Predictors of growth and body composition in HIV-infected children beginning or changing antiretroviral therapy.

OBJECTIVES: The aim of the study was to describe growth and body composition changes in HIV-positive children after they had initiated or changed antiretroviral therapy (ART) and to correlate these with viral, immune and treatment parameters. METHODS: Ninety-seven prepubertal HIV-positive children were observed over 48 weeks upon beginning or changing ART. Anthropometry and bioelectrical impedance analysis results were compared with results from the National Health and Nutrition Examination Survey 1999-2002 (NHANES) to generate z-scores and with results for HIV-exposed, uninfected children from the Women and Infants Transmission Study (WITS). Multivariate analysis was used to evaluate associations between growth and body composition and disease parameters. RESULTS: All baseline lean and fat mass measures were below those of controls from NHANES. Weight, height and fat free mass (FFM) index (FFM/height(2)) z-scores increased over time (P = 0.004, 0.037 and 0.027, respectively) and the waist:height ratio z-score decreased (P = 0.045), but body mass index and per cent body fat z-scores did not change. Measures did not increase more than in uninfected WITS controls. In multivariate analysis, baseline height, mid-thigh circumference and FFM z-scores related to CD4 percentage (P = 0.029, P = 0.008 and 0.020, respectively) and change in FFM and FFM index z-scores to CD4 percentage increase (P = 0.010 and 0.011, respectively). Compared with WITS controls, baseline differences in height and mid-thigh muscle circumference were also associated with CD4 percentage. Case-control differences in change in both subscapular skinfold (SSF) thickness and the SSF:triceps skinfold ratio were inversely associated with viral suppression. No measures related to ART class(es) at baseline or over time. CONCLUSIONS: In these HIV-positive children, beginning or changing ART was associated with improved growth and lean body mass (LBM), as indicated by FFM index. Height and LBM related to CD4 percentage at baseline and over time. Altered fat distribution and greater central adiposity were associated with detectable virus but not ART class(es) received.

Supplements: questions to ask to reduce confusion.

Written and oral statements concerning supplements are delivered daily to audiences that span the full spectrum of demographics. Yet the common reaction of these audiences to these statements is that they are receiving mixed messages. One source of this confusion could be greatly reduced if each statement concerning supplements always defined the specific parameters of the studies on which the statement is based. Those receiving information about supplements must be made aware that extrapolation of data for one form of a supplement to predict the result of another form many be harmful to one's health. If a statement concerning a supplement does not clearly define the route of delivery, its matrix, the quantity of compound, the purity of compound, and the physiologic condition of the recipient, the statement should be disregarded by all audiences. If the creators of all types of supplement information define these parameters, and if audiences critically review the information provided, confusion concerning supplements will be reduced.

Methods of haemostasis in tonsillectomy assessed by pain scores and consultation rates. The Roskilde County Tonsillectomy Study.

OBJECTIVES: To compare four methods of haemostasis after tonsillectomy assessed by pain scores and consultation rates. STUDY DESIGN AND METHODS: A prospective study. The method of sole compression of the tonsillar fossae with gauze tampons was compared to ligation, bipolar diathermy and ligation/diathermy in combination. RESULTS: Highly significantly lower pain scores after discharge were found in the compression group compared to the other three groups (p < 0.025). The consultation rate in person after discharge of the compression group was significantly lower than in the diathermy group (p < 0.01) and the ligation/diathermy group (p < 0.05). CONCLUSION: Sole compression was associated with considerably less morbidity and no higher risk of postoperative haemorrhage. Sole compression should therefore be preferred in tonsillectomy whenever the surgeon considers it to be justified.

Tonsillectomy: assessment of quality by consultation rate after discharge.

The aim of this prospective study was to establish a measure of short-term quality of treatment after tonsillectomy/adenotonsillectomy. One hundred and thirty-four questionnaires, returned after 14 days, from 41 children and 93 adults were analysed. Forty-seven per cent had one or more consultations with health-care professionals. Eighty-three consultations by telephone and 33 consultations in person were made. Two recent studies reported higher consultation rates in person to doctors compared to this study. The predominant reason for consulting health-care professionals was pain. Maximum pain scores were significantly higher among those with consultations vs. no consultations (p = 0.0001). Additionally, the intensity as well as the duration of maximal pain increased with the number of contacts per patient (p = 0.0001, p = 0.0045). Sixty-four per cent felt relieved after consultation by telephone and 83 per cent felt relieved after consultation in person. The present study suggests consultation rate as a parameter of quality of treatment and quality of information.

