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Biomedical subjects

R Subramaniam

Publications and source records attributed to R Subramaniam.

At least 37 records · Page 2Linked to original sources

Nitric oxide synthase is absent in only a subset of cases of pyloric stenosis.

PURPOSE: The aim of this study was to study nitric oxide synthase (NOS) immunohistochemistry in the pyloric muscle and establish the role of nitric oxide in pyloric stenosis. METHODS: Pyloric muscle biopsy specimens were obtained from 20 patients with pyloric stenosis during pyloromyotomy. Ten control specimens without pyloric disease were obtained from autopsy performed less than 4 hours after death on age-matched babies who died of other causes. Tissues were fixed in 4% paraformaldehyde immediately. A monoclonal antibody against the neuronal form of NOS (bNOS) was used for immunohistochemistry. RESULTS: Immunohistochemistry showed activity of bNOS in the control specimens and some pyloric stenosis specimens. This shows that NOS is present in the pylorus in normal cases as well as in a few cases of pyloric stenosis. CONCLUSIONS: NOS deficiency leading to lack of locally available nitric oxide causes a failure of smooth muscle relaxation. This may account for the cause of pyloric stenosis in infants. However, this study shows that this is true probably only in a subset of cases. The etiology of pyloric stenosis may still be multifactorial. Further investigations are required regarding the etiology of pyloric stenosis. J Pediatr Surg 36:616-619.

Biopsy, Needle↗

Making the diagnosis of biliary atresia using the triangular cord sign and gallbladder length.

BACKGROUND: To evaluate the accuracy and utility of the triangular cord sign and gallbladder length in diagnosing biliary atresia by sonography. MATERIALS AND METHODS: Sixty fasted infants with cholestatic jaundice aged 2-12 weeks were examined sonographically using a 5-10 MHz linear array transducer, focusing on the triangular cord sign (as described by Choi et al. [1]), the gallbladder, and ducts. The triangular cord is defined as a triangular or tubular echogenic density seen immediately cranial to the portal vein bifurcation; it represents the fibrotic remnant of the obliterated cord in biliary atresia. The findings were blinded to blood chemistry, (99 m)Tc-DISIDA hepatobiliary scintigraphy, and liver biopsy. Diagnosis of biliary atresia was confirmed at surgery and histology. Non-biliary atresia infants resolved medically. Comparative charges of the various investigations was made. RESULTS: ++ Twelve infants had biliary atresia, and ten demonstrated a definite triangular cord. The two false-negatives had small or nonvisualized gallbladders. No false-positives were recorded. Gallbladder length ranged from 0-1.45 cm with a mean of 0. 52 cm in biliary atresia compared to a mean of 2.39 cm in nonbiliary atresia infants. (99 m)Tc-DISIDA hepatobiliary scintigraphy showed no excretion (false-positive) in 23 % of nonbiliary atresia cases. Scintigraphy and liver biopsy charges were 2 and 6 times that of sonography, respectively. CONCLUSION: The triangular cord sign and gallbladder length together are noninvasive, inexpensive, and very useful markers for biliary atresia.

Bile Ducts, Extrahepatic↗

Xanthogranulomatous funiculitis and epididymo-orchitis in a tetraplegic patient.

STUDY DESIGN: A case report of xanthogranulomatous funiculitis and epididymo-orchitis. Xanthogranulomatous inflammation is an uncommon, non-neoplastic process characterised by destruction of tissue, which is replaced by a striking cellular infiltrate of lipid-laden macrophages. CASE REPORT: A 21-year male sustained complete tetraplegia at C-6 level, after a fall in 1998. The neuropathic bladder was managed with an indwelling urethral catheter. He had many unsuccessful trials of micturition. Sixteen months after the cervical injury, he noticed swelling of the left side of the scrotum following removal of a blocked catheter. He was prescribed antibacterial therapy. Four weeks later, physical examination revealed a hard and irregular swelling encompassing the testis, epididymis and spermatic cord. The clinical diagnosis was epididymo-orchitis progressing to pyocele. Through a scrotal incision, the swollen testis, epididymis and diseased segment of the spermatic cord were removed en masse. Histopathology showed extensive areas of necrosis, with xanthogranulomatous inflammation in the spermatic cord and to a lesser extent in the testis/epididymis. CONCLUSION: Repeated episodes of high-pressure urinary reflux along the vas deferens during dyssynergic voiding, and subsequent interstitial extravasation of urine together with chronic, low-grade, suppurative infection possibly led to development of xanthogranulomatous inflammation in the testis and the epididymis. Since tissue destruction is a feature of xanthogranulomatous inflammation, the definite and curative treatment is either complete (or, where applicable, partial) excision of the affected organ in most of the cases.

