Search PubMed⌕ Search

Biomedical subjects

M Johnson

Publications and source records attributed to M Johnson.

At least 163 records · Page 9Linked to original sources

The indigenous fisherman divers of Thailand: diving-related mortality and morbidity.

The Urak Lawoi are indigenous fishermen on Thailand's west coast. The population includes an estimated 400 divers who dive using surface-supplied compressed air. In a cross-sectional survey conducted among the 6 major communities of Urak Lawoi, questionnaire-based interviews were administered to active divers, ex-divers, and families or colleagues of divers who had died in the previous 5 years. Six deaths resulting from diving-related accidents were identified, indicating a diving-related mortality rate of approximately 300 per 100,000 person-years, while in the same 5-year period 11 divers had been disabled owing to diving-related events, indicating a diving-related disabling event rate of approximately 550 per 100,000 person-years. Among 342 active divers interviewed, one third reported having suffered from decompression illness, although based on reported current symptoms over 50% were classified as suffering from recurring non-disabling decompression illness. Physical examination conducted on a subset of 98 active divers revealed the presence of spinal injury (clonus, raised muscle tone, and heightened reflexes) and of joint damage (pain in one or more joint, crepitus, or restricted movement) in 24 and 30% respectively. Improved primary prevention and medical treatment are needed to reduce mortality and morbidity among this population.

Accidents, Occupational↗

Anesthesia for fetoscopic fetal surgery: twin reverse arterial perfusion sequence and twin-twin transfusions syndrome.

IMPLICATIONS: Twin reversed arterial perfusion sequence and twin-twin transfusion syndrome can be managed by fetoscopic fetal surgery. It is important to consider the fetal, uteroplacental, and maternal issues when choosing an anesthetic technique. We report on three patients with differing anesthetic issues using fetoscopic surgery for umbilical cord coagulation.

Adult↗

An instrument to measure symptom experience. Symptom occurrence and symptom distress.

This article describes the development of an instrument that measures symptom experience (symptom occurrence and symptom distress). The Adapted Symptom Distress Scale-2 (ASDS-2), adapted from the McCorkle and Young Distress Scale, is a 31-item, 5-point, self-report paper-and-pencil instrument that measures patients' perception of the occurrence and distress of 14 symptoms: nausea, vomiting, pain, eating, sleep, fatigue, bowel elimination, breathing, coughing, concentration, lacrimation, changes in body temperature, appearance, and restlessness. Use of the instrument yields a total score for symptom experience, scores for symptom occurrence, scores for symptom distress, and subscale scores for six symptom categories: gastrointestinal, fatigue/restlessness, concentration, pain/discomfort, respiratory, and appearance. Reliability and validity were determined with well adults (n = 97), medical-surgical patients (n = 82), and oncology patients (n = 175). Findings revealed a Cronbach's alpha of 0.91 for symptom experience, 0.90 for symptom occurrence, and 0.76 for symptom distress. Cronbach's alpha for the subscales ranged from 0.38 for appearance symptoms to 0.83 for gastrointestinal symptoms. Inclusion of symptoms reported by patients with cancer strengthened content validity. A contrasted groups approach was used to demonstrate construct validity.

Adolescent↗

Osteosarcoma in preadolescent patients.

The medical records of boys younger than 11 years and girls younger than 10 years of age with osteosarcoma of the pelvis or extremity were reviewed. Thirty patients were identified who were newly diagnosed but untreated for osteosarcoma. None of these patients had pulmonary metastases. The same four protocols were used to treat the patients in the current study as were used to treat adolescents. The event-free and overall survival was calculated and prognostic factors were assessed. The median followup time was 8 years (range, 6-14 years). The results were compared with the results of older patients treated with the same protocols and with published results. Fourteen patients had pulmonary metastases (47%); among these patients, four also had skeletal metastases (in two of the latter, skeletal metastases appeared before the pulmonary metastases). Event-free survival was 53% and overall survival was 57%. This result is comparable with current survival results in adolescent and older patients. Serum alkaline phosphatase and serum lactic dehydrogenase levels before treatment, height percentile greater than 50%, chemotherapy-induced tumor necrosis, surgical procedure, tumor site, tumor histologic features, and patient gender were not prognostic indicators. The prognosis for prepubertal patients with osteosarcoma is similar to the prognosis of their adolescent and older counterparts. There does not seem to be any indication to treat preadolescent patients with osteosarcoma using alternate therapies.

