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Biomedical subjects

J Sweeney

Publications and source records attributed to J Sweeney.

At least 55 records · Page 3Linked to original sources

Renal cell carcinoma treated with continuous-infusion interleukin-2 with ex vivo-activated killer cells.

High-dose recombinant interleukin-2 (rIL-2) results in tumor responses in patients with metastatic renal cell carcinoma ranging from 9 to 31%. Continuous infusion regimens of rIL-2 may be less toxic and may result in greater in vivo lymphokine-activated killer (LAK) cell production. The current trial used a continuous infusion of rIL-2 with ex vivo LAK cells. These cells were pretreated with phenylalanine methyl ester to remove monocytes to allow cell culture at higher concentrations. Twenty-three patients were entered into the trial. Two patients had complete responses (9%) lasting 15+ and 20+ months. Four patients had partial responses (17%) of 9+, 6+, 3, and 3 months, respectively. One partial responder at 9+ months had only minimal residual retroperitoneal disease that may represent scar tissue. All responders had prior nephrectomies. All but one of the responding patients completed a full cycle of rIL-2 at the highest (starting) dose, 6 x 10(6) U/m2. This rIL-2/LAK regimen appears to be an effective therapy for metastatic renal cell carcinoma.

Adult↗

Effects of photodynamic treatment of platelets or endothelial cells in vitro on platelet aggregation.

The purpose of this work was to gain insight into the role played by platelets and endothelial cells in the development of thrombogenic vascular events, observed after in vivo photodynamic therapy (PDT), by studying the in vitro effects of PDT on isolated human platelets and cultured human and bovine endothelial cells. Exposure to Photofrin II (PII) and light caused platelets to rapidly lose their ability to aggregate. Photofrin II alone at high concentrations also exerted inhibitory effects on aggregation. Endothelial cells exposed to PII- and phthalocyanine (GaCl-PcS2,3 or Zn-PCS1,2)-mediated PDT released potent platelet anti- and disaggregating activity which could be identified as prostacyclin by the following criteria: a close correlation between the time and dose dependent anti-aggregating effects and released 6-keto-PGF1 alpha (the spontaneous hydrolysis product of PGI2, determined by radioimmunoassay), the inhibition of these effects by indomethacin, accumulation of 6-keto-PGF1 alpha metabolite in the media of cells treated with PDT (as determined by HPLC analysis), and the absence of evidence for significant nitric oxide production. This prostacyclin release occurred following plasma membrane damage. Although no pro-aggregating activity was observed, endothelial cells were found to release considerable amounts of arachidonic acid and prostaglandin F2 alpha in response to PDT. These data, which indicate powerful anti-thrombogenic effects in vitro, are in sharp contrast to the vascular effects of PDT in vivo which are characterized by severe platelet aggregation, and imply that the in vivo effects involve additional components of the vascular system.

Adenosine Triphosphate↗

Pseudoaneurysm of the inferior gluteal artery.

Aneurysms of the inferior gluteal artery are uncommon, and have not previously been described in detail in the radiologic literature. The authors report the findings of computed tomography and angiography for a patient with a pseudoaneurysm of the inferior gluteal artery who was successfully treated by embolization alone.

Aged↗

Interleukin-2 lymphokine-activated killer cell therapy of non-Hodgkin's lymphoma and Hodgkin's disease.

We conducted a phase II study utilizing interleukin-2 (IL-2) with lymphokine-activated killer (LAK) cells as therapy for non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). IL-2 was given at a fixed dose of 3 x 10(6) U/m2/day administered as a 24-h continuous intravenous infusion with LAK cells. Nineteen extensively treated patients were entered and 15 were evaluable. In general, this regimen was reasonably well tolerated with mild toxicities that were rapidly reversible. Patients who completed therapy did so without dose attenuations. However, discontinuation of therapy was necessary in four patients due to atypical toxicities that were not clearly dose related. Two patients (one NHL and one HD) had partial remissions of brief duration, four had disease stabilization, and seven had progressive disease. While there were not sufficient numbers to evaluate critically any NHL or HD subtype, this regimen does not appear to have significant activity for either disease.

Adult↗

Interleukin-2 with ex vivo activated killer cells: therapy of advanced non-small-cell lung cancer.

A phase II study was conducted to examine the efficacy of interleukin-2 (IL-2) with lymphokine-activated killer (LAK) cells as therapy for advanced non-small-cell lung carcinoma (NSCLC). IL-2 was administered at a fixed dose of 6 x 10(6) U/M2 per day as a 24 h continuous intravenous infusion (CIV) with LAK cells. Eleven patients were entered onto this study and six were evaluable. One patient had a near complete response of 18 months duration. Only two patients were able to complete the regimen without dose reduction. This regimen was poorly tolerated with pulmonary toxicity being the major problem. The partial responder was the only patient to undergo more than one course of therapy. IL-2/LAK therapy may have activity in NSCLC and further studies are warranted in this uniformly fatal disease. However, future studies will have to incorporate less toxic IL-2 regimens.

