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Biomedical subjects

J Whitwell

Publications and source records attributed to J Whitwell.

At least 19 recordsLinked to original sources

Measles vaccine immunogenicity and antibody persistence in 12 vs 15-month old infants.

HYPOTHESIS: Maternal measles immunity in the United States today is primarily vaccine induced, with corresponding lower antibody titers in infants, as compared to infants born in an earlier era to mothers with naturally acquired measles immunity. We hypothesized that, due to lower titer of passively transferred maternal measles antibody, administration of measles vaccine at 12 months of age would result in seroconversion and antibody persistence comparable to vaccination at 15 months of age. POPULATION: Children at both an urban hospital and a suburban clinic. METHODS: Informed consent was obtained from mothers for the infants to receive M-M-R(R)II vaccine at either 12 or 15 months and to have serum samples obtained before vaccination and 4 weeks post-vaccination (PV). Between 9 and 39 months PV, a third serum sample was obtained from 28% of seroconverters. A diary of adverse experiences was kept for 3 weeks PV. Sera were assayed by a microneutralization assay (NT) and an enzyme immunoassay (EIA) for measles antibody. RESULTS: Both age groups tolerated vaccination well with minor and transient side effects. Forty-four of 47 (94%) 12-month-old infants seroconverted by NT, compared to 45 of 46 (98%) 15-month-olds (p=NS). There was no statistically significant decline in median NT titers or EIA titers in nineteen 12-month-olds and thirteen 15-month olds followed for 9-39 months PV. CONCLUSION: This study showed comparable serologic responses in 12- vs 15-month-old infants born to measles vaccine-immune mothers; however, the sample size was too small to have adequate power and further study is indicated. Titers of antibody were constant in both the 12-month-old and the 15-month-old infants, over a 9-39 month period, suggesting that waning immunity over this period of time is not a problem in either age group.

Age Factors↗

Measles vaccine immunogenicity in 6- versus 15-month-old infants born to mothers in the measles vaccine era.

HYPOTHESIS: The low titer of measles antibody in infants of mothers with vaccine-induced immunity may allow immunization against measles before 15 months of age. METHODS: Six- and 15-month-old infants born to mothers < or = 30 years of age with no history of measles were recruited. Infants enrolled at 6 months of age were immunized with monovalent measles vaccine (Attenuvax), and maternal serum and infant pre- and postvaccination sera were obtained. Those enrolled for primary vaccination at 15 months of age received either Attenuvax (N = 12) or M-M-RII (N = 3). Six-month-old infants were revaccinated with M-M-RII at 15 months of age; pre- and postrevaccination sera were again obtained. Three antibody assays were used: a measles neutralizing assay (NT) and two enzyme immunoassays (EIA) for measles IgG and measles IgM. RESULTS: Among primary vaccinees, 14 of 19 infants aged 6 months (74%) developed NT antibody, as did 15 of 15 infants aged 15 months (100%). The reciprocal geometric mean titer of 6-month-old seroresponders was 23.3, significantly lower than that of the 15-month-old primary vaccinees (87.7, P < .001). Primary seroconversion rates by EIA were 53% for 6-month-old infants and 100% for those aged 15 months. Revaccination of infants who had received Attenuvax at 6 months of age resulted in 100% NT positivity; the geometric mean titer rose to equal that of the group given primary immunization at 15 months of age. Measles IgM antibody was detected in 10 of 14 infants tested 1 month after primary vaccination at 15 months, but was not detected in any of the revaccinated infants after the second dose at 15 months of age (P < .001). CONCLUSIONS: 1) Immunization with measles vaccine in infants born to vaccine-immune mothers at 6 months of age induced NT antibody in 74% of infants. 2) Revaccination of prior 6-month-old vaccinees at 15 months resulted in antibody titers equivalent to 15-month-old vaccinees. 3) Lack of an IgM response following revaccination suggests that even seronegative infants may be primed to respond on re-exposure to measles.

Adult↗

Induction of micronuclei in peripheral blood lymphocytes of patients treated for rheumatoid or osteo-arthritis of the knee with dysprosium-165 hydroxide macroaggregates or yttrium-90 silicate.

