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Biomedical subjects

D McKenzie

Publications and source records attributed to D McKenzie.

At least 19 recordsLinked to original sources
PubMed2006

Hyperimmune goat serum for amyotrophic lateral sclerosis.

The authors report a patient with amyotrophic lateral sclerosis (ALS) who showed a lessening of deterioration in respiratory muscle strength during treatment with hyperimmune goat serum (HGS) (Aimspro). Respiratory function tests (RFTs) were measured by established protocols, and all measurements were expressed as a percentage of normal predicted values. The rate of decline was calculated by linear regression analysis. Respiratory muscle strength decline was less during 13 months of treatment with HGS (mean 1.3% per month, range 0.8-1.7%) compared to the preceding 13 months (mean 2.3% per month, range 1.2-3.1%), while a greater decline would be expected with disease progression. Comparison with similarly affected patients in the literature suggest that a decline of 4-5% per month of predicted values may be expected during the treatment phase.

Amyotrophic Lateral Sclerosis↗
PubMed2005

Microbiological culture analysis of the tongue anaerobic microflora in subjects with and without halitosis.

OBJECTIVE: Determination of the microflora present on the tongue dorsum of subjects with and without halitosis using conventional microbiological culture methods. METHODS: Twenty-one halitosis and 20 control patients were recruited using a strict clinical protocol. Samples were collected from the posterior dorsum of the tongue using a sterile brush. Each sample was vortex mixed for 30 s and serial 10-fold dilutions to 10(-7) were carried out. Samples were plated onto fastidious anaerobe agar (FAA) and FAA enriched with vancomycin. These were incubated under anaerobic conditions for 10 days at 37 degrees C. Strict anaerobes were identified by metronidazole sensitivity and bacteria were identified to genus level by a combination of colony morphology, Gram staining and biochemical and enzymatic tests (rapid ID 32 A). RESULTS: The predominant species in test and control groups were Veillonella sp. and Prevotella sp. Greater species diversity was found in the halitosis samples compared with controls. The halitosis samples contained an increased incidence of unidentifiable Gram-negative rods, Gram-positive rods and Gram-negative coccobacilli. CONCLUSIONS: There was no obvious association between halitosis and any specific bacterial genus. The increased species diversity found in halitosis samples suggests that halitosis may be the result of complex interactions between several bacterial species. The role of uncultivable bacteria may also be important in contributing to this process.

Bacteria, Anaerobic↗
PubMed2004

Advanced electronics for the CTF MEG system.

Development of the CTF MEG system has been advanced with the introduction of a computer processing cluster between the data acquisition electronics and the host computer. The advent of fast processors, memory, and network interfaces has made this innovation feasible for large data streams at high sampling rates. We have implemented tasks including anti-alias filter, sample rate decimation, higher gradient balancing, crosstalk correction, and optional filters with a cluster consisting of 4 dual Intel Xeon processors operating on up to 275 channel MEG systems at 12 kHz sample rate. The architecture is expandable with additional processors to implement advanced processing tasks which may include e.g., continuous head localization/motion correction, optional display filters, coherence calculations, or real time synthetic channels (via beamformer). We also describe an electronics configuration upgrade to provide operator console access to the peripheral interface features such as analog signal and trigger I/O. This allows remote location of the acoustically noisy electronics cabinet and fitting of the cabinet with doors for improved EMI shielding. Finally, we present the latest performance results available for the CTF 275 channel MEG system including an unshielded SEF (median nerve electrical stimulation) measurement enhanced by application of an adaptive beamformer technique (SAM) which allows recognition of the nominal 20-ms response in the unaveraged signal.

Cluster Analysis↗
PubMed2003

Pathological sympathoexcitation: how is it achieved?

