Intravenous saline has no effect on blood ethanol clearance.
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Biomedical subjects
Publications and source records attributed to V Patel.
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The isoflavones tectoridin (TTR) and 3'-hydroxy TTR (3'-TTR) were isolated from an Ayurvedic herbal preparation Vacä and evaluated for their affinity and effect on ryanodine receptors (RyR) using junctional sarcoplasmic reticulum vesicles (JSRVs). In [(3)H]ryanodine displacement binding affinity assays, TTR and 3'-TTR exhibited IC(50) values of 17.3 +/- 1.3 microM (K(d) = 6.7 +/- 0.4 microM) and 6.6 +/- 1.4 microM (K(d) = 2.4 +/- 0.2 microM), respectively, for fast skeletal muscle RyR (RyR1) compared with an IC(50) value for ryanodine of 6.2 +/- 0.4 nM (K(d) = 2.4 nM). TTR demonstrated a 3-fold higher affinity for cardiac RyR (RyR2) [IC(50) value of 5.2 +/- 0.6 microM (K(d) = 0.95 +/- 0.3 microM)] than for RyR1. The displacement isotherms for both TTRs paralleled that for ryanodine, consistent with the notion that all three are likely binding to similar site(s) on the receptors. Calcium efflux from and calcium influx into JSRVs were used to measure function effects of TTRs on binding to RyR. In calcium efflux assays, TTR (up to 1 mM) enhanced the release of (45)Ca(2+) from JSRVs in a concentration-dependent manner (EC(50act) of 750 microM). Higher concentrations deactivated (partially closed) RyR1. 3'-TTR had similar effects, but was approximately 2-fold more potent, exhibiting an EC(50act) value of 480 microM. Using passive calcium influx assays, TTR activated and deactivated RyR1 in a time- and concentration-dependent manner. The aglycone tectorigenin also was effective in displacing [(3)H]ryanodine from RyR1 but not from RyR2. These results demonstrate that TTRs are capable of interacting at ryanodine binding sites to differentially modulate fast skeletal and cardiac calcium-release channels.
The Cancer Genome Anatomy Project (CGAP) is a large cooperative effort sponsored by the US National Institutes of Health designed to find, catalog and annotate genes that are expressed during cancer development. In the past 2 years, the CGAP has sequenced over 700,000 clones from approximately 140 cDNA libraries, resulting in the identification of over 30,000 new human genes. As a first step in applying this project to oral cancer we entered four cell lines--two from oral cancer, one from primary oral keratinocytes, and one from oral keratinocytes which had been immortalized by human papillomavirus. Libraries of cDNA were made and sequenced and the data were deposited in GenBank. The expressed genes were then identified where possible. The cell lines, and the total number of expressed genes that were cloned from each were: HN3 (oral cancer), 263 genes; HN4 (oral cancer), 550 genes; HN5 (primary keratinocytes), 237 genes; HN6 (immortalized keratinocytes), 408 genes. The total number of different genes that were found was 1160. A total of 38 new genes, of unknown function, were discovered. The data presented here represent a beginning of the application of the CGAP technology to oral cancer. Even though the data are still quite incomplete, they already represent a large quantity of new information and clones of potential utility to the oral cancer community, and provide a glimpse of the data sets to be forthcoming from the Project. It must therefore be expected that there will soon be a large expansion in the volume of data regarding the genetics of oral cancer. Those who study this disease must be prepared to develop new methods of analysis and storage for handling the oncoming volumes of information.
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We present a study of the information transferred among caregivers in the context of cardiac surgery and use the study to evaluate a system, MAGIC, that we are developing for automated generation of briefings. Our framework integrates cognitive and quantitative evaluation methods and features three standards that reflect current practice in the Cardiothoracic Intensive Care Unit (CTICU). Using experimental design to compare human-generated and machine-generated briefings, we show that MAGIC's current level of performance is useful. Moreover, MAGIC could help improve information flow in the CTICU by providing a consistent set of information earlier than in current practice. The separate standards are also consistent in suggesting specific modifications that may be necessary for iterative design and further system development.
