Seven Countries Study. First 20-year mortality data in 12 cohorts of six countries

Out of the original 16 cohorts in the Seven Countries Study on Cardiovascular Diseases, 12 population samples in six countries have reached the 20 year follow-up deadline. Data on mortality became fully available for a total of 8287 men aged 40-59 at entry examination (two cohorts in Finland, one in the Netherlands, three in Italy, two in Yugoslavia, two in Greece, and two in Japan). Death rates from CHD as well as from all causes follow the traditional falling north to south trend (18 fold between the extremes for CHD; 2.7 fold for total mortality). The differences in all causes mortality are, however, largely accounted for by the variation in CHD mortality. The mean entry levels of serum cholesterol and representative levels of the consumption of saturated fats, mono-unsaturated fats, poly-unsaturated fats and carbohydrates explain a large proportion of inter-cohort difference in CHD mortality (81% for saturated fats). By applying the proportional hazards model to the pools of national cohorts, with CHD deaths as end-point and five risk factors as covariates, only age and mean blood pressure are universally significant predictors of fatal events. Cholesterol, smoking habits, body mass index and physical activity play some part but not in all the pools. Age and mean blood pressure are also the only universal risk factors for all causes of death.     

Structure-activity studies of morphiceptin analogs: receptor binding and molecular determinants of mu-affinity and selectivity

In this study we report the systematic investigation of conformational profiles and electronic properties of a series of analogs of the mu-selective opioid peptide, morphiceptin, together with receptor-binding studies of some of these analogs. In particular, we have investigated the effect of: substitution in the second position, substitution of D-Pro for L-Pro in the second and fourth positions, the addition of an N-methyl group at the third position, and variations in the carboxyl end group. The binding studies confirm the preference of these analogs for mu- versus delta-receptor-binding sites and also indicate differences in mu-receptor affinity among them. The theoretical analyses allow identification of a preferred conformation leading to high mu-receptor affinity and two reliable indicators of relative mu-receptor affinities. These properties are the energy required to obtain the candidate mu-binding conformer and the extent to which each compound overlaps with the highest affinity compound in this conformation. In addition, electronic interactions deleterious to high affinity mu-binding are identified.     

Effects of the antioxidants dithiothreitol and vitamin E on phospholipid metabolism in isolated rod outer segments

Phospholipid peroxidation and the activities of phospholipase A, acyl Coenzyme A:lysophospholipid acyltransferase and lysophospholipase were measured in isolated bovine rod outer segments (ROS) that were incubated in the presence or absence of the added antioxidants, vitamin E and dithiothreitol (DTT), and additionally in light or dark. DTT and vitamin E significantly inhibit both lipid peroxidation and the enzyme activities. These results suggest that one function of the enzymes for molecular replacement of fatty acids in ROS, is removal of peroxidized fatty acids and thus protection of the membrane phospholipids and proteins from further oxidative damage.     

Comparing 4- and 6-week post-flap protocols in patients with spinal cord injury

Objective: For patients with spinal cord injury (SCI) who undergo flap surgery to treat pressure injuries (PIs), the optimal duration of post-operative bedrest to promote healing and successful remobilization to sitting is unknown. At the study center, the minimum duration of post-operative bedrest was changed from 4 to 6 weeks. The purpose of this study is to compare outcomes of patients who underwent flap surgery using bedrest protocols of different duration.Design: This was a retrospective review of all flap procedures completed at VA Puget Sound Health Care System from 1997 to 2016 to treat PIs in patients with SCI. Surgeries were excluded if they were not a flap (i.e. primary skin closure or graft), involved a non-pelvic region, or were a same-hospitalization revision of a prior surgery. The primary outcome of this investigation was the number of days between surgery and the first time the patient mobilized to sitting out of bed for 2 h with an intact surgical incision.Methods: 190 patients received a total of 286 flap surgeries from 1994 to 2016. A chart review of each case was completed to determine the planned duration of bedrest (4- vs 6-weeks), first date of successful mobilization out of bed for 2 h, length of stay post-surgery, and occurrence of complications such as dehiscence or need for operative revisions.Results: Among 286 primary surgeries, 171 surgeries used the 4-week protocol and 115 used the 6-week protocol. When compared to the 4-week protocol, patients treated with the 6-week protocol were slightly older, more likely to have a diagnosis of diabetes, and less likely to be current smokers. Healing was never achieved after 4 surgeries in the 4-week group and 2 surgeries in the 6-week group. With the analysis restricted to a single surgery per subject who achieved healing (109 treated with 4-week protocol and 75 with 6-week protocol), there was a significant difference in days until 2-h sitting: median 54 days for the 4-week protocol compared to 60 days for the 6-week protocol (p = 0.041). Up to about 60 days post-operatively, the 4-week protocol produced a greater proportion remobilized to sitting, and thereafter the proportion of patients successfully remobilized did not differ between protocols.Conclusions: The 6-week protocol was not associated with improved remobilization outcomes (reduced rates of dehiscence or surgical revisions), and the 4-week protocol resulted in a significantly shorter time to remobilization to sitting for 2 h as well as a shorter length of stay. We did not identify any subgroup of patients that benefited from the longer protocol.     

