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Biomedical subjects

H Gupta

Publications and source records attributed to H Gupta.

At least 19 recordsLinked to original sources
PubMed2026

Tumor genomic landscape of older patients with metastatic breast cancer☆.

BACKGROUND: Metastatic breast cancer (MBC) in older patients has distinct clinical and histologic characteristics. Elucidating the genomic basis of MBC helps identify potential therapeutic targets to improve outcomes for older patients with MBC. PATIENTS AND METHODS: Using a prospective database and targeted DNA sequencing (OncoPanel), we examined MBC's genomic landscape in older patients (age &#x2265;70 years at MBC diagnosis) and compared findings with those in younger (aged <50 years) and middle-aged (aged 50-69 years) patients. After classifying single nucleotide variants (SNVs) and copy number variations (CNVs) as oncogenic (via OncoKB), the frequencies of SNVs and CNVs, tumor mutational burden (TMB), and oncogenic signaling pathways were compared by age group using Fisher's exact tests. We estimated the association between continuous age at MBC diagnosis and mutations via multivariate logistic regression analysis, adjusting for race, stage at initial diagnosis, subtype, histology, and sample tested (primary versus metastatic). RESULTS: Our study included 2379 patients [853 (35%) younger, 1311 (55%) middle-aged, and 215 (9%) older] who underwent OncoPanel testing between 2013 and 2020. The most frequent tumor alterations in older patients were SNVs in PIK3CA (44%), TP53 (33%), CDH1 (22%) and amplifications in CCND1 (18%). After adjustment, older age was associated with higher frequency of SNVs in CDH1 [odds ratio (OR) = 1.43, 95% confidence interval (CI) 1.21-1.68, q < 0.001], MAP3K1 [OR = 1.30, 95% CI 1.10-1.54, q = 0.008], and PIK3CA [OR = 1.21, 95% CI 1.11-1.31, q < 0.001] and fewer SNVs in TP53 [OR = 0.84, 95% CI 0.77-0.91, q < 0.001]. Patients in the older group were more likely to have tumors with &#x2265;10 mutations/megabase than the youngest patients (26% versus 17%, P = 0.003). CONCLUSIONS: In this large cohort of patients with MBC, the tumor genomic landscape differed between older and younger patients even after accounting for tumor subtype. Older patients were more likely to have high-TMB and PIK3CA-mutated tumors, highlighting the importance of genomic testing for treatment applications in this population.

NGS↗
PubMed2005

Rotational spectroscopy and equilibrium structures of S3 and S4.

The sulfur molecules thiozone S3 and tetrasulfur S4 have been observed in a supersonic molecular beam in the centimeter-wave band by Fourier transform microwave spectroscopy, and in the millimeter- and submillimeter-wave bands in a low-pressure glow discharge. For S3 over 150 rotational transitions between 10 and 458 GHz were measured, and for S4 a comparable number between 6 and 271 GHz. The spectrum of S3 is reproduced to within the measurement uncertainties by an asymmetric top Hamiltonian with three rotational and 12 centrifugal distortion constants; ten distortion constants, but an additional term to account for very small level shifts caused by interchange tunneling, are required to reproduce to comparable accuracy the spectrum of S4. Empirical equilibrium (r(e)(emp)) structures of S3 and S4 were derived from experimental rotational constants of the normal and sulfur-34 species and vibrational corrections from coupled-cluster theory calculations. Quantum chemical calculations show that interchange tunneling occurs because S4 automerizes through a transition state with D2h symmetry which lies about 500 cm(-1) above the two equivalent C2upsilon minima on the potential energy surface.

Journal Article↗
PubMed2005

Anterior sciatic nerve block--new landmarks and clinical experience.