AIM: Congestive heart failure (CHF) and obstructive sleep apnoea syndrome (OSAS) are both associated with an intense sympathoexcitation, including an increased muscle sympathetic nerve activity (MSNA). We have studied the firing characteristics of single vasoconstrictor fibres to the muscle vascular bed in CHF and OSAS patients, at rest and during transient sympathoexcitatory stimuli, to elucidate the mechanisms by which vasoconstrictor output is augmented in these conditions. RESULTS: The main alternatives for augmenting sympathetic output are an increased firing frequency of individual nerve fibres and an increased recruitment of nerve fibres. Starting with the frequency alternative, the inherent bursting character of MSNA provides two possibilities to increase the firing of individual fibres: (1) by increasing the proportion of neural bursts in which the fibre is active (increased firing probability) and (2) by increasing the number of spikes a fibre generates per burst (increased multiple within-burst firing). At rest and in cardiac sinus rhythm, an increased firing probability is seen in both CHF and OSAS patients, whereas increased multiple within-burst firing is found in OSAS but not in CHF. In response to transient sympathoexcitatory stimuli (such as pre-mature heart beats), both patient groups show marked shifts towards multiple within-burst firing. Thus, both mechanisms for augmenting discharge frequency are operating in these two pathological conditions, but the firing characteristics at rest differ significantly. During recording sessions in sympathoexcited patients, we have encountered vasoconstrictor fibres that are active almost exclusively during periods of transient sympathoexcitation, while being virtually silent at rest. This suggests that recruitment of previously inactive vasoconstrictor fibres, the second main alternative for increasing vasoconstrictor output, contributes to transient sympathoexcitatory responses in these patients. Although it seems reasonable to assume that recruitment may also contribute to the resting level of MSNA in CHF and OSAS, this issue is difficult to resolve in microneurographic studies. CONCLUSION: In conclusion, pathological sympathoexcitation appears to depend on both recruitment and increased firing frequency. A shift towards multiple within-burst firing, at rest or in response to transient stimuli, may constitute a risk factor per se as it entails neural volleys with high instantaneous firing frequencies and consequently higher release of neurotransmitters.

Action Potentials↗
PubMed2001

Growth hormone treatment after cesarean delivery in rats increases the strength of the uterine scar.

OBJECTIVE: We sought to determine whether postcesarean treatment of rats with growth hormone (GH) affected the strength of the uterine incision in the puerperium and in a subsequent pregnancy. STUDY DESIGN: Forty-eight near-term pregnant rats were delivered by cesarean section. Half received subcutaneous recombinant human GH (2.0 mg x kg(-1) x d(-1)) for 7 days; control animals received saline injections. Four weeks after delivery, the uterine bursting pressure was determined in 5 treated and 5 control animals. Eight rats in each group were used to study uterine hydroxyproline concentrations and the histologic characteristics of the scar. Twenty-two animals were rebred 30 to 40 days after their cesarean sections. After repeat cesarean delivery, on day 19, the bursting pressure and hydroxyproline concentrations of the previous hysterotomy scar were determined. RESULTS: The uterine horn bursting pressure in the GH-treated animals was significantly greater than that in the control animals both 28 days postpartum and near term in a subsequent pregnancy. The uterine hydroxyproline concentrations followed the same pattern. Histologic study of the scars showed they were thicker and had less cellularity in the treated animals than in the control animals. CONCLUSION: Postcesarean treatment with GH increased the bursting strength of rat uterine incisions. This effect was accompanied by a significant increase in collagen content and persisted through a subsequent pregnancy.

Animals↗
PubMed2000

Can we improve the diagnostic efficiency and predictive power of prodromal symptoms for schizophrenia?

Prodromal symptoms and other variables for a sample of 200 young people who had experienced a first-onset functional psychosis, were analyzed to examine their diagnostic efficiency and predictive power in relation to a diagnosis of schizophrenia. Two different techniques were utilized to generate optimal cut-off points for a number of prodromal symptoms, and optimal decision rules to maximize diagnostic efficiency. The product of the chance-corrected sensitivity and specificity, or the area under the QROC curve, was used to assess the predictive efficiency of a number of prodromal variables, DSM-III-R prodromal variables, pre-psychotic deterioration, pre-morbid functioning, and prodromal duration. The SPAN technique generated a decision rule that performed equivalently to the single variable 'duration of prodrome'. Implications of these results for future research are discussed.

Adolescent↗
PubMed2000

Characteristics of aggressive subjects in Australian (Melbourne) nursing homes.