The advantages of radiation synovectomy, using preparations containing dysprosium-165 (Dy-165), over conventional materials based on yttrium-90 (Y-90) include a more ideal spectrum of decay energies, and a much shorter half-life permitting quicker and more efficient treatment. A new therapeutic agent, Dy-165 hydroxide macroaggregates, has been developed for the treatment of arthritis making use of these advantages. As part of a clinical trial of this material 42 patients were examined for micronucleus frequency in their peripheral blood lymphocytes prior to, and 2 weeks after, radiation synovectomy using Dy-165 hydroxide macroaggregates or Y-90 silicate. In the majority of patients from each treatment group no significant increase in micronucleus frequency was observed. This indicates that in these cases leakage of material from the site of treatment was not resulting in detectable irradiation of circulating cells irrespective of the choice of radiopharmaceutical. The maximum increase in micronucleus frequency observed corresponded to a radiation dose to circulating cells of approximately 0.3 Gray.

Adult↗

Factors influencing energy expenditure in patients with burns.

Twenty-three consecutive patients with a mean burn size of 39% of total body surface area (%TBSA) were studied prospectively. Expected basal energy expenditure (EBEE) calculated by the Harris-Benedict formula, initial and twice weekly measurements of energy expenditure (MEE) by indirect calorimetry, and simultaneous estimation of nutrient intake were obtained. In the whole cohort the EBEE was 1,715 +/- 24 kcal/day and the MEE was 2,218 +/- 59 kcal/day. The degree of hypermetabolism was 29.0 +/- 2.8%. A subgroup of 16 patients had metabolic rates measured in both the fed and unfed states. The degree of hypermetabolism was only 6.5 +/- 4.5% in the unfed, but increased to 34.1 +/- 3.2% when the same patients were fed (p less than 0.001). The factors affecting MEE were then evaluated by stepwise multiple regression analysis which showed that MEE = -4343 + (10.5 X %TBSA) + (0.23 X Caloric intake [CI]) + (0.84 X EBEE) + (114 X Temp [C]) - (4.5 X Postburn days), r = 0.82, p less than .001. We conclude that 25% of the CI is used to increase the MEE, which suggests that these measurements done in the fasting state cannot be used to predict requirements.

Adult↗

Correlation of the oxygen cost of breathing and length of weaning from mechanical ventilation.

We studied 20 patients (ages 43 to 84 yr), whose forced vital capacity, peak negative inspiratory pressure and alveolar-arterial gradient indicated that they were unlikely to be withdrawn rapidly from mechanical ventilation. Their mean oxygen consumption (VO2) during controlled ventilation (CV) was 292 +/- 21 (SEM) ml/min. During spontaneous ventilation (SV) through endotracheal tube and ventilator circuit, the VO2 rose significantly (p less than .001) to 323 +/- 20 ml/min. The oxygen cost of breathing (OCB) (the difference in VO2 between CV and SV) and the OCB as a fraction of the oxygen consumed during SV (OCB/VO2 SV) both correlated significantly by linear regression analysis with the total time to wean in days (-11.6 + 0.93 for OCB, r = .79; and -12.6 + 293.1 for OCB/VO2 SV, r = .84, p less than .001 for both). As the OCB was correlated with the total wean time, this variable may be a useful index of the effect of many influences on the weaning process.

Adult↗

Metabolic and structural changes in skeletal muscle during hypocaloric dieting.

Hypocaloric dieting and fasting alter the contraction-relaxation characteristics of skeletal muscle and result in low frequency fatigue. We report the metabolic and structural changes in skeletal muscle in five morbidly obese female subjects who had biopsies of the gastrocnemius muscle on a base-line diet (2500 kcal/day) followed by a repeat biopsy after 2 wk of a 400-kcal/day carbohydrate diet. Hypocaloric dieting resulted in a significant increase in the intracellular muscle calcium content (p less than 0.05), which may account for the observed changes in muscle function. There were no significant changes in muscle glycogen, lactate, pyruvate, or free energy stores. There was a significant decrease in muscle enzymes [phosphofructokinase (p less than 0.05), succinate dehydrogenase (p less than 0.02)] and some muscle amino acid levels [glutamine (p less than 0.025), glycine (p less than 0.01), and alanine (p less than 0.02)], while muscle histochemistry showed type II fiber atrophy (p less than 0.025). However, these changes reflect a generalized response to hypocaloric dieting and probably do not explain the specific functional changes. Change in the muscle calcium content is probably an important mediator of the adverse functional effects of malnutrition.

