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Biomedical subjects

R Singh

Publications and source records attributed to R Singh.

At least 19 recordsLinked to original sources
PubMed2007

The long-term impact on offspring of exposure to hyperglycaemia in utero due to maternal glucokinase gene mutations.

AIMS/HYPOTHESIS: There is strong evidence that maternal diabetes while offspring are in utero results in offspring beta cell dysfunction and diabetes or glucose intolerance. Offspring born to mothers with a mutation in the glucokinase gene (GCK) are a good model for studying exposure to moderate hyperglycaemia, as mutation carriers have fasting hyperglycaemia throughout life including during pregnancy. We assessed the long term effects of exposure to maternal hyperglycaemia in utero on beta cell function and glucose tolerance in adult offspring. MATERIALS AND METHODS: We studied 86 adult offspring (mean age 40 years), 49 born to glucokinase mothers (exposed to hyperglycaemia in utero) and 37 born to glucokinase fathers (controls). We measured glucose tolerance during an OGTT and beta cell function using early insulin response (EIR); we also measured anthropometric data including birthweight. RESULTS: Offspring of glucokinase mothers had a higher birthweight by 450 g (p<0.001), but no evidence of deterioration in glucose tolerance (2-h glucose 9.1 vs 8.6 mmol/l p=0.50) or reduced beta cell function (log EIR 1.40 vs 1.26, p=0.11) compared with offspring born to glucokinase fathers. CONCLUSIONS/INTERPRETATION: The marked increase in birthweight shows that offspring born to affected mothers were exposed to increased glycaemia in utero. Despite this, there was no evidence of altered beta cell function or glucose tolerance. As previous human examples of marked programming by hyperglycaemia in utero have been in genetically predisposed offspring, we propose that our finding reflects the lack of genetic predisposition in the offspring to progressive beta cell dysfunction.

Adult↗
PubMed2007

The safety and efficacy of the oral rabies vaccine SAG2 in Indian stray dogs.

India is one of the countries with the highest prevalence of human rabies throughout the world. Dogs are primarily responsible for rabies transmission. Among them, stray dogs play a major role in that country. Parenteral vaccination programmes are insufficient to eliminate rabies partly due to difficulties in establishing satisfactory immunisation coverage in the dog population in view of the high proportion of stray dogs. Oral vaccination may be a useful adjunct to parenteral vaccination by increasing dog vaccination coverage. Safety, immunogenicity and efficacy of Rabidog SAG2 bait were evaluated in Indian stray dogs in captivity. Safety of SAG2 was demonstrated by the absence of adverse clinical sign, salivary excretion and absence of replication of the vaccine strain in brain and salivary glands of 21 vaccinated dogs, even when immunodepressed. Efficacy was shown 109 days post-vaccination after challenge with a highly virulent street rabies virus which killed all five controls whereas all nine vaccinated dogs survived, despite the fact that only five out of nine had seroconverted before challenge.

Administration, Oral↗
PubMed2006

Growth performance and biochemical responses of three rice (Oryza sativa L.) cultivars grown in fly-ash amended soil.

The disposal of fly-ash (FA) from coal-fired power stations causes significant economic and environmental problems. Use of such contaminated sites for crop production and use of contaminated water for irrigation not only decreases crop productivity but also poses health hazards to humans due to accumulation of toxic metals in edible grains. In the present investigation, three rice cultivars viz., Saryu-52, Sabha-5204, and Pant-4 were grown in garden soil (GS, control) and various amendments (10%, 25%, 50%, 75% and 100%) of FA for a period of 90 days and effect on growth and productivity of plant was evaluated vis-a-vis metal accumulation in the plants. The toxicity of FA at higher concentration (50%) was reflected by the reduction in photosynthetic pigments, protein and growth parameters viz., plant height, root biomass, number of tillers, grain and straw weight. However, at lower concentrations (10-25%), FA enhanced growth of the plants as evident by the increase of studied growth parameters. The cysteine and non-protein thiol (NP-SH) content showed increase in their levels up to 100% FA as compared to control, however, maximum content was found at 25% FA in Saryu-52 and Pant-4 and at 50% FA in Sabha-5204. Accumulation of Fe, Si, Cu, Zn, Mn, Ni, Cd and As was investigated in roots, leaves and seeds of the plants. Fe accumulation was maximum in all the parts of plant followed by Si and both showed more translocation to leaves while Mn, Zn, Cu, Ni and Cd showed lower accumulation and most of the metal was confined to roots in all the three cultivars. As was accumulated only in leaves and was not found to be in detectable levels in roots and seeds. The metal accumulation order in three rice cultivars was Fe > Si > Mn > Zn > Ni > Cu > Cd > As in all the plant parts. The results showed that rice varieties Saryu-52 and Sabha-5204 were more tolerant and could show improved growth and yield in lower FA application doses as compared to Pant-4. Thus, Sabha-5204 and Saryu-52 are found suitable for cultivation in FA amended agricultural soils for better crop yields.

