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K Prasad

Publications and source records attributed to K Prasad.

At least 37 records · Page 2Linked to original sources
PubMed2001

Core safeguards for clinical research with adults who are unable to consent.

The National Bioethics Advisory Commission has proposed new safeguards for clinical research with adults who are unable to consent. Three other major U.S. groups have also proposed additional safeguards for this population, and existing Canadian and European guidelines already include such safeguards. While these six guidelines agree on some safeguards, they disagree on others. To allow important research to proceed while protecting adults who are unable to consent, it will be crucial to resolve these differences. This paper uses a side-by-side comparison of these six guidelines to highlight their major points of consensus, analyze their significant differences, and distill six core safeguards.

Adult↗
PubMed2001

Ectopic expression of rice OsMADS1 reveals a role in specifying the lemma and palea, grass floral organs analogous to sepals.

MADS-domain-containing transcription factors play diverse roles in plant development. The prototypic members of this gene family are the floral organ identity genes of the model dicotyledonous plant, Arabidopsis thaliana. Sequence relatedness and function ascribe them to AP1/AGL9, AG, AP3 and PI gene groups. The rice MADS-box gene, OsMADS1, is a member of the AP1/ AGL9 sub-group. Tomato and Petunia members of this sub-group specify floral meristem identity and control organ development in three inner whorls. Reported here are phylogenetic analyses that show OsMADS1 to form a distinct clade within the AGL9 gene family. This sub-group currently has only three other monocot genes. We have studied the expression pattern of OsMADS1 and determined the consequences of its ectopic expression in transgenic rice plants. OsMADS1 is not expressed during panicle branching; earliest expression is in spikelet meristems where it is excluded from the outer rudimentary/sterile glumes. During organogenesis, OsMADS1 expression is confined to the lemma and palea, with weak expression in the carpel. Ectopic OsMADS1 expression results in stunted panicles with irregularly positioned branches and spikelets. Additionally, in spikelets, the outer rudimentary glumes are transformed to lemma/palea-like organs. Together, these data suggest a distinct role for OsMADS1 and its monocot relatives in assigning lemma/palea identity.

Alleles↗
PubMed2001

Reading between the lines: direct-to-consumer advertising of genetic testing in the USA.

This article critiques an advertisement in a theatre playbill by a bio-technology company for its commercial test for the BRCA1 and BRCA2 genetic mutation, which may indicate a higher risk for breast and ovarian cancer. The advertisement targets a vulnerable audience attending a play about one woman's isolated and painful death from ovarian cancer. It promotes a product with incomplete and at times incorrect information, and it misguides women by suggesting that they contact the company directly about this test, rather than encouraging them to talk to their health care providers about genetic testing and their personal risk of breast cancer. In an era in which more genetic tests will be integrated into clinical practice, we can expect an increase in direct-to-consumer marketing for such tests. This advertisement is an example of what we need to be on guard against.

Advertising↗
PubMed2001

Secoisolariciresinol diglucoside from flaxseed delays the development of type 2 diabetes in Zucker rat.

Previous research has suggested that type 1 diabetes mellitus may be due to oxidative stress. The role of oxidative stress in type 2 diabetes is not known. Secoisolariciresinol diglucoside (SDG) antioxidant, obtained from flaxseed, has been reported to prevent type 1 diabetes in a rat model. However, its effectiveness in type 2 diabetes is not known. An investigation was made of the effects of SDG isolated from flaxseed (40 mg/kg body wt, orally in drinking water) on the development of diabetes in Zucker diabetic fatty (ZDF)/Gmi-fa/fa female rats, a model of human type 2 diabetes, to determine whether this type of diabetes is due to oxidative stress and whether SDG could prevent the development of diabetes. A total of 10 Zucker lean control and 26 ZDF rats were used in this study. Incidence of diabetes was 100% in untreated and 20% in SDG-treated ZDF rats by the age of 72 days (P <.01). The rats that did not develop diabetes by 72 days of age in the SDG-treated group developed diabetes later on (age 72 to 99 days) except for 10% of the rats that did not develop diabetes for the duration of the study (101 days of age), suggesting that SDG retarded the development of diabetes. Diabetes was associated with an increase in oxidative stress as suggested by an increase in serum malondialdehyde (P <.01). Also, diabetes was associated with an increase in serum total cholesterol and triglycerides (P <.05) and glycated hemoglobin A(1C) (P <.05). ZDF rats treated with SDG that did not develop diabetes by 70 days of age had no increase in oxidative stress, serum total cholesterol, and glycated hemoglobin. These results suggest that type 2 diabetes is associated with an increase in oxidative stress and that SDG is effective in retarding the development of diabetes.

