Ranitidine effervescent and famotidine wafer in the relief of episodic symptoms of gastro-oesophageal reflux disease

Radioligands that specifically target dopamine uptake sites can provide a means of determining dopamine fiber loss at intrastriatal mesencephalic grafts in Parkinsonian patients, using Positron Emission Tomography (PET). The BTCP derivative, 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-4-(2-hydroxyethyl)-piperazine, shows in vitro high affinity and selectivity for the dopamine transporter. To evaluate the potential of such a compound as a potential dopaminergic PET tracer the positron-emitting analogues, 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-4-(2-[18F]fluoroethyl)-piperazine and 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-4-[11C]methylpiperazine, were synthesized. Radiofluorination was carried out by the reaction of 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-4-(2-chloroethyl)-piperazine with cyclotron-produced n.c.a. 18F-(half life 109.9 min) obtained by the (p,n) reaction on 18O-enriched water. Labelling with carbon-11 (half life 20.4 min) was achieved by 11C methylation of 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-piperazine with [11C]methyl iodide. After intravenous administration to rats these two compounds enter the brain, but despite their high in vitro affinity they display a high non specific binding in vivo which greatly limits their use as PET radioligands.     

Mammographic changes in postmenopausal women on hormonal replacement therapy

The purpose of this study was to investigate the extent of the effects of hormonal replacement therapy (HRT) on the mammographic breast pattern in postmenopausal women. In a hospital-based study mammographic examinations of 81 postmenopausal women were evaluated retrospectively, before and after 1-2 years of treatment with oestrogens or a combination of oestrogens and progestagens. Each individual mammographic film was examined separately, and the glandular tissue was classified according to a modified Wolfe classification. In a screening-centre-based study two consecutive mammograms, with a 2-year interval, of 645 women, of whom 70 were using some kind of hormone therapy, were evaluated retrospectively. In the hospital-based study 31 % of patients treated with combination HRT showed an increase in fibroglandular tissue compared with only 8.7 % in the group treated with oestrogens alone. The difference was statistically significant (p = 0.046). In the screening-based study 14.3 % of the women using hormonal therapy showed an increase, whereas in the non-users no increase was found (p = 1.24 x 10(-10)). After beginning HRT many women (between 14 and 25 % in our experience) can be expected to undergo a mammographically detectable increase in fibroglandular tissue. Radiologists should be aware of the aetiology of such changes, and can obtain information on HRT most conveniently by having the technologist routinely question each patient.     

Alterations of benzodiazepine receptors in type II alcoholic subjects measured with SPECT and [123I]iomazenil

OBJECTIVE: Alterations in cortical benzodiazepine receptor density have been described in postmortem and in vivo studies of alcoholic subjects. The authors attempted to replicate these findings using single photon emission computed tomography and the benzodiazepine receptor radiotracer [123I]iomazenil. METHOD: They measured the distribution volume of benzodiazepine receptors in 11 recently detoxified patients with type II alcoholism and 11 healthy comparison subjects. The tracer was given as a bolus followed by a continuous infusion to achieve sustained binding equilibrium at the benzodiazepine receptors. Data were analyzed by using a region of interest method (regions of interest were identified on coregistered magnetic resonance imaging scans) and by a pixel-by-pixel method (distribution volume maps were analyzed with statistical parametric mapping for between-group differences). RESULTS: The region of interest analysis revealed that alcoholic patients had significantly lower benzodiazepine distribution volume than comparison subjects in the frontal, anterior cingulate, and cerebellar cortices. Statistical parametric mapping revealed two large excursions in which the distribution volume in alcoholic patients was significantly lower than in comparison subjects: the anterior cingulate, extending into the right middle frontal gyrus, and the left occipital cortex. CONCLUSIONS: Benzodiazepine receptor distribution volume is significantly lower in several cortical regions and the cerebellum in alcoholic subjects than in healthy comparison subjects. These results are consistent with previous reports and might indicate either a toxic effect of alcoholism on benzodiazepine receptors or a vulnerability factor for developing alcoholism.     

Isolation of the Bacillus subtilis cdd downstream region and analysis of genetic structure around the cdd vicinity

A 40-year experience consisting of 91 cases of acute slipped capital femoral epiphysis (SCFE) was reviewed to assess the safety of manipulative reduction and to determine whether urgent reduction has an effect on the development of avascular necrosis (AVN) of the capital femoral epiphysis. All patients had a history of sudden onset of severe hip pain and were documented to have an unstable (acute) slipped epiphysis. Treatment modalities included manipulative reduction under general anesthesia followed by internal fixation (41 hips), epiphysiodesis and internal fixation (15 hips), epiphysiodesis and cast immobilization (31 hips), and cast immobilization alone (three hips). One case was treated with cast immobilization after reduction by skeletal traction. Patient follow-up averaged 44 months, and ranged from 12 to 216 months. Radiographic review identified 13 (14%) cases of AVN in the series of 91 hips. Of 42 hips reduced in <24 h from presentation, AVN developed in three (7%). Of 49 hips reduced in >24 h from presentation, AVN developed in 10 (20%). Manipulative reduction of the acute SCFE may be accomplished without increased risk of AVN. Time to reduction may be an important risk factor for development of AVN after acute SCFE.     

