Usefulness of a national registry of alpha-1-antitrypsin deficiency. The Spanish experience

Severe alpha-1-antitrypsin (AAT) deficiency, phenotype Pi ZZ, is a rare condition with an estimated prevalence of 1/4500 individuals in Spain. Given this low prevalence, it seems useful to accumulate all the information derived from the care of these patients. In this context, the Spanish Registry of patients with AAT deficiency was founded in 1993; its main objectives were to establish guidelines adapted to our country for the treatment and management of AAT-deficient patients, offer expert support to physicians all over the country treating these patients, and provide technical support on the determination of Pi phenotyping and genotyping of individuals suspected of being AAT-deficient. From 1993 to January 1998 the number of enrollees increased from 48 to 223, of which 216 were Pi ZZ. Seventy-three per cent were male and only 31.5% were never smokers, mean age was 46 years (SD = 13 years) and mean FEV1 53% predicted (SD = 31%). 83% were index cases who, compared with non-index cases, were older (49 +/- 11 vs. 35 +/- 13 years, P < 0.001), more likely to have a smoking history (85% vs. 47%, P < 0.01) and displayed more severe impairment in pulmonary function (FEV1% = 40% +/- 19% vs. 96% +/- 23%, P < 0.001). Augmentation therapy was administered to 129 patients (58%). Treated patients had more severe impairment in pulmonary function than the untreated (FEV1% = 40% +/- 21% vs. 72% +/- 32%, P < 0.001) and were more likely to be index cases (81% vs. 43%, P < 0.001). Characteristics of the patients included are similar to those described for other Registries. The Registry has extended knowledge of the disease throughout the country and has established local guidelines for treatment and follow-up. It may be a valid database for future co-operation in international initiatives.     

Peritoneal membrane transport function in children receiving long-term dialysis

Accurate characterization of peritoneal solute transport capacity in children has been hampered by a lack of standardized test mechanics and small patient numbers. A standardized peritoneal equilibration test was used to study 95 pediatric patients (mean age, 9.9 +/- 5.6 yr) receiving chronic peritoneal dialysis at 14 centers. Patients were divided into four age groups (< 1, 1 to 3, 4 to 11, 12 to 19 yr) for analysis. Each patient received a 4-h peritoneal equilibration test with an exchange volume of 1100 mL/m2 per body surface area. Dialysate to plasma (D/P) ratios for creatinine (C) and urea (U) and the ratio of dialysate glucose (G) to initial dialysate glucose concentration (D/D0) were determined. Mass transfer area coefficients (MTAC) were calculated for the three solutes and potassium (P). The mean (+/- SD) 4-h D/P ratios for C and U were 0.64 +/- 0.13 and 0.82 +/- 0.09, respectively. The mean 4-h D/D0 for G was 0.33 +/- 0.10. D/P and D/D0 ratio results were similar across age groups. Normalized (for body surface area) mean MTAC (+/- SD) values were as follows: C, 10.66 +/- 3.74; G, 12.93 +/- 5.02; U, 18.43 +/- 4.02; and P, 14.02 +/- 3.94. Whereas a comparison of the normalized MTAC values across age groups with an analysis of variance showed significant age group differences only for glucose (P = 0.001) and potassium (P = 0.036), analysis by quadratic regression demonstrated a nonlinear decrease with age for C (P = 0.016), G (P < 0.001), and P (P = 0.034). In summary, evaluation of D/P and D/D0 ratios obtained from a large group of children in a standardized manner reveals values that are similar across the pediatric age range and not unlike the results obtained in adults. In contrast, normalized MTAC values of young children are greater than the values of older children, possibly as a result of maturational changes in the peritoneal membrane or differences in the effective peritoneal membrane surface area.     

Brainstem auditory evoked potentials and visually evoked potentials in young patients with IDDM

