Comparing different routes and doses of phytonadione for reversing excessive anticoagulation

BACKGROUND: Significant controversy exists concerning how best to reverse excessive anticoagulation (due to warfarin sodium therapy) with phytonadione (vitamin K1) while avoiding overcorrection in patients who need to have anticoagulation therapy maintained. METHODS: A retrospective review of phytonadione use in reversing excessive anticoagulation was performed in 3 institutions. The effectiveness of low-dose (< or =0.5 mg) intravenous (LDIV), high-dose (1-10 mg) intravenous (HDIV), subcutaneous (1-10 mg) (SC), and oral (2.5 or 5 mg) (PO) phytonadione was evaluated within 48 hours of administration. Anticoagulation correction (international normalized ratio [INR], > or =2.0 and < or =5.0) occurred in 5 of 8 patients in the LDIV, 5 of 9 in the HDIV, 7 of 10 in the SC, and 5 of 6 in the PO groups. Correction was inadequate (INR >5.0) in 2 of 8 patients in the LDIV, 0 of 9 in the HDIV, 3 of 10 in the SC, and 1 of 6 in the PO groups. Overcorrection (INR <2.0) occurred in 1 patient in the LDIV, 4 patients in the HDIV, 0 in the SC, and 0 in the PO groups. CONCLUSIONS: Anticoagulation correction was achieved in most patients in all 4 groups. The HDIV method was most effective in lowering the INR to less than 5.0, but overcorrection occurred more frequently (4 patients in the HDIV vs 1 patient in the LDIV and 0 patients in the SC and PO groups). Failure to achieve an INR of less than 5.0 was a greater problem in the SC group (3 patients in the SC vs 2 patients in the LDIV and 1 patient in the PO groups). The LDIV and PO methods appear to be acceptable alternatives to the HDIV and SC methods currently recommended.     

Anthropometric and other risk factors for ovarian cancer in a case-control study

Because it has been suggested that an environmental factor may play a role in the etiology of ovarian cancer, a case-control study was conducted to assess some environmental and other risk factors for ovarian cancer from 1994 to 1996 in northern Kyushu, Japan. We analyzed the data of 89 cases with epithelial ovarian cancer and 323 controls without any cancer or ovarian disorder. After controlling for the effect of potential confounders, the odds ratios of ovarian cancer across increasing quartiles of the heaviest body weight were 1.00, 1.15, 1.71, 2.29 (P = 0.008, test for trend). Significantly increased risks were noted for a history of diabetes mellitus (P < 0.05), and for a family history of ovarian cancer (P < 0.05). Significantly decreased trends for risk were obtained for the number of pregnancies (P < 0.01) and the number of live births (P < 0.001). This study provides additional support for an association between obesity and the risk of ovarian cancer. This relationship may at least partly explain the recent increase in the incidence of ovarian cancer in Japan, although possible contributions of other factors can not be ruled out.     

A case-control study of dietary intake and other lifestyle risk factors for hyperplastic polyps

BACKGROUND & AIMS: Despite the high prevalence of the hyperplastic polyp, little is known about its etiology. The aim of this study was to assess the relationship between diet and other lifestyle factors and the presence of colorectal hyperplastic polyps. METHODS: Information on diet and other known or suspected risk factors for colorectal cancer or adenoma was collected among 81 subjects with hyperplastic polyps and 480 controls. RESULTS: The multivariate-adjusted odds ratio (OR) for hyperplastic polyps for individuals in the upper vs. the lower quartile was 0.30 (95% confidence interval [CI], 0.10-0.88) for dietary fiber, 0.32 (95% CI, 0.11-0.96) for dietary calcium, 0.90 (95% CI, 0.27-2.95) for total fat, and 2.02 (95% CI, 1.05-3.91) for alcohol consumption. Compared with individuals in the lower category, those in the upper category of body mass index had a higher risk for hyperplastic polyps (OR, 4.50; 95% CI, 1.84-10.97). Cigarette smoking was associated with a higher risk (OR, 1.97; 95% CI, 1.02-3.81 for > 20 pack-years vs. never), whereas an inverse association was seen for use of aspirin and other nonsteroidal anti-inflammatory drugs (OR, 0.29; 95% CI, 0.12-0.67 for once per day or more vs. never). CONCLUSIONS: Hyperplastic polyps share common lifestyle risk factors with colorectal adenomas and carcinomas.     

