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Biomedical subjects

R Bliss

Publications and source records attributed to R Bliss.

15 recordsLinked to original sources

AMPA-induced excitotoxicity increases nuclear levels of CAD, endonuclease G, and acinus and induces chromatin condensation in rat hippocampal pyramidal neurons.

Programmed cell death has been linked to AMPA-receptor-mediated excitotoxicity in pyramidal neurons of the hippocampus. The intent of this study was to investigate the roles of caspase-dependent and independent nuclear death-related factors in mediating AMPA-induced nuclear changes in PyNs by use of immunohistochemistry and transmission electron microscopy (TEM). Data indicate increases in the nuclear levels of caspase-activated acinus and DNase and Endonuclease G (a caspase-independent endonuclease) in CA1 and CA3 PyN nuclei with different temporal patterns following an AMPA-insult. Hoechst staining and TEM confirm AMPA-induced chromatin condensation. The presence of active acinus in nuclei suggests it mediates chromatin condensation. Interestingly, a DNA fragmentation labeling protocol showed that there was no chromatin cleavage up to 90 min after AMPA-insult. Overall, we conclude that: 1) AMPA-induced excitotoxicity increases nuclear immunoreactivity of pro-death enzymes from multiple programmed cell death pathways, 2) differential chromatin condensation patterns occur between CA1 and CA3, and 3) there is no chromatin cleavage within our experimental timeframe.

Animals↗

Phaeochromocytomas presenting as acute crises after beta blockade therapy.

OBJECTIVE: Phaeochromocytoma crisis is a life-threatening emergency that may be undiagnosed because of its numerous, nonspecific manifestations. We analysed, retrospectively, the presentation, management and outcome of patients who were admitted to our institution with phaeochromocytoma crises over a 5-year period. RESULTS: Five patients (two males, three females; mean age 34.6 years, range 19-51 years) who presented as emergencies requiring intensive care, with multiple non-specific manifestations and previously undiagnosed pheochromocytoma, were identified. The initial presentation included features of cardiomyopathy (n = 3), atypical pneumonia with myocarditis (n = 1) and acute abdomen (n = 1). Only one of the five cases had a raised blood pressure at the time of the acute presentation. Initiation of beta blockers in four patients was associated with further deterioration in haemodynamic status, labile blood pressure and cardiac arrhythmias, which led to the diagnosis of the underlying phaeochromocytoma. Following intensive supportive therapy and alpha blockade, all five patients recovered and underwent elective surgical removal of phaeochromocytoma, uneventfully. CONCLUSION: Unexplained cardiopulmonary dysfunction, particularly after the institution of beta blockers, should alert clinicians to the possibility of phaeochromocytoma. A high index of suspicion is essential to reduce morbidity and mortality in these patients through early diagnosis and aggressive management.

Acute Disease↗

Ultrasound scan-guided core sampling for diagnosis versus freehand FNAC of the thyroid gland.

BACKGROUND AND AIM: Freehand fine needle aspiration cytology (FNAC) is an obligatory investigation of the thyroid nodule. Between 5.0-43.1% of FNAC samples are reported as being initially unsatisfactory. In our unit, thyroid freehand FNAs are performed with a small needle (21 or 23G). Non-dominant nodules as part of multinodular goitres, difficult to palpate nodules or nodules with previously unsatisfactory freehand FNACs are sampled under ultrasound scan (USS) guidance with the larger 20G cutting core sampling technique. We aimed to compare the satisfactory sampling rate and safety of the two different methods. PATIENTS AND METHODS: Cytology forms were reviewed for 262 freehand FNACs and USS-guided core samples, performed in our unit over a two-year interval (1 July 1999 to 30 June 2001). RESULTS: Ultrasound-guided core samples for cytology were unsatisfactory (AC0-1) in 19/121 (15.6%) of the cases, compared with 66/141 (46.8%) of freehand FNACs (p value = < 0.0001). Ten out of eleven patients (91%) had a satisfactory USS-guided core after an unsatisfactory freehand FNA; 7/15 patients (46.7%) had satisfactory repeat freehand FNACs following an initial unsatisfactory freehand FNAC (p value = 0.0191). There were no complications as a result of either freehand FNAC or USS-guided core sampling. CONCLUSION: USS-guided cores provided more satisfactory samples for assessment than freehand FNACs. The USS-guided technique is safe despite the use of the larger cuffing needle. The USS-guided core sampling was also a useful tool for repeat thyroid nodule sampling after an unsatisfactory freehand FNAC.

Biopsy, Fine-Needle↗

Treatment of spit tobacco users with transdermal nicotine system and mint snuff.

