between chloral hydrate exposure and cancer risk in humans. METHODS: Cancer incidence was previously determined via biennial screening analyses of the 215 most commonly used drugs between 1976 and 1998 for a cohort of 143,574 outpatients at Kaiser Permanente who had prescriptions filled between 1969 and 1973. Among users of chloral hydrate, statistically significant elevations in standardised morbidity ratios were observed during various years for cancer at five anatomical sites, including the lung, stomach, prostate, skin melanoma and mouth floor. In this analysis, these associations were investigated using: (i) a dose-response analysis among exposed subjects; and (ii) a two-stage design with exposed and non-exposed persons. RESULTS: There was evidence of an increasing risk of prostate cancer with increasing number of dispensings of chloral hydrate, which persisted after controlling for benign prostatic hypertrophy, vasectomy and obesity; however, the trend was not statistically significant. There was no evidence of a dose-response relationship between chloral hydrate and risk of any of the other four cancers. In the two-stage design, analyses comparing exposed and unexposed subjects showed no increased risk of cancer after controlling for confounding variables; however, the data were suggestive for prostate cancer, where the increased risk associated with chloral hydrate exposure after adjustment for confounding variables persisted. No dose-response relationship was seen for any of the other four cancer sites. CONCLUSIONS: To our knowledge, this is the first study to examine the relationship between chloral hydrate exposure and cancer risk in humans. There was no persuasive evidence to support a causal relationship between chloral hydrate exposure in humans and the development of cancer. However, statistical power was low for weak associations, particularly for some of the individual cancer sites. Although animal data using much higher doses of chloral hydrate have demonstrated its genotoxicity and carcinogenicity, the effects of chloral hydrate in humans are still uncertain.

Adult↗

Alcohol drinking and risk of hospitalization for heart failure with and without associated coronary artery disease.

Myocardial damage from heavy alcohol intake can cause the heart failure (HF) syndrome, but the relation of lighter alcohol intake to HF has rarely been studied. We examined the risk of HF hospitalization among 126,236 subjects who supplied data about alcohol during health examinations from 1978 to 1985. Among 2,594 subjects who were subsequently hospitalized for HF, record review established an association between coronary artery disease (CAD) and HF (CAD-HF) in 1,559 patients. Among the remaining 1,035 subjects who had HF (non-CAD-HF), we attempted determination of preponderant etiologic and contributory factors. Analyses used Cox models that were controlled for 7 covariates, with usual alcohol intake studied categorically compared with that in subjects who did not drink alcohol. Heavier drinkers (> or =3 drinks/day) but not light to moderate drinkers had increased risk of non-CAD-HF; e.g., relative risk for subjects who reported > or =6 drinks/day was 1.7 (95% confidence interval 1.1 to 2.6). This association of non-CAD-HF with heavy drinking was limited to subsets with cardiomyopathy or of unclear preponderant etiology. Alcohol drinking was inversely related to risk of CAD-HF (e.g., at 1 to 2 drinks/day, relative risk 0.6, 95% confidence interval 0.5 to 0.7), with consistency across subgroups of age, gender, ethnicity, education, smoking status, interval to diagnosis, and presence or absence of baseline heart disease or systemic hypertension. Moderate drinking was inversely related to non-CAD-HF only in subjects who had diabetes mellitus (n = 252). In conclusion, heavy, but not light, alcohol drinking is associated with increased risk of non-CAD-HF and that apparent protection by alcohol drinking against CAD-HF risk provides confirmation of a protective effect of alcohol against CAD.

Adult↗

Early symptoms of ovarian cancer: a case-control study without recall bias.

BACKGROUND: Ovarian cancer is usually diagnosed after it has spread and is difficult to cure. Previous attempts to identify early symptoms have either lacked a control group or have been based on interviews of cases, with possible recall bias. OBJECTIVE: The purpose of this study was to identify early symptoms of ovarian cancer by reviewing prediagnostic medical records, free of recall bias, and comparing women with and without ovarian cancer. METHODS: In an integrated health care delivery system, symptoms recorded in medical records of 102 women with ovarian cancer during the two years before diagnosis were compared with those of 102 matched control women. RESULTS: More cases than controls complained of several symptoms up to one year before diagnosis. Most of these symptoms were abdominal or gastrointestinal in nature and were more prevalent in the advanced stage cases. Other symptom sites included pelvic, urinary, back, and systemic. Because case-control differences were not large and prevalence is low, positive predictive values were generally quite low. CONCLUSION: Previous reports of early symptoms of ovarian cancer were confirmed in a study with a control group and free of recall bias. It is not clear that these symptoms occurred while the disease was still localized. Because hundreds of women would have to be investigated to detect one case of ovarian cancer, the clinical utility of these symptoms is uncertain. Nevertheless, health care providers should keep ovarian cancer in mind, when women present with symptoms such as abdominal pain and bloating.

