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In a double blind design, 1520 children aged < 10 years were individually randomised in vitamin A and placebo group in slums of Chandigarh. Children > 12, 6-12 and < 6 months of age received 200,000, 100,000, 500,000 I.U. of vitamin A respectively every 4 to 6 months during 15 months trial period. The prevalence of vitamin A deficiency was significantly reduced in vitamin A compared to placebo group during the follow-up period. In vitamin A group, incidence of diarrhoea and measles was significantly reduced but incidence of acute respiratory infections was not significantly different compared to control group. Risk of death was also significantly less in vitamin A group. Therefore, promotion of vitamin A rich diet or supplementation with synthetic vitamin A at 4-6 month interval should be a priority in populations where risk of vitamin A deficiency is high.

A novel copper-binding protein was identified in the liver supernatant (100,000 x g) of Indian childhood cirrhosis (ICC), purified to apparent homogeneity and characterized [corrected]. Purified major copper-binding protein (MCuBP) is solely responsible for binding about 35% of the total supernatant copper. Elution profile of ICC liver supernatant on Sephadex G-75 column chromatography showed three peaks. About 60% of the total supernatant copper was resolved in peak II, whereas zinc content was insignificant in this peak. But peak II was almost missing in a gel elution profile of control liver supernatant. The control group included cases of various liver diseases viz. neonatal hepatitis, septicemia, and mixed nodular cirrhosis. Copper-binding proteins of peak II further purified on ion-exchange chromatography and elution profile showed that peak II was a MCuBP with high copper-binding capacity (10 g atoms/mol of native protein). SDS-PAGE of this protein also revealed the existence of a single band with molecular mass of about 50 kD. UV spectra of MCuBP showed the maximal absorbance at 254 nm. Unlike the classical metallothionein, the amino acid composition of MCuBP revealed the presence of aromatic amino acids and higher content of glutamic acid and aspartic acid followed by glycine and serine. The ratio (0.3) of basic amino acids to acidic amino acids strongly indicates that it is an acidic protein. The cysteine content in this protein was insignificant, which further corroborates the possibility that the acidic amino acids might be prominent candidates for binding copper. Thus, the 50-kD MCuBP apparently makes a major contribution to the total copper-binding activity in ICC liver cytosol and may play a significant role in hepatic intracellular copper accumulation.

Wilson's disease is an autosomal recessive disorder of copper accumulation in various organs, with most common clinical manifestations such as hepatic, neurological, and renal dysfunctions. Serum copper and ceruloplasmin in Wilson's disease were significantly lower as compared to normals, controls, and relatives of Wilson's disease patients, whereas marked hypercupriuria (145+/-7 microg/24 h) was observed in Wilson's children only. A good correlation (r=0.92) was found between non-ceruloplasmin-bound copper and 24-h urinary copper excretion in Wilson's disease patients. Further, copper studies among the different phenotypes of Wilson's disease revealed substantially low serum ceruloplasmin and a marked hypercupriuria in Wilson's disease children associated with renal tubular acidosis as compared to the patients with either hepatological or neurological manifestations. Serum ceruloplasmin levels in 14 patients of Wilson's disease were between 14 and 20 mg/dL. These patients of Wilson's disease were confirmed by measuring liver biopsy copper, which was about nine times higher than normal hepatic copper content. During the family screening by copper studies, four asymptomatic siblings were diagnosed for Wilson's disease. These subjects were then started on D-penicillamine therapy because presymptomatic treatment prevents progression of the disease complications.

To investigate the chronological changes in conjunctival epithelium after supplementation with a massive oral dose of vitamin A, conjunctival impression cytology (CIC) with transfer was carried out repeatedly among 200 children aged 6-120 months in a randomized, double-blind, placebo-controlled study in Chandigarh (India). Significant conversion to normal CIC started 71-80 d after vitamin A supplementation and by 101-110 d conversion had taken place in all children. Compared with the placebo group, plasma retinol concentration at 100 d post-supplement was found to be significantly higher in the vitamin A-supplemented group P = 0.04. This study demonstrates that CIC responds to a massive oral dose of vitamin A 3-4 months after supplementation. These findings should guide future studies and evaluations in which CIC is used to assess response to vitamin A interventions.

Objective: To study percentile distance growth pattern of Body Mass Index (BMI) of Punjabi male and female infants., Design: Longitudinal., Setting: Growth Clinic., Subjects: 154 Punjabi infants (Male 86; Female 68), aged birth-12 months., Follow-Up: Nude body weight and crownheel length of all babies at birth and whereafter, were measured at monthly age intervals with time tolerance to +/-3 days by the same investigator upto 12 months of life., Results: Mean (+/- SD) values for BMI measured 12.2 +/- 1.40 kg/m2 and 16.5 +/- 1.40 kg/m2 at birth and 12 months, respectively in male infants. The corresponding figures for female infants were 12.5 +/- 1.60 kg/ m2 and 16.5 +/- 1.50 kg/m2. A rapid increase in BMI values amongst infants of both sexes between birth to about six months followed by flattening of curves upto 12 months of age indicates an age dependent nature of BMI during first half of infancy in comparison to latter half during which these demonstrated stable trend. These findings are in contrast to those of the western infants who showed a regular increase in BMI throughout the first year of life. Sex differences were not significant at majority of the age levels., Conclusions: Percentile grids presented for BMI represent a normal, healthy and well-nourished infant population which can be used to assess the adiposity status of infants of the two sexes during the first year of life.

