The DOTS strategy for treatment of paediatric pulmonary tuberculosis in South Delhi, India.

SETTING: Paediatric Pulmonology Department, TB Institute, New Delhi, India. OBJECTIVE: To evaluate the outcome of the DOTS strategy for paediatric pulmonary tuberculosis (TB). DESIGN: Retrospective analysis of 1098 children. RESULTS: The mean age of the children included in the study was 11.2 years, with more females (61.7%) than males (38.3%). In the 0-5, 6-10 and 11-14 year age groups, the percentage of patients was respectively 18.3%, 26.6% and 55.1%. Patients were registered as new cases (87.7%), relapses (1.9%), failures (1.0%), defaulters (5.0%), transferred in (0.9%) and others (3.5%). Of the total number of cases, 414 were smear-positive and 404 smear-negative, while sputum status was not known for 280 patients. Sputum positivity increased with age. Category I, II and III regimens were started by respectively 50.6%, 10.5% and 38.9% patients. The cure rate was 92.4% (302/327) for new and 92% (80/87) for retreatment cases (chi(2)(1) = 0.02, P = 0.901), but the treatment completion rate was significantly higher for new cases (97%, 636/656) than retreatment cases (53.6%, 15/28) (chi(2)(1) = 100.8, P < 0.001). The overall success rate was 95.4% and 82.6% for new and retreatment cases, respectively (chi(2)(1) = 30.35, P < 0.001). Overall, the rates for default, failure and death in the study were respectively 3%, 1.9% and 1%. CONCLUSION: DOTS appears to be a highly efficacious treatment strategy.     

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

Morbidity compression or expansion? A temporal analysis of the age at onset of non-communicable diseases in India

While there is evidence of morbidity compression in many countries, temporal patterns of non-communicable diseases (NCDs) in developing countries, such as India, are less clear. Age at onset of disease offers insights to understanding epidemiologic trends and is a key input for public health programs. Changes in age at onset and duration of major NCDs were estimated for 2004 (n = 38,044) and 2018 (n = 43,239) using health surveys from the India National Sample Survey (NSS). Survival regression models were used to compare trends by sociodemographic characteristics. Comparing 2004 to 2018, there were reductions in age at onset and increases in duration for overall and cause-specific NCDs. Median age at onset decreased for NCDs overall (57 to 53 years) and for diabetes, hypertension, heart disease, asthma, mental diseases, eye disease, and bone disease in the range of 2–7 years and increased for cancer, neurological disorders, some genitourinary disorders, and injuries/accidents in the range of 2–14 years. Hazards of NCDs were higher among females for cancers (HR 1.51, 95% CI 1.19–1.90) and neurological disorders (HR 1.18, 95% CI 1.06–1.32) but lower for heart diseases (HR 0.88, 95% CI 0.79–0.97) and injuries/accidents (HR 0.87, 95% CI 0.77–0.99). Hazards were greater among those with lower educational attainment at younger ages and higher educational attainment later in life. Unlike many countries, chronic disease morbidity may be expanding in India for many chronic diseases, indicating excess strain on the health system. Public health programs should focus on early diagnosis and prevention of NCDs.

     

Regulation of stimulated integrin surface expression in human neutrophils by tyrosine phosphorylation

The control of the adhesive properties of human neutrophils is an essential element of their defense function. One level at which this control is exerted involves the upregulation of the surface expression of beta 2-integrins. In this study, we have examined the potential involvement of tyrosine phosphorylation in the latter process. Two inhibitors of tyrosine kinases with differing modes of action, erbstatin and herbimycin A, were found to inhibit the expression of CD11b and CD18 stimulated by chemotactic factors (fMet-Leu-Phe or leukotriene B4) or growth factors (tumor necrosis factor alpha). This inhibition was not shared by an inactive analog of erbstatin or by the protein kinase C inhibitor Ro 31-8330. Erbstatin also inhibited the unveiling of activation-specific neoepitopes detected by antibody CBRM1/5. Pretreatment of neutrophils (but not of endothelial cells) with erbstatin inhibited the stimulation of neutrophils' adherence to endothelial cells induced by fMet-Leu-Phe. Augmentation of tyrosine phosphorylation by inhibiting tyrosine phosphatases using hydroperoxyvanadate led to an increased surface expression of CD11b and CD18 and enhanced the adhesion of neutrophils to endothelial cells. Finally, the leumedin NPC 15669, which had previously been shown to inhibit stimulated CD11b expression and neutrophil adherence to endothelial cells and to exhibit anti-inflammatory properties in various in vivo models of inflammation, inhibited the stimulation of tyrosine, phosphorylation induced by fMet-Leu-Phe. Taken together, these data establish a strong correlation between tyrosine phosphorylation and integrin upregulation in stimulated human neutrophils.     

Non invasive ventilation in COPD

Non invasive ventilation refers to the technique of providing ventilatory support without a direct conduit to the airway. It is a promising new technique, which is particularly useful in patients with COPD. Patients with COPD are prone to develop acute exacerbations, which pushes them into acute respiratory failure. Under these circumstances, tracheal intubation and mechanical ventilation is associated with significant morbidity and mortality. A number of well conducted studies support the fact that non invasive positive pressure ventilation (NIPPV) in these circumstances reduces rates of intubation, mortality, complications and duration of hospital stay. The biggest advantage of these techniques is their simplicity, ease of implementation and improved patient comfort allowing them to retain important functions like speech, cough and swallowing. NIPPV should be instituted early in the course of acute respiratory failure due to COPD before irreversible fatigue sets in. The current thinking is that NIPPV rests the respiratory muscles allowing other therapies time to be effective. Facilities for NIPPV should be available in all hospitals admitting patients with respiratory failure. Patients with severe, stable COPD who are hypercapnic and are deteriorating despite maximal conventional treatment should definitely be offered a trial of NIPPV. In such patients NIPPV has been shown to improve quality of life, reverse blood gas abnormalities, improve exercise tolerance and reduce hospital admissions. Physicians must familiarize themselves with this promising new ventilatory technique.     

