In any study there remains a proportion of cases, about 25-40%, where cause of splenomegaly is not identified on usual evaluation, that is labelled as indeterminate group. The aim of this study was to evaluate various causes of splenomegaly. Thereafter the patients with splenomegaly of indeterminate origin were to be re-evaluated with detailed investigations (for the cause of splenomegaly). Causes of splenomegaly were looked into 100 adult patients with splenomegaly, admitted over a period of ten months in a teaching hospital in South India. Patients having ascites were excluded from the study. Malaria was the commonest cause of splenomegaly, observed in 22 patients. Other causes, in order of importance, were chronic myeloid leukaemia (n=11), non-cirrhotic portal fibrosis (n=9), enteric fever (n=9), cirrhosis of liver (n=8) and hyper-reactive malarial splenomegaly also called as tropical splenomegaly syndrome (n=7) and so on. Hyper-reactive malarial splenomegaly was the commonest cause (7 of 24 patients) of massive splenomegaly. Twenty-three patients had splenomegaly of indeterminate origin ie, cause could not be detected on first assessment. Detailed re-evaluation with repeat investigations including liver biopsy revealed the causes as follows: Hyper-reactive malarial splenomegaly -7 (30.4%), non-cirrhotic portal fibrosis - 4 (17.4%), cirrhosis of liver - 4 (17.4%) and iron deficiency anaemia - 5 (21.7%). In 3 patients (13.0%), no diagnosis could be arrived at despite best efforts. Obscure splenomegalies may be due to conditions like hyper-reactive malarial splenomegaly, non-cirrhotic portal fibrosis, iron deficiency anaemia, and even cirrhosis of liver, while malaria is still the most important cause of splenomegaly in India. Whereas the overall incidence of hyper-reactive malarial splenomegaly was only 7% in this study, it stood as the leading cause (29.2%), when analysed among patients with massive splenomegaly. Liver biopsy should be performed in all cases of obscure splenomegaly to arrive at the final diagnosis.

Background Encephalitis caused by flaviviruses, Japanese encephalitis virus (JEV) and West Nile virus (WNV) is responsible for significant morbidity and mortality in many endemic countries. Dengue-2 (Den-2) virus is a recent addition to the list of encephalitogenic viruses, after its Central Nervous System (CNS) invasion capability has been established. There is a wide array of laboratory tools that have helped us not only in the diagnosis of these conditions but also in understanding their pathogenesis and pathology. However, there are no reports of Shell Vial Culture (SVC), a centrifuge enhanced tissue culture assay that has revolutionized viral culturing in terms of rapidity and sensitivity being optimized for these flaviviral encephalitic conditions. The present study is an attempt to standardize and evaluate the usefulness of SVC for the laboratory diagnosis of JE, WN and Den-2 encephalitis cases and to compare it with Indirect Immunofluorescence (IIF) technique that detects cell associated virus antigen. Analysis of the various clinical parameters with respect to viral etiology has also been carried out. Results Pediatric patients constituted the major group involved in the study (92%). Etiological diagnosis of viral encephalitis could be established in twenty nine (58%) patients. JE encephalitis was the commonest with 19 (39%) cases being positive followed by, WN (9 cases-18%) and Den-2 (one case). IIF test could detect antigens of JE, WN and Den-2 viruses in 16(32%), 7(14%) and 1 case respectively. Shell vial culture assay picked up all cases that were positive by IIF test. In addition, SVC assay could detect 3 and 2 more cases of JE and WN encephalitis respectively, that were negative by the IIF test. Conclusion Shell vial culture is a rapid and efficient tool for the etiological diagnosis of JE, WN and Den-2 encephalitis cases. Early, prompt collection, transport and processing of the CSF samples, would make SVC a better method for the rapid diagnosis of these flaviviral infections.

