Relatively high mortality risk in elderly Swedish subjects with low selenium status.

BACKGROUND/OBJECTIVES: The daily dietary intake of selenium (Se), an essential trace element, is still low in Sweden in spite of decades of nutritional information campaigns and the effect of this on the public health is presently not well known. The objective of this study was to determine the serum Se levels in an elderly Swedish population and to analyze whether a low Se status had any influence on mortality. SUBJECTS/METHODS: Six-hundred sixty-eight (n=668) elderly participants were invited from a municipality and evaluated in an observational study. Individuals were followed for 6.8 years and Se levels were re-evaluated in 98 individuals after 48 months. Clinical examination of all individuals included functional classification, echocardiography, electrocardiogram and serum Se measurement. All mortality was registered and endpoints of mortality were assessed by Kaplan-Meier plots, and Cox proportional hazard ratios adjusted for potential confounding factors were calculated. RESULTS: The mean serum Se level of the study population (n=668) was 67.1 µg/l, corresponding to relatively low Se intake. After adjustment for male gender, smoking, ischemic heart disease, diabetes, chronic obstructive pulmonary disease and impaired heart function, persons with serum Se in the lowest quartile had 43% (95% confidence interval (CI): 1.02-2.00) and 56% (95% CI: 1.03-2.36) increased risk for all-cause and cardiovascular mortality, respectively. The result was not driven by inflammatory effects on Se concentration in serum. CONCLUSION: The mean serum Se concentration in an elderly Swedish population was 67.1 µg/l, which is below the physiological saturation level for several selenoprotein enzymes. This result may suggest the value of modest Se supplementation in order to improve the health of the Swedish population.

Recovery entails bridging the multiple realms of best practice: towards a more integrated approach to evidence-based clinical treatment and psychosocial disability support for mental health recovery.

While mental health recovery is a very personal process, the approach also offers possibilities as a meta-framework for improving quality of services to support people with severe and enduring mental illness. This paper explores how a recovery paradigm offers opportunities to better understand how efforts within the personal, clinical, and psychosocial disability domains of well-being relate and need bridging and integration with an evidence-based framework of practice to optimise outcomes. Recovery from a severe and persisting mental illness such as schizophrenia is optimised by a holistic approach integrating the domains of clinical treatment and psychosocial rehabilitation with the personal efforts of individuals. For service providers, a monolithic or single paradigm approach with an exclusive or predominant biological, psychological, social, or cultural focus is unable to offer effective guidance on the treatment and rehabilitation support needed to enable community participation and ameliorate the impact which problems associated with mental illness have on individuals, their families, and their wider communities. Moreover, recovery-oriented services need to be effective, embracing evidence-based policy, practice and service delivery by providing treatment and support which actually work to improve outcomes for consumers and families.

Severe encephalopathy, lactic acidosis, vegetative instability and neuropathy with 5-Fluorouracil treatment - pyrimidine degradation defect or beriberi?

We present the case of a 19-year-old female with nasopharyngeal carcinoma, who received two courses of chemotherapy with 5-fluorouracil (5-FU) in combination with folic acid and cisplatin. Upon developing esophageal strictures in the course of her radiotherapy, she required total parenteral nutrition. In the course of therapy, the patient developed severe multisystem failure with encephalopathy, lactic acidosis, vegetative instability and neuropathy. The treatment with 5-FU can lead to severe toxicity due to enzyme deficiencies in the degradation of pyrimidines, but it can also lead to thiamine deficiency with the classic symptoms of beriberi. Beriberi is a rare disorder, usually attributed to malnutrition or alcoholism. 5-FU has been shown to induce thiamine depletion. Reduced food intake or total parenteral nutrition devoid of vitamin supplements may aggravate symptoms. We were unable to find a genetic cause for increased 5-FU toxicity in our patient, ruling out deficiencies of dihydropyrimidine dehydrogenase, dihydropyrimidinase or ß-ureidopropionase and double-strand break repair deficits. We come to the conclusion that, even without any definable enzyme deficiency, treatment with 5-FU can lead to high toxicity due to thiamine deficiency if vitamin supplementation is not undertaken.

