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Biomedical subjects

J Garrett

Publications and source records attributed to J Garrett.

At least 55 records · Page 3Linked to original sources

Major reduction in asthma morbidity and continued reduction in asthma mortality in New Zealand: what lessons have been learned?

Increasing financial barriers to primary health care against a background of social and economic decline are likely to have contributed to asthma morbidity and mortality in New Zealand. Although there would not have been a sufficient increase in asthma prevalence to have accounted for the threefold increase in mortality rates, whether or not there was an increase in asthma severity in the late 1970s remains open to debate. Misuse or poor use of newly available and potent bronchodilator medications by those with the most severe asthma may simply have contributed to further delays in obtaining appropriate care and therefore to an increase in frequency of severe attacks in the community. Despite substantial increases in the use of bronchodilator therapy in New Zealand, there was no immediate improvement in indices of either asthma morbidity or mortality. The initial reduction in mortality rates in the 1980s happened at a time when first admissions for asthma were still increasing and seems to be best explained by an improvement in utilisation of hospital services (which were free until 1992) rather than a reduction in asthma severity. However, the recent reductions in all measures of asthma morbidity and further reduction in asthma mortality since 1989 does now suggest a reduction in asthma severity and would be best explained by the substantial increase in medium and high dose inhaled corticosteroid use, and to the endorsement of the current management strategies for asthma which are being promoted internationally and which were given considerable publicity in New Zealand in 1989 and 1990. Whilst sales of inhaled beta agonists were higher in 1991 than 1989, this may not reflect their pattern of use by individual patients since the need for an increase in inhaled beta agonist treatment has been accepted as indicating a lack of control and the need for either starting or increasing the dose of inhaled steroid treatment.

Adolescent↗

Photodynamic therapy of ocular melanoma with bis silicon 2,3-naphthalocyanine in a rabbit model.

PURPOSE: To investigate bis (tri-n-hexylsiloxy) silicon 2,3-naphthalocyanine (SINc; 0.5 mg/kg) for photodynamic therapy of an experimental ocular melanoma in pigmented rabbits. METHODS: SINc was dissolved in canola oil by heating, emulsified with Tween 80, and administered by ear vein. Pharmacokinetics were studied in frozen tumor sections by fluorescence microscopy using a charge coupled device, camera-based, low-light detection system with digital image processing at 1 and 24 hours. A Ti:sapphire laser and a microlens were used to deliver the light (770 nm; 40 mW/cm2; 20 J/cm2). A control rabbit received light without SINc. RESULTS: Localization studies of SINc showed intravascular distribution shifting to a tumor stromal and perivascular distribution 24 hours after treatment. Tissue thermal damage after irradiation was minimal in the control. Exudative retinal detachments were not observed. Tumor destruction was observed, with sharp demarcation to a depth of 3.5 mm. CONCLUSIONS: Tumor light penetration was good at 770 nm, and thermal effects from the exciting light alone were minimal. Photodynamic therapy with SINc resulted in localized tumor destruction reflecting the light beam path without damage to adjacent tissue or intraocular complications.

Animals↗

The self reported prevalence of asthma symptoms amongst adult New Zealanders.

AIMS: To examine the prevalence of asthma symptoms in a random population sample of New Zealand adults aged 20-44 years drawn from the general and Maori electoral rolls as phase I of an international study of asthma prevalence. METHODS: Subjects aged 20-44 years in Auckland, Hawkes Bay, Wellington and Christchurch, were selected randomly from the electoral rolls and sent a one page screening questionnaire, asking about respiratory symptoms, asthma attacks and asthma treatment. They were also asked to record their ethnic affiliation. Nonresponders were subsequently sent two written reminders followed by a telephone questionnaire where possible. RESULTS: A response rate of 84% was achieved. The study found a high prevalence of asthma symptoms, with 26% reporting wheezing in the last year, 8% experiencing an attack of asthma in the last year and 9% currently using asthma medication. Females were more likely to have had wheezing in the last year (26.6%) and be on treatment for asthma (9.8%) compared with males (24.7% and 7.5% respectively). Small regional differences were found with more reported symptoms and asthma treatment in Wellington and Christchurch, compared with Auckland and Hawkes Bay. Maori were more frequently symptomatic (35.2%) than nonPolynesian (24.8%) but were no more likely to report an attack of asthma (Maori 9.0%, nonPolynesian 7.7%) or be currently receiving asthma treatment (Maori 10.0%, nonPolynesian 8.6%). Asthma symptoms tended to decline with age in non Maori but increased with age in Maori. Adjustment of prevalence rates by two independent methods suggests that nonresponse bias has not significantly inflated these rates. CONCLUSIONS: The symptoms of asthma and their treatment are common in young New Zealanders, affecting one in three Maori and one in four nonMaori. One in ten of this adult population currently receive asthma treatment.

