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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 235 records · Page 13Linked to original sources
PubMed2000

Enhanced albuminuric response to atrial natriuretic peptide in normoalbuminuric patients with Type 1 diabetes mellitus--a pilot study.

AIMS: To ascertain whether intravenous infusion of atrial natriuretic peptide (ANP) can induce microalbuminuria in patients with Type 1 diabetes mellitus (DM), as already demonstrated in patients with microalbuminuria, and to compare the albuminuric response to ANP infusion in Type 1 DM and a matched group of healthy non-diabetic controls. METHODS: Eight normoalbuminuric DM patients participated in a three limb, randomized, double-blind, placebo-controlled study. Subjects were kept euglycaemic by insulin infusion, and subsequently water-loaded (20 ml/kg orally plus urinary losses). When in steady state, a 30-min infusion of either placebo, ANP 0.025 mg x kg(-1).min(-1) or ANP 0.05 mg x kg(-1) x min(-1) was administered intravenously. Urine was collected every 15 min for 90 min for the estimation of albumin-creatinine ratio (ACR). In addition, eight nondiabetic volunteers received a single infusion of ANP 0.025 mg x kg(-1) x min(-1). RESULTS: ACR was unaltered by placebo in DM subjects (1.4 +/- 0.7-1.7 +/- 1.1 mg/mmol, mean +/- SD, ANOVA, P > 0.9), and by low dose ANP in controls (1.4 +/- 0.9-2.6 +/- 1.9 mg/mmol, P = 0.4). ACR increased with low dose ANP (1.3 +/- 0.5-14.6 +/- 13.6 mg/mmol, P = 0.02), and high dose ANP (1.3 +/- 0.7-26.4 +/- 31 mg/mmol, P = 0.01) in DM subjects. The ACR response to low dose ANP was greater in the DM than control subjects (P = 0.02). CONCLUSIONS: ANP increases urine albumin excretion rate in normoalbuminuric Type 1 DM patients, and this effect is more pronounced than in healthy volunteers.

Adult↗
PubMed2000

Acute hyperglycaemia causes elevation in plasma atrial natriuretic peptide concentrations in Type 1 diabetes mellitus.

AIMS: To examine the effect of acute hyperglycaemia on atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations in Type 1 diabetes. METHODS: The study was two limb, randomized, and single-blind. Eight Type 1 diabetes subjects were clamped at euglycaemia by intravenous infusion of insulin. When euglycaemia was established, the insulin infusion rate was left unaltered for the remainder of the protocol, and an intravenous infusion of either 500 ml 0.9% saline or 500 ml 10% dextrose was administered over 1 h. Blood was collected for estimation of plasma glucose, ANP and BNP concentrations at 30 min intervals for 2 h from the start of the infusion period. One week later, each subject received the alternate infusion. Results are expressed as mean +/- standard deviation, and were analysed by ANOVA. RESULTS: Baseline plasma glucose (P = 0.8), ANP (P = 0.8) and BNP (P = 0.8) concentrations were similar on the study days. Plasma glucose rose with dextrose (6.1 + 0.5-15.1 + 2.8 mmol/l, P = 0.9). Plasma ANP concentrations were unaltered by saline infusion (76.5 +/- 14.7-77.7 +/- 15.2 pg/ml, P = 0.9), but increased with dextrose infusion (79 +/- 14-134 +/- 17.1 pg/ml, P < 0.0001), and were higher with dextrose than saline infusion (P < 0.0001). Plasma concentrations of BNP were not significantly altered by infusion of either dextrose (5.1 +/- 3.9-9.3 +/- 5.4 pg/ml, P = 0.63) or saline (4.3 +/- 3.5-6 +/- 5.2 pg/ml, P = 0.84). CONCLUSIONS: Plasma concentrations of ANP, but not BNP, rise in response to acute hyperglycaemia in Type 1 diabetes.

Adult↗
PubMed2000

Acute meningococcaemia complicated by late onset gastrointestinal vasculitis.

