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Biomedical subjects

A Shah

Publications and source records attributed to A Shah.

At least 217 records · Page 12Linked to original sources
PubMed1996

Role of Sst2 in modulating G protein-coupled receptor signaling.

Sst2 formally acts as an inhibitor of G protein-coupled receptor signaling in yeast perhaps stabilizing a G protein/unactivated receptor complex. desTrp1,Ala3 alpha-factor (dTA-alpha f), normally a competitive antagonist, activated responses in an sst2 strain. The antagonist to agonist switch was consistent with an Sst2 effect on receptor/G protein coupling, but not with an Sst2 role in global reduction of signaling. Response to alpha-factor, assayed by growth arrest, was independent of level of expressed surface receptor over a 40-fold range in an SST2+ strain, consistent with coupling of only a subset of receptors to G protein. In contrast, in an sst2 strain response to alpha-factor was proportional to receptor expression, consistent with participation of all receptors in signaling. The wt alpha-factor receptor inhibited signaling in response to dTA-alpha f when introduced into a CKC4 chimeric receptor strain. The dominant-negative effect of the receptor might reflect sequestration of G protein.

Fungal Proteins↗
PubMed1996

High density sickle cell erythrocyte core membrane skeletons demonstrate slow temperature dependent dissociation.

We have previously demonstrated that slow dissociation of HDSS membrane skeletons in high ionic strength Triton X-100 buffer was related to a posttranslational modification in beta-actin, in which a disulfide bridge was formed between cysteine 284 and cysteine 373[Shartava et al: J Cell Bio 128:805, 1995]. These previous dissociation assays were limited to two homozygous (SS) sickle cell patients and a single temperature (37 degrees C). In the current work, we have expanded the SS subjects to 9 and have carried out dissociation assays at 0, 24, 30, 34, and 37 degrees C. At 0 degrees C there was limited dissociation of spectrin and actin from normal(AA), low density sickle cell(LDSS), and high density sickle cell (HDSS) core skeleton up to 24 hr. The first order rate constants for dissociation of spectrin, at 0 degrees C, was 0.030-0.035 x 10-4 sec-1 for AA,LDSS, and HDSS core skeletons. However at 24, 30, 34, and 37 degrees C the rate of dissociation of spectrin from HDSS core skeletons was significantly slower than the rate of dissociation from AA core skeletons. Having determined the first order rate constants for spectrin dissociation at these specified temperatures, we then asked whether dithiothreitol (DTT) would hasten the dissociation of core skeletons. The presence of DTT caused the rate of dissociation of the HDSS membrane skeleton to become statistically indistinguishable from the rate of dissociation of AA membrane skeletons. This is consistent with the suggestion that reversible thiol oxidation is responsible for the slow dissociation of the HDSS membrane skeleton.

Actins↗
PubMed1996

Vascular applications of telepresence surgery: initial feasibility studies in swine.

PURPOSE: Telepresence surgery is a novel technology that will allow procedures to be performed on a patient at locations that are physically remote from the operating surgeon. This new method provides the sensory illusion that the surgeon's hands are in direct contact with the patient. We studied the feasibility of the use of telepresence surgery to perform basic operations in vascular surgery, including tissue dissection, vessel manipulation, and suturing. METHODS: A prototype telepresence surgery system with bimanual force-reflective manipulators, interchangeable surgical instruments, and stereoscopic video input was used. Arteriotomies created ex vivo in segments of bovine aortae or in vivo in femoral arteries of anesthetized swine were closed with telepresence surgery or by conventional techniques. Time required, technical quality (patency, integrity of suture line), and subjective difficulty were compared for the two methods. RESULTS: All attempted procedures were successfully completed with telepresence surgery. Arteriotomy closures were completed in 192+/-24 sec with conventional techniques and 483+/-118 sec with telepresence surgery, but the precision attained with telepresence surgery was equal to that of conventional techniques. Telepresence surgery was described as intuitive and natural by the surgeons who used the system. CONCLUSIONS: Blood-vessel manipulation and suturing with telepresence surgery are feasible. Further instrument development (to increase degrees of freedom) is required to achieve operating times comparable to conventional open surgery, but the system has great potential to extend the expertise of vascular surgeons to locations where specialty care is currently unavailable.

Animals↗
PubMed1996

Squalor syndrome and psychogeriatric admissions.

