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Biomedical subjects

K K Ho

Publications and source records attributed to K K Ho.

170 records · Page 10Linked to original sources

Infantile cortical hyperostosis.

Two patients from a family in Nauru with infantile corical hyperostosis are presented. A brief review is made of the main features of the disorder.

Female↗

Enhanced antiopiate activity in peptidomimetics of FMRFamide containing Z-2,3-methanomethionine.

FMRFa is a molluscan peptide that has shown antiopiate activity in a number of mammalian test systems. The current study determined the antiopiate potency of FMRFa and two conformationally constrained peptidomimetics of FMRFa containing stereoisomers of Z-2,3-methanomethionine. Morphine abstinence signs were observed after varying doses (0.25-25.0 micrograms) of these substances were injected into the third ventricle of morphine-dependent rats. Although both peptidomimetics were far more potent than FMRFa itself, they bound with lower affinity than FMRFa to rat spinal cord receptors for the mammalian FMRFa-like peptide, NPFF.

Amino Acid Sequence↗

Improved arterial distensibility in normotensive subjects on a low salt diet.

Arterial pulse wave velocity (PWV), a noninvasive index of arterial distensibility, was measured in 57 normotensive subjects who followed a voluntary low salt diet for a period ranging from 8 months to 5 years (mean, 24.8 months). Subjects who followed a regular diet were matched for age and mean arterial pressure with the low salt (LS) sample and were used as controls (C). For both samples, subjects were divided into three age groups: Group 1 (aged 2 to 19 years, n = 16), Group 2 (29 to 44 years, n = 26), and Group 3 (45 to 66 years, n = 15). There was a marked increase in aortic PWV with age in the control sample but not in the LS sample. There was no significant difference in aortic PWV for Group 1, but in Groups 2 and 3, the LS subjects showed a decrease of 21.8% and 22.7%, respectively, compared to C subjects. Aortic PWV (cm/sec) was: Group 1: C = 581 (SE44), LS = 614 (SE31); Group 2: C = 942 (SE46); LS = 737 (SE27) (p less than 0.001); Group 3: C = 958 (SE77), LS = 741 (SE25) (p less than 0.05]. Arm and leg PWV were also significantly lower in the older age groups. These findings suggest that normotensive adult subjects who follow a low salt diet (mean intake, 44 mmol Na/24 hours) have reduced arterial stiffness and that the effect is independent of blood pressure. This is prima facie evidence that reduced salt intake has a beneficial effect in improving distensibility of the central aorta and large peripheral arteries, which is independent of its antihypertensive action.

Adolescent↗

The effects of age and chemotherapy on gentamicin pharmacokinetics and dosing in pediatric oncology patients.

We attempted to determine the effects of prior antineoplastic chemotherapy and age on gentamicin pharmacokinetics in children (age 1-18 yrs) with cancer and in controls, and to establish a protocol for gentamicin dosing and monitoring to ensure rapid attainment of therapeutic serum concentrations in these patients. In a prospective controlled study, patients with fever who were receiving empiric gentamicin for confirmed or suspected infections were separated into three groups: 29 with cancer who were receiving a continuing chemotherapy protocol with nonnephrotoxic antineoplastic agents; 23 with cancer who were receiving a continuing chemotherapy protocol with nephrotoxic antineoplastic agents; and 25 control patients who did not have cancer. Three blood samples (one predose, two postdose concentrations), collected between the third and sixth gentamicin doses from each patient, were analyzed by the Emit assay. Pharmacokinetic parameters were calculated and gentamicin dosages recommended based on the Sawchuk-Zaske method of serum level interpretation. When normalized by body weight, there was no significant difference in clearance, volume of distribution, and half-life between the control group and either group of patients with cancer. However, when normalized by body surface area, patients receiving prior nephrotoxic chemotherapy appeared to have a lower mean clearance (98.2 ml/min/1.73 m2) than those exposed to nonnephrotoxic chemotherapy (117.4 ml/min/1.73 m2) and controls (113.3 ml/min/1.73 m2; ANCOVA p = 0.033). When kinetic parameters were normalized by body weight, the effect of advancing age yielded a decrease in both clearance (p < 0.001) and volume of distribution (p = 0.02), and an increase in gentamicin half-life (p < 0.001). When normalized by body surface area, age had no significant effect on clearance (p = 0.579). There was no significant difference in gentamicin daily dose requirements (mg/kg) between the chemotherapy groups, which may be due to the lack of significant effects of chemotherapy on gentamicin's volume of distribution and clearance normalized by body weight. The final maintenance doses (mg/kg/day, mean +/- SD) for patients with cancer were 10.8 +/- 1.8 for those age 1-5 years, 8.9 +/- 1.1 for those age 6-12 years, and 7.9 +/- 1.9 for those age 13-18 years. However, when normalized by body surface area, the age-dependent doses became remarkably similar for children in all three age groups (ANOVA p = 0.932), approximately 250 mg/m2/day. We recommend that pediatric patients with cancer who require treatment for fever and neutropenia be given higher than standard gentamicin dosages to achieve therapeutic serum concentrations promptly. In particular, initial empiric doses of 10 mg/kg/day are appropriate for those age 1-5 years.

Adolescent↗

The progression from hypertension to congestive heart failure.

OBJECTIVES: - To study the relative and population-attributable risks of hypertension for the development of congestive heart failure (CHF), to assess the time course of progression from hypertension to CHF, and to identify risk factors that contribute to the development of overt heart failure in hypertensive subjects. DESIGN: - Inception cohort study. SETTING: - General community. PARTICIPANTS: - Original Framingham Heart Study and Framingham Offspring Study participants aged 40 to 89 years and free of CHF. To reflect more contemporary experience, the starting point of this study was January 1, 1970. EXPOSURE MEASURES: - Hypertension (blood pressure of at least 140 mm Hg systolic or 90 mm Hg diastolic or current use of medications for treatment of high blood pressure) and other potential CHF risk factors were assessed at periodic clinic examinations. OUTCOME MEASURE: - The development of CHF. RESULTS: - A total of 5143 eligible subjects contributed 72422 person-years of observation. During up to 20.1 years of follow-up (mean, 14.1 years), there were 392 new cases of heart failure; in 91% (357/392), hypertension antedated the development of heart failure. Adjusting for age and heart failure risk factors in proportional hazards regression models, the hazard for developing heart failure in hypertensive compared with normotensive subjects was about 2-fold in men and 3-fold in women. Multivariable analyses revealed that hypertension had a high population-attributable risk for CHF, accounting for 39% of cases in men and 59% in women. Among hypertensive subjects, myocardial infarction, diabetes, left ventricular hypertrophy, and valvular heart disease were predictive of increased risk for CHF in both sexes. Survival following the onset of hypertensive CHF was bleak; only 24% of men and 31% of women survived 5 years. CONCLUSIONS: - Hypertension was the most common risk factor for CHF, and it contributed a large proportion of heart failure cases in this population-based sample. Preventive strategies directed toward earlier and more aggressive blood pressure control are likely to offer the greatest promise for reducing the incidence of CHF and its associated mortality.

Adult↗