Biomedical subjects
Publications and source records attributed to S Saxena.
Modern vitreoretinal surgery is now one of the most effective tools for treating posterior segment diseases. In the last several years, there has been a surge of interest in submacular surgery which allows removal of submacular choroidal neovascular membranes and haematomas. Various aspects of this rapidly emerging modality of surgery are discussed in this review.
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New treatments for Alzheimer's disease (AD) are more likely to slow or halt disease progression rather than to reverse existing neuronal damage. Identifying persons with mild cognitive complaints who are at risk for AD will allow investigators to apply anti-dementia treatments before extensive brain damage develops. The discovery of the apolipoprotein E epsilon 4 allele (APOE epsilon 4) as a major risk factor for AD offers promise of assisting in early detection and prediction of Alzheimer's disease, particularly when genetic assessments are combined with other biomarkers such as neuroimaging. Studies of relatives at risk for familial AD using neuroimaging (positron emission tomography [PET]) and genetic assessments of APOE suggest that at-risk relatives with APOE epsilon 4 have lower parietal metabolism than those without APOE epsilon 4. Additional techniques that might increase sensitivity and specificity include longitudinal assessment of clinical and brain functional change, pharmacological challenges of short-acting anticholinergic agents, and memory activation paradigms during functional scanning. Such strategies should eventually assist in early detection of AD and in vivo therapeutic monitoring of brain function during experimental anti-dementia treatment trials.
Chronic dietary phosphate restriction is associated with up-regulation of sodium-dependent phosphate (Na/Pi) cotransport by renal proximal tubular epithelial cells in association with increases in Na/Pi cotransporter mRNA and protein. We investigated whether changes in cytosolic calcium mediate this adaptive response in opossum kidney cells, a continuous line of renal epithelial cells. After 24 h of phosphate depletion, steady-state cytosolic calcium levels were increased; this increase was observed at physiologic levels of phosphate restriction and was prevented by the calcium channel blocker verapamil. Chronic phosphate depletion was also associated with parallel increases in Na/Pi cotransport activity, Na/Pi cotransporter mRNA, and Na/Pi cotransporter protein, all of which were blocked in verapamil-treated cells. Actinomycin D, at a dose that prevented the increase in NaPi-4 mRNA during phosphate depletion, also prevented the increase in Na/Pi cotransport activity. Incubation with the calcium ionophore ionomycin or A23187 reproduced the increase in Na/Pi cotransporter mRNA in phosphate-replete cells. Conversely, chelation of cytosolic calcium by quin-2/AM prevented the increase in Na/Pi cotransporter mRNA in phosphate-depleted cells. The effect of an increase in cytosolic calcium was specific for the Na/Pi cotransporter as mRNA levels for the sodium-dependent glucose transporter were not affected. Our observations suggest that chronic phosphate restriction increases steady-state cytosolic calcium, which, in turn, increases transcription of Na/Pi cotransporter mRNA, thereby stimulating Na/Pi cotransport activity.
Necrotizing fasciitis is rare in the orofacial region, with fewer than 20 cases reported in the literature. Extension of the disease process to involve the underlying bone has not been previously reported. A patient is presented in whom destruction of superficial skin and fascia, necrosis of a portion of the mandible, and involvement of the parotid gland complicated reconstruction.
Obsessive-compulsive disorder (OCD) has a long history of speculations concerning its cause. This article reviews human functional neuroimaging studies of OCD, then presents data from a study in the nonhuman primate that concerns the localization of brain systems that may mediate the expression of OCD symptoms. We use these lines of evidence to argue that increased "neural tone" through a section of the behaviorally disinhibiting "direct" basal ganglia pathway, relative to tone in the behaviorally inhibiting or moderating "indirect" basal ganglia system, may mediate the expression of OCD symptoms. The limbic orbital prefrontal cortex, the involvement of which is highly implicated in OCD, may have a greater influence on neural tone in the direct pathway than in the indirect, whereas more dorsal neocortical prefrontal regions may have the opposite effects on these two basal ganglia subsystems. Effective OCD treatments may obtain their results by preferentially decreasing neural tone through the direct relative to the indirect basal ganglia system.
