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Biomedical subjects

M Singh

Publications and source records attributed to M Singh.

At least 127 records · Page 7Linked to original sources
PubMed2002

Combined spinal epidural anaesthesia for vesico-vaginal fistula repair in an achondroplastic dwarf.

A 33-year-old achondroplastic female was scheduled to undergo vesico-vaginal fistula repair by the abdominoperineal route. Preoperative examination suggested a difficult airway so a combined spinal epidural technique was used. Subarachnoid block (sensory loss to T6) was established using 0.5% hyperbaric bupivacaine 1 ml. Anaesthesia was prolonged with incremental doses of epidural bupivacaine 0.5% (total 10 ml) and postoperative analgesia was provided with epidural morphine boluses.

Achondroplasia↗
PubMed2002

Kidney functions in newly diagnosed type 2 diabetic subjects: role of glycemic control.

BACKGROUND: The increased urinary albumin excretion (UAE) found at the diagnosis in type 2 diabetes may at least be functional and, thus reversible, as in type 1 diabetes. Furthermore, a positive correlation has been found between the glycemic control and UAE in type 2 diabetic subjects. MATERIAL AND METHODS: The impact of glycemic control after achieving three months of continuous normo-glycemia was studied in 26 (including 16 males and 10 females) newly diagnosed type 2 diabetic patients to assess renal size/volumes, various renal functions and UAE. RESULTS: A significant reduction was seen in glomerular filtration rate (GFR), UAE and fractional albumin clearance after achieving near normoglycemia (p < 0.01). A decrease in the kidney size/volume, though statistically insignificant, was also observed. Besides a decline in GFR of 4.8% was also noted after three months of stable normoglycemia. UAE normalized in six of these subjects. A statistically significant correlation was also found between the changes in mean fasting plasma glucose and the decline in UAE (r=0.56 and p < 0.01). CONCLUSION: The study emphasizes the necessity to correct the apparently reversible increase in microabuminuria that accompanies hyperglycemia prior to patients recruitment for intervention therapy.

Albuminuria↗
PubMed2002

Evaluation of role of acute intermittent peritoneal dialysis in resistant congestive heart failure.

AIMS AND OBJECTIVES: To evaluate the role of acute intermittent peritoneal dialysis (PD) in resistant congestive heart failure (CHF). MATERIAL AND METHODS: The study was conducted on 20 adult patients of resistant CHF. These patients were subjected to 12 cycles of acute intermittent hypertonic peritoneal dialysis. Improvement was monitored by clinical symptomatology, echocardiography, measurement of ultrafiltration and quantity of sodium transferred. RESULTS: There was improvement in clinical symptomatology. There was significance improvement in left ventricular (LV) function as evidenced by improvement in ejection fraction from a predialysis value of 43.35 +/- 16.73% to a post dialysis value of 53.55 +/- 14.53%. The ultrafiltration and quantity of sodium transferred was also significant. CONCLUSIONS: Acute intermittent hypertonic peritoneal dialysis is an effective and safe treatment modality in patients of resistant CEF. The patients subsequently respond well to medical therapy.

Adult↗
PubMed2001

Novel spermine-amino acid conjugates and basic tripeptides enhance cleavage of the hairpin ribozyme at low magnesium ion concentration.

Combinations of the polyamine spermine and magnesium ions synergize to dramatically enhance cleavage of the hairpin ribozyme. Certain synthetic basic tripeptides stimulate hairpin cleavage significantly at limiting magnesium ion concentration, notably the tripeptide of L-diaminobutyric acid (Dab). Of a range of novel synthetic spermine-amino acid conjugates, L-Dab-spermine (but not D-Dab nor other amino acid conjugates) was more effective than spermine itself.

Amino Acids↗
PubMed2001

Influence of coronary thrombus on outcome of percutaneous coronary angioplasty in the current era (the Mayo Clinic experience).

