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Biomedical subjects

R Saxena

Publications and source records attributed to R Saxena.

At least 163 records · Page 9Linked to original sources

Xanthogranulomatous cholecystitis.

Xanthogranulomatous cholecystitis (XC) is a rare benign disease often confused with carcinoma gall bladder (CaGB). We retrospectively reviewed the clinical, radiological and operative features of 81 patients with XC alone (73) or XC with associated CaGB (8). Patients with XC alone had no gender preponderance, had a mean age 48 years and mean duration of symptoms of 34 months. Most XC patients (75%) had clinical features of chronic cholecystitis. On the other hand, patients with both XC and CaGB had a female preponderance, a mean age of 60 years and mean duration of symptoms of 6 months. In this group, the USG and operative findings often supported the clinical impression/findings. Xanthogranulomatous cholecystitis is a benign condition which is often confused with CaGB. Associated CaGB is however present in a few patients; elderly women with relatively shorter duration of symptoms, have a greater chance of associated CaGB.

Adult↗

Velocity measurements and flow patterns within the hinge region of a Medtronic Parallel bileaflet mechanical valve with clear housing.

BACKGROUND AND AIMS OF THE STUDY: During recent clinical trials the Medtronic Parallel bileaflet mechanical heart valve was found to have an unacceptable number of valves with thrombus formation when implanted in the mitral position. Thrombi were observed in the hinge region and also in the upstream portion of the valve housing in the vicinity of the hinge. It was hypothesized that the flow conditions inside the hinge may have contributed to the thrombus formation. METHODS: In order to investigate the flow structures within the hinge, laser Doppler anemometry (LDA) measurements were conducted in both steady and pulsatile flow at approximately 70 predetermined sites within the hinge region of a 27 mm Medtronic Parallel mitral valve with transparent housing. The pulsatile flow velocity measurements were animated in time using a graphical software package to visualize the hinge flow field throughout the cardiac cycle. RESULTS: The LDA measurements revealed that mean forward flow velocities through the hinge region were on the order of 0.10-0.20 m/s. In the inflow channel, a large vortical structure was present during diastole. Upon valve closure, peak reverse velocity reached 3 m/s close to the housing wall in the inflow channel. This area also experienced high turbulent shear stresses (> 6000 dynes/cm2) during the leakage flow phase. A disturbed, vortical flow was again present in the inflow channel after valve closure, while slightly above the leaflet peg and relief the flow was essentially stagnant. The high turbulent stresses near the top of the inflow channel, combined with a persistent vortex, implicate the inflow channel of the hinge as a likely region of thrombus formation. CONCLUSIONS: This experimental investigation revealed zones of flow stagnation in the inflow region of the hinge throughout the cardiac cycle and elevated turbulent shear stress levels in the inflow region during the leakage flow phase. These fluid mechanic phenomena are most likely a direct result of the complex geometry of the hinge of this valve. Although the LDA measurements were conducted at only a limited number of sites within the hinge, these results suggest that the hinge design can significantly affect the washout capacity and thrombogenic potential of the Medtronic Parallel bileaflet mechanical heart valve. The use of LDA within the confines of the hinge region of a mechanical heart valve is a new application, made possible by recent advances in manufacturing technologies and a proprietary process developed by Medtronic that allowed the production of a transparent valve housing. Together, these modalities represent a new method by which future valve designs can be assessed before clinical trials are initiated.

Evaluation Studies as Topic↗

An in vitro investigation of the retrograde flow fields of two bileaflet mechanical heart valves.