Extra-meningeal and non-cutaneous manifestations of meningococcal infection are well recognized but rare. Herein we report a little recognized complication of meningococcaemia, namely late-onset gastrointestinal vasculitis. In the case presented, the prostacycline analogue iloprost was used in an attempt to minimize incipient digital gangrene ina patient with evidence of protracted immunological phenomena. In addition, diclofenac was used to treat severe arthralgia. Withdrawal of iloprost on day 19 was associated with abdominal pain and peritonism. Laparotomy demonstrated ischaemia and ulceration in the caecum, and histology revealed full thickness mucosal ulceration with a prominent vasculitic process. It is postulated that these findings were immunologically mediated, with possible rebound vasoconstriction following withdrawal of iloprost. It is also possible that NSAID use contributed to the findings via cyto-toxicity to mucosal cells.

Adolescent↗
PubMed2000

Remacemide hydrochloride: a placebo-controlled, one month, double-blind assessment of its safety, tolerability and pharmacokinetics as adjunctive therapy in patients with epilepsy.

Forty patients (33 male, 7 female) with refractory epilepsy were randomized to receive ascending weekly doses of adjunctive remacemide hydrochloride in a b.i.d. or q.i.d. regimen, or placebo for up to 1 month. Assessments included routine physical examination and laboratory tests, recording of adverse events and seizure frequency, and neuropsychological tests. Trough plasma concentrations of concomitant AEDs were measured at weekly intervals. Trough plasma concentrations of remacemide and its desglycinyl metabolite were measured before each dose increment, and complete 24-hour profiles were measured at steady state following administration of 600 mg day(-1)and 1200 mg day(-1). A daily dose of 1200 mg was well tolerated in a q.i.d. regimen and up to 800 mg was well tolerated in a b.i.d. regimen. The most common adverse events were dizziness, diplopia, dyspepsia and abdominal pain. On some occasions, these were considered to be related to raised concentrations of concomitant AEDs. No adverse effects were observed on seizure frequency. Neuropsychology tests revealed no significant changes. Remacemide and the desglycinyl metabolite demonstrated dose proportional pharmacokinetics over the dose range tested.

Acetamides↗
PubMed2000

Comparison of an automated thrombolytic predictive instrument to both diagnostic software and an expert cardiologist for diagnosis of an ST elevation acute myocardial infarction.

Because the electrocardiograms (ECGs) of patients with symptoms suggesting an acute thrombotic coronary occlusion are typically read by physicians relatively inexperienced in this skill, it is important to develop automated decision support. A Thrombolytic Predictive Instrument (TPI) is now available along with the standard diagnostic software in a commercially available electrocardiograph. This study evaluates the performance of the predictive software in comparison to both an expert cardiologist and standard diagnostic software. True sensitivity and specificity cannot be determined because acute coronary angiography was not performed. The specificities determined by this study were excellent (98% and 99%), and the sensitivities were very good (72% and 78%). These results that the TPI will be only rarely applied to patients who do not indeed have an acute coronary thrombosis. However, the reasons for even this small number of presumably falsely TPI positive patients should be determined and analyzed. It is unlikely that alterations of the thresholds for TPI activation will significantly improve on this very good level of sensitivity, without prohibitively decreasing specificity.

Clinical Competence↗
PubMed2000

Evolution of electromyographic signal, running economy, and perceived exertion during different prolonged exercises.