Earlier studies documented an increased risk of percutaneous coronary intervention (PCI) in patients with angiographic evidence of thrombus. With newer antiplatelet agents and stents, it is not known whether thrombus is a risk factor after PCI. This study examines whether outcome of PCI in patients with thrombus has improved, and whether thrombus is associated with adverse outcome after PCI in the current era. This single-institution retrospective analysis of PCI in 7,184 patients was divided into 2 periods: group I, 1990 to 1995 (n = 3,640), and group II, 1996 to 1999 (n = 3,544). The groups were subdivided according to the presence or absence of angiographic thrombus before PCI. We compared the outcome of PCI for patients with and without thrombus in group II. A comparison was made in the 2 groups in patients with angiographic thrombus. Procedural success improved in group II compared with group I patients with thrombus (93% vs 88%, p <0.001). There was significant reduction in abrupt closure in the recent era in patients with thrombus (4% vs 7%, p = 0.01). In group II, procedural success remained lower in patients with (93% vs 96%) than without thrombus (p <0.001). After adjusting for the significant univariate characteristics of group II patients, thrombus remained an independent predictor of Q-wave infarction (odds ratio 3.78; 95% confidence interval [CI], 1.8 to 8.0; p <0.0013) and the composite end point of death, Q-wave infarction, and emergency bypass surgery (odds ratio 2.37; 95% CI 1.4 to 4.1; p = 0.002). There was a trend toward increased in-hospital death among patients with thrombus (odds ratio 2.06; 95% CI 0.9 to 4.8; p = 0.09). The 1-year outcome after successful PCI was similar for those with and without thrombus. Despite improvement in the outcome of patients with thrombus undergoing PCI in recent years, thrombus is still an independent predictor of adverse in-hospital outcomes after PCI.

Aged↗
PubMed2001

Mucosal immunization with HIV-1 gag DNA on cationic microparticles prolongs gene expression and enhances local and systemic immunity.

There is an urgent need to develop vaccines against transmission of HIV through the vaginal and rectal mucosa. In the present study we tested the ability of DNA encoding HIV-1 gag adsorbed onto the surface of cationic polylactide co-glycolide microparticles (PLG-DNA) to induce local and systemic gag-specific immunity following mucosal delivery. We found gag-specific cell- and antibody-mediated responses in local as well as systemic lymphoid tissues following intranasal (IN) immunizations with PLG-DNA but not with naked DNA. IN immunizations with PLG-DNA, but not naked DNA, induced prolonged expression of gag protein in local and systemic lymphoid tissues. These data have important implications for DNA vaccine development.

AIDS Vaccines↗
PubMed2001

Comparison of the effect of fatty alcohols on the permeation of melatonin between porcine and human skin.

Melatonin (MT) is a hormone secreted by the pineal gland that plays an important role in the regulation of the circadian sleep-wake cycle. It would be advantageous to administer MT using a transdermal delivery system for the treatment of sleep disorders such as delayed sleep syndrome, jet lag in travelers, cosmonauts and shift workers. The porcine skin has been found to have similar morphological and functional characteristics as human skin. The elastic fibres in the dermis, enzyme pattern of the epidermis, epidermal tissue turnover time, keratinous proteins and thickness of epidermis of porcine skin are similar to human skin. However, the fat deposition and vascularisation of the cutaneous glands of porcine skin are different from human skin. In addition, porcine skin has been found to have a close permeability character to human skin. However, the comparative effect of chemical penetration enhancers on the permeation of drugs between porcine and human skin has not been reported. The purpose of this study was to compare the effect of fatty alcohols on the permeability of porcine and human skin using MT as a model compound. The effect of saturated fatty alcohols (octanol, nonanol, decanol, undecanol, lauryl alcohol, tridecanol, myristyl alcohol) and unsaturated fatty alcohols (oleyl alcohol, linoleyl alcohol, linolenyl alcohol) at 5% concentration was tested across dermatomed porcine and human skin. Our studies showed a parabolic relationship between the carbon chain length of saturated fatty alcohols and permeation enhancement of MT with both porcine and human skin. Maximum permeation of MT was observed when fatty alcohol carbon chain length was 10. In general, as the level of unsaturation increased from one to two double bonds, there was an increase in the permeation of MT both in porcine and human skin. However, a decrease in the permeation was observed with three double bonds. Regression analysis using the steady state flux data showed a significant positive correlation between porcine and human skin for saturated fatty alcohols (r(2)=0.8868, P=0.0005). However, though a positive correlation was observed between the porcine and human skin (r(2)=0.8638), the correlation was statistically insignificant (P=0.0706). The static diffusion cell system employed in this study has major artifact compared to a flow through system. In conclusion, the permeability of porcine skin to MT in the presence of saturated and unsaturated fatty alcohols was qualitatively similar to human skin but quantitatively different with some fatty alcohols.