Adult↗

Initial response to portoenterostomy determines long-term outcome in patients with biliary atresia.

PURPOSE: The aim of this study was to assess the efficacy of portoenterostomy in biliary atresia and determine factors that predict outcomes. METHODS: The outcomes after portoenterostomy for biliary atresia from 1976 to 1996 were graded into 3 defined groups: G (good, jaundice free); I (intermediate, progressive liver disease with liver transplant if needed after 3 years of age); P (poor, liver transplant or death at less than 3 years of age). RESULTS: Twenty-seven of 49 children (55%) who underwent portoenterostomy responded. Of these, 13 (26%) were jaundice free (G). Of 14 children (28%) in I, 6 underwent liver transplant after 3 years of age. Of 22 children (44.8%) in P, 14 (28%) died before 3 years and 8 underwent liver transplant before 3 years. Thus, 42% of the children in this series are surviving with native liver. Age at operation in P was significantly different compared with G. Preoperative values of bilirubin and alanine transaminase were comparable in the 3 groups. Postoperative values of bilirubin and alanine transaminase were lower in G and I compared with P Complications were significantly lower in group G. CONCLUSIONS: Portoenterostomy alone in biliary atresia is beneficial in 40% of cases. Factors associated with the outcome include age at operation, postoperative cholangitis, and change in values of bilirubin and alanine transaminase. A classification based on decline of bilirubin and enzyme levels 3 months after portoenterostomy is proposed to predict the long-term outcome of an individual case of biliary atresia. It is particularly relevant in the intermediate group in which timing of referral may preclude or compromise liver transplant.

Alanine Transaminase↗

Long-term outcome of Boix-Ochoa and Nissen fundoplication in normal and neurologically impaired children.

PURPOSE: The aim of this study was to compare the results of Boix-Ochoa and Nissen fundoplication performed in the authors' department in normal and neurologically impaired children. METHODS: The medical records of all children who underwent fundoplication in the span of 10 years from 1988 to 1997 were reviewed. Boix-Ochoa procedure was the preferred operation before 1993. Since 1993, the Nissen fundoplication has been used as the operation of choice for surgical antireflux treatment. RESULTS: A total of 109 fundoplications were performed during that period, of which 64.2% of the children involved were neurologically impaired. The Boix-Ochoa procedure and Nissen fundoplication were the 2 types of operations performed for antireflux surgical treatment. There were 22 recurrences of gastroesophageal reflux, 14 in the neurologically impaired group and 6 in the normal group. All except 2 recurrences were after the Boix-Ochoa procedure. Neurological impairment increased the morbidity rates after these procedures and dictated the effectiveness of the operation. Nissen fundoplication fared better in comparison with the Boix-Ochoa procedure in both the neurologically impaired and the normal group. CONCLUSIONS: Antireflux surgery is beneficial in children with significant gastroesophageal reflux, irrespective of their neurological status, although complications are more common in the neurologically impaired group. Nissen fundoplication is more effective and has fewer complications.

Case-Control Studies↗

PBF-2 is a novel single-stranded DNA binding factor implicated in PR-10a gene activation in potato.

Elicitor-induced activation of the potato pathogenesis-related gene PR-10a requires a 30-bp promoter sequence termed the ERE (elicitor response element) that is bound by the nuclear factor PBF-2 (PR-10a binding factor 2). In this study, PBF-2 has been purified to near homogeneity from elicited tubers through a combination of anion-exchange and DNA affinity chromatography. Evidence demonstrates that inactive PBF-2 is stored in the nuclei of fresh tubers and becomes available for binding to the ERE upon elicitation. A protein with an apparent molecular mass of 24 kD (p24) is a DNA binding component of PBF-2. A cDNA encoding p24 has been cloned and encodes a novel protein with a potential transcriptional activation domain that could also act as a single-stranded DNA binding domain. Both PBF-2 and the cDNA-encoded protein bind with high affinity to the single-stranded form of the ERE in a sequence-specific manner. The inverted repeat sequence of the ERE, TGACAnnnnTGTCA, is critical for binding of this factor in vitro and for PR-10a expression in vivo, supporting the role of PBF-2 as a transcriptional regulator.

