Prevalence and description of psychotic features in bipolar mania

Psychotic symptoms are common in both the manic and depressive phases of bipolar disorder. More than half of patients with bipolar disorder will experience psychotic symptoms in their lifetime. Grandiose delusions are the most common type of psychotic symptom, but any kind of psychotic symptom, including thought disorder, hallucinations, mood-incongruent psychotic symptoms, and catatonia can present as part of a manic episode. Psychotic symptoms suggest poor prognosis when they occur in the absence of affective symptoms. However, psychotic symptoms can mask affective symptoms and make the distinction between manic-depressive illness and other psychiatric disorders difficult, especially in minorities. Careful assessment of prior psychiatric history, family history, and treatment response can aid in the differentiation of affective disorders with psychotic features from psychotic disorders.     

SIALYL-Tn ANTIGEN DISTRIBUTION IN HELICOBACTER PYLORI CHRONIC GASTRITIS IN CHILDREN: AN IMMUNOHISTOCHEMICAL STUDY

Sialyl-Tn antigen (STn) is a mucin-type carbohydrate normally present in goblet cells of small and large bowel. STn expression has been demonstrated to occur in complete and incomplete intestinal metaplasia as well as in many carcinomas but in no normal gastric cell. The aim of our present study was to evaluate the distribution of STn in Helicobacter pylori chronic gastritis (HpCG) of pediatric patients. Eighteen gastric biopsies from 15 children (mean age: 11.5 years) with HpCG, 9 gastric biopsies from 9 children without H. pylori infection, and 1 heterotopic gastric mucosa in Meckel's diverticulum were immunostained using the anti-STn antibody STn1 (18/18), NCL-MUC-1 (7/18), and NCL-MUC-2 (18/18) antibodies. Also, sulfated mucosubstances were investigated with the Alcian Blue-Periodic Acid Schiff (AB-PAS), pH 1.0 stain. Although with different intensity (weak in 5/18, moderate 9/18, and intense 4/18) all cases with HpCG exhibited STn immunoreactivity. The expression of STn was found to be located mainly to the supranuclear region of the epithelial cells at the foveolae and glandular necks, with occasional cells showing diffuse cytoplasmic staining. When reactivity was intense, it was for the most part found in the cells at the neck of the glands. The mucus out of the luminal border above the positive cells was usually also stained. MUC-1 was negative (2/7) or weakly positive (5/7) in a few surface mucous cells. MUC-2 was negative (16/18) or occasionally detected in some foveolar and surface cells (2/18). AB-PAS pH 1.0 revealed the presence of sulfomucins in the cytoplasm of isolated cells of gastric pits and glands of most cases (11/15). None of these findings was observed in the control group. We conclude that STn can be identified in gastric cells of pediatric patients with HpCG and that this does not correlate with other mucosubtances markers. Thefindings could indicate that minimal intestinal metaplasia takes place in children with HpCG.     

Distinct patterns of glomerular disease in Lima, Peru

AIM: We performed both a retrospective and prospective study to elucidate the types of glomerular diseases present in adults in Lima, Peru. MATERIAL AND METHODS: In the retrospective study, we analyzed 1,263 renal biopsies over a 10-year period (1985 -1995) that were processed at a central reference renal pathology laboratory in Lima. 101 cases were examined in the prospective study. RESULTS: The most common glomerular diseases observed were those due to systemic lupus erythematosus (30.2%), membranoproliferative glomerulonephritis (MPGN, 14.8%), and focal and segmental glomerulosclerosis (FSGS, 13.9%). Although mesangial-proliferative nephritis was observed in 9.5% of cases, IgA nephropathy was rare (0.9%). Examination of the year to year frequency showed that MPGN has tended to decrease in frequency with time whereas FSGS has been increasing. Although there is known to be a high frequency of infections in Peru, only 4.2% of the cases in the retrospective study were associated with infection. Furthermore, in the prospective study, only one case of hepatitis C and no cases of hepatitis B viral infection were detected, including in the 11 cases of MPGN observed. CONCLUSION: We conclude that the epidemiology of glomerular disease in Lima, Peru, is distinct from most areas of the world, but has similarities to certain regions in Africa, in that MPGN is common whereas IgA nephropathy appears to be rare. Further studies are necessary to elucidate the reasons why the patterns of glomerular disease are different from that observed in other parts of the world.     

p53 codon 72 polymorphism and cervical neoplasia: a meta-analysis review.