Biomass↗
PubMed2006

Methotrexate induced differentiation in colon cancer cells is primarily due to purine deprivation.

The folate antagonist methotrexate (MTX) inhibits synthesis of tetrahydrofolate (THF), pyrimidines and purines, and induces differentiation in several cell types. At 1 microM, MTX reduced proliferation and induced differentiation in HT29 colon cancer cells; the latter effect was augmented (P < 0.001) by thymidine (100 microM) but was reversed (P < 0.001) by the purines, hypoxanthine (Hx; 100 microM) and adenosine (100 microM). In contrast 5-fluoro-uracil (5-FU), a specific thymidylate synthase (TS) inhibitor, had no effect on differentiation, suggesting that MTX-induced differentiation is not due to a reduction in thymidine but to the inhibition of purine biosynthesis. Inhibition of cyclic AMP (cAMP) by RpcAMP (25 microM) further enhanced (P < 0.001) MTX induced differentiation, whereas the cAMP activator forskolin (10 microM) reversed (P < 0.001) MTX induced differentiation. These observations implicate a central role of adenosine and cAMP in MTX induced differentiation. By combining Western blot analysis with liquid chromatography-mass spectrometry (LC-MS)and HPLC analyses we also reveal both the expression and activity of key enzymes (i.e. methionine synthase (MS), s-adenosylhomocysteinase, cystathionine beta-synthase and ornithine decarboxylase) regulating methyl cycle, transsulfuration and polyamine pathways in HT29 colon cancer cells. At 1 microM, MTX induced differentiation was associated with a marked reduction in the intracellular concentrations of adenosine and, consequently, S-adenosylmethionine (SAM), S-adenosylhomocysteine, polyamines and glutathione (GSH). Importantly, the marked reduction in methionine that accompanied MS inhibition following MTX treatment was non-limiting with respect to SAM synthesis. Collectively, these findings indicate that the effects of MTX on cellular differentiation and single carbon metabolism are primarily due to the intracellular depletion of purines.

Adenocarcinoma↗
PubMed2006

Results of early surgical intervention after suboptimal ankle fracture fixation.

Ankle fractures are common injuries and commonly require operative stabilisation. The aim of ankle fracture fixation should be reduction and stabilisation, as for any periarticular fracture. Anatomical reduction will lead to good long-term results, but non-anatomically reduced fractures will lead to a poor functional outcome and development of osteoarthritis. We reviewed eight cases of non-anatomical ankle fixations that were revised by M.D. over a 4-year period. All were revised within 1 year of initial fixation. Clinical scoring for functional outcome was performed using the American Orthopaedic Foot and Ankle Society rating system for the ankle and hindfoot. All patients reported improved function after the revision procedure. We conclude that revision surgery is justified if suboptimal fixation is encountered within 12 months of the original surgery.

Adult↗
PubMed2006

Prospective, long-term evaluation of steroid-induced glaucoma.

PURPOSE: To evaluate the intraocular pressure (IOP) after cessation of steroid use in steroid-induced glaucoma and its control with medication or surgery. METHODS: Thirty-four eyes of 34 patients having steroid-induced glaucoma were prospectively evaluated after cessation of steroid for IOP, visual acuity, and optic disc status at 3 months, and every 3 months for 18 months. RESULTS: Topical steroid use (73.5%) was the most frequent cause for glaucoma. The baseline IOP was 35.47+/-12.59 mmHg. The baseline vertical cup-disc ratio correlated with duration of steroid use (P=0.014) and the baseline IOP (P<0.0001). In 25 patients (73.5%), IOP could be controlled by topical medications alone, whereas nine patients (26.5%) required surgery. The mean baseline IOP in eyes requiring surgery was 49.67+/-13.28 mmHg and in eyes managed medically, 30.36+/-7.51 mmHg (P=0.002). The vertical cup-disc ratio in surgically treated patient was 0.87+/-0.13:1 as compared to 0.71+/-0.15:1 (P=0.012) in the medically treated group. At 6, 12, and 18 months follow-up, 22 (64.7%), 33 (97.1%), and all 34 (100%) patients were off treatment, respectively. CONCLUSIONS: Patients with steroid-induced glaucoma, who were <or=20 years old, with a higher IOP, and greater glaucomatous optic neuropathy, were more likely to need surgery. After cessation of steroid therapy, all eyes were off treatment at 18 months.