BACKGROUND AND AIM OF THE STUDY: Fluid stresses occurring in retrograde flow fields during valve closure may play a significant role in thrombogenesis. The squeeze flow and regurgitant jets can cause damage to formed blood elements due to high levels of turbulent shear stress. The aim of this study was to characterize in detail the spatial structure and temporal behavior of the retrograde flow fields of the St. Jude Medical and Medtronic Parallel bileaflet mechanical heart valves. METHODS: Three-component, coincident laser Doppler anemometry (LDA) velocity measurements were obtained facilitating the determination of the full Reynolds stress tensor and the principal stresses in the valve flow fields. The experiments were performed in the Georgia Tech aortic flow chamber under physiologic pulsatile flow conditions. Data were collected over several hundred cardiac cycles for subsequent phase window averaging and generation of mean velocity and turbulence statistics over 20 ms intervals. A region approximately 8 mm x 10 mm was mapped 1.0 mm upstream of one hinge of each valve with an incremental resolution of 0.13-0.25 mm. Animation of the data allowed the visualization of the flow fields and a quantitative display of mean velocity and turbulent stress values. RESULTS: In the St. Jude Medical squeeze flow, the peak turbulent shear stress was 800 dynes/cm2 and the peak reverse velocity was 0.60 m/s. In the Medtronic Parallel squeeze flow, the peak turbulent shear stress was 1,000 dynes/cm2 and the peak velocity 0.70 m/s. The leakage jet fields of the two valves were very different: in the case of the St. Jude Medical valve, turbulent shear stresses reached 1,800 dynes/cm2 and peak jet velocity was 0.80 m/s; in the case of the Medtronic Parallel valve, turbulent shear stresses reached 3,690 dynes/cm2 and the peak jet velocity was 1.9 m/s. CONCLUSIONS: The retrograde flow fields of these two bileaflet mechanical heart valves appear to be design-dependent. The elevated turbulent shear stresses generated by both valve designs may indicate a propensity for blood element damage during the reverse flow phase of the cardiac cycle, but the extent of flow disturbance was twice as high with the Medtronic Parallel than with the St. Jude Medical valve. This research should yield a better understanding of the significance of retrograde flow to the functionality and potential thrombogenicity of bileaflet mechanical heart valves and aid in the development of new designs.

Heart Valve Prosthesis↗

Karyotyping of at risk fetuses by cordocentesis in advanced gestation.

Fetal blood obtained by cordocentesis was cultured to obtain rapid karyotypes of fetuses at risk during the late second trimester. Ninety nine fetal blood samples were studied for chromosomal abnormalities. The commonest indications for the procedure were abnormalities detected on ultrasonography (47.7%), and previous child with Down syndrome. Analysis of the 67 successful cultures showed four (5.9%) karyotypic abnormalities. The technique proved helpful in the obstetrical management of at risk fetuses.

Adult↗

Neonatal cholestasis syndrome: an appraisal at a tertiary center.

OBJECTIVE: To know the magnitude, etiology and clinical profile, the efficacy of various investigations and the outcome in patients with neonatal cholestasis syndrome (NCS). DESIGN: Prospective evaluation of 60 consecutive infants with NCS (mean age 3.9 +/- 1.9 months; 49 males) over a period of 3.5 years. SETTING: Tertiary level referral gastroenterology center in North India. METHODS: Liver function tests, urine examination, serum antibodies against Cytomegalovirus (CMV), Rubella and Toxoplasma; abdominal ultrasonography, hepatobiliary scintigraphy and liver biopsy were done. In appropriate setting, laparotomy and surgical corrections were done for biliary tract disorders. RESULTS: NCS constituted 19% of pediatric liver diseases. Considerable delay in presentation was observed [mean delay, extrahepatic biliary atresia (EHBA) = 4 +/- 2.0 months, neonatal hepatitis (NH) = 2.2 +/- 1.3 months]. Thirty three (55%) infants had EHBA, 14 (23%) NH (4 CMV, 2 galactosemia, 1 urinary tract infection and 7 idiopathic), 2 (3%) paucity of intralobular bile ducts and 11 (18%) were of indeterminate etiology. Liver biopsy was the most accurate (96.4%) investigation in discriminating between EHBA and NH. Of the 18 operated infants with EHBA (portoenterostomy-15 and hepatico-jejunostomy-3), 10 were alive (mean follow up = 22.8 +/- 8.6 months) of which 4 were completely asymptomatic. CONCLUSIONS: (i) NCS is an important cause of liver disease in Indian children. (ii) It requires prompt referral, quick investigative approach and targeted management. (iii) Liver biopsy is highly accurate in differentiating EHBA and NH. (iv) infants with EHBA and compensated status of liver should undergo corrective surgery irrespective of age at presentation.

Biliary Atresia↗

Rare inherited coagulation disorders in India.

