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Biomedical subjects

K MacDonald

Publications and source records attributed to K MacDonald.

At least 19 recordsLinked to original sources

Transverse humeral ligament: does it exist?

The insertion of the tendon of subscapularis is accepted as being on the lesser tubercle of the humerus. The transverse humeral ligament (THL) is described as a distinct entity in most textbooks, overlying the long tendon of biceps as it emerges from the capsule of the shoulder joint. In this study, we dissected 85 embalmed shoulders to clarify the anatomy of the THL and variation in the insertion of the tendon of subscapularis. In all specimens no distinct THL could be identified, but in every shoulder a fibrous expansion arose from the posterior lamina of the tendon of pectoralis major overlying the long tendon of biceps. In 86% of shoulders, fibres from the tendon of subscapularis passed over the long tendon of biceps within this fibrous expansion and inserted on to the greater tubercle of the humerus where one would expect to find the THL. In 33% of dissections, fibres from the tendon of subscapularis lay deep to the long tendon of biceps, inserting either into the bicipital groove or on to the greater tubercle. In only 8% of cases did the tendon of subscapularis insert exclusively on to the lesser tubercle. We conclude that the THL does not exist as a separate entity. We suggest that in the majority of cases, the structure overlying the long tendon of biceps as it emerges from the capsule of the shoulder joint consists of tendinous fibres from subscapularis, contained within a fibrous expansion derived from the posterior lamina of the tendon of pectoralis major. In the minority of shoulders, where the tendon of subscapularis inserts exclusively on to the lesser tubercle, we hypothesise that this fibrous expansion acts as a retinaculum preventing the long tendon of biceps from "bowstringing."

Aged↗

A newly synthesised molybdenum/ascorbic acid complex alleviates some effects of cardiomyopathy in streptozocin-induced diabetic rats.

BACKGROUND: Exogenous insulin does not prevent cardiac failure in patients with type 1 diabetes mellitus and a cardioprotective insulin mimic is greatly needed. Certain transition metals are known to act as insulin mimics and may be cardio- protective. In this study, the ability of a newly synthesised molybdenum/ascorbic acid complex to strengthen cardiac function was investigated. METHODS AND DESIGN: Male CD rats were assigned to one of five groups: non-diabetic control, non-diabetic control treated with molybdenum/ascorbic acid complex, diabetic treated with sodium ascorbate, diabetic treated with molybdenum/ascorbic acid complex and untreated diabetics. Type 1 diabetes was induced by streptozocin injection. Once diabetes was confirmed, treatment was initiated by adding either the molybdenum/ascorbic acid complex or sodium ascorbate to the drinking water and continued for 6 weeks. Following the treatment period, the animals were terminated, and their hearts were excised and mounted in a working heart perfusion apparatus. Blood samples were taken for plasma glucose and plasma lipid level determination. Cardiac function was evaluated using 1 hour of low-flow ischaemic stress followed by 30 minutes of reperfusion. RESULTS: Hearts from the animals treated with the molybdenum/ascorbic acid complex displayed the best aerobic performance of all the diabetic animals. Blood glucose levels and blood lipid levels were significantly lower in animals treated with the complex than in other diabetic animals. The group treated with the complex also had a lower drinking rate than the other diabetic groups. Furthermore, hearts from animals treated with the molybdenum/ascorbic acid complex showed a greater degree of recovery from low-flow ischaemia than any other group. CONCLUSIONS: The molybdenum/ascorbic acid complex showed some significant insulin-mimic and cardioprotective effects. Further development of this complex could provide a drug useful for alleviating some of the cardiovascular problems associated with diabetes mellitus.

Animals↗

Associations between genetic polymorphisms of Phase I and II metabolizing enzymes, p53 and susceptibility to esophageal adenocarcinoma.

