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Biomedical subjects

J M Davis

Publications and source records attributed to J M Davis.

At least 73 records · Page 4Linked to original sources
PubMed1999

Improved pulmonary distribution of recombinant human Cu/Zn superoxide dismutase, using a modified ultrasonic nebulizer.

Prophylactic, intratracheal instillation of recombinant human Cu/Zn superoxide dismutase (rhSOD) has been shown to lessen lung injury produced by 48 h of hyperoxia and mechanical ventilation in neonatal piglets. However, instillation of small volumes of rhSOD intratracheally would not be expected to result in uniform pulmonary distribution. Aerosolization is a technique that may improve pulmonary distribution of drugs, but is limited by the poor efficiency of most nebulizers. A newly modified ultrasonic nebulizer was tested to assess pulmonary distribution of rhSOD compared to that achieved by intratracheal instillation. rhSOD was dual-labeled with technetium-99m (99mTc) and a fluorescent analog (permitting quantitative and qualitative assessments of pulmonary distribution), and administered to neonatal piglets by intratracheal instillation or by aerosolization. Intratracheal instillation of rhSOD to piglets when supine resulted in nonuniform distribution, with most of the drug being found in the right caudal lobe, and localized in airways. Placing animals in 30 degrees of Trendelenburg and administering half the dose in the left and half in the right lateral decubitus positions improved distribution, but alveolar deposition remained patchy. Aerosolization using a modified ultrasonic nebulizer uniformly delivered 45.8 +/- 3.8% of the rhSOD to the lungs that had been placed in the nebulizer. The rhSOD was still active and present in airways and alveoli in a homogeneous fashion. We conclude that intratracheal instillation of rhSOD in small volumes results in nonuniform pulmonary distribution, while aerosolization enhances rhSOD distribution and alveolar deposition. This has important implications for ongoing clinical trials of rhSOD for the prevention of acute and chronic lung injury in premature neonates.

Aerosols↗
PubMed1999

Assessing the human health risk of atmospheric particles.

The health implications of atmospheric particulate matter have become a topic of much interest on both sides of the Atlantic, but especially in the USA, where they were at the centre of the debate over the Environmental Protection Agency's (EPA) revision of the National Ambient Air Quality Standard in 1997. Much of this debate revolves around claims that particulate matter (usually represented by PM10) in the atmosphere directly influences mortality, hospital admissions with respiratory diseases, and so on. In this paper, we take a critical look at one of these issues, the influence of PM10 on deaths in the elderly population. Two data sets are considered, one from Birmingham (Alabama) and the other from Chicago. In both cases we find a significant PM10-mortality relationship in some of the models fitted, but not in others. Other issues considered include the existence of a threshold below which PM10 has no discernible influence, the interaction with other pollutants and the mortality displacement or harvesting effect (the theory that the direct effect of PM10 is limited to a very small subset of the population who are already critically ill and whose death is only advanced by a few hours or days as a result of air pollution). Overall, our conclusion is that there are too many uncertain issues to allow us to make definitive statements about a causal relationship between PM10 and mortality.

Air Pollution↗
PubMed1999

Effect of carbohydrate ingestion and hormonal responses on ratings of perceived exertion during prolonged cycling and running.

This randomized, double-blind, placebo-controlled study was designed to determine the influence of exercise mode, and 6% carbohydrate (C) versus placebo (P) beverage ingestion, on ratings of perceived exertion (RPE) and hormonal regulation to 2.5 h of high-intensity running and cycling (approximately 75% maximum oxygen uptake) by ten triathletes who acted as their own controls. Statistical significance was set at P < or = 0.05. The pattern of change in RPE over time was significantly different between C and P ingestion (P < 0.001) and between running and cycling modes (P = 0.001). The lowest RPE values were seen in the C-cycling sessions and the highest in the P-running sessions. The pattern of change in the respiratory exchange ratio and fat and carbohydrate oxidation rates were significantly different between the C and P conditions but not between the running and cycling modes. C relative to P ingestion (but not exercise mode) was associated with higher plasma levels of glucose and insulin and lower plasma cortisol and growth hormone levels. The pattern of change in plasma levels of catecholamines and lactate did not differ between the C and P conditions. These data indicate that a lower RPE was associated with a higher level of carbohydrate oxidation, higher plasma glucose and insulin levels, and lower plasma cortisol and growth hormone levels during cycle exercise following C supplementation as compared to P feeding. These findings support a physiological link between RPE and carbohydrate substrate availability as well as selected hormonal regulation during cycle exercise.

