The association of increasing dietary concentrations of fish oil with hepatotoxic effects and a higher degree of aorta atherosclerosis in the ad lib.-fed rabbit

The long-term effects of consumption of marine long-chain n-3 polyunsaturated fatty acids (PUFA) on atherosclerosis in the rabbit were examined. Female Dutch rabbits were fed purified diets, containing 40 energy% total fat, for a period of 2.5 years. To study the dose response relationship between fish oil intake and atherosclerosis, four diets were formulated with fish oil levels being 0, 1, 10 and 20 energy%. A fifth and sixth group were fed an alpha-linolenic acid-(C18:3, n-3) and linoleic acid-(C18:2, n-6) rich diet, respectively. Every 6 weeks, blood samples were taken for determination of clinical chemical parameters, triacylglycerol and total cholesterol levels. Feeding 10 and 20 energy% fish oil containing diets, resulted in an increase of liver enzymes (AST, ALT and ALP). Histological evaluation of the liver also revealed adverse effects of fish oil containing diets. Triacylglycerol blood levels were similar in all groups, and remained constant throughout the study. Total cholesterol levels in blood was significantly lower in the animals fed a linoleic acid-rich diet, as compared with the other five groups. An n-3 long-chain PUFA concentration dependent increase in aorta plaque surface area was observed in the fish oil groups. A significant positive relationship was found between the group mean score for severity of liver pathology and the aorta plaque surface area. These results indicate that the long-chain n-3 polyunsaturated fatty acids in fish oil may be hepatotoxic to the herbivorous rabbit, which may interfere with the outcome of atherosclerosis studies. This finding necessitates the exclusion of liver pathology in experimental studies on atherosclerosis in animal models.     

Cost-effectiveness of open versus laparoscopic repair for primary inguinal hernia

A cost-effectiveness (CE) analysis was performed of Bassini versus laparoscopic repair for primary inguinal hernia. Incremental costs per 1-year recurrence-free patient were calculated for the societal and hospital perspective. From the hospital perspective, the incremental CE ratio of laparoscopic repair is 5.348 guilders. From the societal perspective, laparoscopic repair is both less costly and more effective than Bassini repair. Results were sensitive to assumptions about recurrence rates, laparoscopic operating time, and return to work. Laparoscopic repair should replace Bassini repair in order to benefit society. From the hospital perspective, the decision to accept laparoscopic repair depends on the willingness to pay.     

Amiodarone-induced pulmonary toxicity in Fischer rats: release of tumor necrosis factor alpha and transforming growth factor beta by pulmonary alveolar macrophages

Amiodarone is an antiarrhythmic drug with numerous side effects, the most serious being the development of pulmonary toxicity. We have previously reported that a single intratracheal instillation of amiodarone to Fischer 344 rats results in pulmonary fibrosis within 6 wk of treatment. Presently, the mechanism of amiodarone-induced pulmonary toxicity is unknown. Cytokines that stimulate fibroblast proliferation and/or collagen production may play a role in amiodarone-induced pulmonary toxicity. To investigate this possibility, female rats were given a single intratracheal instillation of amiodarone (6.25 mg/kg), its metabolite desethylamiodarone (5 mg/kg), or vehicle (sterile water). At 1, 2, 3, or 6 wk after treatment the lungs were lavaged and the recovered cells were counted and identified. The alveolar macrophages were isolated by attachment to plastic petri dishes, cultured overnight, and the spent media collected for tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) analyses. Desethylamiodarone treatment resulted in a neutrophilic alveolitis, but the levels of TNF-alpha and TGF-beta were not significantly different from control animals. In contrast, amiodarone treatment resulted in a lymphocytic alveolitis and significantly higher amounts of TNF-alpha were observed at 3 and 6 wk after treatment. A trend toward higher levels of TGF-beta was also noted in the amiodarone-treated group at wk 1-3 but the values were not significantly different from those of controls. In conclusion, the release of TNF-alpha may play a role in the development of amiodarone-induced pulmonary toxicity.     

