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States that a higher than expected number of violent deaths and suicides in coronary prevention trials has caused interest in the possibility that low serum cholesterol concentrations are associated in the general population with personality characteristics predisposing to aggressive and suicidal behavior. Details of the Edinburgh Artery Study; Study methods, results and discussion.

Liver transplantation is the only effective treatment for hereditary tyrosinaemia type I (McKusick 276700). We have treated one acute and four subacute-chronic cases with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27), to prevent the formation of maleylacetoacetate and fumarylacetoacetate and their saturated derivatives. The oral daily dose was 0.1-0.6 mg/kg. The excretion of succinylacetoacetate and succinylacetone decreased from 15-103 mmol/mol creatinine to the detection limit or slightly above (ie, to 20-150 mumol/mol creatinine). The concentration of succinylacetone in plasma decreased from 5.8-43 mumol/l to the detection limit (0.1 mumol/l) over 2-5 months of treatment. The almost complete inhibition of porphobilinogen synthase in erythrocytes was abolished and the excretion of 5-aminolevulinate decreased to within or slightly above the reference range. The concentration of alpha-fetoprotein decreased in four patients to 1.3-7.5% of initially high values over 6-8 months. Improved liver function was reflected by normal concentrations of prothrombin complex and in decreased activities of alkaline phosphatase and gamma-glutamyltransferase in serum. Computed tomography revealed regression of hepatic abnormalities in three patients. One patient developed rickets 6 months before treatment and had excreted high concentrations of markers of tubular dysfunction--after 3 weeks of treatment, this excretion had disappeared. No side-effects were encountered. Inhibition of 4-hydroxyphenylpyruvate dioxygenase may prevent the development of liver cirrhosis and abolish or diminish the risk of liver cancer. Normalisation of porphyrin synthesis will eliminate the risk of porphyric crises. This type of treatment may thus offer an alternative to liver transplantation in hereditary tyrosinaemia. [ABSTRACT FROM AUTHOR]

Details the Swedish Aspirin Low-dose Trial (SALT), which was established to study the efficacy of 75 mg aspirin daily in prevention of stroke and death after transient ischaemic attack. Antiplatelet therapy with acetylsalicylic acid; Clinical and demographic characteristics of study groups; Treatment regimens; Outcome events; Results.

To investigate the function of activated T lymphocytes in autoimmune chronic active hepatitis, 7 of 15 T-cell clones from the peripheral blood of 8 patients were studied. These clones showed specificity for liver-membrane antigen with proliferation when stimulated by rabbit liver cell membranes. 6 of these clones reacted with liver-specific lipoprotein complex, and 1 clone (and 3 subclones) responded to the asialoglycoprotein receptor (ASGPR), both known targets of immune attack in autoimmune chronic active hepatitis. 2 of these clones stimulated autologous B lymphocytes to produce liver-membrane-specific autoantibodies and antibody to the ASGPR. These results suggest that liver-membrane-specific activated T lymphocytes in peripheral blood may be important in the autoimmune attack of chronic active hepatitis. [ABSTRACT FROM AUTHOR]

Neutrophil leucocytosis is associated with a poor outcome in the haemolytic uraemic syndrome (HUS). This study tested the hypothesis that neutrophils from HUS patients are activated and through release of their intracellular contents damage endothelium. The proportion of neutrophils adhering to endothelium in culture was twice as high for HUS patients' neutrophils as for control neutrophils (n = 12). In addition, these neutrophils induced endothelial injury, assessed morphologically by degradation of endothelial cell fibronectin. In an attempt to inhibit neutrophil adhesion and subsequent endothelial damage the hyperadhesive neutrophils from HUS patients were incubated with a CD18 antibody directed against the common beta chain of the leucocyte integrin molecules. The CD18 antibody was able to abrogate endothelial damage in four of the ten subjects studied. These observations suggest that the neutrophil is of prime pathophysiological importance in HUS, and that methods aimed at reducing neutrophil adhesion and neutrophil-mediated endothelial damage are likely to be beneficial. [ABSTRACT FROM AUTHOR]

Presents a study investigating whether platelet inhibitory drugs are as good as anticoagulants, whether 50 mg aspirin per day with dipyridamole is sufficient, and questions the length of treatment in patients who had aortocoronary vein bypass surgery. Research methods; Statistics.

Investigates the effect of glutamine-supplemented enteral nutrition on infectious morbidity in patients with multiple trauma. Method of selecting and monitoring patients; Findings; Interpretation of lower incidence of pneumonia sepsis and bacteraemia in patients with multiple trauma receiving glutamine-supplemented artificial nutrition.

