Distinct and interactive effects of d-amphetamine and haloperidol on levels of neurotensin and its mRNA in subterritories in the dorsal and ventral striatum of the rat

Striatal tissue concentrations of neurotensin, expression of neurotensin/neuromedin N (NT/N) mRNA, and numbers of neurotensin-immunoreactive neurons are increased by d-amphetamine (amph), which stimulates dopamine release in the striatum, and haloperidol (hal), a dopamine receptor antagonist with high affinity for D2-like receptors. The possibility that the effects of these drugs involve distinct subpopulations of striatal neurons was addressed in this study, in which the relative numbers and distributions of striatal neuron profiles containing neurotensin immunoreactivity and/or NT/N mRNA were compared following administrations of hal, amph, hal and amph co-administered, and vehicle. Fourteen striatal subterritories in caudate-putamen, nucleus accumbens, and olfactory tubercle were evaluated. Amph produced increases in the expression of neurotensin preferentially in the ventromedial and caudodorsal subterritories of the caudate-putamen, the rostrobasal cell cluster and lateral shell of the nucleus accumbens, and the olfactory tubercle. Haloperidol produced increased neurotensin expression in much of dorsal and ventral striatum, most prominently in the rostral, dorsomedial and ventrolateral quadrants of the caudate-putamen, and in the rostrobasal cell cluster, rostral pole, medial and lateral shell of the nucleus accumbens and the olfactory tubercle. The numbers of neurons responding to amph and hal in all subterritories following co-administration of the two drugs were significantly less than the summed numbers responding individually to amph and hal. Furthermore, in the subterritories where immunohistochemically detectable responses elicited by amph exceeded those produced by hal, co-administration of the two drugs resulted in responses comparable to those elicited by hal given alone. It is suggested that some of the reported anti-dopaminergic behavioral effects of basal ganglia neurotensin may be attenuated in conditions of reduced dopamine neurotransmission.     

Mode of presentation and multisystem involvement in Beh?et's disease: the influence of sex and age of disease onset

OBJECTIVE: To evaluate the correlation between the age at onset of Behcet's disease (BD) and sex distribution, mode of disease appearance, and number of organs involved during the disease. METHODS: BD was defined according to the International Study Group criteria. Data from medical files and from patient interviews were collected. Results were analyzed for children and adults, according to age at disease onset. A systemic involvement index was calculated as the sum of visceral organ systems involved. RESULTS: Fifty-nine patients with BD were studied, 26 male and 33 female. The mean age at disease onset was 8.4 +/- 4.5 years in children and 29.8 +/- 7.9 years in adults. The age of onset was significantly lower in male versus female patients. BD presented in children almost entirely as recurrent aphthous stomatitis, while in adults, less than one-third of patients presented first with oral ulcers. The mean age at disease onset of patients who presented first with oral ulcers was significantly lower than the age of patients presenting first with non-oral aphthosis. The mean systemic involvement index was higher in adult onset than in juvenile onset disease. A significant linear correlation was found between age of disease onset and total number of visceral organ systems involved. CONCLUSION: BD was observed to occur earlier in males than in females. The first manifestation of BD in children is almost exclusively in the form of oral ulcers, while older patients have a large proportion of non-oral aphthosis as their first disease manifestation. Disease onset at an older age is positively correlated with increased disease spectrum.     

Percutaneous ethanol injection into parathyroid adenomas: mid- and long-term results

The aim of this study was to evaluate mid- and long-term results of ultrasonically guided ethanol injection into parathyroid adenomas. From 1988 to 1996, 27 patients (mean age 77 +/- 13 years) were treated for parathyroid adenomas by percutaneous ethanol injection. The survey included clinical information, plasma calcium, phosphorus and PTH (1-84) evaluation. Follow-up lasted 22.6 +/- 10 months. No major complications were observed for 63 ethanol injections. Biochemical recovery was 58%, biochemical improvement at 3 months was 33%, and failure was 7%. Four of 15 cured patients presented a recurrence of the disease 1 or 2 years after the first treatment. Ultrasonically guided ethanol injection can be useful in the treatment of parathyroid adenomas when surgery is not possible. The immediate results are interesting but not as good as those obtained with surgery. A regular biochemical survey is necessary so that recurrences can be recognized and treated at an early stage.     