Penetrating injuries of the subclavian artery are rare; however, the associated morbidity and mortality may be high. Retrospective data on 25 patients who sustained penetrating subclavian artery injuries are reported. Diagnosis of subclavian artery injuries was made clinically and was followed by expedient surgical exploration in 65.4 per cent of patients. Patients who were hemodynamically unstable at presentation (26.9%) underwent immediate operation. The remaining hemodynamically stable group of patients with hard signs indicative of vascular injury were also expediently taken to the operating room after initial evaluation and resuscitation. Angiographic evaluation was performed in 34.6 per cent of patients who were stable hemodynamically. Preoperative angiography localized the injury and helped in planning the optimal incision and approach to obtain vascular control. Vascular flow was reestablished in all patients operated except for three who underwent ligation of subclavian artery. Limb salvage rate was 100 per cent, and operative mortality was less than 5 per cent. Morbidity was related to hemodynamic stability at presentation and associated injuries. A low morbidity and mortality rate was achieved by aggressive initial resuscitation and early surgical intervention coupled with selective use of preoperative angiography in hemodynamically stable patients.
Vacuolar-type H(+)-translocating pyrophosphatases (V-PPases) have been considered to be restricted to plants, a few species of phototrophic proteobacteria and protists. Here, we describe PVP, a thermostable, sequence-divergent V-PPase from the facultatively aerobic hyperthermophilic archaeon Pyrobaculum aerophilum. PVP shares only 38% sequence identity with both the prototypical V-PPase from Arabidopsis thaliana and the H(+)-PPi synthase from Rhodospirillum rubrum, yet possesses most of the structural features characteristic of V-PPases. Heterologous expression of PVP in Saccharomyces cerevisiae yields a M(r) 64¿ omitted¿000 membrane polypeptide that specifically catalyzes Mg(2+)-dependent PPi hydrolysis. The existence of PVP implies that PPi-energized H(+)-translocation is phylogenetically more deeply rooted than previously thought.
Stimulation of a number of cell surface receptors, including integrins and G protein-coupled receptors, results in the activation of a non-receptor tyrosine kinase known as focal adhesion kinase (FAK). In turn, this kinase is believed to play a critical role in signaling to intracellular kinase cascades controlling gene expression such as extracellular signal-regulated kinases (ERKs), by a yet poorly defined mechanism. Furthermore, whether this tyrosine kinase also mediates the activation of other mitogen-activated protein kinase family members, such as c-Jun NH(2)-terminal kinases (JNKs), is still unclear. We show here that the activation of FAK by anchoring to the cell membrane is itself sufficient to stimulate potently both ERK and JNK. These effects were found to be phosphatidylinositol 3-kinase-independent, as FAK effectively stimulated Akt, and wortmannin suppressed Akt but not ERK or JNK activation. As previously reported by others, activation of ERK correlated with the ability of FAK to induce tyrosine phosphorylation of Shc. Surprisingly, however, stimulation of JNK was not dependent on the kinase activity of FAK or on the ability to induce tyrosine phosphorylation of FAK substrates. Instead, we provide evidence that FAK may stimulate JNK through a novel pathway involving the recruitment of paxillin to the plasma membrane and the subsequent activation of a biochemical route dependent on small GTP-binding proteins of the Rho family.
This study examines the proportion of patients with ischemic heart disease who may be candidates for the newer modalities of revascularization. A significant proportion (approximately 5%) of patients who undergo coronary angiography at tertiary referral centers may be eligible for newer methods of therapy.
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This study evaluated penetration of Enterococcus faecalis in canals filled with glass ionomer cement sealers. Canals of 40 extracted teeth in four equal experimental groups were prepared and filled with KT-308 (experimental sealer) and a single gutta-percha cone (SC), ZUT (KT-308 with an antibacterial agent) and SC, Kerr sealer and vertically compacted gutta-percha (VC), or Kerr sealer with the antibacterial agent and VC. Eight additional teeth served as positive controls and four as negative controls. Pulp chambers were inoculated with E. faecalis, and bacterial penetration through the filled canals was assessed over a period of 90 days. Incidence of bacterial penetration was significantly higher for ZUT/SC than for Kerr sealer/VC (p < 0.05). KT-308/SC did not differ significantly from any other material. The positive controls showed significantly faster penetration than all the other groups (p < 0.05). It was concluded that KT-308 effectively prevented penetration of E. faecalis, whereas ZUT required further development.