Adult↗

Drug abuse in schizophrenic patients: clinical correlates and reasons for use.

OBJECTIVE: This study aimed to 1) determine substance abuse prevalence and preference in a diverse sample of schizophrenic, schizoaffective, and schizophreniform inpatients, 2) compare drug-abusing and non-drug-abusing patients on demographic and clinical variables during the acute and stabilization phases of their hospital course, and 3) obtain data from patients on reasons for drug abuse and on acute state-related changes during periods of intoxication. METHOD: Eighty-three psychotic inpatients consecutively admitted to a New York City teaching hospital were evaluated. Sixty-eight had schizophrenia, 12 had schizoaffective disorder, and three had schizophreniform disorder diagnosed according to the Structured Clinical Interview for DSM-III-R. Each patient received ratings on the Brief Psychiatric Rating Scale, the Global Assessment Scale, and the Scale for the Assessment of Negative Symptoms at admission and at discharge, an evaluation of premorbid adjustment, and an extensive interview on drug and alcohol use. RESULTS: Forty (48%) of the patients received diagnoses of drug or alcohol abuse or dependence. The drug-abusing patients primarily used cannabis (N = 26), alcohol (N = 21), and cocaine (N = 14) and reported that they abused drugs to get "high," to relieve depression, and to relax. They had significantly fewer positive and negative symptoms at discharge, better sexual adjustment and worse school performance during adolescence, and more family histories of drug abuse than the non-drug-abusing patients. CONCLUSIONS: Schizophrenic patients who abuse drugs may represent a subgroup of patients with better prognoses and less severe clinical characteristics of schizophrenia, but their drug abuse may adversely affect global outcome.

Adolescent↗

[Comparative study in aged rats of behavioral deficiencies and morphometrical modifications of galanin containing neurons in the medial septal area].

Age-related alterations in cued-training and place-training tasks were evaluated and compared to alterations in the galanin-like (GAL-LI) immunoreactive neurons in the medial septal area of the rat. Young adult (4 months) and aged (25-26 months) male Sprague-Dawley rats performed a modified version of the Morris water maze task. Immunohistochemical and morphometric techniques were used to analyse the distribution, density and morphology of GAL-LI neurons in the medial septum-diagonal band of Broca (MS-DBB) complex. A large variability in performance of the aged rats was evident, with the majority of aged rats exhibiting impaired performance on both parts of the task as compared to the young rats. In addition, there was a significant loss of GAL-LI cells in the MS-DBB complex, a significant reduction of the immunolabeling intensity of the subsisting GAL-LI cells and a non-statistically significant loss of septo-hippocampal GAL-LI neurons. There were no statistically significant correlations between the behavioral performances and the quantitative and qualitative modifications of GAL-LI cell bodies.

Age Factors↗

Acute effects of drug abuse in schizophrenic patients: clinical observations and patients' self-reports.

Substance abuse among schizophrenic patients is an increasingly recognized clinical phenomenon. The authors review experimental and observed clinical effects of drug abuse and patients' subjective experiences of acute intoxication. Though drug abuse may exacerbate psychotic symptoms, abused drugs may also lead to transient symptom reduction in subgroups of schizophrenic patients. Some patients report feeling less dysphoric, less anxious, and more energetic while intoxicated. Models of the relationship of drug abuse and schizophrenia, particularly the self-medication hypothesis, are discussed in reference to these data.

Humans↗

Diagnosis and clinical course of erotomanic and other delusional patients.

Twenty-eight patients with erotomanic delusions were compared with 80 patients with other delusions to clarify questions about diagnosis and course of illness in erotomania. The erotomanic patients were a heterogeneous group with respect to both diagnosis and course. They had significantly more manic symptoms than the comparison group and more affective diagnoses than would be expected from the literature; 25% (N = 7) had schizoaffective disorder and 7% (N = 2) had bipolar disorder. A subgroup of monodelusional erotomanic patients was identified who met the DSM-III-R criteria for delusional disorder, thus supporting the decision to include erotomanic delusions in this diagnostic category in the revision of DSM-III.

Adolescent↗

Modification by fentanyl and alfentanil of the intraocular pressure response to suxamethonium and tracheal intubation.

We have measured in a double-blind study the changes in intraocular pressure (IOP) in 40 consecutive patients (pretreated with fentanyl or alfentanil) who received suxamethonium and tracheal intubation. Although IOP increased significantly following administration of suxamethonium, mean IOP in both groups remained significantly less than control values (P less than 0.002). Tracheal intubation caused a further significant increase in IOP in the fentanyl, but not the alfentanil group. There were no significant differences in mean IOP between the fentanyl and alfentanil groups. Both opioids reduced, but did not abolish the haemodynamic responses to tracheal intubation.

Aged↗

Regulation of bile acid synthesis. Isolation and characterization of microsomal phosphatases.

