Pharmacokinetics and metabolism of β-2′-deoxythioguanosine and 6-thioguanine in man

Summary Resistance to the antileukemic agent 6-thioguanine (TG) inevitably develops in animal tumors. However, a new agent, -2-deoxythioguanosine (-TGdR) can overcome TG resistance in animal tumor models and is therefore of potential clinical use. The pharmacokinetics of radiolabeled TG were compared with those of -TGdR in patients with cancer after intravenous administration. [³⁵S]--TGdR (5.4 mg/kg, 200 mg/m², 200 Ci total) was administered to five patients; the radiolabel in the plasma declined with an initial half-life (t_1/2) of 14 min and a terminal t_1/2 of 19.3 h. Within 24 h, 65% of the radiolabel was excreted in the urine. In contrast, after administration of [³⁵S]-6-TG (3.4 mg/kg, 125 mg/m², 200 Ci total) the average initial t_1/2 was 40 min while the terminal phase t_1/2 was 28.9 h. Urinary excretion of the radiolabel was 75% of the dose 24 h after administration. Both thiopurines were rapidly and extensively degraded and excreted as 6-thioxanthine, inorganic sulfate, S-methyl-6 thioxanthine, and 6-thiouric acid in addition to other products. Small amounts of unchanged drug were also excreted. These studies suggest that -TGdR is merely a latent form of TG.Deceased, to whose memory this paper is dedicated     

Lewy bodies in the presence of Alzheimer's disease.

Large numbers of Lewy bodies in the substantia nigra were found in a case of Alzheimer's disease. Parkinsonian symptoms were not recognized. The patient appears to be an example of an association recognized by Woodard but not yet understood. The case is discussed in the context of reported relationships between Parkinson's disease or "Lewy body disease" and dementia, on the one hand, and reports linking various forms of psychoses with an unusually high incidence of Lewy bodies, on the other.     

Pre and postnatal diagnosis of fetus‐in‐fetu

Differentiation of abdominal masses detected on prenatal ultrasound is difficult and requires careful characterization of the mass and precise localization. Differentiation is required in order to distinguish benign from potentially malignant conditions. We describe a case of fetus‐in‐fetu with pre and postnatal imaging.     

The Effect of 12-Step-Based Fellowship Participation on Abstinence Among Dually Diagnosed Persons: A Two-Year Longitudinal Study

Abstract

A large percentage of individuals are dually-diagnosed with a psychiatric disorder and a substance use disorder. Such persons typically face more difficulties and have poorer outcomes than do single disorder substance users. Among noncomorbid substance users, treatment and participation in 12-Step groups have been shown to enhance the likelihood of abstinence from substance misuse. Specialized 12-Step based fellowships have recently emerged to address the recovery needs of dually-diagnosed persons. The present study is a longitudinal investigation of the effect of such 12-Step based groups on abstinence among dually-diagnosed persons. Participants were members of Double Trouble in Recovery (DTR) who were recruited at community-based meetings in New York City and reinterviewed twice at yearly intervals. Generalized estimating equation analysis indicated that, over the two-year study period, ongoing DTR attendance was significantly associated with a greater likelihood of abstinence after controlling for other pertinent variables, such as mental health symptoms. For clinicians, these findings underline the importance of fostering stable affiliation with specialized 12-Step based groups among their clients.     

Disruptions and Satisfaction in Internal Medicine Resident Continuity Clinic Differ Between Inpatient and Outpatient Rotations

Abstract

Background: Little is known about whether assignment to simultaneous inpatient and outpatient clinical duties causes disruptions during internal medicine resident continuity clinic and impacts trainee satisfaction.

Purpose: Our purpose was to determine whether dual inpatient and continuity clinic responsibilities impact resident stress and document the number, type, and immediacy of interruptions in continuity clinics.

Methods: Methods included a prospective 2-residency survey of 70 internal medicine residents performing 240 half-day continuity clinic sessions.

Results: More than half (52%) of trainees on inpatient rotations felt pressured to return to their ward duties. Half (50%) of residents thought clinic increased work hours, and the majority (70%) did not think continuity clinic detracted from their education on inpatient or elective rotations. Disturbances were more likely to occur on inpatient rotations (odds ratio 4.52, 95% confidence interval = 2.29-8.92) than on outpatient rotations. The time required to address an interruption was 3.9 ± 4.51 min. Residents thought many (46%) problems addressed during clinic could have waited until clinic completion.

Conclusions: Residents on inpatient rotations who were commonly interrupted in clinic felt pressured to return to ward duties and unable to focus on their clinic patients. Internal medicine faculty should modify curriculum to minimize the interference of other duties in resident clinics.     

Hemorrhagic tumor necrosis during a pilot trial of tumor necrosis factor-alpha and anti-GD3 ganglioside monoclonal antibody in patients with metastatic melanoma

Hemorrhagic tumor necrosis is an inflammatory event that leads to selective destruction of malignant tissues, with both potentially toxic and beneficial consequences. A pilot clinical trial was undertaken combining tumor necrosis factor-alpha (TNF-alpha) with the monoclonal antibody R24 (MoAb R24) against GD3 ganglioside in patients with metastatic melanoma. Patients received MoAb R24 to recruit leukocytes to the tumor followed by low doses of recombinant TNF-alpha to activate leukocytes. Eight patients were treated and seven patients had mild toxicity. One patient with extensive metastatic melanoma developed tumor lysis syndrome within hours after treatment with almost complete necrosis of bulky tumors in multiple visceral sites. To our knowledge, this is the first documented case of hemorrhagic tumor necrosis in a patient with metastatic cancer in multiple visceral sites.     

Late outcome of multivessel coronary artery disease after angioplasty or bypass surgery

Background. Results from randomized trials to determine optimal treatment for patients with multivessel coronary disease are not yet available. Thus, the early and late outcomes of 191 PTCA and 221 CABG patients done in 1985-86 were evaluated. Methods and Results. CABG patients selected had more coronary risk factors and more severe coronary artery disease compared to PTCA patients. Comparison of the initial outcome showed that clinical success without major cardiovascular events was similar (93.7% for PTCA vs. 90.0% for CABG; p=n.s.). Five year followup was obtained in 99.0% of PTCA patients and 94.4% of CABG patients. In the PTCA group, 89.8% were alive, 4.8% had sustained an MI, and repeat revascularization was required in 46.8%. In the CABG group, 87.1% were alive, 3.2% had had a MI, and 3.5% required repeat revascularization. Statistical comparison demonstrated no difference between the groups in survival or late cardiac events, but rate of repeat revascularization was significantly higher for PTCA patients (p less than 0.0001). Incompleteness of revascularization (p<0.01) was independently associated with an increased need for repeat revascularization in the PTCA group. In the CABG group, depressed left ventricular function (p less than 0.001) and female sex (p<0.01) were associated with lower survival rates. An analysis of cost per patient showed that the strategies were comparable. Conclusions. PTCA and CABG in multivessel disease patients have similar early results and comparable rates of survival and late cardiac events. Significantly more repeat revascularization is required in PTCA patients to maintain these results.(ABSTRACT TRUNCATED AT 250 WORDS)