The purpose of this study was to compare the electromyographic (EMG) signal of the vastus lateralis muscle obtained during a run section of a triathlon and at the end of a prolonged run performed at the same running velocity. Seven subjects were studied on three occasions: a 2 h 15 min triathlon (30 min swimming, 60 min cycling, and 45 min treadmill running at 75% of the maximal aerobic speed), a 2 h 15 min run, where the last 45 min (Prolonged Run, PR) were run at the same speed as the Triathlon Run (TR) on a motorized treadmill, and a 45 min Isolated Run (IR) performed at the same TR and PR velocity. The three experimental trials were randomised. Oxygen uptake (VO2), heart rate (HR), and EMG data were recorded during the three run sections. The results confirm a greater VO2 and HR during PR compared with IR (P<0.01) and TR (P<0.05). Also the VO2 values obtained during TR were significantly greater compared to IR (P < 0.05). EMG signal, obtained from the vastus lateralis muscle during 4 sec of isometric contraction at 35 % of maximal voluntary contraction (MVC), showed that after PR the mean power frequency (MPF) shifted significantly to lower frequencies (P<0.01) compared with MPF recorded before the prolonged run. Moreover, the signal amplitude (RMS) was increased significantly after PR in comparison to pre-trial (P < 0.01). Similar results were obtained for the TR at P < 0.05. The integrated EMG flow, QIEMG (iEMG/burst duration), recorded during all run sections, was significantly increased near the end of PR (i.e. 2 h 10 min of running) compared with QiEMG recorded after 1 h 30 min of running. No significant increase in QiEMG was observed with TR and IR situations. The results suggest that a long exercise bout of running led to a greater increase in muscle fatigue compared with a triathlon or an isolated run performed at the same running speed. In addition it is suggested that the rating of perceived exertion recorded during isometric contractions is a good indice to approach the level of fatigue during prolonged exercises.

Adult↗
PubMed2000

Energetically optimal cadence vs. freely-chosen cadence during cycling: effect of exercise duration.

The purpose of this study was to examine the relationship between cadence and oxygen consumption with exercise duration. Ten triathletes who trained regularly were examined. The first test was always a maximal test to determine maximal oxygen uptake (VO2max). The other sessions were composed of six submaximal tests representing 80% of the maximal power reached with VO2max (Pmax). During these tests submaximal rides with a duration of 30 min were performed. Each test represented, in a randomised order, one of the following pedal rates: 50, 65, 80, 95, 110 rpm and a freely-chosen rate. VO2, respiratory parameters, and heart rate were monitored continuously. Two periods, between the 3rd and the 6th minute and between the 25th and the 28th minute, were analysed. Results showed that when VO2 and heart rate were plotted against cadence, each curve could be best described by a parabolic function, whatever the period. Furthermore, a significant effect of period was found on energetically optimal cadence (70 +/- 4.5 vs. 86 +/- 6.2 rpm, P < 0.05). Only during the second period was no significant difference found between freely-chosen cadence (83 +/- 6.9 rpm) and energetically optimal cadence (P > 0.05). In conclusion, our results suggest that during prolonged exercise triathletes choose a cadence that is close to the energetically optimal cadence. A change of muscle fibre recruitment pattern with exercise duration and cadence would explain the shift in energetically optimal rate towards a higher pedal rate observed at the end of exercise.

Adult↗
PubMed2000

Capturing the paradigm shift in HIV treatment: changing attitudes in the choice of combination antiretroviral drugs by high HIV caseload Australian GPs (1996-1997).

The use of combination antiretroviral therapy for HIV infection is a rapidly changing field. To assess the impact of recent studies on prescribing patterns, two surveys of 21 high HIV caseload Australian GPs were undertaken in June 1996 and June 1997 to plot changes in the choice of combination antiviral therapy. Of the 17 GPs who responded to the survey in each year, the number of HIV-infected patients seen at their practices were estimated to be 5,061 in 1996 and 5,912 in 1997. In 1996, 40% of their patients were estimated to be on antiretroviral therapy compared to 60% in 1997 (p < 0.05). In 1996, most GPs preferred using dual combination therapy (59%); whereas in 1997, triple combination therapy was preferred (82%). Between 1996 and 1997, there was a significant change by high caseload Australian GPs in the choice of antiretroviral drugs with many combinations being preferred prior to presentation of efficacy data for those combinations, or recommendation through national guidelines.