Adolescent↗

Randomized trial of total parenteral nutrition in critically ill patients: metabolic effects of varying glucose-lipid ratios as the energy source.

We studied 20 critically ill patients receiving ventilatory support to determine both their metabolic requirements and the effect of providing energy substrate regimens containing different lipid to glucose calorie ratios on whole-body protein economy. The measurements used included indirect calorimetry, substrate hormone profile, and whole body protein turnover by [14C]leucine. Measurements were done while patients were receiving all their nonprotein calories as dextrose ( D100 ) and were compared with results obtained when they received all their nonprotein calories as a combination of dextrose and lipid in a calorie ratio either of 3:1 ( D75 ) or 1:3 ( D25 ). To maintain euglycemia, exogenous insulin was infused by attending physicians not cognizant of the total parenteral nutrition regimen used. Energy expenditure before receiving total parenteral nutrition was only 4.6% above basal, and did not rise significantly during any of the regimens. The insulin infusion rate, plasma insulin, CO2 production, and serum lactate were significantly higher with D100 than with D25 , but not with D75 . Correspondingly, plasma free fatty acids were significantly lower with D100 when compared with D25 but not with D75 . Despite this, there were no significant differences in whole-body protein synthesis, breakdown, or net synthesis (synthesis - breakdown) and, in general, the patients in all groups were close to zero protein balance. These data suggest that critically ill patients are not severely hypermetabolic, and that they can maintain protein balance with a modest excess of calories while using a wide range of fuel mixtures.

Adult↗

Skeletal muscle function during hypocaloric diets and fasting: a comparison with standard nutritional assessment parameters.

Skeletal muscle function and standard nutritional assessment parameters were measured in six obese patients. Base-line measurements were made on a weight-maintaining diet, and further measurements after 2 wk of a 400-cal diet, followed by 2 wk of fasting and then after 2 wk of refeeding. The function of the adductor pollicis muscle was assessed by electrical stimulation of the ulnar nerve. The objective parameters of muscle function measured were: 1) force of contraction expressed as a percentage of the maximal force obtained with electrical stimulation at 10, 20, 30, 50, and 100 Hz. 2) Maximal relaxation rate expressed as percentage force loss/10 ms. 3) Endurance expressed as percentage force loss/30 s. Standard nutritional assessment parameters (serum albumin and transferrin, creatinine height index, anthropometry and total body nitrogen and potassium) were also measured. There was a significant increase in the force of contraction at 10 Hz from a base-line of 29.6 +/- 1.0% to 49.0 +/- 2.8% (mean +/- SEM) after 2 wk of a 400-cal diet (p less than 0.01). These was a significant slowing of the maximal relaxation rate from a base-line of 9.8 +/- 0.03% force loss/10 ms to 8.2 +/0 0.3% force loss/10 ms (mean +/- SEM) (p less than 0.01) after 2 wk of a 400-cal diet. After a further 2 wk of fasting these abnormalities in muscle function persisted. There was a significant increase in muscle force loss from a base-line of 3.9 +/- 0.8% force loss/30 s to 13.7 +/- 3.4% force loss/30 s (mean +/- SEM) after fasting (P less than 0.01). After 2 wk of refeeding all aspects of muscle function measured were normal. During the study the standard nutritional assessment parameters did not change significantly.

Adult↗

A comparison between muscle function and body composition in anorexia nervosa: the effect of refeeding.

Skeletal muscle function, body composition (total body nitrogen and total body potassium) and standard parameters of nutritional assessment were measured in six severely depleted patients with primary anorexia nervosa, both on admission and during oral refeeding. The function of the adductor pollicis muscle was assessed by electrical stimulation of the ulnar nerve. On admission muscle function was markedly abnormal in the patients with anorexia nervosa (n = 6) compared with normal subjects (n = 22), with a significant increase in the force of contraction at 10 Hz, with a mean +/- SEM of 48.0 +/- 3.7% and 28.8 +/- 1.2%, respectively (p less than 0.001). There was slowing of the maximal relaxation rate, 6.6 +/- 0.6% and 9.6 +/- 0.2%, respectively (p less than 0.001) and increased muscle fatigue 18.6 +/- 5.9% and 3.5 +/- 0.8%, respectively (p less than 0.01). Initially, the mean serum albumin was normal (4.0 +/- 0.1 g/dl), although there was evidence of severe depletion of somatic protein stores, with a low total body nitrogen and creatinine-height index. Within 4 wk of oral refeeding, maximal relaxation rate and muscle fatigability were restored to normal, and within 8 wk all parameters of muscle function were normal. During the study total body nitrogen increased by only 13% and was still 19.4% below the predicted normal total body nitrogen, whereas total body potassium increased by 32% and body fat by 46%. Normalization of muscle function may be related to restoration of muscle electrolytes rather than repletion of body nitrogen.