Animals↗
PubMed2001

Accelerated intimal thickening in carotid arteries of balloon-injured rats after immunization against heat shock protein 70.

OBJECTIVES: The goal of this study was to test the hypothesis that induction of an immune response to heat shock protein (Hsp) 70 would increase intimal thickening in a rat carotid-injury model. BACKGROUND: Restenosis resulting from intimal thickening poses a major limitation to the long-term success of coronary angioplasty. Several studies have proposed that infectious agents increase restenosis. Heat shock proteins are highly conserved structures, produced by all cells in response to nonspecific forms of stress. Infectious agents are known to contain Hsp70, which is markedly immunogenic and can elicit a strong immune response. METHODS: To investigate whether Hsp70 immunity can affect neointimal thickening, we immunized rats with either Hsp70 (n = 11), bovine serum albumin ([BSA] n = 9) or with a control adjuvant (n = 10). Three weeks later, rats were boosted using the same regimen to achieve a sustained immune response to Hsp70 after which carotid injury was applied to all animals. RESULTS: Arterial injury was associated with upregulation of Hsp70, 3, 7 and 14 days after induction of the injury as evidenced by Western blotting and immunohistochemistry. Intimal area and intimal/medial ratio was significantly increased in Hsp70-immunized rats in comparison with BSA or control-injected rats. CONCLUSIONS: Our results imply that upregulation of Hsp70 in balloon-injured arteries can serve as a target for anti-Hsp70 immune response, thereby facilitating enhanced intimal thickening. These observations may provide a possible mechanism that explains the accelerated intimal thickening that has been associated with the occurrence of infectious pathogens.

Angioplasty, Balloon, Coronary↗
PubMed2001

Conjugation of anti-My9 antibody to stealth monensin liposomes and the effect of conjugated liposomes on the cytotoxicity of immunotoxin.

The carboxylic ionophore, monensin, was successfully entrapped in stealth liposomes by employing the pH-gradient method (interior pH of liposomes 9.5; exterior pH 5.0-5.9). A maximum of 14% of monensin could be entrapped in stealth liposomes by this method. The stealth liposomes could be successfully freeze-dried having mean particle size varying between 197 and 223 nm. The stealth liposomes were conjugated to anti-My9 monoclonal antibody (targeted against CD 33 antigen) by a disulfide linkage with almost full retention of immunoreactivity. The method of conjugation of liposomes with the antibody did not alter the particle size of liposomes and resulted in only 10% leakage of monensin. In-vitro cytotoxicity studies showed that antibody-conjugated monensin liposomes (3.5x10(-8) M monensin) potentiated the cytotoxicity of anti-My9 immunotoxin by a factor of 2070, in comparison to 360-fold potentiation observed with unconjugated monensin liposomes against human HL-60 promyelocytic leukemia cells. These results indicate that it is possible to enhance the in-vitro cytotoxicity of immunotoxin by several folds using antibody-conjugated monensin liposomes.

Antibodies, Monoclonal↗
PubMed2001

Recent developments in adjuvants for vaccines against infectious diseases.

New generation vaccines, particularly those based on recombinant proteins and DNA, are likely to be less reactogenic than traditional vaccines, but are also less immunogenic. Therefore, there is an urgent need for the development of new and improved vaccine adjuvants. Adjuvants can be broadly separated into two classes, based on their principal mechanisms of action; vaccine delivery systems and 'immunostimulatory adjuvants'. Vaccine delivery systems are generally particulate e.g. emulsions, microparticles, iscoms and liposomes, and mainly function to target associated antigens into antigen presenting cells (APC). In contrast, immunostimulatory adjuvants are predominantly derived from pathogens and often represent pathogen associated molecular patterns (PAMP) e.g. LPS, MPL, CpG DNA, which activate cells of the innate immune system. Once activated, cells of innate immunity drive and focus the acquired immune response. In some studies, delivery systems and immunostimulatory agents have been combined to prepare adjuvant delivery systems, which are designed for more effective delivery of the immunostimulatory adjuvant into APC. Recent progress in innate immunity is beginning to yield insight into the initiation of immune responses and the ways in which immunostimulatory adjuvants may enhance this process. However, a rational approach to the development of new and more effective vaccine adjuvants will require much further work to better define the mechanisms of action of existing adjuvants. The discovery of more potent adjuvants may allow the development of vaccines against infectious agents such as HIV which do not naturally elicit protective immunity. New adjuvants may also allow vaccines to be delivered mucosally.

