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Biomedical subjects

S Agarwala

Publications and source records attributed to S Agarwala.

At least 19 recordsLinked to original sources

Sonic hedgehog control of size and shape in midbrain pattern formation.

Little is known about how patterns of cell types are organized to form brain structures of appropriate size and shape. To study this process, we employed in vivo electroporation during midbrain development to create ectopic sources of Sonic Hedgehog, a signaling molecule previously shown to specify different neuronal cell types in a concentration-dependent manner in vitro. We provide direct evidence that a Sonic Hedgehog source can control pattern at a distance in brain development and demonstrate that the size, shape, and orientation of the cell populations produced depend on the geometry of the morphogen source. Thus, a single regulatory molecule can coordinate tissue size and shape with cell-type identity in brain development.

Animals↗

HSV-1 vector-delivered FGF2 to the retina is neuroprotective but does not preserve functional responses.

Fibroblast growth factor 2 (bFGF, FGF2) exhibits mitogenic, angiogenic, wound healing, and neuroprotective properties. Infusion of FGF2 in vivo to treat neurodegenerative disorders in animal models results in increased survival of damaged neurons, but these effects are transient. To test the feasibility of HSV vector-delivered FGF2 for neuroprotection, we inserted the FGF2 gene under the control of the HCMV immediate-early promoter into an attenuated avirulent HSV-1 vector. Transduction with FGF2/HSV-1 virus promoted survival of PC12 cells, induced differentiation of these cells to the neuronal phenotype in vitro, and protected PC12 neuronal cells from death induced by nerve growth factor withdrawal. The attenuated FGF2/HSV-1 virus was able to deliver and direct expression of the FGF2 gene in the eye. Delivery prior to light exposure in a rat model of retinal degeneration resulted in significant protection against photoreceptor loss. However, functional ERG responses were not detected. Treatment of normal eyes with the vector alone suppressed ERGs, which were only partially restored in eyes receiving the FGF2 vector. Thus, although the FGF2-HSV-1 virus induced preservation of cell and tissue structure, this was not sufficient to protect photoreceptor function.

Animals↗

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↗

Thoracoabdominal intestinal duplication with absent inferior vena cava.

We report a rare case of thoracoabdominal intestinal duplication with absent inferior vena cava (IVC). The patient was initially explored with a mistaken diagnosis of diaphragmatic hernia on the basis of a chest radiograph and barium meal. However, a subsequent computed tomography scan revealed a mediastinal mass with an air-fluid level, a hugely dilated azygos vein, and an absent IVC. Thoracoabdominal exploration was required to excise the duplication cyst arising from the jejunum. We believe that this is the first report of this association.

Azygos Vein↗

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↗

Pediatric extragonadal germ cell tumor of the scalp.

Extragonadal germ cell tumors are relatively rare tumors, accounting for 5% to 10% of all germ cell tumors in adults. In children, approximately two thirds of germ cell tumors are extragonadal. Extragonadal germ cell tumor of the scalp is exceedingly rare. The authors report the case of a 1(1/2)-year-old boy with extragonadal germ cell tumor over the occipital region. Examination of the chest, abdomen, and gonads was normal. Computed tomography scan of the head showed a large, well-defined, lobulated, heterogeneously enhancing soft tissue mass lesion in the occipital region. The underlying bone was normal with no evidence of intracranial extension. Biopsy results of the scalp mass showed features consistent with embroynal carcinoma. Serum alpha-fetoprotein (AFP) level was elevated. The child was started on chemotherapy and received 4 cycles of cisplatin, etoposide, and bleomycin (PEB). There was more than 90% reduction in the size of the mass at the end of the fourth cycle. The residual mass was excised and followed up with 2 cycles of postoperative PEB. Ten months after excision the patient is well, without recurrence, and the AFP level is normal.

Antineoplastic Combined Chemotherapy Protocols↗

Transitional cell carcinoma of the urinary bladder following exposure to cyclophosphamide in childhood.

With the increasing survival of children with malignancies, the long-term effects of chemotherapies are now becoming important and one of these dreadful long-term complications is the development of a second malignancy. Described here is a case of transitional cell carcinoma of the bladder developing 8 years following exposure to cyclophosphamide for the treatment of embryonal rhabdomyosarcoma.

