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Biomedical subjects

D K Mitra

Publications and source records attributed to D K Mitra.

At least 19 recordsLinked to original sources

Initial surgical treatment as a determinant of bladder dysfunction in posterior urethral valves.

Bladder function in patients with posterior urethral valves (PUV) has an immense impact on long-term continence and renal function. Bladder dysfunction was corelated with the initial surgical treatment in 67 patients with PUV treated between 1985 and 2000. Age at presentation, current age, duration of follow-up, initial surgical treatment (diversion or valve fulguration), trends of renal function tests, voiding disturbances, and changes in the upper tracts were recorded. Urodynamic studies were done in all patients to determine urine flow rates, residual volume, maximal cystometric capacity (MCC), bladder compliance, involuntary detrusor activity, and pressure-specific bladder volume (PSBV) at 30 cm water. The patients were divided into three groups depending on the initial treatment: fulguration (n = 38), vesicostomy (n = 25), and ureterostomy (n = 4). At the time of this study voiding symptoms persisted in 45 patients. Mean percent MCC (% MCC) was 62%, 96%, and 100% of normal in the vesicostomy, fulguration, and ureterostomy groups, respectively (P = 0.002). Large-capacity bladders were seen in 10.9% of patients, mostly in pubertal and post-pubertal boys who were treated initially by either fulguration or ureterostomy; vesicostomy adversely affected bladder capacity and compliance (P = 0.007). PSBV was decreased in 48% of patients in the vesicostomy group and was significantly lower in the other groups (P = 0.01). Mean percent PSBV was 75%, 95%, and 96% of normal in the vesicostomy, fulguration, and ureterostomy groups, respectively. Uninhibited contractions were present in 21 patients (14 in the vesicostomy group) (P = 0.01). The highest incidence of upper-tract deterioration was seen with %MCC below 60% of normal (P = 0.001). The predominant urodynamic patterns were: (1) fulgurated group: good-capacity, compliant bladder; (2) vesicostomy group: small-capacity, hyperreflexic bladder; and (3) ureterostomy group: good capacity, compliant bladder. Primary valve ablation is associated with better bladder function than vesicostomy and should be the treatment of choice in PUV. Also, vesicostomy and ureterostomy have distinctly different effects on bladder function.

Child↗

Urinary-tract infection affects somatic growth in unilateral symptomatic hydronephrosis.

To assess whether symptomatic unilateral ureteropelvic junction obstruction (SUUPJO) affects somatic growth and, if so, the parameters associated with it, 61 children (54 boys and 7 girls) who underwent pyeloplasty for SUUPJO without any other associated urological abnormalities were retrospectively studied. Height was compared with standard growth charts and was considered to be affected if it was below 2.00 Z-score. Such children were considered group B and the rest group A. Mean (+/-SD) age at presentation and mean (+/-SD) split renal function (SRF) (%) of the affected kidney were 6.0 +/- 4.0 years and 27.3 +/- 13.2, respectively, for the entire group. Somatic growth was affected in 16 (12 boys, 4 girls) children (26.2%). Urinary tract infection (UTI) was the presenting symptom in 11 (69%) and 5 (11%) children in groups B and A, respectively. Impaired somatic growth had no association with age at presentation or SRF, but a significant association (P < 0.001) was found with UTI. The mean post-surgery height percentile (2.92 +/- 4.85) over a mean follow-up of 3.37 +/- 1.86 years was significantly (P < 0.005) better compared with pre-surgery height percentile (0.67 +/- 0.96) in group B, indicating catch-up growth after surgery. In SUUPJO, somatic growth is affected. Presentation with UTI has a significant association, and height significantly improves after surgery in these patients.

Body Height↗

A clinicopathological study of acute necrotising jejunoileitis.