BACKGROUND: Anterior sciatic nerve blocks can be complicated by several problems. Pain can be caused by bony contacts and, in obese patients, identification of the landmarks is frequently difficult. METHODS: In a first step, 100 normal anterior-posterior pelvic X-rays were analyzed. The landmarks of the classical anterior approach were drawn on these X-rays and assessed for their sufficiency. Then, in a prospective case study, 200 consecutive patients undergoing total knee replacement were investigated. These patients received femoral and sciatic nerve catheters for postoperative pain management. Using modified anatomical landmarks, sciatic nerve catheters were inserted 5 cm distal from the insertion site of the femoral nerve block perpendicularly in the midline of the lower extremity. This midline connected the insertion site of the femoral nerve catheter to the midpoint between the medial and lateral epicondyle. Correct catheter positioning was verified by magnetic resonance imaging (MRI) in six patients. RESULTS: Evaluation of pelvic X-rays showed that puncture following the classical landmarks pointed in 51% at the lesser trochanter, in 5% medial to the lesser trochanter and in 42% directly at the femur. In the latter patients, location of the sciatic nerve would have been difficult or even impossible. Using our modified anterior approach, the sciatic nerve could be blocked in 196 patients (98%). In nine patients (4.5%) blockade of the posterior femoral cutaneous nerve failed. Vascular puncture happened in 10 (5%) and bony contact in 35 patients (17.5%). Median puncturing depth was 9.5 (7.5-14) cm. Correct sciatic nerve catheter positioning was verified in all patients who underwent MRI. CONCLUSION: Our landmarks for locating the sciatic nerve help to avoid bony contacts and thereby reduce pain during puncture. Our method reliably enabled catheter placement.

Aged↗
PubMed2004

Congenital hypofibrinogenemia.

Congenital afibrinogenemia/hypofibrinogenemia is an extremely rare coagulation disorder. We describe a case of congenital hypofibrinogenemia in a 6-year female child, who presented with recurrent ecchymotic spots with no frank bleeding.

Afibrinogenemia↗
PubMed2003

The neointimal response to endovascular injury is increased in obese Zucker rats.

BACKGROUND: Restenosis after revascularization procedures is accelerated in persons with type 2 diabetes. AIM: The current study tested the hypothesis that the neointimal response to endovascular injury is enhanced in female obese Zucker (OZ) rats, a model of type 2 diabetes. METHODS: Animals were randomized to receive either a standard diet (SD) or a diabetogenic diet (DD) for 6 weeks. Four weeks later, balloon injury of the right common carotid artery was induced. All rats were euthanized 2 weeks after injury. Lean Zucker (LZ) rats served as controls. RESULTS: At the time of death, plasma glucose was elevated in OZ rats fed a SD (208 +/- 13 mg/dl) and a DD (288 +/- 21 mg/dl) compared to corresponding LZ rats (SD: 153 +/- 8; DD: 132 +/- 7 mg/dl). The ratio of high-density lipoprotein cholesterol (HDLc) to total cholesterol (Totc), an index of atherogenicity, was reduced in OZ rats on both diets (SD: 0.77 +/- 0.06; DD: 0.80 +/- 0.09) compared to LZ controls (SD: 1.11 +/- 0.02; DD: 1.20 +/- 0.05). Histomorphometric analysis of injured arteries showed that the intima to media (I : M) ratio was significantly increased in OZ (1.37 +/- 0.07) compared to LZ (0.79 +/- 0.08) rats. Elevations in plasma glucose and triglycerides (Tg) correlated positively and decreases in HDLc negatively with an increased I : M ratio. Administration of the DD did not further enhance the I : M ratio in LZ (0.87 +/- 0.06) or OZ (1.29 +/- 0.09) rats. CONCLUSIONS: These results suggest that neointima formation following endoluminal injury of the carotid artery is enhanced at an early stage in the development of diabetes mellitus.

Animals↗
PubMed2001

Functional and morphologic comparison of two methods to produce transient retinal ischemia in the rat.