Antineoplastic Combined Chemotherapy Protocols↗

A dose ranging study of the pharmacokinetics, safety, and preliminary efficacy of lamivudine in children and adolescents with chronic hepatitis B.

Fifty-three patients with chronic hepatitis B and active viral replication were studied for 4 weeks while on treatment and for 12 weeks after treatment with the oral nucleoside analogue lamivudine. Children aged 2 to 12 years were randomized to receive twice-daily doses of 0.35, 1.5, or 4 mg of lamivudine solution per kg of body weight or once-daily doses of 3 mg of lamivudine solution per kg. Adolescents aged 13 to 17 years received lamivudine at 100 mg (as tablets). Blood samples for pharmacokinetic assay were taken on days 1 and 28. Lamivudine was rapidly absorbed following oral administration, with the maximum concentration in serum being reached 0.5 to 1 h postdosing. Apparent oral clearance (CL/F) was higher in younger children and decreased with age, with CL/F values for adolescents reaching those seen for adults by the age of 12. All doses produced a dramatic fall in serum hepatitis B virus (HBV) DNA levels, with a median reduction of >/=99.5% after 4 weeks of treatment and with the levels returning to the baseline levels posttreatment. The correlation of dose, area under the concentration-time curve (AUC), and changes in HBV DNA levels, as measured by the Chiron Quantiplex assay, showed maximal antiviral effects (99.9% inhibition and a reduction of the amount of HBV DNA of approximately 3 log(10)) at 3 mg/kg/day, with no discernible increase in effect seen whether the drug was given at 4 mg/kg twice daily or whether it was given once daily or twice daily. The limit of detection of the assay (2.5 pg/ml) was reached for some but not all patients across the dose ranges, with the smallest number (n = 2) of those having values negative by the Chiron Quantiplex assay being in the lowest-dose group. The 13- to 17-year-olds showed a similar overall response in terms of the HBV DNA level reduction compared to that for patients younger than age 13. Analysis of the same samples by PCR, which has a lower limit of sensitivity than the Chiron Quantiplex assay, also showed average drops in HBV DNA levels of about 3 log(10) at 4 weeks for patients for which the AUC was >/=4,000 ng. h/ml, confirming the conclusions given above. Lamivudine treatment was well tolerated at all doses, with no significant adverse events or laboratory data changes. On the basis of pharmacokinetic and pharmacodynamic data, a 3-mg/kg/day dose in children (ages 2 to 12 years) with chronic hepatitis B provides levels of exposure and trough concentrations similar to those seen in adults following the receipt of doses of 100 mg. The 100-mg dose is being evaluated in a large phase III study with HBV-infected pediatric patients.

Adolescent↗

Pharmacokinetics and tolerability of gemifloxacin (SB-265805) after administration of single oral doses to healthy volunteers.

Gemifloxacin (known as SB-265805 or LB-20304) is a potent, novel fluoroquinolone compound with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in healthy male volunteers after a single dose of 20, 40, 80, 160, 320, 600, or 800 mg. Multiple serum and urine samples were collected and analyzed for gemifloxacin using high-performance liquid chromatography with fluorescence detection. Safety assessments included vital signs, 12-lead electrocardiogram readings, hematology, clinical chemistry, urinalysis, and adverse-experience monitoring. Gemifloxacin was rapidly absorbed after all doses. Maximum concentrations of gemifloxacin in serum (C(max)) were achieved approximately 1 h after dosing, after which concentrations in serum declined in a biexponential manner. Values of C(max) and the area under the concentration-time curve in serum from 0 h to infinity (serum AUC(0-infinity)) increased linearly with dose. Serum AUC(0-infinity) values (mean +/- standard deviation) were 0.65+/-0.01, 1.28+/-0.22, 2.54+/-0.31, 5.48+/-1.24, 9.82+/-2.70, 24.4+/-7.1, and 31.4+/-7.6 microg. h/ml following 20-, 40-, 80-, 160-, 320-, 600-, and 800-mg doses, respectively. The terminal phase elimination half-life was independent of dose, with an overall mean of 7.4+/-2.0 h. The profiles indicated that the pharmacokinetic profile is suitable for a once-daily dosing regimen. Approximately 25 to 40% of the administered dose was excreted unchanged in the urine, and renal clearance (ca. 150 ml/min) was independent of dose. There were no significant changes in clinical chemistry, hematology, or urinalysis parameters, vital signs, or 12-lead electrocardiogram readings in subjects, irrespective of dose. The results of these studies support the further investigation of once-daily administration of gemifloxacin.

