Renpenning syndrome in an Indian patient

Renpenning syndrome is one of the well‐characterized causes of X‐linked intellectual disability and is associated with microcephaly and various visceral malformations. Face is considered characteristic but the dysmorphism is subtle. Here we report an Indian adult with a very lean habitus, progressive atrophy of the upper back muscles, microcephaly, loss of cervical lordosis, and upper thoracic scoliosis. Using whole‐exome sequencing, a hemizygous deletion was identified in PQBP1 that leads to a frameshift and premature termination of translation. The loss of normal curvatures of cervical and upper thoracic spine due to muscular atrophy is a characteristic feature, though it may be age dependent.     

Familial hepatocellular carcinoma in an endemic area of Thailand

Hepatocellular carcinoma (HCC), while rare in the United States and other western countries, represents a major cause of death in certain areas of the world, including southeast Asia. While the etiology of HCC remains enigmatic, it is of interest that hepatitis-B viral infection (HBV) has occurred in significant excess in those geographic regions endemic for HCC. Only limited attention has been given to the role of primary genetic factors in HCC, but scattered anecdotal reports have identified familial aggregations of this disease. We report a family in which histologically verified HCC was found in a mother and two of her four sons, all of whom were concordant for HBV infection. We also briefly discuss two additional familial aggregations of HCC from Costa Rica. We propose that greater attention to be given to the role of primary genetic factors in HCC and that appropriate consideration be given to interaction with other environmental factors, such as aflatoxin exposures, nitrosamines, and HBV infection. While our observations document familial clustering of HCC with concordance for HBV, we caution that support of a genetic hypothesis will require more extensive investigation.     

Frequency of medullary thyroid carcinoma in an endemic goiter area

A series of 41 poorly differentiated follicular carcinomas of the thyroid gland without histopathological features of medullary or papillary carcinoma and 9 cases of undifferentiated thyroid carcinoma of the small cell type (diagnosed between 1967 and 1983) were investigated immunohistochemically. Two poorly differentiated follicular carcinomas showed a considerable number of calcitonin-positive cells in addition to the weakly thyroglobulin-positive tumor cells. One of these cases revealed several areas with calcitonin-positive tumor cells with additional squamous metaplasia with keratinization. No medullary carcinomas could be demonstrated among the 9 cases previously diagnosed as undifferentiated thyroid carcinomas of the small cell type. From the epidemiological point of view the application of immunohistochemistry does not significantly increase the proportion of medullary carcinomas detected in our endemic goiter area. The incidence of medullary carcinoma remains surprisingly low when compared with nonendemic areas.     

Transfusion transmission risk of dengue viruses in an endemic area

It is believed that dengue virus (DENV) is transfusion transmittable, only a few transfusion associated cases were reported so far in spite of at least 50 million dengue infections occur globally each year. The equation for calculating DENV transfusion transmission probability was proposed following the West Nile Virus model. In consideration of reported case number, population size in the region around the designated cases, symptomatic infection rate, blood donation rate, and mosquito biological characteristics together, a relative low rate of DENV transmittable donations was presumed in a low-grade endemic area. Both the apparent clinical presentation and the relative short viremia period of DENV infection prevent dengue viruses from being a highly potential transfusion transmittable agent. The geographically based selection and donor deferral strategy seems to effectively mitigate the potential risk of DENV transfusion transmission. The costly minipooled nucleic acid test (NAT) is therefore not recommended unless for ensuring enough safe blood donations in the dengue epidemic area.     

Molecular epidemiology of Streptococcus pyogenes in an area where acute pharyngotonsillitis is endemic.

During an open clinical trial in an area where streptococcal infections are hyperendemic, we studied the genetic polymorphism of Streptococcus pyogenes isolates collected from patients and from healthy carriers living in close contact with them. The clonal diversity of isolates was analyzed by pulsed-field gel electrophoresis with three restriction enzymes (SmaI, ApaI, and SacII). The pharynx of each patient and healthy carrier was colonized by a single clone, suggesting the clonal nature of streptococcal colonization in individuals. Among 52 isolates obtained from patients with acute pharyngotonsillitis, we found 14 genetically unrelated clones, showing the genetic diversity of S. pyogenes. However, two clones belonging to the M1 and M12 serotypes represented about 70% of isolates in carriers and patients. Pharyngeal colonization in cured patients was monitored for 3 to 4 months. After the initial elimination of S. pyogenes following antibiotic therapy, the rate of recolonization was high by day 30 (about 20%) and was also at that level between days 90 and 120; this was similar to the carriage rate in family contacts. Thus, cured patients can be recontaminated by unrelated clones, suggesting that colonization of healthy carriers might be a potential source of spread and redistribution of S. pyogenes isolates.     

