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A Hingorani

Publications and source records attributed to A Hingorani.

48 records · Page 3Linked to original sources
PubMed1999

P53 gene transfer to the injured rat carotid artery promotes apoptosis.

BACKGROUND: In a previous study we have demonstrated significant reduction of intimal hyperplasia after adenovirus-mediated gene transfer of p53 protein to the injured rat carotid artery. The purpose of this study was to elucidate whether apoptosis is one of the mechanisms responsible for this reduction. Apoptosis, a physiologic cell death process that stabilizes cell numbers in tissues, can be independently induced by p53. METHODS: In vivo gene transfer was used in isolated segments of balloon-injured rat carotid arteries. Genetically modified adenovirus encoding for wild-type p53 protein (AdWTp53) was applied at 8 x 10(10) plaque-forming units/mL. Control rats received either adenovirus null at the same concentration or balloon injury alone. Arteries were harvested at 24 and 48 hours after the procedure. Apoptosis was detected in tissue sections by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Specimens were graded either negative or positive less than 10%, 10% to 20%, 20% to 30%, or greater than 30% according to the number of apoptotic cells in the medial or intimal layer per high power field. Specimens were also subjected to DNA agarose gel electrophoresis and transmission electron microscopy. RESULTS: With the TUNEL assay no apoptosis was visualized at 24 and 48 hours in the controls (n = 5 in each group), whereas in the AdWTp53 groups (n = 5 in each) all specimens presented apoptosis (P < .05, AdWTp53 vs controls). The average grade of apoptotic cells detected in the medial layer in the AdWTp53 groups was less than 10% to 20% at 24 hours and 20% to 30% at 48 hours. The DNA agarose gel electrophoresis failed to detect a DNA laddering pattern, characteristic of apoptosis. Electron microscopy revealed morphologic changes typical of apoptosis in the treated group, whereas specimens from control group did not reveal any apoptotic features. CONCLUSIONS: At 48 hours after balloon injury alone, no apoptosis was observed in the vessel wall. However, when p53 gene was transferred, apoptosis was visualized in all specimens with greater intensity at 48 hours after injury. Promotion of apoptosis may play a key role in the mechanism by which p53 gene decreases intimal hyperplasia.

Animals↗
PubMed1999

Superficial vein thrombophlebitis as a marker of hypercoagulability.

Superficial thrombophlebitis (SVT)is a common disorder with potential morbidity from recurrence and pulmonary embolism (PE), but it has received little attention in the literature. The availability of reliable duplex ultrasonography of the deep and superficial venous systems has made routine determination of the location and incidence of deep vein thrombosis (DVT) in association with SVT practical.

Journal Article↗
PubMed1998

Combined coronary artery bypass grafting and abdominal aortic aneurysm repair.

BACKGROUND: We report here the results of combined coronary artery bypass grafting (CABG) and abdominal aortic aneurysm (AAA) repair and the factors associated with higher mortality following this procedure. METHODS: The authors performed a retrospective chart review of 26 patients who underwent combined CABG and AAA repair between March 1990 and October 1996. RESULTS: No postoperative myocardial infarction or major cardiac complications were noted. A morbidity rate of 38% (n = 10) and mortality rate of 11% (n = 3) were noted. Comparative analysis of nonsurvivors (n = 3) versus survivors (n = 23) revealed the following: ejection fraction (EF) was significantly lower (33% +/- 3% versus 44% +/- 14%, P < 0.05), duration of cardiopulmonary bypass (CPB) was significantly longer (239 +/- 122 minutes versus 141 +/- 54 minutes, P < 0.05), and incidence of postoperative respiratory failure (67% versus 17%, P = 0.001) were significantly higher in nonsurvivors. No differences in mean age, gender distribution, incidence of hypertension or diabetes were noted between the groups. CONCLUSIONS: Combined CABG and AAA repair protected patients from postoperative aneurysm rupture and myocardial infarction. Poor EF, prolonged CPB, and postoperative respiratory failure were associated with higher mortality.