Anti-HIV Agents↗
PubMed2000

Purification and characterization of alpha-N-acetylgalactosaminidase from Clostridium perfringens.

alpha-N-Acetylgalactosaminidase from Clostridium perfringens is an exoglycosidase that degrades the human blood type A epitope. A highly purified preparation of alpha-N-acetylgalactosaminidase was obtained from C. perfringens by salt precipitation, gel filtration, ion-exchange chromatography, chromatofocusing, and high-pressure liquid chromatography. The final preparation was homogeneous by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with a molecular mass of 72.1 kDa. The enzyme was highly selective for terminal N-acetyl-alpha-D-galactosamine residues. No other substantial glycosidase activities, specifically neuraminidase, were detected. The pH optimum of the enzyme was between 6.5 and 7.0, and activity was unaffected by ionic strength. No protease activity was detected and enzyme activity was stable at 4 degrees C for 12 months. ELISA experiments demonstrated activity against blood type A epitope.

Chromatography, Gel↗
PubMed2000

Animal models for experimental tuberculosis.

Animal models for tuberculosis vaccine assays have evolved through a series of sequential experiments aimed at optimizing the activity of a particular vaccine product. As a result, studies that use different animal models do not agree on the potency ranking of antituberculosis vaccines, and each major test-system variable contributes to the disagreement. Disagreements among laboratories about the efficacy of vaccines are in part due to differences in test systems. A survey of potency assays of tuberculosis vaccines suggests that, based on the choice of a specific combination of variables in the test model, an investigator can show that any given vaccine product has superior potency. In view of these problems with animal models for research on tuberculosis vaccines, we recommend that attention should be focused on those animal models that replicate the key aspects of the natural history of human tuberculosis. The development of vaccines by means of new technologies requires animal models to assay the protective potency of vaccines that, ideally, inhibit tubercle bacilli at the point of infection. The development of new tuberculosis vaccines may be handled most efficiently in a joint venture that includes both laboratories involved in vaccine production and laboratories concerned with animal models.

Animals↗
PubMed2000

An analysis of some hypotheses related to the Chingelput bacille Calmette-Guérin trial.

Investigation of several hypotheses related to the outcome of the Chingelput Bacille Calmette-Guérin (BCG) Trial suggests at least 2 factors that might explain the major scientific puzzle of a protective effect expected of 80% and a protective effect observed of 0% (i.e., equivalent protection for BCG and placebo). One factor that explains some of the low efficacy observed for BCG in this trial is the virtual saturation level of exposure to environmental mycobacteria (EM). Studies in animal models demonstrated that the protection afforded by infection with EM was equivalent to the protection that resulted from BCG vaccination. The second factor, pathogenetic pathway, explains why there was still a high case rate for tuberculosis, even though the population was fully vaccinated by EM. This hypothesis states that tuberculosis in India, as well as in most developing countries, results primarily from exogenous reinfection, a pathway against which BCG (or EM) exerts no protective effect beyond that induced by the first episode of infection with Mycobacterium tuberculosis.

BCG Vaccine↗
PubMed2000

Refinements of environmental assessment during an outbreak investigation of invasive aspergillosis in a leukemia and bone marrow transplant unit.