BACKGROUND: Aggressive behavior is common in nursing homes for the elderly. It causes distress to carers and can lead to hospitalization, overmedication, and physical restraint. METHOD: A 6-month prospective study examining the characteristics of aggressive subjects in 11 nursing homes in Melbourne using validated, reliable instruments. RESULTS: During the study, 121 and 143 subjects were rated aggressive on the Rating Scale for Aggressive Behavior in the Elderly and the Staff Observation Aggression Scale, respectively. Aggressive behavior was associated with younger age, men, subsequent mortality, and prescription of psychotropic drugs including neuroleptics, antidepressants, and benzodiazepines. CONCLUSIONS: Educational programs in the use of psychotropic drugs directed at staff involved in the care of nursing home residents may be of value because these drugs have modest efficacy, have significant side effects, and may simply sedate the patient rather than treat aggressive behavior.

Aged↗
PubMed2000

Effects of a 21-day expedition to 6,194 m on human skeletal muscle SR Ca2+-ATPase.

We investigated the effects of a 21-day expedition to the summit of Mount Denali, Alaska (6,194 m) on selected Ca2+ sequestration properties of sarcoplasmic reticulum (SR) calcium pump in vastus lateralis muscle. Muscle samples were obtained by biopsy from 5 male climbers (peak oxygen consumption, VO2peak = 52.3 +/- 2.1 mL.kg(-1).min(-1)) approximately 7 days prior to (PRE) and 4 days following (POST) the expedition. A comparison of PRE versus POST measures of maximal Ca2+-ATPase activities (117 +/- 8.5 vs. 97.6 +/- 5.6 nmol.mg protein(-1).min(-1)) and Ca2+-uptake (204 +/- 15 vs. 161 +/- 11 nmol.mg protein(-1).min(-1)) measured in crude homogenates obtained from pre-exercised muscle, indicated only an effect (p < 0.05) of the expedition on Ca2+-uptake. The reduction in Ca2+-ATPase activity, representing 16.6%, was not significant (p = 0.089). The sarco endoplasmic reticulum calcium (SERCA)-ATPase isoforms, measured using Western blotting techniques, revealed a small reduction (p < 0.05) in SERCA 1 (-4.6 +/- 1.9%), but not in SERCA 2a (+2.0 +/- 1.4%). Prior to the expedition, both Ca2+-ATPase activity and Ca2+-uptake were reduced (p < 0.05) by approximately 34 and 18%, respectively, following 40 min of a two-step continuous cycling task (20 min at 59% VO2peak and 20 min at 74% VO2peak). The exercise-induced reduction in Ca2+-ATPase activity was independent of fiber type. Only in the case of Ca2+-uptake was a lower exercise response (p < 0.05) observed following the expedition, an effect that was due to the lower resting value. It is concluded that acclimatization as experienced during a mountaineering expedition induces changes in the properties of the SR Ca2+-pump, and particularly to Ca2+-sequestering function.

Acclimatization↗
PubMed2000

Adaptation and selection of prion protein strain conformations following interspecies transmission of transmissible mink encephalopathy.

Interspecies transmission of the transmissible spongiform encephalopathies (TSEs), or prion diseases, can result in the adaptation and selection of TSE strains with an expanded host range and increased virulence such as in the case of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease. To investigate TSE strain adaptation, we serially passaged a biological clone of transmissible mink encephalopathy (TME) into Syrian golden hamsters and examined the selection of distinct strain phenotypes and conformations of the disease-specific isoform of the prion protein (PrP(Sc)). The long-incubation-period drowsy (DY) TME strain was the predominate strain, based on the presence of its strain-specific PrP(Sc) following interspecies passage. Additional serial passages in hamsters resulted in the selection of the hyper (HY) TME PrP(Sc) strain-dependent conformation and its short incubation period phenotype unless the passages were performed with a low-dose inoculum (e.g., 10(-5) dilution), in which case the DY TME clinical phenotype continued to predominate. For both TME strains, the PrP(Sc) strain pattern preceded stabilization of the TME strain phenotype. These findings demonstrate that interspecies transmission of a single cloned TSE strain resulted in adaptation of at least two strain-associated PrP(Sc) conformations that underwent selection until one type of PrP(Sc) conformation and strain phenotype became predominant. To examine TME strain selection in the absence of host adaptation, hamsters were coinfected with hamster-adapted HY and DY TME. DY TME was able to interfere with the selection of the short-incubation HY TME phenotype. Coinfection could result in the DY TME phenotype and PrP(Sc) conformation on first passage, but on subsequent passages, the disease pattern converted to HY TME. These findings indicate that during TSE strain adaptation, there is selection of a strain-specific PrP(Sc) conformation that can determine the TSE strain phenotype.

