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Biomedical subjects

T Harris

Publications and source records attributed to T Harris.

At least 91 records · Page 5Linked to original sources

Relative weight, weight change, and risk of coronary heart disease in the Honolulu Heart Program.

Risk of coronary heart disease (CHD) among the Honolulu Heart Program participants was examined in relation to body mass index (BMI) at age 25 and two subsequent periods of weight change: age 25 to examination I (1965-1968) and examination I to examination III (1971-1974). During a maximum follow-up period of 17 years after examination III, there were 479 incident cases of CHD among the study sample of 6,176 Japanese-American men. Levels of BMI at age 25 were positively related to CHD incidence after statistical control for age, smoking, and subsequent weight change. Relative risk between the lowest and highest BMI categories was 2.44 (95% confidence interval (CI) 1.61-3.69). Compared with a weight change of less than 2.5 kg between age 25 and examination I, relative risks were 1.41 (95% CI 1.00-1.97) for a weight gain between 2.6 and 5 kg, 1.60 (95% CI 1.22-2.11) for a weight gain between 5.1 and 10 kg, and 1.75 (95% CI 1.32-2.33) for a weight gain of more than 10 kg. During the examination I-III period, in contrast, the highest risk of CHD was found in men who lost the greatest amount of weight; the relative risk of CHD for men who lost more than 2.5 kg was 1.25 (95% CI 0.98-1.60). The authors conclude that levels of relative weight in early adulthood were positively related to risk of CHD occurring much later in the lives of these men. The association between CHD incidence and weight change appeared to be modified by age, with higher risks for earlier weight gain and later weight loss in the lives of these men.

Adult↗

Intramuscular ketamine for pediatric sedation in the emergency department: safety profile in 1,022 cases.

STUDY OBJECTIVE: To determine the safety of intramuscular ketamine when administered by emergency physicians for pediatric procedures in accordance with a defined protocol. METHODS: We assembled a consecutive case series of children aged 15 years or younger who were given ketamine in the emergency departments of a university medical center and an affiliated county hospital over a 9-year period. A protocol for ketamine use (4 mg/kg, intramuscularly) was followed. Treating physicians were instructed to complete data forms recording complications and adequacy of sedation concurrent with patient care. Subsequent chart review was used to determine indications, adjunctive drugs, time to discharge, and adverse reactions for all patients. RESULTS: Intramuscular ketamine was administered 1,022 times, mainly for laceration repair and fracture reduction. Physicians completed data forms for 431 of treated children (42%). Transient airway complications occurred in 1.4%: airway malalignment (n = 7), laryngospasm (n = 4), apnea (n = 2), and respiratory depression (n = 1). All were quickly identified and treated without intubation or sequelae. Emesis occurred in 6.7%, without evidence of aspiration. Mild recovery agitation occurred in 17.6%, moderate to severe agitation in 1.6%. No child required hospitalization for complications caused by ketamine. Ketamine produced acceptable sedation in 98% of patients. The median time from injection to emergency department discharge was 110 minutes for children given a single dose of ketamine. CONCLUSION: Intramuscular ketamine may be administered safely by emergency physicians to facilitate pediatric procedures in accordance with a defined protocol and with appropriate monitoring. Ketamine is highly effective, has a wide margin of safety, does not require intravenous access, and uniquely preserves protective airway reflexes.

Adolescent↗

Visualization of the human larynx: a three-dimensional computer modeling tool.

The larynx is a complex compact organ. A detailed understanding of the anatomical relationships of its various structures is critical to the various workers in the field. To facilitate this goal, a 3-D model of the human larynx has been developed using multiple thin section MRI and CT images taken through a cadaver larynx. A databank of individual laryngeal structures ('units') has been built up. A software package has then been utilized which allows for representation of any of the stored 'units'. In this manner, elements of the larynx can be viewed from any direction, with the larynx static or in motion. Similarities and differences from current CD-ROM packages of the larynx are discussed.

Computer Simulation↗

Intravenous ketamine for pediatric sedation in the emergency department: safety profile with 156 cases.

OBJECTIVES: To determine the safety of i.v. ketamine when administered by emergency physicians (EPs) for pediatric procedures, and to contrast the sedation characteristics of the i.v. and i.m. routes. METHODS: The study was a retrospective consecutive case series of children aged < or =15 years given i.v. ketamine in the EDs of a university medical center and an affiliated county hospital over a 9-year period. A protocol for ketamine was used by treating physicians. Records were reviewed for adverse effects, indication, dosing, adjunctive drugs, inadequate sedation, and time to release. Results were contrasted with previously reported data for the i.m. route. RESULTS: During the study period i.v. ketamine was administered 156 times, primarily for laceration repair and fracture reduction. Transient apnea and respiratory depression occurred in one patient each; both were quickly identified and were without sequelae. Laryngospasm or aspiration was not noted in any children. There were 6 children with emesis and 2 with mild agitation during recovery. The median time from initial dose to ED release was 103 minutes (25th to 75th percentiles 76 to 146 minutes). The i.v. and i.m. routes were comparable in terms of adverse effects, inadequate sedation, and time to release. CONCLUSION: I.v. ketamine can be administered safely by EPs to facilitate pediatric procedures when used in a defined protocol. The sedation characteristics of the i.v. and i.m. routes appear comparable.

