Assessment of detached podocytes in the Bowman's space as a marker of disease activity in lupus nephritis.

Podocyte damage is an important pathogenic component of glomerular disease progression. This study is a trial to clarify the value of counting and scoring the number of shed Bowman's space podocytes as an activity parameter of lupus nephritis, a trial that has not been conducted before. This study was performed on 42 female patients with the clinical diagnosis of lupus nephritis. Beside the routine stains tissue sections were stained by colloidal iron and anti podocalyxin for sialomucin. Podocytes in the Bowman's space were counted and scored. Thorough statistical work was carried out to correlate the podocyte scores with the morphological lesions of lupus nephritis. This study revealed significant association and correlation of shed Bowman's space podocytes with histopathological parameters of activity in different classes of lupus nephritis. We concluded that counting and scoring shed Bowman's space podocytes is statistically significant as a marker of disease activity in lupus nephritis. It can be one of the parameters of activity index but not of chronicity index.

Plasma endothelin-1 concentrations in children with cirrhosis and their relationship to renal function and the severity of portal hypertension.

BACKGROUND: Plasma endothelin-1 (ET-1) is a potent vasoconstrictor peptide involved in the pathogenesis of several disorders. Endothelin-1 concentrations are increased in adult patients with cirrhosis. However, little is known about ET-1 concentrations in children with cirrhosis. METHODS: Radioimmune assay was used to measure plasma ET-1 concentrations in 19 children with cirrhosis (8 patients with ascites, and 11 without ascites), and 11 age- and sex-matched healthy children. The plasma ET-1 concentrations were correlated with the mean blood pressure, creatinine clearance, and severity of portal hypertension, as measured by portal flow volume and portal flow velocity. RESULTS: Patients with cirrhosis and ascites had increased plasma ET-1 concentrations compared with patients who did not have ascites (6.8 pg/mL +/- 0.62 pg/mL vs. 4.6 pg/mL +/- 0.35 pg/mL; mean +/- SEM; < 0.01) and controls (3.6 pg/mL +/- 0.27 pg/mL; mean +/- SEM; < 0.0005). Plasma ET-1 concentrations were higher in patients with cirrhosis who did not have ascites compared with controls ( < 0.005). No significant differences were observed between concentrations of the patients with cholestasis and those without cholestasis (5.4 pg/mL +/- 0.52 pg/mL vs. 5.2 +/- 0.32 pg/mL; mean +/- SEM; = 0.1). Plasma ET-1 concentrations correlated positively with the mean blood pressure ( = 0.58; < 0.05) and negatively with renal function, as measured by creatinine clearance ( = -0.7; <0.005). However, no correlation was detected between ET-1 concentrations and portal flow volume ( = -0.02; = 0.4) or portal flow velocity ( = -0.16; = 0.4). CONCLUSIONS: Plasma ET-1 concentrations are increased in children with cirrhosis, with or without ascites, compared with controls. Patients with cirrhosis and ascites have increased ET-1 concentrations compared with those without ascites. The degree of increase does not relate to the severity of portal hypertension. This increase tends to maintain systemic blood pressure but is associated with a decrease in renal function.

Gastric myoelectrical activity in diabetics with and without diabetic autonomic neuropathy.

BACKGROUND/AIMS: The effects of diabetes mellitus on gastric myoelectrical activity has not been fully investigated. The aim of the present study was to investigate the pattern of gastric myoelectrical activity in noninsulin dependent diabetics, detected by electrogastrography in an attempt to clarify the relation between diabetic autonomic neuropathy and gastric myoelectrical abnormalities, if any. METHODOLOGY: The study was carried out on 34 noninsulin dependent diabetes (7 males, 27 females). Their age ranged from 35-60 years with mean age of 51.5 +/- 3.5 years. The EGG was recorded for 30 min in both the fasting and postprandial states, using an ambulatory EGG recording device (Digitrapper EGG, Synectics Medical). The adaptive spectral analysis method was used to assess the normality of the EGG. The EGG was defined as abnormal if: the percentage of normal slow waves (2.5-3.7 cycles/min) was below 70% during either the baseline or postprandial recording or there was a decrease in EGG peak power after the meal, or both. RESULTS: EGG abnormalities were detected in 13 patients (38.2%); 1 had tachygastria, 1 had bradygastria, 7 had dysrhythmias, and 4 had decreased EGG peak power after the meal. All diabetic patients with abnormal EGG suffer autonomic neuropathy. CONCLUSIONS: These results suggest that gastric myoelectrical abnormalities occur in a high proportion of noninsulin dependent diabetics and these abnormalities predominate in those patients with autonomic neuropathy.