We describe a variety of acute necrotizing enteritis that is endemic to the Indian subcontinent. During the period 1992-1998, 18 cases of acute jejunoileitis (AJI) were managed. Only those in whom the diagnosis was confirmed at laparotomy have been included in this study. The most common symptoms were abdominal pain (100%), fever (77%), and blood in the stool (100%). A stricture following conservative treatment was present in 1 case. The mean age at presentation was 6.5 years (range 6 months-12 years); the male:female ratio was 1.2:1. All cases were seen during May-October. Routine investigations and X-ray films were nonspecific. Stool cultures did not show any clostridia, shigella, or salmonella. The jejunum was involved most commonly; 28% of patients did not require a bowel resection. Only 1 child presented with shock; the mortality was less than 5%. Short-bowel syndrome resulted in 1 patient due to extensive disease. The histopathologic features that were characteristic of the disease were patchy transmural mucosal necrosis extending centrifugally with submucosal edema, interstitial hemorrhage, type III hypersensitivity reaction, and extensive neovascularization. This type of AJI seen in South/Southeast Asia does not seem to be due a to bacterial infective etiology; immune mediation is suggested. The milder forms can be confused with dysentery. Mild forms of the disease can be managed conservatively, but carry the risk of developing strictures. This disease should be suspected in cases of prolonged dysentery during the summer and autumn months.

Acute Disease↗

Reconstitution of naïve T cells and type 1 function after autologous peripheral stem cell transplantation: impact on the relapse of original cancer.

BACKGROUND: Phenotypic and functional reconstitution of T cells after peripheral blood stem cell transplantation (PBSCT) and its influence on posttransplant immune status is important in terms of immune surveillance and relapse of original cancer. We investigated the relationship between the dominant immune reconstitution pathway and the immune surveillance. We also tested the cytokine bias acquired by T cells after transplantation and its possible influence on relapse of original malignancy. METHODS: Immunophenotyping of naïve and memory T cells was performed by flow cytometry on patients who underwent PBSCT for various cancers. Cytokine production by peripheral memory helper (CD4) and cytotoxic (CD8) T cells was investigated at various pretransplant and posttransplant time points with fluorescein isothiocyanate-based intracellular cytokine assay after short-term in vitro mitogenic stimulation (phorbol myristate acetate + ionomycin). Data on T-cell subsets and polarized cytokines gamma-interferon (Ifn) and interleukin 4 produced by memory T cells were compared with that of healthy controls. RESULTS: The reconstitution of naïve T cells and gamma-Ifn-producing memory cells was significantly lower in patients who experienced relapse of original cancer within 1 year of PBSCT compared to those who showed no signs of relapse even after 2 years and compared to normal subjects. The results indicate that efficient reconstitution of naïve T cells and type 1 function of memory T cells are important in maintaining T-cell repertoire diversity after PBSCT. It also confers appropriate levels of immune surveillance against diverse neoantigens that evolve from residual tumor burden. The data reveal that chemotherapy-induced thymic injuries may impair regeneration of naïve cells that result in a naivopenic state in a susceptible host. CONCLUSIONS: The study highlights the importance of naïve T-cell reconstitution and points towards cell replacement strategies for improving immune surveillance after PBSCT.

Adult↗

The role of DMSA scans in evaluation of the correlation between urinary tract infection, vesicoureteric reflux, and renal scarring.

The correlation between urinary tract infection (UTI), vesicoureteric reflux (VUR) and renal scarring was studied in 89 patients (177 renal units; 1 solitary kidney) during the period 1997-2000. There were 63 males and 26 females; ages ranged from neonates to 14 years. UTI was diagnosed on the basis of a positive urine culture, VUR was diagnosed and graded by micturating cystourethrogram (MCU), and renal scarring was assessed by technetium 99 m Tc-dimercaptosuccinic acid (DMSA) scan. Ultrasonography (US) was done to evaluate renal tract dilatation and other structural abnormalities. A follow up DMSA scan was performed approximately 6 months after the initial scan. VUR was present in 106 of the 171 renal units in which it was studied and absent in 65 units. The majority of the VUR was grade V. Renal scars were seen in 90 of 177 renal units at presentation and in 72 of the 163 renal units studied at follow-up. Some information was lacking in 31 patients; hence, the correlation between UTI, VUR, and renal scarring was done in 58 patients. The majority of the suspected scars at presentation were not seen at follow-up, but most of the established scars persisted. Only 2 renal units showed scars for the first time on follow-up. On US, approximately 50% of normal kidneys showed either suspicious or established scars on DMSA scan, and patients with bilateral abnormality on US showed renal scars. Renal scars were seen in 15 of 23 children without VUR, 17 of 18 with unilateral VUR, and 16 of 17 with bilateral VUR. Thus, there is a cause-and-effect relationship between UTI and renal scarring that is made worse by VUR. DMSA scans have been shown to be the most reliable method of assessing renal scarring, and an abnormal US scan showing upper-tract dilatation or a structural abnormality may have a predictive value in the detection of renal scarring.

