Sivarajan Venugopal

Immediate hypersensitivity in colon of children with chronic Trichuris trichiura dysentery

There are few data on mucosal immune responses to intestinal helminths in human beings, especially those involving the IgE system, which is thought to be important in parasite expulsion. We sought evidence of an immediate hypersensitivity reaction in the colon of children with chronic dysentery due to Trichuris trichiura. 28 children with Trichuris dysentery syndrome (TDS) were compared with 16 control children (with no TDS or worms visible on colonoscopy). All children were aged 1-11 years. Rectal biopsy samples were taken before and after expulsion of the worms by means of mebendazole treatment. Children with TDS had significantly greater numbers than controls of mast cells (mean [SD] 10.9 [1.3] vs 3.9 [0.6]% of all cells; p less than 0.0003) and of cells with surface IgE (median [range] 11.1 [7.5-11.6] vs 1.0 [0-1.5]%; p less than 0.001) in the subepithelial region of the mucosa. On electronmicroscopy, degranulating mast cells were prominent in parasitised children. In culture, rectal biopsy samples from parasitised children showed high rates of spontaneous histamine release, but only low rates of antigen-specific release. After treatment, spontaneous histamine release was significantly reduced and antigen-specific histamine release could be provoked. Thus, an IgE-mediated immune mucosal response to a helminth infection does occur in human beings but is not sufficient to cause appreciable parasite expulsion.

ROLE OF SPLENECTOMY IN HOMOZYGOUS SICKLE CELL DISEASE IN CHILDHOOD

60 Jamaican children with homozygous sickle cell (SS) disease underwent splenectomy, 14 for prophylaxis against recurrent acute splenic sequestration and 46 for treatment of sustained hypersplenism. Age at operation varied from 9 months to 16 years. Patients were followed up for 1 month to 27 years (median 6 years), with a total of 369 years of patient-observation. None of the 3 patients who died, at ages 2 1/2, 6 1/2, and 21 years, had received prophylaxis against infection. Overwhelming sepsis was possible but not confirmed in the first two deaths which occurred 11 months and 2 1/2 years after operation; the third died from chronic renal failure 11 years after splenectomy. After operation, there were no confirmed cases of pneumococcal septicaemia or meningitis, and the commonest clinical event was the acute chest syndrome.

3. Mucosal macrophages and cytokine production in the colon of children with Trichuris trichiura dysentery

Mucosal macrophages and accessory cells have been studied by immunohistochemistry in the lamina propria of the colon of children with Trichuris trichiura dysentery syndrome (TDS). No difference was found in the numbers of cells recognized by the monoclonal antibodies CD11c, CD68, or RFD7 between TDS children and local controls. However, large numbers of cells were recognized by an antibody against calprotectin (an anti-bacterial glycoprotein found in tissue infiltrating-monocytes) in TDS colonic mucosa, but few in control colon. Large numbers of cells containing tumour necrosis factor alpha (TNF alpha) were also seen in TDS mucosa; cells isolated from TDS mucosa secreted more TNF alpha than cells from control mucosa; and children with TDS had high levels of circulating TNF alpha. Non-specific macrophage-mediated inflammation and local cytokine production may therefore play a role in the pathogenesis of TDS.

Postsplenectomy course in homozygous sickle cell disease.

OBJECTIVE To determine whether children with homozygous sickle cell (SS) disease and splenectomy are at greater risk of death, overwhelming septicemia, or other complications. METHODS A total of 130 patients with SS treated by splenectomy (46 recurrent acute splenic sequestration, 84 chronic hypersplenism) over a 22.5-year period at the Sickle Cell Clinic of the University Hospital of the West Indies, Kingston, Jamaica, were compared with a control group matched for sex, age, and duration of follow-up in a retrospective review. Deaths and bacteremias were examined over the whole study period. Painful crises, acute chest syndromes, and febrile episodes were compared in the 90 patients completing 5 years of postsplenectomy follow-up. FINDINGS Mortality and bacteremic episodes did not differ between the splenectomy and control groups. Painful crises were more common in the splenectomy group than in the control group (P =.01) but did not differ between splenectomy indications. Acute chest syndrome was more common in the splenectomy group than in the control group (P <.01) and was more common in the acute splenic sequestration group than in the hypersplenism group (P =.01). Febrile events did not differ between the groups or between the indications for splenectomy. CONCLUSION Splenectomy does not increase the risk of death or bacteremic illness in patients with SS disease and, if otherwise indicated, should not be deferred for these reasons.

