Unanticipated plasma concentrations in two clozapine-treated patients

OBJECTIVE: To report two cases of lower than anticipated clozapine plasma concentrations despite near maximum recommended doses of clozapine 800-900 mg/d in two medication-compliant schizophrenic inpatients. CASE SUMMARIES: Clozapine therapy was initiated in two male schizophrenic inpatients for treatment of psychotic symptoms refractory to other typical and atypical antipsychotics. Despite receiving adequate doses of clozapine for at least two months, these patients remained symptomatic. Therapeutic drug monitoring was used to target a clozapine plasma concentration of > or =250 ng/mL, the minimum value reported in the literature to be associated with increased clinical response. Clozapine plasma concentrations remained at 200 ng/mL in one patient despite dosage increases from 600 to 800 mg/d. In the second patient, administration of the maximum recommended dose resulted in concentrations between 200 and 250 ng/mL. Increasing the clozapine dosage to 1000 mg/d did not increase the clozapine plasma concentration. Evaluation of the ratio of clozapine plasma concentration clozapine to dose yielded lower than expected values compared with those reported in the literature. DISCUSSION: These two patients exhibited lower than anticipated clozapine plasma concentrations despite receiving high doses of clozapine. Several studies evaluating clozapine serum concentrations and clinical response have suggested threshold concentrations of > or =350 ng/mL, > or =370 ng/mL, or > or =420 ng/mL. The only study that randomized patients to three concentration ranges found that patients who achieved a clozapine serum concentration in a medium range (mean 251 ng/mL) responded better than patients in a low range (mean 91 ng/mL) and similar to patients in a high range (mean 396 ng/mL). However, attaining plasma concentrations in this range for these patients proved difficult. Reasons for the low concentrations are unclear and may be related to increased metabolic activity at several cytochrome P450 isoenzymes involved in the metabolism of clozapine. CONCLUSIONS: These cases illustrate lower than anticipated clozapine plasma concentrations despite high-dose clozapine therapy. Strategies to increase clozapine plasma concentrations in such patients might include adding a drug to partially inhibit the metabolism of clozapine. If those strategies are unacceptable based on risk assessment, patient compliance, or other reasons, clinicians may consider addition of a low-dose typical or other atypical antipsychotic drug to augment clozapine response.     

Validity of hand-held systems for otoacoustic emissions in hearing screening

Hearing screening objective is the development of an universal screening. With that purpose, new hand-held system of Otoaccoustic Emissions have been designed, which are easier to perform and to interpret the results, to detect hearing loss disordersas soon as possible. To validate the hand-held systems of Otoaccoustic Emissions in the hearing screening, we have compared the results of the tests with Otoaccoustic Emissions clinic systems and tonal audiometry in two groups of population: new-borns and hearing-loss adults aged between 16 and 56. Our study showed that the hearing screening results in children with hand-held system were similar to classic Otoaccoustic Emissions system, but there were more than 40% of adult hearing losses not detected with this system. These results can invalidate the test.     

Laparoscopic biliopancreatic diversion with a duodenal switch for morbid obesity: a feasibility study in pigs

BACKGROUND and PURPOSE: Biliopancreatic diversion with a duodenal switch is an emerging open procedure that appears as effective as other bariatric operations. Our goal was to determine the safety and feasibility of performing this procedure using a laparoscopic approach in a porcine model. MATERIALS and METHODS: Six 50-kg pigs underwent surgery. Intake was restricted with a sleeve gastrectomy, and malabsorption was obtained by creating a Roux-en-Y. The Roux limb served as a 150-cm alimentary channel following anastomosis to a transected proximal duodenum, while the other limb, or biliopancreatic channel, transported digestive juices. Where the two limbs joined, a 100-cm common channel was formed. RESULTS: The operation was completed in a mean time of 4.5 hours. Two of the six pigs had an intraoperative duodenoenterostomy anastomotic leak detected on methylene blue testing. This leakage was thought to be related to pig anatomy and is not expected to be a problem in humans. At necropsy, all anastomoses were patent, and there were no enteroenterostomy leaks or mesenteric torsions. CONCLUSION: On the basis of the porcine model, laparoscopic biliopancreatic diversion with a duodenal switch is anticipated to be feasible and safe in humans. Substantial weight loss combined with the benefits of laparoscopic surgery can be expected.     

Primary tuberculous otitis media

Tuberculous otitis media is now an infrequent disease, with an incidence of less than 1%. In most cases the origin is a pulmonary focus and primary cases are rarer. We report a case of primary tuberculous otitis media in an immunocompetent patient. A bibliographic review was made of clinical and etiopathogenic aspects, as well as diagnosis and treatment. We highlight the diagnostic difficulty and the fact that this entity should be included in the differential diagnosis of persistent suppurative otitis media.     

The relationship between immigration and mental health: what is the role of workplace psychosocial factors

Background

To study the relationship between immigration and mental health considering the psychosocial factors in the workplace.

Methods

Multistage cluster sampling was used (final sample: 7,612 workers). Workers whose country of origin was unknown were excluded from the study (study population: 7,555). The information was collected between 2004 and 2005 using a standardized questionnaire, and interviews were conducted in respondents’ homes. The risk of poor mental health according to psychosocial factor, using the native, non-exposed workers as a reference, was calculated using log-binomial models. The prevalence ratio (PR) and confidence intervals (CI 95%) were estimated from crude data and from data adjusted for sex, age, and occupational category.