4-thiouridine induces dose-dependent reduction of oedema, leucocyte influx and tumour necrosis factor in lung inflammation.

Recent reports demonstrate a role for nucleotides as inflammatory modulators. Uridine, for example, reduces oedema formation and leucocyte infiltration in a Sephadex-induced lung inflammation model. Tumour necrosis factor (TNF) concentration was also reduced. Previous in vivo observations indicated that 4-thiouridine might have similar effects on leucocyte infiltration and TNF release. The aim of this study was thus to investigate the effects of 4-thiouridine in greater detail. We used a Sephadex-induced acute lung inflammation model in Sprague-Dawley rats. The dextran beads were instilled intratracheally into the lungs, which were excised and examined after 24 h. Sephadex alone led to massive oedema formation and infiltration of macrophages, neutrophils and eosinophils. Microgranulomas with giant cell formations were clearly visible around the partially degraded beads. A significant increase in bronchoalveolar lavage fluid (BALF) content of TNF and leukotrienes was also seen. 4-Thiouridine co-administration affected all variables investigated in this model, i.e. oedema, microscopic and macroscopic appearance of lung tissue, total leucocyte and differential leucocyte counts in BALF, TNF and leukotrienes C(4) (LTC(4)), LTD(4 )and LTE(4) in BALF, indicating a reproducible anti-inflammatory effect. In conclusion, we have demonstrated that 4-thiouridine has anti-inflammatory effects similar to those of uridine. To our knowledge, this is the first demonstration of pharmacological 4-thiouridine effects in vivo. The results suggest nucleoside/nucleotide involvement in inflammatory processes, warranting further studies on nucleoside analogues as attractive new alternatives in the treatment of inflammatory diseases.

Uranium decay products found on Mir space blanket mitt.

The space blanket mitt which covered the Trek detector on Mir during four years of orbital flight has been measured for gamma radiation with HPGe and multidimensional spectrometers. Difference spectra from very-long-period spectrometer runs on the mitt and on a similar non-deployed mitt from the same manufacturer show that the mitt has acquired small but significant amounts of gamma radioactivity during orbital flight. Twelve gamma-ray peaks have been measured in the difference spectra, including peaks identified as due to 214Bi and 214Pb from the uranium-radium alpha decay series, and others possibly due to the uranium-actinium series. This implies the presence of a sparse population of uranium decay products in lower orbital space which can only have come from nuclear explosions, burned-up satellite nuclear batteries, the solar wind, or supernova fragments in the local interstellar medium.

Reliability and responsiveness of three different pain assessments.

The visual analogue scale (VAS) and ordered categorical scales, i.e. numeric rating scales (NRS), are commonly used in the assessment of pain. However, these scales are bounded by fixed endpoints and thus the range of measurement is limited. The disparity in repeated assessments of perceived pain intensity with the VAS, NRS, and electrical stimulation applied as a matching stimulus was studied in 69 patients (48 women and 21 men, 19-72 years) with chronic nociceptive or neurogenic pain. Responsiveness with transcutaneous electrical nerve stimulation (TENS) using the same measurement procedures was evaluated in the same patients. Comparison of results from the three pain assessments showed that the painmatcher is at least as reliable and responsive as VAS and NRS. None of the three measurements showed evidence for systematic disagreement and had only significant random individual disagreement. They also showed evidence for responsiveness.

Neural basis of endogenous and exogenous spatial orienting. A functional MRI study.