Study of skin rashes after antibiotic use in young children.

Immunoglobulin E (IgE)-mediated drug sensitivity in children is uncommon. However, undefined skin rash following antibiotic ingestion in younger children is commonly observed in clinical practice. We studied 86 consecutively referred patients to our allergy clinic over a 5-year period. We found that the majority of children (80%) with skin rashes were under 3 years of age. All the children had been treated with antibiotics for a bacterial upper respiratory infection (URI; otitis media, sinusitis, or pharyngitis), 73 (85%) had erythematous rash, 13 (15%) had urticaria occurring 3-5 days after the treatment, and 43 (50%) reported a repeated rash with the use of two or more different antibiotics. There were no reports of systemic reactions or histories of accompanying food allergy. When patients were given the suspected antibiotics while they were well, none developed rash. However, in the next bacterial infection, 62 (72%) chose to receive dye-free suspensions of the suspected antibiotics. Only three patients (3.5%) elected for the dye-containing suspension. Of the 62 patients who received dye-free suspensions, only eight developed a mild skin rash, which was managed successfully. We conclude that a practical approach for non-IgE-mediated skin rash needs to be evaluated. The current practice of complete avoidance of the suspected antibiotics without further evaluation may be unwarranted.

Efficacy of an aqueous and a powder formulation of nasal budesonide compared in patients with nasal polyps.

Nasal polyps are commonly treated surgically. Intranasal administration of topical corticosteroids has gained increased acceptance as a treatment alternative. The aim of our study was to compare the efficacy of treatment of two formulations of budesonide with placebo on nasal polyps. At four Danish clinics 138 patients suffering from moderate or severe nasal polyps were randomized to a twice daily treatment with Rhinocort Aqua 128 micrograms, Rhinocort Turbuhaler 140 micrograms or placebo (Astra Draco, Sweden) for 6 weeks. Polyp size (primary efficacy variable), nasal symptoms, sense of smell, and patients' overall evaluation of treatment of efficacy were assessed by scores. Polyp size was reduced significantly in both budesonide treated groups compared with placebo, but there was no statistical difference between the two actively treated groups. Patients' nasal symptom scores was significantly more reduced in the Aqua compared to the Turbuhaler treated group, and both reduced symptom scores were significantly better compared to placebo. Sense of smell was significantly improved in the actively treated groups compared to placebo. The proportion of patients rating substantial or total control over symptoms after 6 weeks treatment was 60.9% and 48.2% in the Aqua and Turbuhaler-treated groups, respectively, which was significantly better compared with 29.8% in the placebo-treated group. Rhinocort Aqua and Rhinocort Turbuhaler were equally well tolerated.

Elevation of whole-blood glutathione in peritoneal dialysis patients by L-2-oxothiazolidine-4-carboxylate, a cysteine prodrug (Procysteine).

Glutathione is a major cellular antioxidant that protects protein thiols and inhibits cellular damage due to oxygen free radicals. It has been reported previously that patients undergoing dialysis have low levels of blood glutathione, which may lead to increased susceptibility to oxidant stress. L-2-oxothiazolidine-4-carboxylic acid (OTZ) is a cysteine prodrug that raises cellular glutathione levels by increasing delivery of cysteine, the rate-limiting substrate for glutathione synthesis. This study investigates the effect of OTZ on blood glutathione in a blinded, placebo-controlled study of patients with chronic renal failure treated by peritoneal dialysis. Twenty patients were randomly selected to receive OTZ (0.5 g three times a day orally with meals) or placebo for 14 d. Patients visited the clinic for predose blood collection and safety evaluation at baseline (days 3, 7, and 14 and again at 14 d from the last dose [follow-up]). Glutathione concentrations were determined in whole blood by HPLC. OTZ resulted in a significant rise in whole-blood glutathione at days 7 (594 +/- 129 mumol/L) and 14 (620 +/- 108 mumol/L) compared with baseline (544 +/- 139 mumol/L) (P < 0.01 and P < 0.05, respectively). Glutathione was also significantly increased at days 7 and 14 when normalized by hematocrit (Hct) or hemoglobin to correct for anemic status (e.g., 20.7 +/- 5.7 mumol/L per % Hct [day 7] and 20.9 +/- 4.0 mumol/L per % Hct [day 14] versus 18.0 +/- 4.2 mumol/L per % Hct [baseline]; P < 0.05). Glutathione levels did not change in the placebo group at any patient visit, and levels in the OTZ-treated group returned to baseline at follow-up. There were no serious adverse events attributable to OTZ, and the drug appeared to be well tolerated by patients with renal failure treated by continuous ambulatory peritoneal dialysis. Our results show that OTZ increases blood glutathione levels, which may improve antioxidant status in dialysis patients.

