Widespread growth retardation and variable growth recovery in foster children in the first year after initial placement

OBJECTIVES: To determine children's growth patterns in the first year of foster care placement and to compare catch-up growth with initial height percentile as indicators of prior growth retardation. DESIGN: Inception cohort. SUBJECTS: Forty-five children aged 1 1/2 to 6.0 years in their first year of foster care. SETTING: Urban, community-based primary care center. MAIN OUTCOME MEASURES: Height, weight, weight-for-height, and annual growth velocity z scores 1 year after placement. RESULTS: The group entered foster care with an overall height deficit (height z = -0.21), grew at an above-average rate (velocity z = +0.33), and eliminated the height deficit by the end of the year (height z = -0.02; P < .05). Weight increased (baseline weight z = -0.16; year-end weight z = +0.35) and correlated with height z change (r = 0.385, P = .009). Weight for expected weight-for-height-age was above average and did not change (baseline weight for expected weight-for-height-age z = +0.30; year-end weight for expected weight-for-height-age z = +0.40). Baseline age correlated with velocity z (r = .413, P = .005) but not with change in height z. Baseline height z did not correlate with either velocity z or change in height z. Three patterns of growth were seen: 21 (47%) showed catch-up growth (height velocity z = 1.34; gain in height z = +0.61); 16 (36%) showed stable growth; and 8 (18%) showed poor growth (height velocity z = -1.49; decrease in height z = -0.49). CONCLUSIONS: Almost half of the children showed significant catch-up growth in the first year after foster care placement, indicating probable prior growth failure. Initial height was not predictive of future growth, and simple screening (such as height less than the fifth percentile) would have missed the majority of children who showed catch-up growth. A substantial minority (18%) continued to decline across height percentiles after placement. The initial and subsequent growth failure and catch-up growth in this population did not appear to be related to nutritional changes.     

Developmental variations in factors related to initial and increased levels of adolescent drug involvement

Effects of two 9-month sports programmes (four or two sessions per week) on level of daily physical activity (PA), fat mass (FM), and physical fitness were assessed in children with spastic cerebral palsy (CP; n = 20, 9.2 +/- 1.4 yr), randomly assigned to an experimental and control group after matching. Four sessions per week tended to increase PA ratio (24-h energy expenditure/sleeping (resting) energy expenditure) after 9 months from 1.34 +/- 0.25 to 1.55 +/- 0.18 (P = 0.07; not different versus controls). FM increased continuously in the control group (after 9 months + 1.1 +/- 1.6 kg, P < 0.05), whereas the experimental groups showed no changes. Training (respectively four and two sessions) increased peak aerobic power 35% (P < 0.01; P < 0.05 versus controls) and 21% (P < 0.01; P = 0.17 versus controls). Results also suggest that training has a favourable effect on isokinetic muscle strength. No training-related effects were found on anaerobic power. It was concluded that although aerobic training has a limited effect on PA in children with CP, it may prevent deterioration in body composition and muscle strength. Furthermore, training has a favourable effect on peak aerobic power.     

Increased height gain of children fed a high-protein diet during convalescence from shigellosis: a six-month follow-Up study

The impact of dietary supplementation on catch-up growth was evaluated in 69 malnourished children ages 24-60 mo after recovery from shigellosis. They were fed either a high-protein (HP) diet with 15% of energy as protein, or a standard-protein (SP) diet with 7.5% energy as protein, for 3 wk in a metabolic study ward. Children were followed up bi-weekly for 6 mo by trained health assistants when anthropometric measurements and information of any illness were collected. Thirty-one children in the HP group and 28 children in the SP group completed 6-mo follow-up. The increase in height (mean +/- SD) was 5.3 +/- 1.0 cm vs. 4.1 +/- 1.1 cm for HP and SP groups, respectively (P < 0.001), whereas increase in body weight was 1.39 +/- 0.58 and 1.29 +/- 0.72 kg for children fed HP and SP, respectively (P = 0.59). The proportion of children who were severely stunted (< -2 SD height-for-age) decreased from 45 to 29% in the HP group compared to 50 to 46% in the SP group (P < 0.05) at 6-mo follow-up. The number of diarrheal episodes per child tended to be lower in the HP vs. SP than in the SP group (1.9 vs. 2.3, P = 0.41). These results demonstrate that feeding an HP diet to the malnourished children during recovery from shigellosis enhanced linear growth with a modest reduction in diarrheal morbidity during the 6-mo follow-up period.     

When should expanded criteria donor kidneys be used for single versus dual kidney transplants?

