Low percentage of patients passed the 'Back in Action' test battery 9 months after bone-patellar tendon-bone anterior cruciate ligament reconstruction.

Background: Anterior cruciate ligament (ACL) reconstruction is recommended in patients who intend to return to high-level sports. However, there is only a 55-80% return to pre-injury level of sports after ACL reconstruction, with a re-injury rate up to 20%. The aim of this study was to determine the percentage of patients passing the Back in Action (BIA) test 9 months after primary bone-patellar-tendon-bone (BPTB) ACL reconstruction, and evaluate the association between passing the BIA test and patient reported outcome measurements (PROMs). Methods: Patients underwent the BIA test 9 months after BPTB ACL reconstruction. In total 103 patients were included. Passing the BIA test (PASSED-group) was defined as a normal or higher score at all sub-tests with limb symmetry index (LSI) ≥90% for the dominant leg and LSI >80% for the non-dominant leg. Patients who did not meet these criteria were defined as the FAILED-group. PROMs included the International Knee Documentation Committee, Knee injury Osteoarthritis Outcome Score and Anterior Cruciate Ligament-Return to Sport after Injury. Results: Eighteen patients (17.5%) passed the BIA test 9 months after BPTB ACL reconstruction. PROMs were not statistically significant different between the PASSED- and FAILED-group. Conclusion: Low percentage of patients passed the BIA test 9 months after BPTB ACL reconstruction. Although current PROMs cut-off values were met, the BIA test results show persistent functional deficits. Therefore, the BIA test could be of additional value in the decision-making process regarding return to sport (RTS). This study highlights the need for additional rehabilitation as RTS in a condition of incomplete recovery may increase the risk of re-injury. Level of evidence: II.

Effect of Low-Load Blood Flow Restriction Training After Anterior Cruciate Ligament Reconstruction: A Systematic Review.

Background: Quadriceps strength and mass deficits are common after anterior cruciate ligament (ACL) reconstruction. Postoperatively, heavy load resistance training can have detrimental effects on knee joint pain and ACL graft laxity. Therefore, low-load blood flow restriction (LL-BFR) training has been suggested as an alternative to traditional strength rehabilitation. Purpose: The present systematic review aimed to investigate the effect of LL-BFR training on quadriceps strength, quadriceps mass, knee joint pain, and ACL graft laxity after ACL reconstruction compared to non-BFR training. Study design: Systematic review. Methods: A systematic literature search of PubMed, EMBASE.com, Cochrane Library/Wiley, CINAHL/Ebsco and Web of Science/Clarivate Analytics was performed on 19 February 2021. Studies were included if they compared LL-BFR and non-BFR training after ACL reconstruction with pre- and post-intervention quadriceps strength, quadriceps mass, knee joint pain or ACL graft laxity measurement. Systematic reviews, editorials, case reports and studies not published in a scientific peer reviewed journal were excluded. The risk of bias of randomized studies was assessed with the use of the Cochrane Risk of Bias Tool. Results: A total of six randomized controlled trials were included. Random sequence generation and allocation concealment was defined as high risk in two of the six studies. In all studies blinding of participants and personnel was unclear or could not be performed. The included studies used different LL-BFR and non-BFR protocols with heterogeneous outcome measurements. Therefore, a qualitative analysis was performed. Two of the six studies assessed quadriceps strength and demonstrated significant greater quadriceps strength after LL-BFR compared to non-BFR training. Quadriceps mass was evaluated in four studies. Two studies observed significant greater quadriceps mass after LL-BFR compared to non-BFR training, while two studies observed no significant difference in quadriceps mass. Knee joint pain was assessed in three studies with significantly less knee joint pain after LL-BFR compared to non-BFR training. Two studies evaluated ACL graft laxity and observed no significant difference in ACL graft laxity between LL-BFR and non-BFR training. Conclusion: The results of this systematic review indicate that LL-BFR training after ACL reconstruction may be beneficial on quadriceps strength, quadriceps mass, and knee joint pain compared to non-BFR training with non-detrimental effects on ACL graft laxity. However, more randomized controlled trials with standardized intervention protocols and outcome measurements are needed to add evidence on the clinical value of LL-BFR training. Level of evidence: 2a.

Predictors of patient satisfaction after primary hamstring anterior cruciate ligament reconstruction.