Discusses the progress made in diagnosis and treatment of primary pulmonary hypertension (PPH) over the past 20 years. What PPH is; Who is usually affected by PPH; PPH's etiology; Theories on pathogenesis; Role of endothelial-cell injury; Ion-channel activity in smooth-muscle cells in the pulmonary artery; Survey of various treatments and their effectiveness; Thoracic transplantation as a last resort.

Background: Long-chain polyunsaturated fatty acids (LCPUFA) are important for normal visual and brain development. Although present in human milk, LCPUFA have until recently been absent from artificial formulas, and infants may have limited ability to synthesise LCPUFA. To determine the clinical significance of this relative deficiency of LCPUFA, we undertook a randomised trial of the relation between LCPUFA supplementation and infant cognitive behaviour.Methods: 44 term infants had been randomised to a formula supplemented with LCPUFA (21) or not supplemented with LCPUFA (23), which they had taken from birth to age 4 months. Infant cognitive behaviour was assessed at 10 months of age by a means-end problem-solving test--the intentional execution of a sequence of steps to achieve a goal. The problem required three intermediate steps to achieve the final goal, uncovering and retrieving a hidden toy.Findings: Infants who received LCPUFA-supplemented formula had significantly more intentional solutions than infants who received the no-LCPUFA formula (median 2.0 vs 0, p=0.021). Intention scores (median 14.0 vs 11.5 [maximum 18]) were also increased in this group (p=0.035).Interpretation: These findings suggest that term infants may benefit from LCPUFA supplementation, and that the effects persist beyond the period of supplementation. Since higher problem-solving scores in infancy are related to higher childhood IQ scores, supplementation with LCPUFA may be important for the development of childhood intelligence. [ABSTRACT FROM AUTHOR]

Reports on learning and memory difficulties after environmental exposure to waterways in Maryland containing toxin-producing Pfiesteria or Pfiesteria-like dinoflagellates. Methods of assessing the 24 people; Results showing people with high exposure were more likely than occupationally matched controls to complain of neuropsychological symptoms, including forgetfulness; Interpretation that exposure leads to risk of developing a reversible clinical syndrome of higher cognitive function difficulties.

Presents an overview of hypopituitarism, a partial of complete insufficiency of anterior-pituitary hormone secretion which may result from pituitary or hypothalamic disease. Pathophysiology; Diagnosis and management; Strategies for prevention; Conclusions. INSETS: Causes of hypopituitarism;Clinical symptoms of hypopituitarism.

Presents findings from a randomised controlled trial to assess the role of platelet glycoprotein-IIb/IIIa blockade for use in elective stenting. Background; Methods; Findings; Interpretation.

Background: Hypertransaminasaemia of unknown, cryptogenic, origin occasionally has been found to be the only sign of coeliac disease. Raised concentrations of transaminases, or aminotransferases, have been retrospectively observed in about a half of patients with coeliac disease who are on a gluten-containing diet. We aimed to establish the overall prevalence of coeliac disease among patients with cryptogenic hypertransaminasaemia.Methods: Of the 600 consecutive patients referred to our outpatient clinic for liver disease due to raised serum transaminases from September, 1995, to June, 1997, 55 were classified as having cryptogenic hypertransaminasaemia after the exclusion of every known cause of liver disease. These patients were tested by indirect immunofluorescence for IgA to endomysium and for IgA and IgG to gliadin.Findings: Five patients were positive for both IgA to endomysium and IgG to gliadin, whereas IgA to gliadin was only found in four patients. IgG to gliadin was also present in another patient who was not positive for antibodies to endomysium. The six antibody-positive patients had duodenal biopsy that showed a subtotal villous atrophy consistent with coeliac disease in the five patients with antibodies to endomysium. The patient with only IgG to gliadin had a normal small-intestine mucosa. None of the five patients with coeliac disease had gastrointestinal symptoms. Liver biopsy samples were taken from three of the five patients with flat mucosa and showed a histological picture of nonspecific reactive hepatitis. Transaminase concentrations reverted to normal within 6 months in four patients with coeliac disease who followed a strict gluten-free diet.Interpretation: Our results show that about 9% of patients with cryptogenic hypertransaminasaemia are affected by symptom-free coeliac disease. Gluten-sensitive enteropathy and antibody screening for coeliac disease by means of antibodies to endomysium and gliadin should be considered in these patients. [ABSTRACT FROM AUTHOR]

