Inositol deficiency diet and lithium effects

OBJECTIVES: A major hypothesis explaining the therapeutic effect of lithium (Li) in mania is depletion of inositol via inhibition of inositol monophosphatase. However, inositol is also present in the diet. Restriction of dietary inositol could theoretically enhance the effects of Li. METHODS: We used dietary inositol restriction in animal studies and also devised a palatable diet for humans that is 90% free of inositol. RESULTS: Dietary inositol restriction significantly augmented the inositol-reducing effect of Li in rat frontal cortex. Li reduced inositol levels by 4.7%, inositol-deficient diet by 5.1%, and Li plus inositol-deficient diet by 10.8%. However, feeding with the inositol-deficient diet did not enhance the behavioral effect of Li in the Li-pilocarpine seizure model. Fifteen patients participated in an open clinical study of the inositol-deficient diet: six rapid cycling bipolar patients responding inadequately to Li or valproate in different phases of illness; two Li-treated bipolar outpatients with residual symptomatology, and seven inpatient Li-treated bipolar patients in non-responding acute mania. The diet had a major effect in reducing the severity of affective disorder in 10 of the patients within the first 7-14 days of treatment. CONCLUSION: These results suggest that dietary inositol restriction may be useful in some bipolar patients, but controlled replication is necessary.     

Three-dimensional morphology of the palate in subjects with isolated cleft palate at the stage of permanent dentition.

OBJECTIVE: Three-dimensional analysis of palate size and shape in patients with isolated cleft palate at the stage of permanent dentition. DESIGN: Cross-sectional study using Fourier transform profilometry.Subjects: Twenty-nine randomly selected dental casts of approximately 15-year-old boys with isolated cleft palate and 28 dental casts of normal boys of the same age.Interventions: All patients were operated on by the same method (pushback and pharyngeal flap surgery) at a mean age of 4.5 years. MAIN OUTCOME MEASURES: Data on the palate height in 210 defined locations (pixels). RESULTS: The palate in isolated clefts is narrower throughout its whole extent and lower from the level of the first premolars. The difference, as compared with controls, increases in a posterior direction. At the level of the first molars, palatal height is reduced by one-quarter, the area of the transversal section by more than one-third. The shaping of the palate vault is, on average, symmetrical with a marked interindividual variability. Palatal height does not depend on the width of the dentoalveolar arch, and the height of the primary palate is not reduced. CONCLUSION: The smaller width and reduced height from the level of the first premolars posteriorly confirm the substantially reduced space available for the tongue in patients with isolated cleft palate. Deviations are on the average symmetrical, and the anterior part of the palate is not shallower.     

Ewing sarcoma/PNET: 27 years of experience in Slovenia

The study includes 91 patients treated for Ewing sarcoma between 1972 and 2002. Forty were younger and 51 were older than 16. The overall 5-year survival was 36%: 53.5% in the younger and 22.5% in the older age group. Among patients with localized disease, 5-year survival was 58% in younger and 25.5% in the older. Survival was similar whether patients received three treatment modalities or chemotherapy combined with either surgery or radiotherapy. Recurrence was noted in 47 out of 75 patients with localized disease, most commonly as local recurrence or lung metastases. Among 18 evaluated patients, 14 had minor physical defects and 4 had severe late treatment effects (sterility in 3 and secondary osteogenic sarcoma in 1).     

Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia.

BACKGROUND: An elevated homocysteine level is reported to be a risk factor for several diseases, including Alzheimer's and cerebrovascular disease. Recently, several studies have reported that homocysteine levels are elevated in many schizophrenic patients. Homocysteine levels can be lowered by oral folic acid, B-12, and pyridoxine. METHODS: Forty-two schizophrenic patients with plasma homocysteine levels >15 micromol/L were treated with these vitamins for 3 months and placebo for 3 months in a study with a randomized, double-blind, placebo-controlled, crossover design. RESULTS: Homocysteine levels declined with vitamin therapy compared with placebo in all patients except for one noncompliant subject. Clinical symptoms of schizophrenia as measured by the Positive and Negative Syndrome Scale declined significantly with active treatment compared with placebo. Neuropsychological test results overall, and Wisconsin Card Sort (Categories Completed) test results in particular, were significantly better after vitamin treatment than after placebo. CONCLUSIONS: A subgroup of schizophrenic patients with hyperhomocysteinemia might benefit from the simple addition of B vitamins.     

Immunological activation following transcutaneous delivery of HR-gp100 protein

Transcutaneous immunization aims at taking advantage of the skin's immune system for the purpose of immunoprotection. In the present study, we evaluated the potential of topical delivery of a recombinant melanoma protein, HR-gp100, derived from a shortened sequence of the native gp100 gene. The protein was applied on the skin, with and without the addition of two forms of heat labile enterotoxin (nLT and LTB). HR-gp100 fused to Haptide, a cell penetrating 20mer peptide (HR-gp100H) was also tested. Topical HR-gp100 and HR-gp100H application on the ears of mice elicited the production of specific antibodies, and transcutaneous delivery to intact human skin induced dose-dependent LC activation. nLT and LTB also activated LC, but did not further increase the activation induced by HR-gp100. These results show that HR-gp100, an antigenic tumor-derived protein, activates the immune system following transcutaneous delivery, as shown by both Langerhans cell activation and induction of antibody production.     

Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers

Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n=18 M and 5 F) or placebo (0 mg; n=26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4–6 weeks, assessing cannabis'' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects (‘good effect''). Participants in the placebo group had 7.6 times (95% CI: 1.1–51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of ‘good effect'' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone''s efficacy as a treatment for cannabis use disorder.     

High prevalence of thrombophilia among young patients with myocardial infarction and few conventional risk factors

BACKGROUND: Thrombophilia refers to series of acquired and inherited conditions that confer a tendency to thrombus formation. The exact relationship between thrombophilia and MI is not well established. OBJECTIVES: To determine the prevalence of thrombophilia in young patients with their first MI and few conventional risk factors. METHODS: We evaluated the baseline characteristics and the thrombophilia profile, including anti-cardiolipin antibodies, activated protein C resistance (APCR) with the factor V Leiden mutation, prothrombin G20210A mutation, protein C, protein S, and antithrombin-III levels, among 85 consecutive patients (<50 year old) who were admitted to CCU with their first MI. Patients were divided into two groups: group A-patients with < or =1 risk factor and group B-patients with > or =2 risk factors. RESULTS: 92% were male and 55% with anterior wall MI. Overall, the risk factor profile was: smoking in 60%, hyperlipidemia in 42%, positive family history in 29%, hypertension in 18%, diabetes mellitus in 13%, and obesity in 8%. Forty-seven percent of patients had < or =1 risk factor (n=40, group A) and 53% had > or =2 risk factors (n=45, group B). The prevalence of the prothrombin mutation was 15% in group A compared to 7% in group B (p=0.12). APCR secondary to a heterozygous genotype of factor V Leiden mutation was found in 20% in group A compared to 2% in group B (p<0.01). Anti-cardiolipin antibodies were found in 16% in group A compared to 22% in group B (p=ns). Finally, we have found that the likelihood of identifying at least one thrombophilia marker was 50% in group A compared to 29% in group B (p=0.046). CONCLUSIONS: The likelihood to detect at least one thrombophilia marker in young patients with MI and few conventional risk factors is significantly high. Thrombophilia may contribute to the development of MI in this specific group of young patients.     

Effect of feet hyperpronation on pelvic alignment in a standing position

Hyperpronation may cause malalignment of the lower extremity, frequently leading to structural and functional deficits both in standing and walking. Our aim was to study the effect of induced foot hyperpronation on pelvic and lower limb alignment while standing. Thirty-five healthy subjects were requested to remain in a natural standing position for 20s in four different modes: feet flat on the floor, and on wedges angled at 10 degrees, 15 degrees and 20 degrees, designed to induce hyperpronation. Sequencing was random, repeated three times and captured by eight computerized cameras using the VICON three-dimensional motion analysis system. We found that standing on the wedges at various angles, induced hyperpronation, with 41% to 90% of the changes attributable to the intervention. In addition, a statistically significant increase (paired t-test) in internal shank rotation (p<0.0001), internal hip rotation (p<0.0001) and anterior pelvic tilt (p<0.0001) was identified. A strong correlation was found between segmental alignment in every two consecutive modes at all levels (r=0.612-0.985; p<0.0001). These findings suggest that alignment of the lower extremity up to the pelvic girdle, can be altered, due to forces acting on the foot. Interaction between the foot and pelvis occurs in a kinematic chain reaction manner. Although this study was limited to healthy subjects, clinicians should be aware that when addressing pelvis and lower back dysfunction, foot alignment should be examined as a contributing factor.     

Morphological Features of Breast Cancer Circulating Tumor Cells in Blood After Physical and Biological Type of Isolation

BackgroundCirculating tumor cells (CTCs) have become an important biomarker in breast cancer. Different isolation tech-niques based on their biological or physical features were established. Currently, the most widely used methods for visualization after their separation are based on immunofluorescent staining, which does not provide the information on the morphology.Materials and methodsThe aim of this study was to evaluate how two different separation techniques affect cell morphology and to analyse cell morphology with techniques used in routine cytopathological laboratory. A direct side-by-side comparison of physical (Parsortix®) and biological (MACS®) separation technique was performed.ResultsIn the preclinical setting, both isolation techniques retained the viability and antigenic characteristics of MCF7 breast cancer cells. Some signs of degeneration such as cell swelling, cytoplasmic blebs, villous projections and vacuolization were observed. In metastatic breast cancer patient cohort, morphological features of isolated CTCs were dependent on the separation technique. After physical separation, CTCs with preserved cell morphology were detected. After biological separation the majority of the isolated CTCs were so degenerated that their identity was difficult to confirm.ConclusionsTaken together, physical separation is a suitable technique for detection of CTCs with preserved cell morphology for the use in a routine cytopathological laboratory.Key words: CTC, breast cancer, morphology, Parsortix®, MACS®, Giemsa