The objectives of this exploratory case-control study were to evaluate whether genetic polymorphisms of selected Phase I and II metabolizing enzymes are associated with the risk of developing primary esophageal adenocarcinoma, and to investigate potential associations between genotypes and p53 tumor suppressor gene alterations. Cases comprised 45 patients with surgically resected esophageal adenocarcinomas, defined according to strict clinico-pathologic criteria. PCR-based assays (RFLP/SSCP) were used to genotype cytochrome P450 (CYP) 1A1 [MspI; Ile:Val], microsomal epoxide hydroxylase (mEH) (fast and slow alleles), and glutathione S-transferase (GST) T1, M1 and P1. Healthy controls (n=45) from the same geographic region were matched for age, gender and smoking history. For GSTP1, the Ile/Val (a/b) and Val/Val (b/b) variants were seen at increased frequency in cases compared to controls (49% versus 27% and 15% versus 9%, respectively), although these differences achieved only borderline statistical significance (P=0.09). For mEH (exon 3), the presence of the Tyr polymorphism (slow allele) was reduced in cases (42%) compared to controls (53%; P=0.05). Predicted high mEH activity was seen more frequently in cases than controls (OR, 2.2; 95% CI, 0.7-7.3). Polymorphism frequencies for GSTT1, GSTM1, and CYP1A1 were not statistically different between cases and controls. Cases with the GSTT1 null genotype had tumors with altered p53 more frequently than did cases with the common form of GSTT1 (25 versus 6%, respectively; P=0.08). We conclude that polymorphisms of GSTP1 and mEH may be implicated in individual susceptibility to esophageal adenocarcinoma, possibly as a result of increased Phase I activation (mEH) and impaired Phase II detoxification (GSTP1). GSTT1 may also play a role in esophageal tumorigenesis through a pathway that involves abnormalities in the p53 tumor suppressor gene.

Adenocarcinoma↗

Possible ethnic differences in plasma homocysteine levels associated with coronary artery disease between south Asian and east Asian immigrants.

BACKGROUND: Hyperhomocysteinemia has been identified as a risk factor for coronary artery disease (CAD). South Asians appear to have a high incidence of CAD, while East Asians have a very low incidence. HYPOTHESIS: The present study was undertaken because the relative association of plasma homocysteine levels (PH) with CAD in South Asians (SA = Indian, Pakistani, Sri Lankan) and East Asians (EA = Chinese, Japanese) is not known. METHODS: Fasting PH were drawn on all patients with CAD of SA (age 62.4+/-1.1 years, 72 men, 14 women) and EA (age 61.8+/-3.0 years, 13 men, 4 women) descent. These were compared with PH available from Caucasian (CA) patients (age 61.1+/-1.1 years, 89 men, 17 women) with CAD. RESULTS: The PH in SA, EA, and CA patients were 11.0+/-0.5, 7.6+/-0.5, and 10.8+/-0.6 micromol/l, respectively (p<0.001 between EA and SA/CA). Percentages of SA, EA, and CA with elevated PH (> 12.0 micromol/l) were 33.7, 5.9, and 28.2%, respectively. There were no significant differences in the lipid subfractions between the SA and EA group. History of smoking was significantly higher in the EA (52.9 vs. 26.2%), while hypertension and diabetes mellitus had similar prevalences. CONCLUSION: Significant differences in PH of SA versus EA patients with CAD exist. The relative contribution of homocysteine in the development of CAD appears to be less in EA immigrants. In contrast, the association between CAD and PH in SA immigrants appears to be similar to that of Caucasians.

Analysis of Variance↗

Cloning and disruption of a phenylalanine ammonia-lyase gene from Ustilago maydis.

The enzyme L-phenylalanine ammonia-lyase (PAL) catalyzes the non-oxidative deamination of L-phenylalanine to form trans-cinnamic acid and ammonia. This enzyme is universally present in higher plants and it catalyzes the starting reaction for a central pathway that generates hundreds of different phenylpropanoid metabolites. Genes encoding PAL have been identified in fungi, but the role of the enzyme has not been determined. We cloned and characterized a gene that encodes PAL from the phytopathogenic fungus Ustilago maydis and we constructed fungal strains carrying a null mutation in the gene. These mutants behaved like wild-type strains in terms of growth, mating, and pathogenicity. These results indicate that PAL does not play a major role in the life cycle of U. maydis under laboratory conditions.

Amino Acid Sequence↗

Bitter-sweet symphony: defining the role of dendritic cell gp120 receptors in HIV infection.

BACKGROUND: Dendritic cells (DC) are believed to be one of the first cell types infected during HIV transmission. Recently a single C-type lectin receptor (CLR), DC-SIGN, has been reported to be the predominant receptor on monocyte derived DC (MDDC) rather than CD4. The role of other CLRs in HIV binding and HIV binding by CLRs on other types of DC in vivo is largely unknown. OBJECTIVES AND STUDY DESIGN: Review HIV binding to DC populations, both in vitro and in vivo, in light of the immense interest of a recently re-identified CLR called DC-SIGN. RESULTS AND CONCLUSIONS: From recent work, it is clear that immature MDDC have a complex pattern of HIV gp120 binding. In contrast to other cell types gp120 has the potential to bind to several receptors on DC including CD4 and several types of C type lectin receptor, not just exclusively DC-SIGN. Given the diverse types of DC in vivo future work will need to focus on defining the receptors for HIV binding to these different cell types. Mucosal transmission of HIV in vivo targets immature sessile DCs, including Langerhans cells which lack DC-SIGN. The role of CLRs and DC-SIGN in such transmission remains to be defined.