Background: Highly active antiretroviral therapy (HAART) decreases viral load and increases CD4 T-cell counts in patients with advanced HIV-1 infection. Whether HAART can improve CD4 T-cell function, and the biological characteristics affecting immune reconstitution, remain unclear. We undertook an open prospective pilot study to address these issues. Both treatment-naïve and previously treated patients were included.Methods: 20 patients (seven naïve, 13 previously treated) were treated with one protease inhibitor and two reverse-transcriptase inhibitors and followed up for 12 months. We measured CD4-cell proliferation in response to cytomegalovirus and tuberculin antigens and counted subsets of CD4 cells at baseline and months 1, 3, 6, 9, and 12. Patients who had no antigen-specific reactivity at baseline but developed it while receiving HAART were classified as immunological responders.Findings: Four patients had antigen-specific reactivity at baseline compared with 14 at month 12 (p <0.001). Between month 3 and month 12 viral load fell by a median of 1.5 log copies/mL from baseline (4.6 log copies/mL) and CD4-cell count increased by a median of 63/microL (from 93/microL). Ten patients (six of seven naïve, four of 13 previously treated) were immunological responders. They differed significantly from the ten non-responders in that their viral-load reduction was sustained for 12 months, the increase in CD4 count was greater, and they showed an early increase in memory CD4 T cells with an increase of naïve T cells.Interpretation: HAART can induce sustained recovery of CD4 T-cell reactivity against opportunistic pathogens in severely immunosuppressed patients. This recovery depends not on baseline values but on the amplitude and duration of viral-load reduction and the increase of memory CD4 T cells. [ABSTRACT FROM AUTHOR]

Presents research which studied the effects of recombinant human growth hormone (rhGH) in patients with chronic heart failure due to dilated cardiomyopathy. Methods; Findings; Significant increase in left-ventricular mass in such patients given rhGH but without improvement in clinical status; Changes in left-ventricular mass due to changes in serum IGF-I concentrations; Unknown impact of longer treatment period with rhGH.

Background: Human milk contains a 46 kDa mucin-associated glycoprotein, lactadherin, which binds specifically to rotavirus and inhibits its replication. This study tested the hypothesis that lactadherin protects against symptoms of rotavirus infection.Methods: 200 infants in Mexico City were recruited at birth and monitored by regular stool EIA for rotavirus, serology, and recording of feeding and stool patterns. Milk samples were obtained from the mothers weekly until 4 weeks post partum then monthly. The sample taken immediately before an infant's episode of rotavirus infection was assayed for lactadherin, butyrophilin, mucin, and secretory IgA. An infection was defined as symptomatic if diarrhoea occurred in the 5 days before or after detection of the virus.Findings: 31 infants developed rotavirus infection; 15 were symptomatic and 16 had no symptoms. The median concentration of lactadherin in the milk samples (obtained 4-41 days [median 13] before the infection) was 48.4 (range 5.6-180) microg/mL in the asymptomatic group and 29-2 (6.2-103-4) microg/mL in the symptomatic group. Although these medians did not differ significantly, in logistic regression analysis adjusted for age at infection and secretory IgA concentration there was a significant difference between the groups (p=0O01). No association between symptom status and concentrations of butyrophilin, mucin, or secretory IgA was found.Interpretation: Protection against rotavirus by human milk is associated with the glycoprotein lactadherin. This association is independent of products of the secretory immune system. [ABSTRACT FROM AUTHOR]

Presents research which tested whether breast tumor tissue would show changes based on menstrual cycle in the expression of genes whose products might contribute to metastatic potential. Improved survival rates among women who had breast cancer resected during the luteal and not follicular phase of menstruation; Methods; Findings; Changes in metastatic potential in breast cancer through menstrual cycle; Further research.

Presents research which tested the hypothesis that primary hyperconstriction, or spasm, of coronary microvessels causes myocardial ischemia at rest. Microvascular angina occurring both at rest and during exercise; Role of reduced vasodilator capacity of coronary microvessels; Methods; Findings; Conclusion that coronary microvascular spasm and resultant myocardial ischemia may cause chest pain in some angina.

Reports on a study of randomized trial of the growth hormone in short normal girls. Methods; Findings; Interpretation; The lack of data on the long-term outcome of growth-hormone treatment in short normal children.

Discusses intravascular-catheter-related infections. Pathogenesis; Diagnostic applications; Preventive strategies including tunneling, ionic silver cuff and intraluminal antibiotic locks; Therapeutic directives; Measures to decrease risk of colonisation of central-venous catheters.

