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Biomedical subjects

K Shanmuganathan

Publications and source records attributed to K Shanmuganathan.

At least 55 records · Page 3Linked to original sources
PubMed1996

Detection of bleeding in patients with major pelvic fractures: value of contrast-enhanced CT.

OBJECTIVE: We performed a retrospective review of trauma patients who had undergone both pelvic angiography and preangiographic i.v. contrast-enhanced CT to determine whether CT can accurately demonstrate the presence or absence of pelvic bleeding in patients with multisystem trauma and major pelvic fractures. SUBJECTS AND METHODS: We reviewed the medical records and imaging studies of all patients, identified through a trauma radiology database, who had undergone pelvic angiography and preangiographic contrast-enhanced CT during a 48-month period. Results of CT scans were recorded by consensus interpretation of three radiologists without knowledge of angiographic findings. Sites of contrast material extravasation seen on CT scans were noted and compared with sites of bleeding or vascular injury identified by selective pelvic angiography. RESULTS: Thirty patients with blunt trauma and pelvic fractures underwent both pelvic angiography and preangiographic CT studies. Findings on pelvic angiograms were positive at 26 sites in 19 patients and included contrast agent extravasation at 23 sites and vessel abnormalities without extravasation at three sites. Preangiographic pelvic CT scans showed contrast agent extravasation at 20 sites in 16 patients. Three patients had no contrast agent extravasation demonstrated by CT but had bleeding demonstrated by angiography. CT detected bleeding in 16 of 19 patients who had extravasation or vascular injury demonstrated by angiography, for a sensitivity of 84%. Results of pelvic angiography were negative in 11 patients, and none had evidence of bleeding on preangiographic CT scans. Two sites of contrast agent extravasation identified in two patients by CT did not show bleeding at angiography, for a specificity of 85% for the detection of bleeding. The overall accuracy of CT for determining the presence or absence of bleeding was 90%. CONCLUSION: Knowledge of sites of ongoing hemorrhage is crucial for optimizing the sequence of diagnostic and therapeutic studies in patients with blunt trauma. Contrast-enhanced CT of the pelvis, which is often performed for hemodynamically stable trauma patients, is a noninvasive technique that is highly accurate in determining the presence or absence of ongoing pelvic hemorrhage. This information can assist in initial management decisions involving patients with multisystem trauma and major pelvic fractures.

Adolescent↗
PubMed1996

Traumatic isolation of the cervical articular pillar: imaging observations in 21 patients.

OBJECTIVE: Imaging studies of patients diagnosed with traumatic isolation of a cervical articular pillar were retrospectively reviewed to better understand the mechanism, clinical significance, and management requirements of this injury. MATERIALS AND METHODS: Imaging studies obtained before definitive treatment of 21 patients with traumatic isolation of a cervical articular pillar were reviewed to determine the level and mechanism of injury, fracture patterns, and associated fractures. Lateral cervical radiographs and axial and reformatted sagittal cervical CT images were obtained for all patients. Medical records were reviewed to ascertain the neurologic deficit, if any, and clinical management. RESULTS: Traumatic isolation of a cervical articular pillar was diagnosed at 24 levels in the 21 patients. The imaging studies indicated that the injury mechanisms producing isolation of the articular pillar were hyperflexion-rotation in 17 patients (81%), hyperflexion-distraction in three patients (14%), and hyperextension-rotation in one patient (5%). A fracture through the transverse foramen ipsilateral to the isolated articular pillar was observed in 19 patients (90%). Contralateral injuries at the level of the isolated articular pillar were present in 14 patients (67%). Neurologic deficits were present in 13 patients (62%) and included spinal cord injury (10) and radiculopathy (3). Eighteen patients underwent surgical reduction and internal stabilization. CONCLUSION: On the basis of an analysis of cervical radiography and CT findings, cervical spine fractures resulting in isolation of an articular pillar most commonly occur from hyperflexion-rotation or hyperflexion-distraction mechanisms. Previous literature has indicated that cervical hyperextension is responsible for this injury, but hyperextension accounted for only one case in this series. It is important to identify the isolated cervical articular pillar as a component of other cervical fracture patterns, as the injury creates two levels of mechanical instability requiring internal fixation of three contiguous vertebrae.