Renal hemodynamic changes in children with liver cirrhosis.

To assess the sensitivity of duplex Doppler ultrasonography in detecting early impairment of renal function in childhood cirrhosis, intrarenal arterial pulsatility index (PI) and resistive index (RI) were measured in 10 ascitic and 11 non-ascitic children with liver cirrhosis and normal creatinine clearance and 10 age- and sex-matched controls. PI and RI were higher in ascitic than non-ascitic children [PI 1.54+/-0.4 vs. 1.1+/-0.2 (mean +/- SD), P=0. 006; RI 0.76+/-0.07 vs. 0.68+/-0.07, P=0.03). Non-ascitic patients had higher PI and RI than controls (P=0.002 and 0.0001, respectively). PI was inversely correlated with creatinine clearance (r=-0.54, P=0.01). A significant positive relationship was observed between both PI and RI and Child score (r=0.47, P=0.009; r=0.45, P=0. 01, respectively). However, no significant correlation was observed between PI and RI and portal hypertension. We conclude that renal vascular resistance indexes evaluated by duplex Doppler ultrasonography are increased in the non-ascitic phase of cirrhosis. Development of ascites is associated with a further increase in these indexes. The resistance indexes are best correlated with severity of hepatocellular dysfunction, assessed by Child score, but not with portal hypertension. Hence, monitoring these indexes, especially PI, is a non-invasive means of studying early renal hemodynamic alteration in childhood cirrhosis.

HLA-DQB1 and DRB1 alleles in Egyptian children with steroid-sensitive nephrotic syndrome.

Steroid-sensitive nephrotic syndrome (SSNS) of children has been associated with several HLA-DR and DQ alleles. To investigate this association in Egyptian children, 27 patients with SSNS were typed for HLA-DRB1 and DQB1 alleles using DNA polymerase chain-reverse hybridization technique. The results were compared with 121 healthy subjects for HLA-DRB1 and 59 subjects for DQB1 alleles. We found that: (1) patients have higher frequencies of both DQB1 *0601 (81.5% vs. 10.2% in controls, Pc=0.0001) and DRB1 *01 (44.4% vs. 3.3% in controls, Pc=0.00003). Their relative risks are significantly high [38.9, confidence interval (CI)=10.7-140.7, and 23.4, CI=6.7-81.9, respectively]; (2) the frequency of DRB1 *11 alleles was low in SSNS patients (3.75% vs. 32.2% in controls), but was not significant when P was corrected (P=0.005, Pc=NS). These findings suggest that DQB1 *0601 and DRBI *01 or closely associated unknown genes confer susceptibility to SSNS. However, further studies with larger numbers of patients are needed.

Congenital anomalies in infants with congenital hypothyroidism: is it a coincidental or an associated finding?

During the period between December 1988 and February 1995, a total of 279,482 newborn infants were screened in the regional neonatal screening program for congenital hypothyroidism (CH) in Riyadh province, Saudi Arabia. Eighty-one infants were confirmed to have CH giving an incidence of 1 in 3,450. Variable congenital anomalies, other than those of the thyroid gland, were present in 16 (19.8%). The anomalies most frequently encountered were congenital heart defects (7), unclassified multiple congenital anomalies (5) and Down's syndrome (2). The results of our study confirm this association, and emphasize the need to search for such anomalies in infants born with CH. Nationwide studies, however, on birth defects in the general population and those associated with CH are still needed to help us understanding the role of local genetic and environmental factors.

Congenital hypothyroidism: increased incidence in Najran province, Saudi Arabia.