The purpose of this study was to examine the effects of nicotine patch and mint snuff (a nonnicotine product) on craving, withdrawal symptoms, and treatment outcome. This study involved a 2 x 2 factorial design, with Active Nicotine Versus Placebo Patch as one of the factors and Mint Snuff Versus No Mint Snuff as the other factor. Spit tobacco users (N = 402, n = 100-101 in each condition) were randomly assigned to 1 of the 4 treatment conditions for a period of 10 weeks. Treatment outcome was measured up to 62 weeks. The results showed that the nicotine patch was effective in increasing short-term abstinence over the placebo patch and in reducing craving and withdrawal signs and symptoms from spit tobacco. Although mint snuff was not effective in enhancing treatment outcome, it reduced craving and withdrawal symptoms. No interaction effects were observed. At this time, the use of the nicotine patch and mint snuff should be primarily considered for the reduction of craving and withdrawal symptoms.

Administration, Cutaneous↗

Pathology and outcome of surgical treatment for lithium-associated hyperparathyroidism.

BACKGROUND: Hyperparathyroidism associated with long-term lithium therapy is well described. However, few studies have clearly defined the pathological findings or looked at the outcome of surgical treatment. METHODS: The study was a retrospective review of 11 patients with bipolar affective disorder who had surgery for lithium-associated hyperparathyroidism. RESULTS: Twelve patients were identified who had received lithium therapy, of whom 11 (nine women and two men, aged 46-84 (mean 65) years) had prolonged treatment from 2 to 30 (mean 15.3) years. At operation a single adenoma was identified in six patients, whereas multigland disease was seen in five patients. All patients resumed lithium treatment after operation. One patient had recurrent hyperparathyroidism at 3 years, while another had an increased serum level of parathyroid hormone in the presence of a normal serum calcium level after 1 year. CONCLUSION: Hyperparathyroidism associated with lithium may be due to either parathyroid hyperplasia or adenoma. Observations in the present study supported a true cause and effect relationship. Routine bilateral neck exploration should be performed because of a relatively high frequency of multigland involvement. However, parathyroid resection should be limited to evident disease.

Aged↗

Age is no contraindication to thyroid surgery.

BACKGROUND: There is increased risk of surgical treatment in elderly patients, but little has been written on the safety and efficacy of thyroid surgery in this group. OBJECTIVE: To determine if there is an increased risk of morbidity and mortality of thyroid surgery in patients over 75 years old. PATIENTS AND METHODS: During the period 1986-96, 1631 patients aged 50 and over underwent 1673 procedures by two surgeons in our unit. We retrospectively compared indications for surgery, procedures, pathology complications and mortality in three groups: 50-60-year-olds (725 patients), 61-74-year-olds (685 patients) and those aged 75 years and over (221 patients) RESULTS: The main indication for surgery in all three groups was compression or risk of malignancy. Total thyroidectomy was the main procedure performed. Although benign multinodular goitre was the commonest diagnosis, the over-75-year-olds had fewer benign multinodular goitres than the 61-74 group and more malignancy than the other two groups. There was no significant difference in mortality between the three groups. CONCLUSIONS: Surgery in patients over 75 is as safe as in younger patients with no increase in morbidity and mortality. Benign multinodular goitre is the most common indication for surgery.

Age Factors↗

Safety of cotinine in humans: physiologic, subjective, and cognitive effects.

Preliminary data suggest that cotinine, the major metabolite of nicotine, may be behaviorally active. Studies involving the administration of cotinine at doses that produce high blood concentrations (in excess of those produced by cigarette smoking) may be of interest. This inpatient, 10-day human study examined the safety and the effects from several high doses of oral cotinine fumarate (40, 80, or 160 mg) or placebo in abstinent cigarette smokers. All subjects smoked cigarettes ad lib during the first 2 days of the study, then were required to be abstinent beginning on the third day. All subjects were given placebo on this day to wash out nicotine before the administration of cotinine. Subjects were subsequently randomly assigned in a double-blind manner to cotinine or placebo for the next 3 days to determine the safety profile of cotinine. All subjects were given placebo on the final 3 days to examine cotinine withdrawal symptoms. The results showed no significant physiologic, subjective, or performance effects across the various doses of cotinine and placebo. Furthermore, no cotinine withdrawal effects were observed. This study demonstrates that short-term administration of cotinine to humans at levels as high as 10 times that attained from cigarette smoking is safe with no observable acute or withdrawal effects from cotinine in this setting.

Adult↗

Effects of behavioral and pharmacological treatment on smokeless tobacco users.

The purpose of this study was to examine the effects of 2 mg of nicotine polacrilex versus placebo gum and of group behavioral treatment versus minimal contact on cessation of smokeless tobacco use. Participants (N = 210) were randomly assigned 1 of the 4 treatment conditions. Withdrawal symptoms were assessed throughout the treatment. Follow-up assessments were made at 1, 6, and 12 months posttreatment. Survival curve analysis showed that any of the 3 treatment groups involving group behavioral therapy or placebo gum were equally effective and superior to the minimal contact plus 2 mg of nicotine gum treatment in terms of abstinence. On the other hand, withdrawal symptoms were significantly reduced by nicotine gum, compared with placebo during the initial phases of cessation. The ineffectiveness of nicotine gum on treatment outcome may be attributed to its similarity with smokeless tobacco.