In order to establish a method usable in the field for diagnosis of pre-clinical vitamin A deficiency, conjunctival impression cytology with transfer (CICT) was used in 200 normal slum children aged 6-120 months in Chandigarh, India. Conjunctival impressions taken on cellulose acetate paper were transferred to glass slides which were fixed in ethanol and stained with alcian blue and carbol fuchsin. Sixty samples of cellulose acetate paper were preserved after transfer of impression and were stained later. Transfer was complete in forty-eight samples and in the other twelve it was incomplete. Conjunctival impressions on paper and slide of these twelve cases were comparable. At a plasma retinol concentration of < 0.70 mumol/l measured by HPLC the sensitivity, specificity and positive predictive values of CICT were 90.59%, 100% and 100% respectively. Compared with conventional conjunctival impression cytology, CICT is less time consuming, cheaper and comparable in validity. It is thus more suitable than the conventional method for mass screening.

Indian Childhood Cirrhosis (ICC) is a disease of abnormal copper metabolism commonly characterized by swelling and degeneration of liver cells along with the presence of orcein staining deposits of copper. Hepatic copper content of ICC patients was about 43 fold higher than those of control subjects. The data on sub-cellular distribution of copper revealed massive accumulation of Copper (73%) of total cell copper) in the nuclear fraction (455 micrograms Cu/g tissue nuclei). On further distribution of copper in nuclear fraction, the enrichment of copper in heterochromatin and euchromatin of ICC nuclei was found to be 48 and 15 fold higher over control fractions respectively. The ultra-violet spectra of heterochromatin and euchromatin isolated from ICC nuclear fraction showed a broad absorption maxima as compared to controls. Further, A260/A280 ratio was markedly lower in heterochromatin and euchromatin of ICC liver in comparison to controls. An antioxidant enzyme, catalase activity was also significantly reduced in ICC liver as compared to control. Further, DNA fragmentation studies indicated that there was significantly increased DNA fragmentation in ICC liver. Collectively, these findings suggest that massive accumulation of copper in nucleus and decrease in catalase activity was associated with DNA fragmentation in hepatocyte of ICC disease.

Background and Methods: D-Xylose and 51Cr-labelled ethylenediaminetetraacetic acid (EDTA) absorption tests were evaluated in control and Escherichia coli heat-stable, heat-labile, and both heat-stable and heat-labile enterotoxin-induced diarrhoea in mice., Results: The absorption of D-xylose was greatest 45 min after its ingestion in both control and enterotoxin-treated groups. There was a significant (p < 0.01) decrease in xylose absorption at 45 min in all the three experimental groups as compared with the control group, which may be due to change in membrane fluidity and hence change in membrane permeability, whereas 51Cr-EDTA absorption was at its maximum 15 min after its ingestion in both control and experimental groups. And there was a significant (p < 0.05) increase in 51Cr-EDTA absorption in enterotoxin-treated groups as compared with the control group., Conclusions: These results suggest a change in tight junctional permeability which may be due to change in the cytoskeletal microfilaments. Both these tests hence show that E. coli enterotoxin-induced diarrhoea results in absorption and permeability changes.

The objective of this prospective study was to examine the effect of fluid restriction on body water and the outcome of children with acute meningitis. Fifty consecutively hospitalized children with acute meningitis, divided into two groups (A, without hyponatremia; and B, with hyponatremia), were randomly assigned to receive either normal maintenance (M) or restricted (R subgroup) (65 to 70% of M subgroup) fluids during the first 48 hours. Total body water, extracellular water (ECW), serum and urinary sodium and plasma and urinary osmolality were measured at admission and after 48 hours. In both groups children receiving restricted fluids showed a significant decrease in the mean total body water and ECW whereas body water remained unchanged in those on maintenance fluids. Children having an ECW reduction of 10 ml/kg or more in 48 hours had a significantly lower intact survival (10 of 28, 36%) than those with < 10 ml/kg or no reduction of ECW (15 of 22, 64%) (P < 0.05). The mortality was also higher in the former (7 of 28, 25%) than in the latter (2 of 22, 9%). On multiple stepwise regression analysis, ECW volume at admission (partial r2 0.20), ECW loss in 48 hours (partial r2 0.13) and plasma osmolality at admission (partial r2 0.22) were significantly related to outcome. We conclude that fluid restriction does not improve the outcome of acute meningitis. Indeed a decrease in ECW volume at 48 hours increases the likelihood of adverse outcome.

