Multiple adenomatous polyps of the gallbladder presenting as carcinoma of the gallbladder.
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Adenomatous Polyps↗
Biomedical subjects
A Singh
Publications and source records attributed to A Singh.
Monitoring end-tidal carbon dioxide during weaning from cardiopulmonary bypass in patients without significant lung disease.
End-tidal carbon dioxide tension (PETCO(2)) changes with fluctuations in cardiac output (CO). We compared PETCO(2) to pulmonary artery blood flow (PAQt) during weaning from cardiopulmonary bypass (CPB) in normothermic patients without significant pulmonary disease. Fifteen consecutive adult cardiac surgical patients were prospectively studied during and shortly after weaning from CPB. Before separation from CPB, PETCO(2) and PAQt were measured, the latter by transesophageal Doppler echocardiography. At the time of measurements patients were normothermic, and ventilated at 6 breaths/min with tidal volumes of 10 mL/kg. After separation from CPB, thermodilution cardiac output (TDCO) was measured in addition to PAQt and PETCO(2). Regression and bias analyses were used to compare PETCO(2), PAQt, and TDCO. Seventy measurements were recorded; 31 before separation from CPB and 39 after separation from CPB. A good correlation was seen between PAQt and PETCO(2) (r = 0.88) and between TDCO and PAQt (r = 0.93; mean bias 0.03 L/min; SD 0.52 L/min). The regression analysis of PAQt on PETCO(2) showed greater variability at PETCO(2) levels > 34 mm Hg (n = 22; r = 0.14). Increases in PETCO(2) plateaued at this level, although PAQt continued to increase. When PETCO(2) was more than 30 mm Hg, all PAQt and TDCO values were >4.0 L/min (>2.0 L/min/m(2)). When PETCO(2) exceeded 34 mm Hg, all values of PAQt, and 28/29 values of TDCO were more than 5 L/min (>2.5 L/min/m(2)). One patient had TDCO of 4.69 L/min (2.39 L/min/m(2)). In normothermic patients without significant pulmonary disease, PETCO(2) is a useful index of PAQt during separation from CPB. Under the clinical settings in this study, a PETCO(2) greater than 30 mm Hg was invariably associated with a CO more than 4.0 L/min or a cardiac index >2.0 L/min/m(2).
Aged↗
Hyperglycemia in patients with schizophrenia who are treated with olanzapine.
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Adult↗
Uptake and killing of Listeria monocytogenes by normal human peripheral blood granulocytes and monocytes as measured by flow cytometry and cell sorting.
Cellular components of innate immunity (NK cells, monocytes and granulocytes) play an important role in early resistance to Listeria monocytogenes in the mouse model. Minimally invasive methods of measuring the bacteriocidal capacity of these cells may be useful as a biomarker of susceptibility in humans. A technique was developed whereby the uptake and survival of L. monocytogenes could be measured in human granulocytes and monocytes using small volumes of peripheral blood. This method used flow cytometry to detect the presence of PKH-2-labeled bacteria within these cells. Survival of bacteria was determined by sorting of infected cells based on a combination of fluorescence and light scattering properties. Considerable variation in bacterial recovery was seen between normal volunteers. There was consistently greater survival of a fully virulent strain of L. monocytogenes within monocytes and granulocytes compared with an isogenic strain lacking the hemolysin, listeriolysin O, when measured at baseline. There was no evidence of longer-term bacterial survival or growth at 2 or 24 h. This technique may be useful for assessment of both host resistance and pathogen virulence.
Adult↗
Comparison of efficacies of cysteine protease inhibitors against five strains of Plasmodium falciparum.
Falcipain-2, a cysteine protease and essential hemoglobinase of Plasmodium falciparum, is a potential antimalarial drug target. We compared the falcipain-2 sequences and sensitivities to cysteine protease inhibitors of five parasite strains that differ markedly in sensitivity to established antimalarial drugs. The sequence of falcipain-2 was highly conserved, and the sensitivities of all of the strains to falcipain-2 inhibitors were very similar. Thus, cross-resistance between cysteine protease inhibitors and other antimalarial agents is not expected in parasites that are now circulating and falcipain-2 remains a promising chemotherapeutic target.
