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Biomedical subjects

T Sullivan

Publications and source records attributed to T Sullivan.

At least 55 records · Page 3Linked to original sources

Generalized nonconvulsive status epilepticus after electroconvulsive therapy.

Status epilepticus is a rare complication of conventional single-stimulus electroconvulsive therapy (ECT). We report a case of ECT-induced nonconvulsive generalized status epilepticus (NGS) that lasted 3.5 days. The patient showed regressed psychotic behavior coupled with waxing and waning mutism and unresponsiveness as well as subtle unilateral motor signs. The diagnosis of NGS requires electroencephalographic confirmation.

Adult↗

Evidence that CYP2C19 is the major (S)-mephenytoin 4'-hydroxylase in humans.

The present study assesses the role of members of the human CYP2C subfamily in the 4'-hydroxylation of (S)-mephenytoin. When recombinant CYP2C proteins were expressed using a yeast cDNA expression system, 2C19 stereospecifically 4'-hydroxylated (S)-mephenytoin with a turnover number at least 10 times higher than that of human liver microsomes. 2C9 (both Ile359 and Leu359 alleles) and 2C18 (Thr385 and Met385 alleles) metabolized this substrate at a rate 100-fold lower than 2C19, and metabolism by these 2C proteins was not stereospecific for the S-enantiomer. 2C8 exhibited very little mephenytoin 4'-hydroxylase activity. In contrast, the Ile359 allele of 2C9 had a high turnover number for the hydroxylation of tolbutamide, while the Leu359 allele was less active toward this substrate. Immunoblot analysis of 16 human liver donor samples indicated that (S)-mephenytoin 4'-hydroxylase activity correlated with the hepatic CYP2C19 content, but it did not correlate with the hepatic content of CYP2C9. Moreover, direct sequencing of the polymerase chain reaction (PCR) products of 2C9 mRNA from six of these human livers through areas of known allelic variations indicated that the identity of the allele of 2C9 (Cys144 vs Arg, Tyr358 vs Cys, Ile359 vs Leu, or Gly417 vs Asp) did not appear to influence (S)-mephenytoin 4'-hydroxylase activity in these samples. These data indicate that 2C19 is the principal determinant of (S)-mephenytoin 4'-hydroxylase activity in human liver.

Aryl Hydrocarbon Hydroxylases↗

Rat embryo cells immortalized with transfected oncogenes are transformed by gamma irradiation.

Cesium-137 gamma rays were used to transform rat embryo cells (REC) which were first transfected with activated c-myc or c-Ha-ras oncogenes to produce immortal cell lines (REC:myc and REC:ras). When exposed to 6 Gy of 137Cs gamma rays, some cells became morphologically transformed with focus formation frequencies of approximately 3 x 10(-4) for REC:myc and approximately 1 x 10(-4) for REC:ras, respectively. Cells isolated from foci of gamma-ray-transformed REC:myc (REC:myc:gamma) formed anchorage-independent colonies and were tumorigenic in nude mice, but foci from gamma-ray-transformed REC:ras (REC:ras:gamma) did not exhibit either of these criteria of transformation. Similar to the results with gamma irradiation, we observed a sequence-dependent phenomenon when myc and ras were transfected into REC, one at a time. REC immortalized by ras transfection were not converted to a tumorigenic phenotype by secondary transfection with myc, but REC transfected with myc were very susceptible to transformation by subsequent ras transfection. This suggests that myc-immortalized cells are more permissive to transformation via secondary treatments. In sequentially transfected REC, myc expression was high whether it was transfected first or second, whereas ras expression was highest when the ras gene was transfected secondarily into myc-containing REC. Molecular analysis of REC:ras:gamma transformants showed no alterations in structure of the transfected ras or of the endogenous ras, myc, p53, or fos genes. The expression of ras and p53 was increased in some isolates of REC:ras:gamma, but myc and fos expression were not affected. Similarly, REC:myc:gamma transformants did not demonstrate rearrangement or amplification of the transfected or the endogenous myc genes, or of the potentially cooperating Ha-, Ki-, or N-ras genes. Northern hybridization analysis revealed increased expression of N-ras in two isolates, REC:myc:gamma 33 and gamma 41, but no alterations in the expression of myc, raf, Ha-ras, or Ki-ras genes in any REC:myc transformant. DNA from several transformed REC:myc:gamma cell lines induced focus formation in recipient C3H 10T1/2 and NIH 3T3 cells. The NIH 3T3 foci tested positive when hybridized to a probe for rat repetitive DNA. A detailed analysis of the NIH 3T3 transformants generated from REC:myc:gamma 33 and gamma 41 DNA failed to detect Ha-ras, Ki-ras, raf, neu, trk, abl, fms, or src oncogenes of rat origin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Watershed infarcts, Tc-99m HMPAO SPECT and CT correlation. Case reports.