OBJECTIVES: To investigate an outbreak of aspergillosis in a leukemia and bone marrow transplant (BMT) unit and to improve environmental assessment strategies to detect Aspergillus. DESIGN: Epidemiological investigation and detailed environmental assessment. SETTING: A tertiary-care university hospital with a 37-bed leukemia and BMT unit PARTICIPANTS: Leukemic or BMT patients with invasive aspergillosis identified through prospective surveillance and confirmed by chart review. INTERVENTIONS: We verified the diagnosis of invasive fungal infection by reviewing medical charts of at-risk patients, performing a case-control study to determine risk factors for infection, instituting wet mopping to clean all floors, providing N95 masks to protect patients outside high-efficiency particulate air (HEPA)-filtered areas, altering traffic patterns into the unit, and performing molecular typing of selected Aspergillus flavus isolates. To assess the environment, we verified pressure relationships between the rooms and hallway and between buildings, and we compared the ability of large-volume (1,200 L) and small-volume (160 L) air samplers to detect Aspergillus spores. RESULTS: Of 29 potential invasive aspergillosis cases, 21 were confirmed by medical chart review. Risk factors for developing invasive aspergillosis included the length of time since malignancy was diagnosed (odds ratio [OR], 1.0; P=.05) and hospitalization in a patient room located near a stairwell door (OR, 3.7; P=.05). Two of five A. flavus patient isolates were identical to one of the environmental isolates. The pressure in most of the rooms was higher than in the corridors, but the pressure in the oncology unit was negative with respect to the physically adjacent hospital; consequently, the unit acted essentially as a vacuum that siphoned non-HEPA-filtered air from the main hospital. Of the 78 samples obtained with a small-volume air sampler, none grew an Aspergillus species, whereas 10 of 40 cultures obtained with a large-volume air sampler did. CONCLUSIONS: During active construction, Aspergillus spores may have entered the oncology unit from the physically adjacent hospital because the air pressure differed. Guidelines that establish the minimum acceptable pressures and specify which pressure relationships to test in healthcare settings are needed. Our data show that large-volume air samples are superior to small-volume samples to assess for Aspergillus in the healthcare environment.

Analysis of Variance↗
PubMed2000

Tissue distribution of lycopene in ferrets and rats after lycopene supplementation.

To determine lycopene uptake and tissue distribution in ferrets (Mustela putorius furo) and F344 rats, we supplemented orally 4.6 mg/(kg body wt.d) lycopene in a tomato oleoresin-corn oil mixture (experimental groups). After 9 wk of supplementation, the animals were killed and blood and organs were collected. Plasma and tissue carotenoids were extracted and measured using HPLC. Mean concentrations of lycopene (nmol/kg wet tissue) in saponified tissues of ferrets were as follows: liver 933, intestine 73, prostate 12.7 and stomach 9.3. Levels of lycopene (nmol/kg wet tissue) in saponified tissue of rats were as follows: liver 14213, intestine 3125, stomach 78.6, prostate 24 and testis 3.9. When these organs were extracted without saponification, the lycopene levels were lower, except for rat testis. All-trans-lycopene was the predominant isomer found in tomato oleoresin and in the majority of rat tissues, whereas cis-lycopenes were predominant in rat prostate and plasma. This pattern was reversed in ferrets. The results show the following: 1) lycopene from tomato oleoresin is absorbed and stored primarily in the liver of both animals; 2) saponification generally improves the extraction of lycopene from most tissues of both animals; 3) cis-lycopene and all-trans-lycopene are the predominant isomers in ferret and rat tissues, respectively; and 4) rats absorb lycopene more effectively than ferrets.

Administration, Oral↗
PubMed2000

Primary meningococcal pneumonia in elderly patients.

Neisseria meningitidis infection in humans usually manifests as meningitis and septicemia with skin manifestations. Infections of the respiratory tract with N meningitidis have been documented in the past, but often this organism is not routinely considered in the differential diagnosis of pneumonia. The pathogenic role of N meningitidis in lower respiratory tract infections may be underestimated because its isolation is difficult, particularly when oropharyngeal flora are present. We profile 2 elderly patients with primary meningococcal pneumonia to show the importance of Gram stain and culture in early diagnosis. These modalities helped guide treatment and prophylactic measures.

Aged↗
PubMed2000

Noninvasive fluorescent identification of bacteria causing acute otitis media in a chinchilla model.