Animals↗
Molecular characterization of cryptosporidium oocysts in samples of raw surface water and wastewater.
Recent molecular characterizations of Cryptosporidium parasites make it possible to differentiate the human-pathogenic Cryptosporidium parasites from those that do not infect humans and to track the source of Cryptosporidium oocyst contamination in the environment. In this study, we used a small-subunit rRNA-based PCR-restriction fragment length polymorphism (RFLP) technique to detect and characterize Cryptosporidium oocysts in 55 samples of raw surface water collected from several areas in the United States and 49 samples of raw wastewater collected from Milwaukee, Wis. Cryptosporidium parasites were detected in 25 surface water samples and 12 raw wastewater samples. C. parvum human and bovine genotypes were the dominant Cryptosporidium parasites in the surface water samples from sites where there was potential contamination by humans and cattle, whereas C. andersoni was the most common parasite in wastewater. There may be geographic differences in the distribution of Cryptosporidium genotypes in surface water. The PCR-RFLP technique can be a useful alternative method for detection and differentiation of Cryptosporidium parasites in water.
Animals↗
Newly diagnosed pulmonary sarcoidosis in HIV-infected patients.
PURPOSE: To determine the radiologic and clinical features of newly diagnosed pulmonary sarcoidosis in human immunodeficiency virus (HIV)-infected patients. MATERIALS AND METHODS: Ten HIV-infected patients (seven women, three men; age range, 26-66 years; mean age, 37 years) with newly diagnosed sarcoidosis between 1989 and 1997 were retrospectively identified. Charts were reviewed for the interval between the two diagnoses, CD4 cell count, signs or symptoms, angiotensin-converting enzyme level, and initiation of highly active antiretroviral therapy (HAART). Chest radiographs (n = 10) and computed tomographic (CT) scans (n = 8) were assessed for lymphadenopathy, pulmonary nodules, focal consolidation, reticular or granular opacities (thickened interlobular septa and ground-glass opacities at CT), cysts or cavities, and fibrosis. RESULTS: Mean interval between the two diagnoses was 3 years. Mean CD4 cell count was 213 cells per cubic millimeter. When sarcoidosis was diagnosed, eight patients had pulmonary signs or symptoms. The angiotensin-converting enzyme level was elevated in five of six patients; two developed sarcoidosis after beginning HAART. Chest radiographs revealed lymphadenopathy, pulmonary nodules, focal consolidation, reticular opacities, granular opacities, and cysts or cavities. Chest CT scans revealed lymphadenopathy, nodules, thickened interlobular septa, focal consolidation, reticular opacities, ground-glass opacities, and cysts or cavities. There was no relationship between the radiographic findings of sarcoidosis and the CD4 cell count. CONCLUSION: The radiologic features of newly diagnosed sarcoidosis in HIV-infected patients resemble the findings of sarcoidosis in non-HIV-infected patients. In HIV-infected patients receiving HAART, sarcoidosis may be a manifestation of disease related to restoration of the immune system.
Adult↗
Raising of the mucoperichondrial flap in septal surgery.
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Humans↗
Lipopolysaccharide-mediated immobility in mice: reversal by cyclooxygenase enzyme inhibitors.
Endotoxin (lipopolysaccharide, LPS) is known to activate the hypothalamo-pituitary adrenocortical axis, as well as norepinephrine and indolamine metabolism. In the present study we examined the effects of systemically administered LPS on forced swimming-induced despair behavior in mice. LPS (50 micrograms/mouse i.p.) time-dependently enhanced the forced swimming-induced immobility period. The increase in immobility time was highest after 2 h of LPS administration. Desipramine (10 mg/kg), a tricycle antidepressant, or fluoxetine (10 mg/kg), a serotonin reuptake inhibitor, significantly reversed the LPS-induced increase in immobility time. Cyclooxygenase inhibitors nimesulide (1, 2 and 5 mg/kg), naproxen (10 mg/kg) and rofecoxib (2 mg/kg) did not alter the despair behavior per se. Nimesulide (10 mg/kg) did reverse reserpine-induced immobility. Nimesulide (2 mg/kg), naproxen (10 mg/kg) and rofecoxib (2 mg/kg) significantly reversed LPS-mediated despair behavior. The present study demonstrated that LPS-induced inflammatory responses in the brain may cause despair behavior. Reversal with a cyclooxygenase inhibitor indicates the role of prostaglandins in despair behavior.