Adolescent↗

Hepatobiliary scintigraphic findings in obstructed intrahepatic choledochal cyst before and after surgery.

The authors describe a 10-week-old boy who presented with symptoms of progressive obstructive jaundice and abdominal distension. Clinical examination revealed gross hepatomegaly. A preoperative Tc-99m mebrofenin hepatobiliary study showed a large photopenic area involving the entire right lobe of the liver that did not communicate with the biliary system. Ultrasonography revealed a huge cystic mass with a few intracystic septae involving nearly the entire liver parenchyma. Under ultrasound guidance, a pigtail catheter was inserted into the cyst and produced free drainage of bile-stained fluid. Subsequently, an obstructed choledochal cyst was diagnosed clinically, and a right hepatectomy followed by a Roux-en-Y loop implantation on the raw surface of the left lobe were performed. Serial postoperative Tc-99m mebrofenin hepatobiliary studies showed marked improvement in liver function and biliary drainage with significant regeneration of the liver parenchyma.

Anastomosis, Roux-en-Y↗

Color Doppler and duplex sonography in 5 patients with thoracic outlet syndrome.

PURPOSE: To evaluate the use of color Doppler sonography in the diagnosis of thoracic outlet syndrome. METHODS: We studied color Doppler sonographic findings in 5 clinically suspected cases of thoracic outlet syndrome. The subclavian artery and vein were studied in varying degrees of abduction to assess the severity of the syndrome. RESULTS: Significant changes, i.e., stages of increased velocities, preocclusion, and occlusion in the subclavian artery in varying degrees of abduction, were noted in 4 of 5 cases. Blunted flow in the axillary artery (4 patients) and a rebound increase in velocities on release of abduction were noted in 3 patients. These changes suggested that significant narrowing was causing symptoms. CONCLUSION: Color Doppler sonography is a noninvasive, effective method compared with digital subtraction angiography in the diagnosis of thoracic outlet syndrome.

Adult↗

Gastric teratoma in children.

Gastric teratoma (GT) comprises less than 1% of all teratomas in children. Though GT in the presence of immature neuroepithelial elements is regarded as malignant, the prognosis is excellent after complete excision of the tumor. Because of its rarity the world literature lacks a large study. Clinical experience with ten cases of GT is presented and discussed. Only one patient was female; the mean age at presentation was 3.2 months. Two cases were immature grade III GT; one of these had infiltrated the left lobe of the liver and the transverse colon while the other had metastasized to the regional lymph nodes and omentum. All the patients underwent complete excision. There were no deaths, and after a mean follow-up period of 4.2 years, all the patients had no recurrence and were healthy. Both the mature and immature types of GT have an excellent prognosis after complete excision of the tumor. Even when the immature type infiltrates surrounding structures, complete excision offers recurrence-free survival without requiring chemo- or radiotherapy.

Biopsy↗

Postnatal outcome and natural history of antenatally-detected hydronephrosis.

Routine maternal ultrasonography (US) has revealed a very high incidence of fetal hydronephrosis (HDN), the postnatal outcome and management protocols of which are replete with controversies. Pelviureteric junction (PUJ) obstruction is the commonest postnatal diagnosis, and its management has no consensus to date. This study was carried out to define the postnatal outcome and natural history of fetal HDN and to identify the mode of management to be adopted to the best advantage. All patients were subjected to US 48 h postnatally or at first presentation and isotope renography (DTPA) with nuclear glomerular filtration rate (GFR) was carried out at 3-4 weeks of age or at presentation. Micturating cystourethrography (MCU) and/or direct radionuclide cystography (DRCG) were done in cases with bilateral HDN, nonobstructive HDN, dilated ureter on US, and recurrent urinary tract infection. Patients were then grouped for surgical intervention or conservative follow-up. Investigations were repeated periodically. A total of 56 patients were registered for the study (78 renal units) with a mean follow-up period of 14.6 months; 37 renal units were operated upon or scheduled for surgery and 67 had some organic pathology, of which PUJ obstruction was the commonest. Among patients with PUJ obstruction, indications for surgery included symptoms, a palpable mass, poor or deteriorating function, and a solitary functioning kidney. Patients operated upon showed improvement in function and/or drainage, while those followed conservatively remained stable or improved. Controversy still exists as to the optimal management of PUJ obstruction detected antenatally. While it is the commonest postnatal diagnosis, many other pathologies are now being encountered. In antenatally-diagnosed HDN, there is a good scope for conservative management provided rigid follow-up can be ensured, especially because a good recovery potential exists followed surgery whenever indicated.