Prevalence of human papillomavirus in squamous cell carcinoma of the head and neck determined by polymerase chain reaction and Southern blot hybridization: proposal for optimized diagnostic requirements

OBJECTIVE: To develop Canadian projections for the prevalence and numbers of people with arthritis and arthritis disability, overall and in major age groups. METHODS: Age and sex specific data from the 1991 General Social Survey and the 1994 National Population Health Survey on the prevalence of arthritis and arthritis disability were applied to population projections for Canada for every 5 years between 1991 and 2031. RESULTS: Between 1991 and 2031 we project that the prevalence of arthritis diagnosed by a health professional as a longterm condition in Canada will increase from 10.7 to 15.7%, an increase of 46.7%, and the number of people with arthritis will increase from 2.9 to 6.5 million, an increase of 124%. Comparable changes in prevalence and numbers of people with self-reported arthritis are 17.1% (4.7 million) to 23.6% (9.7 million). Most of the increase will be in the population aged 45+, and not until after 2020 will the comparative increase in the 65+ age group be greater than that for the 45-64 age group. Disability attributed to arthritis in the population aged 15+ is projected to increase from a prevalence of 2.3% (595,000) in 1991 to 3.3% (1.13 million) in 2031. CONCLUSION: There are large projected increases in both the prevalence and numbers of people with arthritis and arthritis related disability that, at least in the next 20 years, will be split between the older half of the working population and those aged 65 and older.     

HLA-DP--part of the concert

Correct decision, when managing the acute abdomen in children, are based on careful clinical assessment. An accurate history and a detailed examination will provide more information than a multitude of investigations. The chronological order to appearance and the progression of each individual symptom must be obtained. Consideration of these dynamic changes will often yield an accurate diagnosis. This article outlines a structured approach to history taking and details the common causes of acute abdomen in childhood.     

Secular changes in radical prostatectomy utilization rates in Olmsted County, Minnesota 1980 to 1995

PURPOSE: We estimated the changes in utilization of radical prostatectomy for treatment of prostate cancer and describe the clinical characteristics of men undergoing radical prostatectomy in a population based setting. MATERIALS AND METHODS: The Rochester Epidemiology Project was used to identify all Olmsted County residents who underwent radical prostatectomy from 1980 to 1995. The community medical records of these men were reviewed to determine the clinical and pathological stage and grade at biopsy and following surgery. RESULTS: From 1980 to 1995, 311 radical prostatectomies were performed on Olmsted County men. From 1980 to 1987 prostatectomy rates ranged from 6.3 to 31.0/100,000 men but rates increased dramatically to 53.6/100,000 in 1988 and 106.2/100,000 in 1992. The rate after 1992 decreased to 53.0/100,000 and then increased slightly to 80.4/100,000. There was a shift to younger age in more recent times (mean patient age 65.4 years in 1980 to 1986 and 62.4 in 1993 to 1995, p = 0.02), a nonsignificant (p = 0.10) trend toward lower pathological stage in recent years (42% stage pT2 in 1980 to 1986 versus 55% in 1993 to 1995) and a significant decrease in the proportion of cases of disease up staged following surgery (53% in 1980 to 1986 versus 37% in 1993 to 1995, p = 0.03). There was no significant trend in pathological grade with time (63% Mayo grade I or II in 1980 to 1986 versus 52% in 1993 to 1995, p = 0.30). CONCLUSIONS: These findings demonstrate an increase in radical prostatectomy rates that coincided with increases in prostate cancer incidence. There was a decrease in population prostatectomy rates in 1993 which was followed by modest increases to levels lower than the peak in 1992. However, the clinical characteristics of patients during this period did not change dramatically, suggesting that in a population based setting the selection factors for patients undergoing surgical treatment may not have changed.     

Serial prostate-specific antigen measurements in men with clinically benign prostatic hyperplasia during a 12-month placebo-controlled study with terazosin. HYCAT Investigator Group. Hytrin Community Assessment Trial

OBJECTIVES: To prospectively analyze whether the treatment of men with clinically benign prostatic hyperplasia (BPH) with alpha blocking agents affects the serum prostate-specific antigen (PSA) levels, and to determine the magnitude of such effect. METHODS: Serial PSA measurements were performed using the Abbott IMx assay over 1 year in 134 men over the age of 55 years participating in the Hytrin Community Assessment Trial (HYCAT). HYCAT is a 1-year, randomized, placebo-controlled, double-blinded study of the alpha1-adrenergic antagonist terazosin. All men had lower urinary tract symptoms and a clinical diagnosis of BPH with an American Urological Association (AUA) symptom index of 13 points or more, an AUA bother score of 8 points or more, and a peak urinary flow rate of less than 15 mL/s. PSA was measured at baseline and at 8, 26, 39, and 52 (end of study) weeks. RESULTS: Baseline serum PSA levels weakly correlated with patients' age at study entry, and modestly with residual urine (positive correlation) and peak flow rate (negative correlation), although none of the levels were statistically significant. Changes of serum PSA during the course of the study did not correlate with either one of the symptom severity or bother assessment tools, residual urine, or peak flow rate. Mean PSA increased from a baseline of 2.5+/-0.22 ng/mL (mean+/-SE) by 0.5+/-0.11 ng/mL in the placebo-, and from 2.7+/-0.23 ng/mL by 0.3+/-0.11 ng/mL in the terazosin-treated patients (P = 0.36 by ANOVA). There were no differences in the changes in serum PSA when patients were stratified by decade of life according to the age-specific PSA reference ranges, or by the final dose of terazosin (2, 5, or 10 mg daily). CONCLUSIONS: The treatment of men with lower urinary tract symptoms and clinical BPH with the alpha1-adrenergic antagonist terazosin does not affect serum PSA concentration, and thus does not confound longitudinal monitoring of serum PSA levels in patients at risk for prostate carcinoma.     