Twenty four cases with rare coagulation disorders were diagnosed over a 4 year period. These included 8 patients with factor X deficiency, 7 with factor XIII deficiency, 4 each with fibrinogen and factor VII deficiency and 1 with factor V deficiency. All these patients had presented with bleeding manifestations. Two patients with factor X deficiency showed interesting clinical presentations, one patient had recurrent deep vein thrombosis and another patient had a pseudotumor of the thigh.

Adolescent↗

Improved outcome for children with hepatoblastoma.

Between 1981 and 1993, 41 children were treated for hepatoblastoma. Clinical, radiological and pathological data were reviewed retrospectively, focusing on surgical aspects of treatment and outcome. Fourteen children underwent primary resection of the hepatic tumour. One infant with severe congenital anomalies received only palliative treatment. Of 26 with irresectable disease, pulsed cytotoxic chemotherapy (cisplatin and doxorubicin) enabled subsequent surgical excision in 22 and one child with persistent extensive intrahepatic disease was successfully treated by liver transplantation. Thus, with a policy of selective preoperative chemotherapy, 90 per cent of hepatoblastomas were resectable. There were no perioperative deaths from haemorrhage but one child died from an intraoperative tumour embolus. A total of 28 survivors, 27 of whom are disease-free, were followed for a median of 5 years. The cumulative probability of survival in patients treated with intent to cure was 67 per cent. Analysis of survival data suggested a favourable outcome for those with a pure fetal histological tumour subtype. These results demonstrate significant progress in the treatment of hepatoblastoma.

Child↗

Inhibition of ras p21 membrane localization and modulation of protein kinase C isozyme expression during regression of chemical carcinogen-induced murine skin tumors by lovastatin.

We investigated the ras p21 membrane localization and the expression and activation of protein kinase C (PKC) isozymes in activated ras oncogene-containing tumors and assessed whether these events were related to tumor growth. We used 7,12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted SENCAR mouse skin tumors, which were shown to contain Ha-ras oncogene activated by point mutation at codon 61, as an in vivo model for these studies. Compared with levels in epidermis, highly elevated levels of membrane-bound Ha-ras p21 were observed in growing tumors, which also showed strong expression and membrane translocation of PKC zeta and beta II and weak expression of PCK alpha. However, when ras p21 membrane localization was blocked in vivo in growing tumors by lovastatin, opposite results were evident. Compared with saline-treated animals, in which tumor growth continued, lovastatin-treated animals had significantly inhibited tumor growth, which led to tumor regression with concomitant inhibition of Ha-ras p21 membrane localization. These regressing tumors from lovastatin-treated animals also showed a decrease in the expression and membrane translocation of PKC zeta and beta II but increased expression of PKC alpha. Taken together, our results indicate that ras p21 membrane localization and the expression and activation of PKC zeta, beta II, and alpha may be the critical events in the regulation of the growth of tumors that contain activated ras oncogenes.

9,10-Dimethyl-1,2-benzanthracene↗

Copper-associated liver disease in childhood.

BACKGROUND/AIMS: Indian childhood cirrhosis is associated with high liver copper concentrations and progressive liver disease with a high mortality. Early treatment with penicillamine was found to reduce mortality and reverse liver damage. We aimed to define the clinical features of copper-associated liver disease outwith the Indian subcontinent and encourage the earlier consideration of the syndrome in cryptogenic liver disease. METHODS: Three European children presented between 10 and 29 months of age with abdominal distension, pyrexia and hepatosplenomegaly. Over 1-5 weeks their condition deteriorated rapidly due to liver failure. Two died within 2 months of onset and one received a successful liver transplant. In two cases consideration of the diagnosis occurred only on examination of the liver after orthotopic liver transplant or death. Light microscopy was used, with haematoxylin and eosin, reticulin and orcein stains. Tissue, plasma and water copper levels were measured by flame atomic absorption spectrometry. RESULTS: All had micronodular cirrhosis and severe hepatocellular necrosis with Mallory bodies and copious-orcein positive material. Liver copper concentrations ranged from 1100-1310 micrograms/g dry weight. For two patients domestic water with high copper content had been used for the preparation of feeds. No environmental source of excess copper could be identified in the third case. CONCLUSIONS: We suggest that the above condition, which is called Indian childhood cirrhosis in the Indian subcontinent and Copper Storage Disease elsewhere, would be better named 'Copper-Associated Liver Disease in Childhood', emphasising the need to consider this disorder in unexplained liver disease and to seek possible sources of excessive copper intake.