Animals↗
PubMed2001

Reactive oxygen species and endotoxic shock: effect of dimethylthiourea.

The effects of endotoxemia on the cardiac function and contractility, oxygen radical production by polymorphonuclear leukocytes (PMNL-CL), cardiac antioxidant reserve (LV-CL), antioxidant enzymes (superoxide dismutase [SOD], catalase, glutathione peroxidase [GSH-P(X)]) and malondialdehyde (MDA); and plasma creatine kinase (CK) and lactate in the absence or presence of dimethylthiourea (DMTU), an antioxidant, in anesthetized dogs were studied. Dogs were assigned to three groups: group 1, control; group II, endotoxin (ET) (5 mg/kg body wt intravenously), and group III, ET + DMTU (500 mg/kg intravenously). ET produced decreases in the cardiac function and contractility, antioxidant reserve, antioxidant enzymes; and increases in PMNL-CL, cardiac MDA, plasma CK, and lactate. Pretreatment with DMTU attenuated the ET-induced cardiac dysfunction and changes in the cardiac MDA, antioxidant reserve, and antioxidant enzymes, PMNL-CL, and plasma CK and lactate levels. These results suggest that reactive oxygen species may be involved in the deterioration of cardiac function and contractility, and cellular injury during endotoxic shock and that antioxidants may be of value in the treatment of endotoxic shock.

Animals↗
PubMed2001

Transnasal access for sampling a skull base lesion.

SUMMARY: Transnasal needle access for sampling was used in two patients with posterior nasopharyngeal lesions. The procedure was performed under CT guidance. This new technique is simple and appears suitable for selected cases. The two cases and the details of the procedure are described.

Adult↗
PubMed2001

A study of factors delaying hospital arrival of patients with acute stroke.

Thrombolytic therapy for acute ischaemic stroke has recently become available in India but its success depends on initiating the treatment in the narrow therapeutic time window. There is commonly a delay of several hours before patients with acute stroke seek medical attention. A prospective study was conducted to assess the factors influencing this delay in admission of acute stroke cases. 110 cases (71 males, 39 females) of acute stroke that arrived within 72 hours at our hospital casualty were recruited. A standardized structured questionnaire was given to patients or their attendants. The median time to casualty arrival was 7.66 hours with 25% cases arriving within 3 hours and 49 % cases within 6 hours. Distance from hospital, contact with a local doctor and low threat perception of symptoms of stroke were independent factors associated with delay in arrival. Living in city, presence of family history and older age were associated with early arrival. There was no correlation with patients' or attendants' sex, educational status, history of previous stroke or transient ischaemic attack, subtype or severity of stroke, time of stroke and availability of transport. Adequate measures need to be taken to improve the public awareness of stroke and the role of local doctors.

Acute Disease↗
PubMed2001

Physician assisted suicide--the perspective of a neurologist.

Modern medicine has resulted in a better control and treatment of many diseases. This has provided a better life for patients with treatable disorders, but at the same times has prolonged the suffering of the patients with diseases that are not treatable. This is of particular importance for the patients with neurological diseases, as some of these conditions have a relentlessly progressive course and cause significant distress to the patient. Recent times have seen an expansion of the scope of the various "rights of the patient" and according to some, this includes the "right to die". As a result of this concept of regarding the autonomy of the patient, the phenomenon of physician assisted suicide has emerged and is a topic of intense debate amongst the physicians, social workers and politicians all over the world. The present article puts forth the current concepts and brings out the exact definitions of the terms like physician-assisted suicide, voluntary active euthanasia and voluntary passive euthanasia. It presents the statements made by the various societies and organisations regarding the PAS. It also brings forth the point of view of the authors about this aspect of medicine. The authors share the view of the various scientific organisations, and opine that though the idea of physician assisted suicide may be morally justifiable in certain circumstances, it should not be made legal.

Attitude of Health Personnel↗
PubMed2001

Planimetric optic disc parameters in normal eyes: a population-based study in South India.