The pathophysiological mechanism of Campylobacter jejuni (enterotoxigenic) induced secretory diarrhoea remains least understood. To investigate the mechanism(s) involved, the unidirectional fluxes of Na+ and Cl- were measured across the C. jejuni live culture infected and control (non infected) rat ileum (unstriped), in vitro by Ussing technique under short circuit conditions, in the presence or absence of: Ca2+ ionophore A23187 (5 microM), 1-verapamil (100 microM), calmodulin (CaM) antagonist W-7 (100 microM), dantrolene (25 microM), protein kinase C (PKC) activator PMA (100 ng/ml) and H-7 (60 microM), selective inhibitor of PKC. There was net absorption of Na+ and enhanced Cl- secretion in infected animals while in control animals there was net absorption of Na+ and marginal secretion Cl-.Ca2+ ionophore A23187 mimicked the effects of C. jejuni infection whereas 1-verapamil had significant antisecretory effect on Na+ and Cl- secretion in infected animals. In vitro measurement of undirectional 45Ca fluxes in Ussing chamber experiments revealed net absorption of Ca2+ in infected rat ileum as compared to net secretion of Ca2+ in control rat ileum. These observations clearly indicate that there is increased stimulation of Ca2+ uptake from extracellular milieu to the enterocytes during C. jejuni-induced diarrhoea. The intracellular calcium levels (Ca2+]i (as measured by fluorescent probe Fura-2AM) were found to be raised significantly (P < 0.0001) in enterocytes isolated from C. jejuni infected ileum as compared to the enterocytes from control ileum. The observed increase in [Ca2+]i in enterocytes isolated from C. jejuni live culture supernatant treated rat ileum further shows the involvement of enterotoxin in diarrhoeal process. Dantrolene decreased significantly C. jejuni-induced net Na+ and Cl- secretion but it could not reverse it to absorption suggesting the partial involvement of Ca2+ mobilised from intracellular stores in mediating secretion. W-7 failed to inhibit the C. jejuni-induced net Na+ and Cl- secretion. In addition the CaM activity estimated in intestinal microvillar core remained same in both the control and C. jejuni infected animals. This indicates that C. jejuni-induced diarrhoea is not mediated through the activation of Ca(2+)-CaM complex pathway of the Ca2+ messenger system. The PKC activator PMA, induced net secretion of Na+ and Cl- in the control animals but it could not enhance further the C. jejuni-induced Na+ and Cl- secretion, suggesting that there is overlapping effect of PMA and C. jejuni live culture infection.(ABSTRACT TRUNCATED AT 400 WORDS)

The epidemiology of acute poisoning in children aged 0-15 years hospitalized between 1970-1989 was retrospectively investigated. Two hundred and seventeen children were admitted during this period with 134 in 1980-1989 vs 83 in 1970-1979. Two distinct patterns were observed: accidental poisoning in under 11's and adult pattern and self poisoning in children over 11's. More children belonged to urban areas (72.3%) as compared to rural areas. In both decades more than half of children belonged to middle income group followed by lower income group and least to upper income group. The overall mortality was low (12.5%), with majority of deaths (78%) occurring in older children. The incidence of kerosene ingestion was noticed to have dropped by more than half between 1980-1989 as compared to 1970-1979 (14.9% vs 42%). The study highlights the unacceptable high rate of preventable accidental poisoning in young children and suicide and parasuicide in older children (11-15 years age group).

Objective: To report 10 children younger than 10 years of age with benign cutaneous polyarteritis nodosa (BCPAN)., Methods: Ten children aged 1.25-10 years (mean 4.7 years; M:F = 7:3) were admitted with an unusual vasculitis. The clinical features, laboratory investigations, treatment and follow up data were analysed., Results: Clinical features of these patients included: fever (10), peripheral gangrene (eight), livido reticularis (four), ulceration, nodules and vesiculobullous lesions alone or in combination (10), black necrotic patches over limbs and trunk (three), and arthralgia or swelling of large joints (seven). Cryoglobulinaemia was transient in three children, lasting for eight months in one of them. Histopathology of the skin lesions revealed vasculitis of small and occasionally medium sized blood vessels in nine of the 10 children. Possible association of BCPAN was noted with diphtheria-pertussistetanus immunisation (one), drugs (two), streptococcal infection (two), wasp sting (one), and falciparum malaria (one). The clinical course was interspersed with remissions and exacerbations. Response to corticosteroids alone occurred in seven patients, while three children needed cytotoxic drugs in addition. In a follow up of 5.6 years (mean) no evidence of systemic involvement was noted., Conclusions: A rare form of vasculitis, BCPAN, is reported in children. The features that distinguished our patients from those reported earlier were onset in the first decade of life and higher incidence of peripheral gangrene.

Unidirectional fluxes of Na+, Cl- and 3-O-methyl-D-glucose (3-MG) were measured in vitro across Campylobacter jejuni live culture-infected and control rat ileal short-circuited tissues by the Ussing Chamber technique. Net secretion of Na+ and enhanced secretion of Cl- ions was observed in the infected animals (P < 0.001, n = 6) as compared to the net absorption of Na+ and marginal secretion of Cl- ions in the control animals. There was a significant decrease in the mucosal-to-serosal fluxes of 3-MG in C. jejuni-infected rat ileum. The specific Na+,K(+)-ATPase activity when measured biochemically in the membrane-rich fraction of enterocytes was found to be significantly lower (58%) in the infected group as compared to the control group (P < 0.001). Our results therefore suggest that infection with an enterotoxigenic C. jejuni inhibits the Na+,K(+)-ATPase activity in rat enterocytes. The impairment of Na+,K(+)-ATPase activity thus appears to induce a secondary change in Na+,Cl- and 3-MG transport in vitro in rat ileum.

Macromolecular absorption of gliadin, a wheat protein and alpha lactalbumin, a milk protein was evaluated in control and Escherichia coli enterotoxin (heat-stable, heat-labile, and both heat-stable and heat-labile enterotoxin) treated mice. The peak concentration of gliadin and lactalbumin was two hours and three hours after their ingestion, respectively. There was also a significant increase (p < 0.01) in the absorption of both the proteins in all the three toxin treated groups compared with the control group. These results suggest that intestinal permeability and macromolecular absorption changes after E coli infection.