Adolescent↗
PubMed1996

MR imaging evaluation of hemidiaphragms in acute blunt trauma: experience with 16 patients.

OBJECTIVE: The aim of this retrospective study was to evaluate the usefulness of MR imaging in excluding or confirming the diagnosis of diaphragmatic injury after blunt trauma. MATERIALS AND METHODS: MR imaging studies were performed in 16 patients with blunt trauma and with indeterminate radiographs of the chest suspicious for but not diagnostic of diaphragmatic injury. T1-weighted images were obtained in all patients, and fast gradient-echo pulse sequence images were obtained in 11 patients. The results of all imaging studies performed before the MR imaging studies and those performed during out-patient follow-up, including chest radiography and thoracoabdominal CT scanning, were reviewed for evidence of diaphragmatic injury. Medical records were reviewed to ascertain the indications for the MR imaging studies as well as the surgical findings and the duration of outpatient follow-up. RESULTS: MR imaging studies confirmed diaphragmatic injury in seven patients (44%) and revealed an intact diaphragm in nine (66%). In seven patients MR imaging studies were able to correctly reveal the site of the diaphragmatic tear and the abdominal viscera that herniated into the thoracic cavity. None of the nine patients with intact diaphragms on MR imaging studies had delayed presentation of a diaphragmatic rupture on outpatient follow-up. CONCLUSIONS: MR imaging studies can be reliably used to diagnose or exclude injury in blunt trauma patients.

Acute Disease↗
PubMed1995

Pictorial review: CT appearances of contrast medium extravasations associated with injury sustained from blunt abdominal trauma.

Contrast-enhanced CT is a valuable imaging modality in detecting extravasation of intravascular, urinary tract of gastrointestinal contrast medium in major blunt trauma victims. This pictorial review illustrates the CT appearance associated with extravasation of contrast medium from these various sites and emphasizes features that differentiate among them.

Abdominal Injuries↗
PubMed1995

Use of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil as a novel antiviral agent for hepatitis B virus and Epstein-Barr virus.

A novel anti-hepatitis B virus (anti-HBV) agent, 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU), was synthesized and found to be a potent anti-HBV and anti-Epstein-Barr virus agent. Its in vitro potency was evaluated in 2.2.15 and H1 cells for anti-HBV and anti-Epstein-Barr virus activities, respectively. In vitro cytotoxicity in MT2, CEM, 2.2.15, and H1 cells was also assessed, and the results indicated high antiviral selectivities of L-FMAU in these cells.

Antiviral Agents↗
PubMed1995

CT evaluation of the liver with acute blunt trauma.

Computed tomography (CT) provides accurate assessment of blunt liver injuries. This article reviews the indications, technique, diagnosis, and role of CT in the management of liver injuries following blunt abdominal trauma. The spectrum of liver injuries and its complications seen on CT have been described and illustrated.

Abdominal Injuries↗
PubMed1994

Enhanced brain delivery of an anti-HIV nucleoside 2'-F-ara-ddI by xanthine oxidase mediated biotransformation.