BACKGROUND & OBJECTIVES:Pneumolysin, a toxin produced by Streptococcus pneumoniae is associated with virulence and is found in all invasive isolates. Its role as a diagnostic tool has recently been exploited. Most of the methods used are based on molecular techniques and are not cost-effective. The present study was undertaken to evaluate a simple, rapid and cost-effective method to detect pneumolysin in CSF as a diagnostic test for pneumococcal meningitis.METHODS:A total of 75 CSF samples from children with presumptive diagnosis of acute pyogenic meningitis or encephalitis were subjected to Gram stain, culture and pneumolysin detection by Cowan 1 staphylococcal protein A co-agglutination technique.RESULTS:Pneumolysin was detected in 26(78.8%) of 33 culture proven CSF samples and 4(9.5%) of 42 culture negative samples. Antigen detection by Co-A had a specificity of 90 per cent and a sensitivity of 79 per cent when compared with culture. Compared to Gram stain, pneumolysin Co-A had a specificity and sensitivity of 91.0 and 92.0 per cent respectively.INTERPRETATION & CONCLUSION:Detection of pneumolysin was found to be a simple, low cost antigen detection assay for rapid diagnosis of pneumococcal meningitis, for routine use in the developing countries.

Extended spectrum beta-lactamase (ESBL) producing strains of Klebsiella pneumoniae have emerged as important nosocomial pathogens. The present report describes an outbreak of ESBL positive K.pneumoniae in a neonatal intensive care unit of a tertiary care center in southern India. The clinical and microbiological significance of multiresistant gram negative ESBL producers have been discussed in light of this outbreak by multi-resistant gram negative bacilli. The review also offers some practical guidance regarding infection control and therapeutic options.

BACKGROUND:Both Herpes simplex infection and duodenal ulcer recur frequently, tend to remain localized, and show remissions and exacerbations. Published data on a link between the two are contradictory, and there are no data on the association of Herpes simplex infection with perforated duodenal ulcer.METHODS:187 patients in four groups were studied: group I--controls (n = 35), group II--non-ulcer dyspepsia (n = 35), group III--chronic non-perforated duodenal ulcer (n = 35), and group IV--perforated duodenal ulcer (n = 82). Titers of IgG antibodies against HSV-1 and HSV-2 were determined using enzyme immunoassays.RESULTS:The seropositivity rate for both HSV-1 (80%) and HSV-2 (77%) was high in the control population. Among patients with perforated duodenal ulcer, antibodies against HSV-1 (94%) but not those against HSV-2 (83%), were found more frequently than in groups I and III. HSV-1 seropositivity was significantly higher in patients with a short duration of preperforation symptoms. Absolute titers for both anti-HSV-1 and anti-HSV-2 were higher in patients with perforated duodenal ulcer than in controls and those with chronic non-perforated duodenal ulcer.CONCLUSION:Herpes simplexvirus, especially HSV-1, may have a role in the causation of perforated duodenal ulcers.

BACKGROUND:Viperine snake bites cause hemotoxicity in the form of coagulation dysfunction. Optimal dose requirement of anti-snake venom (ASV) and duration of therapy in such situation have not yet been fully explored. Our aim in this study was to compare two low-dose continuous infusion regimes with the standard high dose intermittent bolus regime in treating systemic envenomation and preventing its recurrence.METHODS:A prospective interventional study was conducted on 90 adult patients with snake bite with hemotoxicity. Patents were allocated into three treatment regimes, each regime being tried on 30 patients. Regimen I (standard high dose regimen) consisted of conventional, intermittent bolus dosage of 100 ml of ASV as a loading dose followed by 50 ml every six hours till whole blood coagulation time (CT) became normal. Regimen II consisted of 30 ml of ASV as a loading dose followed by 30 ml continuous infusion every six hours till two CTs at an interval of six hours were normal and a further dose of 30ml over 24 hours. Regimen III was similar to Regimen II in all aspects except that loading dose was 70 ml (instead of 30 ml).RESULTS:In patients with mild envenomation, even though the average requirement of ASV was only marginally lower in Regimen II (128.6 ml) as compared to in Regimen I (137.5 ml), one patient on Regimen I had relapse of coagulation dysfunction. In patients with moderate envenomation, average requirement of ASV was 221.3 ml and 179 ml in Regimens II and III respectively, which was much less than in Regimen I (343.8 ml) (p values 0.05 and 0.01 respectively). Further, no patient receiving Regimen III had relapse of coagulation dysfunction. In severe envenomation, average dose of ASV required was almost similar in Regimens II and III, i.e., 213.7 ml and 233.7 ml respectively, as compared to 433.3 ml required in Regimen I (p values 0.02 and 0.001 respectively). However, time lapse for CT normalization was only 18 hours in Regimen III as compared to 23.6 hours and 24 hours in Regimens I and II respectively.CONCLUSION:Regimens consisting of continuous intravenous infusion of ASV i.e., Regimen II in mild envenomation and Regimen III in moderate and severe envenomation are likely to make significant saving of ASV and reduction of recurrence of coagulation dysfunction.