BACKGROUND: Predictors of patient satisfaction (PS) after anterior cruciate ligament (ACL) reconstruction are not well known. This study investigated predictors of PS and whether PS was associated with pre-injury level of sport participation, patient reported knee function and quality of life after ACL reconstruction. METHODS: Patients who underwent primary hamstring ACL reconstruction between January 2015 and December 2017 were retrospectively evaluated. An online survey was used to evaluate PS (yes = satisfied, no = unsatisfied), duration of supervised postoperative rehabilitation, timing of return to pre-injury level of sport, pre-injury level of sport participation, patient reported knee function and quality of life. Preoperative, operative and postoperative variables were collected from the medical records. RESULTS: A total of 183 patients completed the survey at a median of 3.6 (1.5) years after ACL surgery. At final follow-up, 82% of patients were satisfied with the outcome. Preoperative (e.g. age) and operative (e.g. meniscal tear) variables were not predictors of PS (p > 0.05). Duration of supervised postoperative rehabilitation, timing of return to pre-injury level of sport and postoperative ACL injury were predictors of PS (p = 0.018, p = 0.016 and p < 0.001, respectively). Pre-injury level of sport participation was significantly higher in satisfied compared to unsatisfied patients: 44.7% (n = 67) versus 18.2% (n = 6) (p = 0.005). In addition, satisfied patients reported significantly higher patient reported knee function and quality of life compared to unsatisfied patients (p < 0.001). CONCLUSION: This study provided data on predictors of PS after primary ACL reconstruction. Furthermore, PS was associated with pre-injury level of sport participation, patient reported knee function and quality of life.

Coping in crisis: The role of psychologists in response to a pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has had a major impact on the world. In the United States, healthcare systems have been taxed, medical supplies depleted, and healthcare providers overburdened by the increased need. Although psychologists cannot provide medical services, we possess a unique skillset that can alleviate some of the stress placed on healthcare providers, answer important questions about how this disease impacts patients, and support the growing mental health needs of providers and patients alike. The following commentary outlines the ways in which psychologists and mental health workers at one facility, the Southeast Louisiana Veterans Health Care System, supported the medical system and cared for patient and staff mental health in response to the COVID-19 pandemic. Lessons learned from this experience as well as important future steps are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Gastrointestinal stromal tumors of the stomach: A 10-year experience of a single-center.

BACKGROUND: Gastrointestinal tract stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract (GIS). GISTs may cause significant morbidity and mortality rates. AIM: In this study, it was aimed to evaluate 10 years of gastric GIST cases followed in our hospital, and to analyze the prognostic factors. SUBJECTS AND METHODS: In this single-center retrospective study, a total of 64 patients who were operated between May 2010 and May 2020 due to gastric GIST tumor were reviewed. Clinical and pathological features, risk classifications, overall survival (OS) and disease-free survival (DFS) were evaluated. RESULTS: According to the risk classification, 18.8% of the patients were in the high-risk group. The overall 5-year OS and DFS rates were 85.7%. The mean OS of the patients was 47.9 SD36.2 months, and the duration of DFS was 45.5 months. Patients with a 5-year OS rate above 5 cm in diameter (P = 0.024), with a mitotic index above 5/50 high power field (HPF) (P = 0.038), and those with a high-risk group (P = 0.011) were significantly lower than the other group. In the correlation analysis, it was found that tumor diameter correlated significantly with OS (P = 0.034; r = -0.317). Tumor diameter and mitotic index were found to be inversely correlated with DFS duration (P = 0.004; r = -0.425 and P = 0.035; r = -0.316, respectively). CONCLUSION: Our findings showed that in gastric GIST cases, as the primary tumor diameter and mitotic index increase, correlate with survival rates and the mean overall and disease-free survival times decrease.

Preferences in anterior cruciate ligament reconstruction and return to sport: A survey among surgeons in the Netherlands.

OBJECTIVE: The purpose of this study was to investigate the preferences of surgeons on technique for femoral tunnel placement, graft selection and criteria for return to sport in the Netherlands. METHODS: A web-based survey among the Dutch Association of Arthroscopy was conducted. RESULTS: A total of 125 members (24.0%) were included in the analysis. A total of 87.2% (n = 109) used hamstring autografts for primary ACL reconstruction followed by patellar tendon autograft (n = 11, 8.8%) and quadriceps tendon autograft (n = 5, 4.0%). The anteromedial technique was favored by 50.4% (n = 63), whereas 11.2% (n = 14) of the participants favored the transtibial technique. Return to sport after 9 months of primary ACL reconstruction was allowed by 75.2% (n = 94) of the participants. Regarding criteria to evaluate readiness to return to sport, the surgeons stated postoperative period (n = 107, 85.6%) and functional performance tests (n = 96, 76.8%) as important. CONCLUSION: The majority of the participants of the Dutch Association of Arthroscopy favored the hamstring autografts for primary anterior cruciate ligament reconstruction. Furthermore, most participants stated postoperative time and functional performance tests as important criteria to evaluate readiness to return to sport. This is the first survey demonstrating a high preference of surgeons to use functional performance tests in the decision-making of readiness to return to sport.