Abdominal Pain↗

Risk of hemorrhagic stroke in Asian American ethnic groups.

The sparseness of prospective data about hemorrhagic stroke (HS) risk among Asian American ethnic groups led to the investigation of 128,934 persons with self-classified ethnicity at health examinations in 1978-1985. Subsequently, 431 persons were hospitalized for HS; 31% for subarachnoid hemorrhage (SAH) and 69% for intracerebral hemorrhage (ICH). Ethnic predictors of HS were studied by Cox proportional hazard models with 7 covariates. With whites as reference, the adjusted relative risk (95% CI) of all Asians for HS was 1.6 (1.1-2.3, p = 0.01), due substantially to increased risks of SAH in Japanese people and ICH in Filipinos. These data mandate emphasis upon preventive measures in these groups.

Adult↗

Helicobacter pylori infection and the risk of development of esophageal adenocarcinoma.

BACKGROUND: An increase in the incidence of esophageal adenocarcinoma has coincided with a decrease in the prevalence of Helicobacter pylori infection. Whether these 2 phenomena are associated is unknown. METHODS: We conducted a nested case-control study of 128,992 members of an integrated health care system who had participated in a multiphasic health checkup (MHC) during 1964-1969. During follow-up, 52 patients developed esophageal adenocarcinoma. Three randomly chosen control subjects from the MHC cohort were matched to each case subject, on the basis of age at the MHC, sex, race, and the date and site of the MHC. Data on cigarette smoking, alcohol consumption, body mass index (BMI), and education level were obtained at the MHC. Serum samples collected at the MHC were tested for IgG antibodies to H. pylori and to the H. pylori CagA protein. RESULTS: Subjects with H. pylori infections were less likely than uninfected subjects to develop esophageal adenocarcinoma (odds ratio [OR], 0.37 [95% confidence interval (CI), 0.16-0.88]). This significant association was restricted to case subjects and control subjects <50 years old at the MHC (OR, 0.20 [95% CI, 0.06-0.68]). In patients with H. pylori infections, the OR for those who tested positive for IgG antibodies to the CagA protein was similar to that for those who tested negative for it. BMI >/=25 and cigarette smoking were strong independent risk factors for development of esophageal adenocarcinoma. CONCLUSION: The absence of H. pylori infection, independent of cigarette smoking and BMI, is associated with a markedly increased risk of development of esophageal adenocarcinoma.

Adenocarcinoma↗

Changing the convexity and concavity of nasal cartilages and cartilage grafts with horizontal mattress sutures: part I. Experimental results.

Prior studies indicated that horizontal mattress sutures can control the curvature of a convex lateral crus. This study undertook to ascertain the ideal spacing for mattress sutures, determine what effect they have on the subsequent strength of the cartilage, and compare that to the resultant strength after scoring procedures used to control curvature. Curved fresh cadaver septa of various thicknesses (0.5, 1, and 1.5 mm) were used. The ideal spacing (gap between suture purchases) for the mattress suture was sought in 15 specimens. The consequent change in stiffness (modulus) of the cartilage was measured in nine other specimens before and after suture placement and after scoring. If the spacing was too large, instability resulted. If it was too small, curvature correction could not be obtained. An ideal mattress spacing (6 to 8 mm for 0.5-mm specimens and 8 to 10 mm for 1.5-mm specimens) removed most curvature and provided stability. The mattress suture increased the stiffness (modulus) above normal and far above that when the curvature was removed by scoring. The mean composite modulus before suturing was 4.6 MPa. After ideally spaced sutures, it was 6.2 MPa, a 35 percent increase in stiffness. After scoring to improve curvature, it was 2.4 MPa, a 48 percent reduction in stiffness (p = 0.02, Wilcoxon signed rank test). The horizontal mattress suture technique corrects cartilage curvature if the appropriate spacing is used. The corrected cartilage is stiffer/stronger than normal cartilage and much stiffer/stronger than if scored.

Cadaver↗

Changing the convexity and concavity of nasal cartilages and cartilage grafts with horizontal mattress sutures: part II. Clinical results.