Hepatitis C virus (HCV), which is usually transmitted by blood and blood products is emerging as an important agent in the list of sexually transmitted diseases (STDs). The present study was undertaken to document the burden of HCV infection in individuals with STDs in this tertiary care hospital in South India. One hundred serum samples collected from individuals with STDs were tested for antibodies to HCV by a third generation ELISA. All the samples were also screened for HIV infection. Six out of 100 individuals were found to possess antibodies against HCV (95% confidence interval [CI=1.3-10.7%). Fourteen out of 100 samples were positive for HIV (95% CI=7-20.9%). The seroprevalence of HCV in HIV positive individuals was 21.4% (3/14) whereas the corresponding figure for HIV negative individuals was only 3.5% (3/86). The difference was found to be statistically significant (p<0.01).

Mazzocca, Augustus D. MD; Meneghini, R. Michael MD; Chhablani, Ramesh MD; Badrinath, Shyamala K. MD; Cole, Brian J. MDMBA; Bush-Joseph, Charles A. MD Author Information

Japanese encephalitis (JE) is numerically one of the most important causes of viral encephalitis worldwide, with an estimated 50 000 cases and 15 000 deaths annually. About one-third of patients die and half of the survivors have severe neuropsychiatric sequelae. Three hundred patients clinically suspected of JE were tested in the present study. Laboratory confirmation of JE was on the basis of detection of antigen or presence of JE-specific IgM antibody and/or neutralizing antibody in a single CSF sample. The risk factors that were associated with fatal outcome were determined. Japanese encephalitis infection was confirmed in 70.7 per cent (212/300) of the patients. All patients were from rural areas and with low socioeconomic background. Prominent clinical findings were: fever in 100 per cent (212/212) patients, altered sensorium in 87.73 per cent (186/212), convulsion in 85.84 per cent (182/212), headache in 50 per cent (106/212), and vomiting in 47.64 per cent (101/212). The final clinical outcome was available for only 68.39 per cent (145/212) of patients, as children were taken home against medical advice. Of these, 35.86 per cent (52) died while 63.44 per cent (92) of patients survived. Correlations of investigative findings with the final outcome revealed that absence of virus-specific IgM and neutralizing antibodies in CSF were associated with fatal outcome. In patients diagnosed with Japanese encephalitis the presence of a virus-specific immune response is associated with a favourable outcome and an important parameter in recovery from illness.

Seroprevalence of Hepatitis C virus (HCV) among hospital based general population was determined using a third generation ELISA. The study population comprised of 661 individuals (including 36 health care workers) attending a tertiary care hospital in Pondicherry, south India. The overall seroprevalence was found to be 4.8% (95% confidence interval [CI]=3.2-6.4%). The seroprevalence in males and females was 5.9% (95% CI=3.5-8.3%) and 3.3% (95% CI= 1.2-5.4%) respectively. There was no statistically significant difference in the proportion of individuals who were positive in case of males and females (p>0.05). None of the health care workers tested positive for antibodies to HCV.

At present, it is not clear whether a fall in serological titres of anti-H. pylori IgG can be used for confirming eradication. A prospective study was conducted using varying cut-off levels from (10% to 50%) fall in anti-H. pylor IgG levels as a test of eradication in comparison to urease and histology. It was found that sensitivity was highest using a 10% cut-off but specificity wasvery low. Increasing cut-off values increased specificity but resulted in declining sensitivity without altering accuracy much. It appears that in the short term, percentage decline in serological titres can at best serve as a crude test of eradication.