Adaptation, Physiological↗
PubMed2000

Human skeletal muscle exercise metabolism following an expedition to mount denali.

Chronic exposure to high altitude is known to result in changes in the mechanisms regulating O(2) delivery to the contracting muscle. However, the effects of acclimatization on metabolism in the contracting muscle cell remain unclear. In this study, we have investigated the hypothesis that acclimatization would result in a closer coupling between ATP utilization and ATP production and that the improved energy state would be accompanied by a reorganization of the metabolic pathways consisting of an increased oxidative and decreased glycolytic potential. Five men, mean age of 28 +/- 2 (SE) yr, performed a standardized, two-stage submaximal cycling task in normoxia for 20 min at each of 59 and 74% peak O(2) consumption before and 3-4 days after returning from a 21-day expedition to Mount Denali (6,194 m). Acclimatization was without effect in altering the resting values of the adenine nucleotides (ATP, ADP, AMP), inosine monophosphate (IMP), or phosphocreatine (PCr) in the vastus lateralis. During exercise (40 min) after acclimatization compared with preacclimatization, PCr was not as depressed (33.2 +/- 7.1 vs. 40.6 +/- 5.4 mmol/kg dry wt) and IMP (0.289 +/- 0.11 vs. 0. 131 +/- 0.03 mmol/kg dry wt) and lactate (26.1 +/- 6.2 vs. 18.6 +/- 8.8 mmol/kg dry wt) in contracting muscle were not as elevated (P < 0.05). Although no effect of acclimatization was observed for the maximal activity (mol. kg protein(-1). h(-1)) of citrate synthase (4. 76 +/- 0.44 vs. 4.94 +/- 0.45), lactate dehydrogenase was increased by 13% (36.5 +/- 2.6 vs. 41.2 +/- 3.1, P < 0.05). It is concluded that acclimatization results in an improved energy state in the contracting muscle when tested under normoxic conditions; however, these effects are not associated with a higher oxidative potential or a lower glycolytic potential as hypothesized.

Acclimatization↗
PubMed2000

Downregulation in muscle Na(+)-K(+)-ATPase following a 21-day expedition to 6,194 m.

To investigate the hypothesis that acclimatization to altitude would result in a downregulation in muscle Na(+)-K(+)-ATPase pump concentration, tissue samples were obtained from the vastus lateralis muscle of six volunteers (5 males and 1 female), ranging in age from 24 to 35 yr, both before and within 3 days after a 21-day expedition to the summit of Mount Denali, Alaska (6,194 m). Na(+)-K(+)-ATPase, measured by the [(3)H]ouabain-binding technique, decreased by 13.8% [348 +/- 12 vs. 300 +/- 7.6 (SE) pmol/g wet wt; P < 0.05]. No changes were found in the maximal activities (mol. kg protein(-1). h(-1)) of the mitochondrial enzymes, succinic dehydrogenase (3.63 +/- 0.20 vs. 3.25 +/- 0.23), citrate synthase (4. 76 +/- 0.44 vs. 4.94 +/- 0.44), and malate dehydrogenase (12.6 +/- 1. 8 vs. 12.7 +/- 1.2). Similarly, the expedition had no effect on any of the histochemical properties examined, namely fiber-type distribution (types I, IIA, IIB, IC, IIC, IIAB), area, capillarization, and succinic dehydrogenase activity. Peak aerobic power (52.3 +/- 2.1 vs. 50.6 +/- 1.9 ml. kg(-1). min(-1)) and body mass (76.9 +/- 3.7 vs. 75.5 +/- 2.9 kg) were also unaffected. We concluded that acclimatization to altitude results in a downregulation in muscle Na(+)-K(+)-ATPase pump concentration, which occurs without changes in oxidative potential and other fiber-type histochemical properties.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2000

Increases in submaximal cycling efficiency mediated by altitude acclimatization.

