Neuropeptide levels in the basal ganglia of aged common marmosets following prolonged treatment with MPTP

Summary Aged common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 0.5–2.0 mg/kg/week i.p.) for 16 or 24 weeks, observed for a total of 30 weeks and then killed for measurement of biochemical pramaters in basal ganglia. The MPTP treatment induced a marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the caudate nucleus and putamen. In contrast, the concentrations of five neuropeptides: [Met⁵]-enkephalin, [Leu⁵]-enkephalin, cholecystokinin, substance P and neurotensin as measured by a combined HPLC/RIA method, remained unaltered in all basal ganglia regions examined. Enkephalin precursor levels, as reflected by cryptic [Met⁵]-enkephalin content, were increased in the putamen, but not in the caudate nucleus, as a consequence of MPTP administration. Cryptic [Leu⁵]-enkephalin content remained unchanged in the striatum of MPTP treated marmosets. Overall, these results suggest an increase in striatal [Met⁵]-enkephalin release following chronic MPTP treatment of aged marmosets. However, the chronic treatment of aged marmosets with MPTP does not reproduce the neuropeptide alterations characteristic of Parkinson's disease.     

Ischemic rat brain extracts induce human marrow stromal cell growth factor production

Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain.     

Granulocyte antibodies in leukaemic chronic lymphoproliferative disorders

The anti-granulocyte activity of serum from patients with B-cell chronic lymphocytic leukaemia (CLL) and other lymphoproliferative disorders was investigated. Granulocyte-binding IgG was measured in 34 patients with CLL, 13 patients with hairy cell leukaemia, one patient with prolymphocytic leukaemia, two patients with Sézary cell leukaemia, and seven patients with chronic T-cell lymphocytosis who had a predominance of circulating large granular lymphocytes. Anti-granulocyte activity was absent in CLL and its variants, but present in the majority of granulocytopenic patients with chronic T-cell lymphocytosis. In one of these patients, granulocytopenia was associated with complement-activating IgG granulocyte antibody. Thus, antibody-mediated granulocyte injury appears to be an unusual occurrence in chronic lymphocytic leukaemia, but is a frequent complication of chronic T-cell lymphocytosis.     

Thyroid Hormone in the Treatment of Post-transplant Acute Tubular Necrosis (ATN)

Delayed graft function (DGF) in cadaver kidney transplants is a common problem and is often due to acute tubular necrosis (ATN). DGF in transplants may have a deleterious effect on long-term graft survival. Since thyroid hormone has been shown to hasten recovery from ATN in experimental models, we designed a trial to determine if a defined course of triiodothyronine (T3) would improve the short- or long-term outcome of patients with DGF in cadaveric transplants. A prospective, randomized, placebo controlled, double blind trial of T3 was carried out in patients with DGF in cadaveric renal transplants. End-points were percentage requiring dialysis, percentage recovering function, time to recovery and length of hospital stay. Long-term outcomes were percentage grafts functioning at 1 year and mean serum creatinine at 1 year. Forty-four patients were randomized to receive either T3 or placebo. Three patients were dropped from each group when early biopsies disclosed that DGF was due to rejection. The groups were well matched by age, cold ischemia time of the graft, and percentage reactivity to a random panel of antigens. Baseline thyroid function studies, including T3, reverse T3 (rT3), and thyroid stimulating hormone (TSH) levels, were similar between the two groups and typical of 'euthyroid-sick syndrome'. T3 had no effect on percentage requiring dialysis, time to recovery, percentage recovering function, or length of stay. At 1 year follow-up, graft function was similar in both groups and significantly lower than that seen in patients with good initial function. Thyroid hormone, given early in the course of DGF in cadaver kidney recipients, had no effect on the course of DGF. Long-term graft function is impaired in patients who experience post-transplant DGF compared to those who have good initial function.     

Physician evaluation after medical errors: does having a computer decision aid help or hurt in hindsight?

OBJECTIVE: The authors examined whether physicians' use of computerized decision aids affects patient satisfaction and/or blame for medical outcomes. METHOD: Experiment 1: Fifty-nine undergraduates read about a doctor who made either a correct or incorrect diagnosis and either used a decision aid or did not. All rated the quality of the doctor's decision and the likelihood of recommending the doctor. Those receiving a negative outcome also rated negligence and likelihood of suing. Experiment 2: One hundred sixty-six medical students and 154 undergraduates read negative-outcome scenarios in which a doctor either agreed with the aid, heeded the aid against his own opinion, defied the aid in favor of his own opinion, or did not use a decision aid. Subjects rated doctor fault and competence and the appropriateness of using decision aids in medicine. Medical students made judgments for themselves and for a layperson. RESULTS: Experiment 1: Using a decision aid caused a positive outcome to be rated less positively and a negative outcome to be rated less negatively. Experiment 2: Agreeing with or heeding the aid was associated with reduced fault, whereas defying the aid was associated with roughly the same fault as not using one at all. Medical students were less harsh than undergraduates but accurately predicted undergraduate's responses. CONCLUSION: Agreeing with or heeding a decision aid, but not defying it, may reduce liability after an error. However, using an aid may reduce favorability after a positive outcome.