Adolescent↗

Fertility and unilateral undescended testis in the rat model III: ultrastructural changes in the contralateral descended testis.

Fertility is decreased in rats with experimentally-created unilateral undescended testis (UUDT). Although light microscopy has shown changes in the UDT, it has consistently failed to demonstrate any significant damage in the contralateral descended testis (CDT) of these animals in previous experimental studies utilizing the same model. To study the ultrastructural details of the CDT and the ipsilateral UDT using transmission electron microscopy (TEM) in rats with experimentally-created UUDT, in Wistar albino rat pups UUDT was experimentally created in accordance with the model described previously. Ten rats with UUDT were compared with 10 control rats. The UDT and CDT were harvested at 135 days of age and sections from specimens studied by TEM for changes in the seminiferous tubules, Leydig cells, and extracellular matrix. All observations were graded and analyzed for statistical significance. TEM of the testes of control rats was normal, while both the ipsilateral UDT and the CDT showed significant changes. Significant changes in the CDT included thickening of the basement membrane ( P=0.001), a decrease in spermatogenic cell lines ( P=0.02), vacuolation ( P=0.0001) and other features of degeneration ( P=0.02), single cell apoptotic figures ( P=0.02), and an increase in Sertoli-cell numbers ( P=0.01), size ( P=0.01), and endoplasmic reticulum ( P=0.01). Another significant feature was the occurrence of morphologic sperm abnormalities in the form of tail denudation ( P=0.02). The surgically-created UDT showed changes of gross degeneration and atrophy. TEM studies thus revealed gross ultrastructural damage to the UDT and similar subtle but significant changes in the CDT. These may explain the decrease in fertility in rats with UUDT.

Animals↗

Augmentation colocystoplasty in bladder exstrophy.

A good bladder capacity and adequate outlet resistance determine success after staged reconstruction of bladder exstrophy (BE). Augmentation cystoplasty (AC) is an established salvage procedure to treat the small, noncompliant bladders of some of these children. In a series of 89 patients with BE treated over the last 12 years, 19 underwent detubularized augmentation colocystoplasty (ACC) as an adjunctive procedure. Nine underwent ACC at the time of bladder-neck reconstruction (BNR) for small bladder capacity and poor compliance; 10 underwent ACC as a secondary procedure after BNR for persistent urinary incontinence or poor bladder compliance and upper-tract deterioration. The follow-up period ranged between 6 months and 12 years (mean 41 months). Complications included symptomatic urinary-tract infection in 4 patients, recurrent epididymo-orchitis in 2, calculi in 3, colonic anastomotic dehiscence in 1, bladder-patch fistula in 2, and secondary coloureteric-junction obstruction in 1. There was no postoperative reservoir perforation or mortality. The upper tract remained normal or stable in all patients. Nine of the 19 patients are dry both day and night; 4 others are dry during the day but have occasional nocturnal wetting. Three patients have nocturnal wetting with stress incontinence and 2 remain incontinent. Seven patients can void effectively using abdominal contractions and 12 require clean intermittent catherization to ensure complete voiding. The indications and results of AC in BE from other series are reviewed. AC is an important and safe adjunctive procedure in a subset of BE patients with small and poorly compliant bladders. Despite the known complications, more liberal use of AC in BE is warranted.

Adolescent↗

The role of imipramine therapy in bladder exstrophy after bladder neck reconstruction.