To investigate the hypothesis that respiratory gas exchange and, in particular, the O(2) consumption (VO(2)) response to exercise is altered after a 21-day expedition to 6,194 m, five male climbers (age 28.2 +/- 2 yr; weight 76.9 +/- 4.3 kg; means +/- SE) performed a progressive and prolonged two-step cycle test both before and 3-4 days after return to sea level. During both exercise tests, a depression (P < 0.05) in VO(2) (l/min) and an increase (P < 0.05) in minute ventilation (VE BTPS; l/min) and respiratory exchange ratio were observed after the expedition. These changes occurred in the absence of changes in CO(2) production (l/min). During steady-state submaximal exercise, net efficiency, calculated from the rates of the mechanical power output to the energy expended (VO(2)) above that measured at rest, increased (P < 0.05) from 25.9 +/- 1.6 to 31. 3 +/- 1.3% at the lighter power output and from 24.4 +/- 1.3 to 29.5 +/- 1.5% at the heavy power output. These changes were accompanied by a 4.5% reduction (P < 0.05) in peak VO(2) (3.99 +/- 0.17 vs. 3.81 +/- 0.18 l/min). After the expedition, an increase (P < 0.05) in hemoglobin concentration (15.0 +/- 0.49 vs. 15.8 +/- 0.41 g/100 ml) was found. It is concluded that, because resting VO(2) was unchanged, net efficiency is enhanced during submaximal exercise after a mountaineering expedition when the exercise is performed soon after return to sea level conditions.

Acclimatization↗
PubMed1999

The generation of martian floods by the melting of ground ice above dykes.

The surface of Mars is cut by long linear faults with displacements of metres to kilometres, most of which are thought to have been formed by extension. The surface has also been modified by enormous floods, probably of water, which often flowed out of valleys formed by the largest of these faults. By analogy with structures on Earth, we propose here that the faults are in fact the surface expression of dykes, and not of large-scale tectonic movements. We use a numerical model to show that the intrusion of large dykes can generate structures like Valles Marineris. Such dykes can provide a heat source to melt ground ice, and so provide a source of water for the floods that have been inferred to originate in some of the large valleys.

Disasters↗
PubMed1999

Endoneurial microvascular abnormalities of sural nerve in non-diabetic chronic atherosclerotic occlusive disease.

Neuropathic abnormalities are found in chronically ischaemic limbs associated with non-diabetic atherosclerotic peripheral vascular disease (PVD). In chronic ischaemic neuropathy, microvascular alterations play a key role in its development. We undertook morphometric assessment of endoneurial microvessels in the sural nerves, taken from severely ischaemic amputated legs in nine chronic non-diabetic PVD. These subjects had threatened ischaemic limbs and revealed clinical, physiological and pathological evidence of neuropathy. For comparison, sural nerves taken from amputated legs due to non-ischaemic disorders (n=4) and chronic PVD associated with diabetes (n=3) were also assessed. We evaluated the areas of vascular lumen, endothelial cells and whole vessel, as well as the percentage of closed capillaries. Endothelial area of sural nerve microvessels in non-diabetic PVD nerves was significantly greater than in non-ischaemic control nerves. Periendothelial cell area containing pericytes and basement membranes was also significantly increased in non-diabetic PVD nerves when compared with control nerves. Vascular lumen area was significantly less in non-diabetic PVD nerves than in non-ischaemic control nerves. Endoneurial microvessels in diabetic PVD nerves showed similar results: thickened vessel wall and smaller lumen. Periendothelial area in diabetic nerves was significantly greater than in non-diabetic PVD nerves. We demonstrated swollen endothelial cells and increased periendothelial area associated with narrowed lumen in sural nerve endoneurial microvessels of severe chronic PVD. Basement membrane reduplication of endoneurial capillaries was seen in non-diabetic PVD nerves. These microvascular abnormalities could play an important role in the development of chronic ischaemic neuropathy in PVD limbs.