Adjuvants, Immunologic↗
PubMed2001

The trimer-of-hairpins motif in membrane fusion: Visna virus.

Structural studies of viral membrane fusion proteins suggest that a "trimer-of-hairpins" motif plays a critical role in the membrane fusion process of many enveloped viruses. In this motif, a coiled coil (formed by homotrimeric association of the N-terminal regions of the protein) is surrounded by three C-terminal regions that pack against the coiled coil in an oblique antiparallel manner. The resulting trimer-of-hairpins structure serves to bring the viral and cellular membranes together for fusion. learncoil-vmf, a computational program developed to recognize coiled coil-like regions that form the trimer-of-hairpins motif, predicts these regions in the membrane fusion protein of the Visna virus. Peptides corresponding to the computationally identified sequences were synthesized, and the soluble core of the Visna membrane fusion protein was reconstituted in solution. Its crystal structure at 1.5-A resolution demonstrates that a trimer-of-hairpins structure is formed. Remarkably, despite less than 23% sequence identity, the ectodomains in Visna and HIV-1 envelope glycoproteins show detailed structural conservation, especially within the area of a hydrophobic pocket in the central coiled coil currently being targeted for the development of new anti-HIV drugs.

Amino Acid Motifs↗
PubMed2001

Percutaneous absorption and skin irritation of JP-8 (jet fuel).

JP-8 is the major jet fuel used by US Army and Air Force. The purpose of the present study was to investigate the percutaneous absorption of JP-8 across pig ear skin and human skin in vitro and to study the effect of JP-8 exposure on the skin barrier function and irritation in Yucatan minipigs. JP-8 spiked with 5.0 microCi of radiolabeled (14C) tridecane, nonane, naphthalene or toluene (selected components of JP-8) was used for the in vitro percutaneous absorption studies with excised pig ear skin and human skin. For in vivo studies, 250 microl of JP-8 or two of its components (toluene or nonane) was placed in a Hill top chamber(R) and affixed over the marked treatment area for 24 h. Transepidermal water loss (TEWL), skin capacitance (moisture content) and skin irritation (erythema and edema) were evaluated before treatment and at 1,2 and 24 h after removal of the patches. The components of JP-8 such as tridecane, nonane, naphthalene and toluene permeated significantly through pig ear skin and human skin and the permeation rates were found to be proportional to their composition in JP-8. The steady state flux values of tridecane across pig ear skin and human skin did not differ significantly (P>0.05). Though the steady state flux values of nonane, naphthalene and toluene were statistically different between porcine and human skin (P<0.01), the values were close considering the large variations usually observed in the percutaneous absorption studies. Application of toluene, nonane or JP-8 increased the TEWL, JP-8 being the highest (3.5 times at 24 h compared to baseline level). The skin moisture content decreased after the application of JP-8, though it was not significantly different (P>0.05) from the baseline level. JP-8 caused a moderate erythema and a moderate to severe edema. Though the edema decreased after 24 h, the degree of erythema remained about the same until 24 h. The skin irritation caused by JP-8 was greater than neat toluene or nonane. The TEWL data of toluene, nonane and JP-8 correlated well with the skin irritation data (erythema and edema). Exposure of JP-8, which contains hundreds of aliphatic and aromatic hydrocarbons, caused significant changes in the barrier function of the skin as indicated by an increase in TEWL and produced a significant erythema and edema in minipigs. Furthermore, the disruption of barrier function of skin, as indicated by increased TEWL after exposure to JP-8 might result in increased permeation of its own components and/or other chemicals exposed to skin. The present study provides further evidence that pig ear skin may be used as a model for predicting the rates of permeation of chemicals through human skin.

Administration, Cutaneous↗