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Biomedical subjects

G Singh

Publications and source records attributed to G Singh.

At least 235 records · Page 13Linked to original sources
PubMed1998

Mutant human presenilin 1 protects presenilin 1 null mouse against embryonic lethality and elevates Abeta1-42/43 expression.

Mutations in presenilin 1 (PS1) are linked to early onset of familial Alzheimer's disease (FAD) and are shown to foster production of Abeta1-42/43 in FAD patients and transgenic mice. PS1 null mice are embryonic lethal and exhibit axial skeleton malformation and CNS defects. We show that transgenic mouse lines expressing either the wild-type human PS1 protein or human PS1 with the A246E FAD mutation can rescue the PS1 knockout mouse from embryonic lethality to similar degrees, indicating that the mutation does not lead to loss of PS1 function during development. Furthermore, a 50% reduction of PS1 activity in PS1(+/-) mice does not lead to Abeta1-42/43 increase, whereas expression of human mutant PS1 on murine PS1 null background is sufficient to elevate Abeta1-42/43, supporting a gain-of-function activity as the result of the PS1 mutation.

Alzheimer Disease↗
PubMed1998

Early postoperative enteral feeding in patients with nontraumatic intestinal perforation and peritonitis.

BACKGROUND: In our clinical setting, patients with perforative peritonitis are frequently malnourished. Immediate postoperative enteral feeding has been shown effective in reducing septic morbidity in patients with abdominal trauma. This study was designed to investigate the feasibility and efficacy of immediate postoperative enteral feeding in patients with nontraumatic intestinal perforation and peritonitis. STUDY DESIGN: A prospective study spanning 1 year was conducted on patients with nontraumatic intestinal perforation and peritonitis. After laparotomy, patients were assigned randomly to a control or study group. The study group underwent a feeding jejunostomy and received enteral feeding from 12 hours postoperatively. A low-residue, milk-based diet was used. All patients underwent assessment for severity of sepsis and nutritional status at admission. Studies of nutritional status and nitrogen balance were repeated on days 4 and 7. RESULTS: Forty-three patients (21 in the study group; 22 in the control group) were included. The two groups were comparable except for a higher sepsis score in the study group (p < 0.05). Patients in the study group achieved a positive nitrogen balance by the third postoperative day; patients in the control group remained in negative nitrogen balance throughout the study. Abdominal distention (four patients) required temporary withdrawal of feeding. Diarrhea occurred in four patients but was controlled easily. The mortality rate was similar in the control and study groups (18.2% versus 19.1%). The control group had a total of 22 septic complications, versus eight in the study group (p < 0.05). CONCLUSIONS: Immediate postoperative feeding is feasible in patients with perforative peritonitis and reduces septic morbidity.

Adult↗
PubMed1998

A review of the readmissions of patients with tetraplegia to the Regional Spinal Injuries Centre, Southport, United Kingdom, between January 1994 and December 1995.