BACKGROUND: To increase the utilization of cadaveric donor kidneys, we have recently expanded our acceptable criteria to include aged donors (frequently with a history of hypertension), by selectively using both donor kidneys (dual transplant) into a single recipient. METHODS: To define when these expanded criteria donor (ECD) kidneys should be used as a single versus a dual kidney transplant, we retrospectively reviewed 52 recipients of ECD kidneys that had been turned down by all other local centers between 1/1/95 and 11/15/96. Fifteen patients received dual transplants, whereas the remaining 37 received single kidneys. Of the dual kidney recipients, 14 of 15 ECD were > or = 59 years of age, 10 of 15 were hypertensive, and 9 of 15 were both. Of the single recipients, 11 of 37 ECD were > or = 59 years of age, 11 of 37 were hypertensive, and 7 of 37 were both. All patients received cyclosporine-based triple-drug therapy. We compared seven donor (D) and sixteen recipient outcome variables in single versus dual kidney transplants as subgrouped by: (1) donor admission creatinine clearance (D-AdC(Cr)) < 90 ml/min; (2) D-age > or = 59 years; and (3) cold storage (Cld Stg) < or > 24 hr. RESULTS: In the group with D-AdC(Cr) < 90, there was a significantly higher incidence of delayed graft function (DGF) in single versus dual recipients (9 of 20 [45%] vs. 1 of 11 [9%]; P=0.04) and worse early graft function based upon mean serum creatinine at 1 and 4 weeks (5.3+/-3.3 and 2.8+/-2.0 vs. 1.7+/-0.6 and 1.4+/-0.5 mg] dl; P<0.05). In the group with D-age > or = 59, recipients of single kidneys had significantly higher mean serum creatinine at 1, 4, and 12 weeks versus recipients of dual kidneys (5.1+/-3.3, 3.4+/-2.1, 2.8+/-1.5 versus 2.8+/-2.5, 1.5+/-0.6, 1.6+/-0.5 mg/dl; P<0.05). Cld Stg time also had an impact on DGF and early outcome. Recipients of dual kidneys stored less than 24 hr had a significantly lower incidence of DGF versus single kidneys stored more than 24 hr (10% vs. 46%; P<0.05) and better early graft function based on mean serum creatinine at 1, 4, and 12 weeks (1.9+/-0.8, 1.3+/-0.4, 1.5+/-0.2 vs. 6.6+/-3.4, 3.0+/-1.6, 2.9+/-1.9 mg/dl; P<0.05). The overall 1-year patient and graft survivals were 96% and 81% vs. 93% and 87% (P=NS) in recipients of single ECD versus dual ECD kidneys. CONCLUSIONS: In conclusion, we believe that kidneys from ECD with D-AdC(Cr) < 90 ml/min and D-age > or = 59 should be used as dual kidney transplants, keeping the Cld Stg time at < 24 hr to minimize the effect of Cld Stg on early graft function.     

Resting hemodynamics after total versus standard orthotopic heart transplantation in patients with high preoperative pulmonary vascular resistance

OBJECTIVE: Pretransplant pulmonary vascular resistance > or = 4 Wood-units predisposes to right ventricular failure after heart transplantation. Total orthotopic heart transplantation with bicaval and pulmonary venous anastomoses offers synchronous contractions of the atria and a normal ventricular filling pattern, but requires longer ischemic time than standard orthotopic heart transplantation. To test if total orthotopic heart transplantation improves resting hemodynamics in pts with high preoperative pulmonary vascular resistance, we analyzed 65 pts with standard and 65 with total orthotopic heart transplantation transplanted between 12/88 and 7/94. Of these, 18 with total and 15 with standard orthotopic heart transplantation had a preoperative pulmonary vascular resistance > or = 4 Wood-units. METHODS: Right heart catheterization data were obtained at each endomyocardial biopsy. All data from biopsies at both 2 weeks and 1 year posttransplant that were free from humoral or greater than 1A cellular rejection (9 versus 13 pts) were included in a two way ANOVA. Pts with postop pacemakers, atrial fib or beta-blocker therapy at the time of biopsy were excluded. RESULTS: Ischemic time was different (172 +/- 44 versus 142 +/- 28 min, P = 0.03). Demographics, NYHA class, pre-TX hemodynamics, donor age and inotropes were similar. Cardiac output and index were higher in the total orthotopic group at 2 weeks (6.5 +/- 1.7 versus 5.1 +/- 1.0 l/min; 3.4 +/- 0.9 versus 2.8 +/- 0.6 l/min per m2) and 1 year (7.1 +/- 2.0 versus 4.9 +/- 1.1 l/min, P = 0.002; 3.6 +/- 1.1 versus 2.6 +/- 0.5 l/min per m2, P = 0.009). Right atrial and pulmonary arterial mean pressure (mmHg) were lower with total orthotopic heart transplantation at 2 weeks (6 +/- 4 versus 9 +/- 5, P = 0.04; 22 +/- 3 versus 25 +/- 7, P = 0.1) and 1 year (5 +/- 2 versus 7 +/- 3, P = 0.02; 19 +/- 4 versus 25 +/- 7, P = 0.03). Pulmonary capillary wedge pressure (mmHg) was borderline nonsignificant (11 +/- 4 versus 13 +/- 7 at 2 weeks, 8 +/- 3 versus 14 +/- 5 at 1 year, P = 0.055), as well as pulmonary vascular resistance (1.9 +/- 1 versus 2.5 +/- 1 at 2 weeks, 1.5 +/- 0.6 versus 2.7 +/- 1.7 WU at 1 year, P = 0.051). CONCLUSIONS: Total orthotopic heart transplantation improves cardiac output and index in pts with high preoperative pulmonary vacular resistance. There is a lower mean RA and PA pressure perhaps due to less tricuspid and mitral regurgitation. In view of the frequently observed restrictive filling pattern after cardiac transplantation, total orthotopic heart transplantation can be beneficial until this pattern has subsided by preserving atrioventricular synchrony and offering better atrial transport.     

Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind, placebo-controlled, multicenter study. PROWESS Study Group

OBJECTIVES: To compare the long-term effects of finasteride (5 mg/day) and placebo in patients with moderate symptoms of benign prostatic hyperplasia (BPH). METHODS: Patients aged 50 to 75 years, with at least two urinary symptoms indicating moderate BPH, and an enlarged prostate, were followed in a 2-year double-blind, randomized, placebo-controlled multicenter study. The effects of finasteride versus placebo were assessed by total symptom score (modified Boyarsky), obstructive symptom score, maximal urinary flow rate, prostate volume, and urologic end points (acute urinary retention, BPH-related surgical intervention). RESULTS: Of the 3270 men enrolled, 3168 contributed data to the safety analysis, and 2902 to the efficacy evaluation. Significantly greater improvement with finasteride compared to placebo was observed at 12 and 24 months for total symptom score (mean -2.9 versus -1.9 at 12 months, P < or =0.001; -3.2 versus -1.5 at 24 months, P < or =0.001), obstructive symptom score (mean -1.9 versus -1.3 at 12 months, P < or =0.001; -2.1 versus -1.1 at 24 months, P < or =0.001), maximal urinary flow rate (mean +1.2 versus +0.6 mL/s at 12 months, P = 0.010; +1.5 versus +0.7 mL/s at 24 months, P = 0.002), and prostate volume (mean -14.2 versus +5.4% at 12 months, P < or =0.01; -15.3 versus +8.9% at 24 months, P < or =0.001). Greater improvements in placebo-adjusted total symptom score occurred in men with large prostates than in men with small prostates (mean -2.4 versus -1.1 at 12 months; -3.2 versus -1.3 at 24 months, placebo-adjusted data, P = 0.053). Fifteen of 1450 men (1.0%) in the finasteride group experienced an acute urinary retention event, compared with 37 of 1452 (2.5%) in the placebo group, and the corresponding figures for surgery were 51 of 1450 (3.5%) and 86 of 1452 (5.9%), respectively. The hazard rate for occurrence, computed using the log-rank statistic, decreased by 57% for acute urinary retention and by 40% for surgery accompanied by finasteride therapy compared to placebo. CONCLUSIONS: Finasteride causes long-term symptomatic improvement and reduces the risk of acute urinary retention or surgery. Men with enlarged prostates benefit most from finasteride treatment.     

SCH56592 treatment of murine invasive aspergillosis

We analyzed the clinical presentation of 800 severe malaria cases six months to 15 years of age (mean +/- SD = 4.3 +/- 3.0) recruited at the pediatric ward of the Ouagadougou University Hospital, and at the Sourou and Nayala District Hospitals in Burkina Faso. Inclusion criteria followed the World Health Organization (WHO) definition of severe and complicated malaria. The children were treated according to WHO guidelines with a complete regimen of drugs that were provided free of charge as part of the study. The case fatality rate of each sign and symptom of severe malaria was calculated on the 686 children whose outcomes were known. A total of 95 patients (13.8%) died while in the hospital; the mean +/- SD age of these children was 3.2 +/- 2.1 years. The age distribution and the clinical patterns of severe malaria was compared in patients from the urban areas of Ouagadougou characterized by relatively low transmission, and from rural areas where the mean inoculation rates are at least 20-fold higher. The mean +/- SD age of the urban and rural patients was 4.8 +/- 3.0 and 2.2 +/- 1.9 years, respectively (P < 0.001). The prevalence of coma was higher in the urban subsample (53.6% versus 28.9%; P < 0.001) while that of severe anemia (hemoglobin < 5 g/dL) was higher in rural patients (47.4% versus 14.8%; P < 0.001). Our data, in line with previous results obtained comparing rural areas characterized by different inoculation rates, show that the epidemiologic context influences the clinical presentation of severe malaria.     

