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Biomedical subjects

S S Rao

Publications and source records attributed to S S Rao.

At least 19 recordsLinked to original sources
PubMed2001

Two distinct effects on neurotransmission in a temperature-sensitive SNAP-25 mutant.

Vesicle fusion in eukaryotic cells is mediated by SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors). In neurons, the t-SNARE SNAP-25 is essential for synaptic vesicle fusion but its exact role in this process is unknown. We have isolated a SNAP-25 temperature-sensitive paralytic mutant in Drosophila, SNAP-25(ts). The mutation causes a Gly50 to Glu change in SNAP-25's first amphipathic helix. A similar mutation in the yeast homologue SEC9 also results in temperature sensitivity, implying a conserved role for this domain in secretion. In vitro-generated 70 kDa SNARE complexes containing SNAP-25(ts) are thermally stable but the mutant SNARE multimers (of approximately 120 kDa) rapidly dissociate at 37 degrees C. The SNAP-25(ts) mutant has two effects on neurotransmitter release depending upon temperature. At 22 degrees C, evoked release of neurotransmitter in SNAP-25(ts) larvae is greatly increased, and at 37 degrees C, the release of neurotransmitter is reduced as compared with controls. Our data suggest that at 22 degrees C the mutation causes the SNARE complex to be more fusion competent but, at 37 degrees C the same mutation leads to SNARE multimer instability and fusion incompetence.

Amino Acid Sequence↗
PubMed2001

Manometric assessment of anorectal function.

A diagnostic test is useful if it can provide information regarding the underlying pathophysiology, confirm a clinical suspicion, or guide clinical management. In a prospective study, anorectal manometry was shown not only to confirm a clinical impression, but also to provide new information that was not detected clinically. The information obtained from these studies influenced the management and outcome of patients with defecation disorders (Table 1). These findings have been confirmed further by another study that showed colorectal physiologic tests provided a definitive diagnosis in 75% of patients with constipation, 66% of patients with incontinence, and 42% of patients with intractable anorectal pain. A systematic and careful appraisal of anorectal function can provide invaluable information that can guide treatment of patients with anorectal disorders. A more uniform method of performing these tests and interpreting the results is needed to facilitate a wider use of this technology for the assessment of patients with anorectal disorders.

Humans↗
PubMed2001

Clinical neurophysiology and electrodiagnostic testing of the pelvic floor.

This article summarizes our current understanding of the neuroanatomy and neurophysiology of the pelvic floor. The electrodiagnostic evaluation of the pelvic floor muscles and external anal sphincter, including pudendal nerve conduction studies, sacral reflexes, and needs EMG is presented. The discussion reviews the test methodology, the strengths and limitations of each test, and their clinical utility. The authors have tried to critically review the objective evidence to support the use of electrodiagnostic tests in the evaluation and management of pelvic floor disorders. The reader will have a better understanding of the rationale, methodology, clinical utility, and potential pitfalls for each of the commonly used neurophysiological tests of the pelvic floor.

Electrodiagnosis↗
PubMed2001

Dyssynergic defecation.

Dyssynergic defecation is a common clinical problem that affects half of patients with chronic constipation. In many patients, there is a significant overlap with slow transit constipation. The chief underlying pathophysiologic mechanism is a failure of rectoanal coordination. By using a combination of history, prospective stool diaries, detailed clinical evaluation, and anorectal physiologic tests, it is possible to diagnose this problem. Controlled trials are under way to evaluate the efficacy of biofeedback therapy. Meanwhile, it is possible to treat most patients by using neuromuscular conditioning and biofeedback therapy. Further refinements in diagnostic criteria and in rehabilitation therapy programs should facilitate better diagnosis and treatment of patients with dyssynergic defecation.

Abdominal Muscles↗
PubMed2001

Altered periodic rectal motor activity: a mechanism for slow transit constipation.