In this prospective study to evaluate usefulness of ultrasonography for early diagnosis and monitoring of complications of acute pyomeningitis, we performed serial sonographic examinations of skull in 50 infants (with open fontanelle) with proven pyomeningitis. One or more abnormal sonographic findings were detected in 32 infants. These were echogenic sulci (26%), ventriculomegaly with some or other complication (26%), brain abscess (20%), ventriculitis (14%), subdural effusion (6%) and cerebral edema (10%), and were detected mostly after the first week of illness. Ultrasonographic findings were in complete agreement with CT scan diagnosis of ventriculomegaly, ventriculitis, solitary brain abscess and cerebral edema. However, sonography missed cases of subdural effusion (2 out of 5), multiple brain abscesses (1 out of 2), and cerebral infarction (all the four), which were detected on CT Scan. Serial sonographic findings were useful in documenting progressive increase in ventricular size in all the 13 infants with ventriculomegaly and monitoring response to anti-edema therapy in 5 infants with cerebral edema. Sonography is a useful tool for diagnosis of complications of pyomeningitis after the first week of illness, and for monitoring the progress of ventriculomegaly.

The transmucosal fluxes of Na+ and Cl- were studied in Giardia lamblia-infected mice in the presence or absence of dantrolene (1-(5(p-nitrophenyl)furfurilidene-amino) hydantoin sodium hydrate). There was net secretion of Na+ and Cl- in infected animals, while in control animals there was net absorption of these ions. The addition of dantrolene resulted in significant net increase in absorption of Na+ and Cl- in control and experimental groups. Further, mouse intestinal epithelial cells were labelled with [32P]Pi and then treated with G. lamblia trophozoites and their excretory secretory products separately. The optimum time for inositol triphosphate formation was 15 min in control enterocytes as well as in treated enterocytes. A plateau was formed at higher concentrations. Since raised inositol triphosphate levels mobilize Ca2+ from intracellular stores and dantrolene traps Ca2+ within intracellular calcium stores, the present study thus suggests that intracellular calcium stores are involved in G. lamblia-induced diarrhoea in mice.

To determine clinical signs that can predict pneumonia (confirmed by radiography) in infants under 2 months of age, 101 infants with pneumonia and 150 with an upper respiratory infection (but not pneumonia) were studied. Ten infants with pneumonia and 15 with an upper respiratory infection did not have the cough and/or difficult (or rapid) breathing that are recommended as 'entry criteria' by the World Health Organisation (WHO). The remaining infants met WHO entry criteria; in them sensitivity and specificity of respiratory rate > or = 60/min and/or severe chest indrawing to diagnose pneumonia was 85% and 97% respectively. Addition of four non-specific signs (stopped feeding well, looked sick, temperature < or = 38 degrees C, and abdominal distension) to respiratory rate > or = 60/min and/or chest indrawing for case identification resulted in a 7% gain in sensitivity but 22% loss of specificity. Addition of nasal flaring improved the sensitivity by 6% without loss of specificity. However, the non-specific signs were the only clue to diagnosis in five infants weighing < or = 2500 g. At age < 7 days, a weight < or = 2500 g and cyanosis were associated with significantly higher risk of mortality. These findings support the use of a respiratory rate > or = 60/min and/or chest indrawing for identification of pneumonia, and suggest addition of nasal flaring to the criteria for case identification in infants under 2 months with cough and/or difficult or rapid breathing.

The paper reports a syndrome in which oblique placement of one or both the pinnae on face was found to co-exist with congenital anomalies of heart like VSD, PDA and Tetralogy of Fallot, etc. Although clinically discernible in 90% of the subjects, objective evidence of obliquity of pinna was documented by photogrammetry. The values for the ear inclination in subjects categorized clinically as normally placed pinna were 7.9 degrees +/- 3.39 degrees with range 2 degrees-17 degrees. In contrast, subject where the pinna was clinically categorized as oblique had mean AEI 16.5 degrees +/- 5.81 degrees with a range 5 degrees-33 degrees. Eighteen of the 20 subjects with oblique pinna were demonstrated to have some congenital anomaly of heart as indicated by clinical and echocardiographic examination. In contrast, in subjects with normally placed pinna only 3 out of 34 possessed clinical heart defects. Presence of oblique pinna indicates a thorough search for undetected heart defects.

In a prospective study to determine simplified clinical signs predictive of pneumonia in children between 2 months and 5 years of age, and to test the validity of the signs recommended by the World Health Organization, clinical findings were correlated with X-ray evidence of pneumonia in 854 children, 400 with pneumonia and 454 with upper respiratory infections (no pneumonia). A respiratory rate of > or = 50/min in infants 2-6 months of age, > or = 40/min in children 7-35 months, and > or = 35/min in children > or = 36 months was the best discriminator of radiological evidence of pneumonia. Use of a respiratory rate of > or = 50/min instead of > or = 40/min resulted in a 14%, 19% and 32% loss of sensitivity with little gain in specificity in the age groups 7-11 months, 12-35 months and > or = 36 months, respectively. The age-specific respiratory rate (recommended by WHO) and/or chest indrawing, history of rapid or difficult breathing and/or chest indrawing, and nasal flaring were also sensitive and specific indicators of pneumonia in almost all the age groups studied.