Adult↗

Stability of choices about life-sustaining treatments.

OBJECTIVE: To examine the stability of patients' choices for life-sustaining treatments. DESIGN: A longitudinal cohort study. SETTING: Primary care practices in central North Carolina. PATIENTS: Medicare recipients (n = 2536). INTERVENTION: Participants were asked about demographic characteristics, health status, well-being, depression, social support, use of a living will, and desire for life-sustaining treatment if they were to become terminally ill. These questions were repeated 2 years later (n = 2073, 82% follow-up). RESULTS: The population tended to choose to forego one more treatment at follow-up than they did at baseline. A choice to forego treatment was twice as stable as a choice to receive treatment. Patients with a living will were less likely to change their wishes (14%) than those without a living will (41%). Persons were more likely to want increased treatment at a later time if they had been hospitalized (23% compared with 18%), had had an accident (29% compared with 19%), had become more immobile (23% compared with 19%), had become more depressed (25% compared with 15%), or had less social support (25% compared with 14%). CONCLUSIONS: Most patients (85%) who had chosen to forego life-sustaining treatments did not change their choices. Nonetheless, these data suggest that it is important to review patients' preferences for life-sustaining treatments rather than to assume the stability of their choices.

Advance Directive Adherence↗

Peak expiratory flow meters (PEFMs)--who uses them and how and does education affect the pattern of utilisation?

BACKGROUND: Asthma control may be assisted by educating patients to use peak expiratory flow meters (PEFMs). AIMS: To find out the sociodemographic and clinical characteristics of asthmatics attending an Emergency Room (ER) who owned PEFMs. METHODS: We undertook a study of 352 asthmatics aged seven to 55 years who attended an ER. The following were analysed: their pattern of peak flow monitoring (PFM), the factors associated with 'appropriate' or daily PFM on entry to the study and then prospectively; whether asthma education influenced utilisation and whether there was a reduction in ER use or admissions in those who acquired a PEFM. RESULTS: Those owning a PEFM at entry to the study (54%) had more asthma morbidity (p = 0.0001), had had asthma for longer (p = 0.0001), had seen their medical practitioners more often in the previous nine months (p = 0.0001), were on more asthma medications (p = 0.0001) and were more likely to have been to an Asthma Clinic (p = 0.0001). Those not owning a PEFM were more likely to be of lower social class (p = 0.016) and of Pacific Island origin (p = 0.0001) suggesting that distribution is not ideal and is influenced by disease severity, amount of health care use and sociodemographics. Patients with a self-management plan (35% of PEFM owners) and those receiving 'good care' or management, were more likely to use PFM 'appropriately' and to mention PFM in a scenario evaluating their response to worsening asthma control and argues for PEFMs to be distributed only in conjunction with a self-management plan, and therefore in close association with the patients' medical practitioners. Most patients (75%) appeared to prefer making management decisions based on symptoms rather than on their peak expiratory flow (PEF) and few (16%) performed daily PFM at entry to the study and fewer (6%) nine months later. There was an improvement in the pattern of PFM after education, but the acquisition of a PEFM made no difference to the frequency of ER use or admission. CONCLUSION: More realistic goals need to be defined in relationship to PFM which may improve patients' acceptance of the strategy, and therefore, hopefully their compliance. Such strategies need to be consistently reinforced over time for them to have an impact on asthma morbidity.

Adolescent↗

Prospective controlled evaluation of the effect of a community based asthma education centre in a multiracial working class neighbourhood.