Animals↗

The role of dendritic cells in the innate immune system.

Dendritic cells (DCs) are bone-marrow-derived leucocytes that are specialised antigen-presenting cells capable of stimulating a primary T-lymphocyte response to specific antigen. In this chapter we discuss the role DCs play in the innate response acting as a critical link with the adaptive response and the influence of the innate response on dendritic cells.

Animals↗

Comparison of an opsonophagocytic assay and IgG ELISA to assess responses to pneumococcal polysaccharide and pneumococcal conjugate vaccines in children and young adults with sickle cell disease.

Children with sickle cell disease were immunized with either 2 doses of 7-valent pneumococcal conjugate vaccine followed by 1 dose of 23-valent pneumococcal polysaccharide vaccine or a single dose of 23-valent vaccine. Functional antibodies to 7 vaccine serotypes were measured by a flow cytometric opsonophagocytic assay (OPA) and compared with IgG anticapsular polysaccharide antibody concentrations measured by ELISA. Moderate correlations were found between OPA and ELISA antibody titers for all 7 serotypes (r values, 0.41-0.70; P<.001 for all serotypes). After immunization with 23-valent vaccine, geometric mean antibody titers by OPA were significantly higher in the combined schedule group for 5 of 7 vaccine serotypes but were significantly higher for only 2 of 7 serotypes as measured by ELISA. The ability of OPA to show a greater differential response to the 2 immunization schedules used in this study suggests that it may be useful in the evaluation of immunization regimens involving pneumococcal conjugate vaccines.

Adolescent↗

Antecedents of the risk of recovery from DSM-III-R social phobia.

BACKGROUND: This study reports antecedents of recovery from DSM-III-R social phobia. METHODS: Retrospective data were obtained from 1116 individuals age 15 to 64 participating in a large population health survey in the province of Ontario, Canada RESULTS: Approximately 50% of the sample recovered from their illness. Survival analysis revealed a median length of illness of 25 years with peak periods of risk of recovery occurring between 30 and 45 years duration. Using discrete time multivariate hazard regression analysis, statistically significant predictors of recovery from social phobia included: childhood social contextual factors (one or no childhood siblings, a small town childhood place of residence), characteristics of the disorder (onset past the age of 7, less than three disorder symptoms), an absence of co-morbid health-related conditions and psychiatric disorders (chronic health problems and major depression), and the occurrence of co-morbid chronic health problems and major depression prior to the onset of the disorder. CONCLUSIONS: Our data indicate that social phobia in the general population is a chronic and unremittent disorder. Determinants of recovery are rooted in distal childhood circumstances, disorder attributes, and the physical and mental health status of individuals over the life course.

Adolescent↗

Childhood stress and symptoms of drug dependence in adolescence and early adulthood: social phobia as a mediator.

Retrospective data from 7,871 individuals age 16 to 64 were used to investigate whether, among those diagnosed with lifetime social phobia, its symptoms serve to link life events and chronic strains in childhood with symptoms of drug dependence in adulthood. Findings suggest social phobia as a pathway through which early life events and chronic strains affect the development of drug-related problems. Implications for research and clinical practice are discussed.

Adolescent↗

Normal IgG and impaired IgM responses to polysaccharide vaccines in asplenic patients.

Asplenic patients are at increased risk for life-threatening infections with polysaccharide-encapsulated organisms, and reports of responses to polysaccharide vaccines have been conflicting. Thirty-six asplenic patients and 15 healthy controls were immunized with pneumococcal, Haemophilus influenzae type b (Hib), and meningococcal vaccines. Antibody concentrations to Hib and pneumococcal serotypes 14 and 18C were measured by ELISA. IgG antibody responses to all three antigens were similar in asplenic patients and controls at 28 days following immunization. In contrast, asplenic patients had significantly lower IgM concentrations in response to Hib (P<.05) and to both pneumococcal serotypes 14 (P<. 005) and 18C (P<.001). IgA anti-Hib antibody was also lower in the asplenic group, as was total anti-Hib antibody measured by RIA. These results document that IgG responses to polysaccharide vaccines are normal in asplenic patients. The impaired IgM responses of these patients may explain conflicting reports from studies that measured only total antibody-binding concentrations.

Adolescent↗

Combined schedule of 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal vaccine in children and young adults with sickle cell disease.

We compared the immunogenicity of 7-valent pneumococcal-conjugate vaccine plus 23-valent pneumococcal vaccine to immunization with 23-valent vaccine only in individuals > or = 2 years of age with sickle cell disease. IgG pneumococcal antibody concentrations were higher in the combined schedule group with no increase in side effects observed after immunization with 23-valent vaccine.