Adult↗
PubMed1999

Immune response to two hours of rowing in elite female rowers.

The influence of carbohydrate (C) versus placebo (P) beverage consumption on the immune and hormonal responses to normal rowing training sessions was measured in 15 elite female rowers residing at the U.S. Olympic Training Center. In a randomized, counterbalanced design, the athletes received C or P beverages (double-blind) before, during, and after two 2-hour bouts of rowing (one day apart). Blood samples were collected before, and 5-10 minutes and 1.5 hours after rowing. Metabolic measures indicated that training was performed at moderate intensities, with some high intensity intervals interspersed throughout the sessions (mean oxygen uptake of 2,307+/-169 m x min(-1), 57% of VO2max). Glucose and insulin were significantly lower after two hours of rowing with ingestion of P compared to C. The patterns of change in cortisol, growth hormone, epinephrine, and norepinephrine did not differ between C and P rowing trials. Blood neutrophil cell counts and the neutrophililymphocyte ratio were significantly higher following P versus C rowing sessions. The patterns of change in blood lymphocyte and lymphocyte subset counts, and lymphocyte proliferative responses did not differ between P and C trials, except for a slight difference in NK cell counts and activity. In summary, minimal changes in blood hormonal and immune measures were found following two-hour bouts of training in elite female rowers. Carbohydrate compared to placebo ingestion attenuated the moderate rise in blood neutrophil counts, but had slight or no effects on other immune parameters.

Adult↗
PubMed1999

Effects of branched-chain amino acids and carbohydrate on fatigue during intermittent, high-intensity running.

Experimental support for the hypothesized benefits of BCAA supplements on endurance performance is limited. However, it is theorized that the benefits may be enhanced if 1) BCAA are taken along with a pre-event carbohydrate meal as well as during exercise, and 2) the exercise is intermittent in nature. This study tested the effects of ingesting carbohydrate beverages with and without BCAA before and during intermittent high-intensity running to fatigue. Eight subjects performed 3 exercise trials consisting of intermittent shuttle running (walking, sprinting, and running) to fatigue. Subjects drank either carbohydrate drinks given 1 h before (5 mL/kg, 18% carbohydrate) and during exercise (2 mL/kg, 6% carbohydrate) (CHO), carbohydrate drinks with BCAA (7 g) added to the portions consumed 1 h before and immediately before exercise (CHO+BCAA), or flavored water placebos (P). Subjects ran longer when fed either CHO or CHO+BCAA as compared to P, with no differences between CHO and CHO+BCAA. CHO and CHO+BCAA also had higher plasma glucose and insulin, and lower FFA (p < 0.05). These findings confirm a beneficial effect of carbohydrate feedings on fatigue during exercise designed to mimic the activity pattern that occurs in sports like soccer, basketball, and hockey. They do not, however, support the hypothesis of an added benefit of BCAA supplements.

Adult↗
PubMed1999

WAIS-III Matrix Reasoning test performance in a mixed clinical sample.

This study examined the relationship between the Matrix Reasoning subtest (MRT) of the WAIS-III and a selected number of neuropsychological tests in a heterogeneous clinical sample of English-speaking American (n = 41), and non-English-speaking immigrant (n = 14) adults. A moderate association between the Halstead Category Test and the MRT (-.58) was found in the English-speaking sample. Multiple regression analysis revealed a significant association between measures of verbal abstract reasoning and verbal fluency, and performance on the MRT. Among the immigrant sample, the MRT was also found to be significantly associated with verbal fluency task performance, as well as with the Comprehensive Test of Nonverbal Intelligence. Correlational analyses therefore suggest a strong verbal mediation element in the MRT, and that labeling it a nonverbal task may be misleading.

Adolescent↗
PubMed1999

Prolactin levels and adverse events in patients treated with risperidone.