Adolescent↗
PubMed2006

Efficacy of three doses of tramadol with bupivacaine for caudal analgesia in paediatric inguinal herniotomy.

BACKGROUND: This study was designed to evaluate the analgesic efficacy of three doses of tramadol, administered caudally with bupivacaine, in providing postoperative pain relief in children. METHODS: Eighty children, aged between 2 and 8 yr, undergoing inguinal herniotomy were randomly allocated to receive bupivacaine 0.25% 0.75 ml kg(-1) (Group B; n=20), bupivacaine 0.25% 0.75 ml kg(-1) with tramadol 1 mg kg(-1) (Group BT1; n=20), bupivacaine 0.25% 0.75 ml kg(-1) with tramadol 1.5 mg kg(-1) (Group BT1.5; n=20), or bupivacaine 0.25% 0.75 ml kg(-1) with tramadol 2 mg kg(-1) (Group BT2; n=20) by the caudal route immediately after induction of general anaesthesia. Heart rate, arterial pressure and oxygen saturation were monitored. Postoperative pain was assessed at regular intervals for 24 h using All India Institute of Medical Sciences pain score. Analgesia was supplemented whenever pain score was >or=4. Duration of analgesia and requirement for additional analgesics was noted. RESULTS: Duration of analgesia was longer in Group BT2 [(mean (SD) 12 (0.9) h] compared with Group B [4 (1) h], Group BT1 [8 (0.9) h], or Group BT1.5 [11 (1) h]; all P<0.001. Total consumption of rescue analgesic was significantly lower in group BT2 compared with other groups (P<0.001). There were no significant changes in heart rate, arterial pressure and oxygen saturation between groups. Adverse effects were not observed. CONCLUSIONS: Caudal tramadol 2 mg kg(-1), combined with bupivacaine 0.25% 0.75 ml kg(-1), provided longer duration of postoperative analgesia and reduced requirement for rescue analgesic compared with tramadol 1 mg kg(-1) or 1.5 mg kg(-1) in children undergoing inguinal herniotomy.

Acetaminophen↗
PubMed2006

Study on oxidative stress in patients with abdominal trauma.

Reactive oxygen species have been implicated in the etiology of multiple organ dyspepsia syndrome and infection's complications in patients with trauma. But the oxidative stress and antioxidants levels in abdominal trauma have not yet been studied. Therefore, this study was planned to measure lipid peroxidation for oxidative stress and reduced glutathione, catalase and superoxide dismutase (SOD) for antioxidant levels in plasma & heamolysate of 30 patients with abdominal trauma and 30 controls. From this study we can summarize that there was an increase in oxidative stress and decrease in antioxidant levels (causing oxidative stress) on day zero in patients with abdominal trauma. This oxidative stress on day zero was not related to the development of complications. There was no significant difference in oxidative stress between patients with solitary and multiple abdominal organ injury and also between patients with hollow viscus injury and solid organ injury on day zero. From this study, we conclude that in patients with abdominal trauma there was increase in oxidative stress and decrease in antioxidant levels on day zero.

Abdominal Injuries↗
PubMed2006

Choroidal detachment in perforated corneal ulcers: frequency and management.

AIMS: To determine the frequency of choroidal detachment (CD) in eyes with non-traumatic corneal ulcer perforation and, also, to assess the efficacy and safety of cyanoacrylate glue in sealing corneal perforations. METHODS: 18 eyes of 17 patients were studied. Inclusion criterion was any patient with a non-traumatic perforated corneal ulcer. All patients had a thorough history taken and complete ophthalmic examination including B-scan ultrasonography. Patient demographics, presence of CD, and efficacy of corneal gluing were assessed. RESULTS: Eight of the 18 eyes (44%) were documented to have a CD. Among perforations of >2 mm2, six eyes (75%) were documented to have CD compared with two eyes (20%) with perforations of <or=2 mm2 (p = 0.054). No correlation could be determined between perforation duration and incidence of CD. Of the 15 eyes that underwent gluing, there were 13 successes (87%) and two failures (13%). Within the successes four patients (27%) required re-gluing because of infection (one patient) or progression of melt and glue loosening (three patients). Failure was the result of severe progression of melting (one patient) and a very large perforation (one patient). CONCLUSION: Choroidal detachment following corneal ulcer perforation is common and is more likely in larger corneal perforations. Preoperative B-scan should be considered in cases of large corneal perforations requiring therapeutic keratoplasty to document choroidal detachment, which if large may require drainage. Cyanoacrylate glue is an effective and safe method for sealing small corneal perforations. A vigil must be maintained for infection while the glue and bandage contact lens are in situ.