Animals↗
The use of endoscopic argon plasma coagulation in airway complications after solid organ transplantation.
The objective of the study was to describe a safe and effective treatment option for endobronchial complications after solid organ transplantation. A retrospective analysis was performed in a tertiary-care university hospital. The use of bronchoscopic argon plasma coagulation (APC) for the treatment of endobronchial lesions was studied in five solid organ transplant recipients. Four patients presented with variable degrees of endobronchial obstruction, and one patient presented with massive hemoptysis. Two of the patients with endobronchial obstruction were double lung transplant recipients who developed anastomotic strictures. The strictures were opened with endobronchial stents but became obstructed again by inflammatory granulation tissue overgrowth through the stent mesh. APC was used to maintain airway patency. One kidney transplant recipient developed pulmonary zygomycosis with secondary obstruction of the left main bronchus because of granulation tissue growth through endobronchial stents. Airway patency was reestablished with several treatments with APC. Another kidney transplant recipient developed subglottic and tracheal papillomatosis that was effectively removed with APC. A heart transplant recipient was referred with recurrent massive hemoptysis refractory to bronchial artery embolization. The bleeding was caused by hemorrhagic polypoid lesions, which were completely ablated by APC. Bronchoscopic use of the argon plasma coagulator is a safe and simple technique that can be used effectively to treat endobronchial pathology in solid organ transplant patients.
Adult↗
Evaluation of core temperature during laparoscopic and open gastric bypass.
BACKGROUND: Intraoperative hypothermia is a common event during open and laparoscopic abdominal surgery. The aim of this study was to compare changes in core temperature between laparoscopic and open gastric bypass (GBP). METHODS: 101 patients with a body mass index (BMI) of 40-60 kg/m2 were randomly assigned to open (n = 50) or laparoscopic (n = 51) GBP. Anesthetic technique was similar for both groups. An external warming blanket and passive airway humidification were used intraoperatively. Core temperature was recorded at preanesthesia, at baseline (after induction) and at 30-min intervals; intra-abdominal temperature was additionally measured at 30-min intervals in a subset of 30 laparoscopic GBP patients. The number of patients who developed intraoperative and postoperative hypothermia (< 36 degrees C) was recorded. Length of operation for both groups and the amount of CO2 gas delivered during laparoscopic operations were also recorded. RESULTS: There was no significant difference between groups with respect to age, gender, mean BMI, and amount of intravenous fluid administered. After induction of anesthesia, core temperature significantly decreased in both groups; 36% of patients in the open group and 37% of patients in the laparoscopic group developed hypothermia. This percentage increased to 46% in the open group and 41% in the laparoscopic group during the operation, and then decreased to 6% in the open group and 8% in the laparoscopic group in the recovery-room. Core temperature increased during the operative procedure to reach 36.5 +/- 0.6 degrees C in the open group and 36.3 +/- 0.5 degrees C in the laparoscopic group at 2.5 hours after surgical incision. Intra-abdominal temperature during laparoscopic GBP was significantly lower than core temperature at all measurement points (p < 0.05). Operative time was longer in the laparoscopic group than in the open group (232 +/- 43 vs 201 +/- 38 min, p < 0.01). Mean volume of gas delivered during laparoscopic GBP was 650 +/- 220 liters. CONCLUSION: Perioperative hypothermia was a common event during both laparoscopic and open GBP. Despite a longer operative time, laparoscopic GBP did not increase the rate of intraoperative hypothermia when efforts were made to minimize intraoperative heat loss.