Ice-skating injuries to the hand

166 patients with injuries due to ice-skating were seen in the local accident and emergency department over a six-month period; 60% of these involved the upper limb. 28 of the upper limb injuries were closed fractures and 24 were lacerations, almost all to the dorsum of the hand. The use of protective gloves would help to prevent these potentially avoidable injuries. "On-site" first-aid facilities help to reduce the demand on the local accident service.     

Serum cholesterol and cancer mortality in the Seven Countries Study

In the Seven Countries Study, carried out in Finland, Greece, Italy, Japan, The Netherlands, the United States, and Yugoslavia, among 11,325 "healthy" men aged 40-59 years in 15 years, there were 594 cancer deaths. Among 477 cancer deaths five years after cholesterol measurement, there was a significant excess of lung cancer deaths in the bottom 20% of the cholesterol distributions in the populations. Age, blood pressure, smoking habits, occupation, and relative body weight did not help explain this. A U-shaped relationship between cancer and cholesterol was not seen in any population. Trend analysis with various cutting points indicated increasing risk of lung cancer death at cholesterol levels under 170 mg/dl. The 45 men dead from cancer in the first two years had lower cholesterol levels than their compatriots who died from cancer later but they did not differ in relative weight or fatness. In contrast to relationships for individuals within populations, the highest cancer death rates were in northern Europe, where the general level of cholesterol was also highest. Other characteristics of the populations--age, relative weight, smoking habits, blood pressure, physical activity, and vitamin A and ascorbic acid in the diet--did not help in the attempt to understand the regional differences in cancer mortality. There is no evidence that any of the observed cancer-serum cholesterol relationships among or within the populations involve an effect of serum cholesterol concentration on oncogenesis or cancer mortality but the possibility of such an effect cannot be denied.     

Age, period, cohort and geographical area effects on the relationship between risk factors and coronary heart disease mortality. 15-year follow-up of the European cohorts of the Seven Countries study

The effects of three major risk factors (i.e. serum cholesterol, systolic blood pressure and smoking habits) on prediction of coronary heart disease (CHD) mortality in relation to three nuisance variables--i.e. geographical location, age of subject at examination and period of examination--are analyzed using data from three different 5-year apart examinations of the Seven Countries Study and observations on CHD mortality in the corresponding 15-year follow-up period. First, a cross-classification exploratory analysis including both CHD-free subjects at entry and prevalence subjects, by different geographical areas, age classes and examination times is presented. Secondly, a logistic regression including the three major risk factors and the three nuisance variables, regarded both as confounders and effect modifiers is discussed. The prevalence status of the subjects is also considered as a nuisance variable in this second analysis. Results showed that: (a) there is a highly significant (p less than 0.001) marked decrease in the association between cholesterol level and CHD mortality with increasing age of subject; (b) a decreasing association with coronary heart disease mortality as age increases also holds for smoking habits (p less than 0.05). This association, however, tends to be reinforced with time (p less than 0.05), i.e. the relative risk of heavy smokers vs non-smokers is four times bigger in the period 1970-75, than in the period 1960-65, age and all other factors being equal; (c) a possible dependence of the association between systolic blood pressure and CHD on geographical area is suggested, although this finding could be the result of chance with a 10% probability.     