BACKGROUND: Previous work has indicated a high rate of non-attendance at hospital based clinics among young, multiracial asthmatic patients of lower socioeconomic class. The efficacy of delivering asthma education from a community health centre established in a multiracial working class neighbourhood was evaluated. METHODS: A prospective controlled study was performed in which asthmatic subjects aged between two and 55 years attending a hospital emergency room with acute asthma and living within a defined geographical area of high emergency room users were randomised to the usual follow up or the education centre plus usual follow up. Measurements were taken at entry into the study and again nine months later. RESULTS: At nine months patients randomised to the education centre had more preventive medications, more peak expiratory flow meters and better flow meter technique, more self-management plans, better knowledge of appropriate action to take when confronted with worsening asthma, less nocturnal awakening, and better self-reported asthma control than the control group. There was no difference between the study groups in measurements of compliance, hospital admission, days lost from school or work, or emergency room use. CONCLUSIONS: The main effects of education were on asthma knowledge and self-management skills, whilst improvements in asthma morbidity were small. Potential reasons for this include heterogeneous study population (in terms of baseline self-management skills, asthma severity, ethnicity and age), pragmatic study design, insensitivity of many of the measurements of morbidity, the modest effectiveness of a single time limited education programme, and inability to limit the effects of such a large community based study to the intervention group (there was a 67% reduction in asthma admissions during the study period from the geographical area targeted compared with a 22% reduction for the rest of Auckland).

Adolescent↗

Lysis protein S of phage lambda functions in Saccharomyces cerevisiae.

The lambda S lysis gene was cloned into a Saccharomyces cerevisiae expression vector under GAL1 control. Induction with galactose in S. cerevisiae terminated cell growth and prevented colony formation. Several membrane proteins immunoreactive with anti-S antibody accumulated in the membranes, indicating that sodium dodecyl sulfate-resistant oligomers of S are formed, similar to those observed in the membranes of Escherichia coli cells killed by expression of the S gene. These observations suggest that the S gene product functions as a cytotoxic protein in the yeast cytoplasmic membrane as it does in the bacterial membrane.

Amino Acid Sequence↗

The otologic significance of cleft palate in a Sri Lankan population.

The otologic findings from 197 subjects with repaired and unrepaired clefts and 121 noncleft controls are presented. All data were collected in Sri Lanka during a 3-week period attached to the Sri Lanka Project in 1986. Subjects were examined otoscopically and also tested audiometrically if they were able to perform a pure-tone audiogram, a performance test, or a distraction test. Subjects with clefts of the palate were found to have fewer otoscopically normal ears than the controls. A comparison between subjects with unrepaired and repaired palates revealed a similar rate of otoscopically normal ears in subjects older than 10 years of age. Comparisons for younger ages could not be performed because of a lack of subjects less than 10 years of age who had repaired palates. The impedance data were used to verify the accuracy of otoscopy in detecting effusion.

Acoustic Impedance Tests↗

Effects of ovariectomy on GnRH mRNA, proGnRH and GnRH levels in the preoptic hypothalamus of the female rat.

Experiments were carried out to investigate the effects of ovariectomy on gonadotropin-releasing hormone (GnRH) messenger RNA (mRNA), proGnRH and GnRH peptide levels in the hypothalamus of female rats. Intact proestrous female rats and female rats, which had been ovariectomized for 2 weeks, were sacrificed at 9.00 h and the preoptic area (POA) and basal hypothalamus (BH) were dissected out and frozen on dry ice. One group of tissues from proestrous control and ovariectomized females were extracted in acetic acid, centrifuged at 13,000 g and the supernatant purified on a C18 column. The purified extract was then radioimmunoassayed for proGnRH, using a specific antiserum to rat proGnRH (ARK-2), and for GnRH using the E1-14 antiserum. Total cellular RNA was isolated from another group of tissues and prepared as Northern blots. Hybridization with 32P-labeled GnRH cRNA was used to detect GnRH mRNA. A third group of proestrous and ovariectomized female rats were perfused, and 50 microns vibratome sections were cut. These were immunostained with proGnRH or GnRH antiserum, followed by in situ hybridization with 35S-labeled GnRH cRNA to detect GnRH mRNA. Based on the histochemical staining, mRNA was colocalized to the cell soma of neurons containing proGnRH and GnRH throughout the POA and BH. Based on the radioimmunoassay, proGnRH levels were 2 times higher in the POA versus the BH, but GnRH levels were 6-7 times higher in the BH. Ovariectomy significantly decreased proGnRH levels in both the POA and BH, while GnRH decreased in the BH. In contrast, quantitative Northern blot analysis demonstrated that ovariectomy had no effect on mRNA levels in the POA and BH. These data indicate that the effects of ovariectomy on proGnRH and GnRH levels are a result of altered translation, posttranslational processing and/or secretion of GnRH.

Animals↗

Verapamil and diet halt progression of atherosclerosis in cholesterol fed rabbits.

