Children with untreated coeliac disease have sub-clinical cardiac dysfunction: a longitudinal observational analysis

Introduction: We assessed cardiac function (CF) in celiac disease (CD) patients and the effect of gluten-free diet (GFD) on CF.

Methods: Prospective evaluation of CF using conventional and tissue doppler echocardiography in 50 CD patients (age 4.2?±?1.1 years) at diagnosis and after a year of GFD (group 1), 100 CD children (group 2; 47 compliant and 53 non-compliant) in follow-up and 25 healthy controls.

Results: Untreated CD (n?=?50) children had larger left ventricle end diastolic dimension (35.33?±?0.87 vs. 32.90?±?0.91 mm; p?=?.04), reduced (<55%) left ventricular ejection fraction (20% vs. 0%; p?=?.01) and a higher (>0.6) myocardial performance index (MPI, 66% vs. 0%; p ≤ .01) as compared to controls. Re-evaluation after one year with good dietary compliance showed changes in isovolumic relaxation time (72.5?±?4.2 vs. 50.62?±?2.69; p?=?.0001) and deceleration time (121.05?±?10.1 vs. 99.87?±?8.5; p?=?.02), reflecting improved cardiac diastolic function. GFD compliant patients had lower MPI than non-compliant (0.60?±?.03 vs. 0.66?±?.08; p?=?.04), reflecting improvement in load-independent echocardiographic parameters.

Conclusions: Subclinical cardiac dysfunction is common in CD children at diagnosis. Improvement

in echocardiographic parameters occurs with GFD and non-compliant children continue to have

persistent cardiac dysfunction.     

Prostate specific antigen ratio: for diagnosis and assessment of aggressiveness of malignancy of prostate

The search for a perfect tumour marker, which would be able to distinguish benign from malignant enlargement of prostate accurately, is still not complete. Total Prostate Specific Antigen (TPSA), a good test, has it's own inadequacies but Free Prostate Specific Antigen (FPSA) to TPSA ratio is emerging as a better adjuvant to it. This prospective study was done to verify the utility of FPSA to TPSA ratio in diagnosis of malignancy of prostate and its relationship to Gleason grading (indicating the aggressiveness) of adenocarcinoma of prostate. 100 patients with urinary symptoms, who were above fifty years of age and had prostatic enlargement, formed the study group. TPSA and FPSA were assayed by ELISA method and FPSA to TPSA ratio was calculated. Prostatic biopsy of all the cases was obtained and diagnostic histopathology and Gleason grading (in cases where adenocarcinoma was diagnosed) was done. Sensitivity, specificity, predictive value of positive test and predictive value of negative test for TPSA and FPSA to TPSA ratio were calculated. They were found to be 100%, 76.7%, 74.1% and 100% for TPSA and 82%, 100%, 100%, 89% for FPSA/TPSA ratio. Thus making it very obvious that FPSA to TPSA ratio is an excellent adjuvant to TPSA for diagnosis of malignancy of prostate increasing the specificity and predictive value for positive test. An inverse correlation (correlation coefficient = -0.95) was also found between PSA ratio and aggressiveness of prostate cancer, pointing towards its capability to predict the histological (Gleason) grade of the tumour.     

Busulfan/melphalan/antithymocyte globulin followed by unrelated donor cord blood transplantation for treatment of infant leukemia and leukemia in young children: the Cord Blood Transplantation study (COBLT) experience.

A non-total body irradiation-containing preparative regimen was studied in young children (<4 years old) undergoing unrelated donor cord blood transplantation as part of the Cord Blood Transplantation trial for the treatment of acute lymphoblastic leukemia (n = 14), acute myeloid leukemia (n = 13), undifferentiated leukemia (n = 1), juvenile myelomonocytic leukemia (n = 2), and myelodysplastic syndromes (n = 2). Donor/recipient HLA matching based on low-/intermediate-resolution molecular typing for HLA-A and -B and high-resolution HLA-DRB1 typing was 5/6 or 6/6 (n = 21) or 4/6 (n = 11). The preparative therapy consisted of busulfan, melphalan, and antithymocyte globulin, with cyclosporine and corticosteroids for graft-versus-host disease (GVHD) prophylaxis. The median age was 1.6 years (range, 0.5-3.9 years), and the median weight was 10.5 kg (range, 5.8-19.5 kg). Cord blood grafts contained a median of 10.7 x 10 7 nucleated cells per kilogram (range, 4.6-29.2) and 2.6 x 10(5) CD34+ cells per kilogram (range, 0.7-8.3). The cumulative incidence (CINC) of neutrophil recovery (absolute neutrophil count >500/microL) at day 42 was 0.59 (95% confidence interval [CI], 0.44-0.78) at a median of 31 days (range, 23-55 days). The CINC and Kaplan-Meier estimates of platelet engraftment at day 180 were 0.53 (95% CI, 0.34-0.69) and 0.82 (95% CI, 0.61-1.00), respectively. CINC estimates of grade III/IV acute GVHD at day 100 and chronic GVHD at 1 year were 0.25 (95% CI, 0.09-0.41) and 0.26 (95% CI, 0.09-0.44), respectively. The CINC estimate of relapse was 0.31 (95% CI, 0.16-0.47) at 2 years. With a median follow-up of 27.8 months (range, 23.4-46.7 months), the probability of survival at 1 year was 0.47 (95% CI, 0.30-0.64). A preparative regimen containing a busulfan/melphalan/antithymocyte globulin preparative regimen is well tolerated in the setting of unrelated donor cord blood transplantation for childhood leukemia and can serve as a platform preparative regimen for intensifying host immunosuppression and antileukemic therapy to allow for improved engraftment and improved relapse-free survival.     