Aged↗
PubMed1998

The effect of tumor necrosis factor binding protein and interleukin-1 receptor antagonist on the development of abdominal aortic aneurysms in a rat model.

PURPOSE: Tumor necrosis factor (TNF), interleukin 1 (IL-1), and matrix metalloproteases have been noted to be elevated in human abdominal aortic aneurysms (AAAs) as compared with normal and occlusive aortic disease. Because TNF and IL-1 have been shown to cause release of proteases that weaken the aortic matrix, it has been suggested that these cytokines may play a central role in the aortic dilatation process. To substantiate this hypothesis, we investigated the effects of TNF and IL-1 antagonists, tumor necrosis factor binding protein (TNF-BP) and interleukin-1 receptor antagonist (IL-1RA), on the development of AAAs in a well-described rat model. METHODS: Isolated segments of infrarenal aorta of 16 rats were perfused with porcine elastase. In the treated group, eight rats were given intravenous TNF-BP prior to elastase perfusion, at 48 hours and at 96 hours. In the control group, eight rats were given only intravenous vehicle at the same time intervals. Isolated segments of infrarenal aorta of an additional 16 rats were perfused with porcine elastase in a similar fashion. In the treated group, eight rats were given intraperitoneal IL-1RA prior to celiotomy and every eight hours. In the control group, eight rats were given only intraperitoneal vehicle at the same time intervals. On the sixth postoperative day, all rats underwent celiotomy and measurement of the infrarenal aortic diameter with a micrometer while the animal was alive. Aortic specimens were collected on day six for hematoxylin and eosin staining, trichrome staining, and gel polyacrylamide gel electrophoresis (PAGE) zymography. RESULTS: TNF-BP was completely able to block post elastase dilation, whereas IL-1Ra seemed to have no effect. Hematoxylin and eosin staining and trichrome staining revealed that animals treated with TNF-BP had less of an inflammatory response and preservation of the elastin and smooth muscles in the media of the aortic wall as compared with animals treated with IL-1RA or vehicle. Zymography was not able to detect significant protease activity in the aortic wall of any of the rats at six days. CONCLUSION: TNF-BP, but not IL-1RA, may inhibit the development of AAAs in this model.

Animals↗
PubMed1998

Saphenous vein thrombophlebitis (SVT): a deceptively benign disease.

PURPOSE: The association between deep vein thrombosis (DVT) and the hypercoagulable state is a well-established entity. However, the association between saphenous vein thrombophlebitis and coagulation abnormalities has not been investigated. Although thrombosis of varicose veins typically runs a benign course, phlebitis of the saphenous system may propagate to the deep system or saphenofemoral junction that requires more aggressive therapy. Given the potential similarity in clinical outcome between saphenous vein thrombophlebitis (SVT) and DVT, we have investigated the coagulation profile of patients presenting with isolated SVT. METHODS: Seventeen consecutive patients who presented to our vascular laboratory with isolated SVT had a coagulation profile performed that included antithrombin III (AT III), protein C (PC), protein S (PS) antigen and activity levels, activated protein C (APC) resistance, factor V DNA mutation, and coagulation factors II and X. All patients had duplex scans performed on both the superficial and deep venous systems. Patients with SVT only were treated with nonsteroidal antiinflammatory drugs (NSAIDs) and warm soaks as outpatients, whereas those patients found to have DVT or a clot at the saphenofemoral junction were fully anticoagulated with heparin and coumadin therapy. All 17 patients had at least one repeat coagulation profile performed up to 5 months after their SVT occurrence to ensure that the results of hypercoagulability were not transient. RESULTS: Ten (59%) of the 17 patients with SVT had abnormal coagulation profiles on initial presentation. All 10 patients who were hypercoagulable had repeat tests and 6 (35%) remained abnormal. Four patients who had abnormal results converted to normal values. Seven patients with normal coagulation profiles on initial presentation had repeat tests and all remained normal. CONCLUSION: The incidence of the hypercoagulable state in patients with SVT is high. Thirty-five percent of patients with isolated SVT had consistently abnormal coagulation profiles. Patients with SVT may be prone to the development of DVT or saphenofemoral junction thrombophlebitis and should be closely followed after the initial diagnosis of hypercoagulability.