Whole-brain functional magnetic resonance imaging (MRI) was used to examine the neural substrates of internally (endogenous) and externally (exogenous) induced covert shifts of attention. Thirteen normal subjects performed three orienting conditions: endogenous (location of peripheral target predicted by a central arrow 80% of the time), exogenous (peripheral target preceded by noninformative central cue). Behavioral results indicated faster reaction times (RTs) for valid than for invalid trials for the endogenous condition but slower RTs for valid than for invalid trials for the exogenous condition (inhibition of return). The spatial extent and intensity of activation was greatest for the endogenous condition, consistent with the hypothesis that endogenous orienting is more effortful (less automatic) than exogenous orienting. Overall, we did not observe distinctly separable neural systems associated with the endogenous and exogenous orienting conditions. Both exogenous and endogenous orienting, but not the control condition, activated bilateral parietal and dorsal premotor regions, including the frontal eye fields. These results suggest a specific role for these regions in preparatory responding to peripheral stimuli. The right dorsolateral prefrontal cortex (BA 46) was activated selectively by the endogenous condition. This finding suggests that voluntary, but not reflexive, shifts of attention engage working memory systems.

Functional MRI evidence for subcortical participation in conceptual reasoning skills.

Lesions involving the dorsolateral prefrontal lobes may produce deficits on conceptual reasoning (CR) tasks in humans. Such deficits can also occur with subcortical lesions involving the basal ganglia, thalamus, or cerebellum, suggesting a common, yet widespread, neural network supporting this executive function. Here we report the results of a whole brain functional magnetic resonance imaging (fMRI) experiment in healthy volunteers while performing a CR task. Compared to a sensorimotor control condition, the CR task resulted in discrete subcortical activation sites primarily involving the right basal ganglia, right thalamus and left lateral cerebellum. Cortical activation was present in multiple systems, including the dorsolateral prefrontal and inferior frontal/insular areas; posterior parietal, superior extrastriate, and premotor areas; inferior extrastriate and middle temporal regions; and midline pre-supplementary motor and anterior cingulate regions. Our findings provide strong evidence that CR is mediated by interacting neural systems involving the cerebral cortex, basal ganglia, thalamus, and cerebellum.

Homeopathy, other forms of alternative medicine sources of ongoing debate among physicians, patients.

Amy Rosen is the 1994 winner of the Amy Chouinard Memorial Essay Contest. Named in memory of longtime CMAJ and Canadian Journal of Surgery contributor Amy Chouinard, the competition is intended to stimulate interest in medical and health-related writing among journalism students. The winning essay examines the growing public interest in homeopathic medicine and physicians' opinions of the trend.

Short-term restraint stress and s.c. saline injection alter the tissue levels of substance P and cholecystokinin in the peri-aqueductal grey and limbic regions of rat brain.

Rats were exposed to short-term restraint (held by the tail for 1 min), injected s.c. with saline or subjected to the combination of these treatments. Fifteen and 30 min after these treatments the means serum corticosterone level was significantly increased by more than four times, compared to rats taken directly from their home cages, indicating a stress response. In the peri-aqueductal grey, the level of substance P-like immunoreactivity was increased by 45% (P < 0.01) and 65% (P < 0.01) 30 and 60 min after the combined treatment, respectively. Significant increases of the level of substance P-like immunoreactivity in the peri-aqueductal grey were also found after restraint only and after a s.c. saline injection. Similar, but less marked, changes in the level of cholecystokinin-like immunoreactivity in the PAG were also seen. In the accumbens a significantly decreased level of substance P-like immunoreactivity was encountered at 15 and 30 min after treatment, while the levels of cholecystokinin- and neuropeptide Y-like immunoreactivity were not significantly changed. In other regions studied, no effects on peptide levels were seen. The changes in peptide levels had a time course similar to that of the increase in serum corticosterone. Also the successive removal of rats from a common cage was found to increase significantly the serum corticosterone and the substance P-like immunoreactivity in the peri-aqueductal grey in the animals that were taken late in sequence from the cage.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled examination of effects of progressive relaxation training on seizure reduction.

We determined the efficacy of progressive muscle relaxation in reducing seizure frequency. Subjects were 24 people with epilepsy attending an urban neurology clinic. The experimental design consisted of an 8-week baseline period, a treatment period of six sessions of progressive relaxation training (PRT, n = 13) or quiet sitting (QS, n = 11) and an 8-week follow up. In the PRT group, 11 subjects reported a decrease in seizure frequency (p less than 0.01), and in the QS group, 7 reported a decrease (p greater than 0.05). The mean decrease in seizure frequency was 29% for the PRT group (p less than 0.01) but only 3% for the QS group (p greater than 0.05). This is the fifth recent report of a controlled study documenting the success of progressive relaxation therapy in seizure reduction. PRT is inexpensive and noninvasive and facilitates patient participation. Such a technique should be incorporated into clinical practice.