PURPOSE: To study the optic disc parameters of normal eyes in a population-based south Indian study. METHODS: One hundred and fifty three subjects from a population-based sample of 1060 included in the Andhra Pradesh Eye Disease Survey (APEDS) were enrolled in the optic disc study. The male-female ratio, the refractive error and distribution of other ocular parameters in the disc study subjects and the APEDS were not significantly different. Magnification corrected morphometry of optic disc photographs obtained by Zeiss telocentric fundus camera was carried out in one randomly chosen eye of each of these 143 subjects. RESULTS: The mean optic disc parameters with the 95% confidence intervals for the distribution were: disc area 3.37 mm2 (2.04 - 4.7), vertical disc diameter 2.12 mm (1.67 - 2.57), vertical cup to disc ratio 0.37 (0.19 -0.55) and neuroretinal rim area 2.8 mm2 (1.76 - 3.84). The disc area, the vertical cup to disc ratio and the rim area showed a normal distribution. The cup to disc ratio correlated with the vertical disc diameter but the association was not strong. CONCLUSION: The disc area, the vertical cup to disc ratio and the neuroretinal rim area are normally distributed in the South Indian population. The normal optic disc parameters would form a basis for future comparisons in different forms of glaucoma.

Adolescent↗
PubMed2000

A conserved clathrin assembly motif essential for synaptic vesicle endocytosis.

Although clathrin assembly by adaptor proteins (APs) plays a major role in the recycling of synaptic vesicles, the molecular mechanism that allows APs to assemble clathrin is poorly understood. Here we demonstrate that AP180, like AP-2 and AP-3, binds to the N-terminal domain of clathrin. Sequence analysis reveals a motif, containing the sequence DLL, that exists in multiple copies in many clathrin APs. Progressive deletion of these motifs caused a gradual reduction in the ability of AP180 to assemble clathrin in vitro. Peptides from AP180 or AP-2 containing this motif also competitively inhibited clathrin assembly by either protein. Microinjection of these peptides into squid giant presynaptic terminals reversibly blocked synaptic transmission and inhibited synaptic vesicle endocytosis by preventing coated pit formation at the plasma membrane. These results indicate that the DLL motif confers clathrin assembly properties to AP180 and AP-2 and, perhaps, to other APs. We propose that APs promote clathrin assembly by cross-linking clathrin triskelia via multivalent interactions between repeated DLL motifs in the APs and complementary binding sites on the N-terminal domain of clathrin. These results reveal the structural basis for clathrin assembly and provide novel insights into the molecular mechanism of clathrin-mediated synaptic vesicle endocytosis.

Adaptor Protein Complex alpha Subunits↗
PubMed2000

Hsc70 chaperones clathrin and primes it to interact with vesicle membranes.

When Hsc70 uncoats clathrin-coated vesicles in an auxilin- and ATP-dependent reaction, a single round of rapid uncoating occurs followed by very slow steady-state uncoating. We now show that this biphasic time course occurs because Hsc70 sequentially forms two types of complex with the dissociated clathrin triskelions. The first round of clathrin uncoating is driven by formation of a pre-steady-state assembly protein (AP)-clathrin-Hsc70-ADP complex. Then, following exchange of ADP with ATP, a steady-state AP-clathrin-Hsc70-ATP complex forms that ties up Hsc70, preventing further uncoating. This steady-state complex forms only during uncoating in the presence of APs; in the absence of APs, Hsc70 rapidly dissociates from the uncoated clathrin and continues to carry out uncoating. Whether it is complexed with ATP or ADP, the steady-state complex has very different properties from the pre-steady-state complex in that it cannot be immunoprecipitated by anti-clathrin antibodies and is readily dissociated by fast protein liquid chromatography. Remarkably, when the steady-state complex is incubated with uncoated vesicle membranes in ATP, the pre-steady-state complex reforms, suggesting that the clathrin triskelions in the steady-state complex rebind to the membranes and are again uncoated by Hsc70. We propose that Hsc70 not only uncoats clathrin but also chaperones it to prevent it from inappropriately polymerizing in the cell cytosol and primes it to reform clathrin-coated pits.

Adaptor Proteins, Vesicular Transport↗
PubMed2000

A conserved function for Arabidopsis SUPERMAN in regulating floral-whorl cell proliferation in rice, a monocotyledonous plant.

