The clinical use of gabapentin in bipolar spectrum disorders

BACKGROUND: with increasing awareness of lithium's limitations, several new anticonvulsants had been tested for their mood stabilisation during recent years. Among the innovative third generation mood stabilizing anticonvulsants, gabapentin (GBP) seems to have a broad spectrum of efficacy, although no certain data are available as to its efficacy and use in clinical practice. Accordingly, an extensive review on this subject has been carried out. METHODS: A computer-generated search of the biomedical literature and abstract books of the more important scientific psychiatric congresses until June 2000 was undertaken to identify all pertinent case reports, case series and studies of GBP as monotherapy or adjunctive therapy in mood disorders. We identified 40 open-label studies on the use of GBP in at least 600 patients with bipolar disorder (BP), manic, depressed, or mixed episodes and unipolar depression and four controlled studies. RESULTS: The 40 open-label studies and two of the controlled trials suggested that GBP may have a role as adjunctive agent in the treatment of patients with bipolar disorders particularly when complicated by co-morbid anxiety disorder or substance abuse. GBP is usually very well tolerated and has no pharmacological interference with other mood stabilisers. However, in the other two double-blind studies GBP has not been found to be efficacious in the treatment of refractory mania or refractory bipolar depression. CONCLUSIONS: Although failing to show clear antimanic efficacy in randomized trials, gabapentin still remains a clinically useful agent when it comes to combination treatment in refractory and co-morbid patients.     

Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease?

One of the major causes of end-stage renal diseases is hypertensive renal disease, in which enhanced renal prostaglandin (PG) E2 production has been shown. PGE2, a major arachidonic acid metabolite produced in the kidney, acts on 4 receptor subtypes, EP1 through EP4, but the pathophysiological importance of the PGE2/EP subtypes in the development of hypertensive renal injury remains to be elucidated. In this study, we investigated whether an orally active EP1-selective antagonist (EP1A) prevents the progression of renal damage in stroke-prone spontaneously hypertensive rats (SHRSP), a model of human malignant hypertension. Ten-week-old SHRSP, with established hypertension but with minimal renal damage, were given EP1A or vehicle for 5 weeks. After the treatment period, vehicle-treated SHRSP showed prominent proliferative lesions in arterioles, characterized by decreased alpha-smooth muscle actin expression in multilayered vascular smooth muscle cells. Upregulation of transforming growth factor-beta expression and tubulointerstitial fibrosis were also observed in vehicle-treated SHRSP. All these changes were dramatically attenuated in EP1A-treated SHRSP. Moreover, EP1A treatment significantly inhibited both increase in urinary protein excretion and decrease in creatinine clearance but had little effect on systemic blood pressure. These findings indicate that the PGE2/EP1 signaling pathway plays a crucial role in the development of renal injury in SHRSP. This study opens a novel therapeutic potential of selective blockade of EP1 for the treatment of hypertensive renal disease.     

Mandibular intraosseous leiomyoma in a child: report of a case

Leiomyoma is a benign tumor of smooth muscle origin that rarely occurs in the oral cavity. Of the 118 cases occurring in the oral cavity described since 1884, only five involved the mandible. This is a case of an intraosseous leiomyoma in a 9-year old child, who presented to our attention with a firm intraoral mass, involving the angle and the posterior portion of the left mandibular body. The patient was treated with local incision alone, preserving the permanent dental germs and the left inferior alveolar nerve. He remained disease free with regular follow-up for 40 months.     

Topical nitrogen mustard in the treatment of alopecia areata: a bilateral comparison study

Topical nitrogen mustard is an alkylating agent. Its efficacy in treating alopecia areata was reported in an uncontrolled study. We present a preliminary, half-head, controlled 16-week study showing that topical nitrogen mustard was of benefit in 1 of 6 patients treated with 50% to 100% scalp involvement. Another 4 patients did not complete the trial.     

Time course of proliferation and elimination of microglia/macrophages in different neurodegenerative conditions

Ablation of the hindlimb area of the sensorimotor cortex produces degeneration in the cortex (invasive traumatic injury) and leads to retrograde and/or anterograde degeneration in the thalamus (non-invasive injury, distal reaction). This provides an useful model to study the proliferation and elimination of microglia/macrophages in different neurodegenerative conditions. Changes in the morphology, distribution and numbers of microglia in the affected cortex and thalamus were analyzed at various time points (12 h to 30 days) after injury. In parallel, proliferation was determined by immunocytochemistry for the proliferating cell nuclear antigen and cell death by the TUNEL method. Proliferation was an early event in the microglia/macrophage response (from 12 h in the cortex and from 2 days post-lesion in the thalamus) and persisted up to 30 days. The different microglia/macrophage phenotypes proliferated in a specific temporospatial pattern. In the lesioned cortex, early activation and proliferation of intrinsic microglia was accompanied, from the second post-lesion day, by monocyte entrance and proliferation of monocyte-derived cells. In contrast, accumulation of cells in the thalamus resulted from proliferation of intrinsic microglia, without apparent/significant monocytic recruitment. During the subsequent microglia/macrophages removal the majority of the cells in the cortex transformed into ameboid cells devoid of cell processes that progressively accumulated as fully-developed macrophages tissue within the lesion (3-14 days) ultimately migrating out to the meningeal connective tissue (14-30 days). Only some process-bearing cells, remaining in the cortical tissue bordering the lesion, underwent degeneration by 14-21 days post-lesion. In contrast, in the distal affected thalamic nuclei, microglial cell death occurred by 14-30 days post-lesion. Altogether, this study shows that both the origin and fate of microglia/macrophages depend on the nature of the lesion.     

