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Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 145 records · Page 8Linked to original sources

Anisotropic thermal expansion of potassium dinitramide: a variable-temperature crystallographic study.

The structure of potassium dinitramide (KDN), KN(3)O(4), has been refined in the temperature range 85-298 K from single-crystal X-ray diffraction data. The unit-cell axial lengths and the cell volume decrease linearly on cooling with the b axis being the most sensitive to the change of temperature. The beta cell angle increases with decreasing temperature. The thermal expansion of KDN is significantly anisotropic, expanding along the b axis [010] more than three times the amount parallel to any other crystallographic direction. Other eigenvectors of the thermal expansion tensor lie approximately parallel to the diagonals of the ac plane. A rigid-body analysis of the dinitramide ion using the TLS formalism was performed and shows that the thermal motion of the anion is well represented by the rigid-body model. The eigenvalues of the libration tensor show significant anisotropy, whereas the translation tensor is close to isotropic. The variation of all descriptions of the thermal motion with respect to temperature indicates an anharmonic contribution to the mean field potential. The direction of greatest unit-cell expansion coincides with the largest components of the displacement tensor of the potassium ions and the direction of the largest atomic amplitudes due to the libration of the dinitramide anions.

Journal Article↗

Body composition and energy metabolism in normotensive and hypertensive pregnancy.

OBJECTIVE: To determine whether the insulin resistance syndrome and altered body composition are features of hypertensive pregnancy. DESIGN: Women were recruited in the third trimester of pregnancy from the antenatal clinic, day assessment unit, and maternity ward of St George Hospital, Sydney. POPULATION: Women with pre-eclampsia (n = 12), gestational hypertension (n = 12), essential hypertension in pregnancy (n = 11), and normotensive pregnancy (n = 10). METHODS: Energy metabolism was assessed by indirect calorimetry to measure basal metabolic rate and diet-induced thermogenesis. Body composition was measured as lean body mass, total body water and fat mass by bio-electrical impedance. Blood was collected for measurement of glucose, insulin and lipid profiles. Insulin resistance was indirectly assessed by the insulin and glucose concentrations and diet-induced thermogenesis. RESULTS: Women with essential hypertension and gestational hypertension were heavier than women with normotensive pregnancies both pre-pregnancy and in the third trimester, whereas women with pre-eclampsia were similar to those with normotensive pregnancy. Women with essential hypertension were otherwise similar to normotensive pregnancy but women with gestational hypertension had a reduced diet-induced thermogenesis and almost double insulin levels. Women with pre-eclampsia had a similar body composition and insulin levels but reduced basal metabolic rate, diet-induced thermogenesis and glucose levels compared with normotensive pregnancy. CONCLUSIONS: Women who develop gestational hypertension, but not pre-eclampsia, are more likely to be overweight. Women with essential hypertension are similar to women with normotensive pregnancy throughout pregnancy. Both gestational hypertension and pre-eclampsia appear to be associated with some degree of insulin resistance, greater than that occurring in normal pregnancy.

Adult↗

Body composition and energy metabolism in pregnancy.

The objective of the study was to measure energy metabolism and body composition during pregnancy and postpartum, compared to non-pregnant women, using non-invasive techniques. A longitudinal study of eight normotensive pregnant women was carried out at 19 +/- 1 and 36+/-1 weeks gestation, and postpartum. A cross-sectional study was also performed comparing postpartum to 12 non-pregnant women. Indirect calorimetry was performed while fasting to measure basal metabolic rate (BMR) and postprandially to measure diet-induced thermogenesis (DIT). Body composition consists of fat mass, lean body mass (LBM), and total body water (TBW) and was measured by bio-electrical impedance. Insulin resistance was indirectly assessed by glucose and insulin concentration and DIT.

Adult↗

Characterization of recombinant hepatitis A virus genomes containing exogenous sequences at the 2A/2B junction.