Results

Immigrants who experienced high quantitative demands (PR?=?1.46; CI 95%:1.34–1.59), high emotional demands (PR?=?1.42; CI 95%:1.301.56), high demands for hiding emotions (PR?=?1.35; CI 95%:1.21–1.50), low possibilities for development (PR?=?1.21; CI 95%:1.09–1.33), low levels of support from coworkers (PR?=?1.41; CI 95%:1.30–1.53), and low esteem (PR?=?1.53; CI 95%:1.42–1.66) perceived worse mental health. Equally, the study found that the immigrants with a high influence (PR?=?1.19; CI 95%:1.09–1.29) and high control over working times (PR?=?1.25; CI 95%:1.14–1.36) also reported worse mental health. We also found that native workers exposed to these factors also perceived worse mental health than those who were not exposed and that even, at times, they were at greater risk than exposed immigrants.

Conclusions

Differences in mental health between exposed and non-exposed wage earners, whether immigrant or native workers, indicate the importance of taking action to reduce psychosocial factors, as this would benefit both native and immigrant workers.     

Palatonasal Recess on Medial Wall of the Maxillary Sinus and Clinical Implications for Sinus Augmentation via Lateral Window Approach

Background: Anatomic variations of the maxillary sinus determine the degree of difficulty in performing sinus augmentation. Whereas some variations, e.g., the septum and morphology of the sinus, have been extensively studied, the structure of the medial wall has never been investigated. The aims of this study are to measure the location and angulation of the palatonasal recess (PNR) on the medial wall and identify risk sites that are related to the shape of the PNR. Methods: Cone‐beam computed tomography (CBCT) scans were screened from the University of Michigan School of Dentistry database. Edentulous sites with <10 mm between the floor of the maxillary sinus and the alveolar crest were selected. The residual ridge height (RH), the distance between the PNR and the alveolar crest, and the angulation of the PNR were measured on the selected sagittal planes. The percentage of sites (risk sites) with recesses that were <90°and <15 mm from the alveolar crest was calculated. The PNR location and angulation were compared among premolar and molar edentulous sites. Results: Two hundred seventy‐four sites were studied. The mean ± SE PNR location was 14.2 ± 2.8 mm, 13.1 ± 2.2 mm, and 12.5 ± 2.5 mm for the second premolar, first molar, and second molar sites, respectively, with significant differences between the second premolar and second molar sites. The mean PNR angulation was 109.8° ± 25.3°, 121.6° ± 22.1°, and 144.9° ± 23.1° in the corresponding sites, with significant differences among the site groups. The respective percentages of risk sites were 15%, 8.2%, and 2.4% in the second premolar, first molar, and second molar sites. Conclusions: Maxillary sinuses with acute‐angled PNRs might present a challenge for performing sinus augmentation. Therefore, this anatomic structure should be carefully evaluated.     

Mesangial expansion at 5 years predicts death and death‐censored graft loss after renal transplantation

Death with a functioning graft and death‐censored renal allograft failure remain major problems for which effective preventative protocols are lacking. The retrospective cohort study aimed to determine whether histologic changes on a 5‐year surveillance kidney biopsy predict adverse outcomes after transplantation in recipients who had: both Type 2 diabetes (T2DM) and obesity (BMI ≥ 30 kg/m²) at the time of transplantation (T2DM/Obesity, n = 75); neither (No T2DM/No obesity, n = 78); No T2DM/Obesity (n = 41), and T2DM/No obesity (n = 47). On 5‐year biopsies, moderate‐to‐severe mesangial expansion was more common in the T2DM/Obesity group (Banff mm score ≥2 = 49.3%; Tervaert classification MS ≥ 2b = 26.7%) compared to the other groups (p < .001 for both scores). Risk factors included older age, higher BMI, HbA1C, and triglycerides at 1‐year post‐transplant. Moderate‐to‐severe mesangial expansion correlated with death with function (HR 1.74 (1.01, 2.98), p = .045 Banff and 1.89 (1.01, 3.51) p = .045 Tervaert) and with death‐censored graft loss (HR 3.2 (1.2, 8.8), p = .02 Banff and HR 3.8 (1.3, 11.5), p = .01 Tervaert) over a mean of 11.6 years of recipient follow‐up post‐transplant. These data suggest that mesangial expansion in recipients with T2DM and obesity may reflect systemic vascular injury and might be a novel biomarker to predict adverse outcomes post renal transplant.     

Prevalence of HIV and syphilis in pregnant women in Leon, Nicaragua

The objective of this study was to determine the prevalence of HIV and syphilis and to identify risk factors among pregnant women visiting antenatal clinics in León, Nicaragua. During February to April 2004, blood samples from pregnant women were collected after written consent had been obtained. The samples were tested for antibodies against HIV and Treponema pallidum. A questionnaire was also completed. In total, 1,059 women were included. Antibodies against HIV were not detected in any of the women, whereas antibodies against T. pallidum were detected in 16 (1.5%). Risk factors for syphilis included illiteracy, lower education, and two or more pregnancies. HIV does not seem to be highly prevalent among pregnant women in León (prevalence, 0%; 95% CI, 0.0-0.3). The higher proportion of women infected with syphilis than found in earlier studies suggests that sexually transmitted diseases are circulating in the general population and highlights the increasing importance of HIV prevention.