In preliminary experiments, we have shown that rat liver microsomes possess phosphatase activity which was inhibited in the presence of sodium fluoride. We have now separated six microsomal phosphatase fractions appearing to be isoenzymes. They all possess different kinetic constants and are not equally inhibited by tartrate and fluoride ions, inhibitors of phosphatase activity. One phosphatase fraction, in fact, is almost completely unaffected by fluoride ion. More pertinent to our interest, these isoenzymes exhibit differing abilities to modulate the activities of hydroxymethylglutaryl CoA reductase, acyl-CoA:cholesterol O-acetyltransferase, and cholesterol 7 alpha-hydroxylase. Interaction of four of the fractions with rat liver microsomes resulted in a decrease in cholesterol 7 alpha-hydroxylase activity; two were without effect.

Animals↗

Imipramine treatment for chronic depression.

Antidepressant drugs in the treatment of chronic depressions have received little systematic study. We used a two-week, single-blind placebo washout followed by a six-week, double-blind comparison of imipramine hydrochloride and placebo in a sample of 76 outpatients with DSM-III dysthymic disorder entered into a trial at two centers. Subjects were preponderantly female, had insidious onset at an early age, and had depressions of moderate severity; 96% also met the DSM-III criteria for major depressive disorder at the time of presentation. Sixty percent had a history of persistent depressive symptoms sufficient to meet criteria for major depression for longer than two years. Markedly favorable responses occurred in 45% of imipramine-treated (n = 29) and 12% of placebo-treated (n = 25) patients and, respectively, 59% and 13% of those who completed the study. Imipramine produced significant advantage in measures of depressive symptoms, global severity of illness, and self-rated social and vocational function. Recovered patients experienced remission from both long-standing symptoms and deficits as well as more recently exacerbated aspects of their syndrome. Patients with pure dysthymic disorder of a mild, subsyndromal type were uncommon in these clinical settings. However, anti-depressant medication was effective for many moderately severe chronic depressions, which had previously been untreated or undertreated, presumably related to misdiagnosis.

Adult↗

Adrenocortical hyperactivity in depression: effects of agitation, delusions, melancholia, and other illness variables.

In an attempt to determine the relative contributions to adrenocortical hyperactivity in depression of agitation, delusions, and melancholic subtype, we measured cortisol levels before and after dexamethasone in 93 unipolar major depressed inpatients. Stepwise multiple regression showed that agitation predicted 22% of the variance in a.m. cortisol level after dexamethasone. Addition of the variables melancholia and delusionality to the regression model accounted for 27% and 34%, respectively, of the variance in the same cortisol variable. Age, illness severity, and weight loss added no further significant predictive value. Age, weight loss, and illness severity did affect cortisol levels when examined separately from the other variables. Rate of nonsuppression on the dexamethasone suppression test (DST) differed between the nonmelancholic major depressive group and any other group with melancholia. These results suggest why some discrepancies may exist between studies of the DST in delusional depression and indicate that agitation merits careful assessment in future studies of DST response.

Adrenal Cortex↗

Mothers' and fathers' changing perceptions of their male and female infants over the course of pregnancy.

Twelve pregnant women and their spouses who had undergone ultrasonography and knew their child's gender were compared with 12 pregnant women and their spouses who had undergone ultrasonography but did not know their child's gender. Parents were interviewed (a) prior to receiving the ultrasound, (b) immediately after the ultrasound, and (c) following their infant's birth. Using the adjectives rating scales, and replicating the procedures developed by Rubin, Provenzano, and Luria (1974), parents' perceptions of their infants were measured. ANOVA results indicated that parents viewed their infants to be softer, finer, littler, cuddlier, easier, calmer, more inactive, more beautiful, more awkward, quieter, weaker, and somewhat more delicate following birth than during the preceding measurement period(s). Mothers viewed their infants to be softer, more nervous, more fussy, more excitable, and more noisy than did fathers. Supporting Rubin et al.'s (1974) findings, several differences emerged between parents' perceptions of boys and girls, particularly by the time the infants were born. Following birth, parents perceived girls to be finer, smaller, less coordinated, quieter, weaker, and more delicate than boys. No differences were found as a result of parents being informed of their infants' gender prior to birth.

Fathers↗

Mapping and characterization of mutants of the Escherichia coli cell division gene, ftsA.

Eight independent temperature-sensitive mutants of the cell division protein FtsA have been studied. They fall into two classes in terms of their behaviour at 42 degrees C and recovery at 30 degrees C. The first class shows salt-dependent temperature-sensitivity and reversible inactivation of FtsA protein at 42 degrees C. The second shows irreversible inactivation which is not prevented by salt. Recovery of the ability to divide at 30 degrees C is rapid in mutants of the first group, but is delayed for approximately a generation time in the second group. This suggests that irreversible inactivation of FtsA causes extensive damage to the division machinery. The amino acid substitutions show clustering to a limited domain of the protein, and one particular substitution is found in three of the mutants.

Alleles↗