This randomized, double-masked, placebo-controlled, multicenter trial was conducted in 9 countries to assess the safety and efficacy of 2 doses of intravenous ondansetron (8 and 16 mg) for the control of opioid-induced nausea and vomiting. A total of 2574 nonsurgical patients who presented with pain requiring treatment with an opioid analgesic agent participated in this trial. The most common presenting painful condition was back or neck pain, reported by approximately one third of patients. A total of 520 patients (317 females, 203 males) developed nausea or vomiting after opioid administration and were randomly assigned to receive a single dose of 1 of 3 study treatments: placebo (n = 94), ondansetron 8 mg (n = 215), or ondansetron 16 mg (n = 211). Ondansetron 8 and 16 mg led to complete control of emesis in 134 of 215 patients (62.3%) and 145 of 211 patients (68.7%), respectively. Results with both doses were significantly better than those seen with placebo (43 of 94 patients [45.7%]). Complete control of nausea was achieved in 6.8% of placebo patients, 14.8% of ondansetron 8-mg-treated patients, and 19.4% of ondansetron 16-mg treated patients; only ondansetron 16 mg was significantly better than placebo (P = 0.007). Significantly more patients who received ondansetron 8 mg than patients who received placebo were satisfied/very satisfied with their antiemetic treatment, as assessed by 4 patient-satisfaction questions. Significantly more patients who received ondansetron 16 mg compared with placebo were satisfied/very satisfied on 2 of 4 satisfaction questions. In conclusion, based on the observed incidence of opioid-induced nausea and vomiting in this study, it may be more appropriate to treat symptoms on occurrence rather than administering antiemetic agents prophylactically. The results of this study demonstrate that intravenous ondansetron in doses of 8 or 16 mg is an effective antiemetic agent for the control of opioid-induced nausea and vomiting in nonsurgical patients requiring opioid analgesia for pain.
BACKGROUND: Poverty and female gender have been found to be associated with depression and anxiety in developed countries. The rationale behind this paper was to bring together five epidemiological data sets from four low to middle income countries to examine whether key economic and development indicators such as income and poor education, and female gender, were associated with common mental disorders. METHOD: The paper is based on five datasets: three based on primary care attenders in Goa, India; Harare, Zimbabwe and Santiago, Chile; and two based on community samples in Pelotas, Brazil and Olinda, Brazil. All five studies estimated prevalence of common mental disorders along with variables to measure economic deprivation and education. FINDINGS: In all five studies, female gender, low education and poverty were strongly associated with common mental disorders. When income was divided into tertiles, with the lowest tertile as a reference value, there was a significant trend for reduced morbidity for the lower two tertiles. DISCUSSION: These findings have considerable implications since the rapid economic changes in all four societies have been associated with rising income disparity and economic inequality. Examples of population based prevention strategies based on increasing the proportion of those who complete schooling and on high-risk strategies such as providing loan facilities to the impoverished are potential outcomes of these findings. Development agencies who focus on women as a priority group have failed to recognize their unique vulnerability to common mental disorders and need to reorient their priorities accordingly.
