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Bhavesh Patel

Publications and source records attributed to Bhavesh Patel.

9 recordsLinked to original sources
PubMed2006

Evaluation of 99mTc-MAG3-annexin V: influence of the chelate on in vitro and in vivo properties in mice.

We conjugated mercaptoacetyltriglycine (MAG(3)) to rh-annexin V to permit radiolabeling with (99m)Tc in an effort to decrease the high kidney and liver accumulation observed for (99m)Tc-labeled Hynic-annexin V. The 36-kDa protein was conjugated at a 5:1 molar ratio with NHS-MAG(3) in HEPES buffer pH 7.8 at room temperature, then quenched with glycine and purified by dialysis. The biopotency of the resulting MAG(3)-annexin was similar to that of Hynic-annexin as determined by a sensitive red blood cell membrane affinity binding assay and a surface plasmon resonance (SPR) assay. The (99m)Tc radiolabeling of MAG(3)-annexin resulted in radiochemical yields of 90% under mildly basic pH conditions. Biodistribution data in normal mice clearly showed a significant decrease in kidney and liver uptake at 1 h postinjection for the (99m)Tc MAG(3)-annexin compared to the (99m)Tc Hynic-annexin (from 24% ID to 4% ID for the liver, and 45% ID to 15% ID for the kidneys, respectively). Autoradiography of the kidneys showed retention of radioactivity in the collecting tubules following administration of both labeled annexins. The (99m)Tc MAG(3)-annexin biodistribution was also characterized by a lower retention of radioactivity in the whole body, but with small intestine accumulation over fivefold higher than observed with (99m)Tc Hynic-annexin. These findings show a definite improvement in renal and hepatic clearance of the MAG(3) radioligand. However, due to the increased radioactivity uptake in the small intestines, the early in vivo detection of ongoing apoptosis in the lower abdomen might be more difficult with (99m)Tc MAG(3)-annexin. Nevertheless, (99m)Tc MAG(3)-annexin may be an attractive alternative to (99m)Tc Hynic-annexin for the in vivo imaging of phosphatidylserine receptors.

Animals↗
PubMed2006

Corticosteroids influence the mortality and morbidity of acute critical illness.

INTRODUCTION: Use of corticosteroids for adrenal supplementation and attenuation of the inflammatory and immune response is widespread in acute critical illness. The study hypothesis was that exposure to corticosteroids influences the mortality and morbidity in acute critical illness. METHODS: This case-control retrospective study was performed in a single multidisciplinary intensive care unit at a tertiary care institution and consisted of 10,285 critically ill patients admitted between 1 January 1999 and 31 December 2004. Demographics, comorbidities, acute illness characteristics including severity measured by Sequential Organ Failure Assessment, concurrent medications, therapeutic interventions and incidence of infections were obtained from electronic medical records, were examined with multiple regression analysis and were adjusted for propensity of corticosteroid exposure. The primary outcome was hospital death, and the secondary outcome was transfer to a care facility at hospital discharge. RESULTS: Corticosteroid exposure in 2,632 (26%) patients was characterized by younger age, more females, higher Charlson comorbidity and maximal daily Sequential Organ Failure Assessment scores compared with control patients. Corticosteroids potentiated metabolic and neuromuscular sequels of critical illness with increased requirements for diuretics, insulin, protracted weaning from mechanical ventilation, need for tracheostomy and discharge to a care facility. Early exposure to corticosteroids predisposed to recurrent and late onset of polymicrobial and fungal hospital-acquired infections. Corticosteroids increased the risk for death or disability after adjustments for comorbidities and acute illness characteristics. CONCLUSION: Corticosteroids increased the risk for death or disability in critical illness. Hospital-acquired infections and metabolic and neuromuscular sequels of critical illness were exacerbated by corticosteroids. Careful appraisal of the indications for use of corticosteroids is necessary to balance the benefits and risks from exposure in acute critical illness.

Acute Disease↗
PubMed2006

Bronchial mucus transport velocity in patients receiving propofol and remifentanil versus sevoflurane and remifentanil anesthesia.