Female↗

Fulguration of posterior urethral valves using the Nd:YAG laser.

Endoscopic management is the accepted form of treatment for posterior urethral valves (PUV). The Nd:YAG laser has been in clinical use for many decades, but has been used only sporadically for ablating PUV. In this study, PUV were diagnosed by micturating cystourethrogram (MCU). In the 9-month period beginning March 1997, 23 boys 3 months to 9 years of age underwent endoscopic Nd:YAG laser surgery for PUV using a 600 quartz bare fibre through the catheter channel of an 8.5 F cystoscope. The laser power and total energy delivered ranged from 20 to 50 W and 50-1085 J, respectively. Type I PUV were present in 20 boys; 1 had type III, and in 1 boy each there were residual valves and a urethral stricture from a previous electrocautery ablation. All operations were done with the patient under general anaesthesia supplemented by caudal morphine. Routine postoperative cystoscopy was done in the first 5 cases only. All patients had a good stream of urine without bleeding or any other complication after valve ablation. Mucosal tags seen on follow-up cystoscopy in 5 patients were fulgurated by laser. In 4 other patients recystoscopy was required for deterioration of the urinary stream and persistent posterior urethral dilatation on MCU; residual valves were refulgurated by laser. An indwelling catheter was left in only 4 patients, 2 of whom were primarily operated and 2 following refulguration. All except the first 2 were treated as out-patients. Application of the Nd:YAG laser has added a new dimension for treating PUV. The initial experience has been very encouraging: the destruction of valves is precise, there are no complications, and it can be practised on a day-care basis without indwelling catheterisation. The bare fibre can be used repeatedly, thus reducing the cost of treatment.

Catheter Ablation↗

Congenital hepatoportal arteriovenous fistula: report of a case.

Fistulae between the hepatic artery and portal vein, known as hepatoportal arteriovenous fistula (HPAVF), most commonly occur secondary to trauma or malignancy. Congenital HPAVF is an extremely rare anomaly and only 11 pediatric cases have been documented to date HPAVF causes portal hypertension with the reversal of flow in the portal circulation, leading to hyperemia and congestion of the bowel, causing severe ascites, gastrointestinal bleeding, anemia, and malabsorption. The diagnosis is first made by Doppler sonography, then confirmed by angiography. HPAVF is most effectively treated by performing either ligation of the hepatic artery or percutaneous transcatheter embolization. We describe herein the case of an 8-month-old boy diagnosed to have congenital HPAVF by duplex Doppler sonography and confirmed by digital subtraction angiography, who was successfully managed by percutaneous transcatheter embolization of the feeding right hepatic artery. A review of the previously reported 11 cases of infants with this unusual anomaly, examining presentation, management, and outcome, is also presented.

Arteriovenous Fistula↗

High incidence of adriamycin cardiotoxicity in children even at low cumulative doses: role of radionuclide cardiac angiography.

BACKGROUND/PURPOSE: Adriamycin (doxorubicin), a chemotherapeutic agent commonly used in the treatment of pediatric solid tumors, is known to have a dose-related cardiotoxicity, which is reported to be more common in children. The clinical manifestation of this is congestive cardiac failure (CHF), and this is fatal in 50% of the cases. Various strategies, including prospective multiple gated acquisition (MUGA) scan for early detection of the onset of cardiac damage has been recommended to decrease this fatality caused by cardiotoxicity. METHODS: All children receiving Adriamycin for solid tumors, registered at our pediatric solid tumor clinic from January 1998 through June 1999, were included in the study. Cardiotoxicity was evaluated by using electrocardiogram (ECG)-gated radionuclide cardiac angiography (MUGA scan). RESULTS: MUGA scans were performed on 55 patients in the above-mentioned period of 18 months. Twenty-three patients had only 1 baseline MUGA scan done, 12 of these are awaiting further studies at appropriate time and 11 are either dead or lost to follow-up. Of the remaining 32 patients, 13 have shown evidence of cardiotoxicity on MUGA scan done at a cumulative dose of 180 to 200 mg/m(2), in the form of decrease in left ventricular ejection fraction (LVEF) or abnormality in myocardial movements. Three of these 13 patients had clinical evidence of CHF. In 10 patients, timely discontinuation of Adriamycin, based on the MUGA report, probably has helped avoid the development of CHF. CONCLUSION: Routine monitoring of all children receiving Adriamycin is required to avoid the mortality and morbidity of Adriamycin-related cardiotoxicity, which may develop at relatively low cumulative doses also.