Aged↗
PubMed2006

Reduced beta cell function in offspring of mothers with young-onset type 2 diabetes.

AIMS/HYPOTHESIS: Animal models indicate that even exposure to mild maternal hyperglycaemia in utero is detrimental to the beta cell function of the offspring, but evidence of this in humans is limited. In Europids who are diagnosed with type 2 diabetes before the age of 50 years, the risk of diabetes in the offspring of the diabetic mothers is greatly increased compared with the risk in those born to diabetic fathers. We hypothesised that offspring born to mothers with young-onset type 2 diabetes would have been exposed to mild hyperglycaemia in utero, so we studied the impact of this on their beta cell function. SUBJECTS AND METHODS: We measured beta cell function using early insulin response (EIR) after oral glucose; insulin resistance using HOMA; and HbA(1c) in 568 non-diabetic adult offspring born to parents with type 2 diabetes (mean age 55.8 years), split according to which parent was affected (in 327 it was the mother) and parental age of diagnosis: <50 years (n=117) or > or =50 years. To reduce the impact of genetic susceptibility, the offspring of affected fathers were used as control subjects. RESULTS: Offspring of mothers with young-onset type 2 diabetes had lower EIR (log EIR 4.32, 95% CI [4.14-4.51] vs 4.63 [4.43-4.83] p=0.02) and higher HbA(1c) (4.89% [4.79-4.99] vs 4.68% [4.57-4.79] p=0.02) than the offspring of fathers with young-onset type 2 diabetes. Insulin sensitivity was similar in the two groups. There were no differences in EIR or HbA(1c) between the offspring born to mothers and fathers who were diagnosed after the age of 50 years. CONCLUSIONS/INTERPRETATION: We conclude that the offspring of mothers with young-onset type 2 diabetes have a reduction in beta cell function. This is consistent with exposure to mild maternal hyperglycaemia programming beta cell function.

Adult↗
PubMed2006

Bisphosphonates in pregnancy and lactation-associated osteoporosis.

INTRODUCTION: Pregnancy and lactation-associated osteoporosis (PLO) is an uncommon condition characterized by the occurrence of fracture(s) during late pregnancy or the puerperium. The aetiology is uncertain, and its management and natural history poorly defined. METHODS: We report a series of 11 women with PLO seen at our institution over the past 20 years, with follow-up ranging from 1 to 19 years. RESULTS: Ten women presented with painful low-trauma vertebral fractures, at a median of 1 month postpartum. In nine cases the fractures were multiple (median: 3, range: 2-5). At least one recognised risk factor for osteoporosis (low body weight, smoking history, family history of osteoporosis/fracture, vitamin D insufficiency) was present in nine patients. Bone density was in the osteoporotic range at the spine (mean T score: -2.8), with less marked reduction at the proximal femur (mean T score: -1.9). Nine patients received bisphosphonate treatment, for a median duration of 24 months. In the five women who received a bisphosphonate within 1 year of presentation, spinal bone density increased by 23% over baseline values after 2 years of treatment (p=0.0014). Of the 5 women who had subsequent pregnancies, one, who had declined bisphosphonate therapy after the initial presentation, sustained a fracture in the postpartum period. Two patients (both of whom were followed for at least 10 years) sustained fractures outside of pregnancy. CONCLUSIONS: PLO is therefore associated with significant morbidity, a high prevalence of recognized risk factors for osteoporosis and a risk of recurrence in subsequent pregnancies. Bisphosphonate therapy administered soon after presentation substantially increases spinal bone density in patients with PLO.

Adult↗
PubMed2006

A first-principles study of the electronic structure and stability of a lithium aluminum hydride for hydrogen storage.

LiAlH4 holds great promise for reversible hydrogen storage, where a fundamental understanding of hydrogen interaction with the metal elements is essential to further improve its properties. The present paper reports a first-principles study of its stability and electronic structure, using a full potential linearized augmented plane wave (FLAPW) method within the generalized gradient approximation (GGA) for high accuracy. The theoretically calculated heat of formation agrees well with experiment. The electronic structures show that the H atoms bond nonequivalently with the Al in the [AlH4]- ligand, which leads to complex dehydrogenation characteristics of LiAlH4.

Journal Article↗
PubMed2006

Type II lepra reaction: an unusual presentation.