Corpus callosum morphometry: comparison of fresh brain,preserved brain and magnetic resonance imaging values

In recent years interest in the anatomy of corpus callosum (CC) has led to a number of studies on morphometric analysis of CC, either in vivo on magnetic resonance imaging (MRI) or on preserved (formalin-fixed) cadaveric brain specimens. There are very few reports comparing the values obtained by both these methodologies, and to the authors' knowledge no study of CC morphometry in fresh (unfixed) autopsy brains has been done. Morphometric measurements of the CC were done on fresh autopsy brains ( n  = 15), preserved cadaveric brains ( n  = 44) and MRI scans ( n  = 30) in adults (age range: 20–60 years) of both sexes without any intracranial brain pathology, in north-west Indian subjects. Most of the CC measurements were found to be more in the fresh autopsy brain group as compared to the preserved cadaveric brain and MRI group. The distance between the splenium and superior colliculus in the fresh autopsy brain group was almost twice that in the other two groups. In addition, there was a similarity between the preserved cadaveric brain and MRI values for most of the parameters, but the distances between the genu and fornix and between the genu and anterior commissure were larger in the MRI group as compared to the other two groups. The present data may be of value in studying deviations from the normal in various disease processes as well in surgical planning of intraventricular and callosal pathologies.     

Clinical relevance of palmaris longus agenesis: common anatomical aberration

Palmaris longus muscle, although of little functional use to the human upper limb, assumes great importance when used as a donor tendon for transfer or transplant. The variability in the prevalence of palmaris longus agenesis among various ethnic groups has been established, and the surgeon's awareness of the prevalence in a population or ethnic group is desirable. The prevalence of palmaris longus agenesis has, to the best of the authors' knowledge, not been reported in Indian patients. Five hundred Indian patients were examined for the presence or absence of palmaris longus tendon, using the conventional test for presence of palmaris longus. The prevalence and pattern of palmaris longus agenesis was analyzed statistically and any difference in prevalence or pattern of palmaris longus agenesis with regard to body side or sex was looked for. All statistical analysis was done using SPSS (version 12). chi2 test was used to analyze the association of agenesis with limb laterality and sex. The prevalence of palmaris longus agenesis was found to be 17.2% (8% bilateral and 9.2% unilateral). The prevalence of agenesis was significantly more common on the left side. Male subjects had a greater likelihood of unilateral agenesis, while female subjects were more likely to have bilateral agenesis. That prevalence of palmaris longus agenesis is race dependent is reaffirmed in the present study. Although the prevalence of palmaris longus agenesis in Indian patients was found to be much higher than the reported average prevalence in an Asian population, this tendon can still be counted on by surgeons treating Indian patients for use as a donor tendon, which will be present in a vast majority of Indian patients.     

Marked interindividual variability in the response to selective inhibitors of cyclooxygenase-2

BACKGROUND & AIMS: Variability in response to drugs may influence both efficacy and safety. Cyclooxygenase (COX)-2 inhibitors pose a cardiovascular risk by potentially increasing the likelihood of thrombosis, hypertension, and atherogenesis. Differences between individuals in the response to COX-2 inhibitors would be expected to influence their susceptibility to cardiovascular complications. We examined the variability in degree and selectivity of COX-2 inhibition in humans in response to celecoxib and rofecoxib. METHODS: Fifty healthy volunteers received placebo, rofecoxib (25 mg), and celecoxib (200 mg), randomized by order. COX-1 and COX-2 inhibition was determined using ex vivo and in vivo indices of enzymatic activity. A subset of 5 individuals underwent 5 replicate studies to estimate variability in drug response both within and between subjects. RESULTS: Despite the higher COX-2 selectivity of rofecoxib in vitro, the average selectivity attained by 25 mg rofecoxib and 200 mg celecoxib in vivo were not different. However, there was considerable variability at an individual level in the degree of COX-2 inhibition and selectivity attained by both drugs. Approximately one third of the variability was attributable to differences between individuals, suggesting the contribution of genetic sources of variance, such as candidate polymorphisms detected in COX-1 and CYP2C9. CONCLUSIONS: The actual degree of selectivity for inhibition of COX-2 achieved by the coxibs relates both to chemical properties of the drug and to factors within an individual that modulate drug response. These sources of variability might be exploited to identify patients uniquely susceptible to benefit or at developing risk of cardiovascular complications.     

Transabdominal gastroesophageal devascularization without esophageal transection for emergency treatment of variceal hemorrhage.

BACKGROUND: The Suguira procedure is an effective non-shunting operation to treat life-threatening hemorrhage from esophageal or gastric varices. The goal of esophageal transection is interruption of submucosal varices, but this leads to high morbidity and mortality rates from esophageal fistulization. AIM: To evaluate a variant of this procedure in which the esophagus is not transected, but the varices are underrun from outside the lumen. METHODS: During the last four and a half years, we performed this modified gastroesophageal devascularization with or without splenectomy in 18 patients as emergency treatment of bleeding esophageal and gastric varices. The data were analyzed retrospectively. RESULTS: Bleeding was controlled in all patients. Three patients with Child's class C disease undergoing emergency surgery died during the early postoperative period. Rebleeding rate was 17% (3 patients). The overall survival was 72.2% (13 of 18). No patient had encephalopathy over a mean follow up of 30 months. CONCLUSION: Gastroesophageal devascularization with variceal under-running without esophageal transection is an effective and safe alternative to shunt surgery in the emergency situation.