OBJECTIVES: Much of our knowledge of the pathophysiology of retinal ischemic injury is from a multitude of studies that use in vitro or in vivo animal models of retinal ischemia followed by reperfusion. The objective of this study was to compare histopathologic and electrophysiologic (electroretinography) parameters using two different models of transient retinal ischemia: high intraocular pressure (HIOP) and suture ligation of the optic nerve (SL). METHODS: Transient retinal ischemia was induced using the HIOP model or the SL model in the Sprague-Dawley rat for either 30 or 60 minutes. Histopathologic outcome was determined at 1 and 7 days after ischemia. In addition, electroretinography (ERG) was performed at 2 hours, I day, 3 days, and 7 days after ischemia. RESULTS: At 1 and 7 days after 30 minutes of ischemia, there were no significant histopathologic abnormalities in the retina with either model, except for a slight decrease of the cell count in the ganglion cell layer (GCL) with the SL method. After 60 minutes of ischemia, there was significant thinning of the inner retina. There was a significant early dropout of cells at 1 day in the inner nuclear layer (INL) in the HIOP method compared to the SL method where the dropout was delayed and gradually progressive. Dropout of cells in the GCL was early (I day) and gradually progressive in both models but more severe in HIOP than SL. There was a significant decrease in the ERG b-wave amplitudes as early as 2 hours after both 30 and 60 minutes of ischemia compared to preischemic baselines. CONCLUSIONS: The degree of retinal injury after transient retinal ischemia was more severe at 1 day after reperfusion in the HIOP method compared to the SL method but was similar at 7 days in both models. Furthermore, our data suggests that functional assessment of ischemic damage by electroretinography may be a more sensitive parameter than conventional histopathologic quantification. The timing of either measurement relative to the ischemic stimulus is critical because histologic measurements performed too early after ischemia may underestimate the degree of injury.

Animals↗
PubMed2000

Perceptions of and constraints upon pregnancy-related referrals in rural Rajasthan, India.

Mortality associated with complications of pregnancy and childbirth remains disproportionately high in the developing world. This paper reports on a study into the reasons for the poor uptake of referrals to specialist medical units in a group of 276 women in a rural area in the state of Rajasthan, India. Of the 276 cases that were referred, 242 (88%) of the women failed to attend for specialist consultation. In-depth personal interviews were conducted and a series of focus group discussions was held with the women and with their spouses and spouses' mothers. A range of geographic, cultural, socio-economic and medico-administrative factors was identified as influencing decisions to attend referral units. Recommendations for improving uptake include improving facilities at referral units, providing additional training for healthcare staff (covering technical, managerial and behavioural aspects) and in counselling techniques, a better defined role for traditional birth attendants, improved understanding of the mother's needs by her family (particularly the spouse and his mother) and increasing public awareness of the importance of referral. Finally, there is the requirement that women are encouraged to realize and understand their own needs.

Adolescent↗
PubMed1999

Detecting hepatic lesions: the added utility of CT liver window settings.

PURPOSE: To prospectively evaluate the utility of adding computed tomographic (CT) liver windows to conventional soft-tissue windows for the detection of hepatic disease. MATERIALS AND METHODS: One of four radiologists experienced in abdominal imaging interpreted 1,175 consecutive abdominal CT scans from one institution. Hepatic images were first interpreted by using standard soft-tissue windows. The number of lesions and confidence in lesion detection were recorded. The liver-window images were then interpreted in conjunction with the soft-tissue-window images, and the number of lesions and confidence in detection were recorded again. The proportion of patients in whom additional lesions were found by using liver windows was determined. RESULTS: On soft-tissue-window and liver-window scans interpreted together, 869 (74%) patients had no hepatic lesions. Thirty-six (3.1%) patients had new lesions seen with the addition of liver windows. Twelve of these 36 patients had no lesions seen on soft-tissue-window scans. Twenty-six of the 36 patients with additional lesions seen had a history of neoplasm. There was a change in diagnosis in 1.7% of the patients with the addition of liver windows and a change in recommendation for follow-up in 0.85%. CONCLUSION: Routine interpretation of liver-window scans for all abdominal CT scans has limited added utility in detecting hepatic disease.