Irresectable hepatoma treated by intrahepatic iodized oil doxorubicin hydrochloride: initial results.

In this study we describe the investigation and treatment of 14 patients with primary hepatocellular carcinoma. Patients were treated with intra-arterial infusion of iodized oil and doxorubicin hydrochloride. Five of these patients were alive after 1 year. Twelve patients showed a fall in alpha-fetoprotein, and in seven of these patients, the fall in alpha-fetoprotein was greater than 50%.

Accelerated erythropoiesis: the hidden benefit of autologous donation.

The risks associated with the administration of blood products have increased efforts to avoid homologous transfusions. Preoperative autologous donation has received renewed interest as a method of decreasing homologous transfusion requirements. Autologous donations may also stimulate postoperative erythropoiesis. The purpose of this study is to evaluate the effect of an aggressive autologous donation program on postoperative erythropoiesis. Ten adult male baboons were divided into two groups. The autologous group (n = 5) donated an average of 2 units of blood per week for 5 weeks before operation. The control group (n = 5) had no preoperative treatment. All animals then underwent a laparotomy and exchange transfusion with hetastarch to a final hematocrit of 15 percent. The time required to recover to hematocrits of 20 percent (3.3 vs. 5.7 days, p less than 0.01), 25 percent (7.0 vs. 8.8 days, p less than 0.05), and 30 percent (11.1 vs. 17.7 days, p less than 0.01) was shorter in the autologous group. The autologous group had more intense reticulocytosis during the first 4 postoperative days (p less than 0.03). The data show that participation in an aggressive autologous donation program improves the erythropoietic response to anemia in the postoperative setting. This represents a hidden benefit of preoperative autologous donations and suggests that more aggressive donation schedules may be clinically beneficial. Recognition of that acceleration of erythropoiesis by autologous donation could further reduce the need for transfusion of homologous blood.

Erythropoietic response to acute anemia.

Reliance on a brisk erythropoietic response to untreated blood loss is an alternative to transfusion of homologous blood. Slow erythropoiesis has been observed in ICU patients who refused blood. Many of these patients received supplemental oxygen therapy and Fluosol-DA, a temporary red cell substitute. This study reports the erythropoietic response, in the baboon, to moderate (Hct 20%) and severe (Hct 10%) anemia. In addition, the effect of oxygen therapy (FIO2 0.6 for 1 wk) and fluorocarbon emulsions (Oxypherol) on erythropoiesis was evaluated. Baboons uniformly survived acute normovolemic anemia with Hct 10%. In all cases, the response to anemia was characterized by a lag period (with no change in Hct), and a nonlinear recovery period. A lag period of 3 days was observed in both moderate and severe anemia for baboons breathing room air or FIO2 0.6. The lag period was prolonged to 1 wk in the presence of Oxypherol. The recovery period exhibited a uniform and negative correlation between the rate of Hct change and the Hct, in all cases. The theoretical maximum rate of increase of Hct was 2.6%/day. In untreated blood loss, shortening the lag period and increasing the slope of the recovery period will decrease the length of time that the patient is anemic.

Treatment of acute postoperative anemia with recombinant human erythropoietin.