A series of patients with the squalor syndrome who were admitted to a psychogeriatric ward were compared with those without the syndrome. Patients with squalor syndrome received a greater number of services prior to admission, were less likely to be on psychotropic medication prior to admission, had longer length of hospital admission, and were discharged to a "more dependent" accommodation facility. These findings, methodological difficulties, and avenues for future research are discussed.

Activities of Daily Living↗
PubMed1996

Pharmacokinetics of intravenous ciprofloxacin in normal and renally impaired subjects.

The pharmacokinetics of intravenous ciprofloxacin and its metabolites were characterized in 42 subjects with various degrees of renal function (group 1, Clcr (mL/min/1.73 m2) > 90, n = 10; group 2, Clcr 61-90, n = 11; group 3, Clcr 31-60, n = 11; group 4, Clcr < or = 30, n = 10). The dosage regimens were-groups 1 and 2: 400 mg i.v. at 8 hourly intervals; group 3: 400 mg i.v. at 12 hourly intervals and group 4: 300 mg i.v. at 12 hourly intervals. Subjects received a single dose on days 1 and 5 and multiple doses on days 2-4. Multiple plasma and urine samples were collected on days 1 and 5 for the analysis of ciprofloxacin and its metabolites (M1, M2 and M3). Plasma concentrations (Cmax and AUC) of ciprofloxacin and its M1 and M2 metabolites were significantly increased in subjects with reduced Clcr values (Clcr < 60 mL/min/1.73 m2) compared with normal subjects (Clcr > 90 mL/min/1.73 m2). A positive correlation was observed between ciprofloxacin clearance (Cl) and Clcr with a slope of 0.29 (r2 = 0.78) and between renal clearance (Clr) and Clcr with a slope of 0.19 (r2 = 0.84). For patients with severe infections a dosage regimen of 400 mg iv 8 hourly is appropriate in patients with Clcr > 60 mL/min/1.73 m2. In patients with Clcr values of 31-60 mL/min/1.73 m2 a dosage regimen of 400 mg 12 hourly provides similar plasma concentrations to those observed for subjects with Clcr 61-90 mL/min/1.73 m2 receiving 400 mg 8 hourly. Based on modeling of the plasma concentrations in subjects with Clcr < or = 30 ml/min/1.73 m2, a dosage regimen of 400 mg every 24 h will provide plasma concentrations similar to those observed in subjects with Clcr between 61-90 mL/min/1.73 m2 given 400 mg every 8 h.

Adult↗
PubMed1996

Radiofrequency ablation of idiopathic ventricular tachycardia.

BACKGROUND: Radiofrequency ablation (RFA) has been shown to be very effective in the treatment of supraventricular tachycardias and has replaced surgical ablation. Only a few reports of RFA for idiopathic ventricular tachycardia (VT) have appeared in the literature during the last two years. AIM: This paper presents our experience with RFA for idiopathic VT in 19 patients. MATERIAL: The age range of patients was 22-60, with a mean of 37.9 years. Twelve out of 19 were females, two patients had cardiac failure due to almost incessant VT while the rest had normal left ventricular function. Twelve patients had VT arising from the right ventricle (RV); of these, nine were from the outflow tract, two from the RV apex, and one from the mid-anterior RV. Seven patients had VT arising from the left ventricle (LV); of these, five were from the inferobasal portion of the septum and two were from the anterolateral area. METHODS: In all patients the diagnostic study and therapeutic RFA were combined in a single procedure. Pacemapping was used to guide the site of RFA in patients with VT arising from the RV. Local activation time (LAT), Purkinje potentials (PP) and pacemapping were used to guide RFA in those patients with LV septal tachycardias. RESULTS: A total of 21 RF procedures were performed in 19 patients and 15 out of 19 patients had successful VT ablation. Ten of the 12 patients with RV tachycardias and all five patients with LV septal (left axis, right bundle branch block) tachycardias were successfully ablated. One patient with mid anterior RV VT required two attempts for successful ablation. One patient with RV outflow tract (RVOT) VT could not be ablated despite two attempts. Two patients with LV tachycardias arising from the antero-lateral LV could also not be ablated. During a follow up period of two to 16 months none of the successful patients had recurrence of VT. The number of RF applications was one to 27, mean 10; fluoroscopy times were four to 75, mean 26.9 minutes. CONCLUSION: Idiopathic VT frequently arises from the RVOT and inferobasal portion of the LV septum. These tachycardias can be diagnosed on clinical and ECG grounds. RFA for idiopathic VT arising from these areas has a high success rate and this mode of treatment should be considered as a nonpharmacological curative treatment for symptomatic patients.