Patterns of hematopoietic chimerism following bone marrow transplantation for childhood acute lymphoblastic leukemia from volunteer unrelated donors

Hematopoietic chimerism was analyzed in serial bone marrow samples taken from 28 children following T-cell depleted unrelated donor bone marrow transplants (UD BMT) for acute lymphoblastic leukemia (ALL). Chimeric status was determined by polymerase chain reaction (PCR) of simple tandem repeat (STR) sequences (maximal sensitivity, 0.1%). At least two serial samples were examined in 23 patients. Of these, two had evidence of complete donor engraftment at all times and eight showed stable low level mixed chimerism (MC) (<1% recipient hematopoiesis). All 10 of these patients remain in remission with a minimum follow-up of 24 months. By contrast, 13 patients demonstrated a progressive return of recipient hematopoiesis. Five of these relapsed (4 to 9 months post BMT), one died of cytomegalovirus pneumonitis and seven remain in remission with a minimum follow-up of 24 months. Five children were excluded from serial analysis as two serial samples were not collected before either relapse (3) or graft rejection (2). We conclude that as with sibling transplants, ex vivo T depleted UD BMT in children with ALL is associated with a high incidence of MC. Stable donor engraftment and low level MC always correlated with continued remission. However, detection of a progressive return of recipient cells did not universally correlate with relapse, but highlighted those patients at greatest risk. Serial chimerism analysis by PCR of STRs provides a rapid and simple screening technique for the detection of relapse and the identification of patients with progressive MC who might benefit from detailed molecular analysis for minimal residual disease following matched volunteer UD BMT for childhood ALL.     

Evaluation of retinopathy of prematurity screening in reverse Kangaroo Mother Care: a pilot study

Purpose

To evaluate retinopathy of prematurity (ROP) screening practice in reverse Kangaroo Mother Care (R-KMC) with respect to stress and pain to the infant.

Methods

In a pilot study we evaluated ROP screening practice in R-KMC in 20 babies at risk of ROP. The R-KMC differed from the conventional KMC with respect to the baby position where the baby lay supine on mother''s chest. With the mother lying supine and the baby in R-KMC position, screening examinations were done with indirect ophthalmoscope. The outcome measures included stress (quantified by pulse, respiration, and oxygen saturation) and pain to the baby by observing facial expression (eye squeezing, crying, and brow bulge). The heart rate, respiratory rate, and SpO2 (%) were compared before and immediately after the procedure using paired t-test.

Result

Mean (±SD) gestational age and birth weight were 30.8±2.3 weeks and 1362.5±253.9 g, respectively. During examination in R- KMC position 8 babies (40%) were completely relaxed (no eye squeezing and crying), 10 (50%) were partially relaxed (no brow bulge) and 2 babies (10%) were not relaxed. A change in heart and respiration rate both by 10 per minute was recorded in 12 (60%) and 10 (50%) babies, respectively. Five babies (25%) had reduction in blood oxygen concentration below 92%. The majority of the mothers (19 of 20) were relaxed.

Conclusion

ROP screening in R-KMC can be a baby friendly screening practice with respect to stress and pain to the infant and needs further evaluation in a larger cohort.     

Retrieval of fractured dialysis catheter through phlebotomy of internal jugular vein: a case report

A central venous catheter is the most common access for initiating hemodialysis. Prolonged access through a central venous catheter increases the risk of infection and dysfunction of the catheter with potential development of catheter-induced thrombosis and embolism. However, fracture and dislodgement of the catheter with subsequent embolization is an unexpected complication. Endovascular treatment is a promising method to remove intravascular foreign bodies. We herein report a case of a 58-year-old woman undergoing prolonged hemodialysis who required central venous catheter removal because of mechanical fracture of the tunneled cuffed catheter and its migration in the internal jugular vein. An urgent chest X-ray showed that the two free ends of the fractured tunneled cuffed catheter were located in the right atrium and right internal jugular vein. Phlebotomy of the internal jugular vein was successfully performed to retrieve the fractured tunneled cuffed catheter and the associated thrombi. In this case, phlebotomy for retrieval of the embolized catheter fragment extending into the right atrium was a safe alternative to an endovascular technique of catheter fragment retrieval. Phlebotomy preserved the integrity of the catheter fragment and its associated thrombus and was both cost-effective and safe.     

Involvement of guanine nucleotide binding proteins in neutrophil activation and priming by GM-CSF

Pre-incubation of human neutrophils with pertussis toxin significantly inhibited the neutrophil-directed biologic actions of granulocyte- macrophage colony-stimulating factor (GM-CSF) in three separate assays: the induction of c-fos mRNA, the enhancement of both platelet- activating factor-induced mobilization of intracellular calcium, and stimulation of leukotriene synthesis by the calcium ionophore A23187. Cholera toxin did not have an effect on the latter two assays. Pre- treatment of human neutrophils with pertussis toxin did not affect the binding of GM-CSF to its surface receptor. These results provide the first evidence that a pertussis toxin substrate plays an important mediatory role in the mechanism of action of GM-CSF.