In order to enhance the brain delivery of 2'-F-ara-ddI,2'-F-ara-ddP 6 was synthesized and its in vitro and in vivo bioconversion reaction studied. For the study, a new efficient synthetic method for 2'-F-ara-ddP 6 was developed from 5-benzoyl-1,2-O-isopropylidene-3-deoxyribose 1. For in vitro study 2'-F-ara-ddP was incubated in pH 2, mouse liver homogenate, and mouse serum at 37 degrees C. No degradation was observed in pH 2 and serum, while in liver homogenate 2'-F-ara-ddP was almost completely converted to 2'-F-ara-ddI within 20 min (t1/2 = 3.54 min). In order to determine the role of xanthine oxidase in the conversion of 2'-F-ara-ddP to 2'-F-ara-ddI, in vitro studies were conducted in phosphate buffer (pH 7.4) in the presence or absence of allopurinol, in which the half-lives of 2'-F-ara-ddP were 7.4 and 3.4 h, respectively, indicating the conversions were catalyzed by the xanthine oxidase. A similar experiment with aldehyde oxidase isolated from the human liver did not affect the biotransformation. The biotransformation was also detected in the brain homogenate, although the rate of conversion was low and incomplete. In order to assess the bioconversion in vivo, pharmacokinetic studies of 2'-F-ara-ddP and 2'-F-ara-ddI were conducted in mice. The maximum serum concentrations of 2'-F-ara-ddI administered itself and as 2'-F-ara-ddP reached 48.1 +/- 10.00 and 89.3 +/- 26.0 microM and were observed in 1 and 0.25 h, respectively. The data indicate that 2'-F-ara-ddI is absorbed at a slower rate than that of 2'-F-raa-ddP. The bioavailability of the prodrug after oral administration was 60.7%. The concentration of 2'-F-ara-ddI following oral administration of 2'-ara-ddI was close to the detection limits while 2'-F-ara-ddI was detected at significantly higher concentrations in the brain after oral administration of 2'-F-ara-ddP. From this study, we have administered the enhanced brain delivery of anti-HIV nucleoside utilizing an in vivo biotransformation system.

Administration, Oral↗
PubMed1994

Pharmacokinetics of the anticancer agent 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine in rats.

The pharmacokinetics of a new 2-halo-2'-deoxyadenosine analogue, 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) adenine [CL-F-ara-A], was characterized in rats following the development of a new high-performance liquid chromatography (HPLC) technique. This halogenated derivative was thought to have improved gastrointestinal stability that would facilitate oral administration. The HPLC method consisted of a single ethyl acetate extraction and reverse-phase chromatographic conditions. The method resulted in approximately 83% recovery of CL-F-ara-A from plasma and a sensitivity of 20 ng/ml. At i.v. doses of 10 and 25 mg/kg, the total clearance of CL-F-ara-A decreased from 2.1 to 1.5 l h-1 kg-1, with the reduction being attributed to saturation of metabolism. The elimination half-lives following i.v. bolus administrations were estimated to be a mean of 1.35 and 1.84 h at the two respective doses. The volume of distribution at steady state was not significantly different at the two doses, being 3.6 and 3.2 l/kg. The percentage of protein binding of CL-F-ara-A in rat plasma was only 13.3%. Administration of equivalent oral doses resulted in bioavailability estimates of approximately 50%, indicating that oral treatment regimens of CL-F-ara-A are feasible.

Adenine Nucleotides↗
PubMed1994

Rotational injury of cervical facets: CT analysis of fracture patterns with implications for management and neurologic outcome.

OBJECTIVE: Imaging studies of patients with rotational facet injuries of the cervical spine were retrospectively reviewed to determine the prevalence and pattern of associated fractures, to correlate injury pattern with recommended surgical stabilization, and to assess neurologic outcome. MATERIALS AND METHODS: Radiographs and CT scans obtained for 40 consecutive patients with rotational facet injuries of the cervical spine during a 70-month period were retrospectively reviewed to determine injury level, presence, and orientation of facet fractures, and concurrent nonfacet injuries. Imaging findings were reviewed to assess the likelihood of instability and to determine the most appropriate stabilization requirement. Medical records were reviewed to ascertain mechanism of injury, initial neurologic deficit, and surgical findings. RESULTS: Among the 40 patients with cervical rotational facet injuries, 11 (27%) had pure unilateral facet dislocation or subluxation without associated fractures, and 29 (73%) had concurrent facet fractures involving the inferior facet of the rotated vertebra (n = 13), the superior facet of the subjacent vertebra (n = 9), or both (n = 7). Injury of the rotated vertebra was unilateral in 22 patients but bilateral in 18 patients. Facet fractures frequently extended into the ipsilateral lamina or articular pillar or both. An avulsion fracture from the posteroinferior aspect of the rotated vertebral body, indicating disk disruption, occurred in 10 patients (25%), and seven patients (17%) had complete isolation of an articular pillar. Facet fractures were confirmed for 27 patients who underwent surgical stabilization. Neurologic deficits developed in 29 (73%) of the 40 patients and included radiculopathy in 11 patients and cord syndromes in 18 patients. Pure dislocation without a facet fracture was more likely to lead to a cord syndrome (p = .006). CONCLUSION: Cervical rotational facet injuries are often accompanied by facet fractures and bilateral damage of the rotated vertebra. These injuries contribute to rotational instability and require specific internal fixation based on a precise delineation of all injuries. Facet dislocations without fractures have a significantly higher association with cord syndromes than do rotational facet injuries with fractures. CT, particularly with parasagittal reformations, is valuable in identifying all injuries of the rotated and subjacent vertebrae.