Horizontal mattress sutures have previously been shown to remove unwanted bulbosity and convexity of nasal tip cartilages. The purpose of this study was to extend that concept by investigating the universal applicability of the horizontal mattress suture to change and control the curvature (e.g., convexity or concavity) of a wide variety of nasal cartilages and warped cartilage grafts. The horizontal mattress suture was applied to a variety of clinical situations, including nasal tip bulbosity caused by convex lateral crura, collapsed external nasal valves, warped grafts and struts, crooked L-shaped septal struts, and collapsed internal nasal valves. Twenty-nine cases were studied over a period of 10 to 23 months. The horizontal mattress suture proved to be a simple, effective means of achieving satisfactory control of the curvature of various cartilages of the nose (including external valves, internal valves, and septum) and warped cartilage grafts. Curvature control was obtained in all cases where the cartilage was supple. Moreover, the resultant strength was increased above normal. Partial recurrence of the curvature was seen in only two cases. Clinical results indicated that the horizontal mattress suture is universally applicable to a variety of situations in which the curvature of nasal cartilage and cartilage grafts needs to be removed or modified. The mattress suture drastically reduces the need for scoring (with its inherent problems of weakness) and the need for cartilage grafting.

Cartilage↗

Cryptococcosis: the 1981-2000 epidemic.

The annual incidence of cryptococcosis during 1981-2000 was determined in subscribers of a large integrated health care program in Northern California and in those among them who were HIV positive. The incidence of cryptococcosis had been measured in this setting in the previous decade. The 20-year incidence per million person-years was 19.0 in males and 2.6 in females. In males, annual incidence rose sharply but irregularly from 1981 to 1992, then decreased irregularly. In females, trends were less marked, with maximum incidence in 1997. In HIV-positive patients cryptococcosis incidence was highest in 1981-85 and decreased thereafter in men. In women, maximum incidence occurred in 1986-90 and was followed by a decrease. Cryptococcosis was rare in the non-predisposed. Thus, cryptococcosis incidence increased markedly in men early in the AIDS epidemic, and began to decrease in both male and female HIV-positive patients well before highly active antiretroviral therapy became available.

AIDS-Related Opportunistic Infections↗

The risk for malignant primary adult-onset glioma in a large, multiethnic, managed-care cohort: cigarette smoking and other lifestyle behaviors.

PURPOSE: To determine the risk for malignant primary adult-onset glioma (MPAG) associated with cigarette smoking and other lifestyle behaviors in a large, multiethnic, managed-care cohort. METHODS: The study population included a cohort of 133,811 subscribers to the Kaiser Permanente Medical Care Program of Northern California who had received a multiphasic health checkup and questionnaire between 1977 and 1985, were at least 25 years old at their start of follow-up, and had no prior history of benign or malignant brain tumors. In this cohort, patients were followed for up to 21 years for the development of MPAG. RESULTS: Risk for MPAG among women increased with increasing packs of cigarettes smoked per day (p-for-trend = 0.04), adjusting for cigar and pipe smoking, patient age, sex, race, education, alcohol use and coffee consumption. A similar pattern was not observed for men. Individuals who smoked marijuana at least once a month, adjusting for cigarette smoking (packs smoked per day) and for the factors noted above, had a 2.8-fold (CI = 1.3-6.2) increased risk for MPAG. Relative risk for MPAG increased with increasing consumption of coffee (p-for-trend = 0.05). CONCLUSIONS: Cigarette smoking was associated with an increased risk for MPAG among women but not among men. Individuals who smoked marijuana at least once a month had an increased risk for MPAG, although no dose-response relation was observed. Drinkers of >7 cups of coffee per day had a 70% increased risk for MPAG and smaller risk elevation for lower consumption. Alcohol usage was not associated with an increased risk for MPAG.

Adult↗

Wine, liquor, beer, and mortality.

A substantially increased risk for heavy drinkers and a slightly reduced risk for lighter drinkers results in the J-shaped alcohol-mortality curve. Limited data suggest a more favorable mortality experience for drinkers of wine than for drinkers of liquor or beer. To examine these relations, the authors performed a cohort study of participants in a large Northern California prepaid health care program. Demographic and history data were collected from 128,934 adults undergoing health evaluations in 1978-1985, with subsequent death ascertained by an automated linkage system. Cox proportional hazards models with eight covariates were used to determine relative risk estimates according to total alcohol intake and days per week of drinking wine, wine types, beer, or liquor. The J-shaped alcohol-mortality relation was stable for 20 years. Independently, frequency of wine drinking was associated with lower mortality risk (p<0.001) largely because of lower coronary disease risk. Similar risk reductions were associated with red wine, white wine, other types of wine, and combinations of wine types. Much of the lower risk associated with light drinking was related to wine drinking. The authors conclude that drinkers of any type of wine have a lower mortality risk than do beer or liquor drinkers, but it remains unclear whether this reduced risk is due to nonalcoholic wine ingredients, drinking pattern, or associated traits.