Hyperprolactinemia is a common clinical disorder that may lead to sexual dysfunction or galactorrhea. It may arise from a variety of etiologies, including the use of antipsychotic agents, presumably because of a dopamine receptor blockade. This analysis was designed to characterize the relationship between risperidone, serum prolactin levels, and possible clinical sequelae. All data from randomized, double-blind studies of risperidone in patients with chronic schizophrenia were analyzed. The two largest studies (the North American and multinational trials) included 841 patients (259 women, 582 men) with paired prolactin level data and 1,884 patients (554 women, 1,330 men) with data on six adverse events possibly associated with increased prolactin levels (amenorrhea, galactorrhea, and decreased libido in women; erectile dysfunction, ejaculatory dysfunction, gynecomastia, and decreased libido in men). Both risperidone and haloperidol produced dose-related increases in plasma prolactin levels in men and women. Among women, the risperidone dose was not correlated with adverse events, nor were the adverse events correlated with endpoint prolactin levels. Among men, the incidence of adverse events was positively correlated with risperidone dose; however, at risperidone doses of 4 to 10 mg/day the incidence of adverse events was not significantly higher than that observed in patients receiving placebo. Furthermore, adverse events in men were unrelated to plasma prolactin levels. Risperidone-associated increase in serum prolactin levels was not significantly correlated to the emergence of possible prolactin-related side effects.

Adult↗
PubMed1999

Exercise and cellular innate immune function.

Epidemiological evidence suggests a link between the intensity of exercise and infectious and neoplastic disease. One likely way by which exercise exerts its effect on cancer and infection is by altering the function of the immune system. Cells of the innate immune system (i.e., macrophage [Mphi], natural killer [NK] cell, and polymorphonuclear neutrophils [PMN]) are first-line defenders against cancer and infectious disease by nature of their phagocytic, cytolytic, and antimicrobial properties. The purpose of this review is to define the role of cells of the innate immune system (i.e., Mphi, PMN, and NK cells) in infection and cancer, present current information regarding the effects of acute and chronic exercise on the quantification and functional activities of these cells, and briefly to discuss potential mechanisms as to how exercise affects these cells and describe how these changes may potentially affect susceptibility to infection and cancer. The effects of exercise on the number, functions, and characteristics of cells of the innate immune system are complex and are dependent several factors, including 1) the cell function or characteristic being analyzed; 2) the intensity, duration and chronicity of exercise; 3) the timing of measurement in relation to the exercise bout; 4) the dose and type of immunomodulator used to stimulate the cell in vitro or in vivo; and 5) the site of cellular origin. Further studies are needed to determine whether the exercise-induced changes in immune function alter incidence or progression of disease. Likewise, the mechanisms as to how exercise alters innate immune function are as yet unresolved.

Exercise↗
PubMed1999

Mood stabilizers in the prevention of recurrent affective disorders: a meta-analysis.

OBJECTIVE: To determine by meta-analysis the efficacy of mood stabilizers in preventing recurrence of bipolar or unipolar mood disorders and to consider the evidence for a lithium withdrawal-induced relapse syndrome. METHOD: Controlled studies of lithium, valproate and carbamazepine in preventing future episodes of affective disorders were classified according to methodological rigour, and meta-analyses were performed overall and on each type. RESULTS: A total of 19 blinded, randomized, controlled trials of prophylaxis in 865 patients found lithium highly effective (74% recurrence on placebo vs. 29% on lithium). In the mirror-image studies, whose substantial lithium vs. prior treatment difference cannot be explained by withdrawal relapse, lithium reduced relapse by 50% (bipolar) and 58%(unipolar). CONCLUSION: Maintenance lithium produces a highly significant reduction in relapses. The mirror-image studies had not been systematically analysed previously, and they support the effectiveness of lithium. We also failed to find sufficient evidence to prove that the lithium-withdrawal relapse phenomenon exists.

Antimanic Agents↗
PubMed1999

Hyperoxia-induced cell death in the lung--the correlation of apoptosis, necrosis, and inflammation.

Prolonged exposure to hyperoxia causes tissue damage in many organs and tissues. Since the entire surface area of lung epithelium is directly exposed to O2 and other inhaled agents, hyperoxia leads to the development of both acute and chronic lung injuries. These pathologic changes in the lung can also be seen in acute lung injury (ALI) in response to other agents. Simple strategies to mitigate hyperoxia-induced ALI might not be effective by virtue of merely reducing or augmenting the extent of apoptosis of pulmonary cells. Identification of the specific cell types undergoing apoptosis and further understanding of the precise timing of the onset of apoptosis may be necessary in order to gain a greater understanding of the connection between apoptosis and tolerance to hyperoxia and ALI. Attention should also be focused on other forms of non-apoptotic programmed cell death.