Cigarette smoking and other risk factors for silent cerebral infarction in the general population

Control dried organisms as lenticules are a dependable and convenient alternative to wet cultures for quality assurance and process controls in routine food microbiology. Lenticules are designed to give a fixed, reproducible inoculum over an extended period of time without loss of cultural characteristics or viability. During a period of 23 months, 596 paired counts were performed by both Miles and Misra and spiral plating techniques on lenticule controls. Correlation between the two methods and within batches was excellent. Only 14 counts (2.5%) fell outside the standard operating limit of 0.5 log10. All were within 1.0 log10. On two separate occasions, replicate runs were performed on five reconstituted lenticules from a batch. The counts obtained showed variation within and between lenticules only slightly in excess of what is expected by chance. Lenticule replicates performed by three other laboratories also produced satisfactory results. It is thought that lenticules could improve the accuracy of total plate counts and lead to a better standardization of quantitative methods in food microbiology within and between laboratories.     

Association between an excessive body mass index and coronary heart disease risk factors in military personnel

The purpose of this study was to document the extent of coronary heart disease (CHD) risk factors in military personnel (412 men, 50 women) classified as seriously overweight (body mass index [BMI] 27.0-29.9 kg/m2) or obese (BMI > or = 30 kg/m2) and to evaluate the utility of the BMI to discriminate among individuals with an adverse CHD risk profile. Mean body weight and BMI greatly exceeded Canadian norms, whereas mean heights were average. There were low but significant correlations between BMI and resting and submaximal exercise (stage A of the Canadian Aerobic Fitness Test) heart rates and blood pressures, while the correlation with predicted VO2max was negative. Except for blood glucose level (GLU) in men, there were no significant correlations between BMI and various biochemical indices. Compared to "overweight" men, the percentage of "obese" men with abnormal values for risk factors were higher, particularly for an adverse exercise blood pressure response and low predicted VO2max. In summary, the correlations between BMI and the various CHD risk factors, except for GLU and the exercise parameters, were minimal or moderate at best. It was concluded that in overweight and obese individuals, BMI does not appear to be a particularly sensitive indicator of body fat and risk factors.     

Effect of extracranial carotid artery stenosis and other risk factors for stroke on periventricular hyperintensity

BACKGROUND AND PURPOSE: The pathogenesis of periventricular hyperintensity (PVH) is still uncertain. We investigated the relationship between PVH and risk factors for cerebrovascular diseases, especially extracranial carotid artery stenosis (ECAS). METHODS: We studied PVH and ECAS in 323 subjects between 1991 and 1994. Using 1.5-T MRI scan images, we measured PVH quantitatively at eight points and evaluated cerebral infarction. Duplex carotid sonography was performed on the carotid arteries bilaterally and used to divide the severity of ECAS into five grades. Risk factors for cerebrovascular diseases and atherosclerotic complications were assessed from the clinical history. RESULTS: Age was significantly correlated with the size of frontal and whole PVH (P < .01). Frontal PVH was significantly more severe in subjects with hypertension (P < .05). Frontal, occipital, and whole PVH were significantly more severe in subjects with a history of cerebrovascular accident (P < .01). Other risk factors and atherosclerotic complications were not correlated with PVH. There were no significant differences in the severity of PVH among the five groups of ECAS. The severity of PVH in each region was not related to ECAS. There was no significant difference in the age of patients in relation to the five grades of ECAS. However, PVH was significantly more severe in subjects with lacunar infarction or infarction of the deep border zone (P < .05). There was no relationship between PVH and cortical infarction or infarction of the cortical border zone. CONCLUSIONS: PVH correlated with age, hypertension, and past history of cerebrovascular disease but not with ECAS. PVH was significantly more severe in lacunar infarction and infarction of the deep border zone. These results suggest that small-vessel disease may underlie the pathogenesis and development of PVH.     

Urolase laser prostatectomy in patients on warfarin anticoagulation: a safe treatment alternative for bladder outlet obstruction

Three patients with symptomatic bladder outlet obstruction due to benign prostatic hyperplasia underwent laser prostatectomy using a Neodymium:YAG source delivered with the Urolase right-angle laser fiber. All patients had significant underlying medical problems, and all were fully anticoagulated with oral warfarin (mean prothrombin time 17 seconds). Two were in urinary retention with indwelling catheters preoperatively. Laser prostatectomy was performed in each case without change in the medical regimen, including continuous warfarin dosing. No complications occurred, and in particular, no early or late bleeding episodes were encountered. All are symptomatically improved and catheter-free on follow-up. Laser prostatectomy provides a new and safe therapeutic option in the management of these high-risk patients.     