Patients with chronic tetraplegia are prone to develop unique clinical problems which require readmission to specialised centres where the health professionals are trained specifically to diagnose, and treat the diseases afflicting this group of patients. An appraisal of the readmission pattern of tetraplegic patients will provide the necessary data for planning allocation of beds for treatment of chronic tetraplegic patients. Hospital records of patients with tetraplegia readmitted to the Regional Spinal Injuries Centre, Southport, UK between 1 January 1994 and 31 December 1995 were analyzed to find out the number of tetraplegic patients who required readmission, reasons for readmission, duration of hospital stay, and mortality among patients readmitted. During the 2-year period, 155 tetraplegic patients were readmitted and 44 of them (28.4%) required more than one readmission (total readmission episodes: 221); these patients occupied 4.5 beds which is equivalent to 11.5% of the total bed capacity of the spinal unit. Among the reasons for the readmissions, evaluation and care of urinary tract disorders topped the list with 96 readmission episodes (43.43%) involving 70 patients; the median hospital stay was 3 days, and 18 patients (26%) required more than one readmission during this period. One hospital bed was occupied by the tetraplegic patients requiring treatment/evaluation of urinary tract disorders. Assessment and treatment of cardio-respiratory diseases was the second most common reason for readmission with 51 readmission episodes pertaining to 27 patients having a median hospital stay of 6 days; 13 patients (48%) were readmitted more than once within this 2-year period. Treatment of cardio-respiratory diseases in chronic tetraplegic patients required 1.2 hospital beds yearly. Only five tetraplegic patients were readmitted for treatment of pressure sore(s); however they had a prolonged hospital stay (median duration: 101 days). Social reasons accounted for 13 readmission episodes concerning nine patients who stayed in the hospital for varying periods (median: 6.5 days; mean: 35 days). Four tetraplegic patients readmitted with acute chest infection expired. An 81 year-old tetraplegic died of myocardial infarction. Urinary sepsis, renal insufficiency, respiratory failure and intra-cerebral haemorrhage accounted for the demise of a 41 year-old tetraplegic patient following surgical removal of a large, impacted stone at the pelviureteric junction. A tetraplegic patient who was admitted with haematuria subsequently underwent cystectomy for squamous cell carcinoma of the urinary bladder; he developed secondaries and expired 5 months later. As more patients with high cervical spinal cord injury survive the initial period of trauma, and as the life expectancy of tetraplegic patients increases, it is likely that greater numbers of tetraplegic patients will be requiring readmission to spinal injuries centre. Although it may be possible to prevent some of the complications of spinal cord injury and hence the need for a readmission, progress in medicine and rehabilitation technology will create additional demands for readmissions of chronic tetraplegic patients in order to implement the newer therapeutic strategies. Thus a change in the pattern of readmission of chronic tetraplegic patients is likely to be the future trend and this should be taken into account while making plans for providing the optimum care to chronic tetraplegic patients.

Adult↗
PubMed1998

Recurrent bilateral renal calculi in a tetraplegic patient.

An 18-year-old male developed C-5 complete tetraplegia following a motor-cycle accident in May 1975. The neuropathic bladder was managed by an indwelling urethral catheter. He developed recurrent episodes of urinary infection with Proteus species. In September 1975, an X-ray of the abdomen revealed small calculi in both the kidneys. In July 1976, he underwent transurethral resection of the bladder neck and division of the external urethral sphincter; subsequently, he was put on a penile sheath drainage. He continued to suffer from repeated episodes of urinary tract infection with Proteus, Providencia, and Pseudomonas species, and he was treated with antibiotics. In 1980, intravenous urography (IVU) showed two large stones in the left kidney with marked caliectasis. The IVU performed in 1984 showed an increase in the size of the calculi in the left kidney which was grossly hydronephrotic. There were clusters of small calculi in the right kidney. The left renal calculi were treated by percutaneous lithotripsy in two sessions. In 1988, an X-ray of the abdomen revealed staghorn calculus in the right kidney and recurrence of stones in the left kidney. The staghorn calculus in the right kidney was treated by percutaneous nephrostolithotomy in two sessions. In 1991, he was admitted with acute urinary infection. IVU showed a stone in the pelviureteric junction with no excretion of contrast in the left kidney. Percutaneous nephrostomy drainage was established followed by left percutaneous nephrostolithotomy. In 1992, he was found to retain large amount of urine in the bladder; subsequently, his mother was taught to perform regular intermittent catheterisations. In 1995, he was admitted with acute urine infection. Abdominal X-ray revealed recurrence of large stones in both kidneys. With multiple sessions of Extracorporeal Shockwave Lithotripsy (ESWL), about 80% clearance was achieved on the left side. Right staghorn renal stone awaits treatment. This case shows that recurrent urinary infection in spinal cord injury patients is a predisposing factor for renal lithiasis. These patients require annual urological evaluation. Urinary tract calculi, if detected, should be dealt with promptly to prevent renal damage due to urinary obstruction and urosepsis. Renal calculi can be treated effectively and safely by ESWL in spinal cord injury patients, thus avoiding the need for an invasive procedure. It is essential to achieve low-pressure, adequate emptying of the urinary bladder in patients with spinal cord injury in order to prevent recurrent urinary infection and its sequelae. Social issues involved in the care of a tetraplegic patient play a vital role in the implementation of ideal medical treatment and need to be addressed promptly to avoid any compromise in the quality of medical care.

Adolescent↗
PubMed1998

Cloning of the mating type loci from Pyrenopeziza brassicae reveals the presence of a novel mating type gene within a discomycete MAT 1-2 locus encoding a putative metallothionein-like protein.