Amino Acid Sequence↗

Retroperitoneoscopic excision of phaeochromocytoma--haemodynamic events, complications and outcome.

Over a period of 15 months, 11 patients with phaeochromocytoma underwent retroperitoneoscopic excision of their tumours. Five patients had bilateral tumours. All patients underwent thorough preoperative evaluation and preparation with alpha- and beta-blockade. In the majority of the patients a hypertensive response was seen during generation of pneumoretroperitoneum. However, the period of tumour dissection and excision was devoid of large haemodynamic fluctuations. The average time taken was 3.5 to 4 hours per gland. Blood loss in successful laparoscopic excision averaged 240 ml (range 120 to 700 ml). In these patients satisfactory postoperative analgesia could be provided with intramuscular pethidine or intramuscular diclofenac sodium. In three patients the procedure had to be converted to open laparotomy due to haemorrhage. All three patients had preoperative radiological evidence of inferior vena cava and aortic involvement. Patient selection plays an important role in a successful outcome.

Adrenal Gland Neoplasms↗

Profile of a menopause clinic in an urban population in Malaysia.

The object of this study is to determine the status of an urban Malaysian woman in her menopause age group with reference to her menopausal symptoms, lipid profile, breast, pelvis and bone. One hundred and sixty four women attending the Menopause Clinic of University Hospital, Kuala Lumpur who had not previously been on hormone replacement therapy were studied. Forty nine women were perimenopausal, 74 women were in early menopause (within 5 years of menopause) and 41 women were in late menopause (after 5 years of menopause). The most common symptoms were hot flushes (56%) and generalised tiredness (49%). Eighty four percent (84%) of women had high cholesterol levels. Serum triglycerides were highest in the late menopause group. There were 2 cases of intraductal carcinoma diagnosed on routine mammography, with 8 cases of fibrocystic breast disease and 7 cases of suspicious breast lumps. Routine ultrasound (pelvic and abdominal) revealed two women with ovarian cysts, 6 women with an endometrial thickness of more than 5 mm and 8 women with uterine fibroids. Eighty five women (51.8%) had mild osteoporosis while four women had moderate osteoporosis on dual photon measurements for bone mineral density. Menopause clinics should aim at investigating a woman in her menopause as a whole. Vasomotor symptoms were common in the urban Malaysian menopausal woman. There was a high incidence of lipid abnormalities. Routine mammography, pelvic ultrasound examinations and bone mineral density tests detected significant pathology and abnormalities.

Aged↗

Subcostal muscle-split incision in paediatric urology.

The subcostal muscle-split incision (SMSI) has been used in 108 consecutive operations for benign upper urinary tract disease. No wound-related complications have occurred. No conversion to other wounds has been required. The benefits of SMSI are described.

Adolescent↗

Elevated oxidative stress in models of normal brain aging and Alzheimer's disease.

Age-associated neurodegenerative disorders are becoming more prevalent as the mean age of the population increases in the United States over the next few decades. Both normal brain aging and Alzheimer's disease (AD) are associated with oxidative stress. Our laboratory has used a wide variety of physical and biochemical methods to investigate free radical oxidative stress in several models of aging and AD. Beta-amyloid (A beta), the peptide that constitutes the central core of senile plaques in AD brain, is associated with free radical oxidative stress and is toxic to neurons. This review summarizes some of our studies in aging and A beta-associated free radical oxidative stress and on the modulating effects of free radical scavengers on neocortical synaptosomal membrane damage found in aging and A beta-treated systems.

Aging↗

Antenatally detected pelvi-ureteric junction obstruction: concerns about conservative management.