OBJECTIVE: To investigate whether young IDDM patients develop central nervous dysfunction and to establish a possible relationship with various disease parameters. RESEARCH DESIGN AND METHODS: Thirty-two patients, aged 13.5 +/- 2 years, with disease duration of 6 +/- 2.6 years and age of onset of 7.7 +/- 3.2 years (group 1), and 21 patients with short-term disease, age 9.7 +/- 3.5 years, duration of disease < 2 years and age of onset of 9.4 +/- 3.3 years (group 2) were compared with age- and sex-matched control subjects. Exclusion criteria were clinical signs of neuropathy, retinopathy, nephropathy, or hearing impairment. Neurophysiological studies included auditory and visually evoked potentials (EPs). RESULTS: Patients in group 1 revealed increased P100 latencies of visually EPs (103.4 +/- 4.5 vs. 96.8 +/- 3.7 ms) and interpeak latencies I-V of auditory EPs (4.16 +/- 0.10 vs. 3.99 +/- 0.09 ms) and had abnormal latencies (values outside 2.5 SD) in 37%. However, short-term patients (group 2) had results within normal limits compared with control subjects. In group 1, longer disease duration and younger age at onset correlated with an increase of P100 latency (P < 0.001) and IPL I-V (P < 0.001). Patients with a history of severe hypoglycemic episodes had increased latencies compared with patients without hypoglycemia (P < 0.05). Furthermore, metabolic control during the last 2 years was related to P100 latencies (P < 0.05). CONCLUSIONS: EPs noninvasively detect subclinical central nervous system involvement in children and adolescents with IDDM. Most important risk factors are duration of disease and frequency of severe hypoglycemia.     

Chronic exposure to environmental lead in Chilean infants

BACKGROUND: In Chile, there are several sources of environmental lead exposure. However, the few studies about lead levels in Chilean infants, do not allow to establish the prevalence of high lead levels in this population. AIM: To measure blood lead levels in nursing infants, living in rural and urban areas, from birth until two years of age. SUBJECTS AND METHODS: Newborns from public maternity hospitals in Santiago and a rural area were selected for the study. An umbilical cord blood sample was obtained at birth and venous blood samples thereafter, every 6 months until the age of 24 months. Lead levels were measured by atomic absorption spectrophotometry. Atmospheric lead was measured simultaneously every week in Santiago and the rural area. RESULTS: Three hundred twelve children from Santiago and 113 from the rural area completed the 24 months follow-up. The mean lead exposure for infants living in Santiago and in the rural area was 1.23 +/- 0.66 and 0.19 +/- 0.15 micrograms/m3 respectively (p < 0.001). Mean blood levels were always higher in infants from Santiago, compared to those from the rural area. At 24 months, 4.5% of children from Santiago and 0.7% of children from the rural area had blood lead levels over 10 micrograms/dl. Significant risk factors for high lead levels were recent painting of the house where the infant lives, eating soil, biting banisters and familiar labor exposure to lead. CONCLUSIONS: Infants living in an urban area and exposed to increased atmospheric lead levels have higher blood lead levels than infants living in a rural area.     

Pure pancreatic juice from patients with chronic pancreatitis has an impaired antibacterial activity

This case-control study was designed to evaluate the potential advantages and disadvantages of video-assisted thoracoscopic surgery for right middle lobectomy in children. Ten children (6.1 +/- 3.0 yr, mean +/- SD) who underwent right middle lobectomy under videoscopy were compared with 10 controls matched for age (6.8 +/- 3.5 yr) and operated by thoracotomy (muscle-sparing technique) during the same period by the same surgeon. Operating time was significantly longer in the videoscopy group than in the thoracotomy group (146 +/- 28 mn vs 100 +/- 27 mn, P < 0.001). Minimum oxygen saturation values were significantly higher in the videoscopy group whereas oxygen requirements did not differ between groups. Incidence of postoperative respiratory complications (mainly atelectasis) was similar in the two groups. No difference in postoperative analgesic requirements in the postoperative period was demonstrated. No real benefit or disadvantage of videoscopy over standard thoracotomy could be observed in this retrospective case-control study.     

Idiopathic tumoral calcinosis involving the cervical spine

An increase in parasitaemia is not uncommon after initiation of treatment for Plasmodium falciparum malaria, but its exact significance is unknown. The time-course of parasitaemia was assessed retrospectively in 33 patients with severe imported malaria. In 19 patients (group 1) mean parasitaemia (+/- SEM) fell promptly after starting quinine treatment, from 24.9 +/- 4.1% on day 0 to 9.7 +/- 2.3% on day 1 and 1.8 +/- 0.7% on day 2. In 14 other patients (group 2), parasitaemia did not change significantly or increased, with mean parasitaemia (+/- SEM) of 9.5 +/- 2.1% on day 0, 17.2 +/- 2.6% on day 1, and 3.7 +/- 1.8% on day 2. Simplified acute physiology scores on admission (mean +/- SEM) were 17.4 +/- 1.4 in group 1 and 11.7 +/- 1.0 in group 2 (P = 0.006). The mean number of complications of malaria per patient (+/- SEM) was 2.9 +/- 0.5 in group 1 and 1.6 +/- 0.3 in group 2 (P = 0.046). Two group 1 patients died. Initially, more than 95% of peripheral blood parasites were tiny and small rings in both groups, and this distribution was unchanged on day 1, suggesting that the parasitaemia increase in group 2 was not due to release of sequestered mature parasites. In severe falciparum malaria, a rise in parasitaemia after treatment initiation may be of favourable prognostic significance and should not lead to aggressive therapeutic approaches such as exchange transfusion.     