Attitudes of 120 mothers of spastic children aged 2-12 yrs were assessed by using Mother's Attitude Scale. Attitudes of mothers towards spastics were highly influenced by the severity of handicap and IQ of the child (r < 0.74). Mother's education, family income, occupational status, type of habitat had significant but low correlation with her attitudes (0.23 to 0.35). Age, sex of the child and type of family did not influence attitudes. Study group mothers (rural or urban) have better attitudes towards spasticity compared to control group mothers. This difference was more discernible among mothers belonging to age group below 30 years of age. The study emphasizes the necessity of constant counselling of mothers so that their attitudes may improve and help in more effective care of the child.

Calcium has been reported to play an important role in regulating the intestinal electrolyte transport via Ca2+/calmodulin (CaM) and/or protein kinase C (PKC) systems. The role of Ca2+, CaM and PKC in the pathogenesis of Campylobacter jejuni-induced fluid accumulation was studied in vivo in ligated rat ileal loops. Calcium ionophore A23187 (5 microM) and PKC activator, phorbol-12-myristate-13-acetate (PMA, 100 micrograms kg-1) when injected alone induced fluid accumulation in the control loops. However, these modulators did not enhance further C. jejuni-induced fluid accumulation when injected along with C. jejuni live culture in the experimental loops. Both 1-verapamil (100 microM) and PKC antagonist, H-7 (15 micrograms/ml-1) significantly reduced C. jejuni-induced fluid accumulation (P < 0.001). The effect of CaM antagonist W-7 (60 microM) on C. jejuni-induced fluid secretion was not significant (P > 0.05). Our findings suggest that both Ca2+ and PKC appear to be the important second messengers involved in the stimulation of intestinal fluid accumulation in C. jejuni infection.

Twenty three patients with primary immunoglobulin(Ig) deficiency were seen during the last ten years. Nine had hypogamma globulinemia (hypo-Ig) and the rest, selective Ig deficiency. Most were in pediatric age group. There was preponderance of males with only one female. Clinical symptoms pertaining to gastrointestinal and sinupulmonary infections were most common. Complete absence of B cells was not observed in any patient with hypogammaglobulinemia. They could be typed as physiological in one patient, X-linked immunodeficiency in 2 patients and common variable immunodeficiency in the remaining six. Three patients with selective IgA deficiency were above 20 years of age. Two had only secretory IgA deficiency, confirmed by jejunal fluid examination and the rest had both secretory and serum IgA deficiency. Low IgM was seen in one patient. We see a spectrum of immunoglobulin deficiencies varying from subtle defects like absence of secretory IgA only, to severe depletion of all immunoglobulins. Therapy is still not ideal due to economic reasons.

Noncirrhotic portal hypertension is a common cause of upper gastrointestinal bleeding in infants, children, and adolescents in India. More than one major bleeding episode, severe hypersplenism, presence of fundal varices, rare blood group, remoteness from the hospital, and patient noncompliance to sclerotherapy formed the main indications for shunt surgery. One hundred four cases of noncirrhotic portal hypertension (age range, 18 months to 20 years) underwent side-to-side lienorenal shunt (SSLR) without splenectomy in a period of 15 years. Splenic veins varying in diameter from 4 to 18 mm and in length from 3 to 4 cm were skeletonized through the root of transverse mesocolon and a shunt of at least 1.5 cm in diameter was constructed. At a mean follow-up of 54 months, 87% of shunts were patent, 13% of shunts were blocked, and 2% were inadequate. Ten percent of the children had rebled, all of whom had a blocked shunt. Growth and development was normal and no patients developed encephalopathy. There was a good correlation between shunt patency on splenoportography and endoscopic disappearance of varices, reduction in the size of spleen and splenic pulp pressure, and improvement of hypersplenism.

Thirty-five children with G6PD deficiency, who presented with acute intravascular haemolysis, were evaluated to define its aetiology, clinical features and ultimate outcome. All were boys with ages ranging from 6 months to 12 years. Pallor of abrupt onset and passage of cola-coloured urine were universal presenting symptoms. Incriminating factors responsible for haemolysis include hepatitis (7), malaria (4), bacterial sepsis (3) and drug intake (24), with more than one predisposing condition existing in some children. Marked elevations in serum bilirubin, coinciding with intravascular haemolysis, was a feature in all the seven children with hepatitis. Azotaemia was noted in 20 patients, of whom 14 did not have oliguria. All four children with malaria presented with protracted renal failure. Therapy focused on maintaining a high urine output in those without oliguria. A total of 15 peritoneal dialyses and five haemodialyses were required in six patients with acute renal failure, all of whom were oliguric. Supportive therapy consisted of blood transfusions and treatment of the predisposing diseases. Thirty-two children recovered completely while three died, the cause of death being severe anaemia and congestive cardiac failure, malaria with oliguric renal failure and hepatic encephalopathy, respectively.