Purpose: Etiological diagnosis of pneumococcal pneumonia is difficult in small children in whom blood culture cannot be done or who have already been started on antibiotics. A simple technique which can be applied at the bedside or in the outpatient department may help in obviating this problem. Detection of pneumolysin, a product of invasive pneumococci is being exploited as a diagnostic tool. Methods: An attempt was made to detect this protein in urine of seventy children, clinically suspected and radiologically diagnosed cases of pneumonia. Seventy age and sex matched controls were included in the study. Purified pneumolysin was prepared from clinical isolates of invasive pneumococcal infections. This was used to raise polyclonal antisera in rabbits. The antisera was used to sensitise Cowan 1 Staphylococcus aureus (CoA). A slide agglutination was performed with 25 µL urine and equal quantity of the reagent. Results: Results were compared with CoA reagent sensitised with antisera raised against a genetically derived pneumolysoid and capsular polysaccharide for antigen detection in the urine. Pneumolysin could be detected in 42.9% (30/70) urine samples from cases with pneumonia by the genetically derived antigen and in 37.1% samples by the in house prepared antigen, in contrast to 2.1% in healthy controls and 4.2% in children with infections other than pneumonia. The result was statistically significant. Detection of pneumolysin was slightly better than detection of capsular polysaccharide antigen in urine although the result was not statistically significant. Blood culture proved to be positive in only 29.5% cases. Conclusions: Pneumolysin detection in urine showed promising results and was found to be simple and rapid. It will help in quickening the diagnosis of pneumococcal pneumonia.

tion in severity of liver disease may account for the observed differences in mortality and length of stay. Although we attempted to adjust for liver disease severity by looking for diagnosis codes associated with liver disease complications, we could not capture all the clinical data necessary to adequately characterize disease severity. However, he also notes that the observation of increased variceal bleeding and upper endoscopy use among nonspecialist physicians is unclear without knowing liver disease severity. We believe that these differences may reflect factors in addition to liver disease severity, such as variation in the outpatient care given to these patients or necessary differences in referral patterns due to insurance coverage. For example, patients cared for by nonspecialists in conjunction with a gastroenterology consultation had higher degrees of comorbidity than those cared for primarily by gastroenterologists. These patients may have been admitted to nonspecialist physicians who provided outpatient care for their comorbid conditions. Unfortunately, our database was limited in being able to characterize such differences. Dr. Talwalkar mentions some additional limitations inherent in using administrative databases. First, diagnosis coding and listing of conditions as principal or secondary may be inaccurate. However, within any given health care organization, coding algorithms and, therefore, coding inaccuracies should be similar for different physician specialties. Our results should therefore not be markedly affected by this problem. Second, nonhepatic conditions were potentially included under the diagnosis codes biliary cirrhosis and sclerosing cholangitis in the International Classification of Diseases (ninth revision) system. Biliary cirrhosis and sclerosing cholangitis were felt to be the underlying etiology of liver disease in the minority of our patients, and exclusion of patients with these diagnoses is unlikely to have a significant effect on our overall conclusions. Although our study was limited to some degree by the use of administrative data, we believe our results should provide an important stimulus for further study using databases where relevant clinical data are available. This should allow further elucidation of the effect of specialty care in patients with end-stage liver disease. Further work in improving diagnostic coding and classification systems pertinent to liver disease will also facilitate such analyses, and hopefully lead to improved care of patients with this increasingly common condition.