OBJECTIVE: The authors' goal was to study psychiatric morbidity after a natural disaster in rural India. METHOD: As members of a volunteer medical team assigned to 23 households in three villages in India affected by an earthquake, the authors examined the results of semi-structured interviews used to interview all of the adults (older than 14 years) in these households (N=56). DSM-III-R diagnoses were assigned on the basis of these interviews, and non-parametric tests were applied to comparisons of subjects who were or were not given a psychiatric diagnosis. RESULTS: Thirty-three (59%) of the subjects received a psychiatric diagnosis; the most common diagnoses were posttraumatic stress disorder (13 subjects [23%]) and major depression (12 subjects [21%]). Psychiatric morbidity was associated with female sex, destruction of house, and destruction of possessions. CONCLUSIONS: Attention to the mental health needs of disaster survivors in third world countries is indicated.
BACKGROUND: Although serotonin reuptake inhibitors (SRIs) are the mainstay of pharmacologic treatment for obsessive-compulsive disorder (OCD), many patients do not have an adequate response to these medications. One approach to treating SRI-refractory OCD patients has been to add other classes of medications to the SRI. We predicted that augmentation with risperidone would alleviate symptoms in SRI-refractory OCD patients. METHOD: 21 patients were treated openly with the combination of an SRI and adjunctive risperidone (mean dose = 2.75 mg/day). All met DSM-IV criteria for obsessive-compulsive disorder and had a variety of comorbid disorders. Prior to addition of risperidone, all patients had failed to respond to at least one adequate trial of an SRI. Response was determined by clinical judgment and standardized rating scales. RESULTS: 5 (24%) of the 21 patients experienced side effects (most commonly, akathisia), which forced discontinuation of risperidone. Of the 16 patients who tolerated combined treatment, 14 (87%) had substantial reductions in obsessive-compulsive symptoms within 3 weeks. Patients with horrific mental imagery had the strongest and fastest response, often within a few days. Patients with comorbid psychotic disorders improved gradually over 2 to 3 weeks. Patients with comorbid tic disorders had the poorest rate of response and highest rate of akathisia. CONCLUSION: These results suggest that risperidone augmentation is effective and well tolerated in patients with SRI-refractory obsessive-compulsive disorder. Response to risperidone augmentation appears to be influenced by symptom subtypes and comorbid conditions. Controlled trials are required to confirm the efficacy of risperidone augmentation for refractory OCD.
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Advances in the surgical instrumentation and vitreoretinal techniques have allowed intraoperative reapproximation of retina to a more normal position. The use of intravitreally injected liquid materials (viscoelastic liquids, liquid perfluorocarbons and silicone oil), as adjunctive agents to vitreo-retinal surgery play an important role in facilitating retinal reattachment. These materials are used as intraoperative instruments to re-establish intraocular volume, assist in separating membranes adherent to the retina, manipulate retinal detachments and mechanically flatten detached retina. Over the longer term, silicone oil maintains intraocular tamponade. One should be cognizant of the potential uses, benefits and risks of each of these vitreous substitutes.
The incidence of post-transplant diabetes mellitus (PTDM) was evaluated in 250 patients who underwent live-related renal transplantation at our hospital between 1978 and 1992. Twelve (4.8%) patients developed PTDM requiring drug therapy. PTDM occurred in 4 of 197 (2%) patients on conventional prednisolone-azathioprine immunosuppression as compared to 8 of 53 (15.1%) patients receiving cyclosporine in addition (triple-therapy). Three patients (25%) developed PTDM during or immediately following anti-rejection therapy with intravenous methylprednisolone. Eight patients (66.6%) developed PTDM within six months of transplantation. Majority of our patients (66.6%) could be managed successfully with oral hypoglycemic agents. Two patients (16.6%) showed spontaneous resolution of hyperglycemia within six months of onset of PTDM. Eleven patients (91.6%) were symptomatic for their hyperglycemia with two patients presenting as 'pseudorejection' and one with diabetic ketoacidosis. Females were more predisposed to develop PTDM in our study (10% vs. 4.1%). HLA-B15 and DR 3 were the commonest phenotypes in our PTDM patients. No other known predisposing or triggering factors associated with PTDM were found in our patients. The current study suggests, that addition of cyclosporine to the conventional immunosuppression in live-related renal allograft recipients has contributed to an increased incidence of post-transplant diabetes mellitus. Close and regular blood sugar monitoring is thus recommended in post-transplant patients especially those on triple drug immunosuppression.