Adult↗
Participation of residue F552 in domain III of the protective antigen in the biological activity of anthrax lethal toxin.
The protective antigen (PA) component of anthrax toxin translocates the catalytic moieties lethal factor (LF) and edema factor (EF) into the cytosol. The proteolytically activated 63 kDa form of PA (PA63) has the ability to oligomerize and bind LF/EF. PA has four distinct domains performing specialized functions; whereas the function of domains I, II and IV has been well characterized, domain III has no known role in the biological activity of PA. Here we report the role of amino acid residues lining an exposed hydrophobic patch of domain III in the biological activity of PA. The residues Phe552, Phe554, lIe562, Leu566 and lle574 were individually substituted with alanine and the effect was studied. All mutant PA proteins except Phe552Ala were equally active as wild-type PA in exhibiting a toxic phenotype to J774A.1 cells in the presence of LF. Substitution of Ala for Phe552 reduced the ability of PA to intoxicate cells by more than 250-fold. However, Phe552Ala was equally active in receptor binding and susceptibility to trypsin and chymotrypsin as wild-type PA, the activities that have been shown to be essential for the biological activity of PA. This mutated PA protein had a decreased ability to bind LF, oligomerize on cells and to induce release of 86Rb+ from Chinese hamster ovary cells. These results suggest that the residue Phe552 in PA plays an important role in LF binding and oligomerization. Our study provides a basis for further exploration of the biological significance of domain III of PA.
Amino Acid Substitution↗
A multidisciplinary team approach to skull base chordomas.
OBJECT: A multidisciplinary team devised a protocol for long-term care of patients with skull base chordomas. In this study they describe their approach. METHODS: Forty-two patients presented between 1986 and 1998 and were treated by maximum surgical cytoreduction and photon radiation therapy. Tumor volume-doubling time determined on the basis of magnetic resonance imaging, immunostaining, and cell proliferation (Ki67 labeling index [LI]) studies indicated growth rates of individual chordomas. The best outlook was associated with the greatest extent of tumor removal achieved during the first operation. There were no deaths associated with patients who underwent first-time surgery, but there was a 7.1% mortality rate associated with those who underwent subsequent operations. Cerebrospinal fluid leaks, additional cranial nerve palsies, and pharyngeal wound problems were the most difficult management problems encountered after second and subsequent surgeries. The time interval between operations was usually between 2 years and 3 years after the first surgery; very few patients required a second surgery, with a quiescent period in excess of 5 years. Life-table 5- and 10-year survival rates were 77% and 69%, respectively. CONCLUSIONS: The authors believe that this series of skull base chordomas provides new insights into the management of these lesions, particularly with regard to techniques that increase survival times and studies that aid in formulating prognoses.
Adolescent↗
A multidisciplinary team approach to skull base chondrosarcomas.
OBJECT: The authors review their experience with treating skull base chondrosarcomas, which are much rarer than skull base chordomas and differ from them in prognosis and treatment. METHODS: Seventeen patients (12 male and five female patients) with histologically verified chondrosarcomas were followed up prospectively over a 12-year period. The mean age at presentation was 35.9 years. Most patients presented with cranial nerve palsies. Seven had undergone surgery prior to referral to the authors' unit. All underwent maximum surgical cytoreduction by the most direct surgical approach; only the two patients harboring the mesenchymal variant underwent radiotherapy. CONCLUSIONS: One patient died of a pulmonary embolus; the patients harboring mesenchymal chondrosarcomas died at 20 and 36 months, respectively, after treatment. Of the remaining patients, 93% were alive 5 years postsurgery and had a projected 10-year survival rate of 84% (mean survival time 9.3 years). These data emphasize the very slow progression of this tumor compared with skull base chordoma.
Adolescent↗
Clinical and radiological correlates of severity and surgery-related outcome in cervical spondylosis.