A phase I/II evaluation of oral L-2-oxothiazolidine-4-carboxylic acid in asymptomatic patients infected with human immunodeficiency virus.

A randomized double-blind, placebo-controlled study was conducted in 37 asymptomatic HIV-infected individuals (mean CD4 count 707 cells/mm3) to characterize the safety, pharmacokinetics, and effect on blood thiols of three dosage levels of a cysteine prodrug, L-2-oxothiazolidine-4-carboxylic acid (OTC; Procysteine; Clintec Technologies, Deerfield, IL). Single-dose administration of OTC resulted in measurable plasma levels at all dosages, with a mean peak plasma concentration of 734 +/- 234 nmol/mL at the highest dosage studied. After 4 weeks of administration three times daily, a statistically significant increase was seen in whole blood glutathione in the 1,500 mg and 3,000 mg dose groups compared with the placebo group. A significant increase in whole blood cysteine and peripheral blood mononuclear cell (PBMC) glutathione was not seen during the study period.

Common cold and high-dose ipratropium bromide: use of anticholinergic medication as an indicator of reflex-mediated hypersecretion.

UNLABELLED: It was our aim to study the role played by parasympathetic reflexes for the amount and physical characteristics of nasal discharge during a common cold, and to define the maximum anti-rhinorrhoea effect obtainable with anticholinergic medication. Fifty adults with naturally acquired colds were treated with a very high dose of the topically active cholinoceptor-antagonists ipratropium bromide in a randomized, double-blind, placebo-controlled study of parallel groups. A dosage of 400 micrograms was given 4 times daily for 3 days, using a specially manufactured high-dosed pressurized aerosol. This treatment resulted in a 56% reduction in the number of nose blowings (p < 0.01) and a 58% reduction in the weight of blown secretions (p < 0.01). Assessment of the "pourability" of the nasal discharge indicated that ipratropium bromide mainly reduces the watery secretions but not the mucopurulent secretions. The high dose of ipratropium bromide caused nose- and mouth-dryness in a considerable number of the patients. IN CONCLUSION: (1) during the first days of a common cold about 60% of the nasal discharge is a reflex-mediated product from nasal glands; (2) this type of secretion is predominantly watery; and (3) ipratropium bromide can reduce watery rhinorrhoea in the common cold, but a lower dose is required in order to avoid side effects.

A time-dose study of the effect of topical ipratropium bromide on methacholine-induced rhinorrhoea in patients with perennial non-allergic rhinitis.

Intranasal application of the anticholinergic drug, ipratropium bromide, is used for the treatment of watery rhinorrhoea. We have performed a time-dose study of ipratropium bromide in patients with perennial non-allergic rhinitis, using rhinorrhoea, induced by nasal methacholine challenge, as a laboratory model. Two doses of ipratropium bromide, 40 microg and 80 microg, delivered from a pressurized aerosol, were both very effective, reducing the volume of methacholine-induced secretion by 85 to 95%. The maximum effect lasted for at least 4 h and then slowly diminished. A significant effect was demonstrable for 12 h with 40 microg and for 18 h with 80 microg ipratropium bromide. These results from a laboratory challenge study indicate that the presently used frequency of ipratropium bromide, namely four times daily, may not be necessary in many patients. Perhaps once in the morning, followed by an as-needed medication, will be a better way to use intranasal ipratropium bromide in perennial non-allergic rhinitis.