Hepatitis C virus antibodies among risk groups in a South African area endemic for hepatitis B virus

The prevalence of anti-HCV was studied in a South African area endemic for hepatitis B virus. A total of 35,685 volunteer blood donors (22,034 whites, 9,218 Asians, 3,077 Africans, 1,356 coloureds), 71 haemophiliacs, 84 chronic dialysis patients, 100 antenatal attenders, 212 nurses, and 20 HIV-positive male homosexuals were tested for anti-HCV. Repeat positive second generation Ortho HCV EIA was used to determine HCV status for the blood donors; Abbott-II HCV EIA combined with a neutralisation test was used for the other risk groups. Antibody to hepatitis B core antigen (anti-HBc) was also tested in the haemophiliacs, nurses, and chronic dialysis patients. Seroprevalence for the blood donor population was 0.16, 0.34, 0.75, and 0.22% for whites, Asians, Africans, and coloureds, respectively. Of the risk groups tested, 39.4% of haemophiliacs and 4.8% of chronic dialysis patients were positive; of the remainder tested none was positive. Fifty percent of nurses, 47.9% of haemophiliacs, and 22.6% of dialysis patients had serological evidence of past exposure to hepatitis B virus (anti-HBc positive). These findings indicate a low prevalence of anti-HCV in the blood donor population, thus probably resulting in a low prevalence in groups exposed to blood and blood derivatives. The overall difference in prevalence between the race groups was significant (P < 0.0001). The high prevalence of hepatitis B virus compared to the low prevalence of HCV suggests that the main modes of transmission of the two viruses are probably different. © 1993 Wiley-Liss, Inc.     

SOCS in situ expression in tuberculous lymphadenitis in an endemic area

BackgroundThe immune response to Mycobacterium tuberculosis is complex and multifactorial, the cytokine system being a major factor in M. tuberculosis immunity.AimTo analyze the immunohistochemical aspects of tuberculous lymph nodes in immunocompetent patients and search for associations between SOCS and cytokine expression in human tuberculous lymphadenitis.MethodsThirteen lymph nodes were assayed by immunohistochemistry for SOCS-1 and 3, STAT-3, RANTES, MIP-1-α, ICAM-1, IFN-γ as well as CD45RO, CD20, CD34, CD68, trypsin and lysozyme. Additionally, the RT in situ PCR was performed for SOCS-1 and 3 mRNA detection.ResultsDecreased MIP-1α expression together with reduced SOCS-3 (p = 0.042), lysozyme (p = 0.024) and CD45RO (p = 0.05) was observed in the TB lymph nodes compared to the control lymph nodes. In conclusion, the lymphadenitis due to M. tuberculosis was associated with a downregulation of memory T cells (CD45RO), activated lysozymes and SOCS-3 compared to controls, which may play a role in the long-term bacterial replication and altered immune modulation characteristic of the disease.     

Prevalent HBV genotypes and subtypes in a South Indian population.

BACKGROUND: Genotypes or genetic subtypes describe genetically related strains and have been described for viruses belonging to several different families. The eight major genotypes of hepatitis B virus (HBV) have distinct geographic distribution. Recent studies suggest possible pathogenic and therapeutic differences among HBV genotypes. OBJECTIVES: To evaluate the HBV genotypes of 85 samples by RFLP analysis and sequence the desired region to look for variations and identify the subtypes of the surface region. STUDY DESIGN: We studied 85 patients with HBV in order to identify the most prevalent genotype and subtype. Patients with HBV-related liver disease attending the Department of Gastroenterology at Owaisi Hospital and Research Centre were studied. RESULTS AND CONCLUSIONS: Genotype D1 was most prevalent. Genotyping was carried out by RFLP analysis and confirmed by sequencing. Nucleotide sequences showed significant homology (96-97%) with the other genotypes that have been reported. Subtype ayw was the most prevalent subtype within the surface region. Construction of a phylogenetic tree incorporating these isolates and other published HBV sequences showed that the isolates are derived from the same evolutionary tree. The study adds to our understanding of the genetic diversity of HBV and the geographical distribution of its subtypes, and will be useful for reconstructing the evolutionary history of HBV.     

Identification of a novel mutation in an Indian patient with CAII deficiency syndrome

Carbonic anhydrase II (CAII) deficiency syndrome characterized by osteopetrosis (OP), renal tubular acidosis (RTA), and cerebral calcifications is caused by mutations in the carbonic anhydrase 2 (CA2) gene. Severity of this disorder varies depending on the nature of the mutation and its effect on the protein. We present here, the clinical and radiographic details along with, results of mutational analysis of the CA2 gene in an individual clinically diagnosed with renal tubular acidosis, osteopetrosis and mental retardation and his family members to establish genotype-phenotype correlation. A novel homozygous deletion mutation c.251delT was seen in the patient resulting in a frameshift and a premature stop codon at amino acid position 90 generating a truncated protein leading to a complete loss of function and a consequential deficiency of the enzyme making this a pathogenic mutation. Confirmation of clinical diagnosis by molecular methods is essential as the clinical features of the CAII deficiency syndrome are similar to other forms of OP but the treatment modalities are different. Genetic confirmation of the diagnosis at an early age leads to the timely institution of therapy improving the growth potential, reduces other complications like fractures, and aids in providing prenatal testing and genetic counseling to the parents planning a pregnancy.     