Studies of floral organ development in two dicotyledonous plants, Arabidopsis thaliana and Antirrhinum majus, have shown that three sets of genes (A, B and C) can pattern sepals, petals, stamens and carpels [1] [2]. Mechanisms that define boundaries between these floral whorls are unclear, however. The Arabidopsis gene SUPERMAN (SUP), which encodes a putative transcription factor, maintains the boundary between stamens and carpels [3] [4] [5], possibly by regulating cell proliferation. By overexpressing SUP cDNA in rice, we examined whether its effects on whorl boundaries are conserved in a divergent monocotyledonous species. High-level ectopic SUP expression in transgenic rice resulted in juvenile death or dwarf plants with decreased axillary growth. Plants with lower levels of SUP RNA were vegetatively normal, but the flowers showed ubiquitous ventral carpel expansion. This was often coupled with reduced stamen number, or occurrence of third-whorl stamen-carpel mosaic organs. Additionally, proliferation of second-whorl ventral cells produced adventitious lodicules, and flowers lost the asymmetry that is normally inherent to this whorl. We predict that SUP is a conserved regulator of floral whorl boundaries and that it affects cell proliferation.

Arabidopsis↗
PubMed2000

Surgery for primary supratentorial intracerebral haemorrhage.

BACKGROUND: There is considerable international variation in the rate and indications of surgery for primary supratentorial intracerebral haematoma, reflecting the uncertainty about the effects of surgery. OBJECTIVES: The objective of this review was to assess the effects of surgery plus routine medical management, compared with routine medical management alone, in patients with primary supratentorial intracerebral haematoma. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register, Current Opinion in Neurology and Neurosurgery, and Neurosurgical Clinics of North America (1991 to July 1993) and reference lists of articles. SELECTION CRITERIA: Randomised and quasi-randomised trials of routine medical treatment plus intracranial surgery compared with routine medical treatment, in patients with presumed or confirmed primary supratentorial intracerebral haematoma. Intracranial surgery included craniotomy, stereotactic endoscopic evacuation or stereotactic aspiration. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria, assessed trial quality and extracted the data. MAIN RESULTS: Four trials were included. No trial had blinded outcome assessment. Craniotomy and endoscopic evacuation were analysed separately. Craniotomy showed a non-significant trend towards increased odds of death and dependency among survivors (odds ratio 1.99, 99% confidence interval 0.92 to 4. 31). The result was inconclusive in the two trials with patients confirmed as having primary supratentorial intracerebral haematoma by CT. Endoscopic evacuation was not shown to significantly decrease the odds of death and dependency among survivors in one trial involving 100 patients (odds ratio 0.45, 99% confidence interval 0. 15 to 1.33). REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate the effect of craniotomy or stereotactic surgery, or endoscopic evacuation in patients with supratentorial intracerebral haematoma.

Cerebral Hemorrhage↗
PubMed2000

Drugs for treating neurocysticercosis (tapeworm infection of the brain).

BACKGROUND: Anthelminthic drugs may shrink brain cysts in neurocysticercosis, but can also cause severe adverse effects. OBJECTIVES: The objective of this review was to assess the effects of drug treatment in human neurocysticercosis in relation to survival, cyst persistence, subsequent seizures and hydrocephalus. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register and Medline. We contacted researchers and experts in the field and drug manufacturers. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing a cysticidal drug with a placebo or a control group receiving symptomatic therapy, in patients with neurocystercosis. DATA COLLECTION AND ANALYSIS: Assessment of trial quality and data extraction was done independently by two reviewers. MAIN RESULTS: Four studies involving 305 people met the inclusion criteria. None reported on withdrawal of anticonvulsant therapy, headache relief, disability or death as outcomes. A difference just approaching significance was detected between cysticidal therapy and placebo in relation to cyst persistence up to six months (relative risk 0.83, 95% confidence interval 0.70 to 0.99). Two trials reported on seizures after one to two years follow-up and found no difference (relative risk 0.95, 95% 0.59 to 1.51). There was no difference detected for hydrocephalus (relative risk 2.19, 95% confidence interval 0.29 to 16.55). REVIEWER'S CONCLUSIONS: There is insufficient evidence to assess whether cysticidal therapy in neurocysticerosis is associated with beneficial effects.

Albendazole↗
PubMed2000

Steroids for treating cerebral malaria.