Neutralizing antibodies to Escherichia coli Vero cytotoxin 1 and antibodies to O157 lipopolysaccharide in healthy farm family members and urban residents

An enzyme-linked immunosorbent assay (ELISA) to detect antibodies to Escherichia coli O157 lipopolysaccharide (LPS) was developed with sera from 63 children with confirmed recent E. coli O157 infection and from 256 age-stratified urban controls. The median ELISA values for control and case sera were 0.05 (interquartile range, 0 to 0.20; mean +/- standard deviation [SD], 0.15 +/- 0.22) and 1.41 (interquartile range, 1.11 to 1.59; mean +/- SD, 1.41 +/- 0.53), respectively (P < 0.001). With a breakpoint of 0.59 (mean ELISA value of the control sera + 2 SDs), the assay had a sensitivity, specificity, and positive and negative predictive values of 95, 94, 80, and 98%, respectively, for recent E. coli O157 infection. The O157 LPS assay and Vero cytotoxin (VT) 1-neutralizing-antibody (NAb) assay were used to compare the relative frequencies of O157 LPS antibodies and VT1-NAbs in an age-stratified urban population from Toronto, Ontario, Canada, and in 216 healthy family members from dairy farm in southern Ontario. The frequency of O157 LPS antibodies was about threefold higher in dairy farm residents (12.5%) than in urban residents (4.7%) (P < 0.01). Similarly, the frequency of VT1-NAbs was about sixfold higher in dairy farm residents (42.0%) than in urban residents (7.7%) (P < 0.001). These findings are consistent with a greater level of exposure of dairy farm residents to VT-producing E. coli (VTEC) strains. The high rate of seropositivity to VT1 in farm residents probably reflects the booster effect of repeated VTEC exposures and argues against a sustained generalized immunosuppressive effect of VT1. Seroepidemiological studies may help in assessing the level of exposure of different populations to VTEC strains.     

Characterization of gonadotropin-releasing hormone analogs based on a sensitive cellular luciferase reporter gene assay

Blood samples and questionnaire background data were collected from 96 children (age 2-14 years) living in urban, suburban, or rural areas with varying traffic intensity and industrial lead pollution in Uruguay. Spot samples of tap water were collected from the homes of 44 children, and samples of top soil were taken from seven areas. Samples of air-borne dust were collected in central and suburban Montevideo. Blood lead concentrations (B-Pb) in children ranged between 47 and 191 (mean 96) micrograms/L and exceeded in 36% of the children 100 micrograms/L, the intervention level adopted by the United States Centers for Disease Control. Lead in tap water ranged from 0.2 to 230 (mean 15) micrograms/L and exceeded in 39% of the samples the maximum level recommended by WHO, 10 micrograms/L. Lead pipes were used in parts of the water supply systems. Lead in air varied between different locations from 0.15 to 1.7 micrograms/m3, highest in the very center of Montevideo. The median soil lead ranged from 6 to 2100 micrograms/g and was highest in industrially polluted areas. At multiple regression analysis, B-Pb was significantly associated only with age (P = 0.032) and traffic intensity at school (P = 0.045). No significant impact on B-Pb of lead in water or soil could be established.     

Sternal osteomyelitis

The aim of this study was to determine and compare lead concentrations in breast milk between urban and rural women. Colostrum from 51 women living in the city of Thessaloniki (exposed to increased air lead concentration, 0.54 micrograms/m3) and from 40 women living in rural areas (exposed to significantly lower air lead concentrations) was analyzed by atomic absorption spectrometry. Urban women showed slightly higher lead concentrations (mean +/- SD: 0.090 +/- 0.029 micrograms/ml) than rural women (mean +/- SD: 0.084 +/- 0.024 micrograms/ml). This difference was not statistically significant. These results suggest that the lead content of human milk is not influenced by the concentrations of this environmental pollutant in the air.     

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.     

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.     

