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Biomedical subjects

Madhulika Kabra

Publications and source records attributed to Madhulika Kabra.

At least 19 recordsLinked to original sources
PubMed2023

Phylogeny and evolution of SARS-CoV-2 during Delta and Omicron variant waves in India.

SARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India. Delta variant was reported in patients without comorbidity (97%), while Omicron BA.2 was reported in patients with comorbidity (77%). Tissue adaptation studies brought forth higher propensity of Omicron variants to bronchial tissue than lung, contrary to observation in Delta variants from Delhi. Study of codon usage pattern distinguished the prevalent variants, clustering them separately, Omicron BA.2 isolated in February grouped away from December strains, and all BA.2 after December acquired a new mutation S959P in ORF1b (44.3% of BA.2 in the study) indicating ongoing evolution. Loss of critical spike mutations in Omicron BA.2 and gain of immune evasion mutations including G142D, reported in Delta but absent in BA.1, and S371F instead of S371L in BA.1 could explain very brief period of BA.1 in December 2021, followed by complete replacement by BA.2. Higher propensity of Omicron variants to bronchial tissue, probably ensured increased transmission while Omicron BA.2 became the prevalent variant possibly due to evolutionary trade-off. Virus evolution continues to shape the epidemic and its culmination.Communicated by Ramaswamy H. Sarma.

SARS-CoV-2↗
PubMed2007

Prenatal diagnosis for a novel homozygous mutation in PKLR gene in an Indian family.

OBJECTIVE: To provide prenatal diagnosis of pyruvate kinase deficiency by direct DNA analysis in an Indian family. MATERIALS AND METHOD: This case report describes diagnosis of a novel homozygous mutation in PKLR gene that subsequently helped the family in the next pregnancy. RESULTS: Advancement in molecular genetics has resulted in the prenatal diagnosis of relatively uncommon genetic disorders like pyruvate kinase deficiency. CONCLUSION: This case reiterates the importance of application of molecular genetics in clinical practice and prenatal diagnosis especially for rare, incurable genetic disorders.

Child, Preschool↗
PubMed2007

Detection of fetomaternal hemorrhage following chorionic villus sampling by Kleihauer Betke test and rise in maternal serum alpha feto protein.

OBJECTIVES: To assess incidence and volume of fetomaternal hemorrhage (FMH) after chorionic villus sampling (CVS) by Kleihauer Betke test (KBT) and rise in maternal protein (MSAFP). METHODS: A prospective study was conducted on 61 cases requiring CVS. FMH due to CVS was assessed by KBT and MSAFP. RESULTS: Out of 61 cases, 60 (98.36%) cases showed FMH by MSAFP while all showed FMH by KBT. Median volume of FMH detected by MSAFP was 0.06 mL (25 to 75th interquartile (IQR) 0.01 to 0.12 mL) and by KBT was 0.45 mL (25 to 75th IQR 0.09 to 0.90). Mean volume of FMH detected by MSAFP was 0.1 + 0.1424 mL and by KBT was 0.58 + 0.637 mL. Significant FMH up to 0.1 mL was found in 20 (32.8%) and 45 (60.6%) by MSAFP and KBT respectively. CONCLUSION: MSAFP and KBT are sensitive to detect FMH. KBT estimates more FMH than MSAFP. Fifty micrograms of anti-D is sufficient to cover FMH during CVS.

Adult↗
PubMed2006

Griscelli syndrome.

A 4-month-old child had silvery gray hair, light-colored skin, recurrent chest infections, hepatosplenomegaly, and episodes of pancytopenia and hemophagocytosis in the liver, spleen, and bone marrow. Light microscopy of hair showed characteristic large aggregates of pigment granules distributed irregularly along the hair shaft. Peripheral blood smear examination did not show giant granules in granulocytes. Enlarged hyperpigmented basal melanocytes with sparsely pigmented adjacent keratinocytes were seen on the skin biopsy specimen. On the basis of these clinical and laboratory findings, Griscelli syndrome was diagnosed. The child succumbed to infection during an accelerated phase of the disease.

Bone Marrow↗
PubMed2006

Combination growth hormone and gonadotropin releasing hormone analog therapy in 11beta-hydroxylase deficiency.