Refined mapping and YAC contig construction of the X-linked cleft palate and ankyloglossia locus (CPX) including the proximal X-Y homology breakpoint within Xq21.3

STUDY OBJECTIVES: To investigate topographical changes in electroencephalographic (EEG) frequencies and spectral power density in relation to different surgical procedures (abdominal hysterectomy versus mastectomy) during steady-state isoflurane-nitrous oxide (N2O) anesthesia. DESIGN: Prospective, nonrandomized, open study. SETTING: University hospital. PATIENTS: 34 ASA status I and II patients scheduled for elective abdominal hysterectomy or mastectomy. INTERVENTIONS: 12 patients were studied without surgery (Group I, control). 22 patients were studied for the first 14 minutes following skin incision during hysterectomy (Group 2, n = 11) or mastectomy (Group 3, n = 11). MEASUREMENTS AND MAIN RESULTS: Anesthesia was maintained with 0.6% isoflurane in 66% N2O in oxygen (O2). EEG was recorded via 17 channels followed by calculation of spectral power densities in selected frequency bands for each recording site. In addition, heart rate, mean arterial pressure (MAP), end-tidal carbon dioxide tensions, and isoflurane concentration were recorded. Total observation time was 20 minutes in all groups. At baseline, EEG variables were comparable in all groups. The EEG demonstrated slow wave activity superimposed with alpha waves. Start of surgery resulted in increases of slower waves and decreases in alpha activity. In both surgical groups, these EEG changes were most pronounced at frontal recording sites (p < 0.05) with differences in the frequency content. In Group 2 (hysterectomy), delta-activity became dominant, whereas in Group 3 (mastectomy), a shift to theta waves was observed. During surgery MAP was increased by 40% (Group 2; p < 0.05) and 21% (Group 3; p < 0.05), respectively. CONCLUSIONS: These results show that specific surgical procedures may induce EEG slow wave activity to a different degree. The EEG response varied in relation to the surgical procedure and/or the intensity of noxious stimulation. Mastectomy resulted in the appearance of theta activity whereas, during laparotomy, the EEG frequency content was shifted to delta waves. The topographical analysis indicates spatial inhomogeneities in the EEG responses with a dominance at frontal areas. From this findings, it may be concluded that the electrode montage used for intraoperative EEG recordings has to be carefully selected.     

The use of collagen-based model peptides to investigate platelet-reactive sequences in collagen

Simple collagen-like peptides comprising a repeat Gly-Pro-Hyp sequence are highly platelet-reactive when presented to platelets in triple-helical and polymeric form. This activity is not mediated by the platelet collagen receptor integrin alpha 2 beta 1. This may imply the existence of an intrinsic platelet reactivity associated with the collagen triple helix as such or perhaps that the Gly-Pro-Hyp sequence in collagen serves as a specific cell-recognition site. In our view this basic alpha 2 beta 1-independent reactivity is modulated by the presence in collagen of sequences that may either enhance or diminish the interaction with platelets. Inhibition studies with short linear peptides have allowed the tentative identification of sequences in collagen such as XPGEP(Q)GPX and D(N)GE(Q)X that may promote the activation of platelets and so enhance collagen-platelet interaction. Sequences serving as integrin alpha 2 beta 1-binding sites may also promote platelet reactivity by permitting interaction with the collagen receptor. Using triple-helical peptides based on the sequence of the platelet-reactive collagen type III fragment alpha 1(III)CB4, we have been able to locate an alpha 2 beta 1-binding site in collagen type III within a 30-mer sequence representing residues 508-537 of the alpha 1(III) constituent alpha-chain. Despite their alpha 2 beta 1-independent platelet reactivity, signalling by the (Gly-Pro-Hyp)n-based peptides shows many features in common with signalling by collagen fibers, including activation of p72SYK and p125FAK the latter of which has until now been considered a specific consequence of ligand binding to alpha 2 beta 1.