The mating type loci were cloned from Pyrenopeziza brassicae by chromosome walking from a mating type-linked polymerase chain reaction (PCR) fragment and shown to be idiomorphic by sequence analysis. The MAT 1-1 locus is approximately 3.2 kb and contains a single gene encoding a putative high-mobility group (HMG) domain protein. The MAT 1-2 locus is approximately 3.9 kb with three open reading frames (ORFs) encoding a putative HMG domain, an alpha-1 domain and metallothionein-like proteins. The putative alpha-1 domain ORF on MAT 1-2 is transcribed in the opposite orientation to the other two transcripts and extends into non-idiomorphic sequence. This is the first report of sequence analysis of the mating type loci from a discomycete fungus, which has revealed an interesting mating type infrastructure within the MAT 1-2 locus. Although metallothionein-like proteins have been implicated in a number of processes in animals and plants, they have not to date been implicated in the mating process of filamentous fungi. Possible roles for metallothionein-like proteins in the mating process are discussed.

Amino Acid Sequence↗
PubMed1998

Effect of long-term hyperosmolality on the Na+/H+ exchanger isoform NHE-3 in LLC-PK1 cells.

The effects of long-term exposure to hyperosmotic medium on the Na+/H+ exchanger isoform NHE-3 were examined in cultured renal epithelial cells (LLC-PK1). LLC-PK1 cells were grown to confluence in control medium (310 mOsm/kg H2O) and then either switched to a hyperosmotic medium (510 mOsm/kg H2O; addition of NaCl or mannitol) or maintained in the control medium for 48 hours. The Na+/H+ exchanger activity was then assessed in isosmotic solutions by measurement of amiloride-sensitive acid-stimulated 22Na+ influx or Na+-dependent acid extrusion. Acid-stimulated 22Na+ influx was decreased significantly in cells incubated in hyperosmotic medium (10.5 +/- 0.9 nmol/mg protein, control vs. 5.8 +/- 0.6, hyperosmotic; P < 0.01). Incubation in hyperosmotic medium also decreased the initial rate of Na+-dependent acid extrusion by approximately 60% over the intracellular pH range 6.9 to 7.3. Intracellular buffering power did not differ in the control and hyperosmotic groups. The Na+/H+ exchanger isoform NHE-3 mRNA and protein, assessed by Northern hybridization and immunoblot analysis, respectively, were unchanged in LLC-PK1 cells incubated in hyperosmotic medium compared with controls, suggesting post-translational regulation by high osmolality. These results demonstrate that long-term exposure to hyperosmotic medium causes an adaptive decrease in Na+/H+ exchange (NHE-3) activity in LLC-PK1 cells, and that this effect is unlikely to involve antiporter gene regulation or a change in protein abundance.

Acids↗
PubMed1998

Arteriovenous malformation of knee masquerading as juvenile arthritis.

This is a rare case of involvement of knee joint by an arteriovenous malformation. A nine year old girl had recurrent monoarticular pain and swelling of long duration and had been treated as juvenile rheumatoid arthritis. Angiographic and histological features suggested an arteriovenous malformation of lower thigh with knee joint involvement.

Angiography↗
PubMed1998

Abdominal wall defects: anatomic classification and a scheme for management.

Defects created after excision of abdominal wall tumors pose a challenge to the reconstructive surgeon. The task is made more difficult by the wide variety of flaps available for this purpose. We present a simple classification of abdominal wall defects and our choice of flaps for reconstruction. The abdomen was divided into six regions for the purpose of reconstruction. The deep inferior epigastric artery flap alone is the flap of choice for central supraumbilical defects. For lateral supraumbilical defects the latissimus dorsi flap fulfills all the requirements. Infraumbilical defects, central or lateral, are ideally suited to reconstruction by unilateral or bilateral tensor fascia lata flaps. Patients representing each scenario are presented.

Abdominal Muscles↗
PubMed1998

Maternal exposure to environmental tobacco smoke alters Clara cell secretory protein expression in fetal rat lung.