OBJECTIVE: To assess the role of imipramine therapy after bladder neck reconstruction in patients with bladder exstrophy. PATIENTS AND METHODS: Seventeen children with bladder exstrophy who achieved partial continence after bladder neck reconstruction received imipramine (1.5-2 mg/kg body weight) for a mean duration of 9.5 months. Assessment before and after therapy included an objective classification of the continence status and artificial slow-fill cystometry. RESULTS: Eleven of the 17 patients had a good clinical response to imipramine, with an increase in the continent period to > 2 h, and in nocturnal continence. The urodynamic findings showed a significant improvement in the capacity, end-fill pressure, uninhibited contractions and '20 below' capacity. Only minor side-effects of the drug were reported. CONCLUSION: Imipramine has a role in patients who achieve partial continence after reconstruction, and who have a moderately small capacity bladder with poor compliance and uninhibited contractions.

Antidepressive Agents, Tricyclic↗

Urinary citrate excretion in idiopathic nephrolithiasis.

OBJECTIVE: To determine urinary citrate excretion in children with nephrolithiasis and normal controls. DESIGN: Prospective. SETTING: Tertiary care center in New Delhi. METHODS: This study was done on 50 children, below the age of 12 years, with idiopathic urinary calculi and 150 age and weight matched controls. The children were divided into 3 groups: Group 1 (1-4 years), Group 2 (5-8 years) and Group 3 (9-12 years). Urinary citrate was estimated in a 24-hour urine sample using colorimetric method. The stones removed from these children were also analysed. RESULTS: There was a preponderance of urinary stones in males; the highest incidence being in Group 1. Excretion of citrate in 24-hour urine sample was significantly lower in patients compared to controls, for males in all age groups and for females in Group 3. However, there was no statistically significant difference in the urinary citrate value between males and females in a given age group for either controls or patients. The urinary citrate excretion increased with age in patients and controls, but the levels in patients were lower. Depending upon the constituents, four types of stones were identified, calcium phosphate, calcium oxalate, uric acid and magnesium ammonium phosphate. Nine stones had at least more than one major constituent. Hypocitraturia was detected in 43 percent cases. The incidence was 76 percent for calcium phosphate, 87 percent for calcium oxalate, 40 percent for uric acid stones and 50 percent for magnesium ammonium phosphate. CONCLUSION: This study shows that low urinary citrate is associated with urinary stones in children, especially in endemic areas, in the absence of obvious etiological factors. Urinary citrate excretion should be determined in all children with nephrolithiasis.

Case-Control Studies↗

Cholelithiasis in thalassaemia major.

The incidence of gall stones in thalassaemia is less than that in sickle cell anaemia or hereditary spherocytosis. With adequate blood transfusions, the incidence is as low as 2%. There are not many reports on cholelithiasis in thalassaemia. A case of 24-year-old female with thalassaemia major and gall stone is reported here.

Adult↗

A monoclonal antibody cytolytic to androgen independent DU145 and PC3 human prostatic carcinoma cells.

BACKGROUND: While a range of therapeutic products is available for androgen-dependent prostatic cancer, no specific intervention modality exists for androgen-independent prostatic cancer. The objective of this research was to explore whether epitopes exist on androgen-independent prostatic DU145 cancer cells, which could be susceptible to cytotoxic action of specific antibodies. METHODS: Hybrid cell clones were developed by immunization of mice with DU145 cells and tested for immunoreactivity by solid phase EIA and cytotoxicity in vitro on DU145 in the presence of the complement, employing colorimetric quantitation by MTS (3- (4-, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-(4-sulfophenyl)-2H-tetrazolium). Binding and cytotoxicity studies were also carried out by flow-cytometry. RESULTS: Of 15 stabilized clones immunoreactive with DU145 cells, one monoclonal antibody (mAb 730) manifested cytotoxicity on DU145 cells. Approximately 80% of cells in the DU145 cell line were susceptible to lysis with this antibody at saturating levels. This figure corresponded quantitatively to the number of cells binding with this antibody as determined by Flow-cytometry. Staining with ethidium monoazide bromide (EMA) showed that the cell binding the antibody was also the one killed by the antibody in the presence of the complement. MAb 730 was also cytotoxic to PC3, another androgen-independent human prostatic cancer cell line. This antibody is devoid of classical autoantibody reactivities and does not react with normal human liver, thyroid, kidney, pancreas, and adrenal tissues, as determined by immunofluorescence. Also, it shows negative immuno-reactivity to benign glandular tissue but is observed to positively react with neoplastic prostate tissue. CONCLUSIONS: Epitopes exist on androgen-independent prostatic cancer cells that are susceptible to cytolysis by monoclonal antibodies and these could be investigated for potential immunotherapy.