Adult↗

Skeletal muscle function in malnutrition.

Skeletal muscle function was studied in 10 malnourished patients with various gastrointestinal disorders and in 22 normal subjects. The function of the adductor pollicis muscle was assessed by electrical stimulation of the ulnar nerve. The objective parameters of muscle function measured were: 1) Force of contraction expressed as a percentage of the maximal force obtained with electrical stimulation at 10, 20, 30, 50 and 100 Hz. 2) Maximal relaxation rate expressed as percentage force loss/!10 ms. 3) Endurance expressed as percentage force loss/30 s. The force of contraction at 10 Hz was higher in malnourished patients compared with normal subjects, with a mean +/- SEM (n) of 43.0 +/- 4.2% (n = 10) and 28.8 +/- 1.2% (n = 22), respectively, (p less than 0.001). The maximal relaxation rate was slower in patients compared with normals with a mean +/- SEM (n) of 7.2 +/- 0.4% (n = 9) ad 9.6 +/- 0.2% (n = 22), respectively, (p less than 0.001). Muscle endurance testing showed an increased force loss with prolonged tetanic stimulation in patients compared with normals, with a mean +/- SEM (n) of 29.1 +/- 4.0% (n = 7) and 3.5 +/- 0.8% (n = 22), respectively, (p less than 0.001). Four patients were restudied after a 4-wk period of total parenteral nutrition, with a significant improvement in muscle function parameters. Malnutrition results in both increased muscle fatiguability and an altered pattern of muscle contraction and relaxation which are reversible by nutritional supplementation. This technique promises to be valuable in assessing the functional effects of malnutrition and the response to nutritional support.

Adolescent↗

A possible role of vitamin D in the genesis of parenteral-nutrition-induced metabolic bone disease.

Patients receiving long term parenteral nutrition may develop metabolic bone disease. In all 11 patients studied, histologic studies of bone showed excessive unmineralized bone tissue despite normal plasma 25-hydroxyvitamin D levels. Three patients also had bone pain and fractures and severe urinary loss of calcium and phosphate. Withdrawal of vitamin D from parenteral nutrition solutions was associated with improved histologic findings of bone in all patients, shown by a decrease in osteoid tissue and an increase in tetracycline uptake. In the three patients with symptoms, bone pain subsided, fractures healed, and urinary loss of calcium and phosphate decreased. Thus, vitamin D may be a factor in the genesis of parenteral nutrition-induced metabolic bone disease.

25-Hydroxyvitamin D 2↗

Copper metabolism and requirements in total parenteral nutrition.

Copper metabolism and requirements in patients receiving total parenteral nutrition were studied in 28 patients with gastrointestinal diseases. During each of the 3 wk of the study period, each of 24 patients received in their total parenteral nutrition solutions, a daily dose of copper amounting to 0.25 mg, 1.05 mg, or 1.85 mg, in a random order. The other 4 patients received a fixed daily dose of 1 mg throughout the 3 wk. Increased losses of copper through the gastrointestinal tract occurred in patients with diarrhea or high-output stomas or fistulas. Patients with abnormalities of liver excretory functions had decreases in gastrointestinal copper losses. Urinary copper excretion was twice that of normal subjects. Copper infused in excess of the requirements was retained and not excreted. Plasma copper did not reflect the copper balance and cannot be used as a guide for copper supplementation. Copper requirements were found to be 0.3 mg/day in patients with normal amounts of gastrointestinal excretion. In the presence of diarrhea or increased fluid loss through gastrointestinal stomas or fistulas, the copper requirements for total parenteral nutrition are 0.4--0.5 mg/day.

Adolescent↗