Antineoplastic Agents↗

Post hoc economic analysis of temozolomide versus dacarbazine in the treatment of advanced metastatic melanoma.

PURPOSE: To determine the potential economic implications resulting from oral temozolomide (TEM) compared with intravenous (IV) dacarbazine (DTIC) for metastatic melanoma. PATIENTS AND METHODS: We performed a cost-effectiveness (CE) analysis using hazard ratios (HRs) from the phase III (Schering I95-018) trial comparing TEM 200 mg/m(2)/d orally for 5 days every 28 days with DTIC 250 mg/m(2)/d IV for 5 days every 21 days. Sensitivity analyses assessed a range of TEM's efficacy and costs, direct nonmedical costs, and the DTIC schedule. RESULTS: The trial found an overall survival trend favoring TEM; median survival times of patients treated with DTIC and TEM were 6.4 and 7.7 months, respectively (HR = 1.18; 95% confidence interval [CI], 0.92 to 1.52; intention to treat, P =.20). The mean increase in survival of TEM over DTIC was 1.1 months. The projected average costs per patient were greater with TEM than DTIC ($6,902 v $3,697, respectively). The incremental CE ratio using TEM was $36,990 per life-year or $101 per day of life gained. The CE ratio's 95% CI ranged from -$65,180 (DTIC is more effective) to $18, 670 per year of life gained. The CE ratios decreased 50% if direct nonmedical costs were included and increased 50% if DTIC's efficacy was unchanged if given as a single daily dosage. Sixty percent of simulations found TEM with a CE threshold of less than $50,000 per life-year gained. CONCLUSION: Although the base-case efficacy of TEM compared with DTIC was not statistically significant, its associated incremental CE would be comparable with many interventions. TEM for metastatic melanoma illustrates the tension confronting providers choosing between similar agents that markedly differ in convenience and costs.

Administration, Oral↗

Herpes simplex virus-mediated gene delivery to the rodent visual system.

PURPOSE: To determine the types of cells in the visual system of the mouse and rat that can express a transgene delivered by an attenuated replication competent Herpes simplex virus-1 (HSV-1) vector. METHODS: C57/BL6 x BALB/C mice and Albino rats were treated with 1 x 10(7) pfu of the HSV-1 ribonucleotide reductase mutant (hrR3) expressing the Escherichia coli lacZ gene. The hrR3 virus was delivered by topical application to the cornea, intravitreal (IV) injection, intracameral injection (IC), or stereotactic injection into the visual cortex (VC). At specified times postinfection, animals were killed and tissues were removed, fixed, sectioned, and stained with X-gal or hematoxylin and eosin for histochemical and histopathologic examination. RESULTS: Topical delivery after corneal scarification in both mouse and rat resulted in lacZ expression in 25% of the corneal epithelial cells and 25% of the retinal pigment epithelium (RPE) cells. Topical application without concurrent scarification also resulted in transgene delivery to 20% of the RPE cells of the rat but not the mouse. IV injection resulted in expression primarily in RPE cells, with up to 100% of the cells expressing lacZ in the mouse and rat. Other cells expressing the transgene included ciliary body (CB) and optic nerve cells. Up to 25% of the retinal ganglion cells in the rat expressed lacZ, but only rarely in mice. IC delivery in rats resulted in expression in trabecular meshwork, CB cells, RPE, and iris epithelium. Injection into area 17 of the rat VC resulted in efficient labeling of the VC neurons and neurons in the lateral geniculate nucleus without any evident pathology or inflammation. Neither inflammation nor disease pathology was observed in either the mouse or rat after any route of delivery. CONCLUSIONS: It was demonstrated that the hrR3 HSV-1 virus can deliver a functioning gene to several cell types in the eye and neurons in the VC and that the virus can move via retrograde transport to nuclei that project to the VC.

Animals↗