The role of endothelin-1 as a mediator of the pressure response after air embolism in blood perfused lungs

BACKGROUND: Irritable bowel syndrome is a common cause of abdominal pain and discomfort and may be related to disordered gastrointestinal motility. Our aim was to assess the effects of long-term treatment with a prokinetic agent, cisapride, on postprandial jejunal motility and symptoms in the irritable bowel syndrome (IBS). METHODS: Thirty-eight patients with IBS (constipation-predominant, n = 17; diarrhoea-predominant, n = 21) underwent 24-h ambulatory jejunal manometry before and after 12 week's treatment [cisapride, 5 mg three times daily (n = 19) or placebo (n = 19)]. RESULTS: In diarrhoea-predominant patients significant differences in contraction characteristics were observed between the cisapride and placebo groups. In cisapride-treated diarrhoea-predominant patients the mean contraction amplitude was higher (29.3 +/- 3.2 versus 24.9 +/- 2.6 mm Hg, cisapride versus placebo (P < 0.001); pretreatment, 25.7 +/- 6.0 mm Hg), the mean contraction duration longer (3.4 +/- 0.2 versus 3.0 +/- 0.2 sec, cisapride versus placebo (P < 0.001); pretreatment, 3.1 +/- 0.5 sec), and the mean contraction frequency lower (2.0 +/- 0.2 versus 2.5 +/- 0.4 cont./min, cisapride versus placebo (P < 0.001); pretreatment, 2.5 +/- 1.1 cont./min] than patients treated with placebo. No significant differences in jejunal motility were found in the constipation-predominant IBS group. Symptoms were assessed by using a visual analogue scale before and after treatment. Symptom scores relating to the severity of constipation were lower in cisapride-treated constipation-predominant IBS patients [score, 54 +/- 5 versus 67 +/- 14 mm, cisapride versus placebo (P < 0.05); pretreatment, 62 +/- 19 mm]. Diarrhoea-predominant IBS patients had a higher pain score after cisapride therapy [score, 55 +/- 15 versus 34 +/- 12 mm, cisapride versus placebo (P < 0.05); pretreatment, 67 +/- 19 mm]. CONCLUSION: Cisapride affects jejunal contraction characteristics and some symptoms in IBS.     

The fate of intraperitoneally retained gallstones with different morphologic and microbiologic characteristics: an experimental study

Calcium deficiency is a major etiological determinant of rickets in Nigerian children and is accompanied by undermineralization of the developing bone matrix which is composed largely of type I collagen. We have assessed types I and III collagen metabolism by measuring the circulating concentrations of teh N- and C-terminal pro-peptides (intact PINP and PICP) and the C-terminal telopeptide (ICTP) of type I collagen, and the N-terminal pro-peptide (PIIINP) of type III collagen in 94 healthy Nigerian children and in 44 children aged 1-5 years with active calcium-deficiency rickets. In active rickets the mean levels of the four collagen metabolites were approximately twofold higher than in the healthy children, despite a wide variation of individual values. Mean intact PINP was 812 +/- 279 versus 403 +/- 189 microg/liter; PICP was 573 +/- 265 versus 348 +/- 299 microg/liter; PIIINP was 16.8 +/- 8.6 versus 10.8 +/- 3.6 microg/liter, and ICTP was 28.4 +/- 17.2 versus 11.9 +/- 4.1 microg/liter (all P < 0.001), in rachitic and healthy children, respectively. Healthy children younger than 3 years had higher levels of all the collagen metabolites than those between 3 and 5 years (all P < 0.05). Alkaline phosphatase was greater in rickets than in the healthy group (P < 0.001) whereas mean osteocalcin levels were slightly lower (P = 0.009). 1,25(OH)2D correlated with all the collagen propeptides, but not with ICTP in the healthy children. No such correlations were found in rickets, where there was a poor inverse correlation between 1,25(OH)2D and ICTP. These data suggest that collagen turnover is elevated in cases of calcium-deficiency rickets, where vitamin D status is adequate, possibly indicating increased turnover of undermineralized osteoid.     

Pediatric hepatic trauma: does clinical course support intensive care unit stay?