Adult↗

C-reactive protein, Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus and risk for myocardial infarction.

PURPOSE: C-reactive protein (CRP), Chlamydia pneumonia, Helicobacter pylori, and cytomegalovirus (CMV) have each been associated with atherosclerosis. We assessed how infection and CRP related to risk for subsequent myocardial infarction (MI). METHODS: Using a nested case-control design, we assessed how these factors independently and jointly affected risk for myocardial infarction (MI). Cases of first MI (N = 121) were identified from among participants in a multiphasic health check-up cohort. Controls without MI (N = 204) were matched to cases by gender, age, race, and date of serum collection. Sera collected at enrollment were tested for antibodies to infection and for CRP. RESULTS: In multivariate analysis (mean follow-up of 5.1 years), CRP was associated with MI only in subjects older than 51 years (p = 0.004). Although H. pylori infection increased risk for MI, this association was modest (OR = 1.90, 95% CI = 0.97-3.71) and was not evident in non-smokers or when adjusted for education. No association between C. pneumoniae or cytomegalovirus and MI was observed, nor was the association between CRP and MI explained by these infections. CONCLUSIONS: Elevated CRP is a risk factor for subsequent MI in older individuals. The relationship between Hp and MI may be due to confounding or co-linearity with socioeconomic status.

Adult↗

Risk of subsequent cancer following invasive or in situ squamous cell skin cancer.

PURPOSE: Determine the risk of subsequent cancer following squamous cell skin cancer. METHODS: Using computerized surgical pathology records and membership data from a health maintenance organization, we retrospectively identified 822 individuals with primary squamous cell skin cancer (SCSC) and 3662 comparison subjects matched for age, sex, race, residence area, and length of membership. Patients were included in the study if they had no prior history of cancer, and received at least one multiphasic health checkup and questionnaire (MHC). Patients were followed for subsequent invasive cancer up to 24 years, with a mean follow-up time of 7.8 years. RESULTS: SCSC patients had a significantly greater risk [adjusted for body mass index (BMI) and education] for subsequent cancer overall (excluding non-melanoma skin cancer) [risk ratio (RR) = 1.4, 95% confidence interval (CI) = 1.2-1.6], and for basal cell skin cancer (RR = 13.8, 95% CI = 8.8-21.9), digestive (RR = 1.6, 95% CI = 1.1-2.4), and genitourinary cancers (RR = 1.5, 95% CI = 1.0-2.0). An increased, but not statistically significant, adjusted risk (RR > or = 1.4) was also observed for lip, oral cavity, and pharynx cancer (RR = 3.9, 95% CI = 0.6-25.0); non-cutaneous squamous cell cancer (RR = 1.9, 95% CI = 0.9-4.4); and respiratory and intrathoracic cancer (RR = 1.4, 95% CI = 0.8-2.6). The addition of alcohol consumption, combined occupational exposure, marital status, and smoking history to the multivariate model did not materially change any significant positive associations with SCSC. CONCLUSIONS: Our results suggest that patients diagnosed with SCSC may be at an increased risk of subsequent cancer at many sites, although several estimated risk estimates were within the limits of chance given no true association.

Aged↗

Suture algorithm for the broad or bulbous nasal tip.

The history and current status of suture techniques to correct a broad or bulbous nasal tip are reviewed. General principles for suture techniques to control tip shape are discussed; they include leaving an approximately 6-mm-wide lateral crus. The algorithm presented includes four sutures, all of which are not necessary in every case. These sutures include (1) the transdomal suture (to narrow the individual domes), (2) the interdomal suture (to provide symmetry and tip strength and sometimes to narrow the tip complex), (3) the lateral crural mattress suture (to reduce lateral crural convexity), and (4) the columella-septal suture (to prevent tip drop and adjust tip projection). The lateral crural mattress suture is the newest of these sutures. It specifically controls undesirable convexity of the lateral crus. The four-suture algorithm is principally designed for primary open rhinoplasties. However, it is also recommended for secondary rhinoplasties. A minor modification is suggested for use in closed rhinoplasties. The algorithm is intended to reduce the difficulty of determining which of the currently available rhinoplasty sutures are useful and in what order they should be used. Illustrative cases are provided. The advantages and disadvantages of this particular algorithm, compared with others that have been proposed, are also reviewed.

Algorithms↗