Neonatal screening for congenital hypothyroidism using cord serum thyroid-stimulating hormone (TSH) was initiated in Najran health region in September 1990. A total of 30810 newborn infants were screened by April 1995. Of the 24 infants with abnormal thyroid function tests on recall, 22 had permanent primary congenital hypothyroidism (incidence; 1:1400) and in two male siblings transient congenital hypothyroidism (incidence; 1:15400) was proved on follow-up. There was a significantly higher incidence of dyshormonogenesis. Eight (57 per cent) of the 14 infants who were adequately studied thyroid scan revealed ectopic glands with increased 99mTc uptake, while thyroid ectopy and aplasia were present only in three (22 per cent) infants each. Furthermore, goiter was evident clinically in two other patients.

Sex reassignment: A challenging problem - current medical and islamic guidelines.

Sexual ambiguity is a complex and often confusing medical problem. In addition to the life-threatening adrenal crises which may accompany some forms, ambiguity of the genitalia may lead to incorrect sex assignment by parents and/or health personnel. Children who present to medical attention beyond the neonatal period constitute a challenging problem due to the grave consequences of this condition. Thirty cases in whom sex reassignment was indicated were seen at King Khalid University Hospital, Riyadh, over a 10-year period. Of these, 27 (90%) were genetic females (20 were 21- and seven were 11-hydroxylase deficient) and three (10%) were genetic males (two partial androgen insensitive and one 5alpha-reductase deficient). All genetic males who were incorrectly assigned as females accepted reassignment. But 9 out of 27 (33%) of the genetic females who were incorrectly assigned as males refused reassignment. Preference for male sex assignment, delayed diagnosis and sociocultural circumstances seem to be the contributing factors for refusal. A national consensus about this important issue strengthened by the existing religious recommendations in demanded.

Neonatal screening for congenital hypothyroidism in Riyadh: Analysis of six year's experience.

The regional screening program for congenital hypothyroidism (CH) in Riyadh Province was started as a pilot study in December 1988. By September 1990, the program covered all deliveries at the Ministry of Health (MOH) and King Saud University hospitals. The program utilizes cord serum thyroid-stimulating hormone (TSH) with a low recall rate of 0.1%. The average cost per specimen was SR 12 (US$ 3.20). Among 283,647 infants screened, 83 infants were confirmed to have CH (incidence 1:3417). In 17 infants, however, the diagnosis was not confirmed due to difficulties in recall. Eleven infants with cord serum TSH of more than 100 mU/L proved to be clinically and biochemically euthyroid at recall. Three of these were secondary to maternal proplthiouracil (PTU) therapy. The female to male ratio was 1.5:1. The majority of infants lacked clinical symptoms and signs of hypothyroidism. Thyroid scans showed the most common etiology to be thyroid ectopy (50%), followed by dyshormonogenesis (26%) and athyrosis (24%). Although there was no significant difference in the mean cord T4 values among the different groups, the mean T4 value at recall in the athyrotic group was significantly (P <0.001) lower than the cord results (14.8 versus 62.7) and that is of recall for the ectopic and dyshormonogenesis groups (14.8 versus 47.0 and 51.3 respectively0. There was bo significant difference in the mean TSH among the different groups in the cord and recall samples. Skeletal maturation was more delayed in the athyrotic group. The mean age at the time of recall was 16.4 days (range 4 to 64), and the mean age at the start of therapy was 17.8 days (range 5-64).

Congenital adrenal hypoplasia: A disorder frequently missed.

Congenital adrenal hypoplasia is a rare disease which is known to cause severe salt wasting in the neonatal period. In this report, we describe three patients from two different families who were seen at King Khalid University Hospital, Riyadh, Saudi Arabia. All patients presented with classical clinical, biochemical, hormonal and radiological findings of congenital adrenal hypoplasia. To the best of our knowledge, no similar cases were reported from this part of the world.

Ambiguous genitalia: comparative role of pelvic ultrasonography and genitography.