Adult↗

Effects of treatment on cardiovascular risk among smokeless tobacco users.

BACKGROUND: Studies show sustained levels of nicotine among young males using smokeless tobacco, causing concern for subsequent cardiovascular risk. Also, there is little information on effects of nicotine replacement on cardiovascular risk in cessation programs. This study investigates the effects of nicotine gum replacement in smokeless tobacco cessation on cardiovascular risk factors. METHODS: Smokeless tobacco users, ages 18-65, were randomly assigned in a double-blind fashion to 2-mg nicotine or placebo gum. At baseline, Week 4, and Week 8, dependent measurements, heart rate, blood pressure, and weight were recorded, and fasting lipoprotein profiles were drawn. RESULTS: This paper focuses on the smokeless tobacco users who refrained from use during the study period (N = 56). The nicotine gum group weighed less (P = 0.033) than the placebo group throughout the study and weight increased at a significant rate between Weeks 4 and 8 for both groups as gum decreased. Triglycerides were higher for the nicotine gum group than the placebo group (P = 0.031), with triglycerides decreasing between Weeks 4 and 8, with a similar effect seen among nonabstinent smokeless tobacco users. There was no dose, time, or dose by time effect for the other dependent measures. CONCLUSIONS: Among smokeless tobacco users who were abstinent, weight increased, with subjects on nicotine gum weighing less throughout the study. The lipoprotein profile, heart rate, and blood pressure did not improve over time, contrary to smokers in whom HDL increases and heart rate decreases with cessation. This could relate to different routes of administration, pharmacokinetics, or by-products of tobacco smoking being absent in smokeless tobacco. In addition, nicotine gum appeared to have neither an adverse nor a positive effect on heart rate, blood pressure, LDL, HDL, or total cholesterol.

Adult↗

Adherence among children and adolescents with insulin-dependent diabetes mellitus over a four-year longitudinal follow-up: I. The influence of patient coping and adjustment.

An onset cohort of adolescents and children with insulin-dependent diabetes mellitus was studied over a 4-year period. Individual patient psychosocial and demographic factors were assessed at study inception and used to examine aspects of adherence over the follow-up. We found that initial assessment of patient coping (defense level, adaptive strength, and locus of control) and adjustment at study inception were predictive of the level of patient adherence to diabetic regimen over the 4 years of study. Psychosocial variables predicted adherence outcomes independent of patient age. This was found for three domains of adherence, i.e., diet, insulin adjustment, and metabolic monitoring, and for the composite index derived from the separate adherence scales. Preadolescents (ages 9-12) at study entry were more adherent than patients who were already adolescent (ages 13-16) when diagnosed. Using multiple regression, three factors (age, adjustment, ego defense level) accounted for 47% of the variance in adherence. No factors were predictive of change in adherence during the follow-up. Thus, psychosocial characteristics of diabetic children assessed shortly after diagnosis predicted typical or average adherence over a 4-year period. Identification of such characteristics may be useful in developing strategies for intervention early in the course of illness.

Adaptation, Psychological↗

Adherence among children and adolescents with insulin-dependent diabetes mellitus over a four-year longitudinal follow-up: II. Immediate and long-term linkages with the family milieu.

Cross-sectional and longitudinal findings drawn from a 4-year longitudinal study of an onset cohort of preadolescents and early adolescents with insulin-dependent diabetes and their families are presented. Patient and parent perceptions of the family environment near the time of diagnosis are used to examine patterns of adherence in the first year of illness as well as over the four follow-up years. We found that family conflict, cohesion, and organization were strongly associated with independently rated first-year adherence levels. The strongest predictor of longer term adherence was family conflict, as experienced by the patients. In addition, parents' and youngsters' perceptions of family cohesion predicted improved adherence as well as overall higher levels of patient adherence. The findings are discussed with respect to the clinical implications of discovering those family characteristics that can, shortly after diagnosis, predict short- and long-term adherence. In addition, we present planned investigations intended to further clarify paths from family perceptions to individual diabetes behaviors.

Adaptation, Psychological↗

Characteristics of smokeless tobacco users seeking treatment.

Previous studies have described smokeless tobacco (ST) treatment seekers with minimal detail. In the present study, ST users (N = 402), who enrolled in a ST cessation treatment study, were asked to complete an extensive questionnaire that inquired about their ST use patterns, use of other tobacco products, extent of dependence, previous attempts to quit, situations associated with use and support for quitting. The results showed that this population experiences a high level of nicotine exposure and physical dependence on ST. ST use frequently is associated with negative affect situations and times of hunger. A high frequency of users have smoked cigarettes as well as cigars. A supportive social environment for ST cessation exists for these individuals. These results have implications for ST treatment content.

Adaptation, Psychological↗