Differential reactivity of cardiac and skeletal muscle from various species in a cardiac troponin I immunoassay

The effects of 2-butoxyethanol (2-BE) on poly(ADP-ribosyl)ation were studied in Syrian hamster embryo (SHE) cells by measuring the cellular concentrations of the polymer poly(ADP-ribose) (pADPr) and of NAD+, the substrate of poly(ADP-ribose) polymerase (PARP). As biotransformation pathways of ethylene glycol ethers involve NAD+-dehydrogenases, it was hypothesized that 2-BE could reduce poly(ADP-ribosyl)ation by consuming NAD+. As a result DNA repair could be altered, which would explain that 2-BE had been shown to potentiate the effects of clastogenic substances such as methyl-methanesulfonate (MMS). In this study, the effects of 2-BE on MMS-induced pADPr metabolism were analyzed. The results indicated that: (i) 2-BE (5 mM) by itself did not influence significantly pADPr or NAD+ levels. (ii) 2-BE inhibited pADPr synthesis in MMS (0.2 mM)-pretreated cells, without any change in NAD+ concentrations. (iii) MMS treatment, which rapidly increased pADPr levels, also affected the poly(ADP-ribosyl)ation system as a secondary effect by damaging cell structures. Membrane permeabilization, which occurred at concentrations >1 mM MMS, led to a dramatic leakage of cellular NAD+ resulting in a strong reduction in pADPr levels. (iv) A bleomycin pulse (100 microM) applied after MMS and/or 2-BE treatment confirmed that 2-BE reduced poly(ADP-ribosyl)ation capacities of MMS-treated cells, though the glycol ether had no effect alone. This study confirmed that the inhibition of pADPr synthesis could be responsible for the synergistic effects of 2-BE with genotoxic substances. The mechanism of this inhibition cannot be explained by a lack of NAD+ at the concentrations of 2-BE tested.     

Topoisomerase I inhibitors: the relevance of prolonged exposure for present clinical development

Topoisomerase I inhibitors constitute a new class of anti-cancer agents. Recently, topotecan and irinotecan were registered for clinical use in ovarian cancer and colorectal cancer respectively. Cytotoxicity of topoisomerase I inhibitors is S-phase specific, and in vitro and in vivo studies have suggested that, for efficacy, prolonged exposure might be more important than short-term exposure to high concentration. Clinical development of those topoisomerase I inhibitors that have reached this stage is also focused on schedules aiming to achieve prolonged exposure. In this review, we summarize all published preclinical studies on this topic for topoisomerase I inhibitors in clinical development, namely 20-S-camptothecin, 9-nitro-camptothecin, 9-amino-camptothecin, topotecan, irinotecan and GI147211. In addition, preliminary data on clinical studies concerning this topic are also reviewed. The data suggest that prolonged exposure may indeed be relevant for anti-tumour activity. However, the optimal schedule is yet to be determined. Finally, clinical data are yet too immature to draw definitive conclusions.     

Bilateral hyperplastic nephromegaly, nephroblastomatosis, and renal dysplasia in a newborn: a variety of universal nephroblastomatosis

A preterm boy was born at 34 weeks. Prenatal ultrasonography showed oligohydramnios, fetal ascites, large kidneys, and small thorax. He died 21 h after birth of respiratory insufficiency. Autopsy revealed Potter's-like facies, hypoplastic lungs, ascites, and bilateral nephromegaly (renal weight almost 10 times normal). The kidneys were finely nodular externally, solid, and cerebriform on cut section. Histologically, they showed a diffusely distorted architecture of jumbled lobules, hyperplasia of cortical-type tissue with inconspicuous proximal tubules, relative hypoplasia of medullary tissue, tubulointerstitial dysplasia, and perilobar nephrogenic rests. The renal features represent a variety of the universal or panlobar (also called pancortical or infantile) type of nephroblastomatosis. To our knowledge, this is only the third such case reported. In the brain, each lateral ventricle contained a yellow gelatinous mass. Histologically, the masses consisted of a pseudomyxoid matrix with delicate fibers and focal adipocyte clusters, all confined within choroid plexus. We consider these lesions fibrolipomatous hamartomas.     

Role of intestinal bacteria in nutrient metabolism

Perfluorocarbons are now being used as oxygen carriers in clinical settings. Because these chemicals may have a role as a blood substitute, in organ preservation, and in the management of respiratory failure, we have reviewed some of the research leading to these applications.