Spontaneous 24-hour growth hormone profiles in prepubertal small for gestational age children

To evaluate spontaneous GH secretion in terms of both secretory rate and pulsatile pattern in prepubertal children born small for gestational age (SGA) and still short (below -2 SD scores) at or after 2 yr of age, 24-h GH profiles were investigated in 106 such patients (75 boys and 31 girls; mean age, 7.3 +/- 0.3 yr), 14 of whom (10 boys and 4 girls) had Silver-Russell syndrome. The 24-h secretion of GH was compared with that in 2 reference populations of prepubertal children born at an appropriate size for gestational age (AGA): 179 short healthy children (143 boys and 36 girls; mean age, 10.2 +/- 0.2 yr) and 73 children of normal stature (54 boys and 19 girls; mean age, 10.4 +/- 0.3 yr). Plasma GH concentrations from the 24-h profiles were transformed to GH secretion rates by means of a deconvolution technique. For the SGA children, the mean GH secretion rate was 0.3 U/24 h, with a positive correlation with age, whereas for the reference groups it was higher, 0.5 U/24 h for the short children (P < 0.05) and 0.7 U/24 h for the children of normal stature (P < 0.001). Interestingly, the GH secretion rate correlated positively with weight for height, expressed as the SD score, in girls born SGA (r = 0.40; P < 0.05), whereas an inverse correlation was found for the short AGA girls (r = -0.44; P < 0.05). The mean baseline GH level in the SGA children correlated negatively with age (r = -0.53; P < 0.01), with the highest values found for children younger than 6 yr of age. On the average, 8 GH peaks/24-h period were found in all groups of children, and using Fourier time-series analyses, a similar rhythmicity was found in all groups. In the SGA group, the children younger than 6 yr of age had more GH peaks with lower amplitudes than the older children. It is concluded that children born SGA and still short at or after 2 yr of age spontaneously secrete less GH than healthy children of short stature born AGA. Both of these subgroups of prepubertal short children, however, secrete less GH than children of normal height. This finding might in part explain the growth failure in SGA children. Moreover, in the youngest SGA children (2-6 yr of age) there was another pattern of GH secretion, with a high basal GH level, a low peak amplitude, and a high peak frequency.(ABSTRACT TRUNCATED AT 400 WORDS)     

Survival after accidental poisoning with a triple lethal dose of paraquat (Gramoxon)

Anti-Helicobacter pylori antibodies were determined in 157 institutionalised Cantonese children, mean age 9.5 +/- 3.9 (SD) years, with profound neurodevelopmental disabilities. Eighty-seven (55.4%) were H. pylori seropositive compared with four of 50 (8%, P > 0.0002) of an age-matched control group, mean age 7.2 +/- 4.3 (SD) years. Eight of 15 seropositive children with a recent history of upper gastrointestinal bleeding underwent endoscopy and in all cases gastric infection with H.pylori was confirmed. Anthropometric data from institutionalised children revealed marked malnutrition but showed no significant difference between seropositive and seronegative children. Disabled children receiving long-term residential care in Hong Kong are confirmed to be at increased risk of H.pylori infection.     

CENP-G: a new centromeric protein that is associated with the alpha-1 satellite DNA subfamily

Lead is a highly toxic metal, the main source of which is contamination from combustion of unleaded petrol. The aims of this work were to detect the degree of lead exposure in a large sample of children; determine the relationship between blood lead levels (BPb) and age, sex, habitat and season of the year; and correlate BPb with zinc protoporphyrin (ZPP) values. A cross-sectional study was carried out. Blood from routine extractions drawn at our centre was used. BPb and ZPP were measured by atomic absorption spectrophotometry and haematofluorimetry, respectively. We analysed 1158 blood samples from children. BPb (mean +/- SEM): 0.22 +/- 0.04 mumol l-1. Correlation BPb-age: BPb = 0.19 + 0.086 x age (months), r = 0.129, P < 0.0001. BPb was greater in boys (0.23 +/- 0.007 versus 0.20 +/- 0.006 mumol l-1, P < 0.0002). No differences were observed between habitats (urban versus rural). BPb were higher in the warm months (0.24 +/- 0.013 versus 0.21 +/- 0.007 mumol l-1, P < 0.0001). Prevalence of lead intoxication (BPb > 0.48 mumol l-1) was 4.2%. No differences in prevalence were found among the different groups. The correlation between BPb and ZPP showed r = 0.0969, P = 0.0024. Utility for screening: sensitivity of 53.7% and specificity of 59.3% (cut-off point of 60 mumol ZPP mol-1 haem). We can conclude that lead exposure in children in our sample was in the range reported in similar studies in other areas and countries, and below the toxic limit. None of the factors analysed significantly influenced lead intoxication prevalence. There was no good correlation between ZPP and BPb in our samples and the ZPP cut-off point used did not present good specificity and sensitivity values.     