Adolescent↗
PubMed1994

Diffuse small-bowel ischemia in hypotensive adults after blunt trauma (shock bowel): CT findings and clinical significance.

OBJECTIVE: The purpose of this study is to describe CT findings of shock bowel (diffuse abnormality of the small bowel observed in hypotensive or hypoperfused patients after blunt abdominal trauma) and to determine the clinical significance of CT-diagnosed shock bowel. MATERIALS AND METHODS: A data base search of a radiology data registry indicated 13 patients had CT scans obtained at admission that showed diffuse abnormalities of the small bowel and a corresponding medical history of profound clinical shock preceding CT study. All patients sustained blunt abdominal trauma: nine were involved in motor vehicle collisions, three were struck by motor vehicles, and one had a crushing injury. Vehicular impacts were typically high speed, inducing multisystem injury. Admission and follow-up CT studies were reviewed to characterize and assess the evolution of the abdominal CT findings that occur with shock bowel. Medical records were reviewed to determine blood pressure at the accident scene or on admission, surgical findings, and patient outcome. RESULTS: All patients were severely hypotensive in the field or on admission; three were in cardiac arrest at the scene of the accident. CT scans showed diffuse thickening of the small-bowel wall in all patients, ranging from 7 mm to 15 mm (mean, 11 mm); fluid-filled, dilated small bowel in nine patients; subjectively increased contrast enhancement of the small-bowel wall in six patients; and a flattened inferior vena cava (< 9 mm anteroposterior diameter at renal veins) in 10 patients. The colon appeared normal in all cases. Celiotomy in eight patients revealed normal-appearing small bowel by inspection in two and localized bowel injuries, with the remaining bowel appearing normal in six. Three patients, including one who had celiotomy, had normal-appearing small bowel on repeat CT scans obtained within 5 days of admission, and three had no clinical evidence of small-bowel disease. Three patients died of causes unrelated to bowel pathology. CONCLUSION: In trauma patients with hypotension, early abdominal CT may show diffuse abnormalities of the small bowel due to prolonged hypoperfusion--shock bowel--with a normal appearing colon. In this study, the CT findings of shock bowel were reversible and were not associated with clinical symptoms.

Abdominal Injuries↗
PubMed1993

Structure-activity relationships of beta-D-(2S,5R)- and alpha-D-(2S,5S)-1,3-oxathiolanyl nucleosides as potential anti-HIV agents.