Hepatitis A virus (HAV) differs from other members of the family Picornaviridae in that the cleavage of the polyprotein at the 2A/2B junction, commonly considered to be the primary polyprotein cleavage by analogy with other picornaviruses, is mediated by 3C(pro), the only proteinase encoded by the virus. However, it has never been formally demonstrated that the 2A/2B junction is the site of primary cleavage, and the actual function of the 2A sequence, which lacks homology with sequence of other picornaviruses, remains unknown. To determine whether 2A functions in cis as a precursor with the nonstructural proteins, we constructed dicistronic HAV genomes in which a heterologous picornaviral internal ribosome entry site was inserted at the 2A/2B junction. Transfection of permissive FRhK-4 cells with these dicistronic RNAs failed to result in the rescue of infectious virus, indicating a possible cis replication function spanning the 2A/2B junction. However, infectious virus was recovered from recombinant HAV genomes containing exogenous protein-coding sequences inserted in-frame at the 2A/2B junction and flanked by consensus 3C(pro) cleavage sites. The replication of these recombinants was less efficient than that of the parent virus but was variable and not dependent upon the length of the inserted sequence. An HAV recombinant containing a 420-nt insertion encoding the bleomycin resistance protein Zeo was stable for up to five passages in cell culture. Inserted sequences were deleted from replicating viruses, but this did not result from homologous recombination at the flanking 3C(pro) cleavage sites, since the 5' and 3' segments of the inserted sequence were retained in the deletion mutants. These results indicate that the HAV polyprotein can tolerate an insertion at the 2A/2B junction and that the 2A polypeptide does not function in cis as a 2AB precursor. Recombinant HAV genomes containing foreign protein-coding sequences inserted at the 2A/2B junction are novel and potentially useful protein expression vectors.

Animals↗

Manubriosternal joint dislocation in contact sport.

A 17 year old man developed chest pain and shortness of breath immediately after a scrummage while playing rugby football. A lateral chest radiograph showed a dislocated manubriosternal joint, with no associated injuries. This has not been previously reported in a sporting setting. This injury should be considered in flexion-compression injury of the thorax.

Adolescent↗

Equity in access to exercise tolerance testing, coronary angiography, and coronary artery bypass grafting by age, sex and clinical indications.

OBJECTIVES: To assess whether patients with heart disease in a single UK hospital have equitable access to exercise testing, coronary angiography, and coronary artery bypass graft surgery (CABG). METHOD: Retrospective analysis of patients' medical case notes (n = 1790), tracking each case back 12 months and forward 12 months from the patient's date of entry to the study. SETTING: Single UK district hospital in the Thames Region. PATIENTS: Patients (elective and emergency) with a cardiac ICD inpatient code at discharge or death, or who were referred to cardiology or care of the elderly unit over a 12 month period in 1996-7 (new episodes) were included. RESULTS: Analysis of 1790 hospital case notes revealed that, despite having indications for intervention identical to those of younger patients, older patients (that is, those aged > 75 years) and women, independently, were significantly less likely to undergo exercise tolerance testing (exercise ECG) and cardiac catheterisation. The similar trends for age and access to CABG did not achieve significance. While clinical priority scores also independently predicted access to cardiac catheterisation and CABG, considerable numbers of patients in high clinical priority groups were not referred for either procedure. CONCLUSIONS: The management and treatment of older patients and women with cardiac disease may be different from that of younger patients and men. Given the similarity of the indications for treatment and the lack of significant contraindications or comorbidities as a cause for these differences, one possible explanation is that these patients are being discriminated against principally because of their age and sex. Although clinical priority scores independently predicted access to catheterisation and CABG, large proportions of patients in high priority groups were not referred. This implies that the New Zealand priority scoring system may be more equitable than UK practice. The cost implications of redressing these inequities in service provision would be considerable.

Age Factors↗

Electrical and mechanical H(max)-to-M(max) ratio in power- and endurance-trained athletes.