Volatile anesthetics reduce ciliary beat frequency in vitro. It has been reported that impaired bronchial mucus transport velocity (BTV) is associated with significantly increased pulmonary complications. In this study, we sought to determine in vivo differences in BTV, comparing patients having total IV anesthesia (TIVA) with propofol and remifentanil to anesthesia with sevoflurane and remifentanil. Twenty-two patients scheduled for elective general surgery were randomized to one of two groups: TIVA (propofol/remifentanil) or SEVO (sevoflurane/remifentanil). Thirty minutes after tracheal intubation, BTV was assessed by fiberoptic observation of the movement of methylene blue dye applied to the dorsal surface of the right main bronchus. BTV was significantly reduced in the SEVO group compared with the TIVA group (mean, 1.5 +/- 0.7 [0-2.3] versus 4.8 +/- 2.1 [2.3-8.8] mm/min; P < 0.0001). Anesthesia with sevoflurane may lead to significantly impaired bronchociliary clearance in comparison to TIVA. This could have implications for perioperative pulmonary complications, in particular in patients at risk for pulmonary complications.

Adolescent↗
PubMed2006

Improved detection of cell death in vivo with annexin V radiolabeled by site-specific methods.

UNLABELLED: Labeled annexin V is widely used to detect cell death in vitro and in vivo. Nearly all studies have been done with annexin V derivatized via amine-directed bifunctional agents; it was thought that these molecules retained full bioactivity compared with unmodified protein. We now show that this assumption is incorrect by measuring the affinity of annexin V for cells in vitro by quantitative calcium titration under conditions of low membrane occupancy. METHODS: Annexin V was modified with 4 different amine-directed agents: the N-hydroxysuccinimide esters of hydrazinonicotinic acid, mercaptoacetyltriglycine, and biotin; and with fluorescein isothiocyanate. RESULTS: In all cases, the membrane-binding affinity was decreased by derivatization, even at very low average stoichiometries. A statistical model based on the Poisson distribution accurately predicted the observed heterogeneity of derivatization as a function of average derivatization stoichiometry. This model also showed that multiply derivatized forms, which are the ones most likely to have compromised bioactivity, contributed disproportionately to the binding and imaging signals. The in vitro binding assay correctly predicted in vivo uptake in a mouse liver model of apoptosis for all proteins tested. The annexin V-128 protein, labeled at a single specific site at the N terminus, showed twice as much apoptosis-specific liver uptake as did all forms of annexin V derivatized randomly via amino groups. CONCLUSION: The membrane-binding activity of annexin V is much more sensitive to amine-directed chemical modification than previously realized. New annexin V molecules labeled by site-specific methods will greatly improve sensitivity for detecting cell death in vivo.

Animals↗
PubMed2005

Cortisol levels and corticosteroid administration fail to predict mortality in critical illness: the confounding effects of organ dysfunction and sex.

BACKGROUND: Corticosteroid supplementation based on plasma cortisol measurement was reported to decrease mortality in vasopressor-dependent critical illness. HYPOTHESIS: Random levels or maximal increments of plasma cortisol measured after short adrenal stimulation may predict mortality independent of concurrent organ dysfunction or sex, and corticosteroid supplementation may decrease mortality in vasopressor-dependent critical illness. DESIGN: An observational descriptive study. PATIENTS: Critically ill patients receiving vasopressors for treatment of hemodynamic instability. METHODS: Random levels (n = 522 patients) and maximal increments (n = 282 patients) of plasma cortisol were measured after 250 microg of adrenocorticotropic hormone was administered for short stimulation tests before patients received corticosteroid supplementation. The severity of acute illness was measured by sequential organ failure assessment. MAIN OUTCOME MEASURE: Hospital mortality. RESULTS: The overall mortality was 24%. A random plasma cortisol level of 15 microg/dL or less was associated with lower mortality than a random plasma cortisol level greater than 15 microg/dL in men (12% vs 26%, respectively; P<.01) and women (13% vs 31%, respectively; P<.01). A maximal plasma cortisol increment of 9 microg/dL or less increased mortality as compared with an increment greater than 9 microg/dL in men (31% vs 11%, respectively; P<.01) but not in women (30% vs 29%, respectively; P = .8). Random levels and maximal increments of plasma cortisol did not influence hospital mortality predicted by the sequential organ failure assessment score. Corticosteroids were given to 244 patients (47%) without an effect on mortality (mortality rate of 27% for patients given corticosteroids vs mortality rate of 22% for patients who did not receive corticosteroids; P = .6). Corticosteroids did not influence mortality when plasma cortisol was a random level of 15 microg/dL or less (mortality rate of 14% for patients who received corticosteroids vs mortality rate of 10% for those who did not receive corticosteroids; P = .4) or when plasma cortisol was a maximal increment of 9 microg/dL or less (mortality rate of 30% for patients who received corticosteroids vs mortality rate of 31% for patients who did not receive corticosteroids; P = .9). CONCLUSIONS: Remote organ dysfunction and sex influenced mortality associated with cortisol levels measured in critical illness. Corticosteroid supplementation guided by arbitrary levels or increments of plasma cortisol in critical illness did not improve survival. Better guidelines for corticosteroid supplementation in critical illness should be developed to avoid potential adverse effects from unwarranted treatment.