Adolescent↗

Association between insulin-like growth factor I and bone mineral density in older women and men: the Framingham Heart Study.

Few studies of the GH axis and bone have focused specifically on elderly people. The objective of this study was to determine the association between insulin-like growth factor I (IGF-I) and bone mineral density (BMD) in 425 women and 257 men aged 72-94 who participated in the Framingham Osteoporosis Study component of the Framingham Heart Study in 1992-1993. Serum IGF-I level was determined by RIA. BMD at three femoral sites and the lumbar spine was determined by dual x-ray absorptiometry, and at the radius by single-photon absorptiometry. IGF-I level was positively associated with BMD at all five sites (Ward's area, femoral neck, trochanter, radius, and lumbar spine) in women after adjustment for weight loss and other factors (P < or = 0.01) and protein intake in a subset of participants (0.006 < P < 0.07). A threshold effect of higher BMD was evident at each of the 3 femoral sites and the spine (P < 0.03) but not at the radius for women in the highest quintile of IGF-I (> or = 179 g/liter) vs. those in the lowest four quintiles. IGF-I was not significantly associated with BMD in men. These results indicate that higher IGF-I levels are associated with greater BMD in very old women, and suggest that future clinical trials employing GH may have a role in the development of treatments for older women with osteoporosis.

Absorptiometry, Photon↗

The influence of continuous intravenous prostacyclin therapy for primary pulmonary hypertension on the timing and outcome of transplantation.

BACKGROUND: Primary pulmonary hypertension (PPH) is a progressive disease with a median survival of less than 3 years from diagnosis. Medical management has typically consisted of anticoagulation and oral calcium channel blocking agents, whereas lung transplantation (LT) has been reserved for patients who are unresponsive to medical therapy. Continuous intravenous prostacyclin was introduced for patients who did not respond to calcium channel blockers and who would have required LT. We reviewed our experience with prostacyclin in LT candidates to study its effects on the timing and outcome of LT. METHODS: We retrospectively reviewed the clinic and hospital records of patients with PPH who were both treated with prostacyclin and evaluated for LT. Additional information was obtained from the pulmonary vascular disease and lung transplantation databases. RESULTS: A total of 42 patients were identified who received prostacyclin for the treatment of PPH and were evaluated for LT. Thirty-seven patients were accepted as LT candidates, 22 at The University of Maryland Medical Center (UMMC), 15 at other LT programs. Overall, 70% (27/37) of LT candidates were removed from the LT waiting list or had listing for LT deferred because of clinical improvement. In patients listed for LT before initiation of prostacyclin therapy, 55% (12/22) were removed from the active waiting list for 27.2+/-17 months (range 8 to 60), and 92% (11/12) remain on the inactive status. In patients who received prostacyclin before listing for LT, listing for LT was deferred in 94% (14/15) for 17.4+/-9 months (range 6 to 33 months) because of clinical stability or improvement. In all, 93% of patients (39/42) experienced an improvement in 1 or more New York Heart Association functional class. The hemodynamic profiles of the eight patients removed from the active waiting list at UMMC demonstrated increases of 55%+/-18% in cardiac output, and decreases of 14.3%+/-4.9% in mean pulmonary artery pressure and 36%+/-8.3% in total pulmonary resistance (p < 0.05). The 1-year survival rate for LT after prostacyclin therapy was 88% (7/8) at UMMC and 60% (3/5) at the other centers. CONCLUSION: We conclude that prostacyclin therapy is an effective means of delaying, possibly indefinitely, the need for LT in patients with PPH and that excellent results can be obtained when LT is performed after prostacyclin therapy. Consideration should be given to initiating prostacyclin therapy in all patients whose conditions do not respond to conventional therapy before proceeding with transplantation.

Adult↗

The association of peripheral monocyte derived interleukin 1beta (IL-1beta), IL-1 receptor antagonist, and tumor necrosis factor-alpha with osteoarthritis in the elderly.