The aim of this study was to compare the mechanical and electromyographic (EMG) characteristics of soleus motor units activated during maximal H reflex and direct M response among subjects with different histories of physical activity. Power-trained athletes produced stronger twitches, with a higher rate of twitch tension buildup and relaxation, than their endurance counterparts for both maximal H-reflex and maximal M-wave responses. The maximal H-reflex-to-maximal M-wave ratios for both force output (twitch) and EMG wave amplitude were significantly lower in power-trained than endurance-trained athletes. However, power-trained athletes exhibited a significantly greater twitch-to-EMG ratio for the reflexly activated motor units with respect to the entire motor pool, whereas endurance-trained athletes had comparable twitch-to-EMG ratios for both reflexly and directly activated units. Power training increases the force output of the whole ensemble of the motor units, thereby compensating for the lower efficacy of the reflex transmission between Ia spindle afferent input and soleus alpha-motoneuron. On the other hand, the lower level of force evoked by the reflexly activated units in endurance-trained athletes is associated with a greater motor pool reflex excitability. Therefore, endurance-trained athletes produce the necessary force by recruitment of more slow-twitch units than do other subjects for comparable levels of force and type of task.

Adult↗

Pedestrian deaths following collisions with heavy goods vehicles.

Pedestrian fatalities following collisions with heavy goods vehicles ('lorries') in south-east Scotland were studied between 1992 and 1998. Data sources included police and ambulance reports, forensic medicine records, hospital casenotes and the Scottish Trauma Audit Group database. All injuries were scored according to the Abbreviated Injury Scale, yielding Injury Severity Scores (ISS). Sixteen pedestrians (mean age 60.2 years) died after being hit by a lorry. Actions of pedestrians were implicated in causing all the collisions--four of which appeared to be suicides. Four of the apparently accidental deaths involved pedestrians with significant blood alcohol levels. Thirteen pedestrians were dead when found. Ten pedestrians had an ISS of 75, having a total of 13 injuries acknowledged to be unsurvivable (Abbreviated Injury Scale = 6), largely to the head and chest. The unsurvivable injuries reflect huge forces, explaining why only a small proportion of the pedestrians survived to hospital. There is little potential to reduce the number of deaths by improving hospital treatment, rather the focus needs to be directed towards injury prevention. Although pedestrians appeared to be responsible for the collisions, the results suggest it may be more feasible and effective to direct injury prevention measures towards lorry drivers.

Accidents, Traffic↗

Efficient fat storage in premenopausal women and in early pregnancy: a role for estrogen.

There is a sexual dimorphism in body fat in humans. Adipose tissue increases with puberty and early pregnancy in women, suggesting gonadal steroids can influence body fat. Previously, we have observed that oral estrogen, compared with transdermal estrogen, reduced postprandial lipid oxidation and increased body fat, possibly due to suppressed hepatic lipid oxidation. If estrogen effects lipid oxidation, we predicted that subjects with significantly different endogenous estrogen production would oxidize lipids at different rates. The aim of this study was to compare energy metabolism in 12 pregnant (19 wk gestation, 29 +/- 1 yr, 1.66 +/- 0.02 m, 73.5 +/- 2.4 kg), 11 nonpregnant premenopausal (29 +/- 2 yr, 1.68 +/- 0.02 m, 63.1 +/- 1.8 kg), and 28 postmenopausal (58 +/- 1 yr, 1.62 +/- 0.01 m, 69.9 +/- 1.0 kg) women who were not receiving estrogen, and to relate these findings to endogenous estrogen concentrations. All women underwent indirect calorimetry under identical situations in the basal and postprandial state following a standard mixed meal. Basal (5998 +/- 184 vs. 5712 +/- 184 vs. 5800 +/- 121 kJ.24 h, respectively) and postprandial energy expenditure (7172 +/- 239 vs. 6964 +/- 210 vs. 6955 +/- 147 kJ.24 h) was similar among groups. However, basal lipid oxidation was reduced in pregnant (45.3 +/- 6.1 mg/min, P < 0.05) and nonpregnant women (44.5 +/- 6.3 mg/min, P < 0.05) compared with postmenopausal women (58.4 +/- 2.9 mg/min). Postprandial lipid oxidation differed among groups, being least in pregnant women (8.8 +/- 6.2 mg/min) compared with nonpregnant (28.9 +/- 6.4 mg/min, P < 0.04) and postmenopausal (48.1 +/- 4.0 mg/min, P = 0.0001) women. There was a significant reciprocal increase in postprandial carbohydrate oxidation. Mean postprandial glucose levels were slightly but nonsignificantly higher in pregnant women. Insulin levels were significantly higher in postmenopausal compared nonpregnant, but not pregnant, women. In a multiple regression analysis, serum estradiol (log transformed) correlated negatively with postprandial lipid oxidation (r = -0.66, P = 0.0001) and positively with postprandial nonesterified free fatty acid levels, whereas no correlation was found with postprandial insulin, glucose, fat free mass, and fat mass. In summary, postprandial lipid oxidation is reduced in pregnancy compared with that in healthy nonpregnant women, who in turn have lower postprandial lipid oxidation than postmenopausal women. This implies that the premenopausal years and early pregnancy are states of efficient fat storage, possibly mediated through reduced lipid oxidation due to estrogen, therefore increasing body fat for reproduction, thus supporting the notion that fat mass can be regulated.