The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene has been implicated as a risk marker in cervical neoplasia. However, research on this topic has produced controversial results. We reviewed the published literature to summarize the association and to identify methodological features that may have contributed to the heterogeneity. Information on specific methodological features of studies addressing this topic published between 1998 and 2002 were obtained. Study-specific odds ratios (ORs) were combined in a meta-analysis, assuming random effects. To identify characteristics that significantly contributed to heterogeneity, we used meta-regression analysis. We identified 50 articles, of which 45 were included in the meta-analyses and regressions. No evidence of association or heterogeneity was detected for preinvasive lesions. For invasive cervical cancer with undefined histology, the Arg/Arg genotype was not found to affect risk (OR, 1.1; 95% confidence interval (CI), 0.9-1.3). However, a slightly increased risk was observed for squamous cell carcinoma (OR, 1.5; 95% CI, 1.2-1.9) and adenocarcinoma (OR, 1.7; 95% CI, 1.0-2.7). Meta-regression analysis identified that the most important factor contributing to heterogeneity among results for invasive lesions was departures from Hardy-Weinberg equilibrium in the control group. Summary ORs for studies in equilibrium were essentially null. A possible susceptibility role by the p53 codon 72 polymorphism at a late carcinogenetic stage in cervical cancer cannot be ruled out. However, various methodological features can contribute to departures from Hardy-Weinberg equilibrium and consequently to less than ideal circumstances for the examination of this polymorphism. Future investigations require appropriate attention to design and methodological issues.     

Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study.

PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.     

Pharmacodynamic evaluation of the epidermal growth factor receptor inhibitor OSI-774 in human epidermis of cancer patients.

BACKGROUND: OSI-774 is an inhibitor of the epidermal growth factor receptor tyrosine kinase (EGFR-TK) currently in clinical development. In preclinical models, the antitumor activity of OSI-774 was directly related to its ability to inhibit the EGFR-TK. On the basis of these data, we hypothesized that inhibition of the EGFR-TK will be required for this agent to be effective in the clinic. This study evaluated the pharmacodynamic effects of OSI-774 in normal skin tissues collected from patients treated with the agent in a Phase I study. METHODS: Patients with advanced cancer who were treated in a Phase I study of OSI-774 underwent a biopsy of normal skin epidermis at baseline and after the last dose of drug in the first course of treatment. The expression and activation of the EGFR, downstream signaling extracytoplasmatic-regulated kinase (Erk), and cell cycle regulator p27 were determined in paraffin-embedded skin tissues using an immunohistochemical method (IHC). The IHC data were analyzed using both a semiquantitative scoring system and an automatic absorbance quantitative IHC method. The number of cells with nuclear staining of p27 per 500 cells was determined. Plasma samples were collected to quantitate OSI-774 plasma concentrations. RESULTS: A total of 56 skin specimens was collected from 28 patients treated with OSI-774 at doses ranging from 25 to 200 mg/day. There was a significant decrease in phospho-EGFR (Tyr 1173) expression as determined semiquantitatively with OSI-774 treatment [2.75 +/- 0.51 (mean +/- SD) pretreatment versus 2.36 +/- 0.76 after treatment, pair comparison P = 0.01]. The quantitative ratio [(phopho-EGFR/EGFR) x 100] of phospho-EGFR (Tyr1173) decreased from 64.16 +/- 36.58 pretreatment to 48.87 +/- 35.37 post-treatment (pair comparison, P = 0.02). No significant differences were observed in phospho-Erk (Thr202/Tyr204) expression. The mean number of cells with nuclear staining for p27 increased from 185 +/- 101 (mean +/- SD) pretreatment to 253 +/- 111 post-treatment (pair comparison P = 0.02). A total of 12 (42.8%), 7 (25%), and 14 (50%) patients had >25% variation in the ratio of phospho-EGFR (Tyr1173), phospho-Erk (Thr202/Tyr204), and p27 expression, respectively. Only changes in p27 expression were related to the administered dose of OSI-774. CONCLUSIONS: OSI-774 exerted pharmacodynamic effects in skin tissues of 30-50% of patients treated with the agent. Up-regulation of p27, which is a downstream effect of EGFR inhibition, was dose related. Although there was a significant decrement in phospho-EGFR (Tyr1173), it was not related to the administered dose of OSI-774. On the basis of these findings and the relatively simple and reliable method to measure p27 expression, this biomarker appears to be the most promising and is being evaluated in Phase II studies as a predictor of clinical outcome.     

