The use of selegiline in Alzheimer's patients with behavior problems

BACKGROUND: Currently there is no regimen for managing the inappropriate behavior seen in Alzheimer's disease that does not cause significant patient sedation. Preliminary evidence suggests selegiline may be effective in behavioral modification without the adverse effects observed with other regimens. The purpose of this study was to document the efficacy of selegiline in Alzheimer's patients with behavior problems. METHOD: Eight Alzheimer's patients (6 women and 2 men) ranging in age from 50 to 82 years (mean +/- SD = 74.0 +/- 10.5) were enrolled in this single-blind study. Patients received selegiline 10 mg each day for 8 weeks. Prior to drug administration and at the end of Weeks 1, 2, 4, 6, and 8, patients were evaluated for behavior (BEHAVEAD), cognitive function (Mini-Mental State Examination), and caregiver stress (Caregiver Burden Scale). RESULTS: Of eight enrolled patients, five were available for analysis. No statistically significant differences were found between mean baseline and mean 8-week scores for any of the three tests. However, clinical significance was noted by improvement in cognition (orientation and recall), caregiver stress, and behavior. Behavior was noted to improve in the areas of paranoid and delusional ideation, hallucinations, activity disturbances, anxiety, and phobias. CONCLUSION: These data suggest that some Alzheimer's patients with behavior problems may benefit from selegiline therapy.     

A psychobiological perspective on the personality disorders

A preliminary but growing body of evidence supports the existence of genetic and biological substrates of personality, suggesting the utility of a psychobiological perspective on the personality disorders. The investigation of biological correlates of personality disorders can provide an empirical base to explore the relationship between biological predispositions and psychological function. The authors propose a psychobiological model based on dimensions of cognitive/perceptual organization, impulsivity/aggression, affective instability, and anxiety/inhibition. These dimensions span the DSM-III-R axis I and axis II disorders. The authors review phenomenological, genetic, and biological evidence in relation to each of these dimensions. Although such an approach remains heuristic, this model provides a promising vantage point from which to generate investigation of the development and treatment of the personality disorders.     

Exercise training ameliorates progressive renal disease in rats with subtotal nephrectomy

To determine the effect of chronic exercise training on renal function in animals with moderate renal insufficiency, rats with 75% renal ablation were either exercise trained by swimming for two months or remained sedentary. Glomerular filtration rate was significantly higher in trained (1.89 +/- 0.07 ml/min) than in sedentary rats (1.52 +/- 0.11 ml/min). No change was observed in renal blood flow or the degree of hypertension. Proteinuria was reduced in trained (13.6 +/- 4.9 mg/24 hr) compared to sedentary animals (33.5 +/- 9.2 mg/24 hr). The degree of glomerulosclerosis was much less prominent in trained animals. Plasma, low-density lipoprotein cholesterol-levels and total triglycerides were reduced in trained compared to sedentary rats. This study suggests that chronic exercise training ameliorates the progression of renal disease and improves plasma lipids in rats with moderate renal insufficiency. The mechanism for this improvement in renal function appears to be independent of the influence of systemic blood pressure.     

Neuroendocrine and neurochemical measurements in depression

The authors performed dexamethasone suppression tests (DST), TRH infusions, 72-hour urine collections, and lumbar punctures on a group of male depressed patients. Approximately 60% of the patients were DST positive and 33% had a blunted TSH response. Two biologic variables, the 8 a.m. postdexamethasone cortisol and the postprobenecid CSF 5-hydroxyindoleacetic acid (5-HIAA), accounted for over half of the variance in the behavioral measure, the Hamilton score. Plasma cortisol elevation was associated with high 3-methoxy-4-hydroxyphenyl glycol (MHPG) excretion; TSH blunting was associated with low urinary MHPG excretion. Comprehensive biologic measures showed certain significant interrelationships and correlations with the severity of depression.     

Proton magnetic resonance spectroscopy of the brain in schizophrenic and affective patients.

Water-suppressed 1H magnetic resonance spectra were recorded from two brain regions of psychiatric patients and normal volunteers. The two regions studied were (a) the basal ganglia structures surrounding the anterior horn of the lateral ventricle and (b) the occipital cortex. N-Acetylaspartate (NAA), phosphocreatine-creatine (PCr-Cr), choline and inositol resonances were seen in both regions. Ratios of metabolite peak integrals to PCr-Cr peak integral were calculated for each spectrum. To control for partial volume effects, comparisons between patients and controls were made only from identical regions i.e. basal ganglia vs basal ganglia, and likewise for occipital cortex. Metabolite ratios from the occipital region of patients were similar to those from the occipital region of normal subjects. Bipolar patients being treated with lithium had elevated NAA/PCr-Cr in the basal ganglia region when compared to normals. These patients also demonstrated elevated choline/PCr-Cr and inositol/PCr-Cr ratios in the basal ganglia region.     

No-scalpel vasectomy: a technique for family physicians.

Family physicians frequently perform outpatient vasectomies. A new approach to exposing the vas deferens, called the no-scalpel vasectomy, results in fewer complications and, the authors believe, improved patient acceptance. This technique, which calls for two specialized instruments, is described, along with patient selection and education issues, vasal occlusion techniques and post-vasectomy follow-up.     

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.     

Abnormal rabbit heterophil chemotaxis following thermal injury. An in vivo model of an abnormality of the chemoattractant receptor for f-met-leu-phe

Previous studies have shown that the decreased neutrophil migratory responsiveness seen in burned patients correlates with the extent of thermal injury and the extent of the neutrophil-specific granule deficiency. To understand better the relationship between the neutrophil dysfunction, degranulation, and thermal injury, a rabbit model was studied. Eighteen rabbits were burned over 20% of their surface area. Assay of peripheral blood heterophils disclosed decreased migratory activity compared with preburn levels and decreased lysozyme content vs preburn levels, but no change in the beta-glucuronidase content. The specific binding of tritiated formyl-methionyl-leucyl-phenylalanine to peripheral blood heterophils was increased fivefold over that of control cells. These studies indicate that, following thermal injury, there is a selective decrease of specific granule contents and an increase in chemoattractant binding to the cell and also suggest an abnormality in chemoattractant receptor processing. The rabbit provides a convenient model for the study of compromised host defenses following thermal injury.     

Lymph node biopsy in patients with human immunodeficiency virus infections

Twenty-one male homosexuals were followed up by repeated lymph node biopsy for a mean (+/- SEM) follow-up of 99 +/- 18 weeks. Four histologic patterns were seen on biopsy: explosive follicular hyperplasia (EFH), follicular involution (FI), a mixed pattern of EFH with FI in the same node, and lymphocyte depletion. Patients with FI and lymphocyte depletion had mean survival times that were significantly less than those for the subjects with EFH. The percentage of lymph node follicles with suppressor cell clusters (T8) in EFH lymph nodes was significantly higher (43% vs 8%) than in nodes from patients without risk for human immunodeficiency virus infection. Helper/suppressor T-cell ratios in control nodes were 1.6; in EFH nodes, 0.97; and in FI nodes, 0.88. A remarkable 33% of patients in this lymphadenopathy group ultimately developed large-cell (B-cell) lymphoma, suggesting that the follicular stimulation noted histologically played a role in the development of this neoplasm. These data show that there is a progressive destruction of lymph node follicles that correlates with the progression of the disease and that lymph node histologic features may provide important prognostic information.