Ulcers with maculo-papular rash are an unusual presenting feature of leprosy. They occur as result of neuropathy, type-2 lepra reaction or Lucio's phenomenon. The hall mark of type-2 reaction is erythema nodosum. Very rarely it manifests as ulcerative skin lesions. We describe one such unusual case of a young male who presented with multiple ulcers and maculo-papular rash over the legs, chest and abdomen. In addition to this, he had fever, heart murmur, pulmonary infiltrates, neuropathy, and deranged liver function. A clinical differential diagnosis of infective endocarditis and systemic nectrozing vasculitis was made. Skin biopsy showed dense inflammation with lepra bacilli consistent with type-2 lepra reaction.

Abdomen↗
PubMed2006

Cyclooxygenase-2 expression and oxidative DNA adducts in murine intestinal adenomas: modification by dietary curcumin and implications for clinical trials.

The natural polphenol, curcumin, retards the growth of intestinal adenomas in the Apc(Min+) mouse model of human familial adenomatous polyposis. In other preclinical models, curcumin downregulates the transcription of the enzyme cyclooxygenase-2 (COX-2) and decreases levels of two oxidative DNA adducts, the pyrimidopurinone adduct of deoxyguanosine (M1dG) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG). We have studied COX-2 protein expression and oxidative DNA adduct levels in intestinal adenoma tissue from Apc(Min+) mice to try and differentiate between curcumin's direct pharmacodynamic effects and indirect effects via its inhibition of adenoma growth. Mice received dietary curcumin (0.2%) for 4 or 14 weeks. COX-2 protein, M1dG and 8-oxo-dG levels were measured by Western blot, immunochemical assay and liquid chromatography-mass spectrometry, respectively. In control Apc(Min+) mice, the levels of all three indices measured in adenoma tissue were significantly higher than levels in normal mucosa. Lifetime administration of curcumin reduced COX-2 expression by 66% (P = 0.01), 8-oxo-dG levels by 24% (P < 0.05) and M1dG levels by 39% (P < 0.005). Short-term feeding did not affect total adenoma number or COX-2 expression, but decreased M1dG levels by 43% (P < 0.01). COX-2 protein levels related to adenoma size. These results demonstrate the utility of measuring these oxidative DNA adduct levels to show direct antioxidant effects of dietary curcumin. The effects of long-term dietary curcumin on COX-2 protein levels appear to reflect retardation of adenoma development.

Adenomatous Polyposis Coli↗
PubMed2006

Non-hyperinsulinemic hypoglycemia in a patient with a gastrointestinal stromal tumor.

One of the authors (JvD) recently reported a case of non-islet cell tumor hypoglycemia caused by the production of "big" IGF-II by a gastrointestinal stromal tumor (GIST). Here, we report a patient with a GIST in whom non-hyperinsulinemic hypoglycemia was not attributable to aberrant tumoral IGF-II processing, but instead was caused by a combination of cachexia, renal and hepatic dysfunction, and tumoral glucose consumption.

Journal Article↗
PubMed2006

Resting pulse rates in a glaucoma clinic: the effect of topical and systemic beta-blocker usage.

INTRODUCTION: Beta-blockers have, for 25 years, been a commonly used agent in the treatment of raised intraocular pressure (IOP). Beta-blockers can also reduce the pulse rate. With no available literature examining a cohort of patients, this study aims to investigate the resting pulse rates in patients attending a specialist glaucoma clinic in order to identify if routine review of ophthalmic medication use is indicated. METHOD: The resting pulse rates of patients attending a glaucoma clinic were measured using pulseoximetry, with a medical and drug history established for each patient. RESULTS: In all, 205 patients were included in the study. A total of 101 (49%) of patients were using beta-blockers in some form. The mean pulse rate for patients not using beta-blockers (104 patients) was 76 beats per minute (bpm), for topical use only (68 patients) it was 70.3 bpm, for oral use (18 patients) it was 64.7 bpm, and 58 bpm for patients using both topical and oral beta-blockers (15 patients). Groups using beta-blockers (oral, topical, oral and topical) were considered in relation to patients not using beta-blockers. All groups using beta-blockers showed a significant association with causing a bradycardia of less than 60 bpm. Patients with a pulse rate of less than 50 bpm were significantly more likely to be using topical and oral beta-blockers than oral beta-blockers alone (P=0.01). CONCLUSION: Topical beta-blockers should be used with caution, even in the presence of established systemic beta-blocker use. Routine pulse rate monitoring and review of ophthalmic medication are indicated in patients using beta-blocker therapy.

Administration, Oral↗