Delayed lumbar epidural hematoma. Discussion of the risk factors: hypertension, anticoagulation and spinal anesthesia]

We report a case of intracystic papillary carcinoma of the breast in a 62-year-old Japanese man, who came to our hospital complaining of a right subareolar mass. Imaging diagnosis was a cyst with an intracystic component. Since repeated aspiration biopsy cytology was interpreted as a borderline lesion, no additional treatment had been given. Because he wanted the removal of the mass 14 months after his first visit, an excisional biopsy was performed under local anesthesia. Pathological examination revealed the intracystic component to be non-invasive papillary carcinoma. Although the incidence of male breast cancer is approximately 1% of all breast cancer, intracystic papillary carcinoma in the male is very rare. From a review of the literature on this disease in Japanese men, an intracystic component can often be demonstrated by ultrasound. However, it is difficult to confirm malignant cells by aspiration biopsy cytology of cyst fluid. Since some cases have a local relapse, excisional biopsy and long-term follow-up are indicated.     

Dysplastic nevi and other risk markers for melanoma

Risk markers for cancer are genetic or behavioral attributes that are statistically associated with increased incidence of cancer. Risk may be assessed either in case-control studies, or in cohort studies in which individuals with particular attributes are followed and cancer risk is determined by direct observation. Both of these methods have been used to determine the major risk markers for melanoma. The single most important risk marker is the presence on the skin of dysplastic nevi. Dysplastic nevi may be regarded as intermediate lesions of tumor progression, in that approximately 30% of melanomas arise in association with a precursor nevus, which is most commonly dysplastic. However, paradoxically, because they are vastly more numerous than melanoma, most dysplastic nevi are stable lesions that do not progress. Additional important melanoma risk factors include a family and/or personal history of melanoma. A third major category of risk markers includes indicators of acute and chronic exposure to the sun, including freckles, actinic skin damage, and a history of sunburn. Evaluation of these markers in oncological patients and their first-degree relatives can identify a population of individuals whose risk for melanoma ranges from several-fold to more than 100-fold greater than that of random population members. Efforts directed at early diagnosis in these individuals can result in recognition of melanomas in their early, curable stages.     

Occurrence of diabetes, hyperinsulinism and other risk factors for atherosclerosis in patients with pernicious anemia]

The anticonvulsant action of felbamate (25, 50, 100 and 150 mg/kg i.p.) was tested against motor seizures induced by pentylenetetrazol in five age-groups of rats (7, 12, 18, 25 and 90 days old). In adult rats, felbamate suppressed generalized tonic-clonic seizures leaving intact minimal clonic seizures. In all groups of rat pups felbamate exhibited a specific action against the tonic phase of generalized tonic-clonic seizures. In addition, the highest dose of felbamate was found to suppress minimal seizures in 18-day-old rats. The changes of felbamate action during ontogeny might be due to multiple mechanisms of anticonvulsant action with an uneven developmental profile.     

Lifestyle risk factors for osteoporosis

The lifestyle risk factors of lack of exercise, smoking, alcohol intake, and caffeine consumption are reviewed for physiological effects which place women at risk for osteoporosis.     

Deficient counterregulation: a possible risk factor for excessive fetal growth in IDDM pregnancies

OBJECTIVE: The rate of macrosomia in infants born to women with IDDM remains high despite intensive insulin therapy and good glycemic control. We hypothesized that one of the factors contributing to this high rate of macrosomia is deficient counterregulatory hormonal responses to hypoglycemia. RESEARCH DESIGN AND METHODS: Hypoglycemia was induced in 17 women with IDDM and 10 normal control subjects at 24-28 and at 32-34 weeks' gestation, using the hypoglycemic clamp technique. Plasma glucose concentrations were decreased to 3.3 mmol/l and maintained at this level for 1 h. Blood samples were drawn every 15 min for measurement of counterregulatory hormone concentrations. RESULTS: All 17 women with IDDM had diminished epinephrine responses to hypoglycemia, compared with control subjects. Eight of the women with IDDM (nonresponders) had minimal or no responses (< 165 pmol/l above baseline) and nine women (responders) had a moderate response (244-764 pmol/l). Of the eight nonresponders, seven had large infants (birth weight in the upper quartile), while only three of the nine responders had large infants (P < 0.05). CONCLUSIONS: Severely impaired counterregulatory epinephrine responses to hypoglycemia in pregnant women with IDDM may be a factor contributing to excessive fetal growth. We speculate that in these women, recurrent episodes of hypoglycemia may result in frequent bouts of increased caloric intake, with repeated episodes of transient hyperglycemia leading to fetal hyperinsulinism and excessive fetal growth.     