Histopathology and immunohistochemistry of the caecum in children with the Trichuris dysentery syndrome.

Caecal biopsy specimens from Jamaican children with the Trichuris dysentery syndrome (TDS) and age matched Jamaican controls were investigated by immunohistochemistry and by light microscopy. Biopsy specimens from all children (with TDS and controls) showed a mild to moderate increase in inflammatory cells. Except in the vicinity of the worm, where the epithelium was flattened, there was no other epithelial abnormality. Compared with controls, children with TDS had increased IgM lamina propria plasma cells and decreased intraepithelial T cells. There was also an increase in crypt epithelial cell proliferation. Lamina propria T cells (both activated and non-activated) were no more common in children with the Trichuris syndrome than controls. Epithelial cell HLA-DR and VLA-1 expression (which are increased in other colitides) were the same in both groups. Despite the presence of large worm burdens and chronic dysentery, therefore, only minor changes were seen in the caecal mucosa of children with TDS.

Acceleration in linear growth after splenectomy for hypersplenism in homozygous sickle cell disease.

Chronic hypersplenism in homozygous sickle cell (SS) disease markedly increases haemolysis and the resulting erythropoietic expansion is likely to have a high metabolic cost. Splenectomy for hypersplenism in SS disease is followed by highly significant changes in haematological indices and an increase in height, but not weight, velocity. This pattern is similar to that observed in the trichuris dysentery syndrome after treatment, and differs from the increases in both height and weight velocity that follow nutritional supplementation of severely malnourished children. It is postulated that accelerated linear growth after the reduction in erythropoietic stress may implicate a specific nutrient deficiency in hypersplenic children with SS.

The low frequency of reflux in Jamaican children.

Fifty consecutive micturating cystourethrograms (MCUG) performed at the UHWI between June 1989 and December 1991 were reviewed. There were forty boys and ten girls. Infants under the age of one year accounted for 58%. Urinary tract infection was the commonest presenting feature (72%), voiding difficulties (10%) and associated malformations (14%) were the other reasons for doing the MCUG. Only 10% of the children revealed vesico-ureteral reflux (VUR) which supports the view that reflux is less common in the non-caucasian population. In our population, the yield from MCUG is low. However, when detected, the reflux was of significant degree as to warrant active therapy. All but one of the VU refluxes diagnosed by MCUG had ultrasonographic abnormalities. Black children with single urinary infections have a low likelihood of VUR. A clear history of pyelonephritis and abnormalities on ultrasound or radionucleide cystogram may be used as criteria to select those in whom MCUG will be useful.

The Effect of Splenectomy on Whole Body Protein Turnover in Homozygous Sickle Cell Disease

In individuals with homozygous sickle cell (SS) disease, haemolysis creates a demand for increased red cell production. In children with hypersplenism haemolysis may be further increased and in such cases the excessive red cell production may be reduced by splenectomy (1). Whole body protein turnover is increased in SS disease and a large part of this increase is the consequence of increased turnover of red blood cells (2). Whole body protein turnover has therefore been measured in children with SS disease before and after splenectomy to find out if the reduction of the haemolytic rate following splenectomy was associated with a decrease in protein turnover.

Urethral prolapse in girls

Urethral prolapse is a benign lesion of the terminal urethra, usually seen in young Negroid girls. Twenty-seven children with urethral prolapse treated at the University Hospital of the West Indies between January 1982 and December 1991 were prospectively studied; 74% were between the ages of 3 and 7 years. Bloody discharge was the most common symptom. Vulval bleeding together with a bruised appearance of the urethra resulted in erroneous initial suspicion of sexual abuse in 3 children. Prolapse was graded from I to IV depending on the extent of prolapse and degree of inflammation. Initial therapy in the 25 prepubertal girls consisted of sitz baths and topical application of either an antimicrobial ointment (15 girls) or 0.5% oestrogen cream (10), chosen randomly. Complete resolution of the prolapse occurred in only 4 children, 3 of them from the oestrogen group. Although the oestrogen led to a better response, it also caused theliarchy in 2 girls. Three children who had only transient improvement and 2 post-pubertal patients had surgical excision of the prolapse. Post-excision there were no complications or recurrence of prolapse. Three girls who had improvement with non-operative therapy continued to have grade II prolapse even after puberty. Initial therapy of urethral prolapse in prepubertal girls can be non-surgical, however, when this fails to achieve resolution surgical excision is simple, safe, and curative.