The pathophysiology of slow transit constipation is poorly understood. Both decreased and increased distal colonic motility have been reported. In healthy humans, a 3 cycles per minute (cpm), periodic rectal motor activity (PRMA) has been described. Our aim was to investigate the characteristics of PRMA and to assess its role in the pathogenesis of constipation. A six-sensor solid-state probe was placed with the tip sensor in the mid-transverse colon, without sedation, and prolonged colonic motility was recorded in nine patients with slow transit constipation (1M, 8F) and in 11 healthy subjects (3M, 8F). Subjects were free to ambulate. We examined the frequency, nocturnal vs. diurnal variation, and characteristics of PRMA, and its relationship to proximal colonic motility. All subjects showed PRMA. The rhythm was similar (2.5-4 cpm) in both groups. However, constipated patients exhibited a greater (P < 0.001) number of PRMA cycles than controls. The duration of each cycle and amplitude of pressure waves during PRMA were also greater (P < 0.05) at night in patients compared with controls. In patients, 40% of PRMA cycles were associated with a proximal colonic motor event compared with 81% in controls (P < 0.02). The area under the curve of all colonic pressure waves and incidence of specialized propagating pressure waves was lower (P < 0.05) in patients during daytime. When compared with controls, constipated patients exhibited reduced daytime colonic pressure waves and a higher frequency of PRMA. Most of the PRMA was unrelated to proximal colonic activity in constipated patients in contrast with findings in control patients. In addition to decreased colonic motility, this excessive and unco-ordinated phasic rectal activity may further impede stool transport and contribute to the pathogenesis of slow transit constipation.

Adult↗
PubMed2001

Rhinoorbitocerebral actinomycosis.

PURPOSE: To report a case of actinomycotic orbital abscess with subdural empyema and pansinusitis, an unusual presentation of a rarely seen infection. METHODS: Case report. RESULTS: A 35-year-old man sought treatment for signs and symptoms of an orbital abscess 22 days after a dental extraction. Computed tomography demonstrated a left orbital abscess with left pansinusitis and a large subdural empyema. Surgical clearance of all purulent material was done followed by prolonged penicillin therapy. Culture of pus from all sources yielded Actinomycosis israelii. At the time of discharge and 1-month follow-up, the patient had 20/20 vision with no neurologic deficits. CONCLUSIONS: In orbital infections with atypical presentations, unusual pathogens should be considered as the causative agents.

Abscess↗
PubMed2001

Pathophysiology of chest pain in patients with nutcracker esophagus.

OBJECTIVES: Nutcracker esophagus is a manometric pattern that is commonly seen in patients with functional (noncardiac) chest pain. However, this pattern is often unassociated with pain. Consequently, the pathophysiology of chest pain in these patients is unclear. METHODS: We prospectively examined the sensory perception and biomechanical properties of the esophagus in 10 patients with chest pain and a nutcracker esophagus, along with those properties in 12 healthy controls using impedance planimetry. RESULTS: Stepwise balloon distentions reproduced typical chest pain in 9/10 (90%) patients. The threshold for chest pain was lower (p < 0.05) in patients than in controls (mean +/- SD 43+/-5 vs 62+/-4 cm H2O) but only 2/12 controls experienced pain. The thresholds for first perception and moderate discomfort were also lower (18+/-8 vs 30+/-11 cm H2O, p < 0.01 and 28+/-9 vs 62+/-5 cm H2O, p < 0.001) in patients than in controls, but only 3/12 controls experienced moderate discomfort. The esophageal reactivity to balloon distention was higher in patients than in controls (p < 0.001). The tension-strain curve shifted to the left in the patient group when compared to that in the controls (p < 0.05). CONCLUSIONS: Patients with a nutcracker esophagus demonstrate a hypersensitive and stiff esophagus. Because balloon distention reproduced their chest pain, visceral hyperalgesia of the esophagus may be relevant to the pathogenesis of their pain. Balloon distention test may be more useful in the evaluation of patients with functional chest pain and a nutcracker esophagus.