OBJECT: The aim of this study was to determine if radiological features could be used to predict outcome in patients with cervical spondylotic myelopathy (CSM). METHODS: The authors studied 69 patients consecutively referred to The National Hospital, Queen Square, for decompressive surgery. Data obtained from preoperative cervical spine magnetic resonance (MR) imaging studies were each analyzed on two separate occasions by two blinded radiologists. The parameters determined were signal change and the presence and severity of compression. Clinical outcome was determined by pre- and postoperative timed walks, as well as by evaluation of myelopathy disability index scores, Ranawat classification, and Nurick grades. There was good inter- and intraobserver reliability for determination of radiological data. A significant relationship was found between MR imaging signal change and surgery-related outcome, as reflected by improvement in walking parameters; however, this was confounded by the fact that signal change also related to preoperative walking parameters, and those patients for whom preoperative walking function was worse experienced greater functional improvement in walking postoperatively. The relationships between ambulatory-related data and severity or extent of spinal cord compression were less marked. CONCLUSIONS: Cervical cord compression and intrinsic MR imaging signal change correlate with clinical severity, and, in this population, the presence of signal change was correlated with better surgery-related outcome. However, confounding factors and the lack of strong correlation indicate that these radiological measurements are insufficient to be used as a reliable tool for predicting surgery-related benefits in individual patients.
Aged↗
Solitary retinal capillary hemangioma: hereditary (von Hippel-Lindau disease) or nonhereditary?
OBJECTIVE: To estimate the probability of von Hippel-Lindau (VHL) disease in patients with solitary retinal capillary hemangioma. METHODS: Risk estimation was performed mathematically on the basis of the Bayes theorem using the published data on prevalence of VHL disease, prevalence of solitary retinal capillary hemangioma, and age-dependent penetrance of VHL disease. RESULTS: The probability of VHL disease in patients with solitary retinal capillary hemangioma was estimated to be 46%. When adjusted for age at the time of diagnosis, the risk varied from 45% in the young age group (</=10 years) to 0.5% in the older age group (61-70 years). CONCLUSIONS: Approximately half of the patients with solitary retinal capillary hemangioma are expected to have underlying VHL disease and the risk progressively diminishes with increasing age at diagnosis. Detailed clinical evaluation in such patients is recommended using standard screening protocols. Knowledge of the age-dependent risk for VHL disease can help the clinician modify recommendations regarding systemic and genetic testing.
Adolescent↗
Which patients with ulcer- or reflux-like dyspepsia will respond favorably to omeprazole?
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Anti-Ulcer Agents↗
Ligand-receptor-mediated drug delivery: an emerging paradigm in cellular drug targeting.
Receptor-mediated cellular events have received major attention in the field of drug/gene delivery in the past few years. These events, which are mediated through the endogenous ligands/epitopes, could be exploited for designing site-specific and target-oriented delivery systems. The past decade has seen the development of endogenous ligands and their mimics of exogenous origins to selectively deliver the contained or immobilized moieties to the cellular interiors using a wide range of cell surface receptors/epitopes. Ligand-mediated active targeting has emerged as a novel paradigm in targeting either vascular compartment (first-order), cellular (second-order), or intracellular (third-order) levels. Most carrier systems or bioconjugates explored so far can be used as cargo units for the site-specific presentation and delivery of various bioactives using biorelevant ligands, including antibodies, polypeptides, oligosaccharides (carbohydrates), viral proteins, fusogenic residues, and molecules of endogenous origin. In this review, we describe various ligand-receptor systems that have been investigated to date for targeted or cellular drug delivery. These include blood carbohydrate (lectin) receptors, Fc receptors, complement receptors, interleukin receptors, lipoprotein receptors, transferin receptors, scavenger receptors, receptors/epitopes expressed on tumor cells, and cell adhesion receptors. The role of receptors as molecular target has opened new opportunities for cellular or intracellular targeting using carrier systems appended with targeting handles (ligands). Research in the field of ligand-receptor-based targeted system is expected to be an armamentarium and the focal point of research in the next millennium.
Drug Carriers↗