The beta-D-(2S,5R)- and alpha-D-(2S,5S)-1,3-oxathiolanylpyrimidine and -purine nucleosides with natural nucleoside configuration were synthesized and evaluated against HIV-1 in human peripheral blood mononuclear (PBM) cells. The key intermediate 14, which was utilized for the synthesis of various nucleosides, was synthesized from D-mannose or D-galactose. Condensation of the acetate 14 with thymine, uracil, cytosine, and 5-substituted uracils and cytosines gave various pyrimidine nucleosides. The acetate 14 was also condensed with 6-chloropurine and 6-chloro-2-fluoropurine which were converted to various purine nucleosides. In the case of thymine, uracil, and 5-substituted uracil derivatives, most of the compounds did not exhibit any significant anti-HIV activity except 5-fluorouracil (alpha-isomer) derivative 55. Among 5-substituted cytosine analogues, 5-bromocytosine derivative (beta-isomer) 68 was found to be the most potent anti-HIV agent. In the case of purine derivatives, inosine analogue (beta-isomer) 78 was found to be the most potent anti-HIV agent in the 6-substituted purines and 2-amino-6-chloropurine derivative (beta-isomer) 90 showed the most potent activity in the 2,6-disubstituted purine series. The beta-isomers of 6-chloropurine (74), adenine (76), and N6-methyladenine (77) derivatives showed similar potencies against HIV-1, and the corresponding alpha-isomers also exhibited significant anti-HIV activity, although they were generally less potent than the beta-isomers.

Antiviral Agents↗
PubMed1993

L-beta-(2S,4S)- and L-alpha-(2S,4R)-dioxolanyl nucleosides as potential anti-HIV agents: asymmetric synthesis and structure-activity relationships.

In order to study the structure-activity relationships of L-(2S,4S)- and L-(2S,4R)-dioxolanyl nucleoside as potential anti-HIV agents, various enantiomerically pure L-(2S,4S)- and (2S,4R)-dioxolanylpyrimidine and -purine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear (PBM) cells. The enantiomerically pure key intermediate 8 has been synthesized in six steps from 1,6-anhydro-beta-L-gulose (2), and compound 8 was condensed with 5-substituted pyrimidines, 6-chloropurine, and 2,6-disubstituted purine to obtain various dioxolanylpyrimidine and -purine nucleosides, respectively. Among the compound synthesized, 5-fluorocytosine derivative 29 was found to exhibit the most potent anti-HIV activity (EC50 = 0.0012 microM) although it was toxic (IC50 = 10.0 microM). The order of anti-HIV potency of pyrimidine analogues was as follows: 5-fluorocytosine (beta-isomer) > cytosine (beta-isomer) > 5-fluorocytosine (alpha-isomer) > 5-iodocytosine (beta-isomer) > cytosine (alpha-isomer) > 5-bromocytosine (beta-isomer) > thymine (beta-isomer) > 5-methylcytosine (alpha-isomer) > 5-iodocytosine (alpha-isomer) > 5-chlorocytosine (beta-isomer). The anti-HIV potency of purine analogues was found to be in the following decreasing order: 2,6-diaminopurine (beta-isomer) > 2-chloroadenine (alpha-isomer) > 2-fluoroadenine (beta-isomer) > adenine (beta-isomer) > 2-amino-6-chloropurine (alpha-isomer) > 2-amino-6-chloropurine (beta-isomer) > guanine (beta-isomer) > 2-fluoroadenine (alpha-isomer) > adenine (alpha-isomer) > 2,6-diaminopurine (alpha-isomer) > N6-methyladenine (beta-isomer). It is interesting to note that the alpha-5-fluorocytosine analogue exhibited an excellent anti-HIV activity (EC50 = 0.063 microM) without cytotoxicity up to 100 microM in PBM cell.

Antiviral Agents↗
PubMed1993

Asymmetric synthesis and biological evaluation of beta-L-(2R,5S)- and alpha-L-(2R,5R)-1,3-oxathiolane-pyrimidine and -purine nucleosides as potential anti-HIV agents.