Administration, Oral↗

Automated measurement of unsaturated iron binding capacity is an effective screening strategy for C282Y homozygous haemochromatosis.

BACKGROUND: C282Y hereditary haemochromatosis is an appropriate condition for population screening. Transferrin saturation, the best screening test to date, is relatively expensive, labour intensive, and cannot be automated. Unsaturated iron binding capacity is a surrogate marker of transferrin saturation and its measurement can be automated. AIMS: To evaluate a screening strategy for C282Y hereditary haemochromatosis in a tertiary hospital environment based on unsaturated iron binding capacity as the initial screening test. METHODS: Measurement of unsaturated iron binding capacity was adapted to the main laboratory analyser. An unsaturated iron binding capacity of less than 30 micromol/l was identified as an appropriate decision point and 5182 consecutive subjects were screened over 28 consecutive days. RESULTS: Of those screened, 697 had an unsaturated iron binding capacity less than 30 micromol/l. Of these, transferrin saturation was greater than 40% in 294. A total of 227 were able to be genotyped for the C282Y mutation. Nine subjects homozygous for C282Y were identified. Based on full cost recovery, affected persons were identified at a cost of Aus$2268.77 per case (approximately US$1496). CONCLUSION: Automated measurement of unsaturated iron binding capacity enables a cost effective, large scale population screening programme for C282Y hereditary haemochromatosis to be developed.

Adult↗

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↗

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↗

Outcome indicators for direct and indirect caregiving.

Informal caregiving and outcomes for caregiving are an important part of health care and of particular importance in nursing. The purpose of this research is to report the results of a survey mailed to nursing experts for validation of the outcome labels Caregiver Role Performance: Direct Care and Caregiver Role Performance: Indirect Care and their accompanying indicators. Experts were asked to rate how important the identified indicators were for assessing those two outcomes. In addition, the respondents were asked to what extent nursing interventions influence the achievement of each identified indicator for Caregiver Role Performance: Direct Care and Caregiver Role Performance: Indirect Care. In general, the validity of the concept analysis work by the caregiver focus group was supported. Ten indicators for Caregiver Performance: Direct Care were retained, 1 was dropped that was considered most appropriate for indirect care, and 3 new indicators were added to reflect the nurse experts surveyed. For Caregiver Performance: Indirect Care, all of the indicators were retained.

Caregivers↗

Association of estrogen receptor-alpha genotypes with body mass index in normal healthy postmenopausal Caucasian women.

Several lines of evidence suggest the importance of the estrogen receptor (ER) in determining body mass index (BMI). Our purpose was to investigate whether genetic polymorphisms at the restriction enzyme PvuII site of the ER-alpha gene locus are associated with BMI variation. Data on BMI, age, and ER-alpha genotypes were obtained from 108 healthy midwestern U.S. postmenopausal Caucasian women. The study subjects were unrelated and aged 65 yr and over (mean age +/- SD, 73.4 +/- 5.1 yr), with an average BMI of 25.25 (SD, 4.04). The ER-alpha genotypes were obtained by PCR followed by restriction enzyme PvuII digestion. We found that in our study subjects the ER-alpha genotypes are significantly associated with BMI (by ANOVA, P = 0.04), explaining about 6.2% of the BMI variation in our study sample. The allelic effects of this locus on BMI are approximately additive. In our sample, individuals of the PP and Pp genotypes have, respectively, 11.4% and 4.8% higher BMI than individuals of the pp genotype. There is a significant ER-alpha genotype by age interaction, so that in our sample PP individuals tend to gain weight with age, whereas Pp and pp individuals tend to lose weight with age. Therefore, the ER-alpha polymorphisms are associated with BMI variation in healthy postmenopausal Caucasian women aged 65 yr and over. Our result is consistent with some recent findings suggesting the potential effects of the ER on BMI. The importance of the ER-alpha genotypes in other populations and other age groups needs to be demonstrated. Although the results of the ER-alpha genotype by age interaction are obtained here from cross-sectional data, direct confirmation may come from longitudinal studies in which individuals are measured multiple times over several years. The importance of the ER-alpha genotypes on BMI should be confirmed by further studies using methods robust to the potential problem of population substructuring that may confound the conclusions of population association studies.