OBJECTIVE: To review the conservative management of antenatally detected pelvi-ureteric junction (PUJ) obstruction in children. PATIENTS AND METHODS: The study included 121 children (142 kidneys) with antenatally diagnosed PUJ obstruction managed over an 8-year period, including 21 who were affected bilaterally; the main focus of the study was on the 100 children affected unilaterally. The intent was to manage these patients conservatively, with immediate surgery (early pyeloplasty) only if renal function was initially compromised (renographic function < 40%). The indications for surgery subsequently (delayed pyeloplasty) included either a deterioration in renal function, the onset of symptoms or increasing hydronephrosis. RESULTS: The anteroposterior diameter and renal function were weakly and negatively correlated. The kidneys in the delayed pyeloplasty group had a greater initial mean anteroposterior diameter than had those in the early or the conservative groups (P<0. 05). The improvement in renal function was the lower in the delayed pyeloplasty group than in the early pyeloplasty group; the improvement was inversely related to the anteroposterior diameter. CONCLUSIONS: The conservative management of some antenatally detected PUJ obstructions probably results in greater loss of function, which is not recovered after surgery.

Child, Preschool↗

Vitamin E as an antioxidant/free radical scavenger against amyloid beta-peptide-induced oxidative stress in neocortical synaptosomal membranes and hippocampal neurons in culture: insights into Alzheimer's disease.

Amyloid beta-peptide (Abeta), the major constituent in senile plaques in Alzheimer's disease (AD) brain, is thought by many researchers to be central to neurotoxicity in AD brain. Increasing evidence from many laboratories indicates that AD brain is under oxidative stress, with strong evidence of protein oxidation, lipid peroxidation, and peroxynitrite damage. A link between the central role of Abeta and oxidative stress in AD brain may be Abeta-associated free radical oxidative stress. If so, antioxidants such as vitamin E should modulate Abeta-induced oxidative damage and neurotoxicity in brain cells. This review summarizes studies of Abeta-associated free radical oxidative stress and its inhibition by vitamin E in cortical synaptosomal membranes and hippocampal neuronal cells in culture. Taken together with the recent report that vitamin E slows the progression of AD, this review strongly supports a central role of Abeta-associated free radical oxidative stress in neurotoxicity in AD brain.

Alzheimer Disease↗

Structural and functional changes in proteins induced by free radical-mediated oxidative stress and protective action of the antioxidants N-tert-butyl-alpha-phenylnitrone and vitamin E.

The free radical theory of aging proposes that reactive oxygen species (ROS) cause oxidative damage over the lifetime of the subject. It is the cumulative and potentially increasing amount of accumulated damage that accounts for the dysfunctions and pathologies seen in normal aging. We have previously demonstrated that both normal rodent brain aging and normal human brain aging are associated with an increase in oxidative modification of proteins and in changes in plasma membrane lipids. Several lines of investigation indicate that one of the likely sources of ROS is the mitochondria. There is an increase in oxidative damage to the mitochondrial genome in aging and a decreased expression of mitochondrial mRNA in aging. We have used a multidisciplinary approach to the characterization of the changes that occur in aging and in the modeling of brain aging, both in vitro and in vivo. Exposure of rodents to acute normobaric hyperoxia for up to 24 h results in oxidative modifications in cytosolic proteins and loss of activity for the oxidation-sensitive enzymes glutamine synthetase and creatine kinase. Cytoskeletal protein spin labeling also reveals synaptosomal membrane protein oxidation following hyperoxia. These changes are similar to the changes seen in senescent brains, compared to young adult controls. The antioxidant spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) was effective in preventing all of these changes. In a related study, we characterized the changes in brain protein spin labeling and cytosolic enzyme activity in a series of phenotypically selected senescence-accelerated mice (SAMP), compared to a resistant line (SAMR1) that was derived from the same original parents. In general, the SAM mice demonstrated greater oxidative changes in brain proteins. In a sequel study, a group of mice from the SAMP8-sensitive line were compared to the SAMR1-resistant mice following 14 days of daily PBN treatment at a dose of 30 mg/kg. PBN treatment resulted in an improvement in the cytoskeletal protein labeling toward that of the normal control line (SAMR1). The results of these and related studies indicate that the changes in brain function seen in several different studies may be related to the progressive oxidation of critical brain proteins and lipids. These components may be critical targets for the beneficial effects of gerontotherapeutics both in normal aging and in disease of aging.

Adult↗

Effects of mitochondrial respiratory stimulation on membrane lipids and proteins: an electron paramagnetic resonance investigation.