PURPOSE: The objective of this study is to determine if grade of liver injury predicts outcome after blunt hepatic trauma in children and to initiate analysis of current management practices to optimize resource utilization without compromising patient care. METHODS: A retrospective review of 36 children who had blunt hepatic trauma treated at a pediatric trauma center from 1989 to present was performed. Hepatic injuries graded (AAST Organ Injury Scaling) ranged from grade I to IV. Injury Severity Score (ISS), Glasgow Coma Score (GCS), transfusion requirements, liver transaminase levels, associated injuries, intensive care unit (ICU) length of stay, and survival were analyzed. RESULTS: Mean (+/-SEM) age was 6.6+/-0.8 years, mean grade of hepatic injury was 2.4+/-0.2, mean ISS was 17+/-2.6, mean GCS was 13+/-1, and mean transfusion was 15.4 mL/kg of packed red blood cells (PRBC). There were three deaths with a mean ISS of 59+/-9 and a mean GCS of 3+/-0. Death was not associated with a high-grade liver injury, survivors versus nonsurvivors, 2.3+/-0.2 versus 2.7+/-0.3, but was associated with ISS, 13+/-1.4 versus 59+/-9 (P = .005) and GCS, 14+/-1 versus 3+/-0 (P = .005). Only one patient (grade III, ISS = 43) underwent surgery. There were no differences in mean ISS or GCS between grades I to IV patients. The hepatic injury grades of patients requiring transfusion versus no transfusion were significantly different, 3.4+/-0.2 versus 2.2+/-0.2 (P = 0.04). Abused patients had high-grade hepatic injuries and significant laboratory and clinical findings. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher in grade III and IV injuries than in grades I and II, 1,157+/-320 versus 333+/-61 (P= .02) and 1,176+/-299 versus 516+/-86 (P= .04), respectively. No children with grade I or II injury had a transfusion requirement or surgical intervention. There were no liver-related complications. CONCLUSIONS: Mortality and morbidity rates in pediatric liver injuries, grades I to IV, correlate with associated injuries not the degree of hepatic damage. ALT, AST, and transfusion requirements are significantly related to degree of liver injury. Low-grade and isolated high-grade liver injuries seldom require transfusion. Blunt liver trauma rarely requires surgical intervention. In retrospect, the need for expensive ICU observation for low-grade and isolated high-grade hepatic injuries is questionably warranted.     

Transthoracic Doppler echocardiography of normally originating coronary arteries in children

Transthoracic Doppler color flow and spectral velocity patterns of normal coronary arteries in children have not been well studied. We designed this study to evaluate coronary artery flow velocity characteristics in normal and hypertrophied hearts. Sixty-eight children with optimal two-dimensional echocardiographic images of the left coronary artery (LCA) and right coronary artery (RCA) were prospectively studied. The heart was normal in 45 children, and 23 had left and/or right ventricular hypertrophy assessed by echocardiography (mean age 5.8 versus 5.2 years, p = NS). Color flow signals were detected in the LCA in 63(92%) of the 68 children studied, and pulsed Doppler spectral waveforms were recorded in 47 (69%). The latter were recorded in 26 (58%) of 45 normal children and in 21 (91%) of 23 children with left ventricular hypertrophy. Diastolic RCA flow signals were detected mostly in those with right ventricular hypertrophy (10 of 10). Higher levels of LCA maximum diastolic velocity (42 +/- 23 versus 24 +/- 6 cm/sec, p = 0.0004), increased diastolic flow (16 +/- 15 versus 6 +/- 4 ml/min, p = 0.01), and delayed time to peak diastolic velocity expressed as a percentage of diastolic spectral duration (38% +/- 14% versus 20% +/- 8%, p = 0.0001) were observed in children with left ventricular hypertrophy than in those in normal children. A strong correlation was present between Doppler-derived LCA flow and left ventricular mass/m2 (r = 0.7, p = 0.001). In normal hearts, LCA spectral velocity pattern did not change with increasing age, but the time velocity integral became progressively larger, resulting in a strong correlation with weight (p < 0.001, r = 0.78). This study demonstrates (1) LCA flow signals can be detected and quantitated in the majority of children with and those without left ventricular hypertrophy. (2) Left ventricular hypertrophy is associated with increased LCA flow, higher diastolic velocity, and delayed peak diastolic velocity. (3) RCA flow signals are mostly detected when there is right ventricular hypertrophy. Studies on larger groups of patients are needed to further confirm our observations and to enhance understanding of coronary artery flow reserve.     

