Clomipramine vs desipramine crossover trial in body dysmorphic disorder: selective efficacy of a serotonin reuptake inhibitor in imagined ugliness

BACKGROUND: Body dysmorphic disorder (preoccupation with an imagined or slight defect in appearance) is a common and disabling disorder associated with high rates of delusional symptoms and suicide attempts. Although preliminary studies suggest that serotonin reuptake inhibitors may be effective for body dysmorphic disorder, to date no controlled treatment studies have been published. METHODS: Forty patients were enrolled and 29 were randomized into a 16-week, double-blind, crossover-design study of clomipramine, a potent serotonin reuptake inhibitor, and active control desipramine, a selective norepinephrine reuptake inhibitor. Outcome measures included specific ratings of body dysmorphic disorder severity, delusionality, and functional impairment. RESULTS: Clomipramine was superior to desipramine in the acute treatment of body dysmorphic disorder symptoms as measured by assessment of patients' obsessive preoccupation with perceived body defects, repetitive behaviors in response to this preoccupation, and global ratings of symptom severity. Treatment efficacy was independent of the presence or severity of comorbid diagnoses of obsessive-compulsive disorder, depression, or social phobia. Likewise, clomipramine was equally effective regardless of whether the patients had insight or held their dysmorphic misperception with delusional intensity. Clomipramine was also superior to desipramine in improving functional disability. CONCLUSIONS: Clomipramine is more effective than desipramine in the treatment of body dysmorphic disorder and is effective even among those patients who are delusional.     

Intensity modulated radiation therapy with electrons using algorithm based energy/range selection methods.

BACKGROUND AND PURPOSE: In recent years photon intensity modulated radiation therapy (IMRT) has gained attention due to its ability to improve conformity of dose distributions. A potential advantage of electron-IMRT is that the dose fall off in the depth dose curve makes it possible to modulate the dose distribution in the direction of the beam by selecting different electron energies. This paper examines the use of a computer based energy selection in combination with the IMRT technique to optimise the electron dose distribution. MATERIALS AND METHODS: One centimetre square electron beamlets ranging from 2.5 to 50 MeV were pre-calculated in water using Monte Carlo methods. A modified IMRT optimisation tool was then used to find an optimum mix of electron energies and intensities. The main principles used are illustrated in some simple geometries and tested on two clinical cases of post-operated ca. mam. RESULTS: It is clearly illustrated that the energy optimisation procedure lowers the dose to lung and heart and makes the dose in the target more homogeneous. Increasing the energy at steep gradients compensates for lack of target coverage at beam edges and steep gradients. Comparison with a clinically acceptable four segment plan indicates the advantage of the used electron IMRT technique. CONCLUSIONS: Using an intensity optimised mix of computer selected electron energies has the potential to improve electron treatments for mastectomy patients with good target coverage and reduced dose to normal tissue such as lung and heart.     

Multigenic control of skin tumor susceptibility in SENCARA/Pt mice

Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg TPA) protocols were found to be under multigenic control. Eighty- one N2 mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were either solidly resistant (no papillomas) or highly susceptible (> or = 7 papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite markers to check for associations with susceptible and resistant phenotypes. A locus on Chr 5 (Skts4) was found to control the susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to papilloma formation. In addition, higher than expected linkage scores were seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is required to establish whether genes determining papilloma formation are located in these regions of the genome. In general, no evidence was seen for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in 17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice.      

Intensity modulated radiation therapy with multileaf collimators of different leaf widths: a comparison of achievable dose distributions.