Previous studies have implicated mitochondria-derived reactive oxygen species (ROS) in both the aging process and age-related diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease etc. The current study, utilizing electron paramagnetic resonance (EPR) spectrometry, was designed to determine if mitochondrial respiratory stimulation, under state 4 conditions, caused extensive oxidative modifications to membrane cytoskeletal proteins and lipids in the brain. A mixed population of cortical synaptosomes and mitochondria, prepared by centrifugation techniques using rat brain cortex from adult (4-6 months) female Brown Norway rat brains, were labeled with the lipid-specific spin probe, 5-nitroxyl stearate (5-NS). Stimulation of the mitochondrial electron transport chain was accomplished using 20 mM succinate at 25 degrees C for 3 h. Mitochondrially derived free radicals, when reacted with the paramagnetic center of the spin probe, result in a loss of paramagnetism resulting in loss of intensity. A significant lowering (23%, P<0.0001) in the signal amplitude (B0) of 5-NS, indicative of generation of oxyradicals, was found. The order parameter, an inverse EPR-measure of membrane fluidity of the 5-NS spin labeled mitochondrial and synaptosomal membranes, also decreased following mitochondrial respiratory stimulation (P<0.005). Changes in the physical state of cytoskeletal and transmembrane proteins due to succinate oxidation were measured using MAL-6 (2,2,6, 6,-tetramethyl-4 maleimidopiperdin-1-oxyl), a thiol-specific nitroxide spin label. The ratio of the amplitudes of the weakly to strongly immobilized spin label reaction sites (W/S ratio) in the low-field region of the spectrum was used to determine any alteration in protein conformation. Previous studies in our laboratory have established that increased protein oxidation is associated with a decreased W/S ratio. In the current study, our results indicated significant lowering of the W/S ratio in cortex (30%, P<0.0001) upon stimulation of the mitochondria with 20 mM succinate. Thus, we conclude that respiratory stimulation of mitochondria, due to a hypermetabolic stress with succinate, caused significant oxidative modifications of cortical membrane lipids and proteins.

Animals↗

The free radical antioxidant vitamin E protects cortical synaptosomal membranes from amyloid beta-peptide(25-35) toxicity but not from hydroxynonenal toxicity: relevance to the free radical hypothesis of Alzheimer's disease.

Amyloid beta-peptide (Abeta) is a key factor in the neurotoxicity of Alzheimer's disease (AD). Recent research has shown that Abeta-mediated neurotoxicity involves free radicals and that Abeta peptides can initiate multiple membrane alterations, including protein oxidation and lipid peroxidation, eventually leading to neuronal cell death. Research also has emphasized the role of 4-hydroxynonenal (HNE), a downstream product of lipid peroxidation, in being able to mimic some of the effects of Abeta peptides. In the current investigation, electron paramagnetic resonance (EPR) studies of spin labeled cortical synaptosomal membrane proteins has been employed to study conformational changes in proteins, spectrophotometric methods have been used to measure protein carbonyl content, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for mitochondrial function has been used to study the effect of vitamin E on samples that were treated with Abeta or HNE. The free radical dependence of beta-amyloid-associated toxicity was confirmed by the ability of the free radical scavenger vitamin E to prevent the toxic effects of Abeta. In contrast, HNE was still toxic in the presence of vitamin E. These results support our Abeta-associated free radical model for neurotoxicity in AD brain and are discussed with reference to potential therapeutic strategies for AD.

Aldehydes↗

Delleman syndrome: anesthetic implications.

An infant with oculocerebrocutaneous (Delleman) syndrome (1), only 26 cases of which have been reported (2), presented with focal alopecia of scalp, periorbital skin appendages, hypertrophy of the skin (Fig. 1A), left-sided orbital cyst, lid coloboma, cleft palate (Fig. 1B), neonatal seizures, cerebral hemiatrophy, multiple intracranial cystic spaces, and enlarged lateral ventricles. The anomalies often require multiple anesthetics for examination of the eye, drainage of the orbital cyst, repair of lid coloboma, enucleation of the eye, excision of skin tags, and repair of cleft palate. Although this infant's perioperative course was uneventful, he had significant preoperative problems, such as neonatal seizures and an episode of aspiration pneumonia. Because the Delleman syndrome is rare, this case is presented to illustrate possible anesthetic implications of the disease.

Abnormalities, Multiple↗