Antiparasite adherence activity in Thai individuals living in a P. falciparum endemic area

Two types of antimalaria antibodies in the serum of 54 villagers living in a malaria endemic area of Thailand were determined by indirect immunofluorescence assay in order to define the status of malaria immunity within the group. Antibodies to parasite-derived antigens in the membrane of ring stage-infected erythrocytes were very high (> or = 1:1,250) in 44%, moderate to low (< or = 1:250) in 37% of the sera, and the rest did not have the antibody. However, all the sera had antibodies to antigens of the intraerythrocytic mature parasites, showing a very high level in 65% and moderate to low levels in 37% of the sera. Sera with high antibody titers to either type of antigen significantly inhibited cytoadherence of P. falciparum-infected erythrocytes. All the sera variably inhibited rosette formation of the parasites but showed no association with the antibody titers. These results suggest that the antibodies to cytoadherence and rosette formation can be elicited and sustained in the malaria experienced host while living in the endemic area. This may be a natural preventive mechanism against the severity of P. falciparum infection in the infected host. How long the antiparasite adherence activity will last remains to be investigated.     

Inbreeding and fertility in a South Indian population

Among 1913 women in Karnataka State, South India, 37.74% had married a relative (a consanguineous union), 60.79% were non-consanguineously married, and 1.46% did not know whether they had married a relative. Mean number of living offspring for consanguineously married women who had completed their reproduction was 3.89, and for the non-consanguineous 4.07. There is no significant difference in the mean level of fertility for the two groups measured in this way. Pre-natal mortality is lower (but not significantly) among consanguineously married women who have completed their reproduction than among the non-consanguineous group, but post-natal mortality is significantly higher among the conceptuses of the consanguineously married women. Although consanguineously married women conceive more frequently, that is, are more fecund than the non-consanguineous women (mean number of conceptions being 6.61 and 6.28, respectively), the difference is not significant. The differential survival of the offspring results in the consanguineous group having slightly lower net fertility, although the difference is not statistically significant. The lower sterility rates of the consanguineously married women (3.21% of all consanguineously married women show primary sterility compared to 3.47% of the non-consanguineous) may be due to greater compatibility of uniting gametes in the consanguineous marriages. The data reveal that women married to a relative and having completed their reproduction show higher fecundity, lower pre-natal mortality, higher post-natal mortality, lower sterility rates, and thus no significant difference in net fertility to those who had not married a relative.     

Reporting an abrupt-onset persistent hypotensive transfusion reaction in an Indian female patient

Blood transfusion [BT] may sometimes result in a rare type of adverse event causing an isolated fall in blood pressure, commonly referred to as a hypotensive transfusion reaction [HyTR]. It is mediated by the biological response mediators, in particular cytokines such as bradykinin characterized by a sudden and unforeseen onset of hypotension as the predominant clinical manifestation during BT. In this case, the authors wish to highlight two consecutive episodes of abrupt-onset HyTR following blood administration in an Indian female patient, which, however, characteristically subsided on stopping the BT. She received appropriate management for the same. In fact, on discharge, we advised the patient to receive washed blood components, if needed, to prevent the recurrence of HyTR in future.     

Thyroid gland volumes of healthy adults in an area with endemic goiter

Thyroid volume was measured by ultrasonography in 500 healthy adults living in an area with endemic goitre: in all subjects the mean value was 13.35 ml, in males (14.94 ml) the volume was significantly greater than in females (12.09 ml). The thyroid volume was significantly correlated with age, body weight and body surface. These data are compared with the results of other investigators. The ultrasonic procedure is the only exact method for thyroid volume calculation, the palpation of thyroid gland only is less accurate.     

Absence of Leishmania infantum in cave bats in an endemic area in Spain

Though dogs have been historically considered the main reservoir of Leishmania infantum, the role of wildlife in its epidemiology is attracting increasing attention. Rodents, wild carnivores and, recently, hares (Lepus spp.) have been proposed as sylvatic reservoirs for this parasite. Bats have never been tested for L. infantum infection in Europe. Nevertheless, bats have a widespread distribution, they live in abundant colonies, and some species inhabit caves, where constant temperatures and humidity provide ideal habitat for the sand fly vector. We tested blood samples from 35 Schreibers’ bats (Miniopterus schreibersii), abundant cave bats in NE Spain, which is an enzootic area of leishmaniasis. A PCR-amplifying fragment of the high copy of Leishmania donovani group kDNA minicircles was used. None of the analyzed samples were positive (maximum possible prevalence?=?8.20 %). Though the susceptibility of this bat to parasitization by L. infantum cannot be ruled out, our survey indicates that this species may not be a relevant sylvatic reservoir of L. infantum in the Mediterranean area. Nevertheless, even if the prevalence of infection in bats is low, such an abundant taxonomic group would still provide a significant maintenance population for the parasite.