OBJECTIVE: To examine the association of peripheral blood mononuclear cell (PBMC) derived interleukin 1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), tumor necrosis factor alpha (TNF-alpha), and radiographic osteoarthritis (OA) in the elderly. METHODS: A total of 703 subjects (436 women, 267 men, mean age 78.5+/-4.5 yrs) had both knee and hand radiographs, and cytokines were measured during the 22nd biennial examination of the Framingham Cohort. PBMC derived IL-1beta , IL-1Ra, and TNF-alpha production was assessed using a non-cross reacting polyclonal radioimmunoassay. Knee OA was defined as a score of > 2 using a modified Kellgren and Lawrence scale. The presence of osteophytes and joint space narrowing were scored separately on a 0-3 scale, in which disease was defined a priori as a score > 0 for each feature. Sex-specific odds ratios were calculated for knee OA after adjusting for weight, history of knee injury, and use of estrogen and nonsteroidal antiinflammatory drugs. RESULT: No uniform associations were found for IL-1beta or IL-1Ra in men, or for TNF-alpha production and radiographic OA in either sex. We found possible associations for the highest levels of IL-1beta production and the presence of knee osteophytes [OR=2.0 (1.2-3.5)] and joint space narrowing [OR=1.7 (1.1-2.8)] in women. Our data suggested a possible protective effect for IL-1Ra production and hand OA in women [OR=0.6 (0.4-1.0)]. CONCLUSION: We found no consistent association of PBMC cytokine production and radiographic OA. However, women with the highest production of IL-1beta and IL-1Ra had respectively higher rates of knee OA and lower rates of hand OA than expected.

Aged↗

Bereavement care in general practice: a survey in South Thames Health Region.

BACKGROUND: Studies have shown that bereaved individuals suffer increased rates of physical and mental ill health. Bereavement support has recently been advocated as an area of prevention in primary care, with suggestions that general practitioners (GPs) should adopt protocols for the active follow-up of their bereaved patients, which relies on the early notification of deaths by hospitals and hospices. Little is known about the routine care currently provided by GPs and primary health care teams (PHCTs) to support their bereaved patients. AIMS: To explore GPs' perceptions of patient death notifications by hospitals and hospices. To describe practice policies relating to patient deaths and the provision of bereavement support. METHOD: Postal questionnaires were sent to senior partners of a random sample of 500 general practices in South Thames Health Region. RESULTS: Three hundred and fifty-three practitioners responded (71%). Hospitals were perceived to be significantly slower than hospices in notifying deaths (P < 0.0001). One hundred and ninety-six practices (56%) kept death registers, 230 (65%) discussed deaths together, and 142 (40%) identified bereaved relatives. One hundred and thirty-seven practices (39%) routinely offered bereaved relatives contact with a PHCT member; while 133 (38%) supported only those who asked for help. Routine support was significantly more likely to be provided by practices that kept a death register, discussed deaths together, identified bereaved relatives, and had a special interest in palliative care. CONCLUSIONS: GPs perceive hospitals to be slower than hospices at notifying deaths, particularly in the first 24 hours. They are divided over whether bereavement support should be proactive or reactive. Keeping a practice death register, discussing deaths together, and identifying newly bereaved relatives are activities related to providing routine bereavement care.

Attitude of Health Personnel↗

Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons.

BACKGROUND: The importance of total cholesterol level as a risk factor for coronary heart disease in older adults is controversial. OBJECTIVE: To determine whether findings showing that total cholesterol level is not an important risk factor for coronary heart disease in older adults are the result of inadequate adjustment for co-occurring diseases and frailty. DESIGN: Multicenter, longitudinal study with 5-year follow-up for death. PARTICIPANTS: 4066 men and women from East Boston, Massachusetts; Iowa and Washington counties, Iowa; and New Haven, Connecticut. MEASUREMENTS: In 1988, participants were interviewed about their health status and had blood samples taken. Mortality follow-up was through 1992. RESULTS: In analyses that included all fatal coronary heart disease events (252 deaths) and did not adjust for risk factors for coronary heart disease and measures of frailty, persons with the lowest total cholesterol levels (< or = 4.15 mmol/L [< or = 160 mg/dL]) had the highest rate of death from coronary heart disease, whereas those with elevated total cholesterol levels (> or = 6.20 mmol/L [> or = 240 mg/dL]) seemed to have a lower risk for death from coronary heart disease (P for trend = 0.04). After adjustment for established risk factors for coronary heart disease and markers of poor health (including chronic conditions, low serum iron and albumin levels) and exclusion of 44 deaths from coronary heart disease that occurred within the first year, elevated total cholesterol levels predicted increased risk for death from coronary heart disease, and the risk for death from coronary heart disease decreased as cholesterol levels decreased (P for trend = 0.005). CONCLUSIONS: Elevated total cholesterol level is a risk factor for death from coronary heart disease in older adults, and the apparent adverse effects associated with low cholesterol levels are secondary to comorbidity and frailty. This suggests that excluding older persons from cholesterol screening is inappropriate, but interpretation of screening results in older persons requires clinical judgment. Results from controlled clinical trials are needed to clarify this issue.