With the object of studying the profile of infective endocarditis in Indian children younger than 16 years of age, a retrospective study of 37 patients with infective endocarditis admitted to this hospital between January 1984 and December 1990 was carried out. There were 26 boys and 11 girls (aged 2-16 years (mean (SD) 10.3 (3.8)). Eighteen (48.6%) patients had underlying congenital heart disease, 13 (35.1%) had associated rheumatic heart disease whilst the remaining six had no pre-existing heart disease. All six patients with a normal heart and infective endocarditis had preceding extra-cardiac bacterial illnesses (epididymitis and orchitis in one, pneumonia in five). Blood cultures were positive in only 16 (43.2%): Staphylococcus aureus was grown in nine, Streptococcus viridans in six and Candida albicans in one. Sixteen (43.2%) of the 37 patients died owing to worsening cardiovascular haemodynamics, uncontrolled septicaemia and our inability to offer emergency surgery. The profile of infective endocarditis in developing countries is different from that in Europe and the United States of America, and the disease carries a very high mortality.

Percentile growth charts for head circumference of Punjabi infants (male 86 and female 68) measured serially at monthly intervals during the first year of life are presented. Besides, constancy of sample size and strict adherence to time tolerance limit of +/- 3 days, on the day of monthly measurements other factors considered responsible for the natural smooth course of the percentile grids are highlighted. The presented data would enable easy detection of infants with abnormal course of head growth.

Triceps skinfold thickness measured in ten adults aged 19 to 50 yr by a Holtain skinfold caliper, was compared with subcutaneous fat thickness obtained on cross-sections of the left upper arm by computerized axial tomography (CAT). The thickness of subcutaneous fat was measured on CAT scan film directly with the inbuilt computer graphic technique. The measurements taken on CAT scan film were found to be significantly higher (by 21-45%; P less than 0.001) than those by the skinfold calipers. Our findings suggest that skinfold calipers may not be very accurate tools for the assessment of body fat in human beings. Therefore, its use in the determination of body composition, for which great precision is required calls for re-thinking.

We have investigated the direct effect of copper on malondialdehyde formation in rat isolated hepatocytes. Copper was found to decrease the cell viability with concomitant production of malondialdehyde in a time related manner. In addition the protein kinase C activator, PMA, was found to have a synergistic effect with copper on rat hepatocytes. These results indicate that protein kinase C may be important in mediating hepatotoxicity after exposure to copper.

The cases of three young children (mean age 5.8 years) in whom fulminant hepatic failure and acute intravascular haemolysis were the presenting manifestations of Wilson's disease are reported. Although diagnosis was made ante-mortem and chelation therapy instituted, the course was relentlessly fatal in all three cases. This presentation of Wilson's disease at such a young age is noteworthy.

The transmucosal fluxes of Na+ and Cl- were studied in Giardia lamblia infected mice in the presence or absence of phorbol-12-myristate-13-acetate (PMA), the activator of protein kinase C (PKC) or 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H-7), the inhibitor of PKC or Ca(2+)-calmodulin. There was net secretion of Na+ and Cl- in infected animals, while in control animals there was net absorption of these ions. The addition of ionophore or PMA resulted in net secretion of Na+ and Cl- in the control group while in the infected group there was no change in the fluxes of these ions. The selective potent inhibitor of protein kinase C, H-7, reversed the secretion of Na+ and Cl- in infected group to absorption. The addition of PMA and Ca(2+)-ionophore together in the infected group had a partial additive effect. This study suggests that G. lamblia induced fluid secretion involves protein kinase C and further protein kinase C acts in synergism with calcium.

Unidirectional Na+ and Cl- fluxes were studied in rats treated with S. typhimurium enterotoxin (S-LT). There was net absorption of Na+ and Cl- in the control group, while in the toxin treated animals there was net secretion of Na+ and Cl- (P less than 0.001). There was no change in the transport of D-glucose in the toxin treated group as compared to the control animals. The Na+, K(+)-ATPase pump was unaltered in the S-LT treated animals (198.67 +/- 11.23 nmoles Pi/mg protein/min) as compared to the control group (189.93 +/- 10.09 nmoles Pi/mg protein/min). There was no change in the unidirectional fluxes of Ca+2 in the S-LT treated animals as compared to the control animals, suggesting no change in the permeability of the S-LT treated intestinal membrane to Ca+2.

One hundred children with beta-thalassemia major were studied prospectively. A one time analysis of serum samples was carried out for a battery of hepatitis B viral markers viz., HBsAg, anti-HBs and anti-HBc. Seven mutually different serological patterns were observed. The commonest profile seen in 49 patients was a combined seropositivity for anti-HBc and anti-HBs indicating past HBV infection with persisting immunity. Definite evidence of active HBV infection (seropositivity for HBsAg and/or HBeAg) was demonstrated in 10 cases, six of these were HBsAg positive. Anti-HBc positivity alone was detected in 17 patients. The remaining 24 children were seropositive for anti-HBs alone suggesting a possible passive transmission of anti-HBs through blood transfusion.

Enteric fever caused by Salmonella typhi resistant to all the standard first-line antibiotics is emerging as a major problem in developing countries. Fifteen such culture-proven cases were treated with ceftriaxone (6), cefotaxime (5) or ciprofloxacin (4). The earliest defervescence occurred with ceftriaxone (mean 3.3 days). Clinical cures were obtained with all three drugs with only one child having a relapse. Ciprofloxacin, by virtue of its cost and an oral route of administration, is the ideal choice in a developing country.