Characterisation of Exiguobacterium aurantiacum isolates from blood cultures of six patients

Exiguobacterium spp. are alkaliphilic, halotolerant, non-spore-forming Gram-positive bacilli, hitherto uncharacterised from human infections. Six isolates of Exiguobacterium aurantiacum were obtained from patients with bacteraemia, three of whom had myeloma. All isolates formed orange–yellow pigmented colonies on blood agar, were catalase- and DNase-positive, and grew on nutrient agar at pH 10 and in the presence of NaCl 6% w/v. The six isolates were susceptible to all antimicrobial agents tested and were uniform in their fatty acid and mass spectrum profiles.     

Long-Term Changes in Brain Following Continuous Phencyclidine Administration: An Autoradiographic Study using Flunitrazepam,Ketanserin, Mazindol,Quinuclidinyl benzilate,Piperidyl-3,4-3H(N)-TCP,and AMPA Receptor Ligands

Abstract: Phencyclidine induces a model psychosis which can persist for prolonged periods and presents a strong drug model of schizophrenia. When given continuously for several days to rats, phencyclidine and other N-methyl-D-aspartate (NMDA) antagonists induce neural degeneration in a variety of limbic structures, including retrosplenial cortex, hippocampus, septohippocampal projections, and piriform cortex. In an attempt to further clarify the mechanisms underlying these degeneration patterns, autoradiographic studies using a variety of receptor ligands were conducted in animals 21 days after an identical dosage of the continuous phencyclidine administration employed in the previous degeneration studies. The results indicated enduring alterations in a number of receptors: these included decreased piperidyl-3,4-³H(N)-TCP (TCP), flunitrazepam, and mazindol binding in many of the limbic regions in which degeneration has been reported previously. Quinuclidinyl benzilate and (AMPA) binding were decreased in anterior cingulate and piriform cortex, and in accumbens and striatum. Piperidyl-3,4-³H(N)-TCP binding was decreased in most hippocampal regions. Many of these long-term alterations would not have been predicted by prior studies of the neurotoxic effects of continuous phencyclidine, and these results do not suggest a unitary source for the neurotoxicity. Whereas retrosplenial cortex, the structure which degenerates earliest, showed minimal alterations, some of the most consistent, long term alterations were in structures which evidence no immediate signs of neural degeneration, such as anterior cingulate cortex and caudate nucleus. In these structures, some of the receptor changes appeared to develop gradually (they were not present immediately after cessation of drug administration), and thus were perhaps due to changed input from regions evidencing neurotoxicity. Some of these findings, particularly in anterior cingulate, may have implications for models of schizophrenia.     

Hepatic abscess after liver transplantation: 1990-2000

BACKGROUND: Infections following solid-organ transplants are a major cause of morbidity and mortality. Few studies have reported the complications of hepatic abscesses. METHODS: This investigation consisted of a retrospective chart review of all solid-organ transplant recipients from 1990 to 2000. Criteria for diagnosis included parenchymal hepatic lesions, positive cultures from liver aspirates or blood cultures, or both, and a compatible clinical presentation. RESULTS: Of 2,175 recipients of all organ transplants (heart, lung, kidney, liver, pancreas), we identified 12 patients who had experienced 14 episodes of hepatic abscess, all in liver transplant recipients. Median time from transplant to hepatic abscess was 386 days (range 25-4,198). The most common predisposing factor was hepatic artery thrombosis (HAT), which occurred in eight patients, and was diagnosed at an average of 249 days (range 33-3,215) after transplantation. Clinical presentation of hepatic abscess was similar to that described in non-immunosuppressed patients. All but one patient showed hypoalbuminemia (<3.5 g/dL); those with HAT also had significantly elevated lactate dehydrogenase. Liver aspirates grew gram-positive aerobic bacteria (50% of isolates), gram-negative aerobic bacteria (30%), and anaerobes and yeasts (10% each). Patients received an average of 6 weeks of intravenous antibiotic therapy. Catheter drainage was successful in 70% of cases; and five patients required retransplantation. Altogether, five of the patients died, yielding a mortality rate of 42%. CONCLUSIONS: Hepatic abscess, a rare complication after liver transplantation, was frequently associated with hepatic artery thrombosis. Mortality was higher than in patients who had not undergone transplantation. Prolonged antibiotic therapy, drainage, and even retransplantation may be required to improve the outcome in these patients.