Adult↗

Blastomyces dermatitidis with large yeast forms.

Yeast forms of Blastomyces dermatitidis typically range from 8 to 20 microm in largest diameter. We report a rare case of primary pulmonary blastomycosis with an unusual morphology, in which we found significant numbers of large yeast forms ranging from 30 to 35 microm in diameter. To our knowledge, this is only the second reported case of giant forms of B dermatitidis. We also review the literature and discuss the possible association of this unusual morphology with immunosuppression in general and glucocorticoid use in particular.

Aged↗

Structural variability and originality of the Bordetella endotoxins.

Structural studies of Bordetella endotoxins (LPSs) have revealed remarkable differences: (i) between their LPSs and those of other bacterial pathogens; (ii) among the LPSs of the seven identified Bordetella species; and (iii) among the LPSs of some Bordetella strains. The lipid As have the "classical" bisphosphorylated diglucosamine backbone but tend to have fewer and species-specific fatty acid components compared to those of other genera. Nevertheless, three strains of B. bronchiseptica have at least three different fatty acid distributions; however, the recently identified B. hinzii and B. trematum LPSs had identical lipid A structures. The B. pertussis core is a dodecasaccharide multi-branched structure bearing amino and carboxylic groups. Another unusual feature is the presence of free amino sugars in the central core region and a complex distal trisaccharide unit containing five amino groups of which four are acetylated and one is methylated. The B. pertussis LPS does not have O-chains and that of B. trematum had only a single O-unit, unlike the LPSs of all the other species of the smooth-type. The O-chain-free cores of non-B. pertussis LPSs were always built on the B. pertussis core model but most were species-specifically incomplete. The LPS structures of three B. bronchiseptica strains were found to be different from each other. The O-chains of B. bronchiseptica and B. parapertussis were almost identical and had some features in common with B. hinzii O-chain. Serological analyses are consistent with the determined LPS structures.

Bordetella↗

Ability of hand radiographs to predict a further diagnosis of rheumatoid arthritis in patients with early arthritis.

OBJECTIVE: To evaluate the ability of hand radiographs collected at study inclusion to predict a diagnosis of rheumatoid arthritis (RA) 2 years later, in a cohort of patients with early arthritis. METHODS: We evaluated 270 patients with arthritis of less than one year duration. At the first visit, all patients underwent a standardized evaluation including laboratory tests and radiographs. Followup was 30+/-11.3 mo. The hand radiographs were read by observers blinded to patient data who looked for item 7 of the 1987 ACR criteria for RA and used Sharp's method to score erosions and joint space narrowing. RESULTS: The kappa coefficient for ACR item 7 was < 0.65 for bony decalcification and > 0.8 for erosions. Intra and interobserver correlation coefficients for Sharp score ranged from 0.90 to 0.95. The "erosion" component of ACR item 7 was more specific than the full item 7 (96% versus 87.5%; p = 0.02). Sharp erosion score was not better than the erosion component of item 7 (sensitivity 17%; specificity 96%). CONCLUSION: Regardless of the criterion used, hand radiographs were of limited value to predict which patients would be considered as having RA 2 years later. Diagnostic performance was similar for the "erosions" component of the 1987 ACR item 7 and for Sharp erosion score. The full 1987 ACR item 7 (erosions or bony decalcification) performed less well.