The effects of recombinant human growth hormone (r-hGH, SM-9500, genotropin) on growth failure in children with uremia. Japanese Multi-Center Study (Genotropin) Group on Children with Renal Disease

We treated 90 pediatric patients with chronic renal failure with recombinant growth hormone (r-hGH) for 12 months to improve their growth retardation due to uremia. They were divided into two groups, non-dialyzed and dialyzed children. The dose of r-hGH was 0.5 or 1.0 IU/kg/week in dialyzed children. After 12 months of the treatment using r-hGH, growth velocity was significantly increased in any group of children. Growth velocity was stimulated to about twice as much as before treatment (that were: in non-dialyzed group, 4.2 +/- 2.6cm/year vs. 6.2 +/- 2.0cm/year, P < 0.05, in dialyzed children treated with 0.51U of r-hGH: 2.7 +/- 1.8cm/year vs. 5.2 +/- 2.6cm/year, P < 0.001, and in dialyzed children treated with 1.01U of r-hGH: 3.0 +/- 1.5cm/year vs. 6.3 +/- 2.2cm/year, P < 0.001). No severe side effects was noted and no disturbance of renal function. Our results were consistent with those reported from Europe and USA. We conclude that r-hGH treatment is very effective in improving retarded growth in children with renal disease.     

Factors relating to urinary protein excretion in children with autosomal dominant polycystic kidney disease

Adults with autosomal dominant polycystic kidney disease (ADPKD) who have overt proteinuria (>300 mg/d) have higher mean arterial pressures, lower creatinine clearances, larger renal volumes, and a more aggressive course of renal disease than ADPKD patients without proteinuria. This study examines the relationship between proteinuria and microalbuminuria and similar factors in ADPKD children. A total of 189 children from 81 ADPKD families was included in the analysis. The ADPKD children (n = 103) had significantly greater urine protein excretion rates than the non-ADPKD children (n = 86) (3.9+/-0.3 versus 2.8+/-0.2 mg/m2 per h, P < 0.001). Children with severe renal cystic disease (> 10 cysts; n = 54) had greater protein excretion than those with moderate disease (< or = 10 cysts; n = 49) (4.4+/-0.5 versus 3.3+/-0.2 mg/m2 per h, P < 0.05). The ADPKD children had significantly greater albumin excretion rates than the non-ADPKD children (32+/-6 versus 10+/-2 mg/m2 per 24 h, P < 0.001), and a higher percentage of ADPKD children had significant microalbuminuria (>15 mg/m2 per 24 h in boys and >23 mg/m2 per 24 h in girls) than their unaffected siblings (30% versus 10%, P < 0.05). Thirty percent of ADPKD children had albuminuria and 23% had overt proteinuria. For all ADPKD children, there was no correlation between proteinuria and hypertension. However, there was a significant correlation between urinary protein excretion and diastolic BP among children diagnosed after the first year of life (r = 0.23, P < 0.05). Therefore, proteinuria and albuminuria occur early in the course of ADPKD and may be markers of more severe renal disease.     

Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate

Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s-PIIINP changed significantly with age and pubertal development stages. For s-PIIINP, a peak was seen at 12 yr for girls and 13 yr for boys; no peak could be discerned for s-PICP. The prepubertal (Tanner stage 1) s-PICP value (mean +/- SD) for girls was 374 +/- 132 micrograms/L, the midpubertal value (stage 3) was 442 +/- 135 micrograms/L, and the postpubertal value (stage 5) was 203 +/- 103 micrograms/L. The mean s-PIIINP levels for girls were 9.1 +/- 2.4, 15.0 +/- 4.3, and 6.8 +/- 3.1 micrograms/L, respectively. For boys, levels were 362 +/- 119, 544 +/- 138, and 359 +/- 256 micrograms/L for s-PICP and 8.5 +/- 2.2, 14.5 +/- 5.0, and 8.6 +/- 3.8 micrograms/L for s-PIIINP (P < 0.001 for both propeptides in both boys and girls). There was, however, a large variation in normal values for both propeptides within the age groups and pubertal stages. There was a significant correlation of s-PICP and s-PIIINP levels to height velocity in girls (r = 0.35; P < 0.001 and r = 0.33; P < 0.001, respectively), while in boys, only s-PIIINP showed significant correlation to height velocity (r = 0.40; P < 0.001). In untreated girls with CPP, serum levels of s-PIIINP were elevated [PIIINP SD score (SDS), 2.13]. Levels of s-PICP were normal (PICP SDS, 0.39). Levels of both propeptides decreased within 2 months after initiation of therapy and remained below initial values (P < 0.01). The decrease in s-PIIINP after 2 months of therapy showed a significant correlation with the fall in height velocity SDS for chronological age after 6 months of therapy (r = 0.64; P < 0.01). We conclude that s-PIIINP and, to a lesser degree, s-PICP reflect growth in normal children, but due to the large variation, both propeptides seem unsuitable as markers for screening of growth disorders in children.     