Adolescent↗
PubMed1996

Displacement of the nearest relative under the Mental Health Act 1983.

A case of displacing the nearest relative under s.29 of the Mental Health Act 1983 is described. Difficulties in achieving displacement and some ethical dilemmas, particularly in an elderly couple married for nearly 50 years, are discussed. Improvements to the Mental Health Act to avoid delays in displacing the nearest relative and to ensure financial safeguards to the patient are suggested.

Aged↗
PubMed1996

The effect of the Community Care Act 1990 on discharge from a psychogeriatric unit to residential and nursing homes.

This study compares the proportion of patients discharged to residential and nursing homes from a psychogeriatric unit and the length of hospital admissions before and after the introduction of the National Health Service and Community Care Act 1990. This Act appeared not to influence the proportion of patients discharged to residential and nursing homes and the length of hospital admission. A year after the introduction of this Act may be too soon to observe an effect as the actual implementation of the Act by the health and social services may take considerable time.

Aged↗
PubMed1996

Complex task performance in Cyberspace. Surgical procedures in a telepresence environment.

To assess the capabilities of our fully functional, prototype telepresence surgery system, experienced surgeons performed complete operative procedures on live, anesthetized pigs. Cholecystectomy, the prototypical procedure for evaluating the integration of surgical skills, was successfully performed in six animals. There were no aborted attempts or complications. Other procedures completed included gastrotomy and enterotomy closures, anastomosis of the small intestine, and nephrectomy. No specific training was required for using the telepresence surgery system, and the "feel" of the system was described as intuitive. Operative times were longer than required in conventional, open surgery, most likely the result of the four degrees of freedom available in the manipulators of the current-generation system. Force feedback and high-resolution, stereoscopic video input facilitated performance. Surgeons operating through a first-generation telepresence system can achieve technical results equivalent to those obtained in conventional surgery.

Animals↗
PubMed1996

Prolonged exposure to agonist results in a reduction in the levels of the Gq/G11 alpha subunits in cultured vascular smooth muscle cells.

Recent studies have shown that G proteins are a potential regulatory site in the transmembrane signaling cascade. The aim of this study was to examine the effects of prolonged agonist exposure on expression of the Gq class of G protein alpha subunits (G alpha q/G alpha 11) in cultured rat vascular smooth muscle cells (VSMC). Treatment with 100 nM angiotensin II (Ang II) led to a substantial sustained down-regulation of cellular levels of immunologically detectable G alpha q/G alpha 11 by 50% within 6 hr. The effect of Ang II was dose dependent with an EC50 of 2 nM and was specifically blocked by the vascular type-1 Ang II receptor-specific antagonist losartan. The Ang II-induced reduction in cellular levels of G protein alpha subunits was specific for G alpha q/G alpha 11. The calcium ionophore ionomycin or activators of ubiquitous protein kinases (phorbol-12-myristate-13-acetate, forskolin, and 8-bromo-cGMP) did not mimic the effects of Ang II. However, [Arg8]vasopressin also induced a significant loss in cellular G alpha q/G alpha 11 levels. Ang II-induced G alpha q/G alpha 11 down-regulation was reversed by prevention of cellular receptor processing with phenylarsine oxide or chronic potassium depletion. The effects of Ang II on G alpha q/G alpha 11 levels were inhibited when protein kinase C activity was abolished. G alpha q mRNA levels were down-regulated by 30% after 4-hr incubation with Ang II, in part by transcriptional regulation. Although a short term vasopressin pretreatment had no effect on inositol-1,4,5-trisphosphate (IP3) generation in response to subsequent Ang II stimulation, a partial heterologous desensitization of the IP3 response was induced after a long term vasopressin pretreatment, which concurrently down-regulated cellular G alpha q/G alpha 11 levels. Homologous desensitization of IP3 generation on a second Ang II stimulation was observed after both a short and long term Ang II pretreatment. In conclusion, prolonged exposure to Ang II induces down-regulation of cellular G alpha q/G alpha 11 levels in intact VSMC. The effect of Ang II appears to be mediated by the signaling pathway sensitive to inhibition of receptor processing. The present study raises the possibility that agonist-induced G alpha q/G alpha 11 down-regulation participates in the mechanism of long term desensitization of the G alpha q/G alpha 11-mediated signaling system in VSMC.