Adrenal Cortex Hormones↗
PubMed2004

Synthesis, properties and structures of eight-coordinate zirconium(IV) and hafnium(IV) halide complexes with phosphorus and arsenic ligands.

Eight-coordinate [MX(4)(L-L)(2)] (M = Zr or Hf; X = Cl or Br; L-L = o-C(6)H(4)(PMe(2))(2) or o-C(6)H(4)(AsMe(2))(2)) were made by displacement of Me(2)S from [MX(4)(Me(2)S)(2)] by three equivalents of L-L in CH(2)Cl(2) solution, or from MX(4) and L-L in anhydrous thf solution. The [MI(4)(L-L)(2)] were made directly from reaction of MI(4) with the ligand in CH(2)Cl(2) solution. The very moisture-sensitive complexes were characterised by IR, UV/Vis, and (1)H and (31)P NMR spectroscopy and microanalysis. Crystal structures of [ZrCl(4)[o-C(6)H(4)(AsMe(2))(2)](2)], [ZrBr(4)[-C(6)H(4)(PMe(2))(2)](2)], [ZrI(4)[o-C(6)H(4)(AsMe(2))(2)](2)] and [HfI(4)[o-C(6)H(4)(AsMe(2))(2)](2)] all show distorted dodecahedral structures. Surprisingly, unlike the corresponding Ti(iv) systems, only the eight-coordinate complex was found in each system. In contrast, the ligand o-C(6)H(4)(PPh(2))(2) forms only six-coordinate complexes [MX(4)[-C(6)H(4)(PPh(2))(2)]] which were fully characterised spectroscopically and analytically. Surprisingly the tripodal triarsine, MeC(CH(2)AsMe(2))(3), also produces eight-coordinate [MX(4)[MeC(CH(2)AsMe(2))(3)](2)] in which the triarsines bind as bidentates in a distorted dodecahedral structure. There is no evidence for seven-coordination as found in some thioether systems.

Journal Article↗
PubMed2004

Noninvasive measurement of systemic vascular resistance using Doppler echocardiography.

BACKGROUND: Systemic vascular resistance (SVR) is an integral therapeutic component of patients with heart failure and shock. We hypothesized that the ratio of the peak mitral regurgitant velocity (MRV) (m/s) to left ventricular outflow time-velocity integral (TVI(LVOT)) (cm) by Doppler would provide a noninvasive correlate of SVR. METHODS: SVR was correlated to MRV/TVI(LVOT) in 33 patients undergoing right heart catheterization. Receiver operating characteristic curves were generated to determine the best-balanced sensitivity and specificity to identify SVR > 14 Wood units (WU) and <10 WU. RESULTS: MRV/TVI(LVOT) correlated well with SVR (r = 0.842, 95% confidence interval 0.7-0.92, P <.001, Y = 0.459 + 49.397*X). By receiver operating characteristics, MRV/TVI(LVOT) > 0.27 had a 70% sensitivity and a 77% specificity to identify SVR > 14 WU. MRV/TVI(LVOT) < 0.2 had a 92% sensitivity and a 88% specificity to identify SVR < 10 WU. CONCLUSION: Doppler echocardiography provides a reliable noninvasive assessment of SVR.

Aged↗
PubMed2002

Reading speed test for potential central vision measurement.

This study examines the validity and reliability of a reading speed test as a measure of potential central vision. Reading speed was calculated in words per minute (wpm) from the time taken to read 30 words of 1.20 logMAR size text. Scores were obtained from subjects with cataract (n = 48), macular disease(n = 35), peripheral vision loss(n = 14) and normal eyes (n = 10). Subjects with macular disease (27.0 +/- 13.2 wpm) read much slower than subjects with cataract (91.9 +/- 13.6 wpm). Little difference was found between subjects with cataract, peripheral vision loss (91.5 +/- 14.7 wpm)and normal eyes (103.8 +/- 15.5 wpm). Repeat testing gave values within +/- 16% of reading speed. These results suggest that a reading speed test using large text could be useful as a potential central vision test in cataract patients.

Aged↗