Aged↗

Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase, and thymidine phosphorylase.

We had previously shown that high gene expressions (mRNA levels) of thymidylate synthase (TS; Leichman et al., J. Clin. Oncol., 15: 3223-3229, 1997) and thymidine phosphorylase (TP; Metzger et al., Clin. Cancer Res., 4: 2371-2376, 1998) in pretreatment tumor biopsies could identify tumors that would be nonresponsive to 5-fluorouracil (5-FU)-based therapy. In this study, we investigated the association between intratumoral gene expression of the pyrimidine catabolism enzyme dihydropyrimidine dehydrogenase (DPD) and the response of colorectal tumors to the same 5-FU-based protocol. DPD expressions were measured by quantitative reverse transcription-PCR in 33 pretreatment biopsies of colorectal tumors from patients who went on to receive treatment with 5-FU and leucovorin (LV). The range of DPD gene expression in those tumors that were nonresponsive to 5-FU was much broader than that of the responding tumors. None of the tumors with basal-level DPD expressions above a DPD:beta-actin ratio of 2.5 x 10(-3) (14 of 33) were responders to 5-FU/LV therapy, whereas those tumors with DPD gene expressions below DPD: beta-actin ratio of 2.5 x 10(-3) had a response rate of 50%. There was no correlation among DPD, TS, and TP expression values in this set of colorectal tumors, which indicated that these gene expressions are independent variables. All of the tumors that responded to 5-FU therapy (11 of 33) had expression values of all three of the genes, TS, TP, and DPD, below their respective nonresponse cutoff values, whereas, in each of the nonresponding tumors, at least one of these gene expressions was high. The patients with low expression of all three of the genes had significantly longer survival than patients with a high value of any one of the gene expressions. The results of this study show that intratumoral gene expression level of DPD is associated with tumor response to 5-FU and that the use of more than one independent determinant of response permits the identification of a high percentage of responding patients.

Antimetabolites, Antineoplastic↗

The effects of inositol hexaphosphate on the inflammatory response in transformed RAW 264.7 macrophages.

Inositol hexaphosphate (IP6) has received much attention for its role in interfering with tumor progression and slowing the metastasis of neoplastic cells. However, there is little information regarding the antioxidant properties of IP6 or its ability to enhance the natural disease resistance of the body. The specific objectives of this experiment were to investigate the effects that IP6 might have on the proliferation and viability of RAW 264.7 transformed macrophages and to morphologically and biochemically investigate the role of IP6 as a free radical scavenger. Transformed RAW macrophages were obtained from the American Type Culture Collection (Rockville, MD) and maintained in sterile media (RPMI) supplemented with 10% fetal bovine serum and 1% antibiotics and antimycotics. The cells were plated on to 24 well plates at a density of 1 x 10(5) cells/well. The cells were divided into five groups of four wells per group per phase (24, 48, and 72 hours). Cells in Group I were treated with media alone and served as controls. Cells in Group II were treated with lipopolysaccharide (LPS) only. Cells in groups III, IV, and V were treated with 1000 microliters of IP6 + LPS, 500 microliters of IP6 + LPS, and 100 microliters of IP6 + LPS, respectively. Cell numbers, as well as, morphology, MDA, and protein were determined at the end of 24, 48, and 72 hours. Data obtained from this investigation revealed that the rate of cell proliferation was totally dependent on the dose of IP6. At 24 and 48 hours and upon the exposure of high dose of IP6 the mitotic ability of the cells was higher (p < 0.05) than the rate at the 72 hour phase. Morphological evaluation of cells at all three phases revealed that there were significant changes in the architecture of cells upon the exposure of IP6 compared to the control group. The results of this study suggest that IP6 may have had an excitatory effect on the inflammatory cell secretions and this phenomenon was found to be dose dependent.

Animals↗

Breastfeeding and Chinese mothers living in Australia.

