Objective

To establish incidence rates, clinic referrals, hospitalisations, mortality rates and baseline determinants of morbidity among infants in an Indian slum.

Design

A community-based birth cohort with twice-weekly surveillance.

Setting

Vellore, South India.

Subjects

452 newborns recruited over 18 months, followed through infancy.

Main outcome measures

Incidence rates of gastrointestinal illness, respiratory illness, undifferentiated fever, other infections and non-infectious morbidity; rates of community-based diagnoses, clinic visits and hospitalisation; and rate ratios of baseline factors for morbidity.

Results

Infants experienced 12 episodes (95% confidence interval (CI) 11 to 13) of illness, spending about one fifth of their infancy with an illness. Respiratory and gastrointestinal symptoms were most common with incidence rates (95% CI) of 7.4 (6.9 to 7.9) and 3.6 (3.3 to 3.9) episodes per child-year. Factors independently associated with a higher incidence of respiratory and gastrointestinal illness were age (3-5 months), male sex, cold/wet season and household involved in beedi work. The rate (95% CI) of hospitalisation, mainly for respiratory and gastrointestinal illness, was 0.28 (0.22 to 0.35) per child-year.

Conclusions

The morbidity burden due to respiratory and gastrointestinal illness is high in a South Indian urban slum, with children ill for approximately one fifth of infancy, mainly with respiratory and gastrointestinal illnesses. The risk factors identified were younger age, male sex, cold/wet season and household involvement in beedi work.

Aims

To evaluate the efficacy and acceptability of solar irradiation in the prevention of diarrhoeal morbidity in children under 5 years of age, in an urban slum in Vellore, Tamil Nadu.

Methods

A total of 100 children were assigned to receive drinking water that had been subjected to solar disinfection in polyethylene terephthalate bottles. One hundred age and sex matched controls were also selected. Both groups were followed by weekly home visits for a period of six months for any diarrhoeal morbidity. At the end of the follow up period, the acceptability of the intervention was assessed by interviews, questionnaires, and focus group discussions.

Results

There was significant reduction in the incidence, duration, and severity of diarrhoea in children receiving solar disinfected water, despite 86% of the children drinking water other than that treated by the intervention. The incidence of diarrhoea in the intervention group was 1.7 per child‐year, and among controls 2.7 per child‐year, with an incidence rate ratio of 0.64 (95% CI −0.48 to 0.86). The risk of diarrhoea was reduced by 40% by using solar disinfection. In qualitative evaluation of acceptability, most women felt that solar disinfection was a feasible and sustainable method of disinfecting water.

Conclusions

Solar disinfection of water is an inexpensive, effective, and acceptable method of increasing water safety in a resource limited environment, and can significantly decrease diarrhoeal morbidity in children.

Objective

Infant and child mortality are important indicators of the level of development of a society, but are usually collected by governmental agencies on a region wide scale, with little local stratification. In order to formulate appropriate local policies for intervention, it is important to know the patterns of morbidity and mortality in children in the local setting.

Methods

This retrospective study collected and analyzed data on infant mortality for the period 1995 to 2003 in an urban slum area in Vellore, southern India from government health records maintained at the urban health clinic.

Results

The infant mortality rate over this period was 37.9 per 1000 live births. Over half (54.3%) of the deaths occurred in the neonatal period. Neonatal deaths were mainly due to perinatal asphyxia (31.9%), pre-maturity (16.8%) and aspiration pneumonia or acute respiratory distress (16.8%), while infant deaths occurring after the first mth of life were mainly due to diarrheal disease (43%) and respiratory infections (21%).

Conclusion

These results emphasize the need to improved antenatal and perinatal care to improve survival in the neonatal period. The strikingly high death rate due to diarrheal illness highlights the requirements for better sanitation and water quality.

Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licenced vaccines are either animal-human reassortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies.

SUMMARY

Asymptomatic enteric infections are important where sequelae or protection from subsequent illness is an outcome measure. The use of reverse transcription–polymerase chain reaction (RT–PCR) to identify asymptomatic enteric infections in a birth cohort followed for rotaviral infections in a south Indian urban slum is reported. Of 1191 non-diarrhoeal samples from 371 children collected in May–June 2003, 22 (1·9%) were positive by ELISA. A total of 147 (40·6%) of 362 samples tested by VP6 RT–PCR were positive. In those samples that could be typed, a high diversity of G types including G1, G2, G4, G8, G9 and G10, and a high proportion (34·4%) of mixed infections were detected. Noroviruses were identified in 6/28 (21·4%) samples tested. The identification of infections undetectable by conventional techniques indicates the importance of the use of sensitive diagnostic techniques in research studies. Asymptomatically infected children may also act as a source of infection for other susceptible hosts.