We have previously demonstrated that aged and diluted sidestream cigarette smoke (ADSS) alters the development of bronchiolar epithelial cells in postnatal animals (C. M. Ji, C. G. Plopper, H. P. Witschi, and K. E. Pinkerton. Am. J. Respir. Cell Mol. Biol. 11: 312-320, 1994). This study was designed to examine the effects of maternal exposure to ADSS on the development of fetal Clara cells in rats with Clara cell 10-kDa protein (CC10; also designated Clara cell secretory protein) and CC10 mRNA as differentiation markers. Immunohistochemistry, Northern blots, and in situ hybridization were used to determine the abundance and distribution of CC10 at gestational days 14, 18, and 21. CC10 and CC10 mRNA were absent at gestational day 14 but were detectable at gestational day 18 and further increased by gestational day 21. Maternal exposure to ADSS was found to significantly increase fetal expression of CC10 and CC10 mRNA by gestational day 21 but not by gestational day 14 or 18. These findings demonstrate that in utero exposure to ADSS alters the normal developmental expression of CC10 in the fetal rat lung.

Animals↗
PubMed1998

Glucocorticoid-induced effects on pattern formation and epithelial cell differentiation in early embryonic rat lungs.

In this study, we examined the effects of dexamethasone (DEX) on airway branching and subsequent lung maturation. DEX treatment of fetal rat lung explants was initiated during the early pseudoglandular stage of development. Day 14 fetal lung explants were cultured with and without DEX for 4 d. Explants treated with 10 nM or higher concentrations of DEX showed features of both distorted and accelerated maturation. DEX-treated lungs had growth retardation, distorted branching, dilated proximal tubules, and suppressed proliferation of epithelial cells of the distal tubules. Several biochemical and morphologic features of accelerated maturation were also observed: 1) the epithelial cells lining the distal tubules (prospective respiratory airways) were generally cuboidal or flattened; 2) the cuboidal cells often contained lamellar bodies and abundant glycogen; 3) rudimentary septa and large airspace were present; 4) mesenchymal tissue was attenuated and compressed between adjacent epithelial tubules; 5) the distribution of SP-C mRNA in distal tubules was more mature, with individual and clusters of cells expressing SP-C transcripts; and 6) the transcript levels of several genes related to epithelial growth [keratinocyte growth factor (KGF), KGF receptor, and hepatocyte growth factor receptor] and differentiation [surfactant proteins, SP-A, SP-B and SP-C and the Clara cell secretory protein, CC10] were precociously increased. These results show that DEX treatment of the lung during the early pseudoglandular stage accelerates the acquisition of several features of advanced maturation that normally accompany late stages of fetal development. We postulate that KGF mediates at least some effects of DEX on lung maturation and gene expression.

Animals↗
PubMed1998

Antagonistic effects of dexamethasone and retinoic acid on rat lung morphogenesis.

We have reported that dexamethasone (DEX) treatment of early embryonic rat lungs in culture induced features of both distorted and accelerated maturation. In this report, we investigated the effects of retinoids on normal and DEX-induced lung development in vitro. Lung maturation was assessed by examining the morphology and the expression of genes related to epithelial differentiation (surfactant proteins, SP-A, SP-B and SP-C and Clara cell protein, CC10) and growth [keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF)]. We cultured d 14 and 15 fetal rat lungs in the presence of DEX (1-1000 nM) and/or all-trans-retinoic acid (RA) (10(-7)-10(-5) M) for 4 d. RA at 10(-6) and 10(-5) M inhibited branching and dilated the distal tubules, and at 10(-5) M caused dilatation of the proximal tubules destined to form the trachea and the main bronchi. The adverse effects of DEX, such as distorted branching, tubular dilatation, and suppression of both lung growth and epithelial cell proliferation, were all prevented by RA. In addition, RA inhibited several features of DEX-induced accelerated maturation, such as: 1) the increased levels of SP-A, SP-B, and CC10 mRNAs; 2) the attenuation of mesenchymal tissue; and 3) the mature distribution of cells expressing SP-C mRNA. In contrast, RA potentiated the increase of KGF and decrease of HGF transcripts induced by DEX. In conclusion, the study shows antagonism by RA of DEX-induced effects on lung morphology and gene expression. We postulate that normal lung development requires a balanced action of endogenous retinoids and glucocorticoids.

Animals↗
PubMed1998

An overview of anaesthetic issues in phaeochromocytoma.

Recent developments in the anaesthetic management of phaeochromocytoma are reviewed. A brief summary of its pathophysiology and clinical features is also considered. The main anaesthetic issues involved in the assessment and preparation of these patients in light of the current information are then discussed.

Adrenal Gland Neoplasms↗