BACKGROUND: Cerebral malaria is associated with swelling of the brain. Corticosteroid drugs could reduce the harmful effects of this swelling, but could also suppress host immunity to infection. OBJECTIVES: This review aimed to assess the effects of steroids in patients with cerebral malaria in relation to survival and long-term disability. SEARCH STRATEGY: The Cochrane Controlled Trials Register, the Cochrane Infectious Diseases Group Trials Register, existing reviews, and contact with experts in the field. SELECTION CRITERIA: Randomised controlled trials comparing steroids and no steroids in otherwise identical treatments for patients with cerebral malaria. DATA COLLECTION AND ANALYSIS: Assessments of inclusion criteria, trial quality and data extraction were done by each author independently. The outcomes sought were death, death with life-threatening complications, other complications, and disability. MAIN RESULTS: Two trials met the inclusion criteria. Out of a total of 143 patients, there were 30 deaths, distributed evenly between the steroid and the comparator group. The researchers reported clinical complications as the number of events in each trial arm, and did not exclude complications occurring in fatalities. This makes it difficult to interpret the reports of significantly more episodes of gastro-intestinal bleeding and seizures in the steroid group. No studies examined disability. REVIEWER'S CONCLUSIONS: There is currently no evidence of benefit from steroids in this condition, but the small number of participants means it is difficult to exclude an effect on mortality in either direction. Data on clinical complications are difficult to assess.

Adrenal Cortex Hormones↗
PubMed2000

Steroids for treating tuberculous meningitis.

BACKGROUND: Even though corticosteroids have been used alongside antituberculosis drugs for tuberculous meningitis (TBM) since the 1950s their role remains controversial. Some believe corticosteroids improve outcome while others point to the lack of supportive evidence. In patients who are immunocompromised because of HIV infection the risks and benefits of steroids are unknown. OBJECTIVES: To assess the effects of steroids on death and disability in patients with TBM. SEARCH STRATEGY: Electronic searching of MEDLINE, Cochrane Controlled Trials Register, and Cochrane Infectious Diseases Group Trials Register. SELECTION CRITERIA: Randomised controlled trials of steroids in people on TB treatment for TBM. DATA COLLECTION AND ANALYSIS: Two independent reviewers applied study selection criteria, assessed methodological quality and extracted data. MAIN RESULTS: Six trials of 595 patients met the inclusion criteria. No study described allocation concealment. Steroids were associated with fewer deaths (relative risk [RR] 0.79; 95% confidence interval [CI] 0.65 to 0.97) and a reduced incidence of death and severe residual disability (RR 0.58, 95% CI 0.38 to 0.88). Subgroup analysis suggests an effect on mortality in children (RR 0.77, 95% CI 0.62 to 0.96) but the results in a smaller number of adults are inconclusive (RR 0.96, 95% CI 0.50 to 1.84). There is little evidence that the severity of disease influences the effects of steroids on mortality. REVIEWER'S CONCLUSIONS: Adjunctive steroids might be of benefit in patients with TBM. However, existing studies are small, and poor allocation concealment and publication bias may account for the positive results found in this review. No data are available on the use of steroids in HIV positive persons. Future placebo-controlled studies should include patients with HIV infection and should be large enough to assess both mortality and disability.

Adult↗
PubMed2000

Antioxidant Activity of Secoisolariciresinol Diglucoside-derived Metabolites, Secoisolariciresinol, Enterodiol, and Enterolactone.

Secoisolariciresinol diglucoside (SDG), an antioxidant isolated from flaxseed, is metabolized to secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (EL) in the body. The effectiveness of SDG in hypercholesterolemic atherosclerosis, diabetes, and endotoxic shock could be due to these metabolites. These metabolites may have antioxidant activity. However, the antioxidant activity of these metabolites is not known. The antioxidant activity of SECO, ED, and EL was investigated using chemiluminescence (CL) of zymosan-activated polymorphonuclear leukocytes (PMNLs) [PMNL-CL]. Other antioxidants (SDG and vitamin E) were also used for comparison. SDG, SECO, ED, EL, and vitamin E, each in the concentration of 0.5, 1.0, 2.5, 5.0 and 10.0 mg/ml, produced a concentration-dependent reduction in zymosan-activated PMNL-CL. SDG, SECO, ED, EL, and vitamin E, in the concentration of 2.5 mg/ml, produced a reduction of zymosan-activated PMNL-CL by 23.8%, 91.2%, 94.2%, 81.6% and 18.7%, respectively. Activated PMNLs produce reactive oxygen species and luminol-dependent CL reflects the amount of oxygen species generated from activated PMNLs. The reduction of PMNL-CL, therefore, reflects the antioxidant activity of the compounds studied. These results suggest that the metabolites of SDG have antioxidant activity. The antioxidant activity was highest with SECO and ED and lowest with vitamin E. The antioxidant potency of SECO, ED, EL, and SDG was 4.86, 5.02, 4.35, and 1.27 respectively, as compared to vitamin E. SECO, ED and EL are respectively 3.82, 3.95, and 3.43 more potent than SDG.

Journal Article↗