Adult↗
PubMed2001

Functional chest pain of esophageal origin: hyperalgesia or motor dysfunction.

OBJECTIVE: Many patients with functional (noncardiac) chest pain exhibit both hypersensitivity and motor dysfunction of the esophageal wall. We aimed to determine whether the sensory or motor dysfunction plays an important role in the pathogenesis of chest pain. METHODS: We performed graded balloon distentions of the esophagus using impedance planimetry in 16 consecutive patients with chest pain and otherwise normal cardiac and esophageal evaluations and in 13 healthy controls. In those patients who experienced chest pain with balloon distention, the test was repeated after atropine was given. Sensory and biomechanical parameters were measured. RESULTS: Balloon distention reproduced typical chest pain in 13/16 patients (81%) and at lower (p < 0.01) sensory thresholds than controls. Pain was reproduced in all 13 patients and at lower (p < 0.05) sensory thresholds after atropine. Also, after atropine, the esophageal cross-sectional area and wall tension increased (p < 0.05), the tension/strain association shifted to the right (p < 0.05), and reactivity decreased (p < 0.002) relative to results before atropine or in healthy controls (i.e., the esophageal wall relaxed and became more deformable). CONCLUSIONS: Even after relaxing the esophageal wall, most patients experienced chest pain and at lower sensory thresholds. Hence, hyperalgesia rather than motor dysfunction appears to be the predominant mechanism for functional chest pain of esophageal origin.

Adult↗
PubMed2001

Ambulatory 24-h colonic manometry in healthy humans.

Our aim was to investigate motor activity of the healthy, relatively unprepared colon in the ambulatory state. Twenty-five age- and gender-matched adults had a six-sensor solid-state probe inserted into the proximal transverse colon without sedation. Subjects ambulated freely and ate standard meals. In 528 h of recording, we found a lower (P < 0.05) area under the curve during the night. Waking induced a threefold increase in motility, whereas meals induced a twofold increase. Women showed less activity (P < 0.05) in the transverse/descending colon than men. The transverse/descending colon showed more (P < 0.05) activity than the rectosigmoid colon. Seven patterns were recognized; predominantly, they were simultaneous, propagated, or periodic bursts of 3-cycles/min (cpm) waves. A specialized propagating pressure wave with a high amplitude (>105 mmHg) and a prolonged duration (>14 s) occurred in all subjects (mean 10/day), mostly after waking, after meals, or with defecation. A 3-cpm motor activity was seen in the rectosigmoid region predominantly at night. The colon exhibits a wide spectrum of pressure activity around the clock, with gender and regional differences and circadian rhythm. This comprehensive study provides qualitative and quantitative normative data for colonic manometry.

Aged↗
PubMed2000

Investigation of dissolution enhancement of itraconazole by solid dispersion in superdisintegrants.

Solid dispersions of itraconazole (ITR) in lactose, microcrystalline cellulose (MCC), and three superdisintegrants (Primogel, Kollidon CL, and Ac-Di-Sol) and their formulation into tablets were investigated with an objective of enhancing the dissolution rate of ITR from tablet formulations. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to characterize the dispersions. A marked enhancement in the dissolution rate of ITR was observed with all the excipients. The order for the excipients to enhance the dissolution rate was Ac-Di-Sol > Kollidon CL > Primogel > MCC > lactose. Solid dispersions in superdisintegrants gave much higher rates of dissolution than the dispersions in other excipients. Ac-Di-Sol gave the most improvement (28-fold) in the dissolution rate of ITR at a 1:1 drug:excipient ratio. Solid dispersions in superdisintegrants could be formulated into tablets. These tablets, apart from fulfilling all official and other specifications, exhibited higher rates of dissolution and dissolution efficiency (DE) values. XRD indicated the presence of ITR in amorphous form in the dispersions. DSC indicated a weak interaction between ITR and the excipients. Micronization and conversion of the drug into the amorphous form and the fast disintegrating and dispersing action of the superdisintegrants contribute to the enhancement of the dissolution rate of ITR from its solid dispersions in superdisintegrants and their corresponding tablet formulations.