The prevalence of insulin resistance and other cardiovascular disease risk factors in healthy elderly southwestern Nigerians

A derivative of coumarin, 8-nitro-7-hydroxycoumarin (8-NO2-7-OHC), was synthesised, purified and characterised. The cytostatic and cytotoxic nature of this compound was determined using both human and animal cell lines grown in vitro for 96 h in the presence of drug (0-500 microM, equivalent to 0-104 microg/ml). 8-NO2-7-OHC was shown to be cytotoxic to three cell lines, but cytostatic to all cell lines tested. With K562 and HL-60 cells, cell death was found to occur by apoptosis. This cytotoxic effect was found to be irreversible, with cell death continuing to occur following a 96 h recovery period. The cytostatic effects were found to be irreversible in four of the five cell lines tested. 8-NO2-7-OHC demonstrated its cytostatic effects within 24 or 48 h, while its cytotoxic effects appeared more gradually. The IC50 of 8-NO2-7-OHC was 475-880 microM, depending on the cell line tested. It was shown to exert its cytostatic effect through an alteration of cell cycle. It also inhibited DNA synthesis. The toxicity of 8-NO2-7-OHC does not appear to be mediated through the multi-drug resistance (MDR) protein since it caused significant cytostatic and cytotoxic effects to CHrC5 cells, which have an increased expression of this protein. This compound was shown to be non-mutagenic in a standard Ames test, both with or without a mammalian enzyme activation system. The applications and mode of actions of coumarins are discussed.     

Contribution of job control and other risk factors to social variations in coronary heart disease incidence

BACKGROUND: The first Whitehall Study showed an inverse social gradient in mortality from coronary heart disease (CHD) among British civil servants--namely, that there were higher rates in men of lower employment grade. About a quarter of this gradient could be attributed to coronary risk factors. We analysed 5-year CHD incidence rates from the Whitehall II study to assess the contribution to the social gradient of psychosocial work environment, social support, coronary risk factors, and physical height. METHODS: Data were collected in the first three phases of examination of men and women in the Whitehall II study. 7372 people were contacted on all three occasions. Mean length of follow-up was 5.3 years. Characteristics from the baseline, phase 1, questionnaire, and examination were related to newly reported CHD in people without CHD at baseline. Three self-reported CHD outcomes were examined: angina and chest pain from the Rose questionnaire, and doctor-diagnosed ischaemia. The contribution of different factors to the socioeconomic differences in incident CHD was assessed by adjustment of odds ratios. FINDINGS: Compared with men in the highest grade (administrators), men in the lowest grade (clerical and office-support staff) had an age-adjusted odds ratio of developing any new CHD of 1.50. The largest difference was for doctor-diagnosed ischaemia (odds ratio for the lowest compared with the highest grade 2.27). For women, the odds ratio in the lowest grade was 1.47 for any CHD. Of factors examined, the largest contribution to the socioeconomic gradient in CHD frequency was from low control at work. Height and standard coronary risk factors made smaller contributions. Adjustment for all these factors reduced the odds ratios for newly reported CHD in the lowest grade from 1.5 to 0.95 in men, and from 1.47 to 1.07 in women. INTERPRETATION: Much of the inverse social gradient in CHD incidence can be attributed to differences in psychosocial work environment. Additional contributions were made by coronary risk factors--mainly smoking--and from factors that act early in life, as represented by physical height.     

Epidemiology of and risk factors for pancreatic cancer

In the United States, incidence of and mortality from pancreatic cancer increased for several decades earlier in this century but have tended to level off in recent years. Rates increase with age and are higher in blacks than in whites and higher in men than in women. Cigarette smoking increases the risk of pancreatic cancer, while alcohol consumption largely shows no relationship, coffee consumption shows little, if any, association, and a number of occupational exposures seem to be associated but the results are not fully consistent. Finally, human studies have suggested positive associations with meat consumption and carbohydrate intake and a protective effect of dietary fiber and consumption of fruits and vegetables. Thus, much progress has been made in the last two decades in identifying risk factors, but much epidemiologic work is needed to identify and reduce putative exposures.     

Maternal education and risk factors for small-for-gestational-age births

OBJECTIVES: This article examines the association between maternal education, smoking and other risk factors and small-for-gestational-age (SGA) births. DATA SOURCE: The data are from the 1994/95 National Longitudinal Survey of Children and Youth. The analysis was restricted to a subsample of 4,181 children younger than age 2 and was based on information provided by their biological mothers. ANALYTICAL TECHNIQUES: Logistic regression was used to estimate the odds ratios for SGA by maternal education, controlling for maternal smoking during pregnancy, household income, family status, maternal age at birth of child, and use of prenatal care. MAIN RESULTS: Maternal education and smoking during pregnancy appear to have independent effects on SGA, after controlling for other risk factors. The effects of maternal education, smoking and other risk factors are likely underestimated, as the analysis pertains only to children who had survived at the time of the interview.