Comparison between the effect of ipratropium bromide as a pressurized aerosol and as an aqueous pump spray on methacholine-induced rhinorrhoea.

Topical application of the anti-cholinergic drug ipratropium bromide is used for the treatment of rhinorrhoea. As the commercially-available pressurized aerosols are now largely being replaced by aqueous pump sprays, not containing CFC gases, we have compared these two types of sprays in a time-effect study of 20 normal persons, using the secretory response to nasal methacholine challenge as the effect parameter. Pre-treatment has been given as a single dose of 80 mg of ipratropium bromide, and 24 mg methacholine was used for challenge. The pressurized aerosol reduces rhinorrhoea with 60% (p < 0.05) and the effect lasts for at least 8 h. The corresponding value for the aqueous pump spray is 40% (p < 0.05) and the effect lasts for less than 4 h. The differences between the two sprays is significant 30 min, 1, 2 and 4 h after medication (p < 0.05). This finding is unexpected and we cannot offer a satisfactory explanation. The result indicates that changes in dosing and dose-frequency of ipratropium bromide may be necessary when patients are transferred from a pressurized spray to an aqueous pump spray.

A clinical study to evaluate the efficacy of the antihistamine doxylamine succinate in the relief of runny nose and sneezing associated with upper respiratory tract infection.

Antihistamines are widely used in common cold medications, although the role of histamine in the development of common cold symptoms is unclear and the use of antihistamines for the treatment of common cold is controversial. It is clear that antihistamines do not offer a cure for common cold but they may alleviate symptoms of sneezing and runny nose. The present study was designed to investigate the efficacy of an antihistamine, doxylamine, on the symptoms of runny nose and sneezing associated with common cold. We conducted a randomized double-blind study in cold sufferers. One thousand and one volunteers with cold symptoms were screened in four centres (UK, Denmark, Belgium, Germany) and 688 satisfied the entry criteria of the study. The main reasons for excluding subjects were a low nasal secretion weight (secretion weight < 0.2g, 72%) and a low subjective rhinorrhoea score (24%). Volunteers were randomized to receive either doxylamine succinate 7.5 mg by mouth four times a day up to nine doses (n = 345) or placebo (n = 343). The principal measurements were prospectively defined as runny nose and sneezing symptom scores. Data were analysed on an intention-to-treat basis, using Cochran-Mantel-Haenszel statistics controlling for baseline symptom scores. A between-group comparison showed that doxylamine-treated volunteers benefited from a significantly greater reduction in runny nose scores (P < 0.01) and sneezing scores (P < 0.001), than those volunteers in the placebo group. Doxylamine therapy was well tolerated; the incidence of unexpected side-effects was comparable with placebo. Of the expected side-effects, 13.3% of doxylamine-treated patients reported drowsiness. The incidence of sedative effects was lower than has been reported for other commonly used first-generation antihistamines.

Carnitine in neonatal nutrition.

Experimental evidence from several investigators suggests that carnitine is a conditionally essential nutrient for neonates. If carnitine is a conditionally essential nutrient for the neonate, most neonates on total parenteral nutrition in the United States are not receiving adequate nutritional support. The metabolic functions of carnitine are varied and important in several aspects of neonatal physiology. All neonates receiving breast milk receive dietary carnitine and most neonates receiving enteral infant formulas receive dietary carnitine at a level similar to that of the breast-fed neonate. However, most neonates on total parenteral nutrition receive no dietary carnitine. Investigators have been testing the working hypothesis that carnitine is a conditionally essential nutrient for the neonate for many years. This review discusses (1) data supporting the hypothesis, (2) reasons why it has not been either proved or disproved by now, and (3) the author's view of a prudent approach to dietary carnitine supplementation of neonates.

Hearing loss after neurosurgery. The influence of low cerebrospinal fluid pressure.

A prospective study was performed to investigate the effect of neurosurgery on hearing. Thirty-two patients underwent neurosurgery while 32 patients who had surgical procedures not involving puncture or drainage of the subdural space, served as a control group. In the neurosurgical group, a significant loss of hearing was observed in the immediate post-operative period, with recovery over one week. No average threshold shift was observed in the control group. It is suggested that following neurosurgery the mechanism of hearing loss results directly from a decrease in pressure and/or volume of the cerebrospinal fluid, which is reflected within the perilymphatic fluid, comparable to a transitory endolymphatic hydrops.