Effects of renin inhibition compared to angiotensin converting enzyme inhibition in conscious dogs with pacing-induced heart failure

OBJECTIVE: To compare the effects of angiotensin converting enzyme inhibition (ACEI) (captopril 1 mg/kg i.v.) to direct renin inhibition (CP80794 3 mg/kg i.v.) on left ventricular and systemic hemodynamics and peripheral blood flows in advanced congestive heart failure (CHF). METHODS: Conscious chronically instrumented dogs (n = 14) were treated with captopril, 1 mg/kg, i.v., or CP80794, 3 mg/kg, i.v., before and after development of advanced CHF induced by 4-7 weeks of rapid ventricular pacing. After advanced CHF, comparisons between the inhibitors were made at equihypotensive doses. RESULTS: In advanced CHF, both agents caused comparable reductions in mean arterial pressure (MAP) (-22% from 79 +/- 4 mmHg) and comparable increases (P < 0.01) in cardiac output (CP80794, 1.4 +/- 0.3 to 1.8 +/- 0.1 l/min; captopril, 1.4 +/- 0.1 to 1.9 +/- 0.1 l/min). Neither agent had a significant effect on LV contractility. In contrast, CP80794 caused a greater (P < 0.05) increase in renal blood flow (66 +/- 6% from 64 +/- 5 ml/min) compared to captopril (33 +/- 4% from 66 +/- 7 ml/min). CONCLUSIONS: Renin inhibition with CP80794 and ACEI with captopril caused comparable hemodynamic effects in advanced CHF. However, CP80794 caused significantly greater increases in renal blood flow and suppressed renin activity to a greater degree than captopril.     

Hyperinsulinism in patients with coronary artery disease

AIM: To assess the clinical impact of hyperinsulinism and major coronary risk factors in patients with angiographically documented or excluded coronary artery disease (CAD), a clinical study was carried out in 268 men admitted for left heart catheterization. METHODS: Fasting immunoreactive insulin (IRI) levels were correlated to all major cardiovascular risk factors and to the presence and degree of CAD. RESULTS: IRI levels were correlated significantly with the degree of CAD (one-vessel disease: mean IRI 9.45 microU/ml +/- 0.43 SEM; two-vessel disease: mean IRI 10.4 microU/ml +/- 0.71 SEM; three-vessel disease: mean IRI 11.88 microU/ml +/- 0.98 SEM) and inversely to the high-density lipoprotein level (P < 0.05). In patients with arterial hypertension, IRI levels were elevated, without a significant difference between those with and those without CAD, whereas the IRI levels of non-hypertensive men with CAD (n = 81; mean IRI 9.85 microU/ml +/- 0.51 SEM) differed significantly (P < 0.05) from those of non-hypertensive men without CAD (n = 59; mean IRI 7.76 microU/ml +/- 0.43 SEM). IRI levels were significantly higher (P < 0.05) in obese patients (n = 65; mean IRI 11.68 microU/ml +/- 0.70 SEM versus n = 203; mean IRI 9.32 microU/ml +/- 0.34 SEM), in patients with elevated triglycerides (n = 58 mean IRI 11.59 microU/ml +/- 0.81 SEM versus n = 210; mean IRI 9.42 microU/ml +/- 0.33 SEM), and in patients with lowered HDL cholesterol (n = 178; mean IRI 11.06 microU/ml +/- 0.63 SEM versus n = 90; mean IRI 9.29 microU/ml +/- 0.34 SEM). Diabetic patients on angiotensin converting enzyme inhibitor therapy (n = 11; mean IRI 7.91 microU/ml +/- 0.91 SEM) had significantly (P < 0.05) lower IRI levels than those not treated with ACE inhibitors (n = 25; mean IRI 12.96 microU/ml +/- 1.47 SEM). IRI levels exceeding 8 microU/ml were associated with a 1.98-fold risk for CAD compared with IRI levels below 8 microU/ml. Stepwise logistic regression showed that insulin was an independent determinant of CAD. CONCLUSION: Knowledge of the fasting insulin level is an important contribution to the identification of patients with, or at risk of, CAD.     

Role of transcranial Doppler and stump pressure during carotid endarterectomy

BACKGROUND AND PURPOSE: The aim of our study was to clarify the pathophysiology of perioperative cerebral complications during carotid endarterectomy in our series. METHODS: By means of transcranial Doppler ultrasonography and stump pressure measurement, we monitored 112 patients who underwent carotid endarterectomy under general anesthesia for symptomatic or asymptomatic severe carotid stenosis. RESULTS: Of 18 patients who underwent carotid endarterectomy with intra-arterial shunt, 2 (11.1%) developed an ischemic stroke. Of the other 94 patients, one suffered a nucleocapsular hemorrhage and 5 had cerebral ischemic complications. In these 5 patients, the duration of clamping was significantly longer (mean +/- SD, 16.4 +/- 1.1 versus 12.7 +/- 2.6 minutes; P = .0019), and the decrease of middle cerebral artery mean velocity on clamping was significantly greater (mean +/- SD, 56.4 +/- 4.9% versus 28.8 +/- 20.2%; P = .0031), while stump pressure was not significantly different. Microembolic signals were recorded in 70 patients (62.5%) and were not associated with cerebral ischemic complications. The 7 patients who developed cerebral ischemic complications had a significantly higher percentage of stenosis in the contralateral internal carotid artery (mean +/- SD, 82.0 +/- 17.8% versus 29.3 +/- 36.4%; P = .0018). CONCLUSIONS: The results of our study suggest that the major complications of carotid endarterectomy may be due to hemodynamic factors. Stump pressure alone is not a reliable indicator of hemodynamic changes that predict cerebral ischemia. Particulate microembolism may cause more subtle changes in cerebral parenchyma, but further studies are needed to clarify this point.     