BACKGROUND: This study aimed to investigate the onset and predictors of common mental disorders (CMD) in primary-care attenders in Harare, Zimbabwe. METHOD: Two (T1) and 12-month (T2) follow-up of a cohort of primary-care attenders without a common mental disorder (N = 197) as defined by the Shona Symposium Questionnaire (SSQ), recruited from primary health care clinics, traditional medical practitioner clinics and general practitioner surgeries. Outcome measure was caseness as determined by scores on the SSQ at follow-up. RESULTS: Follow-up rate was 86% at 2 months and 75% at 12 months. Onset of CMD was recorded in 16% at T1 and T2. Higher psychological morbidity scores at recruitment, death of a first-degree relative and disability predicted the presence of a CMD at both follow-up points. While female gender and economic difficulties predicted onset only in the short-term, belief in supernatural causation was strongly predictive of CMD at T2. Caseness at both follow-up points was associated with economic problems and disability at those follow-up points. CONCLUSIONS: Policy initiatives to reduce economic deprivation and targeting interventions to primary-care attenders who are subclinical cases and those who have been bereaved or who are disabled may reduce the onset of new cases of CMD. Closer collaboration between biomedical and traditional medical practitioners may provide avenues for developing methods of intervention for persons with supernatural illness models.
This study examined the metastatic capacity of clonal populations of 4NQO-induced rat malignant oral keratinocytes following orthotopic transplantation to athymic mice. Polygonal and spindle cells formed well-differentiated squamous cell carcinomas (keratin positive and vimentin negative) and undifferentiated spindle cell tumours (keratin negative and vimentin positive), respectively, in almost 100% of animals at the site of inoculation (floor of mouth). Transplantation of 5x 10(6) cells of either cell type at high cell density resulted in approximately 50% of animals forming pulmonary metastases. By contrast, inoculation of 2x 10(6) differentiated polygonal cells resulted in the formation of significantly fewer pulmonary metastases than the undifferentiated spindle cells. A single well-differentiated clone of polygonal cells and 3 of 4 of the undifferentiated spindle cell lines produced comparable levels of TGF-beta1. One undifferentiated spindle cell line expressed significantly more TGF-beta1 and, following transplantation orthotopically, fewer animals formed pulmonary metastases despite the formation of primary tumours in almost all grafted animals, suggesting that TGF-beta1 can act as a tumour suppressor in this cell type. All cell lines produced comparable amounts of TGF-beta2. The clones of polygonal cells were markedly inhibited and the spindle cells were only partially inhibited by exogenous TGF-beta1. Both cell types expressed high-affinity TGF-beta cell surface receptors; the ratio of type I to type II TGF-beta receptors was 1.0:<3.0 in the spindle cells and 1.0:17.9 in the polygonal clone. The results suggest that differentiated rat malignant oral keratinocytes are less aggressive and have a decreased potential to metastasise than their undifferentiated spindle cell counterparts. This may be attributable, in part, to a change in TGF-beta receptor profile leading to the partial loss of response to exogenous TGF-beta1.
The histopathology and ultrastructural features of an adrenocortical oncocytoma are reported. The tumour was discovered incidentally during investigation for hypertension in a 72 year old female. Oncocytic tumours of the adrenal cortex are rare, with only 20 examples described in English language reports. Most have been non-functioning and benign, like the present example. Molecular studies may help assess the significance of oncocytic change in the pathogenesis and behaviour of oncocytic neoplasms.
Because Helicobacter pylori infection is localized in the gastric mucus layer and at the mucus layer-epithelial cell interface, we have developed amoxycillin- and metronidazole-containing chitosan microspheres for stomach-specific drug delivery. Drug-loaded porous chitosan microspheres were prepared by simultaneous crosslinking and precipitation with sodium tripolyphosphate. The release of antibacterial agents into simulated gastric fluid (SGF, pH 1.2), and the stability and permeability through gastric mucin, were examined at 37 degrees C. Because of the high porosity of drug-loaded chitosan microspheres, all the amoxycillin and metronidazole were released in 2 h. High-performance liquid chromatography assays of the antibacterial agents in SGF at 37 degrees C indicated 40% degradation of amoxycillin after 10 h. Metronidazole was completely stable for up to 24 h in SGF. Amoxycillin and metronidazole were highly permeable through the gastric mucin gel layer. The results of this study show that acid-stable antibacterial agents, such as metronidazole, that rapidly permeate the gastric mucus layer would be very effective for the complete eradication of H. pylori infection when delivered specifically at the site of infection in the stomach.