Alcoholism: independent predictor of survival in patients with head and neck cancer

BACKGROUND: Despite recognition of the high prevalence of alcoholism among patients with head and neck cancer, the prognostic importance of alcoholism has not been evaluated adequately. Previous investigators have speculated that alcoholic patients may have a poorer prognosis than nonalcoholic patients because of more advanced stage of cancer, the immunosuppressive effects of alcohol, and an increased rate of death due to other alcohol-related diseases. PURPOSE: The goal of this population-based study was to identify the features of alcoholism that are associated with survival for patients with head and neck cancer and to develop an alcoholic severity staging system from a composite of the independent features of alcoholism. METHODS: This prospective study included 649 patients who were diagnosed with cancer of the oral cavity, oropharynx, hypopharynx, or larynx during the period from September 1, 1983, through February 28, 1987, in a three-county area of western Washington state that participates in the Surveillance, Epidemiology, and End Results Program of the U.S. National Cancer Institute. Details on lifetime alcohol consumption, treatment for alcoholism, abstinence from alcohol prior to the diagnosis of cancer, and alcohol-related health problems were ascertained through in-person interviews near the time of diagnosis. Patients were classified as either nonalcoholics or alcoholics according to their responses to questions from the Michigan Alcoholism Screening Test. The measures of alcohol consumption and abuse that were found to be independently associated with 5-year survival by logistic regression analysis were combined using conjunctive consolidation to create a final composite variable, called an alcoholic severity stage. Cox proportional hazards regression analysis was done to estimate the relative risk (R) of death within 5 years due to specific causes of death for each of the alcoholic severity stages. RESULTS: Alcoholism (RR = 2.06; 95% confidence interval [CI] = 1.43-2.98) and a history of alcohol-related systemic health problems (i.e., liver disease, pancreatitis, delirium tremens, or seizures) (RR = 2.76; 95% CI = 1.69-4.49) were associated with an increased risk of death, whereas abstinence (i.e., the consumption of fewer than one drink per week at 1 year prior to the diagnosis of cancer) (RR = 0.62; 95% CI = 0.39-0.97) was associated with a decreased risk of death. These associations were independent of age, site of cancer, anatomical stage, histopathologic grade, smoking, and type of antineoplastic treatment. Patients in the two worst alcoholic severity stages had an increased risk of dying not only of head and neck cancer but also of cardiovascular disease, pulmonary disease, and other alcohol-related causes. CONCLUSIONS: Alcohol abuse, measured by alcohol consumption, functional impairment, a history of alcohol-related health problems, or abstinence, can provide important prognostic information for patients with head and neck cancer. Our results suggest that sobriety among alcoholic patients can lead to prolonged survival.     

Comparison of PF4/heparin ELISA assay with the 14C-serotonin release assay in the diagnosis of heparin-induced thrombocytopenia

The diagnosis of heparin-induced thrombocytopenia (HIT) may be affirmed by demonstrating heparin-dependent anti-platelet antibodies using the 14C-serotonin release assay (SRA). In this study, results of the SRA was compared with the recently described platelet factor 4 (PF4)/heparin enzyme-linked immunosorbent assay (ELISA). Compared with the SRA, the sensitivity and specificity of a PF4/heparin ELISA was 87% and 92%, respectively, using an assay developed in our laboratory; and 90% and 98%, respectively, using a commercially developed kit (Diagnostica Stago, Asnieres, France). However, antibodies to PF4/heparin were also detected in up to 8% of patients whose plasma was negative by SRA, and 23% of patients receiving heparin who were not thrombocytopenic. These data indicate that results obtained with the PF4/heparin ELISA and the SRA are generally in accord in patients with a clinical diagnosis of HIT. However, discrepant results occur in approximately 20% of cases because of the greater sensitivity of ELISA and the possible involvement of other heparin-binding proteins. The fact that each assay contributes independent information in some cases must be considered in the sequence of test performance and in providing consultation to the practicing hematologist.     

The kappa opioid receptor expressed on the mouse R1.1 thymoma cell line down-regulates without desensitizing during chronic opioid exposure