Discusses the pathophysiology of leptin. Attention given to the discovery of leptin; Leptin thought of as a cure for obesity; Leptin first described as a adipocyte-derived signaling factor; Role of leptin in reproduction and neuroendocrine signaling; Complexity of human obesity; Leptin a cytokine acting as an adipostat; Sites of action; Leptin as signal of plenty; Leptin's regulatory role; Regulation of leptin expression; Its future.

Presents research which sought to develop a method for measuring local creatine concentrations in the healthy and diseased human heart. Preserved energy metabolism and myocardial viability; Role of creatine kinase reaction in energy production; Use of spatially-localized, water-suppressed hydrogen magnetic-resonance spectroscopy (1H-MRS); Success of method; Use for detection of regional creatine depletion.

Background: Three strategies are used to prevent relapse in patients with acute myeloid leukaemia in first remission. Most of those with suitable donors are offered allogeneic haemopoietic-stem-cell transplant. Other patients may receive intensive chemotherapy or autologous transplantation; we undertook this randomised prospective trial to assess which is the better option.Methods: After three courses of intensive chemotherapy, bone marrow was harvested from patients (<56 years of age) in remission who lacked an HLA-matched sibling donor. These patients were then randomised to receive, after one more course of chemotherapy, no further treatment (n=191) or an autologous bone-marrow transplant (BMT) after preparation with cyclophosphamide and total-body irradiation (n=190). Outcome comparisons were by intention to treat with adjustment for the most important risk factors for relapse.Findings: 381 patients were randomised (38% of those eligible). Of the 190 patients allocated autologous BMT, 126 received it. On intention-to-treat analysis the number of relapses was substantially lower in the autologous BMT group than in the group assigned no further treatment (64/190 [37%] vs 101/191 [58%], p=0.0007), resulting in superior disease-free survival at 7 years (53 vs 40%; p=0.04). These benefits were observed in all risk groups and age-groups. There were more deaths in remission in the autologous BMT group than in the no further treatment group (22 [12%] vs 7 [4%], p=0008). In children (<15 years) and patients with good-risk disease, survival from relapse in the no further treatment group was 35% and 38% at 2 years. There was an overall survival advantage in the autologous BMT group at 7 years (57 vs 45%, p=0.2).Interpretation: The addition of autologous BMT to four courses of intensive chemotherapy substantially reduces the risk of relapse in all risk groups, leading to improvement in long-term survival. The good chance of salvage for children or patients with good-risk disease who relapse from chemotherapy, and the mortality, morbidity, late effects, and expense of autologous BMT, suggest that delay of autograft until second remission in these two groups may be appropriate. [ABSTRACT FROM AUTHOR]

Presents research which studied the risks and benefits of two long-term maintenance regimens of cyclosporin in kidney allograft recipients. Risk of renal toxicity from long-term administration of cyclosporin; Tie between immunosuppressants and malignant disorders; Endpoints of research; Methods; Findings; Effect of halving trough blood cyclosporin; Effect of low-dose regimen; Design of long-term maintenance protocols.

Looks at the establishment of donor-derived haemopoiesis in the recipients of allogeneic bone-marrow transplants (BMT) which involves extensive proliferation of haemopoietic stem cells. The biological consequences of this replicative stress being ill defined; The consideration of any aging effect that would carry risk of an increased frequency of clonal disorders during later life; The study comparing blood-cell mean telomere lengths in donor/recipient pairs; Methods and findings.

Considers the reduced growth in utero associated with type 2 (non-insulin-dependent) diabetes and impaired glucose tolerance in adult life. The question of evidence in human beings that maternal nutrition during gestation affects insulin-glucose metabolism; The investigation of glucose tolerance in people born around the time of famine; The study, methods and findings.

Considers the studies of chronic hepatitis C virus (HCV) infection. The virological response of patients when treated with a combination of interferon cx-2b and ribavirin than with interferon cx-2b alone; How the study was conducted and the results of those findings.

Presents the results of a study investigating sodium sensitivity as a common factor in cardiovascular events of patients with hypertension. Background; Methods; Findings; Interpretation.

Considers the use of histamines in the treatment of patients with chronic obstructive lung disease. The airway responsiveness of the treatment; The study as to the remission of chronic respiratory symptoms with increased airways responsiveness; The methods; The findings; The interpretation.

Assesses the benefits of total cholesterol concentrations on specific and all-cause mortality in people 85 years of age and over. How total serum cholesterol decreases as a risk factor for cardiovascular disease with age; The doubts for cholesterol-lowering therapy in the elderly.