This study sought information on the breastfeeding rates, knowledge and beliefs of 101 migrant Chinese mothers living in south-west Sydney. Differences in beliefs about breastfeeding and bottle-feeding practices between migrant and indigenous groups of mothers were also examined. Sixty-five percent of Chinese mothers were fully breastfeeding their infants on discharge, with a further 6.9% partially breastfeeding. However, only 34% were still breastfeeding at three months. The most important factor to influence mothers' choice to breastfeed was the belief that it was 'good for the baby', whilst mothers choosing to bottle-feed were influenced by low milk supply and the belief that it was easier. Similar beliefs about breastfeeding and bottle-feeding were held by indigenous and migrant Chinese mothers, although concerns about the baby becoming too attached were markedly higher in the migrant group and may be related to sudden drops in breastfeeding rates at three months. Focusing ethno-specific services upon continuation of breastfeeding throughout the first six months of the infant's life is recommended, with a Chinese mothers' breastfeeding support network being posed as a possible approach.

Acculturation↗

Effects of high peak power microwaves on the retina of the rhesus monkey.

We studied the retinal effects of 1.25 GHz high peak power microwaves in Rhesus monkeys. Preexposure fundus photographs, retinal angiograms, and electroretinograms (ERG) were obtained to screen for normal ocular structure and function and, after exposure, as endpoints of the study. Histopathology of the retina was an additional endpoint. Seventeen monkeys were randomly assigned to receive sham exposure or pulsed microwave exposures. Microwaves were delivered anteriorly to the face at 0, 4.3, 8.4, or 20.2 W/kg spatially and temporally averaged retinal specific absorption rates (R-SAR). The pulse characteristics were 1.04 MW ( approximately 1.30 MW/kg temporal peak R-SAR), 5.59 micros pulse length at 0, 0.59, 1. 18, and 2.79 Hz pulse repetition rates. Exposure was 4 h per day and 3 days per week for 3 weeks, for a total of nine exposures. The preexposure and postexposure fundus pictures and angiograms were all within normal limits. The response of cone photoreceptors to light flash was enhanced in monkeys exposed at 8.4 or 20.2 W/kg R-SAR, but not in monkeys exposed at 4.3 W/kg R-SAR. Scotopic (rod) response, maximum (combined cone and rod) response, and Naka-Rushton R(max) and log K of scotopic b-waves were all within normal range. Retinal histopathology revealed the presence of enhanced glycogen storage in photoreceptors among sham (2/5), 8.4 W/kg (3/3), and 20.2 W/kg (2/5) exposed monkeys, while enhanced glycogen storage was not observed in the 4.3 W/kg (0/4) exposed group. Supranormal cone photoreceptor b-wave was R-SAR dependent and may be an early indicator of mild injury. However no evidence of degenerative changes and ERG depression was seen. We concluded that retinal injury is very unlikely at 4 W/kg. Functional changes that occur at higher R-SAR are probably reversible since we saw no evidence of histopathologic correlation with ERG changes. Bioelectromagnetics 21:439-454, 2000. Published 2000 Wiley-Liss, Inc.

Absorption↗

Delusions associated with elevated muscarinic binding in dementia with Lewy bodies.

The relation between disturbances of cholinergic neurotransmission and delusions (DELs) has not been investigated in degenerative dementias such as dementia with Lewy bodies (DLB). A cohort of dementia patients were assessed with standardized clinical evaluations (including the Columbia University Scale for Psychopathology in Alzheimer's Disease), which were repeated annually until death. DLB was confirmed neuropathologically in 21 patients. Neurochemical evaluation included M1 receptor autoradiography (pirenzepine binding), biochemical measurement of choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) histochemistry in brain regions hypothesized to be involved in the genesis of psychosis. Compared with 11 age-matched controls, CHAT and pirenzepine levels were most extensively reduced in the temporal and parietal neocortex of DLB patients. In Brodmann area 36, DELs were significantly associated with elevated pirenzepine binding (131.0 vs 93.5, t = 2.7), whereas visual hallucinations were associated with significant reductions in ChAT (1.7 vs 2.5, t = 2.5). There were no significant associations with other areas or with cholinesterase. Although DELs and visual hallucinations were both linked with disturbances in cholinergic neurotransmission, the nature of the associations was different. Upregulation of the postsynaptic muscarinic receptor may be central in the genesis of DELs, with important treatment implications.

Aged↗