Bilateral macular hemorrhage after laser in situ keratomileusis

· Background: This is the first report of a bilateral submacular hemorrhage after LASIK surgery in an extreme myo pic patient. A 31-year-old man underwent bilateral surgery for correction of –16.75+0.75×70° and –16.50+0.50×55°. · Methods: Case report. · Results: One day after surgery the patient’s uncorrected visual acuity was in the 20/50 range OU and by 17 days after surgery his visual acuity had declined to 20/200 range. Fundus examination showed multifocal subretinal macular and posterior pole hemorrhages. Fluorescein angiography showed some macular lesions compatible with lacquer cracks. · Conclusions: Preoperative and postoperative fundus examination is important to detect this phenomenon. Patients should be informed of this rare complication. Received: 2 June 1998 Revised version received: 16 November 1998 Accepted: 17 November 1998     

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.     

Benefit-risk assessment of antileukotrienes in the management of asthma.

Antileukotrienes are a relatively new class of anti-asthma drugs that either block leukotriene synthesis (5-lipoxygenase inhibitors) like zileuton, or antagonise the most relevant of their receptors (the cysteinyl leukotriene 1 receptor [CysLT1]) like montelukast, zafirlukast or pranlukast. Hence, their major effect is an anti-inflammatory one. With the exception of pranlukast, the other antileukotrienes have been studied and marketed in the US and Europe for long enough to establish that they are useful drugs in the management of asthma. Their effects, significantly better than placebo, seem more pronounced in subjective measurements (i.e. symptoms scores or quality-of-life tests) than in objective parameters (i.e. forced expiratory volume in 1 second or peak expiratory flow rate). Also, there is some evidence that these drugs work better in some subsets of patients with certain genetic polymorphisms - probably related to their leukotriene metabolism - or patients with certain asthma characteristics. There are a small number of comparative studies only, and with regard to long-term asthma control differences between the agents have not been evaluated. Nevertheless, their overall effect appears comparable with sodium cromoglycate (cromolyn sodium) or theophylline, but significantly less than low-dose inhaled corticosteroids. Antileukotrienes have been shown to have a degree of corticosteroid-sparing effect, but salmeterol appears to perform better as an add-on drug. Montelukast is probably the most useful antileukotriene for continuous treatment of exercise-induced asthma, performing as well as salmeterol without inducing any tolerance. All antileukotrienes are taken orally; their frequency of administration is quite different ranging from four times daily (zileuton) to once daily (montelukast). Antileukotrienes are well tolerated drugs, even though zileuton intake has been related to transitional liver enzyme elevations in some cases. Also Churg-Strauss syndrome (a systemic vasculitis), has been described in small numbers of patients taking CysLT1 antagonists. It is quite probable that this disease appears as a consequence of an 'unmasking' effect when corticosteroid dosages are reduced in patients with severe asthma once CysLT1 antagonists are introduced, but more data are needed to definitely establish the mechanism behind this effect. Overall, however, the benefits of antileukotrienes in the treatment of asthma greatly outweigh their risks.     

Pharmacological Profile of the Vascular Responses to Dopamine in the Canine External Carotid Circulation*

Abstract: The present study investigated the effects of dopamine on the canine external carotid circulation. One min. intracarotid artery (i.c.) infusions of dopamine (10–310 μg min.^?1) produced dose‐dependent decreases in the canine external carotid conductance without affecting blood pressure or heart rate. This effect was mimicked by the D_1/2‐like receptor agonist apomorphine (1–310 μg min^?1), but not by the D₂‐like receptor agonist, bromocriptine (31–310 μg min.^?1). In contrast, fenoldopam (1–310 μg min.^?1, intracarotid), a D₁‐like receptor agonist, produced dose‐dependent increases in external carotid conductance. The vasoconstrictor response to dopamine was abolished after intravenous administration of the antagonists, phentolamine (α_1/2; 2000 μg kg^?1) or rauwolscine (α₂; 100 μg kg^?1), but remained unaffected after prazosin (α₁; 100 μg kg^?1) or haloperidol (D₂‐like; 1000 μg kg^?1). Interestingly, after phentolamine not only were the vasoconstrictor responses to dopamine abolished, but even a dose‐dependent vasodilator component was unmasked. These vasodilator responses to dopamine remained unchanged after intravenous haloperidol or propranolol (1000 μg kg^?1 each). On the other hand, the vasodilator responses to fenoldopam, which remained unchanged after intravenous saline (0.1 ml kg^?1), propranolol (1000 μg kg^?1) or vagosympathectomy, were abolished by the D₁‐like receptor antagonist, SCH‐23390 (10 μg kg^?1). Lastly, the responses to dopamine and fenoldopam were not significantly altered after intraperitoneal pretreatment with reserpine (5 mg kg^?1; ?24 hr). The above results suggest that the canine external carotid vasoconstrictor responses to dopamine: (i) are mainly mediated by α₂‐adrenoceptors; and (ii) overshadow a vasodilator component, which involves vascular D₁‐like receptors.     

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.     

Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients.

PURPOSE: To evaluate safety and preliminary efficacy of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy (RT) in unresectable head and neck cancer patients. Secondary end points were the measurement of h-R3 serum levels and the assessment of the potential mechanisms of antitumor effect on patient biopsies. Anti-idiotypic response to h-R3 was assessed. To predict pharmacologic effect, a mathematical model for antibodies recognizing antigens expressed in tumors and normal tissues was built. PATIENTS AND METHODS: Twenty-four patients with advanced carcinomas of the head and neck received six once-weekly infusions of h-R3 at four dose levels in combination with RT. Pretreatment tumor biopsies were obtained to evaluate epidermal growth factor receptor expression as an enrollment criterion. Second biopsies were taken to evaluate the proliferative activity and angiogenesis in comparison with the pretreatment samples. Patient serum samples were collected to measure h-R3 levels and anti-idiotypic response. RESULTS: The combination of h-R3 and RT was well tolerated. Antibody-related adverse events consisted in infusion reactions. No skin or allergic toxicity appeared. Overall survival significantly increased after the use of the higher antibody doses. Immunohistochemistry studies of tumor specimens before and after treatment revealed that antitumor response correlated with antiproliferative and antiangiogenic effect. One patient developed antibodies to h-R3. The mathematical model predicted that the maximum difference between the area under the curve in tumors and normal tissues is reached when the antibody has intermediate affinity. CONCLUSION: h-R3 is a well-tolerated drug that may enhance radiocurability of unresectable head and neck neoplasms.     

Predictors of cervical coinfection with multiple human papillomavirus types.

Women infected with multiple human papillomavirus (HPV) types seem to be at higher risk of cervical intraepithelial neoplasia, although there is controversy about whether coinfections are associated with lower or higher grades of dysplasia. There is no established risk factor profile for infection with multiple HPV types. We analyzed data from a prospective cohort of 2,075 Brazilian women to identify determinants of HPV coinfection. Cervical specimens were collected for cytology and HPV DNA detection. Data on baseline and time-dependent putative risk factors were obtained by interview. Baseline predictors of HPV coinfection included younger age, greater number of recent sexual partners, a history of condyloma but not of other sexually transmitted diseases, and younger age at first sexual intercourse. In repeated measures analyses, there was a weak positive association between the number of sexual partners in the time interval between two study visits and the risk of coinfection. Our results suggest that the risk factor profile for HPV coinfection among HPV-infected women shares several similarities with risk factors for any HPV infection.