Animals↗
PubMed1999

Influence of exercise mode and carbohydrate on the immune response to prolonged exercise.

The influence of exercise mode and 6% carbohydrate (C) versus placebo (P) beverage ingestion on lymphocyte proliferation, natural killer cell cytotoxicity (NKCA), Interleukin (IL)-1beta production, and hormonal responses to 2.5 hr of intense running and cycling (approximately 75% VO2max) was measured in 10 triathletes serving as their own controls. The C versus P condition (but not exercise mode) resulted in higher plasma glucose concentrations, lower plasma cortisol concentrations, reduced postexercise lymphocytosis and NKCA, and a lessened T-cell reduction during recovery, No condition or mode effects were observed for concanavalin A and phytohemagglutinin-induced lymphocyte proliferation. Significant mode (but not condition) effects were observed for lipopolysaccharide-induced IL-1beta production over time. However, when expressed per monocyte, the mode effect was abolished and a sustained suppression in IL-1beta/monocyte was observed in all sessions throughout recovery. These data indicate that carbohydrate ingestion significantly affects plasma glucose and cortisol concentrations, blood lymphocyte counts, and NKCA, whereas exercise mode has no effect on these parameters.

Adult↗
PubMed1999

Isolation, identification, and molecular characterization of strains of Photorhabdus luminescens from infected humans in Australia.

We describe the isolation of Photorhabdus (Xenorhabdus) luminescens from four Australian patients: two with multiple skin lesions, one with bacteremia only, and one with disseminated infection. One of the patients had multiple skin lesions following the bite of a spider, while the lesions in the other patient were possibly associated with a spider bite. The source of infection for the remaining two patients is unknown. As a member of the family Enterobacteriaceae, P. luminescens is unusual in that it fails to reduce nitrate and ferments only glucose and mannose. It gives negative reactions for lysine decarboxylase, arginine dihydrolase, and ornithine decarboxylase (Moeller). The species is motile, utilizes citrate, hydrolyzes urea, and usually produces a unique type of annular hemolysis on sheep blood agar plates incubated at 25 degrees C. A weak bioluminescence is the defining characteristic. P. luminescens is an insect pathogen and is symbiotically associated with entomopathogenic nematodes. Its isolation from human clinical specimens has been reported previously from the United States. Restriction fragment length polymorphism-PCR analysis of the 16S rRNA gene demonstrated a high level of similarity among the Australian clinical strains and significant differences between the Australian clinical strains and the U.S. clinical strains. However, numerical analyses of the data suggest that the two groups of clinical strains are more similar to each other than they are to the symbiotic strains found in nematodes. This is the first report of the isolation of P. luminescens from infected humans in Australia and the second report of the isolation of this species from infected humans worldwide.

Aged↗
PubMed1999

Ischemic preconditioning prevents postischemic P-selectin expression in the rat small intestine.

Ischemic preconditioning (IPC) prevents the deleterious effects of prolonged ischemia and reperfusion (I/R). Because leukocyte infiltration is required to produce the microvascular dysfunction induced by I/R in the small intestine, and P-selectin-dependent leukocyte rolling is a requisite step in this process, we hypothesized that IPC would attenuate postischemic P-selectin expression. To address this postulate, P-selectin expression was evaluated in nonischemic (control) rat jejunum and in rat jejunum subjected to I/R alone (20 min ischemia/60 min reperfusion), or IPC (5 min ischemia/10 min reperfusion) + I/R using a dual radiolabeled monoclonal antibody approach. I/R was associated with a sevenfold increase in jejunal P-selectin expression, an effect that was completely abolished by IPC. Exposing the bowel to adenosine deaminase or an adenosine A1, but not an A2, receptor antagonist during the period of preconditioning ischemia or to selective PKC antagonists during prolonged ischemia prevented the beneficial effect of IPC to limit I/R-induced P-selectin expression. Our data indicate that P-selectin expression is a novel downstream effector target of the adenosine-initiated, PKC-dependent, anti-inflammatory signaling pathway in IPC.

Adenosine↗
PubMed1999

Does a four-week delay in the introduction of medication alter the course of functional psychosis?