Papillary immature metaplasia (PIM) is a distinctive exophytic lesion of the uterine cervix and shares some histologic and cytologic features with ordinary squamous metaplasia (SM), atypical immature squamous metaplasia (AIM), high-grade squamous intraepithelial neoplasia (HSIL) and papillary squamous cell carcinoma (PSC). PIM has been suggested to be a subset of condyloma associated with low-risk type human papilloma virus (HPV), however, the etiologic role of HPV and biologic behavior of the disease are still elusive. We compared the clinical and histopathological findings, immunohistochemical expression of Ki-67 and p53 protein, and HPV typing of 5 cases of PIM with SM (n=9), HSIL (n=6), and PSC (n=4) to know the helpful features for the differential diagnosis. Histologically, all 5 cases showed a papillary proliferation of immature metaplastic cells involving the proximal transformation zone and endocervix. On HPV typing by polymerase chain reaction-restriction fragment length polymorphism, 2 out of 5 PIM were confirmed to have HPV 6 or HPV 11, while 2 out of 4 PSC were proved having HPV 31 and HPV 16 each. Ki-67 labeling index and mitotic index of PIM were significantly lower than those of HSIL or PSC. There were no significant differences of Ki-67 labeling index and mitotic index between PIM and SM. The expression of p53 varied among the groups and thus it was not helpful for the differential diagnosis.

Kaposi's sarcoma (KS) appears to develop in association with kidney transplantation, but unlikely with dialysis. We report two cases of classic KS that occurred in patients receiving short-term (less than 3 yr) dialysis. They have been suffering from chronic renal failure due to tuberculosis and diabetes mellitus, respectively. Several to multiple, reddened-violaceous patches, plaques and nodules were found on the hand and the lower extremities. Laboratory studies showed no evidence suggesting immunosuppressed state and there was no history of taking immunosuppressive agents. The biopsies of the two cases revealed proliferation of spindle-shaped cells focally arranged in bundles and multiple dilated vascular spaces outlined by an attenuated endothelium with intravascular and extravasated erythrocytes. The specimens expressed positivity with CD34 antigen. Human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) was detected in one case by polymerase chain reaction method.

Recent evidence shows that transcriptional silencing as a consequence of hypermethylation of CpG islands is an important mechanism in the inactivation of p16INK4 tumor suppressor gene. This study is designed to clarify the significance of p16INK4 hypermethylation in 23 cases of glioblastomas (GBMs) by methylation-specific polymerase chain reaction (PCR) and p16 immunostaining. Fourteen cases (60.9%) out of 23 GBMs revealed hypermethylation on p16. p16 immunostaining revealed that 13 (93%) of these 14 hypermethylation cases showed complete loss of immunoreactivity and only one (7%) case retained immunoreactivity. Among 9 methylation-negative cases, 4 were immunonegative, which might be related to mutations or deletions other than hypermethylation. The most significant finding was that of 17 cases with immunonegativity, 13 cases (76.5%) showed hypermethylation. We reconfirmed that p16 hypermethylation may be one of the major mechanisms of tumorigenesis of GBMs and the results between the methylation specific-PCR study and p16 immunostaining had a good correlation.

Isolated splenic metastasis arising from colorectal carcinoma is very rare and there has been only 6 cases reported in the English literature. A new case is presented, and its possible pathogenesis was considered with previously reported cases. A 65-year-old male patient had received a right hemicolectomy for ascending colon cancer 36 months earlier. He was followed up regularly with serial measurement of serum carcinoembryonic antigen (CEA). Rising serum CEA was discovered from 33 months postoperatively and CT revealed an isolated splenic metastasis. He therefore underwent splenectomy, which was proven to be a metastatic adenocarcinoma with similar histological feature to the original tumor. As all reported cases showed elevated serum CEA at the time of metastasis, isolated splenic metastasis might be associated with CEA in regard to its biological functions of immunosuppression and adhesion.