A phase I/II trial of intravenous L-2-oxothiazolidine-4-carboxylic acid (procysteine) in asymptomatic HIV-infected subjects.

Twenty-four asymptomatic, HIV-1-seropositive subjects with CD4 cell counts of > or = 400/microliters participated in a Phase I/II, dose escalation trial of intravenous L-2-oxothiazolidine-4-carboxylic acid (OTC: Procysteine). Four groups of six subjects each were consecutively assigned to receive OTC at an initial dose of 3, 10, 30, or 100 mg/kg, followed by the same dose given twice weekly for 6 weeks. Increases in whole-blood glutathione were observed in the highest dosage group after 6 weeks of therapy. No effects on changes in CD4 cell counts, viral load, or proviral DNA frequency were observed among the four dosage groups, although a decline in beta 2-microglobulin levels was apparent in the highest dosage group. One subject withdrew due to headaches; other probable adverse events including rash, flushing, pruritus, lightheadedness, and diminished concentration were self-limited.

Feeding practices and nutrition recommendations for infants with cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive disease characterized clinically by recurrent respiratory tract infections and malabsorption caused by pancreatic insufficiency. Typically diagnosed during infancy or childhood, CF impairs weight gain and growth, increases susceptibility to infection, and decreases longevity. Until recently, no guidelines for infant feedings were available. A consensus report prepared through the Cystic Fibrosis Foundation summarizes guidelines for the optimal nutrition management of patients with CF. This study identified current feeding practices and nutrition recommendations of dietitians who treat infants with CF and compared them with the recommendations of the consensus report. A survey was developed and sent to dietitians (n = 130) who work in accredited cystic fibrosis centers. Eighty-six dietitians (66%) responded after two mailings, and 75 usable surveys were analyzed. The survey investigated practitioners' recommendations for infant formulas, energy intake, nutritional supplements, and pancreatic enzyme supplementation. Protein hydrolysate infant formulas were recommended by most respondents (69%). Energy intake greater than 130% of the Recommended Dietary Allowances (RDAs) was recommended for well-nourished infants with CF and greater than 140% of the RDAs for malnourished infants with CF at 1 year of age. Formula additives, including fat and carbohydrate modules, were used by all respondents and were frequently added to infant foods to increase caloric density. Enteric coated pancreatic enzymes were used by the majority (76%) of dietitians. These findings indicate that most dietitians follow the nutrition guidelines established by the Cystic Fibrosis Foundation consensus report for goals for energy and protein intake, use of nutritional supplements, and replacement of pancreatic enzymes in infants with CF.

Use of the colostrum-deprived piglet to evaluate parenteral feeding formulas.

Several different neonatal and infant piglet models have been invaluable as animal models in nutrition research. A preterm colostrum-deprived piglet model has been developed that is delivered at the desired gestational age, is cared for using the standard of care provided preterm human neonates including procedures for nutritional support and can be studied during pathological conditions induced under controlled conditions. The absolute values for each nutrient requirement would not be expected to be identical for preterm piglets and preterm human neonates. However, the effect of different levels of gestational maturity and superimposed pathophysiologies on nutrient requirements should be similar in the piglet and human neonate.

Medium-chain triglycerides in formula for preterm neonates: implications for hepatic and extrahepatic metabolism.

Medium-chain fatty acids are an important energy source for preterm neonates. Based on assumptions from earlier investigations, 40% to 60% of fatty acids in formula designed for preterm neonates are C6:0 to C12:0. This review will reevaluate these assumptions about C6:0 to C12:0 fatty acids. More recent investigations have indicated that when C6:0 to C12:0 fatty acids are administered in high concentrations, they are metabolized in several tissues by carnitine-dependent mechanisms. Incomplete oxidation of C6:0 to C12:0 fatty acids may result in elevated dicarboxylic acid levels. Feeding formulas high in C6:0 to C12:0 fatty acids has not improved nitrogen retention or growth of preterm neonates. Current data indicate that the fatty acid profiles of formula for preterm neonates are not optimal. Optimization of the fatty acid profile in the diet awaits an improved understanding of the metabolism of fatty acids of all chain lengths in the preterm neonate.