We report on the use of Tc-99m hexamethylpropylene amineoxime (HMPAO) in watershed infarcts in five patients who had focal neurologic symptoms. Good correlation between Tc-99m HMPAO and CT was found in two patients. In three patients only Tc-99m HMPAO SPECT in a watershed distribution showed a perfusion abnormality that explained the clinical findings. Tc-99m HMPAO SPECT may be more sensitive than CT in the detection of infarctions in the watershed distribution.

Adult↗

Changes in the steady-state pharmacokinetics of theophylline during treatment with dirithromycin.

The steady-state plasma concentrations and pharmacokinetic characteristics of theophylline were studied during intermittent treatment with dirithromycin. The addition of dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained-release theophylline dosing regimen (200 mg every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline. Mean steady-state plasma theophylline trough concentrations (Cmin) were invariant before, during, and after dirithromycin treatment; however, mean average steady-state plasma theophylline concentrations (Cav) declined by 18% during dirithromycin treatment (P less than .05), and mean peak plasma concentrations (Css,max) declined by 26% (P less than .01). Theophylline clearance (CL/F) exhibited an increase of comparable magnitude during dirithromycin treatment, although the increase in CL/F was not statistically significant (.05 less than P less than .1). Dirithromycin treatment alters the steady-state pharmacokinetics of theophylline; however, the magnitude of the changes is small and is not likely to modify treatment outcomes.

Administration, Oral↗

Substance use in borderline personality disorder.

The authors investigated the prevalence of substance abuse in 137 inpatients with DSM-III borderline personality disorder. Ninety-two (67%) of these patients were given DSM-III substance use disorder diagnosis. The most frequently used substances were alcohol and sedative-hypnotics. When substance abuse was not used as a diagnostic criterion for borderline personality disorder, 32 (23%) of the 137 patients no longer met borderline criteria. These patients differed significantly from the rest of the patients in severity and course of illness. These data suggest that there might be a subgroup of borderline patients for whom substance use plays a primary role in the development of borderline psychopathology.

Adult↗

Effects of trihexyphenidyl on plasma chlorpromazine in young schizophrenics.

This study investigated the effects of trihexyphenidyl on chlorpromazine (CPZ) plasma levels and clinical state in 20 relatively young schizophrenic patients diagnosed using the DSM-III. Spontaneous changes in CPZ plasma levels over time were also examined. Trihexyphenidyl significantly increased CPZ plasma levels (average 41%) but did not produce clinical change. The trihexphenidyl-induced increase in CPZ plasma levels was independent of CPZ oral dosage and of CPZ plasma levels. Chlorpromazine plasma levels decreased non significantly (about 13%) over the four weeks following steady state, but there was marked inter-subject variability, and CPZ levels rose in some subjects. Although identical CPZ doses produced widely variable plasma levels, CPZ plasma levels correlated significantly with oral dose. The views that antiparkinsonian drugs interfere with neuroleptic efficacy, and do so by lowering neuroleptic plasma levels, are questioned.

Adolescent↗

Animal model for evaluating bone repair with and without adjunctive hyperbaric oxygen therapy (HBO): comparing dose schedules.

The effect of hyperbaric oxygen (HBO) on the healing of standardized metaphyseal defects in the cortices of rat femurs was studied. The question was whether a known total amount of HBO given twice a day (BID) would have a different effect than once a day (QD) treatments. A microvascular casting technique was developed whereby vessel ingrowth at the repair site could be monitored using scanning electron microscopy (SEM). Bone repair morphology was evaluated by light microscopy (LM) and various tissue components were quantified by histomorphometry (HM). Animals were sacrificed 1, 2, 3, or 5 weeks postoperatively. SEM revealed that endosteal bone ingrowth was totally responsible for the repair of the cortical defects. Moreover, endosteal vessel ingrowth did not differ between controls and either group of HBO treated animals. LM displayed enchondral ossification in controls and BID treated animals and a pronounced osteoclastic activity in the latter group throughout the repair process. By contrast the QD treated group healed by primary ossification. Judged by the HM data, QD treatment appeared to accelerate bone repair and vessel ingrowth compared to controls, while BID treatment seemed to retard these processes.

Animals↗

Effect of serial casting for the prevention of equinus in patients with acute head injury.

Ten adults with traumatic head injury received serial casts within 14 days of injury for the prevention or correction of equinus. Eighteen limbs (16 bilateral) with spasticity were involved. An average of five casts for a total duration of four to 64 days were used for each limb. Comparisons of passive dorsiflexion measures before and after casting showed a mean gain of 21 degrees (paired t-test, P less than .05). Of the 18 limbs, 13 reached a passive dorsiflexion of 0 degrees or more (ie, no equinus) which could be maintained without force for at least one hour. The procedures appeared safe and the results of the trial were clinically judged to be favorable. There is a need to further assess the efficacy of serial casting through randomized controlled trials and long-term followups.

Adult↗

Hepatic rupture in pregnancy.