The R1.1 mouse thymoma cell line expresses a single class of kappa opioid receptors that is negatively coupled to adenylyl cyclase through a Bordetella pertussis toxin-sensitive inhibitory guanine nucleotide-binding protein. The aim of the present study was to determine whether chronic opioid treatment of R1.1 cells altered either the binding properties or the functional response associated with the kappa opioid receptor. Culturing of R1.1 cells with the kappa-selective agonist (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide methane-sulfonate hydrate (U50,488) for 3 hr and longer, followed by extensive washing of R1.1 cell membranes, produced a concentration- and time-dependent reduction in the binding of the kappa-selective ligand (5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1- oxaspiro(4,5)dec-8-yl) benzeneacetamide ([3H]U69,593). Culturing of R1.1 cells with 100 nM U50,488 for 24 hr produced approximately a 50% reduction in the Bmax value for [3H]U69,593 and [3H]naloxone binding. In contrast to the reduction in binding, there was no change in the inhibition of adenylyl cyclase activity by (-)-U50,488. To determine whether kappa opioid receptor function was maintained by spare receptors after agonist-induced down-regulation, membranes from untreated R1.1 cells were incubated with 400 nM of the irreversible opioid antagonist beta-chlornaltrexamine (beta-CNA) followed by extensive washing. beta-CNA produced a 50% reduction in the [3H]U69,593 binding and a 6-fold increase in the IC50 value for (-)-U50,488 inhibition of adenylyl cyclase activity, with no change in the maximal inhibition of cyclic AMP levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

The possible influence of the menstrual cycle on the adherence of Candida albicans to human buccal epithelial cells in vitro

Although the influence of the menstrual cycle on both vaginal candidosis and Candida albicans adherence to vaginal epithelial cells in vitro has been shown to be significant, similar studies have not been made on oral candidosis and adherence to buccal epithelial cells. The aim of this study was therefore to use an in vitro adherence assay to investigate the possible influence of the menstrual cycle on the adherence of C. albicans to buccal epithelial cells. Epithelial cells were collected from a single, healthy, female volunteer on days 5, 15, 22 and 28 of six menstrual cycles. Adherence of C. albicans was significantly higher to buccal epithelial cells collected on day 5 of the menstrual cycle when compared with days 15, 22 and 28, both in terms of the percentage of buccal epithelial cells with adherent C. albicans and the number of C. albicans adhering per 200 buccal epithelial cells in four out of six menstrual cycles (p < 0.001). This result indicates that hormonal influences should be considered when buccal epithelial cells are used in vitro to assess candidal adherence and may implicate hormonal factors in the aetiology of oral candidosis.     

Randomized trial of breast self-examination in Shanghai: methodology and preliminary results

BACKGROUND: The efficacy of breast self-examination in helping to reduce mortality from breast cancer has not been rigorously demonstrated. PURPOSE: To assess efficacy, a large, randomized trial was initiated in Shanghai, China. METHODS: From October 1989 to October 1991, 267040 current and retired female employees associated with 520 factories in the Shanghai Textile Industry Bureau were randomly assigned on the basis of factory to either a self-examination instruction group (133375 women) or a control group (133665 women). The women were born within the period from 1925 through 1958. Women in the instruction group were given intensive training in breast self-examination, including the use of silicone breast models and personalized instruction, plus two subsequent reinforcement sessions and multiple reminders to practice the technique. Women in the control group were asked to attend training sessions on the prevention of low back pain. All women have been followed for the development of breast diseases and for death from breast cancer. RESULTS: A high level of participation during the first 4-5 years of the trial was documented among women in the instruction group. Randomly sampled women in this group demonstrated greater proficiency in detecting lumps in breast models than did randomly sampled women in the control group. Approximately equal numbers of breast cancers were detected in the two groups (331 in the instruction group and 322 in the control group) through 1994, which is the last year for which case-finding efforts have been completed. The breast cancers detected in the instruction group were not diagnosed at an appreciably earlier stage or smaller size than those in the control group. More benign breast lesions were detected in the instruction group than in the control group (1457 versus 623, respectively), suggesting a higher index of suspicion for women who received training. Cumulative breast cancer mortality rates through 5 years from entry into the study were nearly equivalent for the two groups. CONCLUSIONS: Breast self-examination has not led to a reduction in mortality from breast cancer in this study cohort in the first several years since the trial began. A shift toward the diagnosis of disease at a less advanced stage in women given instruction has also not been demonstrated. Longer follow-up of participants in this trial is required before final assessment can be made of the efficacy of breast self-examination. IMPLICATIONS: At this time, there is insufficient evidence to recommend for or against the teaching of breast self-examination.     

Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial

BACKGROUND: The efficacy of antiresorptive therapy in preventing fractures in women at highest fracture risk, such as very elderly women or those with severe osteoporosis, is uncertain. PARTICIPANTS AND METHODS: Using data from a double-blind, randomized, placebo-controlled clinical trial that enrolled 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density (BMD) and existing vertebral fractures, we examined the consistency of the effect of treatment with alendronate sodium in preventing fractures within a priori-specified risk subgroups defined at baseline by age, bone density, number of preexisting vertebral fractures, and history of postmenopausal fracture. The women were randomized to oral administration of alendronate or placebo and followed up for an average of 2.9 years. The initial dose of alendronate sodium was 5 mg/d; the dosage was increased from 5 to 10 mg/d at 24 months. New vertebral fractures, the primary end point of this arm of the trial, were defined by morphometry as a decrease of 20% and at least 4 mm in any vertebral height between baseline and a follow-up radiograph at 36 months. Incident clinical fractures, the secondary end point, included nonspine and clinical (symptomatic) vertebral fractures. All clinical fractures were confirmed with x-ray film reports or, in the case of clinical vertebral fractures, x-ray films. RESULTS: Overall, there was a 47% significant reduction in risk of new vertebral fractures in the alendronate group compared with the placebo group. The reduction in risk of new vertebral fracture was consistent across fracture risk categories including age (relative risk [RR], 0.49 in women < 75 years compared with 0.62 in those > or = 75 years), BMD (RR, 0.54 in women with a femoral neck BMD < 0.59 g/cm2 [median] compared with 0.53 in those with a BMD > or = 0.59 g/cm2), and number of preexisting vertebral fractures (RR, 0.58 in women with 1 vertebral fracture compared with 0.52 in those with > or = 2). The overall significant 28% reduction in risk of incident clinical fractures in the alendronate group compared with the placebo group was also observed within these subgroups. Compared with the number of lower-risk women, a similar or smaller number of high-risk women needed to be treated to prevent 1 fracture. For example, 8 women aged 75 years or older compared with 9 women younger than 75 years, or 4 women with 2 or more existing vertebral fractures compared with 16 women with 1 existing vertebral fracture, needed to be treated with alendronate for 5 years to prevent 1 new vertebral fracture. CONCLUSIONS: Alendronate effectively reduces fracture risk in postmenopausal women with vertebral fractures and low BMD, including those women at highest risk because of advanced age or severe osteoporosis. Since the risk reductions observed with alendronate treatment were consistent within fracture risk categories, more fractures were prevented by treating women at highest risk.     

Erythrocyte sodium lithium countertransport in normal and hypertensive pregnancy: relation to haemodynamic changes

OBJECTIVE: To establish the changes in erythrocyte sodium lithium countertransport (SLC) with advancing normal pregnancy and to determine if these changes were different in pregnancy induced hypertension (PIH). The changes in both groups were assessed in relation to haemodynamic changes. DESIGN: SLC, mean arterial pressure (MAP), cardiac output (CO) and total peripheral vascular resistance (TPVR) were determined serially during normal pregnancy and cross-sectionally in PIH. Women were studied again 20 weeks after delivery where possible. SETTING: Routine antenatal clinic and antenatal ward of a regional reference centre. SUBJECTS: Fifty-one normal primigravid women were studied serially and 41 primigravid women with PIH were studied at time of diagnosis. RESULTS: During normal pregnancy SLC (mmol Li/h/l cells) increased from a nonpregnant value of 0.24 +/- 0.02 (mean +/- SEM) to 0.32 +/- 0.02 at 14 weeks, and 0.37 +/- 0.02 at 20 weeks gestation. This was maintained until 38 weeks (0.40 +/- 0.02). The increase until 20 weeks occurred at the time of greatest change in CO (5.10 +/- 0.18 to 6.79 +/- 0.20 l/min) and TPVR (1327 +/- 58 to 969 +/- 33 dyn/s/cm-5). The decrease in TPVR with a rise in SLC is opposite to the relation reported in essential hypertension so that a functional relation is unlikely. However, the changes within pregnancy were positively correlated (r = 0.43, P < 0.01). In hypertensive pregnancies TPVR was elevated compared with normotensive pregnancies (1543 +/- 100 vs 1090 +/- 37) but the SLC was not different from that found in normotensive pregnancies (0.43 +/- 0.02 vs 0.40 +/- 0.02). CONCLUSIONS: The changes in SLC activity suggest dynamic effects on erythrocyte membrane function during pregnancy. However, no differences could be found between normal and hypertensive pregnancy and SLC is unlikely to be of value as a marker of hypertensive risk during pregnancy.     

Laparoscopic cholecystectomy in pancreas transplant recipients

Laparoscopic cholecystectomy is the treatment of choice for symptomatic cholelithiasis. Since its introduction in 1987, this procedure has been employed with increasing frequency as its safety has been documented in numerous studies. Absolute contraindications to laparoscopic cholecystectomy have become relative contraindications, and patients previously felt to be at excessive risk for laparoscopic cholecystectomy are viewed as patients who may benefit from laparoscopic cholecystectomy. The use of this procedure in patients with comorbid medical conditions has the potential to decrease patient morbidity. Patients who have previously undergone solid organ transplantation and require immunosuppressive therapy are a group of patients who may benefit from laparoscopic cholecystectomy. We report four patients who have previously undergone combined renal and pancreas transplantation who underwent successful laparoscopic cholecystectomy.