OBJECTIVES: To evaluate a noninvasive method of bacterial identification via fluorescence spectroscopy in the setting of acute otitis media in a chinchilla model. STUDY DESIGN: Prospective. METHODS: For each chinchilla, transbullar inoculation with Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus was performed bilaterally and clinical infection was determined by otoscopy. An optical fiber coupled to a spectrofluorometer allowed for the delivery of an excitation wavelength to the inflamed tympanic membrane and the acquisition of the resulting emission signal. Sequential emission spectra obtained over a range of excitation wavelengths were assembled by a computer algorithm, and a single, three-dimensional plot was created for each test ear. Similarly, plots from the healthy external auditory canal (EAC) were also recorded. Twelve animals were used to establish a library of four reference plots representing the three bacteria and the EAC. Of the 24 ears available for study, 10 were excluded from analysis because of lack of clinical infection or presence of tympanic membrane perforation with purulent drainage. From four additional animals, four samples from ears infected with the above bacteria and three samples of the EAC served as unknowns. The unknown plots were analyzed by an investigator blinded to their identity. RESULTS: Using a multiple correlation of the unknown to the reference plots, seven of seven samples were correctly identified. CONCLUSIONS: We were able to establish a prototype method for the noninvasive identification of a limited library of pathogens in a chinchilla model of acute otitis media.

Acute Disease↗
PubMed2000

Adherence to medication regimens among children with human immunodeficiency virus infection.

BACKGROUND: Rigorous adherence to antiretroviral medication regimens is necessary to achieve and maintain undetectable viral levels. This study describes adherence in a population of children with HIV infection. METHODS: Caregivers of HIV-infected children were interviewed about their experiences with administration of medications for treatment of HIV, opinions regarding medication-related issues and the potential usefulness of interventions to improve adherence. RESULTS: In the 90 caregiver interviews completed, 78% of the children were taking 3 or more medications, 17% missed a dose in the previous 24 h and 43% missed at least 1 dose in the previous week. Children whose caregivers reported no missed doses in the previous week (adherent) were more likely to have an HIV viral load <400 copies/ml (50% vs. 24%, P = 0.04). Nonadherent caregivers (who reported 1 or more missed doses in the previous week) were more likely than adherent caregivers to agree with a statement that full adherence is impossible (44% vs. 12%, P = 0.001) and express the need for more help with medication administration (26% vs. 6%, P = 0.02). They were less likely to have informed the school or day-care site about the child's HIV infection (42% vs. 67%, P = 0.05) and more concerned about the child's teachers and friends finding out (54% vs. 31%, P = 0.05). Of 10 potential interventions 6 were rated by a majority of respondents as "very helpful": better tasting medications (81%); longer dosing intervals (72%); medications that did not require refrigeration (63%); access to 24-h telephone advice (62%); a follow-up call from a health care provider (57%); and a pill organizer (56%). CONCLUSIONS: Caregivers' perceptions that adherence is too difficult or concerns about loss of privacy may affect their ability to adhere to complicated medication regimens. Caregivers felt that the most helpful interventions would be modifications to improve the convenience and palatability of medications and increased access to medical advice.

Adolescent↗
PubMed2000

Reliability and validity of women's recall of mammographic screening.

OBJECTIVE: To assess the reliability and validity of self-reported attendance for mammographic screening. METHODS: To assess reliability of recall of attendance for a screening mammogram, 100 women selected at random were interviewed twice (approximately one week apart). To assess validity, 127 women who reported having a mammogram within the national breast screening program (BreastScreen Australia) consented to having their reports verified by the national program. RESULTS: Test-retest reliability for the question "Have you ever had a mammogram?" was perfect (agreement 100%, kappa 1). Validity was also high. About one-quarter of women (24.4%) recalled the exact date of their last mammogram and a further third (39.4%) correctly reported the month in which the mammogram was done. Almost all (91.3%) women reported the mammogram date accurately to within 12 months of the recorded date. CONCLUSIONS: These data suggest that Australian women provide reliable and valid information in relation to mammographic screening attendance. IMPLICATIONS: Self-reported data about attendance for mammographic screening are likely to provide reliable and valid estimates for research and health services evaluation purposes.

Adult↗