Carcinoid tumors having distinct paranuclear clear zones seen on hematoxylin and eosin stain are rare and few cases have been reported in the literature. Furthermore, primary hepatic carcinoid tumor with a paranuclear clear zone is extremely rare. We recently experienced a case from a 48-year-old man who presented a large single mass, 12 cm in largest diameter, in the right lobe of the liver. Histologically, the tumor revealed characteristic organoid pattern with central hyaline degeneration. The tumor cells had a prominent paranuclear vacuolated dear zone. On immunohistochemistry, tumor cells were diffusely positive for synaptophysin and focally stained for chromogranin A. Ultrastructural examination revealed paranuclear aggregation of intermediate filaments and membrane-bound clear vesicles, which corresponded to the paranuclear vacuolated clear zone.

G-DNA, a polymorphic family of four-stranded DNA structures, has been proposed to play roles in a variety of biological processes including telomere function, meiotic recombination and gene regulation. Here we report the purification and cloning of TGP1, a G-DNA specific binding protein from Tetrahymena thermophila. TGP1 was purified by three-column chromatographies, including a G-DNA affinity column. Two major proteins (approximately 80 and approximately 40 kDa) were present in the most highly purified column fraction. Renaturation experiments showed that the approximately 80 kDa protein contains TGP1 activity. Biochemical characterization showed that TGP1 is a G-DNA specific binding protein with a preference for parallel G-DNAs. The TGP1/DNA complex has a dissociation constant (Kd) of approximately 2.2 x 10(-8) M and TGP1 can form supershift in gel mobility shift assays. The cDNA coding TGP1 was cloned and sequenced based upon an internal peptide sequence obtained from the approximately 80 kDa protein. Sequence analyses showed that TGP1 is a basic protein with a pI of 10.58, and contains two extensively hydrophilic and basic domains. Homology searches revealed that TGP1 is a novel protein sharing weak similarities with a number of proteins.

Kaposi's sarcoma (KS) had been a rare and unusual vascular tumor until a recent epidemic of a disseminated and fulminant form of KS in AIDS patients. Infectious agents have been suspected of causing KS, and recently partial genomic DNA sequences of human herpesvirus 8 (HHV8) have been identified in AIDS-associated KS lesions. Since then, genomic DNA sequences of HHV8 have been isolated in other forms of KS. Although the partial genomic DNA sequence of HHV8 was reported to be, if rare, identified in vascular tumors other than Kaposi's sarcoma (KS), the presence of HHV8 in a very large fraction of KS indicates that detection of HHV8 by PCR is a useful auxiliary tool in differentiating KS from other KS-mimicking vascular tumors. We examined whether the 233-bp segment of the viral DNA was detected in Korean patients with KS and other KS-mimicking vascular tumors. HHV8 sequences were identified in all of nine classic type of KS but not in three epithelioid hemangioendotheliomas and seven angiosarcomas. Our results confirm the relatively restricted distribution of HHV8 and also argue against the likelihood of secondary colonization of KS cells by HHV8.

We report an unusual primary case of pulmonary sarcoma that developed in the lung of a 36-year-old woman. The tumor had histologic, immunologic and ultrastructural features identical to those of biphasic synovial sarcoma of the soft tissue. It consisted of an intimate admixture of cytokeratin and epithelial membrane antigen(EMA)-positive neoplastic epithelial cells and vimentin-positive fibroblast-like spindle cells with areas of hyalinization. The patient had a lobectomy and showed no evidence of recurrence or tumor at other sites 15 months after surgery. This case is an useful addition to the small number of published reports on pulmonary synovial sarcoma. The distinctive features of this neoplasm allow it to be different from other types of primary and metastatic malignancies in the lung.