Validity of bone mineral density measurements in distal sites as an indicator of total bone mineral density in a group of pre-adolescent and adolescent women

BACKGROUND: The study of bone mineral density (BMD) has received attention due to the importance of osteoporosis as a public health problem in Mexico. The objective of this study was to assess the validity of BMD measures in distal forearm and calcaneus with portable densitometers as indicators of BMD on other anatomic sites. METHODS: We conducted a cross-sectional study with 219 women from 9 to 22 years of age in Cuernavaca, Morelos, Mexico. We measured BMD in central sites (the entire skeleton, excluding head, proximal femur, and lumbar spine) using dual X-ray absorptiometry (DXA) and in peripheral sites (distal forearm and calcaneus) using a portable densitometer with DXA technology. Measurements of height, weight, body composition, physical activity, and demographic characteristics were collected. Agreement of measurements of BMD was assessed using correlation and regression analysis, and the method proposed by Bland and Altman. RESULTS: Higher levels of BMD were found in total skeleton (0.88 g/cm(2)) than in calcaneus (0.48 g/cm(2)) and distal forearm (0.38 g/cm(2)) (p <0.05). Moderate-to-high positive correlation coefficients (all significant) (p <0.05) were found between BMD in distal forearm and calcaneus vs. central anatomic sites, ranging from r = 0.49 to r = 0.78. BMD was higher in central sites compared with distal forearm and calcaneus. CONCLUSIONS: Measurement of BMD in distal forearm and calcaneus with portable densitometers provided valid indicators of BMD in central anatomic sites among pre-adolescent and adolescent women in Mexico.     

Evaluation of endotoxin release and cytokine production induced by antibiotics in patients with Gram-negative nosocomial pneumonia

OBJECTIVE: To determine the plasma concentrations of lipopolysaccharide, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in a homogeneous group of septic patients and to evaluate the effect of antibiotic treatment, imipenem or ceftazidime, on the release of lipopolysaccharide and cytokines. DESIGN: Prospective, randomized study. SETTING: Sixteen-bed multidisciplinary intensive care unit. PATIENTS: Twenty-four septic patients with documented Gram-negative nosocomial pneumonia. Controls were 20 patients admitted without sepsis and 20 healthy volunteers. INTERVENTIONS: Septic patients were randomized between imipenem and ceftazidime. Blood samples were collected before (0 hrs) and after (4 and 12 hrs) antibiotic treatment. Concentrations of lipopolysaccharide were measured by using the limulus assay, and cytokine concentrations were measured by enzyme-linked immunosorbent assay. Statistical analyses were performed by Kruskal-Wallis test, Mann-Whitney U test, and Student's t-test. MEASUREMENTS AND MAIN RESULTS: The mean age was 48.5 +/- 19.5. The mean Acute Physiology and Chronic Health Evaluation II score was 18.4 +/- 4.5. Overall mortality rate was 45.4%. All septic patients showed significant higher concentrations of lipopolysaccharide (p <.001), tumor necrosis factor-alpha (p <.04), and interleukin-6 (p <.001) than the controls, but interleukin-1 beta was never detected. We did not find statistically significant changes in lipopolysaccharide or cytokine plasma concentrations over time within any of the two arms of the study (ceftazidime vs. imipenem). There were no statistically significant differences in lipopolysaccharide and interleukin-6 plasma concentrations between the two antibiotic treatments. Although tumor necrosis factor-alpha plasma concentrations were significantly higher in the group treated with ceftazidime compared with the group treated with imipenem at the baseline and 4 hrs later, these differences were not statistically significant after 12 hrs of initiation of both treatments. CONCLUSIONS: Patients with Gram-negative nosocomial pneumonia have high plasma concentrations of lipopolysaccharide, interleukin-6, and tumor necrosis factor-alpha, but the antibiotic therapy evaluated did not significantly modify these concentrations.     

Didactic psychodrama: strategy for the humanization of work relations

The aim of this study is to analyze the use of pedagogical psychodrama as a strategy for reflecting on the humanization of health care. Five meetings were held from May to June 2000. In these meetings the following themes were developed: context of work in emergencies; updating of the personal and professional, individual and group reference, and acknowledgement of users. In view of the need of rethinking humanization in emergency care, we consider that the psychodrama approach alerted health professionals for the necessary commitment and responsibility in their work.