Child, Preschool↗

Asymptomatic visceral leishmaniasis in a child with acute lymphoblastic leukaemia.

Visceral leishmaniasis was detected incidentally in a patient with acute lymphoblastic leukaemia in remission, during maintenance therapy. Absence of fever, a normal haemogram, normal serum globulins, a negative serology and testicular involvement were the hallmarks of the case. Treatment with sodium stibogluconate (20 mg/kg for 55 days) failed. Subsequent therapy with pentamidine resulted in complete parasite clearance. Prolonged therapy with pentavalent antimony compounds or a higher dose of second line drugs such as pentamidine are recommended for complete clearance.

Antimony Sodium Gluconate↗

Circulating autoantibodies as serological markers in the differential diagnosis of pulmonary renal syndrome.

OBJECTIVES: Pulmonary renal syndrome (lung haemorrhage and glomerulonephritis) is a fulminant condition that warrants a rapid diagnosis and treatment to prevent mortality and preserve renal functions. However, the patients frequently present with non-specific pulmonary symptoms in the early phase of the syndrome and the diagnosis is often missed. Recently, several autoantibodies have been described in association with various forms of glomerulonephritis. We evaluated the association as well as the diagnostic and the prognostic significance of these antibodies in pulmonary renal syndrome. DESIGN: Retrospective clinical study. SETTING: University Hospital. SUBJECTS: Forty consecutive patients with biopsy verified glomerulonephritis and overt haemoptysis or pulmonary infiltrates compatible with lung haemorrhage. INTERVENTIONS: Analysis of proteinase 3 antineutrophil cytoplasm antibodies (PR3-ANCA), myeloperoxidase (MPO)-ANCA, antiglomerular basement membrane (GBM) and anti-entactin antibodies. RESULTS: Thirty-six (90%) patients possessed one or more autoantibodies. Twenty-seven (70%) patients had ANCA (PR3-ANCA, MPO-ANCA or both). The remaining positive patients (n = 9) had anti-GBM antibodies. Only two patients had anti-entactin antibodies, suggesting a poor association of these antibodies with PRS. The majority of patients with anti-GBM antibodies had a very poor clinical outcome (five irreversible renal failure; three deaths). On the other hand, despite no significant difference in clinical features or renal morphology from patients with anti-GBM antibodies, 19 patients (70%) with ANCA recovered completely following treatment. CONCLUSIONS: Our study demonstrated that the presence of autoantibodies is a predominant feature of PRS and that the type of immunologic injury is of paramount importance in determining the course of illness in this syndrome. Analysis of the aforementioned antibodies can help in an early differential diagnosis and thus, in better management of PRS.

Adult↗

A clinical and cytogenetic study of Turner syndrome.

Forty five case of Turner syndrome diagnosed in the Genetics Clinic, between January 1986 and December 1993, were analyzed. The most commonly observed karyotype was 45, X (44.4%), followed by 45, X/46, XX mosaicism (24.4%). Less frequently demonstrated karyotypes were 45, X/46, X, i (Xq) mosaicism and 46, X, i (Xq) (13.3%). Mosaicism for chromosome was seen in 6.7% of patients. Patients with 45, X karyotype had short stature (85%), dysmorphic facies (60%), delayed appearance of secondary sexual characters (100%) and primary amennorhea (100%). Those with 45, X/46, XX mosaicism were less often dysmorphic and presented with either primary or secondary amenorrhea. Patients with 45, X karyotype were younger at diagnosis and had a significantly shorter mean adult height than those with 45, X/46, XX mosaicism. The phenotype in patients with other karyotypic abnormalities was similar to the 45, X group. Short stature and primary or secondary amenorrhea occurring together in a female strongly suggests the possibility of Turner syndrome, which should be confirmed by chromosomal analysis.

Adolescent↗