Risks inherent in the administration of blood products have increased efforts to avoid homologous transfusion. Although this has increased interest in autologous transfusion and intraoperative salvage, little attention has been focused on efforts to enhance endogenous erythropoiesis as a method of minimizing exposure to homologous blood. Recombinant human erythropoietin (rHuEPO) has been shown to enhance erythropoiesis. The purpose of this study is to evaluate the effect of rHuEPO, administered postoperatively, on a model of acute blood loss. Eleven adult male baboons were randomized into two groups. All animals underwent a laparotomy and an exchange transfusion, with 6% hetastarch, to a final hematocrit of 15%. Group I (N = 6) received 1,000 units/kg of recombinant human erythropoietin daily for the first 14 postoperative days. Group II (N = 5) received an equivalent volume of placebo. All animals were given supplemental vitamin B12, folate and 200% of shed iron, as iron dextran IV, after exchange transfusion. Response was observed for a period of 35 days. All animals survived the protocol. There were no adverse reactions to rHuEPO or surgical complications. The hematocrits were similar between groups at baseline and after exchange transfusion. The maximal rate of erythropoiesis was significantly faster in the rHuEPO group (2.1 vs. 1.3%/day; p less than 0.01). The time required to return to hematocrits of 30% (9.9 vs. 17.4 days, p less than 0.001) and to baseline hematocrits (11.9 vs. 32.1 days, p less than 0.01) were both significantly shorter in the rHuEPO group. The data show that rHuEPO accelerates the recovery from anemia in the postoperative setting. Acceleration of erythropoiesis represents another alternative to homologous transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Lower GI bleeding: updated diagnosis and management.

Lower GI bleeding in the elderly can be attributed to diverticula or vascular ectasias in most cases. Usually, a diagnosis is established by colonoscopy, but often this test must be supplemented by radiographic and additional endoscopic techniques, especially in the evaluation of obscure GI bleeding. Responsible lesions are frequently remediable by non-operative therapy. However, if surgical intervention is called for, it should not be delayed solely because of the patient's advanced age.

Recombinant human erythropoietin and autologous blood donation.

Risks of transfusion are minimized with autologous blood. However, autologous donation programs require 2 to 5 weeks to yield only 2.2 units per patient. Recombinant human erythropoietin (r-HuEPO) has been shown to increase erythropoiesis. This study evaluated the effects of r-HuEPO on an aggressive autologous donation program. Twelve adult male baboons were randomized into two groups of six. All animals were studied three times per week for 5 weeks. A unit of blood was donated when on any study day the hematocrit was greater than 30%. Animals received intravenously either 750 units/kg of r-HuEPO (n = 6) or placebo (n = 6) on each study day. Iron dextran was given intravenously to replace 150% of shed iron. The r-HuEPO group had an earlier onset of reticulocytosis (2.7 vs 5.5 days, p less than 0.01) and donated 35% more blood (13.5 vs 10.0 units, p = 0.01) than the control group. No adverse reactions to r-HuEPO were observed. The data show that an aggressive autologous donation program can yield 10 units of blood over a 5-week period. Further, r-HuEPO increases that yield by an additional 35%. This aggressive autologous donation program with r-HuEPO may significantly reduce the need for homologous transfusion and its attendant risks.

Unresectable fibrolamellar hepatocellular carcinoma treated with intra-arterial lipiodolised doxorubicin. A case report.

Hepatocellular carcinoma is often an aggressive tumour and, if unresectable, carries a poor prognosis, especially in the presence of jaundice. We report on a jaundiced patient with an unresectable fibrolamellar hepatocellular carcinoma treated with intra-arterial lipiodolised doxorubicin (Adriamycin). The initial response of the patient has been encouraging. This form of therapy deserves further evaluation in patients with unresectable hepatocellular carcinoma.

Barium appendicitis: fact or fancy? Report of a case and review of the literature.

Whether barium retained in the appendix can be a cause of acute appendicitis is debatable. We describe a 40-year-old man who developed nonspecific right abdominal pain 7 weeks after a barium enema, which proved to be normal. On abdominal film a distended appendix containing barium was seen, and at laparotomy acute appendicitis was present. Thus far, 26 cases of "barium appendicitis" have been reported. On the basis of the relevant literature and the cases collected, it is appropriate to draw the following conclusions: 1) With present knowledge it is not possible to state whether retained barium plays any etiologic role in the development of subsequent uncomplicated acute appendicitis. 2) If a later appendicitis does supervene, it carries a high risk of being complicated; barium seems to be responsible for the complication. 3) The longer the interval between the barium study and the subsequent appearance of acute appendicitis, the higher will be the risk of complications.