Quantification of creatinine kinetic parameters in patients with acute renal failure

BACKGROUND: Urea kinetic modeling (UKM) and creatinine (Cr) kinetic modeling (CKM) are used in the nutritional evaluation of end-stage renal disease (ESRD) patients. Both the UKM-derived normalized protein catabolic rate (nPCR) and the CKM-derived estimate of lean body mass (LBM) may also provide important information in critically ill acute renal failure (ARF) patients. Estimation of LBM may be particularly useful as previous data demonstrate that malnutrition adversely influences outcome in ARF patients. METHODS: Eleven critically ill ARF patients (age 52 +/- 21 years; mean +/- SD) treated with continuous venovenous hemofiltration (CVVH) were the study group. They were analyzed at steady state with a single-pool variable-volume model that determined the creatinine generation rate (GCr) by a methodology that we have previously described. RESULTS: The CVVH ultrafiltrate production rate was 913 +/- 49 ml/hr, yielding a blood Cr clearance of 15.2 +/- 0.9 ml/min and a steady state serum Cr of 3.4 +/- 1.7 mg/dl. Daily creatinine generation normalized to body wt (creatinine index: CI) was 6.3 +/- 0.8 and 10.6 +/- 3.0 mg/kg/day for females (N = 4) and males (N = 7), respectively (P < 0.05). Estimated mean LBM was 30.0 +/- 2.0 and 41.2 +/- 7.0 kg in females and males, respectively (P < 0.05), while the same parameter normalized to body wt was 0.50 +/- 0.05 and 0.52 +/- 0.10, respectively. These values are substantially lower than those previously reported for both normal and ESRD patients. Regression analysis demonstrated both GCr (r2 = 0.96; P < 0.001) and LBM (r2 = 0.96; P < 0.001) were significantly correlated with steady state serum Cr in a linear manner. However, no significant correlation (r2 = 0.06; P = 0.24) between nPCR and CI was observed. CONCLUSIONS: These data suggest critically ill ARF patients have severe somatic protein depletion. This malnourished state is likely due to deficits established prior to the development of ARF, such as those secondary to underlying chronic illnesses or prolonged hospitalization, and deficits related to acute hypercatabolism. Quantitative assessment of malnutrition in ARF patients with this CKM-based methodology may permit a better understanding of predisposing factors and, consequently, facilitate the development of interventions designed to prevent malnutrition in these patients.     

Outcome of differentiated thyroid cancer diagnosed in pregnant women

The clinical features and outcome of thyroid cancer in 61 pregnant women (mean age, 26.0 +/- 5.9 SD yr) and in 528 female, age-matched controls who were not pregnant (mean age, 26.3 +/- 5.9 SD yr) were compared. Median follow-up was 22.4 and 19.5 yr [P = not significant (NS)] in the two groups, respectively. The thyroid nodule was asymptomatic and discovered on routine examination more often in the pregnant women (74%) than in controls (43%, P < 0.001); other clinical and tumor features were similar in the two groups. Most of the pregnant women underwent thyroidectomy after delivery (77%) or during the second trimester of pregnancy (20%). Near-total thyroidectomy was done in 43 (73%) of the pregnant women and 265 (59%) of the controls (P = NS), and nearly the same proportion of both groups (30% and 25%, respectively) were treated with 131I postoperatively. Outcome in the pregnant women and controls, respectively, was: cancer recurrence 9 (15%) and 107 (23%, P = NS); distant recurrences 1 (2%) and 12 (3%, P = NS), and cancer deaths 0 and 6 (1.2%, P = NS). Outcomes were similar when surgery was done during or after pregnancy, despite a longer delay in treatment of the latter (1.1 +/- 1.0 vs. 16.1 +/- 19.7 months, P < 0.001). This study suggests that the prognosis of differentiated thyroid cancer is the same in pregnant women and nonpregnant women of the same age, and that the diagnosis and treatment of thyroid cancer occurring during pregnancy can be delayed until after delivery in most patients.     