Angiotensin II↗
PubMed1996

Allergic bronchopulmonary aspergillosis with aspergilloma mimicking fibrocavitary pulmonary tuberculosis.

A 47-year-old male, who presented with chronic fibrocavitary pulmonary disease, had received three courses of antituberculous therapy over a period of 17 years without relief. Four years prior to referred he had developed hemoptysis and rhinitis. Evaluation of the patient led to the diagnosis of allergic bronchopulmonary aspergillosis with coexistent aspergilloma, a rather uncommon association. Both his pulmonary and nasal symptoms showed a remarkable response to treatment with oral prednisolone. However, the possibility of concomitant allergic Aspergillus sinusitis remained open as the patient refused to undergo any invasive procedure.

Adult↗
PubMed1995

Free radicals, anticonvulsants, and the neuronal ceroid-lipofuscinoses.

The relationship between free radicals and scavenger enzymes, and the disorders called the neuronal ceroid-lipofuscinoses, has long been an argumentative one. Recent evidence would seem to support the fact that such a relationship might exist but that it is indirect. The relationship does not seem due to an inborn error of free radical scavenger enzyme metabolism. Anticonvulsants play a role, as they influence free radical generating systems. At this juncture, no one has studied the relationship of anticonvulsant therapy, neuronal ceroid-lipofuscinosis, and the free radical-scavenging enzyme system, and their interplay. We have studied a large number of patients with epilepsy who are on either monotherapeutic or polytherapeutic regimens of most of the common anticonvulsants. We have found excessive free radical production in many of these patients, ranging from minor effects in the simpler anticonvulsants when used monotherapeutically, to more complex changes in polytherapeutic combinations. Likewise, we have found subtle and inconsistent findings in the free radical-scavenging enzyme system in a variety of examples of neuronal ceroid-lipofuscinosis. When refractory seizure disorders stimulate the vigorous use of polytherapy with a variety of free radical-facilitating anticonvulsants, free radical production becomes deleterious. Likewise, in certain types of neuronal ceroid-lipofuscinosis, polypharmacy with anticonvulsants, by enhancing the production of free radicals or suppressing scavenging enzymes, tends to be deleterious and induces a worsening in the disease process.

Adolescent↗
PubMed1995

Pharmacokinetics of dolasetron following single- and multiple-dose intravenous administration to normal male subjects.

Dolasetron, Anzemet, a 5-hydroxytryptamine receptor antagonist, is under investigation as an antiemetic agent. The keto-reduced metabolite of dolasetron has been identified in human plasma and is probably responsible for the majority of the antiemetic activity. This study evaluated the pharmacokinetics of dolasetron and the reduced metabolite following single and multiple intravenous (IV) infusions of dolasetron mesylate in healthy male subjects. Four groups of subjects (six active/two placebo) received either dolasetron mesylate or placebo in single IV doses ranging from 0.30 to 0.60 mg kg-1 on day 1 and multiple IV doses ranging from 0.60 to 1.20 mg kg-1 d-1 on days 2-9. Dolasetron could be detected for less than 1 h, while the reduced metabolite appeared rapidly in the plasma, reaching a maximal plasma concentration in less than 1 h. Reduced metabolic maximal plasma concentration was proportional to the dose and the area under plasma concentration curve was linear based on regression analysis. The half-life of reduced metabolite ranged from 3.82 to 7.46 h. The mean renal clearance of reduced metabolite was 2.20-4.43 mL min-1 kg-1 and was dose independent. All of the evidence supports dose independent pharmacokinetics for the reduced metabolite. Upon multiple dosing, the reduced metabolite AUC can be predicted from the single-dose pharmacokinetics of this metabolite.

Adult↗
PubMed1995

Lobular carcinoma of the breast can be managed by breast-conserving therapy.

There has been a reluctance to treat patients with invasive lobular carcinoma by breast-conserving therapy because of the possibility of increased rates of local recurrence. This study is a retrospective review of 226 patients with pure invasive lobular carcinoma 4 cm or less treated by breast conservation therapy or mastectomy. Local relapse occurred in four of 52 patients (8 per cent) after breast conservation compared with 21 of 174 (12 per cent) after mastectomy. Breast conservation for invasive lobular carcinoma did not result in a higher incidence of local relapse and patients with invasive lobular and ductal carcinomas may be managed in a similar fashion.

Adult↗