Trials and tribulations in the meta-analysis of treatment differences: Comment on Wampold et al. (1997).

A fair test of the Dodo bird conjecture that different psychotherapies are equally effective would entail separate comparisons of every pair of therapies. A meta-analysis of overall effect size for any particular set of such pairs is only relevant to the Dodo bird conjecture when the mean absolute value of differences is 0. The limitations of the underlying randomized clinical trials and the problem of uncontrolled causal variables make clinically useful treatment differences unlikely to be revealed by such heterogeneous meta-analyses. To enhance implications for practice, the authors recommend an intensified focus on patient–treatment interactions, cost-effectiveness variables, and separate meta-analyses for each pair of treatments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Results of selective goiter resection in functional autonomy

BACKGROUND: Active colitis in patients with inflammatory bowel disease is associated with mucosal vasodilation, increased intestinal permeability and abnormal colonic motility. Nitric oxide is a messenger molecule with many functions, including regulation of local blood flow, vasomotor tone, and inflammation. Increased nitric oxide production and inducible nitric oxide synthase activity have been demonstrated in experimental models of colitis. This study was designed to determine the relationship between nitric oxide production and colonic inflammation in children with active colitis and in control subjects and whether expression of inducible nitric oxide synthase protein is demonstrable in the intestinal epithelium of these patients. METHODS: Nitrate + nitrite were measured in urine, stool, and plasma using the Griess assay. Expression of inducible nitric oxide synthase protein in intestinal tissue was determined by immunohistochemical localization. RESULTS: Urinary nitrate + nitrite levels were not significantly different in patients and control subjects. In contrast, stool and plasma nitrate + nitrite concentrations were significantly higher in children with inflammatory bowel disease compared with levels in control children (stool: 162.4 +/- 31.0 mumol/l versus 77.2 +/- 22.1 mumol/l; plasma: 65.2 +/- 9.9 mumol/l versus 38.1 +/- 6.6 mumol/L; p < 0.05). Stool nitrate + nitrite levels significantly correlated with plasma values. Immunohistochemical staining of colonic tissue from children with inflammatory bowel disease demonstrated inducible nitric oxide synthase protein located exclusively in epithelial cells. CONCLUSION: Increased nitric oxide production and enhanced intestinal epithelial cell expression of inducible nitric oxide synthase protein are associated with active colonic inflammation.     

Platelets induce monocyte differentiation in serum-free coculture

In southeastern Turkey during the period of 1955-57, women were accidentally exposed to the fungicide hexachlorobenzene (HCB) after eating contaminated seed grain and developed porphyria cutanea tarda (PCT). While HCB has been shown to be a potent oocyte toxicant in primates and has been identified as an ovarian follicular fluid contaminant in women, its effect on human reproduction is poorly understood. This study was undertaken to evaluate the effects of HCB on women with a known high dose exposure. A retrospective controlled cohort comparison study of three groups was conducted. Group 1, those with confirmed PCT; Group 2, controls for the region and Group 3, controls for the country of Turkey, were followed-up after approximately 40 years (n=42/group). Blood samples were taken for analysis of serum HCB, estradiol, follicle-stimulating hormone (FSH) and inhibin. Frequency of HCB detection was greatest in Group 3, while number of cases with HCB values exceeding 1 ng/mL was significantly greater in Groups 1 and 2. There were no differences in the other biochemical measures. Interviews were completed for each patient regarding reproductive history (number of pregnancies, live births, spontaneous abortions, still births and sex of live babies). Multiple comparisons of the three groups, based on Fisher's test found the groups were inhomogeneous. When serum HCB was analyzed using correlated response logistic regression, there was a strong relationship between serum HCB levels and risk for spontaneous abortion but not sex ratio of children. The following findings were made. HCB is detectable and ubiquitous in serum samples from women in the country of Turkey with identified and unidentified exposure events. Spontaneous abortion risk is not restricted to women with identifiable exposure to HCB but to a surrogate marker of exposure (serum HCB sample). The risk of spontaneous abortion with HCB exposure requires further investigation.     