Aged↗
PubMed1998

Reversibility of scrapie inactivation is enhanced by copper.

The only known difference between the cellular (PrPC) and scrapie-specific (PrPSc) isoforms of the prion protein is conformational. Because disruption of PrPSc structure decreases scrapie infectivity, restoration of the disease-specific conformation should restore infectivity. In this study, disruption of PrPSc (as monitored by the loss of proteinase K resistance) by guanidine hydrochloride (GdnHCl) resulted in decreased infectivity. Upon dilution of the GdnHCl, protease resistance of PrP was restored and infectivity was regained. The addition of copper facilitated restoration of both infectivity and protease resistance of PrP in a subset of samples that did not renature by the simple dilution of the GdnHCl. These data demonstrate that loss of scrapie infectivity can be a reversible process and that copper can enhance this restoration of proteinase K resistance and infectivity.

Animals↗
PubMed1998

Mycobacterial lymphadenitis in eastern Sydney.

BACKGROUND: There has been a resurgence of tuberculosis (TB) in the developed world, especially extrapulmonary manifestations, of which lymphadenitis is the most common. We reviewed all cases of mycobacterial lymphadenitis notified in the eastern suburbs of Sydney from 1989 to 1996. AIMS: To review all cases of mycobacterial adenitis in eastern Sydney. METHODS: This was a retrospective review of the medical records of 54 patients (aged 1.2 to 84 years), recruited from all notifications of TB presenting as lymphadenitis at Prince of Wales, Sydney Children's and St Vincent's Hospitals. RESULTS: There were two distinct groups: Group 1, patients with Mycobacterium tuberculosis (MTB), n = 37 (68.5%), Group 2, patients with atypical mycobacteria, n = 17 (31.5%). For Group 1, 83.3% were foreign born and 18.9% were positive for the human immunodeficiency virus (HIV). Disease involved single node groups in 73% (the cervical chain was involved in 70.1%). Complete resolution of lymphadenopathy at conclusion of treatment occurred in 73.1%. Outcome was not documented in 13.5%, of the rest; 83.8% completed treatment; 2.7% were lost to follow up before treatment concluded; 2.7% were still being seen at the time of writing and 10.8% died within six months of treatment starting (all were HIV positive). HIV positive patients had more diffuse disease. Group 2 were all Australian born. They comprised children less than six years who were all HIV negative and adults (aged 30-55 years) who were all HIV positive. The children were all treated surgically with 80% having complete resolution of their modes. Those adults with HIV had a mortality of 83.3% during treatment. CONCLUSIONS: In eastern Sydney lymphadenitis caused by MTB in the HIV negative population is mostly seen in those who are immigrants. Our large proportion of HIV positive patients tended to have diffuse disease and a high mortality. The reporting of outcomes was poor and in a greater than expected number of outcome and follow up were inadequately documented.

AIDS-Related Opportunistic Infections↗
PubMed1998

Effect of energy restriction on muscle function and calcium stimulated protease activity in recreationally active women.

The purpose of this study was to investigate whether changes in substrate oxidation that are caused by energy restriction influenced muscle function and skeletal muscle calcium stimulated protease activity in female athletes. Endurance athletes were randomly assigned to maintenance energy (100% kcal) or energy restricted (75% kcal) diet treatment groups for 14 days while maintaining regular activity. Body weight significantly decreased in the 75% diet group (-1.7 +/- 0.3 kg; p < .05), while fat oxidation increased (p < .05). Minimal changes in quadriceps function (assessed using the Kin/Com isokinetic dynamometer) were observed following diet treatment, except selected loss of muscle function in the 75% diet group at a movement velocity of 120 deg/s. These results suggest that increased fat oxidation that is induced by an acute energy restriction does not promote loss of general muscle function and activation of calcium-sensitive muscle proteases.

Adult↗