Adult↗
PubMed1998

Hemodynamic instability following carotid endarterectomy does not affect early discharge.

Over the last few years, there has been increased emphasis on early discharge of patients following carotid endarterectomy in the United States. Recent studies have shown that short-stay hospitalization for carotid endarterectomy may be safe and cost-effective. However, this is not always possible because of reasons that are not clearly delineated. In order to optimize the early discharge of patients following carotid endarterectomy, an analysis of the causes of delayed discharges was performed in the present series. Since hemodynamic instability has been shown to be the most frequent complication following carotid endarterectomy, the authors investigated whether it was an important factor preventing early postoperative discharge. This study reviewed the data of 100 consecutive patients admitted for elective carotid endarterectomy. The incidence of post-carotid endarterectomy hemodynamic instability was 37% (n = 37), with hypertension occurring in 25 patients (68%) and hypotension occurring in 12 patients (32%). Hemodynamic instability tended to occur with the use of general anesthesia as compared with regional anesthesia. Hemodynamic instability did not correlate with pre-existent history of hypertension, nor with the type of drug used when general anesthesia was applied. All the patients were successfully treated either in the recovery room or in a monitored area. The average total length of stay was 1.65 days with 79% of the patients being discharged on the first postoperative day and 21% having delayed discharge ranging from 2 to 15 days (mean 4 days). The main reasons for delayed discharges were cardiac and urinary tract complications. Blood pressure instability accounted for only 2% of cases. Thus, these data show that hemodynamic instability does not significantly affect early discharge.

Aged↗
PubMed1998

Positive association of tyrosine hydroxylase microsatellite marker to essential hypertension.

Despite advances in the understanding of monogenic hypertensive disorders, the genetic contribution to essential hypertension has yet to be elucidated. The position of tyrosine hydroxylase (TH) as the rate-limiting enzyme in catecholamine biosynthesis renders it a candidate gene for the etiology of hypertension. The TH gene contains an internal, informative microsatellite marker (TCAT)9. We undertook (1) an association study in a group of well-characterized hypertensive subjects (HT) and control subjects (NT) and (2) an affected sibling pair (ASP) study using sibships from our local family practices. Two hundred twenty-seven hypertensive patients (pretreatment systolic/diastolic blood pressure [BP] range, 139/94 to 237/133 mm Hg; age range [SD], 30 to 71 [8.5] years) were age- and gender-matched with 206 control subjects (BP range, 96/62 to 153/86 mm Hg; age range, 40 to 70 [7.6] years). One hundred thirty-six affected sibling pairs were recruited for our linkage study; 73 young borderline hypertensive subjects (YHT) (pretreatment BP range, 123/76 to 197/107 mm Hg; age range, 20 to 51 [9.4] years) were also recruited in whom recent pretreatment norepinephrine and epinephrine levels were available. All subjects were white. The TH short tandem repeat (STR) was amplified using specific polymerase chain reaction cycling conditions in all subjects, and products were run on an ABI 373A sequencer. TH alleles were assigned using Genescan and Genotyper software. Five TH alleles were present and designated A through E. Allele frequencies in the NT population (A, B, C, D, and E: 0.24, 0.17, 0.13, 0.20, and 0.26, respectively) were significantly different from the HT cohort (A, B, C, D, and E: 0.24, 0.19, 0.11, 0.11, and 0.35, respectively), P<0. 0005 (Pearson's test chi2=19.94; 4 df). The E allele appears overrepresented in the HT group, whereas the D allele appears to be overrepresented in the NT group. TH genotype frequencies were also significantly different between cases and controls (P<0.001; chi2=36. 57; 14 df). Both groups were in Hardy-Weinberg proportion. There was a trend (NS) for the D allele to be associated with a lower BP when BP was analyzed as a quantitative trait. ASP linkage data was analyzed using Splink, a nonparametric program. Expected values for sharing 0, 1, and 2 alleles (Z0, Z1, and Z2, respectively) may be expected to be 25%, 50%, and 25%, respectively, by chance (assuming identity by descent). These probabilities were calculated by Splink as 34, 68, and 34, respectively, and compared with observed values of 36.8, 67.9, and 31.3, respectively; thus, there was no excess sharing of TH alleles among affected sibling pairs (P=0.59; logarithm of odds ratio score, 0.0). TH allele frequencies in our YHT group (A, B, C, D, and E: 0.24, 0.20, 0.12, 0.15, and 0.29, respectively) were similar to those of our NT cohort (P>0.05). There was a trend for lower pretreatment plasma norepinephrine levels with the D allele in this YHT cohort. A common and potentially functional variant at codon 81(Val-->Met) within exon 2 of the TH gene (which we show to be in linkage disequilibrium with TH-STR) was also typed in our YHT but did not associate with catecholamine levels and is therefore unlikely to account for our findings with D and E TH-STR. In conclusion, the TH locus strongly associates with essential hypertension in a case-control model using well-characterized hypertensive and control groups. An ASP linkage model was negative, presumably because of lack of power. This study suggests that the TH gene, or a nearby gene, may be involved in the etiology of essential hypertension.