Tratamiento del cáncer de esófago localizado y localmente avanzado: ¿algo ha cambiado?

Esophageal cancer has a dismal prognosis and the surgical treatment only cures a small percentage of patients. The survival achieved by traditional surgical procedures is being improved with extended resections, but at the cost of greater morbidity. Concurrent radiochemotherapy can obtain results similar to those of surgery. Nowadays, locally advanced esophageal cancer should have a multimodal approach, because neoadjuvant chemotherapy, with or without radiotherapy, has demonstrated to improve the survival of chemosensitive patients. Recently, the role of hyperfractionated radiotherapy and new drugs such as paclitaxel, docetaxel and irinotecan in neoadjuvant treatment is being evaluated.     

Intraplatelet cyclic guanosine-3',5'-monophosphate levels during pregnancy and preeclampsia.

OBJECTIVE: To investigate the intraplatelet cyclic guanosine-3',5'-monophosphate (cGMP) levels during normal pregnancy and preeclampsia. STUDY DESIGN: Pregnant women (n = 15), women with preeclampsia (n = 15), and nonpregnant, normotensive women (n = 15) were included. Intraplatelet cyclic guanosine-3',5'-monophosphate levels were measured by an enzyme-linked immunosorbent assay. RESULTS: Intraplatelet cGMP levels were significantly different among all groups (p < 0.02). The values were higher in normal pregnant women (mean 19.8 SD 2.6 fmol/10(5) platelets) in comparison to nonpregnant women (mean 7.6 SD 0.3 fmol/10(5)platelets; p = 0.001) and women with preeclampsia (mean 11.3 SD 1.8 fmol/10(5) platelets; p = 0.05). Plasma nitric oxide levels did not reveal differences between all groups. CONCLUSIONS: The results of this study in a high-risk Andean population demonstrated that intraplatelet cyclic guanosine-3',5'-monophosphate levels are decreased during preeclampsia compared to normal pregnancy, suggesting a lack in action of nitric oxide.     

The effects of the ketogenic diet in refractory partial seizures with reference to tuberous sclerosis.

PURPOSE: Tuberous sclerosis complex (OMIM 191100) is a multiorgan disease commonly associated with epilepsy refractory to anticonvulsants. Individual reports indicate that seizures in children with tuberous sclerosis might benefit from a ketogenic diet. We studied the effects of the diet introduced at 3.5 years of age in three boys with tuberous sclerosis and refractory partial seizures. METHODS: On admission a classical LCT ketogenic diet was initiated and patients were followed for 12 months. Antiepileptic drugs were maintained unless adverse effects required reduction. RESULTS: Two patients became seizure-free within 2 months on the diet. In the third patient drop attacks decreased significantly. On follow-up the diet was well accepted and without adverse effects. CONCLUSION: The ketogenic diet should be considered as a treatment option for children with tuberous sclerosis and partial seizures refractory to anticonvulsants. Our data support the need for further studies in larger cohorts to confirm the effectiveness of the ketogenic diet in this entity.