Lifestyle and 15-year survival free of heart attack, stroke, and diabetes in middle-aged British men

BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by local or diffuse wall motion abnormalities in the right ventricle (RV), associated with recurrent ventricular tachycardia (VT) of RV origin. Brain natriuretic peptide (BNP) was first isolated from a porcine brain extract. In humans, BNP is expressed predominantly in the ventricles of failing hearts, and its expression has been observed primarily in myocytes in the interstitial fibrous area in dilated cardiomyopathy. We hypothesized that BNP is increasingly secreted from the residual myocytes within the atrophic tissue in patients with ARVD. METHODS AND RESULTS: Plasma BNP levels were measured in 17 patients with ARVD, 12 patients with idiopathic RV outflow tract tachycardia (RVOT), and 120 control subjects. We performed cardiac catheterization, RV endomyocardial biopsy, electron- beam CT, and biventricular endomyocardial mapping in the ARVD patients. There was a significant increase in plasma BNP levels in the ARVD patients compared with the RVOT patients and control subjects (61.4+/-59.6 pg/mL versus 8.3+/-5. 5 pg/mL and 9.3+/-5.8 pg/mL; P<0.0001, respectively). The plasma BNP levels had no correlation with any of the hemodynamic data, but they had a significant correlation with the RV ejection fraction (r=-0. 588, P=0.025) and with the fractionated-area scores (r=0.705, P=0. 005). Light microscopic immunohistochemistry showed strong BNP immunoreactivity in residual myocytes with fibrofatty replacement. CONCLUSIONS: These results suggest that plasma BNP levels were not increased in RVOT patients but were increased in ARVD patients, and that the increased BNP levels indicate the severity of both the RV dysfunction and the arrhythmogenic substrate.     

Kidney transplantation: the use of living donors with renal artery lesions

PURPOSE: A shortage of organs for transplantation has forced surgeons to optimize the use of marginal organs, such as kidneys with arterial disease. We present a retrospective study of the outcome of donors with renal artery disease and recipients of kidneys from living related and unrelated donors. MATERIALS AND METHODS: Kidneys with vascular abnormalities from healthy living donors were grafted into 11 recipients. These kidney transplants comprised 1.8% of those performed at our institution. The vascular abnormalities were aneurysms in 3 cases, atherosclerotic lesions in 4 and fibromuscular dysplasia in 4. After nephrectomy all abnormalities were corrected under hypothermic conditions during bench surgery except in 3 cases of ostial atherosclerotic plaque, which was left in the donors. The renal artery was anastomosed to the external iliac artery in 5 cases and to the internal iliac artery in 6. The ureter was reimplanted using an extravesical technique. RESULTS: All patients had immediate diuresis and no delayed post-transplant graft dysfunction was observed. One patient died of an unrelated cause and 3 had post-transplant graft function loss due to acute vasculopathy in 1, post-diarrhea with acute arterial thrombosis in 1 and recurrence of the hemolytic-uremic syndrome in 1. All remaining patients are well with median serum creatinine of 1.4 mg./dl. (normal 0.4 to 1.4). All donors are well and normotensive with normal renal function. CONCLUSIONS: The use of kidneys with arterial disease from living donors with unilateral disease is safe. Complete informed consent regarding the risks and benefits by donor and recipient is mandatory.     

Waddell signs: distributional properties and correlates

OBJECTIVE: To determine what percentage of patients have none of the five nonorganic behavioral processes known as Waddell signs, and the relational pattern between Waddell signs and somatic complaints, disturbed functional performance, negative treatment attitudes, physical pathology, depression, generalized anxiety, and MMPI-2 validity scales. DESIGN: Case series survey. SETTING: A referral-based multidisciplinary pain center affiliated with a state medical school. PATIENTS: Seventy-five consecutive patients with chronic back pain. INTERVENTION: Medical evaluation and completion of self-report inventories. MAIN OUTCOME MEASURE: Total number of Waddell signs, physical pathology, and pain intensity ratings were assessed by a physician during an initial medical evaluation. Degree of disturbed functional performance and psychological symptoms were assessed by self-report measures at the initial evaluation. RESULTS: Sixty-four percent of the patients had no Waddell signs. Total number of Waddell signs yielded positive and statistically significant correlations (p < or = .05) with depression, disturbed functional performance, somatic complaints, and pain intensity ratings. Correlations of slightly smaller and statistically nonsignificant magnitudes were revealed for Waddell signs with generalized anxiety, negative treatment attitudes, and physical pathology. Waddell signs were unrelated to age, duration of pain, gender, number of lumbar surgeries, and MMPI-2 validity scales. CONCLUSIONS: Taken together, multiple Waddell signs and some of their correlates present various factors that might interfere with optimal response to treatment.     

The value of synthetic linear epitope analogues of La/SSB for the detection of autoantibodies to La/SSB; specificity, sensitivity and comparison of methods

Aflatoxin M1 (AFM1) is the principal hydroxylated aflatoxin metabolite present in the milk of dairy cows fed a diet contaminated with aflatoxin B1, (AFB1) and the metabolite is also present in the milk of human nursing mothers consuming foodstuffs containing the toxin. AFM1 is usually considered to be a detoxification product of AFB1 and this appears warranted if the biological endpoints involved are carcinogenicity and mutagenicity. However, it may not be a valid conclusion in the case of cytotoxicity. The metabolism of AFM1 and AFB1 have been studied in vitro using human liver microsomes. Formation of primary metabolites associated with metabolic activation to the respective epoxides reflected the differences between the carcinogenic potentials of the two toxins and, similar to AFB1, the conjugation of AFM1 epoxide with reduced GSH was catalyzed by mouse, but not human liver cytosol. Although the majority of the binding of [3H]AFB1 to microsomal protein was dependent on metabolic activation, a high level of retention of [3H]AFM1 by microsomes, nonextractable in methanol and unrelated to metabolic activation, was observed. It appears possible that this property is related to the high cytotoxicity of AFM1. Experiments using human cell line cells either expressing or not expressing human cytochrome P450 enzymes in assays of acute toxicity (MTT assays) have demonstrated a directly toxic potential of AFM1 in the absence of metabolic activation, in contrast to AFB1. Caution therefore needs to be exercised in designating the formation of AFM1 as essentially detoxification when considering a biological response in which cytotoxicity may play a significant role, e.g., immunotoxicity.     