The present study was designed to evaluate the effects of oral verapamil and normal diet on regression of atherosclerotic plaque in cholesterol fed rabbits. Forty-three rabbits were separated into 6 groups and studied for 24 weeks. All groups had a cholesterol diet for the first 12 weeks. Group I was then sacrificed and had 38 +/- 23% (mean +/- standard deviation) aortic plaque. During weeks 13 to 24, group II (cholesterol diet) and group III (normal diet) had similar percentages of aortic plaque: 80 +/- 7% and 78 +/- 22%, respectively. Group IV (cholesterol diet), was treated with oral verapamil for 24 weeks and had significantly less plaque (54 +/- 10%) than group II, (80 +/- 7%). In group V (cholesterol diet), treatment with oral verapamil during weeks 13 to 24 did not significantly reduce plaque (70 +/- 23%), compared to group II, (80 +/- 7%). In group VI, normal diet and verapamil during weeks 13 to 24 significantly reduced aortic plaque (46 +/- 25) when compared to group II (80 +/- 7%). Group VI (46%) did not differ from group I (38%). It is concluded that verapamil combined with a normalized diet can halt the progression of aortic atherosclerosis after a 12 week atherogenic diet in rabbits. Verapamil or diet alone was ineffective in the second 12 weeks. Overall, verapamil was effective in preventing atherosclerosis but was ineffective in causing regression of atherosclerosis.

Animals↗

The preventive effect of verapamil on ethanol-induced cardiac depression: phosphorus-31 nuclear magnetic resonance and high-pressure liquid chromatographic studies of hamsters.

Alcoholic depression of left ventricular function was produced in normal hamsters by the administration of increasing concentrations of alcohol in drinking water (up to 50%) for 6 months. The result was assessed by phosphorus-31 nuclear magnetic resonance of isolated perfused hearts and high-pressure liquid chromatography of freeze-clamped tissues. Hemodynamic data and myocardial oxygen consumption were also monitored. Alcoholic hamsters had significantly higher inorganic phosphate and lower ATP levels, while maintaining normal intracellular pH, phosphocreatine, and creatine. Although coronary flow and oxygen consumption were maintained at normal levels, hamsters ingesting 50% ethanol had significantly lower left ventricular developed pressure and dP/dt. Treatment with verapamil during long-term ethanol consumption prevented the development of these metabolic and functional abnormalities. It is hypothesized that alcohol produces membrane abnormalities leading to adverse ion flux, and that these are largely prevented by concurrent administration of verapamil.

Adenosine Triphosphate↗

Quantitation of regional myocardial function by cine computed tomography: pharmacologic changes in wall thickness.

To determine the capability of high speed computed transmission tomography to quantitate regional wall thickening dynamics over a wide range of physiologic states, left ventricular wall thickening was studied in nine anesthetized mongrel dogs in the control state and during separate infusions of dobutamine (10 micrograms/kg per min) and phenylephrine (25 micrograms/kg per min). After an intravenous bolus of contrast medium the heart was imaged from base to apex with serial transverse images in eight short-axis cine computed tomographic planes. In each dog during each experimental condition, 50 ms scans spanning the cardiac cycle were acquired at each anatomic level. Left ventricular epicardial and endocardial boundaries were identified on end-diastolic and end-systolic images at the equatorial left ventricular planes by an objective threshold contour method validated in a series of experiments performed on ex vivo anatomic specimens. End-diastolic and end-systolic frames were automatically realigned by superposition of epicardial centers of gravity and then rotated using a cross correlation function. The left ventricular wall thickness was measured manually at 16 points around the circumference by two independent observers. For the group of dogs the average percent wall thickening was 40.5 +/- 28.2% and varied among segments from 18 to 70% in the control state. After dobutamine was administered, significant increases in heart rate and cardiac output (p less than or equal to 0.01) were accompanied by an increase in the average wall thickening (73.6 +/- 51.2%; p less than or equal to 0.001) in the left ventricle; the average wall thickening among segments ranged from 46 to 97%. After phenylephrine administration, significant increases in mean blood pressure and cardiac output (p less than or equal to 0.01) were noted along with a significant increase in average left ventricular wall thickening (60.3 +/- 52.5%; p less than or equal to 0.001). Despite an overall increase in the percent wall thickening, no statistically significant changes in segmental contraction pattern between control and drug intervention states were observed. The wall thickness measurements were highly reproducible between the two independent readers (reliability coefficient = 0.99). Cine computed tomography-derived measurements can potentially be used for quantitative assessment of left ventricular wall thickening dynamics of a single heartbeat during acute interventions, such as the administration of drugs.

Animals↗