Discusses the findings from the Collaborative Group on Hormonal Factors in Breast Cancer that has reanalyzed about 90 percent of the worldwide evidence on the relation between risk of breast cancer and use of hormone replacement therapy (HRT). Methods; Results.

Looks at the serious problem of recurrent bleeding in the injection treatments for ulcer hemostasis. The large clinical trials of a random nature that show differences between treatment modalities for gastrointestinal bleeding; The study showing the safety and efficacy of repeated endoscopic injection of fibrin glue (FG) and that of an injection of polidocanol in the prevention of bleeding; Methods; Findings; Interpretation.

Reports a study in which the biological effects of chronic low-dose ionizing radiation on residents of buildings constructed with cobalt-60-contaminated steel rods was compared with that in controls. Background; Methods; Findings; Interpretation; Discussion; References.

Investigates the association between risk of non-Hodgkin lymphoma and body burden of selected organochlorine in the general population in a nested case-control study. Background; Methods; Findings; Interpretation; Results; Discussion.

Discusses a study which evaluated the extent of infant exposure to phyto-estrogens from soy formula. Methods; Findings; Interpretation.

Discusses the reduction of acetylcholinesterase activity in patients with Alzheimer's disease. Demonstration of regional acetylcholinesterase activity in vivo in rodent and primate brains with radioactive acetylcholine analogues; Study of one of the analogues to map acetylcholinesterase activity in the brains of living people; Methods; Findings; Interpretation.

Discusses a study investigating the angiotensin-converting enzyme (ACE) inhibitor lisinopril in men and women with insulin-dependent diabetes with normoalbuminuria or microalbuminuria. Methods; Findings; Interpretation.

Discusses a study that measured the effects of alpha-tocopherol and beta-carotene on male smokers who had a previous myocardial infarction. Methods; Findings; Interpretation.

Examines the Acute Infarction Ramipril Efficacy (AIRE) Study. Aim of the study to assess the long-term magnitude, duration, and reliability of the survival benefits of patients with clinical heart failure after acute myocardial infarction (AMI) observed after treatments with ramipril; Methods; Findings; Interpretation.

Presents a study that assessed the clinical benefit of the addition of lamivudine to zidovudine-based regimens in patients infected with HIV-1. Methods; Findings; Interpretation.

Examines a study that investigated whether inhibition of the platelet glycoprotein IIb/IIIa integrin with eptifibatide (Integrilin) could prevent platelet-mediated thrombosis. Platelet-mediated thrombosis being implicated in the development of ischaemic complications of percutaneous coronary intervention; Methods; Findings; Interpretation.

Probes a study that measured the circulating concentrations of inhibin A, pro-alpha-C-containing inhibins, and activin A in the serum of women with pre-eclampsia, and to establish the molecular-weight forms of circulating inhibin A and activin A in pre-eclampsia. Methods; Findings; Interpretation.

Looks at a study that investigates the association of adverse clinical muscoskeletal and neurological events in healthy postpartum women with live attenuated rubella-virus vaccine. Assessment of the frequency of acute and recurrent muscle pain and neurological manifestations; Methods of the study; Findings of the study; Interpretation.

Describes the clinical evaluation of the nervous-system effects of solvent exposure. General classes of organic solvents; Clinic assessment and evaluation of suspected solvent-induced toxic effects; Diagnosis and treatment; Clinical assessment of behavioral effects of solvent exposure; Diagnostic systems and toxic encephalopathy.

Looks at a study of the association between a first myocardial infarction and current oral contraceptive use in women from Africa, Asia, Europe, and Latin America. Methods of the study; Findings; Interpretation.

Analyzes a study on the effects of a low-protein diet on the renal function and growth in children with chronic renal failure (CRF). Methods of the study; Findings of the study; Interpretation of the findings.

Analyzes a study that aimed to find out the proportion of cases of apparently non-syndromic coronal craniosynostosis that are attributable to the C749G (Pro250Arg) mutation in the gene for fibroblast growth factor receptor 3 (FGFR 3). Methods of the study; Findings of the study; Interpretation of the findings.

Presents a study aimed at assessing whether lowering of brain serotonin activity by depletion of its aminoacid precursor, tryptophan, could provoke a short-term relapse of clinically significant symptoms in women vulnerable to major depressive disorder. Methods; Findings; Interpretation.

Looks at possible methods which would facilitate clinical xenotransplantation of solid organs. The pig thought to be the most suitable organ donor; Therapeutic strategies attempting to circumvent hyperacute rejection, the process whereby the organ is rejected by the human body; Possibility that other immune and non-immune barriers to transplantation of pig organs into humans may arise; Strategies needed to overcome the barriers.