Adult↗
PubMed1997

Upper extremity versus lower extremity deep venous thrombosis.

BACKGROUND: In contrast to lower extremity deep venous thrombosis (LEDVT), it is widely believed that upper extremity deep venous thrombosis (UEDVT) is associated with minimal morbidity or mortality. METHODS: In an attempt to compare the two disease processes with respect to pulmonary embolism and mortality, we have reviewed records and performed interviews of 430 patients with LEDVT and 52 patients with UEDVT presenting to our institution between January 1994 and June 1995. RESULTS: Pulmonary embolism was documented by ventilation/perfusion lung scan in 9 of 52 patients (17%) with UEDVT and 33 of 430 patients (8%) with LEDVT (P <0.05). Twenty-five of the UEDVT patients (48%) died within 6 months of the diagnosis of UEDVT. Conversely, 14 patients (13%) in the LEDVT group died within 6 months of the diagnosis of LEDVT (P <0.0002). CONCLUSION: Contrary to previous reports, this study suggests that UEDVT is associated with a higher morbidity and mortality as compared with LEDVT. These data show that UEDVT has been an underrecognized predictor of morbidity and mortality.

APACHE↗
PubMed1997

Upper extremity deep venous thrombosis and its impact on morbidity and mortality rates in a hospital-based population.