In order to study the structure-activity relationships of L-oxathiolanyl nucleosides as potential anti-HIV agents, a series of enantiomerically pure L-oxathiolanyl pyrimidine and purine nucleosides were synthesized and evaluated for anti-HIV-1 activity in human peripheral blood mononuclear (PBM) cells. The key intermediate 8 was synthesized starting from L-gulose via 1,6-thioanhydro-L-gulopyranose. The acetate 8 was condensed with thymine, 5-substituted uracils and cytosines, 6-chloropurine, and 6-chloro-2-fluoropurine to give pyrimidine and purine nucleosides. Upon evaluation of these final nucleosides, the 5-fluorocytosine derivative 51 was found to be the most potent compound among those tested. In the case of 5-substituted cytosine analogues, the antiviral potency was found to be in the following decreasing order: cytosine (beta-isomer) > 5-iodocytosine (beta-isomer) > 5-fluorocytosine (alpha-isomer) > 5-methylcytosine (alpha-isomer) > 5-methylcytosine (beta-isomer) > 5-bromocytosine (beta-isomer) > 5-chlorocytosine (beta-isomer). Among the thymine, uracil, and 5-substituted uracil derivatives, thymine (alpha-isomer) and uracil (beta-isomer) derivatives exhibited moderate anti-HIV activity. In the purine series, the antiviral potency is found to be in the following decreasing order: adenine (beta-isomer) > 6-chloropurine (beta-isomer) > 6-chloropurine (alpha-isomer) > 2-NH2-6-Cl-purine (beta-isomer) > guanine (beta-isomer) > N6-methyladenine (alpha-isomer) > N6-methyladenine (beta-isomer). The cytotoxicity was also determined in human PBM cells as well as Vero cells. None of the synthesized nucleosides was toxic up to 100 microM in PBM cells.

Antiviral Agents↗
PubMed1993

1,3-dioxolanylpurine nucleosides (2R,4R) and (2R,4S) with selective anti-HIV-1 activity in human lymphocytes.

In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV-1 agents, various enantiomers of pure dioxolanylpurine nucleosides were synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 1, which was synthesized in nine steps from 1,6-anhydro-beta-D-mannose, was condensed with 6-chloropurine, 6-chloro-2-fluoropurine, and 2,6-dichloropurine in the presence of TMS triflate. The chloro or fluoro substituents were readily converted into amino, N-methylamino, hydroxy, methoxy, thiol, and methylthio under appropriate reaction conditions. Upon evaluation of these dioxolanes, the guanine derivative 24 exhibited the most potent anti-HIV-1 activity without cytotoxicity up to 100 microM in various cells. The decreasing antiviral activity order of beta-isomers was as follows: guanine > 6-chloro-2-aminopurine > 2-fluoroadenine > or = adenine > or = 2,6-diaminopurine > hypoxanthine > 2-chloroadenine > 6-chloropurine approximately equal to N6-methyladenine approximately equal to 6-mercaptopurine approximately equal to 6-(methylthio)purine.

Antiviral Agents↗
PubMed1993

Complications of ultrasound-guided transperineal prostate biopsy. A prospective study.

A prospective study of the complications of transperineal prostate biopsy was undertaken in 171 patients; 150 (88%) returned a questionnaire 1 week after biopsy. The incidence of serious complications was low, with 1 patient requiring admission for presumed septicaemia and another developing acute retention of urine. Many patients had minor complications, with 42% having haematuria, 13% haemospermia and 31% pain. Only 18% needed analgesia following biopsy. Since transperineal prostate biopsy has such a low incidence of infective complications, we suggest that it should be considered in frail or elderly patients in whom septicaemia may be especially hazardous.

Biopsy, Needle↗
PubMed1993

Transsphenoid basilar skull fracture: CT patterns.

The authors studied computed tomographic (CT) scans obtained in 40 patients with transsphenoid basilar skull fractures to establish if there were reproducible patterns of fracture along lines of weakness. Medical records were reviewed. Four major fracture patterns were identified: anterior transverse (n = 22), lateral frontal diagonal (n = 7), posterior transverse (n = 16), and mastoid diagonal (n = 3). Eight patients had two fracture patterns. Eleven of 40 patients (28%) died as a result of their head injury. The diagonal patterns were statistically significantly more frequently associated with in-hospital mortality than were the transverse fractures (P = .014). Complications included blindness, cranial nerve injury, cerebrospinal fluid leak, and hearing loss. These results indicate that transsphenoid basilar skull fractures occur along reproducible lines of weakness, including a coronal plane through the anterior sphenoid body and pterygoid plates, a coronal plane through the posterior sphenoid body and clivus, and the sphenopetrosal synchondrosis.

Adolescent↗