Adolescent↗
PubMed1999

Cytological study of serous effusions with the aid of tumour markers.

Clinicocytological evaluation with the help of tumour markers was done in 25 cases presenting with serous effusions. The main aim was to differentiate between reactive mesothelial cells and malignant cells, type the tumour cells in effusions with the aid of tumour markers--carcino-embryonic antigen (CEA), epithelial membrane antigen (EMA), cytokeratin and vimentin. It was observed that immunocytochemistry has complemented conventional cytology in diagnosis of carcinoma specially in cases labelled as suspicious of malignancy. EMA was found to be the most reliable epithelial marker and very useful in differentiating carcinoma cells from reactive mesothelial cells.

Abdominal Neoplasms↗
PubMed1999

Two in-office bleaching systems: a scanning electron microscope study.

The purpose of this investigation was to analyze by scanning electron microscopy the effects of heated and light-absorbing bleaching agents on enamel surface morphology. Twelve freshly extracted human anterior teeth were selected for this study. The teeth were randomly divided into four equal groups: Group I (control), Group II (teeth treated with Opalescence Quick, a heated bleaching agent), Group III (teeth treated with Opalescence Xtra, a light-absorbing bleaching agent), Group IV (teeth treated with Ultra-Etch 35% phosphoric acid etchant). After receiving a prophylaxis with a slurry of pumice, the bleaching materials were applied to the facial enamel surfaces following the manufacturer's specifications. The teeth in Group IV were etched for 15 to 20 seconds, washed, and air-dried. All specimens were prepared for scanning electron microscope evaluations. Scanning electron microscope micrographs indicated that only those specimens etched with phosphoric acid (Group IV) exhibited an etching pattern on the enamel surface. No differences in enamel surface morphology were observed between the untreated control specimens and the specimens treated with the bleaching materials.

Carbamide Peroxide↗
PubMed1999

Lipid peroxide levels in chronic renal failure.

To determine presence of oxidant stress in chronic renal failure and to evaluate the efficacy of vitamin E in its amelioration, we studied 34 patients (Group I, age 32.4 +/- 11 years, M:F 3:1) and 10 healthy controls (Group II, age 27.4 +/- 5 years, M:F 4:1). The difference in baseline values of lipid peroxide (nmol/ml) was statistically significant (Group I 4.19 +/- 1.69, Group II 1.87 +/- 1.39, p = 0.004). Values of vitamin E (mg/l) were also significantly lower in Group I as compared to Group II (12.18 +/- 4.27 vs. 19.32 +/- 2.03, p = 0.003). Serum lipid peroxide values decreased significantly after supplementation with 400 mg/day of vitamin E for six weeks in Group I (4.19 +/- 1.69 to 3.21 +/- 1.13, p = 0.053) but not in Group II (1.87 +/- 1.39 to 1.03 +/- 0.87). Levels of vitamin E increased in both the groups (Group I: 12.18 +/- 4.27 to 16.01 +/- 5.13, Group II: 19.32 +/- 2.03 to 23.21 +/- 1.94, p < 0.005). No significant difference was observed in values of serum creatinine and urea before and after intervention.

Adult↗
PubMed1998

Comparison of six rapid agglutination tests for the identification of Staphylococcus aureus, including methicillin-resistant strains.

Six rapid agglutination tests for the identification of Staphylococcus aureus were evaluated by testing 416 strains of staphylococci. The sensitivities and specificities of the tests were as follows: Staphyloslide, 97.7% and 99.3% respectively; Prolex Staph Latex, 96.9% and 93.6%; Staphaurex, 95.4% and 94.2%; Staphaurex Plus, 100% and 93.4%; Slidex Staph Plus, 98.9% and 99.3%; and Staphytect Plus, 99.6% and 88.2%. The three tests utilizing latex particles coated with staphylococcal capsular antibodies were better able to identify methicillin-resistant S. aureus, but only Staphyloslide and Slidex Staph Plus had adequate specificity.