PURPOSE: A planning study to analyze the impact of different leaf widths on the achievable dose distributions with intensity modulated radiation therapy (IMRT). METHODS: Five patients (3 intra- and 2 extra-cranial) with projected planning target volume (PTV) sizes smaller than 10 cm by 10 cm were re-planned with four different multileaf collimators (MLC). Two internal collimators with an isocentric leaf width of 4 and 10 mm and two add-on collimators with an isocentric leaf width of 2.75 and were evaluated. The inverse treatment planning system KonRad (Siemens Medical Solutions) was used to create IMRT 'step & shoot' plans. For each patient the same arrangement of beams and the same parameters for the optimization were used for all MLCs. The beamlet size for all treatment plans was chosen to coincide with the leaf width of the respective MLC. To evaluate the treatment plans 3D dose distributions and dose volume histograms were analyzed. As indicators for the quality of the PTV dose distribution the minimum dose, maximum dose and the standard deviation were used. For the organs at risk (OAR) the equivalent uniform dose (EUD) was calculated. To measure the dose coverage of the PTV the volume (V(90)) that received doses higher than 90% of the prescribed dose was calculated where for the conformity the dose conformity index given by Baltas et al. was determined. RESULTS: The MLC with the smallest leaf width yields the best mean value of all five patients for the PTV coverage and for the conformity. For the MLCs with the same leaf width, the add-on MLC leads to superior treatment plans than the internal MLC. This is due to the sharper penumbra of the add-on MLC. The number of IMRT field segments to deliver increased by approximately a factor of two if 2. MLC leafs are used instead of the standard 10 mm leafs. In case of the para-spinal patients the EUD value for the spinal cord is only reduced slightly by using MLCs with leaf widths smaller than 5 mm. For the intra-cranial the EUD value for some organs improved with reduced leaf widths while for some organs the 10 mm MLC leafs give comparable values. CONCLUSION: As expected the MLC with the smallest leaf width always yields the best PTV coverage. Reducing the leaf width from 4 to 2.75 mm results in a slight enhancement of the PTV coverage. With the selected organ parameters no significant improvement for most OAR was found. The disadvantage of the reduction of the leaf width is the increasing number of segments due to the more complex fluence patterns and therefore an increased delivery time.     

Helicobacter pylori infection upregulates endothelial nitric oxide synthase expression and induces angiogenesis in gastric mucosa of dyspeptic patients

BACKGROUND: Helicobacter pylori (H. pylori) infection induces nitric acid (NO) overproduction through inducible NO synthase (NOS) expression, subsequent DNA damage and enhanced antiapoptosis signal transduction sequence in the human gastric mucosa, whereas its possible effect on endothelial nitric oxide synthase (eNOS) expression has not as yet been investigated. The aim of this study was to evaluate the effect of H. pylori infection in the expression of eNOS in gastric mucosa. PATIENTS AND METHODS: We prospectively studied 30 nonsmoking dyspeptic patients (12 men, 18 women, mean age 54.26+/-12.89 years). The diagnosis of H. pylori infection was based mainly on histology. The histological grading of H. pylori infection was evaluated according to the modified Sydney classification. Histological grading of eNOS expression and microvessel density as estimated by CD34 expression were determined by immunohistochemistry (degree 0-3) and correlated with H. pylori infection and histological degree of gastritis. RESULTS: Twelve patients were H. pylori-positive and 18 patients were H. pylori-negative. The two groups were matched for age (P=0.139), sex (P=0.342) and similar degree of gastritis. Intensity of eNOS and CD34 expression in the corpus and antrum were significantly correlated (P<0.001). eNOS expression was correlated with H. pylori infection in the mucosa of the body and antrum (P=0.013 and 0.037, respectively) but not with gastric inflammation and activity (P=0.848 and 0.871, respectively, for the corpus and P=0.565 and 0.793, respectively, for the antrum). H. pylori-positive patients showed higher expression of CD34-positive blood vessels in the mucosa of the antrum (P=0.048). CD34 expression was correlated with gastric inflammation and activity (P=0.03 and 0.044, respectively) in the mucosa of the antrum of H. pylori-positive patients. CONCLUSION: H. pylori infection upregulates eNOS, and induces angiogenesis, contributing to H. pylori-associated pathophysiology in gastric mucosa.     

Elucidation of conditions allowing conversion of penicillin G and other penicillins to deacetoxycephalosporins by resting cells and extracts of Streptomyces clavuligerus NP1

Using resting cells and extracts of Streptomyces clavuligerus NP1, we have been able to convert penicillin G (benzylpenicillin) to deacetoxycephalosporin G. Conversion was achieved by increasing by 45× the concentration of FeSO₄ (1.8 mM) and doubling the concentration of α-ketoglutarate (1.28 mM) as compared with standard conditions used for the normal cell-free conversion of penicillin N to deacetoxycephalosporin C. ATP, MgSO₄, KCl, and DTT, important in cell-free expansion of penicillin N, did not play a significant role in the ring expansion of penicillin G by resting cells or cell-free extracts. When these conditions were used with 14 other penicillins, ring expansion was achieved in all cases.