Adolescent↗

Effect of inositol treatment on the behavior of rhesus monkeys: preliminary results.

1. The effects of inositol (20 g/day, oral) on spatial learning and spontaneous home-cage behavior of four Rhesus monkeys, were studied in a crossover design. 2. Results indicate no marked inositol effect on learning, memory, or behavior. There was a suggestion of an effect of chronic inositol in reducing cage-induced repetitive behavior as indicated by increased switching between modes of behavior, and reduction in length of longest behavioral about. Furthermore inositol may increase time spent in environmentally- rather than self-oriented behavior. 3. Previous behavioral studies of inositol were performed in rats, which maintain low brain inositol levels compared to primates, including humans. The present study demonstrates the feasibility of primate behavioral studies with inositol, and shows the need for longer time experiments and increased variety of behavioral tests.

Animals↗

Effect of cytomegalovirus infection on 1-year mortality rates among recipients of allogeneic bone marrow transplants.

The effect of cytomegalovirus (CMV) infection on 1-year mortality rates among allogeneic bone marrow transplant recipients who are receiving a standard protocol as prophylaxis for CMV infection is unclear. We determined the risk factors for death within 1 year among 103 bone marrow transplant recipients by performing a multivariate analysis. The results of donor and recipient CMV serologies did not predict 1-year mortality, although there was a trend towards higher mortality among CMV-seropositive recipients who received marrow from seronegative donors (P = .077). Multivariate analysis revealed that the factors independently associated with 1-year mortality were the development of CMV antigenemia (relative risk [RR] = 2.74; confidence interval [CI] = 1.28-5.86), bone marrow transplantation (BMT) from unrelated donors (RR = 3.20; CI = 1.30-7.92), and severe acute graft-versus-host disease (RR = 3.50; CI = 1.50-8.17). Although significant on univariate analysis, advanced underlying disease before BMT and the development of active CMV disease after BMT were not independent risk factors. In conclusion, the development of CMV antigenemia after BMT was associated with increased 1-year mortality, while the development of active CMV disease was not. Reactivation of CMV infection may represent a marker of poor immune reconstitution or may contribute to further immunosuppression after BMT.

Adolescent↗

Meeting the challenge of managed care through clinical pathways for bariatric surgery.

BACKGROUND: The 1990s will bring sweeping changes in managed care and capitation. Health care providers are continually searching for new ways to improve the quality of patient-care outcomes in the obese. Improving clinical care by promoting the use of processes that have been proved to yield optimal outcomes has become a powerful strategy for measuring the value of services provided. METHODS: To address this cost/quality paradox, an optimal care path (OCP) was developed as a guideline for all patients undergoing gastric bypass or laparoscopic adjustable gastric banding. A transdisciplinary team developed the OCP, preprinted orders, discharge home instruction sheet, and daily guidelines for patients. All patients were provided with OCPs from July 1995 to September 1997. RESULTS: Length of stay decreased from 6.5 days to 5.4 days (16.9%); the average total charges decreased 17.6%, or $2,683; the percentage of wound infections decreased; and communication between, and collaboration of, interdisciplinary team members increased across the continuum of care. CONCLUSIONS: The study suggests that the use of OCP does not impair quality of care and can produce significant cost savings to a health care facility.

Critical Pathways↗

Six opinions on IT security. Panel discussion.

Physicians consult over the Internet. Diagnoses are delivered via E-mail. Data is kept in multimedia repositories. Health care IT is filled with data security challenges. Here's what six experts think about the possibilities and vulnerabilities.

Chronology as Topic↗

The role of cytotoxic T-cells in HIV infection.

HIV-specific cytotoxic T lymphocytes (CTL) are believed to play a major role in controlling virus levels through the asymptomatic period of HIV infection. For the rational design of an HIV vaccine, we need to know whether protective immunity can ever develop following HIV exposure in people who remain uninfected. We have detected HIV-specific CTL in 5/6 repeatedly exposed, persistently seronegative female sex-workers in The Gambia. Their CTL, repeatedly detected over two years, recognise epitopes presented by HLA-B35 which are cross-reactive between HIV-1 & HIV-2, suggesting they could have been primed first by HIV-2 exposure and subsequently boosted by exposure to HIV-1. Using previously identified clade B HIV-1 epitope peptides, we have now detected HIV-specific CTL in 6/15 highly exposed and apparently HIV-resistant Kenyan prostitutes, predominantly towards epitopes highly conserved between B and the Kenyan A & D clades of HIV-1. This CTL activity towards conserved virus epitopes may represent protective immunity to HIV generated in response to repeated exposure, and prophylactic HIV vaccines should aim to generate similar CTL responses.

Cells, Cultured↗