Opposite effects of bezafibrate and gemfibrozil in both normal and hypertriglyceridemic rats

The diagnostic value of zinc protoporphyrin (ZPP) as an indicator of iron-deficient anemia (IDA) in hospitalized patients is assessed in this study. ZPP was measured using an AVIV hematofluorometer with a coefficient of variation (CV) less than 5% and a recovery of greater than 97%. A reference range of 53-70 mu mol/mol heme was determined for ZPP in non-anemic patients in a hospital population. Hospitalized patients (221) with low hemoglobin (< 120 g/l) were evaluated for their iron status. ZPP and other anemia tests were performed. Macrocytic patients with mean corpuscular volume (MCV) greater than 98 fl) were excluded from the study. Seventy-four microcytic patients (MCV < 80 fl) were determined as having IDA according to a diagnostic algorithm. A distribution study of these microcytic patients showed that there was a significant overlap of values between the IDA and non-IDA patients for all serum anemia tests. A receiver-operator curve analysis revealed that ZPP has a relatively high degree of diagnostic efficiency better than iron and ferritin for this patient population. At a cutoff value > 170 mu mol/mol heme, ZPP has a sensitivity of 93% and a specificity of 90%. In addition, ZPP is also elevated in normocytic patients (MCV = 80-98 fl) with low ferritin values, who may have iron depletion. From these data, it is proposed that ZPP may be used as a screening tool for IDA in hospitalized patients.     

Characterization of electron beam irradiated polypropylene: Influence of irradiation temperature on molecular and rheological properties

The aim of the investigations was to analyze the influence of the temperature during the irradiation process of polypropylene on the molar mass, the formation of long chain branching and the final branching topology. A linear isotactic polypropylene homopolymer was modified by electron beam irradiation at different temperatures, with two irradiation doses to insert long chain branching. The samples were analyzed by size exclusion chromatography coupled with a multiangle laser light scattering detector, by differential scanning calorimetry, and by shear and elongational rheology. The shear and elongational flow behavior is discussed in terms of the influence of molecular parameters and used to analyze the topology of the irradiated samples. With increasing temperature, a slight reduction of the molar mass, an increase of long chain branching and an increase of crystallization temperature were found. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2770–2780, 2006     

BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group

PURPOSE: The HD9 trial aims to evaluate whether moderate dose escalation and/or acceleration of standard polychemotherapy is beneficial for advanced-stage Hodgkin's disease (HD). Two variants of a novel bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) scheme (standard and escalated dose) are compared with cyclophosphamide, vincristine, procarbazine, and prednisone (COPP)/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). PATIENTS AND METHODS: The randomized, three-arm trial recruited patients in stages IIB and IIIA with risk factors and stages IIIB and IV. BEACOPP in baseline dose contains all drug dosages of COPP/ABVD (except vincristine and procarbazine) rearranged in a shorter, 3-week cycle. Escalated BEACOPP uses higher doses of cyclophosphamide, doxorubicin, and etoposide with granulocyte colony-stimulating factor (G-CSF) support. After eight chemotherapy cycles, initial bulky and residual disease is irradiated. The trial is monitored and analyzed by means of a sequential strategy. RESULTS: An interim analysis with 505 assessable patients and a median follow-up of 23 months showed a significant inferiority (according to sequential monitoring strategy) of the COPP/ABVD regimen in progression rate and freedom from treatment failure (FFTF) compared with the pooled results of both BEACOPP variants. The 24-month FFTF rate was 75% for COPP/ABVD and 84% for BEACOPP pooled (P = .034). There was 12% progressive disease with COPP/ABVD and 6% with BEACOPP pooled. Differences in survival were not significant in sequential analysis. The acute toxicity of baseline BEACOPP resembled that of COPP/ABVD; escalated BEACOPP showed increased but manageable hematologic toxicity. CONCLUSION: Combined with local irradiation, BEACOPP in one or both variants shows superior disease control compared with COPP/ABVD, with acceptable acute toxicity. Further follow-up is required to assess the effect of dosage and the effect on survival and late toxicities.