Antifungal Agents↗
PubMed2000

Effects of fat and carbohydrate meals on colonic motor response.

BACKGROUND: Ingestion of a meal stimulates colonic motility. It is unclear whether the nutrient composition of a meal affects colonic motor response. AIMS: To investigate and compare the effects of a predominantly fat or carbohydrate meal on colonic motility. METHODS: In 18 healthy subjects, ambulatory colonic manometry was performed by placing a six sensor, solid state probe from the mid-transverse colon to the rectum. In a randomised, crossover design, 10 and 27 hours after probe placement, subjects received 4.18 MJ meals containing 60% calories from fat or carbohydrate sources. Preprandial and postprandial pressure activity and motor patterns were evaluated. RESULTS: Both meals induced phasic activity with a greater area under the curve (p<0.03) in the first postprandial hour, compared with the control period. Fat induced motor activity persisted longer (p<0.05) than that of the carbohydrate meal, but the onset of motor response was slower (p<0.001). Although both meals induced more (p<0.001) propagating pressure waves, only the fat meal induced more (p<0.05) simultaneous and retrograde waves. After both meals, 50% of subjects exhibited high amplitude (more than 103 mm Hg), prolonged duration (more than 13 seconds) propagating waves. Both meals induced greater activity (p<0.05) in the transverse/descending colon than in the rectosigmoid colon. CONCLUSIONS: Carbohydrate meals induce colonic motor response, but the effects are short lived when compared with fat meals. The prolonged, segmental, and retrograde phasic activity induced by the fat meal may delay colon transit. Thus meal composition influences colonic motor response.

Adult↗
PubMed2000

Perspectives of an African American mother on parent-professional relationships in special education.

A case study focused on the perspectives of a low-income, African American mother of a child with disabilities was presented. How an African American parent may begin to perceive characteristics of special education services and aspects of professional behavior as problematic was discussed as was her growing dissatisfaction with the services and eventual decision to withdraw her participation in the special education process The mother's perspective on specific encounters with professionals and the cumulative ways in which these encounters build toward her sense of growing dissatisfaction have implications for professional practice. Further understanding of how African American parents perceive their initial interactions with professionals and how they come to interpret these interactions may contribute towards building increased parental participation and parental satisfaction.

Adult↗
PubMed1999

Preferential Zn2+ influx through Ca2+-permeable AMPA/kainate channels triggers prolonged mitochondrial superoxide production.

Synaptically released Zn2+ can enter and cause injury to postsynaptic neurons. Microfluorimetric studies using the Zn2+-sensitive probe, Newport green, examined levels of [Zn2+]i attained in cultured cortical neurons on exposure to N-methyl-D-asparte, kainate, or high K+ (to activate voltage-sensitive Ca2+ channels) in the presence of 300 microM Zn2+. Indicating particularly high permeability through Ca2+-permeable alpha-amino3-hydroxy-5-methyl-4-isoxazolepropionic-acid/kainate (Ca-A/K) channels, micromolar [Zn2+]i rises were observed only after kainate exposures and only in neurons expressing these channels [Ca-A/K(+) neurons]. Further studies using the oxidation-sensitive dye, hydroethidine, revealed Zn2+-dependent reactive oxygen species (ROS) generation that paralleled the [Zn2+]i rises, with rapid oxidation observed only in the case of Zn2+ entry through Ca-A/K channels. Indicating a mitochondrial source of this ROS generation, hydroethidine oxidation was inhibited by the mitochondrial electron transport blocker, rotenone. Additional evidence for a direct interaction between Zn2+ and mitochondria was provided by the observation that the Zn2+ entry through Ca-A/K channels triggered rapid mitochondrial depolarization, as assessed by using the potential-sensitive dye tetramethylrhodamine ethylester. Whereas Ca2+ influx through Ca-A/K channels also triggers ROS production, the [Zn2+]i rises and subsequent ROS production are of more prolonged duration.