Animals↗

Immunobiology of CD28 expression on human neutrophils. I. CD28 regulates neutrophil migration by modulating CXCR-1 expression.

CD28, described as a T cell costimulatory molecule so far, is expressed on human peripheral blood neutrophils, as shown by cell surface staining and immunoprecipitation with anti-CD28 monoclonal antibody, and by reverse transcription PCR. The phorbol 12-myristate 13-acetate-augmented expression of CD28 on these cells can be blocked by actinomycin D, an RNA transcription inhibitor, and staurosporin, a protein kinase inhibitor. Cross-linking of CD28 results in an early increase in IL-8 receptor A (IL-8RA or CXCR-1) expression and a concurrent increase in IL-8-induced chemotaxis. The expression of CXCR-1 is down-regulated by receptor internalization 3 h after CD28 cross-linking with concurrent decrease in IL-8-induced chemotactic migration. Thus, our results demonstrate for the first time that CD28 is expressed on human peripheral blood neutrophils and that CD28 may play an important role in the regulation of IL-8RA expression and migration of neutrophils in response to IL-8.

Adult↗

Association between lower hair zinc levels and neural tube defects.

Though folic acid supplementation has reduced the incidence of Neural Tube Defects (NTD), NTD still constitutes one of the important congenital malformations having wide medical, social and ethical implications. Zinc deficiency has been reported to produce NTD in animals. This study was designed to evaluate zinc status of the newborn babies with NTD and their mothers. Eighty newborn babies with NTD and their mothers served as cases. Eighty apparently normal newborn babies and their mothers served as controls. Serum and scalp hair zinc levels were analyzed by atomic absorption spectrophotometry. The mean (+/- SD) serum and hair levels in normal mothers were 74.1 +/- 4.1 micrograms/dl and 142.3 +/- 8.0 micrograms/g respectively. The mean (+/- SD) serum and hair levels of the mothers who delivered NTD babies were 75.7 +/- 5.6 micrograms/dl and 129.9 +/- 5.3 micrograms/g respectively. The mean (+/- SD) serum and hair levels in normal newborn babies were 77.8 +/- 5.3 micrograms/dl and 188.8 +/- 6.2 micrograms/g respectively. The mean (+/- SD) serum and hair levels in NTD babies were 80.1 +/- 12.9 micrograms/dl and 174.2 +/- 10.7 micrograms/g respectively. The hair zinc levels of the affected babies and their mothers were significantly lower (P < 0.001) than the controls. This study has found association between NTD and decreased hair zinc levels and large population based studies are recommended to confirm the association between zinc and NTD and to investigate whether zinc supplementation would reduce the overall incidence of NTD.

Developing Countries↗

Silo construction from a sterile adhesive film and polypropylene mesh in the repair of gastroschisis and omphalocele.

A simple technique of constructing a silo for the treatment of gastroschisis (GS) and omphalocele (OMP) is described. A polypropylene mesh covered on both sides with a sterile transparent adhesive film (incise drape) was used; both these items are freely available in the operating room. The resultant silo is sterile, soft, flexible, sturdy, internally smooth, provides a reasonable barrier, and allows enough visibility of the bowel. This silo was used in the treatment of 25 cases of GS and 13 cases of OMP with acceptable results. Survival was better in patients in whom primary closure could be achieved in both OMP and GS. Silo treatment was associated with higher mortality from septic causes.

Gastroschisis↗

Evaluation of developing rat testis by phosporus 31P magnetic resonance spectroscopy and DNA flowcytometry.