Dietary phosphate restriction produces an adaptive increase in renal tubular Na/Pi cotransport. A similar adaptation occurs during phosphate depletion in opossum kidney cells, a continuous line of cultured renal epithelial cells. We investigated the cellular changes associated with adaptation to phosphate depletion in OK cells, in isolation from the complex systemic changes that occur with in vivo phosphate restriction. Phosphate depletion for up to 24 hours was associated with increases in Na/Pi cotransport activity, Na/Pi cotransporter mRNA, and Na/Pi cotransporter protein. Moreover, the increases in Na/Pi cotransport, and Na/Pi cotransporter mRNA and protein occurred at physiologically relevant degrees of phosphate restriction. The experimental results suggest that increases in Na/Pi cotransporter mRNA and protein may mediate the increase in Na/Pi cotransport activity in OK cells during phosphate depletion.
Results of 34 recipients of living related renal allografts initially treated with cyclosporine, azathioprine, and prednisolone and later electively converted to AZA and PRED are presented. Thirteen (group A), 14 (group B), and 7 (group C) patients were converted before 9 months, between 9 and 12 months, and after 12 months, respectively. Thirty-four patients who were on AZA and PRED and had never received CsA served as controls. Of the 34 patients, 33 were HLA haploidentical with their donors and 1 was HLA identical. All patients received a mean 8.62 +/- 7.39 third-party blood transfusions. In the control group, 29 patients received haploidentical grafts. The number of blood transfusions given to this group was 7.09 +/- 9.13. Of the 34 patients receiving triple-drug therapy, 9 (26%) had acute rejection within 3 months after conversion, as compared with 5 (14.7%) in the control group (P > 0.05). Although 1 case had acute rejection before conversion, all recipients had stable graft function at the time of conversion. Of these 9 recipients, 7 had conversion over 4-7 weeks, while 2 had rapid conversion. Following treatment of the rejection episodes, 4 patients in the study group responded to therapy, as compared with 3 cases in the control group (P > 0.05). After a mean follow-up of 18.62 +/- 10.31 months (range 3-41 months) following conversion, 4 patients were normal, 4 had chronic rejection (mean serum creatinine = 3.0 mg/100 ml), and 1 was back on regular dialysis. Eventually, of the 34 patients who were converted from triple-drug to double-drug therapy, 25 were normal, 5 had stable chronic rejection, 2 were back on regular dialysis, 1 was retransplanted, and 1 died due to failed graft. At the end of follow-up, graft survival in the study group was 88.2%, as compared with 85.5% in controls (P > 0.05). We conclude that conversion from triple-drug to double-drug therapy is not without risk, even in living related primary renal transplantation. Degree of HLA matching, number of pretransplant blood transfusions, and rejection before conversion did not have any significant effect on rejections following conversion, and the graft loss following conversion is unpredictable.
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Four bacterial strains (I-IV) capable of optimum growth on 0.1% naphthalene, anthracene or a mixture of naphthalene and phenanthrene were isolated from soil near an oil refinery. Two isolates (I and II) were identified as belonging to the genus Micrococcus, while strains III and IV were identified as Pseudomonas and Alcaligenes respectively. All the isolates were found to bear high molecular weight plasmid DNA (isolate I and IV 89%, II 67.5% and III 92.1% of lambda DNA), which is presumed to aid in the metabolism of polycyclic aromatic hydrocarbons. The strains also showed appreciable growth at high concentrations of NaCl (up to 7.5%).
A 43-kDa beta-xylosidase from Clostridium cellulolyticum was purified to homogeneity. The enzyme releases xylose from p-nitrophenylxylose and xylodextrins with a degree of polymerization ranging between 2 and 5. The N-terminal amino acid sequence of the enzyme showed homologies with three other bacterial beta-xylosidases. By proton nuclear magnetic resonance spectroscopy, the enzyme was found to act by inverting the beta-anomeric configuration.