Objective: To detect antibiotic resistance in Streptococcus pneumoniae associated with invasive infection in a tertiary care referral center. Methods: Clinical isolates from patients with invasive pneumococcal infections were screened by the Kirby-Bauer disc diffusion method for their susceptibility to some of the commonly used antibiotics in the hospital. Minimum inhibitory concentrations of the antibiotics were determined by standard method. Results: Of the 124 isolates screened, MICA ranging between 0.1 to 1 μg/ml of penicillin was detected in 11.6% of the strains. Resistance to erythromycin and chloramphenicol were found in 1.8% of the organisms. However, a high level of resistance to cotrimoxazole was seen in 24% of the isolates. MIC of cefotaxime was well within the sensitive break point. Conclusion: A low level resistance in spite of high antibiotic consumption is a surprising finding in this study. Detection of resistance to some common antibiotics in use however, underlines the need to screen all clinically significant strains of S. pneumoniae.

Anthrax continues to remain a problem in parts of India. Meningitis is often a complication encountered among cases with cutaneous anthrax. We have encountered a dozen cases of anthrax meningitis in our hosptal in the past decade. A sudden unexplained rise in cases in the past two years with hundred percent mortality stresses the need for rapid confirmatory diagnosis. Most of the cases admitted with central nervous system involvement had a provisional diagnosis of conditions other than anthrax meningitis. A strong clinical suspicion with a simple Gram stain smear of the CSF will help confirm anthrax meningitis in endemic areas.

BACKGROUND:The possible advantage of eradication of Helicobacter pylori in patients with perforated duodenal ulcer is unknown. This study was planned to assess the prevalence of H. pylori after simple closure of a perforated duodenal ulcer and to study the effect of H. pylori eradication on ulcer persistence and recurrence.METHODS:Some 202 patients were followed prospectively for 2 years after simple closure of a perforated duodenal ulcer (prospective group). A second group of 60 patients was reviewed 5 years or more after perforation closure (retrospective group). The prevalence of H. pylori in patients with perforated duodenal ulcer was compared with that in controls. Patients in the prospective group were randomized to receive either ranitidine alone or quadruple therapy (ranitidine, colloidal bismuth subcitrate, metronidazole and tetracycline) after operation. The incidence of H. pylori infection after the two treatments and the association with residual or recurrent ulcer were studied. In the retrospective group long-term ulcer recurrence was correlated with H. pylori status.RESULTS:The prevalence of H. pylori in patients with perforated duodenal ulcer was not significantly different from that in controls. At every interval of follow-up in the prospective group and in the retrospective group the H. pylori infection rate was significantly higher in patients who had recurrent or residual ulcers.CONCLUSION:Eradication of H. pylori after simple closure of a perforated duodenal ulcer should reduce the incidence of residual and recurrent ulcers.

This study was undertaken to determine the seroprevalence of H.pylori in asymptomatic children and compare it with that seen in the asymptomatic adult population from south India. One hundred and five children and one hundred adults admitted to the wards for conditions other than gastrointestinal disorders were included for this study. H.pylori status was determined by ELISA for IgG. The prevalence of H.pylori in children of various ages varied from 44% to 46% with an overall prevalence of H.pylori in children of 45%. 67% of adults were infected with H.pylori which was significantly higher than children (P = 0.002). The prevalence of H.pylori increased markedly with age with the maximum colonization (74%) occurring in young adults (16-30 years). The antibody levels too followed a similar pattern. In conclusion, it was seen that almost half the children in south India acquire H.pylori infection early in life which increases slowly and steadily with a peak prevalence in the young adults. Gender does not affect the prevalence in children and adults. As age advances further there is a slight decline in the prevalence of H.pylori infection. The immune response reflected by the levels of the antibody levels also follows the same pattern.

OBJECTIVES:To study the distribution of H. pylori in the stomach before and after truncal vagotomy and drainage (TV + D) for chronic duodenal ulcer.METHODS:Twenty two consecutive patients studied prospectively. H. pylori positivity detected by urease test and histology (Giemsa stain). One or both tests positive indicated positive H. pylori status. Biopsies taken from antrum, body, fundus and stoma (postoperatively) to document H. pylori status before and 6 months after TV + D.RESULTS:Antral prevalence of H. pylori significantly decreased after surgery while fundal colonization significantly increased. No change was seen in body of stomach.CONCLUSION:There is significant redistribution of H. pylori after TV + D. This has important diagnostic implications in evaluation of postoperative symptoms.