PURPOSE: Although much attention has been focused on lower extremity deep venous thrombosis (LEDVT), there is a relative paucity of data regarding the impact of upper extremity deep venous thrombosis (UEDVT) on morbidity and mortality rates. To increase our knowledge with the latter disease, we have reviewed our experience at our institution with 170 patients who had brachial, axillary, and subclavian vein thromboses. METHODS: Over the past 5 years, UEDVT was diagnosed in 170 patients by duplex scanning. The indications for duplex examination were either upper extremity swelling (95%) or as part of the workup for pulmonary embolism (5%). There were 103 women (61%) and 67 men (39%), with ages ranging from 9 to 101 years (mean, 68 +/- 17 years). The diagnosis was made in 152 patients (89%) while they were admitted to the hospital and in 18 patients (11%) in the outpatient clinic. Risk factors included presence of a central venous catheter or pacemaker in 110 patients (65%), malignancy in 63 patients (37%), concomitant LEDVT in 19 patients (11%), and history of LEDVT in 18 patients (11%). Fifty-six patients (33%) had multiple risk factors, whereas 36 patients (21%) had no obvious risk factor. RESULTS: The 1-month and 3-month mortality rates for the entire study group were 16% and 34%, respectively. Patients who had concomitant LEDVT, were 75 years of age or older, and were not treated with anticoagulation medication had a significantly higher 1-month mortality rate. Patients whose diagnoses were made in the outpatient setting were statistically younger and had a lower 3-month mortality rate when compared with the patients whose diagnoses were made as inpatients. Pulmonary embolism was documented by ventilation/perfusion scan in 12 patients (7%). Although no patient in the group in which UEDVT was diagnosed on an outpatient basis was documented to have a pulmonary embolism and 12 patients (8%) in the inpatient group had pulmonary emboli, this difference was not statistically significant. Anticoagulation medication did not totally prevent pulmonary embolism in this review. All patients were followed-up for between 0 to 49 months (mean, 13 +/- 1 months). No swelling of the affected arm was observed in 145 patients (94%); four patients complained of mild intermittent swelling (2%), and seven patients reported significant swelling (4%). CONCLUSIONS: Contrary to previous reports, these data suggest that UEDVT is associated with a low incidence of postthrombotic upper extremity swelling, but a significant incidence of pulmonary embolism and rate of mortality. This review suggests that UEDVT is at least as serious a disease entity as LEDVT and should be managed as aggressively as LEDVT.

APACHE↗
PubMed1997

Flow associated or flow mediated dilatation? More than just semantics.

Dilatation of the brachial artery occurs after flow is increased, and an attenuation in this response is seen in subjects with cardiovascular risk factors, and in those with established coronary artery disease. The mechanisms linking ischaemia, flow changes, and brachial artery dilatation are unclear, and it is not known how these are affected by arterial disease. For the present it might be more appropriate to refer to flow associated rather than flow mediated dilatation, to describe the phenomenon in the brachial artery. Despite these caveats, the non-invasive measurement of brachial artery following ischaemic dilatation represents a significant advance, and its suitability as a surrogate marker for coronary artery dysfunction appears promising. The technique has potential as a tool for screening those at high risk of vascular disease, and as a surrogate endpoint in intervention studies. Further research should clarify the mechanisms involved, and lead to greater insights into the nature of endothelial dysfunction and cardiovascular disease.

Brachial Artery↗
PubMedDate not supplied

Does repeat duplex ultrasound for lower extremity deep vein thrombosis influence patient management?

The clinical significance of lower extremity deep vein thrombus (DVT) propagation in the setting of anticoagulation therapy remains unclear. The purpose of this study is to compare results of thrombus outcome found with repeat duplex ultrasonography to the incidence of pulmonary embolism and mortality. During a recent 18-month period, 457 patients were diagnosed with lower extremity DVT with duplex ultrasonography and their data were retrospectively analyzed. Repeat examinations were available for review in 118 patients (51 men, 67 women). Results of repeat duplex exams were divided into 4 groups: resolved, improved, unchanged, or extended proximally. All patients received heparin and warfarin therapy. Ventilation-perfusion (V/ Q) scans were obtained only for signs and symptoms of pulmonary embolism (n=30). Mortality, the prevalence of high-probability V/ Q scans, frequency of intracaval filter insertion, gender, mean age, mean prothrombin time (PT), mean partial thromboplastin time (PTT), mean number of repeat ultrasounds per patient, and mean time over which the repeat ultrasounds took place were compared among the 4 groups. Patients who had proximal extension of DVT (19%) on repeat duplex ultrasound had an increased prevalence of pulmonary embolism (p<0.05). Also, patients whose DVT resolved were younger (p<0.05). There was no difference among the 4 groups in mortality, placement of Greenfield filters, mean PT, mean PTT, mean number of ultrasound exams per patient, or mean follow-up time over which the exams took place. Proximal extension of DVT documented by repeat duplex ultrasound is a significant risk factor for pulmonary embolism. Repeat duplex ultrasound can identify a group of patients who may benefit from insertion of an intracaval filter device.

Adult↗