Previous studies have led to the hypothesis that the gross hepatic copper storage characteristic of Indian childhood cirrhosis (ICC) is due to the early introduction of animal milk feeds which have been contaminated with copper from brass household utensils. Amongst the families of 100 cases of ICC, the incidence of ICC in children born after dietary advice had been given (1/86) was significantly lower than in older siblings (12/125). This study attempted to document the incidence of ICC and the usage of brass before and after an intervention programme in Pune District advising against this pattern of infant feeding. The study encountered numerous difficulties in data gathering, but documented a fall in ICC prevalence resulting in its virtual disappearance in Pune District. This contrasted with an unchanged incidence in Chandigarh. Although a fall in brass usage was seen in Pune District, this was actually a spontaneous sociological change rather than a result of health education.

The unidirectional fluxes of Na+ and Cl- were studied in Salmonella typhimurium enterotoxin-treated rats. There was net secretion of Na+ and Cl- in toxin-treated animals, while in control animals there was net absorption of these ions. In the presence of the Ca(2+)-ionophore, there was net secretion of Na+ and Cl- in the control group, while the ionophore enhanced the secretion of these ions in experimental animals. The calcium channel blocker, verapamil, decreased the secretion induced by salmonella toxin, but could not reverse the secretion to absorption. There was no difference in the net absorption of Ca2+ in both the control and experimental animals. There was a significant increase in the intracellular free calcium concentrations in enterocytes isolated from toxin-treated rat intestines as compared to that in enterocytes isolated from control animals. In the presence of PMA (phorbol-12-myristated-13-acetate) there was net secretion of Na+ and Cl- in the control group, while in the experimental group there was no change in the fluxes of these ions. The selective, potent inhibitor of protein kinase C, H-7 (1-(5-isoquinolinylsulphonyl)-2-methylpiperazine) reversed the secretion of Na+ and Cl- in the toxin-treated group to absorption. The addition of indomethacin also inhibited the secretion induced by salmonella toxin, but failed to reverse it to absorption. However, the addition both H-7 and indomethacin to the experimental group had a partial additive effect. These studies demonstrate that the Salmonella enterotoxin-mediated fluid secretion involves protein kinase C and the arachidonic acid metabolites and perhaps does not involve the extracellular calcium pools.

To explore the relationship between vitamin A deficiency and persistent diarrhea among young children, we studied the vitamin A status of 23 children greater than 5 years of age with persistent diarrhea by performing conjunctival impression cytology (CIC) and the relative dose-response test (RDR) as a measure of liver reserve of vitamin A. The control group consisted of 23 age- and sex-matched children who were otherwise healthy in whom CIC was performed and fasting plasma retinol values were determined. The criteria for vitamin A deficiency in CIC were paucity of goblet cells and scanty, abnormal epithelial cells. None of these children had ocular manifestations of vitamin A deficiency. Among the children with persistent diarrhea, CIC characteristic of vitamin A deficiency was found in 17 (group 1) and CIC results were normal in six (group 2). In group 1, the serum retinol levels were 1 +/- 1 microgram/dl, and RDR was 88 +/- 14. In group 2, the serum retinol levels were 8 +/- 4 micrograms/dl (p less than 0.001) and the RDR was 16 +/- 12 (p less than 0.001). In the control group, the CIC results were normal in all the children and the plasma retinol levels in these children were 19 +/- 8 micrograms/dl. In conclusion, 17 of 23 children with persistent diarrhea had abnormal CIC results, significantly low serum retinol levels, and significantly high RDR results, although they had not yet manifested xerophthalmia.(ABSTRACT TRUNCATED AT 250 WORDS)

Eight children who satisfied all the diagnostic criteria of classic Indian childhood cirrhosis were treated with d-penicillamine. Clinical recovery in a 3- to 12-month period was accompanied histopathologically by accentuation of micronodules with regression of hepatocytic degenerative changes, Mallory's hyaline, pericellular fibrosis, lobular inflammation, and disappearance of hepatocytic copper staining protein. The nodules in the posttreatment biopsies were so small as to be categorized as "micronodular cirrhosis." In one case clinical recovery was associated with an almost normal liver histology after passing through a micronodular phase. This report is the first documentation of the histologic sequence of changes in Indian childhood cirrhosis on d-penicillamine treatment.

The unidirectional fluxes of Na+, Cl- and Ca2+ across the small intestinal epithelium of normal and Giardia lamblia-infected mice were studied in vitro in short-circuited tissue. Net secretion of Na+ and Cl- was observed in infected animals, whereas in non-infected (control) animals there was net absorption of Na+ ions and marginal secretion of Cl- ions. In infected animals, net absorption of Ca2+ was observed as compared to little secretion observed in control animals. Although the presence of Ca(2+)-ionophore in the medium resulted in a net secretion of Na+ and Cl- in controls, it could not cause any change in the fluxes of these ions in infected animals. Verapamil, a calcium channel blocker, reversed the effects of infection and Ca(2+)-ionophore. Further W7 (n-(6-aminohexyl)-5 chloro-1-naphthalene sulphonamide), a calmodulin antagonist, also reversed the effects of infection. The addition of the neurotoxin, tetrodotoxin caused net absorption of Na+, Cl- and net secretion of Ca2+ in the control group, but it could not produce any effect on the fluxes of these ions in the infected group. These findings demonstrate that, in G. lamblia infection, the secretion of Na+ and Cl- is associated with an increase in absorption of Ca2+ and an increase in calmodulin activity in intestinal microvillar core. These findings further suggest that the enteric nervous system plays a marginal role in Giardia infection.