Ambiguous genitalia represents a true medical and social emergency which needs a multi-disciplinary team approach for elucidation. The paediatric radiologist plays an important role in defining the genital anatomy which remains one of the most important factors in sex determination. Aiming to compare the predictive value of pelvic ultrasonography and genitography in sex determination in patients with ambiguous genitalia, we retrospectively reviewed the medical records of 69 patients, 53 females and 16 males, where both procedures were employed. In female pseudohermaphroditism, the presence of a uterus with or without vagina was predicted in 46 (86.8%) patients by ultrasound compared with 44 (83%) patients in whom a genitogram revealed a vagina +/- uterus. In six (11.3%) patients, a genitogram revealed a male-type urethra. The combination of ultrasound and genitogram, however, was more sensitive and predicted the presence of a uterus with or without vagina in 52 (98.1%) patients. In male pseudo-hermaphroditism, there was no false positive by ultrasound, and a genitogram revealed a male-type urethra in 12 (75%) patients. In conclusion, although real time pelvic ultrasonography is less invasive than genitography, its yield in elucidating genital anatomy is comparable. The combination of both procedures is more informative and has a better yield.

Congenital adrenal hyperplasia in a referral hospital in Saudi Arabia: Epidemiology, pattern and clinical presentation.

Eighty-two children (30 males and 52 females) with congenital adrenal hyperplasia (CAH) were seen at King Khalid University Hospital (KKUH) over a 10-year period. Of these, 74 (90.2%) were Saudis and eight (9.8%) non-Saudis. Fifty-nine (72%) patients were 21-hydroxylase deficient. Of these, 56 (95%) had variable degrees of salt depletion. Nineteen (23.2%) patients had a deficiency of 11-ss-hydroxylase enzyme and four (4.8%) showed deficiency of 3-ss-hydroxysteroid dehydrogenase. The consanguinity rate was high (71.2%) and positive family history was documented in 45.8%. Thirty-nine infants deaths occurred within 25 families. The diagnosis was often delayed. Of the 52 females, 27 (52%) were initially assigned male sex. These results indicate the importance of physicians' awareness and the need for a neonatal screening program for early detection and appropriate management.

Growth hormone and IGF1 profile in short children with osteopetrosis.

Osteopetrosis is commonly associated with short stature. To identify the cause, 8 children with osteopetrosis and short stature were studied. One showed evidence of renal tubular acidosis, none showed evidence of anaemia, and all were clinically and biochemically euthyroid. Growth hormone profile was assessed using night sampling (8 patients), growth hormone provocative testing using insulin-induced hypoglycaemia (6 patients), and L-dopa-propranolol (8 patients). The mean nocturnal growth hormone values taken at 60 and 90 min after onset of sleep and at 4 a.m. were 5.5, 12.8, and 11.5 mu/L respectively. The peak stimulated growth hormone mean values with the insulin-induced hypoglycaemia (glucose 1.6-3.0 mmol/L, mean = 2.2) was 14 mu/L (range 7.3-24.5 mu/L) and with the L-dopa-propranolol was 25.6 mu/L (range 12.3-49 mu/L). IGF1 levels taken at 0 and 120 min of insulin-induced hypoglycaemia (0 min for L-dopa-propranolol), and at 120 min of L-dopa-propranolol, showed normal values for age. We conclude that: (1) growth hormone profiles in these children are normal; (2) tissue unresponsiveness to growth hormone and/or IGF1 is not likely to be the cause of short stature in children with osteopetrosis; and (3) osteopetrosis per se is not an indication for assessment of growth hormone status.

Childhood bacterial meningitis in Al-Baha province, Saudi Arabia.

A retrospective review of 71 paediatric patients admitted with bacterial meningitis to the King Fahad Hospital at Al-Baha, Saudi Arabia, during an 8-year period revealed a preponderance of males (67.6%) and young subjects with 88.7% being below 24 months of age. The commonest cerebrospinal fluid pathogens in the series were Haemophilus influenzae type B (HIB), Streptococcus pneumoniae and Group B-beta haemolytic streptococcus, which were responsible for 47.3, 34.5 and 9.1% of cases respectively. Neisseria meningitidis which is a major cause of meningitis in most other reports was uncommon in the present series, and was isolated from only two patients. All the children with Group B-beta haemolytic streptococcal meningitis were below 3 months of age while 96.2% of the children with HIB meningitis were younger than 2 years. Mortality was highest (40%) among the infants with Group B-beta haemolytic streptococcal meningitis. Six (23.1%) of the HIB isolated were resistant to ampicillin and two (7.7%) were resistant to both ampicillin and chloramphenicol. There is a need for greater emphasis on prevention through the use of available vaccines including the newly introduced conjugate vaccines against HIB which are capable of eliciting immune responses in infants as young as 2 months.