Aged↗

Isolation and characterization of mycophenolic acid-resistant mutants of inosine-5'-monophosphate dehydrogenase.

Mycophenolic acid (MPA) is a potent and specific inhibitor of mammalian inosine-monophosphate dehydrogenases (IMPDH); most microbial IMPDHs are not sensitive to MPA. MPA-resistant mutants of human IMPDH type II were isolated in order to identify the structural features that determine the species selectivity of MPA. Three mutant IMPDHs were identified with decreased affinity for MPA The mutation of Gln277 --> Arg causes a 9-fold increase in the Ki of MPA, a 5-6-fold increase in the Km values for IMP and NAD, and a 3-fold decrease in kcat relative to wild type. The mutation of Ala462 --> Thr causes a 3-fold increase in the Ki for MPA, a 2.5-fold increase in the Km for NAD, and a 1.5-fold increase in kcat. The combination of these two mutations does not increase the Ki for MPA, but does increase the Km for NAD 3-fold relative to Q277R and restores kcat to wild type levels. Q277R/A462T is the first human IMPDH mutant with increased Ki for MPA and wild type activity. The third mutant IMPDH contains two mutations, Phe465 --> Ser and Asp470 --> Gly. Ki for MPA is increased 3-fold in this mutant enzyme, and Km for IMP is also increased 3-fold, while the Km for NAD and kcat are unchanged. Thus increases in the Ki for MPA do not correlate with changes in Km for either IMP or NAD, nor to changes in kcat. All four of these mutations are in regions of the IMPDH that differ in mammalian and microbial enzymes, and thus can be structural determinants of MPA selectivity.

Amino Acid Sequence↗

Sagittal diameter minus subcutaneous thickness. An easy-to-obtain parameter that improves visceral fat prediction.

Two groups of 99 and 98 women were studied to test if correcting sagittal diameter by subtracting the thickness of subcutaneous abdominal adipose tissue improves its degree of association with visceral adipose tissue. The first group (age, 40 +/- 14 years; body mass index [BMI], 36 +/- 6 kg/m2) was used to calculate the predictive equations for visceral adipose tissue. The second group (age, 43 +/- 14 years; BMI, 37 +/- 6 kg/m2) was used for cross-validation. Various anthropometric parameters were measured by ultrasound and computed tomography. Correlation coefficients with single-slice visceral adipose tissue area, after sagittal diameter was corrected by subtracting subcutaneous thickness, rose from 0.63 to 0.72 in the first group and from 0.64 to 0.71 in the second group. The standard error of residuals of the regression formula for visceral adipose tissue area was 10% lower with modified sagittal diameter than with sagittal diameter alone. During cross-validation, the standard error of differences was 5% lower with modified sagittal diameter. The visceral adipose tissue estimate was also less biased by the size of the area when sagittal diameter minus subcutaneous thickness was used. Results show that subtracting the thickness of abdominal subcutaneous adipose tissue from sagittal diameter significantly improves the predictive power of sagittal diameter for visceral adipose tissue and could be a useful tool for epidemiological studies.

Adipose Tissue↗

The genetics of obesity.

Despite the influence of obesity in predisposing to many diseases, and evidence for high heritability, efforts to identify human genes with major effects on bodyweight have not yet been successful. In contrast, remarkable progress has been made in the identification and characterization of the genes mutated in five monogenic mouse models of obesity. These genes have led to new insights into the etiology of obesity and provide promising targets for therapeutic intervention.

Animals↗

Anti-M and anti-N reactivity with Tn and T activated cells.

Monoclonal (MoAB) anti-N and anti-M were tested against normal, T-activated, and Tn-activated RBCs. In vivo T and Tn activation affects the sialic acid expression on the RBCs which may affect the binding of antibodies to the M and/or N antigens. The majority of MoAB anti-M and anti-N in this workshop demonstrated some effect from in vivo T and Tn activation.

Antigen-Antibody Reactions↗

Summary of serological test results on the monoclonal antibodies to non-specific erythrocytes antigens.

Monoclonal antibodies from the 2D3 Section (Other Non-specific Erythrocyte Antigens) of the Third International Workshop & Symposium on Monoclonal Antibodies Against Human Red Blood Cell and Related Antigens were tested using standard serological tube methods. Each antibody was tested to determine the presence of prozoning. A selected panel of red blood cells was tested against each antibody at different phases. Anti-CD44 specificities were weaker or non-reactive with Lu(a-b-) InLu cells and 2 sources (2D3-1 and 2D3-2) were slightly decreased with Ko cells. Anti-CD47 and antibodies to Rh related molecules showed decreased or no reactivity with Rh null cells. Anti-CD99 showed weak or no reactivity with Gy-, LW:-3 and cord blood cells.

Antibodies, Monoclonal↗