Diagnosis of 11beta-hydroxylase deficiency was made in a boy at the age of 2 1/2 years on the basis of peripheral precocious puberty, growth acceleration (height standard deviation score +4.4) with advanced skeletal maturation (bone age 8.4 years) and elevated deoxycortisol levels. Glucocorticoid supplementation led to normalization of blood pressure but was associated with progression to central precocious puberty and increase in bone age resulting in decrease in predicted adult height to 133.7 cm (target height 163 cm). The child was started on GnRH analog (triptorelin 3.75 mg every 28 days), which led to improvement in predicted adult height by 3.1 cm over 15 months. Addition of growth hormone (0.1 IU/kg/day) resulted in improvement in predicted adult height (151 cm) and height deficit (12 cm) over the next 3.6 years. Final height (151 cm) exceeded predicted height at the initiation of GnRH analog treatment by 17.3 cm. This report suggests that combination GH and GnRH analog treatment may be useful in improving height outcome in children with 11beta-hydroxylase deficiency and compromised final height.

Adrenal Hyperplasia, Congenital↗
PubMed2006

Ovarian cysts in young girls with hypothyroidism: follow-up and effect of treatment.

Ovarian cysts have been reported in girls with longstanding uncompensated primary hypothyroidism. Restoration of euthyroid state has been associated with resolution of these cysts; long-term follow-up of these patients is however lacking. We evaluated the outcome in ten girls with ovarian cysts and hypothyroidism managed at our hospital with special emphasis on subsequent pubertal development and ovarian imaging. Patients were diagnosed at the age of 8.6 +/- 2.3 years (mean +/- SD) with severe uncompensated primary hypothyroidism (TSH levels >100 mIU/l in all; 509.3 +/- 651 mIU/l) and growth retardation (height SDS -4.1 +/- 1.8). Nine girls had vaginal bleeding at diagnosis; five also had thelarche. LH and FSH levels were prepubertal in all patients. Ovarian cysts were bilateral in eight girls (80%); internal septation was noted in six. Thyroxine replacement (4.1 +/- 0.7 microg/kg/day) led to normalization of TSH levels with reversal of pubertal changes and regression of ovarian cysts in all patients 2.2 +/- 1.0 months after treatment. At last follow-up 3.5 +/- 2.6 years after initiation of treatment at the age of 12.0 +/- 2.3 years, all patients had normal ovarian size in ultrasound evaluation with six girls progressing to normal puberty. Our study emphasizes the need to exclude hypothyroidism in young girls with ovarian cysts. Identification of hypothyroidism in these girls obviates the need for extensive investigations.

Child↗
PubMed2006

Growth pattern and skeletal maturation following growth hormone therapy in growth hormone deficiency: factors influencing outcome.

OBJECTIVE: To evaluate pattern of growth and skeletal maturation following growth hormone (GH) therapy in children with GH deficiency (GHD) with special emphasis on factors influencing outcome. METHODS: Records of ninety-six children (67 boys, 29 girls) with GHD treated with GH for 2.3 +/-2.1 years were reviewed. RESULTS: Height SDS at the end of treatment was significantly higher than that at initiation (-3.4 +/- 1.7 versus -4.8 +/-1.6, P < 0.001); it was however lower than target height SDS (corrected height SDS (1.8 +/- 1.6, P < 0.001). The greatest increase in height SDS was observed during the first two years of treatment. Kaplan Meier survival analysis showed that 92%; of all subjects achieving end height SDS in the target height range did so within the first two years of treatment. Height SDS for bone age increased by 0.7 +/-0.9 during treatment (from -2.5 +/- 1.0 to -1.8 +/- 1.5, P < 0.001); the increase was however lower compared to that for height SDS for chronological age (P < 0.01) suggesting inadvertent skeletal maturation. End height SDS was influenced by duration of treatment and corrected height SDS on multivariate analysis. CONCLUSION: GH treatment improves growth parameters in GHD; height however still remains compromised. Most of the catch-up growth occurs within two years of treatment emphasizing the need of optimal treatment during this period. Inadvertent skeletal maturation during treatment indicates a need for evaluating the role of agents effective in retarding skeletal maturation.

Adolescent↗
PubMed2005

Carrier frequency of F508del mutation of cystic fibrosis in Indian population.