For the assessment of germ-cell maturation of the seminiferous tubules, DNA flowcytometry is a rapid and sensitive method. Phosporus 31P magnetic resonance spectroscopy (MRS) is a non-invasive alternative that demonstrates the metabolic status of the testis, reflecting the type and relative proportion of germ cells in the testis. This study was designed to evaluate the utility of 31P MRS in reflecting the haploid-cell population of the testis as measured by DNA flowcytometry. A single testicle was evaluated in male Wistar pre-pubertal rats at 30, 40, 50, and 60 days of age. In order to minimize the contamination of signals from the contralateral testis, scrotum, and tail, the technique was modified and the testis was evaluated ex-vivo with an intact blood supply. At 30 days of age the percentage of haploid cells was 43.6 +/- 1.8, and this increased to 72.7 +/- 1.4 at 60 days of age. During this period, the testicular phosphomonoester/adenosine triphosphate (PM/ATP) ratio changed from 1.70 +/- 0.21 to 0.32 +/- 0.08. There was a significant (P < 0.001) linear correlation between the proportion of haploid cells evaluated by DNA flowcytometry and the PM/ATP ratio evaluated by 31P MRS. 31P MRS is thus a reliable, noninvasive technique for accurately assessing the status of the seminiferous epithelium.

Animals↗

Functional outcome after pyeloplasty for unilateral symptomatic hydronephrosis.

The functional outcome and factors influencing improvement after pyeloplasty for ureteropelvic junction (UPJ) obstruction are still debated. This retrospective study was aimed at evaluating the factors associated with functional improvement in symptomatic unilateral hydronephrosis (HDN). Patients (n = 68) who underwent successful pyeloplasty for unilateral symptomatic UPJ obstruction without any other associated urological abnormality were included. Preoperative evaluation included a diuretic renogram (DR) to confirm obstruction and assess the split renal function (SRF). A follow-up DR was obtained 3 months and 1, 2, and 5 years postoperatively. An absolute increase in the differential function of the operated kidney by over 5% was considered significant; such kidneys were classified as improved (group A) and the others as unimproved (group B). The difference between the preoperative and 3-month SRF was highly significant (P < 0.001). Significant (P < 0.01) improvement in SRF continued until 1 year after pyeloplasty. Patients who presented with a mass had significantly greater improvement (P < 0.05) than those who presented with other clinical features. In group A, a significantly higher number of patients presented with a mass. It was also evident that patients aged less than 1 year showed significantly greater (P < 0.01) improvement in SRF than older patients. Thus, in unilateral symptomatic HDN with impaired function, patients who present with a mass or those in whom pyeloplasty was performed before 1 year of age showed significantly greater improvement.

Child↗

Cystometric evaluation of reconstructed classical bladder exstrophy.

OBJECTIVE: To evaluate the association of urodynamic variables with continence and upper tract status after reconstruction in patients with classical bladder exstrophy. PATIENTS AND METHODS: Thirty-one patients with bladder exstrophy were assessed 1 year after a modified bladder neck reconstruction. The evaluation included a detailed history, radioisotope renography, voiding cysto-urethrography, ultrasonography and artificial slow-filling cystometry. RESULTS: Fifteen of the 31 patients were satisfactorily continent; their maximum cystometric capacity was higher than that of the incontinent patients. The compliance, assessed as the maximum bladder capacity at a detrusor pressure of < 20 cmH2O, was significantly higher in the continent patients. There was a 45% incidence of unstable contractions in the 31 patients. Persistent sphincteric activity was detected on electromyography in 10 patients during voiding. Twenty-one patients could initiate a detrusor contraction during voiding. The residual volume was significant in nine of the 21 patients who attempted to void. Patients with a high end-fill pressure (> 40 cmH2O) had a significantly higher incidence of unobstructive hydronephrosis than had patients who had an end-fill pressure of < 40 cmH2O. CONCLUSIONS: Bladder abnormalities are common after reconstruction of bladder exstrophy, with poor compliance, small capacity and unstable contractions. These factors hinder any increase in capacity and cause persistent incontinence. Hypocompliance and high end-fill pressure can lead to upper tract damage even in continent patients. Detailed urodynamic evaluation is vital to assess the results and to plan subsequent treatment.

Bladder Exstrophy↗