Hepatic rupture is a rare and serious complication of pregnancy. A case of hepatic rupture is presented along with a review of the recent literature.

Adult↗

Comorbidity of borderline personality disorder.

In a retrospective study of 180 inpatients with DSM-III borderline personality disorder (BPD), the degree and direction of psychiatric comorbidity were used to examine the extent to which BPD is a homogeneous entity with clearly defined boundaries. Ninety-one percent of patients with BPD had one additional diagnosis, and 42% had two or more additional diagnoses. Both patients with BPD and controls with other personality disorders had similar rates and directions of comorbidity. The two groups did not differ significantly in prevalence of affective disorder. The DSM-III BPD appears to constitute a very heterogeneous category with unclear boundaries, overlapping with many different disorders but without a specific association with any one Axis I disorder. Comorbidity in patients with BPD may reflect base rates of psychopathology rather than anything inherent to BPD. Future studies should control for comorbidity to ensure homogeneity of comparison groups.

Adolescent↗

Suicide attempts in patients with borderline personality disorder.

Among 180 patients with DSM-III borderline personality disorder, patients with concurrent affective and substance use disorders had a higher rate of serious suicide attempts than other patients. Clinicians should be alert to axis I disorders in assessing suicide potential in borderline patients.

Adult↗

Chemiluminescent responses of macrophages exposed to biomaterials: a biocompatibility screening test.

Chemiluminescence (CL) response of alveolar macrophages (AM) exposed to either phagocytosable or nonphagocytosable particles of polymethylmethacrylate (PMMA) or titanium in vitro was monitored. The results were correlated to known in vivo bone tissue compatibility of the materials. Moreover, the quantity and morphology of adherent AM on titanium and PMMA disks were assessed using scanning electron microscopy (SEM). Our results with PMMA indicated that a high CL response to phagocytosable as well as nonphagocytosable particles of the biomaterial in question, correlated with poor bone tissue compatibility. By contrast, a low CL response to phagocytosable particles and no response to nonphagocytosable particles correlated with a satisfactory bone tissue compatibility, as in the case of titanium. SEM showed 48% more AM adherent to PMMA than titanium per unit area. Also, the percentage of cells with membrane damage was three times higher on PMMA than on titanium. It appears that the CL response of AM exposed to biomaterials in vitro thus can be used as an easy to do screening test for potential orthopaedic implant materials before in vivo tests are considered.

Animals↗

Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis.

Better methods are needed to assess mast-cell activation in vivo and to distinguish the activation of mast cells from that of basophils. Tryptase, a neutral protease selectively concentrated in the secretory granules of human mast cells (but not basophils), is released by mast cells together with histamine and serves as a marker of mast-cell activation. In 17 patients with systemic mastocytosis, concentrations of tryptase in plasma were linearly related to those of histamine (P less than 0.01). Eleven of the 17 patients had tryptase levels of 4 to 88 ng per milliliter, indicating ongoing mast-cell activation. In each of six patients who experienced corresponding anaphylactic reactions after penicillin, aspirin, or melon ingestion, a wasp sting, exercise, or antilymphocyte globulin injection, tryptase levels in serum ranged from 9 to 75 ng per milliliter, indicating mast-cell activation during each of these events. In contrast, serum tryptase levels were less than 5 ng per milliliter in all patients presenting with myocardial disease (n = 8, 6 with hypotension) or sepsis (n = 6, 3 with hypotension) and in the controls (n = 20). One patient had a myocardial infarction after anaphylaxis in response to a wasp sting and an elevated tryptase level of 25 ng per milliliter. Thus, the plasma or serum tryptase level is a diagnostic correlate of mast-cell-related events.

Anaphylaxis↗

Functional electric stimulation to enhance systemic fibrinolytic activity in spinal cord injury patients.

Functional electric stimulation (FES) of muscle has been used to decrease the incidence of postoperative deep vein thrombosis (DVT) in neurologically intact individuals. This study was undertaken in order to determine whether a large-scale trial should be initiated using FES to prevent DVT in spinal cord injury (SCI) patients. The goals of this pilot study were to demonstrate the value of FES of calf musculature in (1) increasing plasma fibrinolytic activity and (2) promoting venous blood flow in the lower extremities. Plasma fibrinolytic activity was monitored in ten SCI patients before, immediately after, and 100 minutes after 60 minutes of calf FES. A significant increase in plasma fibrinolytic activity was noted using whole blood and platelet-rich plasma clot lysis assays. Continuous photoplethysmographic and Doppler ultrasound monitoring of venous flow was attempted during FES in four spinal cord patients, and a mild to moderate increase in flow was achieved. FES was not as successful as manual compression in promoting venous emptying of the lower extremity. FES may be a useful tool in the prevention of DVT in SCI patients due to a significant increase in fibrinolytic activity and a mild to moderate increase in venous blood flow. FES merits full-scale clinical evaluation for this purpose.

Electric Stimulation Therapy↗