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Biomedical subjects

D McKenzie

Publications and source records attributed to D McKenzie.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

The Oral History Program: I. Personal views of health sciences librarianship and the Medical Library Association.

The Medical Library Association Oral History Program uses accepted oral history techniques to collect and preserve interviews with members. The original taped interviews and transcripts are kept in the Medical Library Association archives and made available for research purposes; edited copies of the interviews are distributed through the National Network of Libraries of Medicine, and members are encouraged to borrow and read the histories. Summaries of forty-three interviews provide personal views on health sciences librarianship and the Medical Library Association.

History, 20th Century↗

The Oral History Program: II. Personal views of health sciences librarianship and the Medical Library Association.

The Medical Library Association Oral History Program uses accepted oral history techniques to collect and preserve interviews with members. The original taped interviews and transcripts are kept in the Medical Library Association archives and made available for research purposes; edited copies of the interviews are distributed through the National Network of Libraries of Medicine, and members are encouraged to borrow and read the histories. Summaries of forty-three interviews provide personal views on health sciences librarianship and the Medical Library Association.

Archives↗

The Oral History Program: III. Personal views of health sciences librarianship and the Medical Library Association.

The Medical Library Association Oral History Program uses accepted oral history techniques to collect and preserve interviews with members. The original taped interviews and transcripts are kept in the Medical Library Association archives and made available for research purposes; edited copies of the interviews are distributed through the National Network of Libraries of Medicine, and members are encouraged to borrow and read the histories. Summaries of forty-three interviews provide personal views on health sciences librarianship and the Medical Library Association.

History, 20th Century↗

Investigation of 100 consecutive negative cone biopsies.

OBJECTIVE: To investigate the reasons for cone biopsies reported as not containing intraepithelial or invasive malignancy and thereby find ways to decrease their incidence. DESIGN: One hundred cone biopsies reported as negative were identified out of a total of 436 consecutive cone biopsies. The patients' cytology, colposcopy and histology reports and cytology and histology slides were reviewed. Further opinions in cases of doubt were obtained in cytology and histology. In cone biopsies still considered negative after reviews, deeper levels were cut, exhausting all paraffin blocks. Follow up cytology, colposcopy and histology were reviewed. SETTING: Gynaecological oncology unit in a university teaching hospital. RESULTS: After re-evaluation the final diagnoses of cone biopsies initially reported as negative were positive (n = 21), unsatisfactory (n = 27) and true negative (n = 51), with one case excluded because of insufficient material for review. The positive cases were diagnosed on review (n = 11) or extra levels (n = 10). The unsatisfactory cases were all due to denudation. The 51 true negative cases were divided into those which never had had histologic confirmation by punch biopsy or endocervical curettage (n = 47) and those with a previously confirmed histological abnormality (n = 4). CONCLUSIONS: The number of negative cone biopsies can be reduced by: 1. taking Pap smears after correction of atrophy and inflammation; 2. more scrupulous colposcopy aimed at reducing the number of unsatisfactory colposcopies or misinterpreted colposcopic findings; this through examination should include the vagina and vulva; 3. confirmation of smear and colposcopic findings by biopsy prior to cold-knife conisation and performing a large loop excision of the transformation zone (LLETZ) for cases where there is a discrepancy between the smear abnormality and colposcopy/biopsy findings; 4. good quality cone biopsies using a technique that does not handle the mucosa and is performed after the mucosa has had time to regenerate following the colposcopic investigations; and 5. exhausting all blocks with multiple levels before reporting a cone biopsy as negative.

Adult↗