Arthritis, Rheumatoid↗

Rural rotations for interns: a demonstration programme in South Australia.

The Commonwealth Government of Australia, through policy initiatives and increased funding, has placed significant emphasis on increasing undergraduate rural experiences for medical students. However, in the immediate postgraduate years, rural community based rotations are uncommon, with the vast majority of intern experiences remaining hospital based. Since 1997, Flinders Medical Centre, Flinders University and the rural communities of Cleve and Jamestown have run a preregistration rural intern-training position based in rural general practice. The present article describes the programme, its evolution and the problems that have been overcome. The term provides a blend of hospital and community based experiences appropriate for junior doctors not yet familiar with ambulatory care. At the same time, the junior doctors have consistently reported a high-quality learning experience, with ready access to patients and procedural work. We describe the qualitative and quantitative methods we have recently introduced for evaluation of the programme.

Family Practice↗

Non-Hodgkin lymphoma in Uganda: a case-control study.

BACKGROUND: Lymphomas are a relatively common complication of AIDS in western countries, but little is known of the impact of the AIDS epidemic in Africa on the risk of these tumours. OBJECTIVE: To investigate the types of non-Hodgkin lymphoma (NHL) occurring in Kampala, Uganda, their association with Epstein-Barr virus (EBV), and how their risk is modified by HIV and other variables. METHODS: A case-control study comparing NHL cases with age/sex-matched controls. Lymphoma cases included 50 histologically diagnosed adults (31 with validation and phenotyping) and 132 histologically diagnosed children (61 with validation and phenotyping). Controls were adults with cancers unrelated to HIV and children with non-infectious diseases. RESULTS: Most (90%) childhood lymphomas were EBV-positive Burkitt's lymphoma (BL), with no association with HIV. Adult lymphoma cases were mainly BL (mostly EBV positive) or diffuse B cell lymphomas (71%). Only a weak association was found with HIV infection; a more precise estimate was obtained with the total series (OR 2.2, 95% CI 0.9-5.1) than validated/phenotyped cases (OR 2.1, 95% CI 0.3-6.7). Higher socioeconomic status adults, who travelled away from home, or had a history of sexually transmitted diseases, appeared to have a moderately increased risk of lymphoma. CONCLUSION: Childhood lymphomas were predominantly endemic BL, the risk of which was not modified by HIV. In adults, the risk associated with HIV was much lower in Uganda than in western countries, possibly because of the poor survival of immunosuppressed HIV-positive individuals. Future studies will require careful attention to subtyping of lymphomas, to investigate the possible differences between them.

Adolescent↗

Key role for the epsilon isoform of protein kinase C in painful alcoholic neuropathy in the rat.

Chronic alcohol consumption produces a painful peripheral neuropathy for which there is no reliably successful therapy, attributable to, in great part, a lack of understanding of the underlying mechanisms. We tested the hypothesis that neuropathic pain associated with chronic alcohol consumption is a result of abnormal peripheral nociceptor function. In rats maintained on a diet to simulate chronic alcohol consumption in humans, mechanical hyperalgesia was present by the fourth week and maximal at 10 weeks. Thermal hyperalgesia and mechanical allodynia were also present. Mechanical threshold of C-fibers in ethanol fed rats was lowered, and the number of action potentials during sustained stimulation increased. The hyperalgesia was acutely attenuated by intradermal injection of nonselective protein kinase C (PKC) or selective PKCepsilon inhibitors injected at the site of nociceptive testing. Western immunoblot analysis indicated a higher level of PKCepsilon in dorsal root ganglia from alcohol-fed rats, supporting a role for enhanced PKCepsilon second-messenger signaling in nociceptors contributing to alcohol-induced hyperalgesia.

Action Potentials↗