Mechanoreceptors observed in a ligamentous structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament.

PURPOSE: A histological study of a structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament. METHODS: Bilateral fresh-frozen cadaveric knees of two male donors (age 71 and 76 years) with no history of prior knee injury were examined. All dissections were performed by one experienced orthopaedic surgeon. Haematoxylin and Eosin staining was used to reveal tissue morphology. Goldner trichrome staining was used to evaluate the connective tissue. S100 and PGP 9.5 labelling were used for immunohistochemical analysis. RESULTS: In all cadaveric knees, a structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament was identified. Histological analysis confirmed the ligamentous nature of this structure. Furthermore, Golgi tendon organs were observed within the ligamentous structure. CONCLUSION: This is the first study showing the presence of mechanoreceptors within the ligamentous structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament. The ligamentous structure could contribute to stability of the knee by providing proprioceptive input, while preservation of the ligamentous structure might ensure a better functional outcome after surgery.

A Modified Extensile Anterior Approach to the Acetabulum for Severe Acetabular Defects.

A modified extensile Smith-Petersen approach was used to access the acetabulum and pelvis in cases with complex acetabular defects requiring extensive reconstructions. Between 2010 and 2014, a total of 49 hips (48 patients) with a variety of acetabular defects were reconstructed using highly porous hemispherical acetabular cups and different reconstruction methods. Preoperative diagnoses included isolated aseptic loosening of the acetabular component, aseptic loosening of both acetabular and femoral components, infection, and other. Five patients (5 hips) died prior to the 2-year follow-up, with death being unrelated to the index operation. Mean follow-up of the remaining 44 hips was 40 months. There were no intraoperative complications. Ten patients had postoperative complications; all occurred within the first 12 months postoperatively. Complications occurred in 30% and 70% of type 2 and type 3 defects, respectively. Half of the complications were treated nonoperatively. The all-cause reoperation rate was 10%. All implants were radiographically stable. The modified extensile anterior approach to the acetabulum and pelvis is safe and allows for excellent exposure and successful reconstruction of bony defects. The exposure is less successful in addressing instability due to abductor or soft tissue deficiencies, with a re-revision rate of 4% to a constrained liner for recurrent instability. Seventy percent of all complications and 83% of all dislocations occurred in the Paprosky type 3 defect group. To decrease complications with a complex acetabular defect and associated deficiency of the abductor mechanism and soft tissue constraints, a constrained liner or dual mobility socket should be considered to simultaneously address both bony defects and soft tissue deficiencies. [Orthopedics. 2018; 41(2):e194-e201.].

A Phase II, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with ß-Thalassemia Major.

We conducted a prospective, phase II, multicenter, single-arm study to evaluate the efficacy and safety of deferasirox in patients age >2 to <18 years with ß-thalassemia major (TM) who underwent hematopoietic stem cell transplantation (HSCT) and had evidence of iron overload (serum ferritin >1000 µg/L; cardiac MRI T2* <20 ms, or liver iron concentration [LIC; by MRI R2] ≥5 mg/g). Patients received deferasirox at an initial dose of 10 mg/kg/day, with up-titration to a maximum of 20 mg/kg/day. The study continued for 52 weeks and included a total of 27 patients (mean age, 9.1 ± 3.8 years; 70.4% male). One patient (3.7%) was lost to follow-up. The majority of patients (n = 20; 74.1%) were able to achieve the intended dose of 20 mg/kg/day. No deaths occurred. A total of 134 adverse events (AEs) were reported in 25 patients (92.6%) during the study. The majority of patients had grade 1 or 2 AEs, with only 8 patients (29.6%) experiencing grade 3 AEs. Only 10 AEs occurring in 4 patients (14.8%) were suspected to be related to deferasirox (ALT/AST increase, n = 4; urinary tract infection, n = 1). The deferasirox dose had to be adjusted or interrupted for 6 AEs occurring in 4 patients (14.8%). A total of 6 serious AEs occurred in 3 patients (11.1%), none of which were suspected to be related to deferasirox. From baseline to week 52, there were decreases in median concentrations of alanine aminotransferase (ALT), from 30.0 to 17.0 IU/L, and aspartate aminotransferase (AST), from 35.5 to 26.0 IU/L. Median serum creatinine and cystatin C concentrations were similar at baseline and week 52. There was a continuous and significant decrease in median serum ferritin level from 1718.0 µg/L at baseline to 845.3 µg/L following 52 weeks of therapy (P < .001); 9 patients (33.3%) achieved a level of <500 µg/L. There was also a significant decrease in median LIC (from 8.6 to 4.1 mg/g; P < .001) and an increase in median cardiac T2* (from 26.0 to 28.0 ms; P = .520) from baseline to week 52. Our findings indicate that deferasirox treatment at doses up to 20 mg/kg/day reduces the iron burden in children with TM post-HSCT, with a manageable safety profile.