Growth retardation and zinc nutrition

Based on a previous report of a zinc deficiency syndrome in children characterized by low hair zinc, anorexia, poor growth, and hypogeusia, 12 children attending a pediatric endocrinology clinic for growth retardation and judged as having short stature as a variant of normal (SVN) were evaluated as to their zinc nutriture to learn whether zinc deficiency was a contributory factor. None was found to have the above syndrome, although one child did have a hair zinc concentration below 70 mug/g. The mean hair zinc of the SVN subjects was lower than the hair zinc of 40 apparently normal adolescents, 131+/-37 mug/g vs. 168+/-44 mug/g (P less than 0.02), but there was no difference found in plasma levels of zinc or in taste acuity. In contrast, five patients with total growth arrest secondary to juvenile Crohn's disease (CD) were found to have multiple findings consistent with zinc deficiency including low plasma zinc, low hair zinc, or hypogeusia.     

Cardiovascular outcome in white-coat versus sustained mild hypertension: a 10-year follow-up study

BACKGROUND: The aim of this study was to compare the risk conferred by white-coat versus sustained mild hypertension for the development of cardiovascular disease. METHODS AND RESULTS: Patients (n=479) who underwent 24-hour intra-arterial ambulatory blood pressure monitoring on the basis of a persistently elevated clinic systolic blood pressure of 140 to 180 mm Hg were followed up for the development of subsequent cardiovascular events during a 9.1+/-4. 2-year period. White-coat hypertension, defined as a clinic systolic blood pressure of 140 to 180 mm Hg associated with a 24-hour ambulatory systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg, was present in 126 patients, and the remainder had sustained mild hypertension. A subgroup of patients without complications underwent follow-up echocardiography and carotid ultrasound. White-coat hypertensives were younger (44+/-12 versus 52+/-10 years, respectively; P<0.001) and had a significantly lower incidence of cardiovascular events (1.32 versus 2.56 events per 100 patient-years, respectively; P<0.001) than sustained hypertensives. Multivariate analysis revealed age (P=0.002), sex (P=0.007), race (P=0.001), smoking (P=0.005), and the presence of white-coat hypertension (hazard ratio, 0.29; 95% CI, 0.09 to 0.90; P=0.04) to be independent predictors of subsequent cardiovascular events. Subgroup analysis in patients without complications revealed a lower incidence of left ventricular hypertrophy and lesser degrees of carotid hypertrophy in the white-coat group. CONCLUSIONS: These findings indicate a relatively benign outcome in white-coat hypertension compared with sustained mild hypertension.     

The serum growth hormone-binding protein is reduced in young patients with insulin-dependent diabetes mellitus

Despite elevated serum concentrations of GH, longitudinal growth is stunted in a considerable number of children and adolescents with insulin-dependent diabetes mellitus (IDDM). To elucidate, whether reduced peripheral action of GH contributes to this phenomenon, GH-binding protein (GH-BP) activity was measured in 117 children and adolescents with IDDM (mean age 14.6 yr, range 4.5-28 yr) and 132 healthy controls (13.1 yr, 6.3-26 yr). Serum was incubated with 125I-GH, then chromatographed on a Sephacryl S200 column (1.8.100 cm), apparent binding of 125I-GH to GH-BP was corrected for the amount of endogenous GH present in the sample. GH-BP activity was significantly lower in IDDM patients, with a corrected binding of 16.8 +/- 0.6% compared to 21.3 +/- 0.7% in control children (mean +/- SE; P < 0.0001, Wilcoxon-test). Previous studies demonstrated that GH-BP is increased in healthy overweight children. In contrast, in IDDM children, GH-BP was reduced despite a moderate degree of overweight (z-score for weight: +0.94 +/- 0.12; mean +/- SE). Reduced serum GH-BP activity in IDDM children is further accentuated when compared to healthy children with a similar degree of overweight (22.8 +/- 0.5%; n = 44). Based on this novel finding, we conclude that decreased GH receptor density may explain reduced growth velocity despite increased secretion of GH in some IDDM children.