Group B streptococcal meningitis in adults: report of twelve cases and review

Group B streptococcus (GBS) is the leading etiologic agent of bacterial meningitis and sepsis during the neonatal period, but it is an infrequent cause of meningitis in adults. We report 12 episodes of group B streptococcal meningitis in adults and review 52 cases reported in the literature. A total of 24 men and 40 women were included in the study; the mean age (+/- SD) was 49.2 +/- 20.5 years (range, 17-89 years). All the patients had cerebrospinal fluid cultures positive for GBS. Eighty-six percent of the patients had comorbid conditions, 50% had a distant focus of infection, and blood cultures yielded GBS for 78.7%. The overall case-fatality rate was 34.4% (22 patients). Factors associated with a poor outcome were advanced mean age (+/- SD) (61.5 +/- 17.4 years vs. 42.8 +/- 19.2 years; P = .0003) and the presence of complications on admission (P = .0001). Seven percent of survivors had neurological sequelae. Group B streptococcal meningitis in adults has become increasingly frequent in recent years; it tends to occur in patients with severe underlying conditions and is associated with a high case-fatality rate. Factors associated with a poor prognosis are advanced age and the occurrence of neurological and extraneurological complications.     

An ovarian leiomyoma: a case report

OBJECTIVES: To investigate the dynamic parathyroid response to rapidly induced, sustained hypocalcaemia in patients with acute malaria and in healthy volunteers. DESIGN: Serum intact parathormone (PTH) concentrations were measured on samples taken before and during a variable-rate tri-sodium citrate infusion designed to 'clamp' the whole blood ionised calcium concentration 0.20 mmol L-1 below baseline for 120 min. SUBJECTS: Six Malaysian patients aged 17-42 years with acute malaria, four of whom were restudied in convalescence, and 12 healthy controls aged 19-36 years. MAIN OUTCOME MEASURES: Whole-blood ionised calcium and serum intact PTH concentrations. RESULTS: The mean (SD baseline ionised calcium was lower in the malaria patients than in controls (1.09 +/- 0.06 vs. 1.18 +/- 0.03 mmol L-1, respectively; P = 0.01) but PTH concentrations were similar (3.0 +/- 1.8 vs. 3.3 +/- 1.3 pmol L(-1); P = 0.33). Target whole-blood ionised calcium concentrations were achieved more rapidly in the controls than the patients (within 15 vs. 30 min) despite significantly more citrate being required in the patients (area under the citrate infusion-time curve 0.95 (0.25 vs. 0.57 +/- 0.09 mmol kg-1; P < 0.01). The ratio of the change in serum PTH to that in ionised calcium (delta PTH/ delta Ca2+), calculated to adjust for differences in initial rate of fall of ionised calcium, was similar during the first 5 min of the clamp (132 +/- 75 x 10(-6) vs. 131 +/- 43 x 10(-6) in patients and controls, respectively, P > 0.05), as were steady-state serum PTH levels during the second hour (7.0 +/- 2.2 pmol L-1 in each case). Convalescent patients had normal basal ionised calcium levels but the lowest serum intact PTH levels before and during the clamp, consistent with an increase in skeletal PTH sensitivity after treatment. CONCLUSIONS: There is a decreased ionised calcium 'set point' for basal PTH secretion but a normal PTH response to acute hypocalcaemia in malaria. Skeletal resistance may attenuate the effects of the PTH response but patients with malaria appear relatively resistant to the calcium chelating effects of citrated blood products.     

Severe malaria in children in Togo

BACKGROUND: The definition of severe malaria is no longer limited to cerebral malaria, but is as well extended to other clinical forms of the disease. This work analyses epidemiological, clinical and evolutive aspects of severe malaria in Togo. PATIENTS AND METHODS: This study included 549 children, aged from 0 to 15 years, hospitalized in 1994-5 in the pediatric department of the Lome-Tokoin University Teaching Hospital for severe malaria as defined by World Health Organization (WHO) criteria. RESULTS: The hospitalization frequency was 7.44%; the maximum frequency was from 1 to 5 years of age, but 6.56% of patients were more than 10 years old. The most frequent clinical form was that of severe anemia, followed by cerebral complications, as seen in many African countries. The death rate was 18.94% and the proportional mortality was 8.21%; 2.73% of the patients had neurological sequelae (behaviour disturbances in five cases, aphasia in four, hemiplegia in three, mumbling in one, oculomotor paralysis in one, and cerebellar ataxia in one). Hypoglycemia was fairly frequent (11.6%) and was associated with a poor prognosis. CONCLUSION: It is possible to improve severe malaria prognosis in Africa by insisting not only on better equipment in intensive care wards, but also on improved and early management of hypoglycemia.     

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.