Immune status of 22 patients of ataxia telangiectasia was studied over a period of 8 yr (mean age of patients: 9.5 +/- 3 yr; 9 of 22 were siblings). Low T-cell number was observed in 14 of 19 patients but the response to PHA challenge done in 10 patients was normal and migration inhibition to BCG antigen was positive in 6 of 6 patients. IgM defect was seen in 2 out of 18 patients and serum IgA was deficient in 10 out of 18 patients. Salivary IgA was also absent in these children. Four children had high spontaneous NBT reduction. None of the patients had lymphoma, leukemia or any other malignancy at the time of presentation. Candida killing was normal in all patients. The presenting feature related to the CNS in almost all children and gross infections were not seen.

Five strains of Salmonella typhimurium were examined to determine the parameters of virulence. The virulent species significantly resisted the macrophage bactericidal activity (p less than 0.05). The chemiluminescent (CL) response was studied to determine the level of Oxygen-free radicals (OFR) generated and the antioxidant enzymes superoxidase dismutase (SOD), catalase and glutathione peroxidase were assayed to determine the antioxidant mechanism of S. typhimurium to subvert these microbicidal pathways. The levels of the various enzymes were correlated with the virulence (as determined by LD50) and the ability of the microorganisms to induce diarrhoea. Oxygen free radical (OFR) generation elicited by macrophages, in the presence of virulent and avirulent salmonellae was not statistically significant (p greater than 0.05). No correlation was found between the levels of the antioxidant enzymes and the LD50 values. Thus the oxygen-dependent pathways do not appear to play a role in the pathogenesis of salmonellosis, and do not specify the virulence of the microorganism. Immunological and biological assays revealed the virulent strain to be more toxigenic than the avirulent strain. Therefore, the basis of differing virulence in S. typhimurium may be the ability to make and release more toxin in vivo.

We studied the reliability of some simple clinical signs in the diagnosis of paediatric lower respiratory infection (LRI). Seventy infants and 148 children attending the outpatient department for cough of less than 15 days duration were studied. These children were examined by a paediatrician, and a proforma of simple clinical signs of LRI was filled in. A chest X-ray was taken on the same day and interpreted by a radiologist who did not know the clinical features of the patient. Clinical signs were then compared with X-ray changes, the latter being taken to indicate the presence of LRI. Respiratory rates of greater than 40/min in infants and greater than 30/min in older children were found to be the best indicators of LRI as revealed by a receiver-operating-characteristic curve. Chest indrawing and nasal flaring were found to be associated with moderate and severe disease.

In a prospective controlled evaluation of steam therapy, in severe acute lower respiratory tract infection (ALRI) requiring hospitalization, 16 cases of bronchiolitis and 20 cases of pneumonia were assigned alternately to receive steam therapy in a cloth tent (Study Group); others served as controls. Respiratory status was assessed at the time of admission and subsequently at 6 hourly interval for 48 hours. No advantage of steam therapy could be identified in children with pneumonia. Bronchiolitis patients on steam therapy, as compared to the controls, showed a significant decrease in respiratory distress within first 24 hours after hospitalization and took significantly shorter time for recovery from the distress. The study patients also showed a tendency for rapid improvement in hypoxemia. Further critically controlled studies with a larger sample size are warranted.

Psychosocial problems faced by parents and other family members were studied in 50 families with a physically disabled child (PD group), 50 with a mentally retarded child (MR group) and 50 with a healthy child (control group). A semi-structured questionnaire assisted interview and standardized scales were used to measure social burden, marital adjustment and maternal neuroticism. Families with disabled children perceived greater financial stress, frequent disruption of family routine and leisure, poor social interaction, and ill effects on their physical and mental health as compared to families of control children. The overall social burden scores were significantly higher in both the groups with disabled children as compared to controls (mean scores PD 17.8, MR 14.6, C 0.72, p less than .001), and showed a significant inverse correlation with the socio-economic and educational status of parents. The neuroticism scores were also significantly higher (PD 23.7, MR 19.0, C 9.6, p less than .01), and the marital adjustment scores lower (PD 75, MR 79, C 86, p less than .01) in families with disabled children. Appropriate management of these problems should be part of rehabilitation programmes.

Children with persistent diarrhea may be at a higher risk of developing vitamin A deficiency. Impression cytology of the conjunctiva has been shown to be a simple and objective diagnostic test for detection of early, physiologically significant vitamin A deficiency. We studied, changes in conjunctival impression cytology using millipore HAWG filter paper in 25 children aged less than 5 years suffering from persistent diarrhea, who had no ocular manifestations of vitamin A deficiency (Group I). Twenty five age matched healthy children constituted the control group (Group II). Seventeen of the 25 children with persistent diarrhea (68%), showed the following abnormalities: (i) the shape of the epithelial cells were abnormal, and (ii) goblet cells were absent. The study could be repeated after 2 weeks of administration of vitamin A in 7 children. Reappearance of PAS-positive mucous glycoproteins and presence of normal epithelial cells was demonstrated in all 7 children retested. This test can prove to be of significant value in assessment of response to vitamin A therapy. This study shows that children with persistent diarrhea appear to be at high risk for developing vitamin A deficiency, which can be detected by the technique of conjunctival impression cytology. This is a cheap and reliable method of detecting preclinical vitamin A deficiency which can be performed by a pediatrician in the office laboratory.