This study is an analysis of findings of a follow-up study of 105 patients with functional psychotic illness who had participated in a random and blind 4-week trial of pimozide, lithium, both and placebo. The intention was to examine the question of whether a 4-week delay in initiating antipsychotic treatment has a detrimental effect 2.5 years later. Detailed follow-up measures included need for care over the 2.5 years, treatments required, occupational decline, police contact, substance misuse, psychopathology and cognitive function. There was no evidence at all that those initially randomized to placebo had a poorer outcome in terms of any of these variables. It is concluded that a 4-week delay in initiating active treatment in patients with functional psychosis has no long-term adverse effects.

Adolescent↗
PubMed1999

Influence of fibre length, dissolution and biopersistence on the production of mesothelioma in the rat peritoneal cavity.

A range of respirable man-made mineral fibres were tested for evidence of carcinogenicity by injection into the peritoneal cavity of male SPF Wistar rats; and differences in carcinogenicity were related to the dimensions and biopersistence of the injected fibres. The fibres tested included an amosite asbestos, a silicon carbide whisker, a special purpose glass microfibre, and a range of other man-made vitreous fibres (MMVFs) and refractory ceramic fibres (RCFs) from the TIMA fibre repository. The injected dose of each was designed as the estimated mass required to contain 10(9) fibres > 5 microns in length, as determined by optical microscopy. The numbers of long fibres (> 15 microns) contained in these doses ranged across fibres from 0.1 x 10(9) to 0.8 x 10(9) fibres; the number of long fibres thinner than 0.95 micron ranged from 0.015 x 10(9) to 0.4 x 10(9). The treatment groups contained between 18 and 24 animals. Animals were killed when they showed signs of debilitation. At autopsy, the diagnosis of mesothelioma was usually obvious macroscopically. Otherwise, histological examination of peritoneal organs was used to search for early tumour development. Judged by median survival time, four of the fibre types, in the doses administered, presented higher mesothelioma activity than amosite asbestos. The other fibres tested were less carcinogenic than the amosite. Only a ceramic material derived by extreme heating to simulate the effect of furnace or oven conditions, produced no mesotheliomas. Attempts were made, using regression models, to relate these differences to fibre dimensions and to measures of durability from separate experiments. The results pointed principally to a link with the injected numbers of fibres > 20 microns in length and with biopersistence in the rat lung of fibres longer than 5 microns. Improved quantification of the relative importance of fibre dimensions and biopersistence indices requires experimentation with a range of doses.

Animals↗
PubMed1999

Influence of characteristics of inhaled fibres on development of tumours in the rat lung.

The objective was to examine and quantify the influence of fibre dimensions, persistence in the lung, and dissolution and cell toxicity in vitro, on the risks of developing lung tumours in rats. Data were brought together from the studies carried out at the IOM under the Colt Fibre Research Programme, and from studies carried out in Switzerland and the USA under the programme of the Thermal Insulation Manufacturers Association. In both studies, groups of rats were exposed by inhalation to a range of airborne fibres. At the end of their lives they were examined for the presence of benign and malignant lung tumours and mesothelioma. The studies differed in a number of details, but were combined on the basis of approximate equivalence of cumulative exposure to airborne fibres. Logistic regression models were used to relate differences in carcinogenicity to fibre characteristics; dimensions, persistence in the lung after intratracheal injection, dissolution rates from bench-top flow-through experiments, measures of inflammation, and other cell responses to fibres in vitro. Despite the small number of data points, the results suggested a primary influence of the airborne concentrations of the numbers of fibres thinner than 1 micron diameter and longer than 20 microns, and of the measured dissolution rate of the fibres. While these results are based on only a small number of fibre types, the statistical model fits the data reasonably well, and enables some cautious insights into the quantitative influences of dimensions and biopersistence. Results were broadly consistent with those from intraperitoneal injection studies of the same fibres, in that the responses were dependent on both the durability of the fibres and the numbers of long thin fibres. In vitro and in vivo cell responses did not predict significantly the risk of cancer following inhalation.

Air Pollutants, Occupational↗
PubMed1999

Delivery room resuscitation of the newborn.

Expertise in neonatal resuscitation is essential for all hospital personnel involved in the care of newborn infants. The guidelines to resuscitation reviewed here have been established by the American Academy of Pediatrics and the American Heart Association and have resulted in significantly improved training and expertise of delivery room personnel. Although widely accepted, many of these guidelines are only now being rigorously studied in controlled trials. This lack of rigorous testing has raised some questions regarding routine resuscitative practices and indicates that present-day standard therapies must always be under constant review.

Clinical Competence↗