Monogenean neuromusculature: some structural and functional correlates

Monogenean neuromuscular systems are structurally and functionally well-differentiated, as evidenced by research on the fish-gill parasite, Diclidophora merlangi. The nervous system in the worm exhibits a raft of putative intercellular signalling molecules, localised in neuronal vesicles. There is cytochemical evidence of co-localisation of neuropeptides and cholinergic substances, with aminergic components generally occupying separate neurons. The phalloidin-fluorescence technique for F-actin has enabled the demonstration of muscle organisation in the worm. Body wall musculature comprises circular, longitudinal and diagonal arrays of myofibres whose contractions are believed to be largely myogenic; circular fibres predominate in the walls of the reproductive tracts. The major somatic muscles are longitudinal muscle bundles that traverse the mesenchyme, the most extensive of which extend from the pharynx to the clamps of the haptor. Experiments have shown that some of these muscles may serve in a withdrawal reflex in the worm, which can be evoked by water turbulence. These and the muscles of the suckers, pharynx, clamps, male copulatory organ and ootype are provided with extensive synaptic innervation that is strongly immunoreactive for FMRFamide-related peptides (FaRPs), suggesting contractions may be neurogenic. Examination of the physiological effects of known flatworm FMRFamide-related peptides on muscle contractility in vitro has shown those FMRFamide-related peptides isolated from turbellarians to be the most excitatory. Results are discussed with respect to neuromuscular function in adhesion, alimentation, and reproduction in the worm.     

Clinical and epidemiological aspects of controlled short-term chemotherapy

The relationship is examined between the length of stay of 134 cancer patients at a hospice and the subsequent adjustment to loss by their spouses. Regression analysis found no significant correlation between the independent variables of length of hospice stay, gender, duration of time spent bedridden, time elapsed since death, and year of diagnosis and the dependent variables of psychological adjustment by their surviving spouses as assessed by the brief symptom inventory (BSI), the psychosocial adjustment to physical illness scale (PAIS), and the Texas revised inventory of grief (TRIG) scale. An analysis of covariance, however, found that a short hospice stay (1-7 days) had a beneficial effect on the spouse's bereavement compared to a long stay (8+ days).     

An in vitro comparison between laser fluorescence and visual examination for detection of demineralization in occlusal pits and fissures

Metabolism of xenobiotics such as alcohol and organic solvents can be divided roughly into two types: functional and conjugation reactions. Cytochrome P450 (CYP) is the primary group of enzymes involved in the former. Therefore, CYP analysis is essential for the study of the metabolism and toxicity of these chemicals. Of the isozymes, CYP2E1 is a low-km isozyme and has a high affinity for volatile hydrocarbons of low molecular mass, and is primarily involved in the metabolism of alcohol and organic solvents. There are many methods for analysis of CYPs including CYP2E1. The measurement of the metabolic rate of the target chemical in the liver is the most common. When combined with monoclonal or polyclonal antibody to CYP, contribution of the isozymes to the metabolism can be resolved, and the expression level is also identified by western blot analysis. The use of the reconstituted system of purified CYP isozymes is useful to determine the true activity (specific activity), but not common especially in that of human tissue. There are sometimes species differences in the enzymatic character of CYP isoforms, which causes difficulties in extrapolating to humans. In these case, the use of a cDNA expression system of human CYPs can cover the difficulties. The use of transgenic animals can answer the contribution of each CYP isoform in the in vivo metabolism and toxicity. The genotype of each isozyme is analyzed by PCR method, which can identify the polymorphism as well as the susceptibility to the chemicals.     

Simian immunodeficiency virus replicates to high levels in sooty mangabeys without inducing disease

A serologic survey of primates living in a French zoo allowed identification of three cases of infection with simian immunodeficiency virus in sooty mangabeys (Cercocebus atys) (SIVsm). Viral isolates, which were designated SIVsmFr66, SIVsmFr74, and SIVsmFr85, were obtained after short-term culture of mangabey lymphoid cells. Phylogenetic analysis of gag and env sequences amplified directly from mangabey tissues showed that the three SIVsmFr were genetically close and that they constituted a new subtype within the diverse SIVsm-SIVmac-human immunodeficiency virus type 2 (HIV-2) group. We could reconstruct the transmission events that likely occurred in 1986 between the three animals and evaluate the divergence of SIVsmFr sequences since transmission. The estimated rate of mutation fixation was 6 x 10(-3) substitutions per site per year, which was as high as the rate found for SIVmac infection in macaques. These data indicated that SIVsmFr replicated at a high rate in mangabeys, despite the nonpathogenic character of infection in this host. The viral load evaluated by competitive PCR reached 20,000 viral DNA copies per 10(6) lymph node cells. In addition, productively infected cells were readily detected in mangabey lymphoid tissues by in situ hybridization. The amounts of viral RNA in plasma ranged from 10(5) to 10(7) copies per ml. The cell-associated and plasma viral loads were as high as those seen in susceptible hosts (humans or macaques) during the asymptomatic stage of HIV or SIVmac infections. Thus, the lack of pathogenicity of SIVsm for its natural host cannot be explained by limited viral replication or by tight containment of viral production.