Benign recurrent hematuria usually indicates a good prognosis. This condition is associated with abnormally thin glomerular basement membranes. Of 680 renal biopsy cases in which lower urinary tract disease had been excluded by careful study, 25 cases from seven children and eighteen adults met the criteria for thin glomerular basement membrane disease, placing the incidence of the disease at 3.7%. The mean patient age was 32.4 years and the male to female ratio was 1 to 5.3. The primary finding was microscopic hematuria in eighteen patients and gross hematuria in five patients. Among eighteen patients who had microscopic hematuria, one patient also exhibited proteinuria and one patient suffered from acute renal failure due to acute drug-induced interstitial nephritis. Proteinuria was only found in one patient. All of the patients had normal renal function, with the exception of one who suffered from acute renal failure. The duration of hematuria from the time of detection to the date of biopsy ranged from 3 months to 30 years with a mean interval of 56.6 months. No apparent evidence of familial hematuria in any patient was noted. Under light microscopy most glomeruli were normal. However, five cases showed focal global sclerosis. Under immunofluorescence microscopy seventeen cases were negative for all immunoglobulins, for complement, and for fibrinogen. Eight cases showed nonspecific mesangial deposition of fibrinogen and/or IgM. Ultrastructurally, extensive diffuse thinning of the GBM was a constant finding. The mean thickness of the GBM was 203.2 +/- 28.3 nm (n = 25); the thickness in adult (201.4 +/- 27.5 nm; n = 18) did not differ from that in children (208.1 +/- 32.0 nm; n = 7).

We studied the biological effect of a magnetic field on murine brain and kidney. Magnetic field we used was generated by Magno-DR apparatus (Hanil Co., Korea) which produced a high density unipolar square pulsating magnetic field, about 0.3 approximately 0.5 Tesla at 7 Hertz. Animals were placed in the chamber of the machine for various times from 4 hours to 24 hours. Histological sections of brain and kidney were made after perfusion fixation with paraformaldehyde. The light microscopic examination showed eosinophilic change of cytoplasm and positive immunohistochemical reaction to amyloid precursor protein in the neurons of the cerebral cortex. However, the thalamus and brain stem were less affected. The changes in the brain was seen in the mouse exposed more than 12 hours. The renal tubular epithelium showed degenerated tubules scattered in cortical area but little change was noted in glomeruli in the cortex and collecting tubules in the medulla. Immunohistochemistry of the kidney showed weakly positive reaction for the amyloid precursor protein in the distal tubular epithelium after 4 hours of exposure. These data suggest that strong pulsating magnetic fields could induce deleterious effect on the murine brain tissue and renal cortical tubules.

We report a case of adamantinoma of the tibia resembling fibrous dysplasia. The patient was a 55-year-old male, and complained of pain in the right lower leg. Roentgenographs showed a well demarcated osteolytic lesion with small foci of calcification and septation within the diaphysis of the distal tibia. The cortex was partially disrupted. Histologically, initial biopsy specimen showed fibrous connective tissue and trabeculae of immature woven bone, strongly suggestive of fibrous dysplasia. The lesion recurred and the second biopsy revealed nests of spindle cells and tubular epithelial structures embedded in granulation type-fibrous tissue. Immunohistochemically, both the nests of spindle cells and the tubular structures gave a positive reaction for cytokeratin. The present case emphasizes once again that histological diagnosis of fibrous dysplasia of the tibia should be made carefully with exclusion of the possibility of adamantinoma.

A simplified HEp-2 cell adhesion assay was performed with stored Escherichia coli isolates from 761 children with acute diarrhea and 531 matched controls, and the results were evaluated by means of fluorescent actin staining and hybridization with DNA probes. The prevalence rates of localized adherence and aggregative adherence were significantly higher for patients (9.9 and 7.6%, respectively) than for controls (3.7 and 3.9%, respectively).

A simple passive haemmagglutination assay (PHA) was developed to detect Vi antibodies, to improve the diagnosis of typhoid fever by small laboratories. The Vi capsular antigen of Salmonella typhi was extracted by alternate alcohol and acetone precipitation. Formalin fixed, sheep red blood cells treated with chromium chloride were sensitised with this Vi antigen and antibodies detected and measured by PHA. The test had a sensitivity of 83.3% among 30 cases of typhoid fever confirmed by culture. The specificity of the test was 94%, making it suitable for use in laboratories without facilities for IFAT or ELISA.

An autopsy case of congenital tuberculosis is described in a 41-day-old female infant who was born to a mother having active pulmonary tuberculosis. The primary complex was seen in the liver and portal lymph nodes, and there was a generalized miliary dissemination including lung, liver, spleen, pancreas, adrenals, thyroid, thymus, kidneys, brain, and bowel. The organism was confirmed to be Mycobacterium tuberculosis. The tubercles were histopathologically of various chronicity and characterized by massive caseation and fairly poor peripheral lymphohistiocytic reaction. Giant cell response was also minimal. It should be stressed that although rare, tuberculosis is still an important disease in Korea that can involve fetus or newborn infants if pregnant women are untreated or unnoticed for her tuberculosis.