BACKGROUND: Cystic fibrosis (CF) is considered to be very rare in Indian subcontinent. Based on reports of CF in migrants from Indian subcontinent to United Kingdom and United States of America, the prevalence of CF is estimated to be between 1/10,000 and 1/40,000 in this ethnic group. The present study was done to estimate the carrier frequency of F508del mutation among neonates using cord blood samples to reflect the prevalence of CF in the study population. METHODS: 955 mothers delivering at our hospital between December 1999 and November 2000 were enrolled. Cord blood samples were analyzed for F508del mutation using polymerase chain reaction and gel electrophoresis. The frequency of patients homozygous for F508del mutation in the population was estimated using Hardy-Weinberg principle. The prevalence of CF was estimated by using the proportion of F508del homozygous cases out of all CF patients, as reported in various studies (19-44%) from Indian subcontinent. RESULTS: Out of 955 cord blood samples, 4 were positive for F508del mutation. The carrier frequency and gene frequency of F508del mutation in the Indian population was calculated to be 1/238 (0.42%) and 1/477 (0.21%), respectively. Frequency of CF patients homozygous for F508del mutation is 1/228,006. The estimated prevalence of CF is 1/43,321 to 1/100,323 in Indian population. CONCLUSION: CF does occur in Indian subcontinent though the prevalence is lesser than the Caucasian population.

Cystic Fibrosis↗
PubMed2005

Mutations in TRIOBP, which encodes a putative cytoskeletal-organizing protein, are associated with nonsyndromic recessive deafness.

In seven families, six different mutant alleles of TRIOBP on chromosome 22q13 cosegregate with autosomal recessive nonsyndromic deafness. These alleles include four nonsense (Q297X, R788X, R1068X, and R1117X) and two frameshift (D1069fsX1082 and R1078fsX1083) mutations, all located in exon 6 of TRIOBP. There are several alternative splice isoforms of this gene, the longest of which, TRIOBP-6, comprises 23 exons. The linkage interval for the deafness segregating in these families includes DFNB28. Genetic heterogeneity at this locus is suggested by three additional families that show significant evidence of linkage of deafness to markers on chromosome 22q13 but that apparently have no mutations in the TRIOBP gene.

Alternative Splicing↗
PubMed2005

Hydroxyurea in thalassemia intermedia--a promising therapy.

Pharmacological agents such as hydroxyurea (HU) have been known to cause induction of fetal hemoglobin and possibly may alleviate the symptoms in thalassemia intermedia patients. Thirty-seven patients with beta-thalassemia intermedia were enrolled to assess response to HU therapy. Major response was defined as transfusion independence or hemoglobin rise of more than 20 g/l and minor response as rise in hemoglobin of 10-20 g/l or reduction in transfusion frequency by 50%. The median age was 10 years (range: 4-50 years) and median follow-up was 12 months (range: 4-36 months). Twenty-six patients (70.2%) showed response to HU therapy. Seventeen patients (45.9%) were major responders, and nine patients (24.3%) showed minor response. There was no correlation of response with beta-thalassemia mutation or XmnI polymorphism; however, the presence of alpha(3.7) deletion was associated with major response in three patients. Mean fetal hemoglobin (HbF) levels rose on HU therapy. Older age, low baseline F cell percent, and low baseline HbF levels (below 10%) were predictors of poor response. Response was evident within 1 month of starting HU therapy in the majority of responders. Thus, a short trial of HU therapy can predict durable response.

Administration, Oral↗
PubMed2005

Nephrogenic diabetes insipidus presenting with developmental delay and intracranial calcification.

A one-year-boy presented with constipation, fever, failure to thrive and developmental delay from the neonatal period. Investigations revealed persistent hypernatremia and deranged renal functions. Diagnostic work-up was suggestive of nephrogenic diabetes insipidus (NDI). Computerized tomography of head revealed calcification in the frontal, thalamic and basal ganglia region. The rare association of NDI and intracranial calcification is discussed.

Brain Diseases↗
PubMed2005

Juvenile rheumatoid arthritis with myelofibrosis with myeloid metaplasia.

Myelofibrosis with myeloid metaplasia is defined as a myeloproliferative disorder characterized by leukoerythroblastosis, tear drop erythrocytes, extramedullary hematopoesis and varying degree of myelofibrosis. It may be idiopathic or secondary to a large number of conditions. Here is a rare case of myelofibrosis occurring in a patient with juvenile rheumatoid arthritis.

Anti-Inflammatory Agents↗
PubMed2005

Behavioral problems in children with Down syndrome.