Agglutination Tests↗
PubMed1998

Preconditioning provides complete protection against retinal ischemic injury in rats.

PURPOSE: The objectives of this study were to examine whether preconditioning can decrease ischemic damage to the retina, by electroretinographic assessment of visual function and by histologic examination of retinal structure; to investigate the time course of the effectiveness of preconditioning; and to determine whether protein synthesis is involved. METHODS: Retinal ischemia was produced for 60 minutes in anesthetized Sprague-Dawley rats. Recovery after ischemia was measured by electroretinography for a maximum period of 7 days. Retinal sections that were sliced 1 micron thick were examined 7 days after ischemia. Retinal ischemia for 5 minutes constituted the preconditioning stimulus. To assess the time course of preconditioning, animals first underwent preconditioning and then 60 minutes of ischemia 1, 24, 72, or 168 hours later; or they underwent a 5-minute sham experiment and 60 minutes of ischemia 24 hours later. An additional group of rats received 0.4 mg/kg cycloheximide, the protein synthesis inhibitor, intraperitoneally before preconditioning and underwent 60 minutes of ischemia 24 hours later. RESULTS: In contrast to the nonpreconditioned rats, preconditioned rats had complete recovery of the a- and b-waves compared with preischemic baseline amplitudes, and ischemia-induced histologic damage was completely prevented when preconditioning was performed 24 or 72 hours (but not 168 hours) before ischemia. Separation of preconditioning and 60 minutes of ischemia by 1 hour caused an even greater impairment of functional retinal recovery compared with that seen in sham-preconditioned rats. Severe histologic damage was also noted. Block of protein synthesis by cycloheximide completely attenuated the protective effect of preconditioning. CONCLUSIONS: Preconditioning induces profound retinal tolerance to ischemia in vivo. The absence of a protective effect of preconditioning when there was a 1-hour or a 168-hour separation between the preconditioning stimulus and ischemia and the inhibition of preconditioning by cycloheximide support the hypothesis that a transient change in protein expression is necessary to provide this protection.

Animals↗
PubMed1998

The role of the p53 protein in the selective vulnerability of the inner retina to transient ischemia.

PURPOSE: To determine whether the p53 protein plays a role in the selective vulnerability of the inner retina to transient ischemia. METHODS: Transient retinal ischemia was induced using a high intraocular pressure (HIOP) model in the Sprague-Dawley rat for 60 minutes. Histopathologic outcome was determined 7 days after ischemia. In addition, analysis for evidence for apoptosis (TdT-dUTP terminal nick-end label [TUNEL] staining) and p53 protein expression (immunohistochemistry) was performed at several points during the reperfusion period. In a separate set of experiments, wild-type mice and two groups of transgenic mice, one homozygous and the other heterozygous for the p53 null gene, were also subjected to HIOP for 60 minutes, and histopathology was performed 7 days later. RESULTS: At 7 days subsequent to 60 minutes of ischemia in the rat, there was marked thinning of the inner retinal layers. There were scattered TUNEL-positive cells within the inner retina, peaking at 24 to 48 hours and persisting for at least 7 days. p53 immunochemistry demonstrated elevated protein levels within the inner retina; this finding peaked at 24 to 48 hours but was no longer present at 4 days after ischemia. TUNEL staining of the inner retina of the mouse was most prominent 24 hours subsequent to ischemia but persisted at 48 hours. Seven days subsequent to 60 minutes of ischemia in the wild-type and transgenic mice, histopathologic evaluation demonstrated preservation of the retinal histoarchitecture in the heterozygous group compared with the wild-type or homozygous animals. CONCLUSIONS: These data further support the hypothesis that the delayed cell death that occurs after transient retinal ischemia is, in part, apoptotic. In addition, they suggest a role for the p53 protein in the selective vulnerability of the inner retina to transient ischemia. p53 protein may be a target for future therapeutic agents in the treatment of disorders of the retina where ischemia plays a pathogenetic role.

Animals↗