Calcium↗
PubMed1999

A novel clinical application for endoscopic mucosal clipping.

BACKGROUND: Endoscopic hemoclipping has been shown to be effective in the treatment of gastrointestinal bleeding. Here we describe a novel clinical application for endoscopic application of metal clips. METHODS: A middle-aged man with inoperable squamous cell cancer of the esophagus underwent per protocol a barium esophagogram to document tumor margins prior to radiation therapy. This study failed to localize the full extent of the tumor. At endoscopy, the tumor margins were clearly visible. To delineate the proximal and distal margins, detachable metallic clips were passed through the accessory channel of a standard endoscope and using a clip fixing device the clips were placed at each level. Subsequently, a chest x-ray was obtained. RESULTS: Placement of mucosal clips facilitated radiotherapy. CONCLUSIONS: Endoscopic mucosal clipping may serve as a useful technique for localizing or marking gastrointestinal lesions, especially for demarcating a precise radiation field when conventional techniques fail.

Carcinoma, Squamous Cell↗
PubMed1999

Three dimensional upper extremity motion during manual wheelchair propulsion in men with different levels of spinal cord injury.

This investigation compared three dimensional upper extremity motion during wheelchair propulsion in persons with 4 levels of spinal cord injury: low paraplegia (n=17), high paraplegia (n=19), C7 tetraplegia (n=16), and C6 tetraplegia (n=17). Upper extremity motion was recorded as subjects manually propelled a wheelchair mounted on a stationary ergometer. For all motions measured, subjects with paraplegia had similar patterns suggesting that the wheelchair backrest adequately stabilizes the trunk in the absence of abdominal musculature. Compared with paraplegic subjects, those with tetraplegia differed primarily in the strategy used to contact the wheel. This was most evident among subjects with C6 tetraplegia who had greater wrist extension and less forearm pronation.

Adult↗
PubMed1999

Analysis of photocontrol of aspartate kinase in barley (Hordeum vulgare L.) seedlings.

Aspartate kinase (AK) activity is regulated by light. The activity was more in light exposed barley seedlings than those grown in the dark. The light effect was manifested even with small exposures of 5 min duration and red light was more effective than white light in this respect. The effect of 5 min red light could be reversed by a 5 min pulse of far-red light indicating the involvement of phytochrome in this response. The phytochrome is also involved in long term light effects (24 hr exposures with white light). Ca++ takes part in the signal transduction pathway for this light response. Western blot analysis using antibodies raised against the purified lysine- and threonine-sensitive AK isoenzymes from spinach leaves showed no cross reaction with the antibodies to the threonine-sensitive AK in the dark and 5 min far-red light exposed seedlings. But the protein band was detected in the white and red lights. Northern blot analysis of seedlings grown under dark and exposed to white, red and far-red lights and probed with the gene encoding aspartokinase-homoserine dehydrogenase (AKHSD) protein indicated that the gene was differentially expressed. In dark grown seedlings, AKHSD transcript was in low concentration as compared to white light where the transcript concentration was high. A 5 min red light pulse increased the transcript concentration significantly in contrast to 5 min far-red light. The transcript concentration was reduced when 5 min red light was followed by a 5 min far-red light pulse. The AK activity in dark-raised seedlings is attributed to the presence of only one isoenzyme that is sensitive to lysine but insensitive to Ca++ and calmodulin (CAM). In both white and red light exposed seedlings, three isoenzymes of AK were detected. Two of these were sensitive to threonine while one was sensitive to lysine. Both of the threonine sensitive isoenzymes were activated by Ca++ and CAM. Also one of these isoenzymes seems to be located and synthesized in chloroplasts because its synthesis was completely inhibited by chloramphenicol but not by cycloheximide.

Aspartate Kinase↗