Forty consecutive children with Down syndrome were included as the Study Group (SG). The Control Group (CG) consisted of forty children attending the immunization clinic in pediatric OPD. Behavior Screening Questionnaire (BSQ) was used to screen the study groups as well as their siblings and control group for behavioral problems. The assessment of parental attitudes was done on Attitude Screening Questionnaire which includes 2 separate questionnaire for mother and father. Twenty two children (55%) with Down's syndrome showed behavioral problems as compared to 5 (12.5%) in control group. Children with Down's syndrome showed behavioral problems related to all the spheres (feeding, socialization, toilet training and sleep) as compared to control group. Mothers showed highly indulgent attitude as related to feeding to nearly total neglect as related to socialization and toilet training whereas in Paternal Attitude Screening Questionnaire, there was total neglect in all the spheres as compared to control group. There is higher prevalence of psychiatric disorders in children with Down's syndrome and their siblings.

Adult↗
PubMed2005

Detection of 22 q11.2 hemizygous deletion by interphase FISH in a patient with features of CATCH 22 syndrome.

We report an eight years female child with clinical and molecular cytogenetic findings consistent with CATCH 22 syndrome characterized by cardiac defect, typical facial dysmorphism, mental deficiency and chromosome 22 q11.2 deletion. Interphase FISH with 22q 11.2 probe demonstrated hemizygous deletion in 98.5% nuclei. Interphase FISH for diagnosis of CATCH 22 syndrome has not been reported previously from India to our knowledge.

Abnormalities, Multiple↗
PubMed2004

Intermittent hyperammonemic encephalopathy in a child with ornithine transcarbamylase deficiency.

Ornithine transcarbamylase (OTC) deficiency is an X-linked disorder and the most common inherited cause of hyperammonemia. Clinical manifestations are more severe in hemizygous males who often present in neonatal period. Heterozygous females may be asymptomatic until juvenile or adulthood. Fluctuating concentration of ammonia, glutamine and other excitotoxic amino acids result in a chronic or episodically recurring encephalopathy. The authors report a heterozygous female with OTC deficiency who presented with recurrent encephalopathy.

Brain Diseases, Metabolic↗
PubMed2004

Genetics of deafness in India.

Linkage analysis in families with hereditary hearing loss have revealed a plethora of chromosomal locations linked to deafness reflecting the extreme heterogeneity of the disorder. 40 of the genes contained within these loci have been mapped lending an insight into the diverse molecules operating in the inner ear and the remarkable complexity of the cellular and molecular processes involved in the transucdation of sound in the auditory system. Among this diversity, Connexin 26 has been found to be the most common cause of deafness the world around. The authors review here the prevalence of this gene in the Indian population as found in their study, together with other deafness genes segregating non-syndromic deafness, accounting for approximately 40% of all cases. This indicates there are several more to be identified yet. Knowledge of the genetic cause of deafness in our families is important for accurate genetic counseling and early diagnosis for timely intervention and treatment options.

Connexin 26↗
PubMed2004

Detecting fetomaternal hemorrhage after first-trimester abortion with the Kleihauer-Betke test and rise in maternal serum alpha-fetoprotein.

OBJECTIVE: To compare the incidence and detect the volume of fetomaternal hemorrhage (FMH) during first-trimester abortion with the Kleihauer-Betke test (KBT) and rise in maternal serum alpha-fetoprotein (AFP). STUDY DESIGN: Blood samples were drawn immediately before and after first-trimester termination of pregnancy in 48 women. AFP was estimated using an enzyme-linked immunosorbent assay technique. Fetal cells were counted using the acid elution technique described by Kleihauer. Volume of FMH with both techniques was calculated using standard formulae. Significant FMH was reported when there was a > 40% rise in AFP or > 0.25 mL bleed detected by KBT. RESULTS: Of the 48 cases studied, 18 (37.5%) showed no indication of FMH by either AFP or KBT. In 30 (62.5%) cases there was evidence of FMH; in 7 (14.6%) this was shown by both AFP and KBT. Another 10 (21%) showed significant changes in AFP concentration only, and 13 (27%) showed abnormal KBT results with stable AFP levels. The incidence of detectable FMH after first-trimester abortion in this series was 35% when assessed by AFP and 42% when assessed by KBT (P > .05). The mean volume of FMH detected by KBT was 0.5+/-0.05 mL and by AFP was 0.01+/-0.02 mL. CONCLUSION: This study showed that AFP and KBT are equally sensitive methods of detecting the incidence of FMH in first-trimester abortion, but concordance between the 2 tests is poor. The volume of FMH detected by KBT and FMH is also significantly different.

Abortion, Induced↗