Effectiveness of Early Warming With Self-Warming Blankets on Postoperative Hypothermia in Total Hip and Knee Arthroplasty.

BACKGROUND: Hypothermia is an important complication in joint arthroplasty. Commonly, forced air warming (FAW) devices are used intraoperatively to maintain body temperature in patients undergoing surgery. However, it is believed that these convective warming systems could increase the risk of deep surgical site infections due to disruption of unidirectional downward laminar airflow. Conductive warming devices have no noticeable effect on ventilation airflow. Nevertheless, the effectiveness of the self-warming (SW) blanket, a novel conductive warming device, on postoperative hypothermia in elective joint arthroplasty is unknown. PURPOSE: The purpose of this study was to evaluate the effectiveness of early warming with SW blankets in the prevention of postoperative hypothermia in elective total hip (THA) and knee arthroplasty (TKA) compared with FAW devices. METHODS: Patients who underwent elective THA or TKA between May and June 2014 were assigned in the FAW or SW group. A total of 105 patients were enrolled into the study. In the FAW group, the FAW devices were applied after disinfection of the surgical site. In the SW group, the SW blankets were already applied in the orthopaedic department. The duration of warming with SW blankets before anesthetic induction was documented. The body temperature was measured preoperatively upon arrival in the orthopaedic department and postoperatively upon arrival in the postanesthesia care unit. The patient's body temperature was measured at the tympanic membrane, and hypothermia was defined as a body temperature of less than 35.5°C. RESULTS: The SW blankets were applied for a median of 86.8 minutes (78.8-94.8) before anesthetic induction. Postoperative hypothermia was observed in 15 (31.3%) and eight (14.0%) patients in the FAW group and the SW group, respectively (p = .029). The median postoperative body temperature was 35.59°C (35.44-35.74) and 35.95°C (35.83-36.06) in the FAW group and the SW group, respectively (p < .001). CONCLUSION: Early warming with SW blankets was more effective than FAW devices in the prevention of postoperative hypothermia in elective THA and TKA.

Endoscopic debridement and fibrin glue injection of a chronic Morel-Lavallée lesion of the knee in a professional soccer player: A case report and literature review.

A Morel-Lavallée lesion is a post-traumatic closed degloving injury of soft tissue. The lesion is due to a shearing trauma with separation of subcutaneous tissue from underlying fascia. When conservative treatment fails, surgical treatment is imperative. Commonly, open drainage and debridement is performed. This case report describes a Morel-Lavallée lesion of the knee in a professional soccer player who was successfully treated with endoscopic debridement and fibrin glue injection after failure of conservative management. This method achieves the goal of an open surgical debridement without exposing patients to an increased morbidity.

Single- and multiple-dose pharmacokinetics of ziprasidone in healthy young and elderly volunteers.

AIMS: To compare the pharmacokinetics of ziprasidone in healthy young (18-45 years) men and women, and healthy elderly (> or = 65 years) men and women. METHODS: Eight young men, 11 young women, 8 elderly men and 8 elderly women were given oral ziprasidone 40 mg day(-1), in two evenly divided daily doses, for 7 days, followed by a single 20 mg dose on day 8. Serum samples were collected immediately before the morning dose on days 1-8, for up to 12 h after dosing on day 1 and for up to 96 h after dosing on day 8. The resulting data were used to derive pharmacokinetic parameters of ziprasidone in each age and gender group. RESULTS: Steady-state serum concentrations of ziprasidone were achieved within 2-3 days. The steady-state pharmacokinetics of ziprasidone, determined 8 days after the initiation of treatment, were similar in the young men, elderly men and young women. Assessment of gender effects by analysis of variance revealed statistically significant differences in Cmax (85 vs. 69 ng ml(-1) and tmax (3.19 vs. 4.81 h) but no differences in AUC(0,12 h) or lambda(z). Assessment of age effects by analysis of variance revealed statistically significant differences in AUC(0,12 h) (560 vs. 465 ng ml(-1) h), Cmax (85 vs. 69 ng ml(-1) and lambda(z) (0.126 vs. 0.197 l h(-1) but no difference in tmax. Assessment of age and gender effects by analysis of covariance, with body weight as the covariate, did not reveal any significant differences. The mean t(1/2), z in the young men, young women, elderly men and elderly women were 3.1, 4.1, 5.7 and 5.3 h, respectively. Standard deviations of the means for the pharmacokinetic parameters for the elderly women tended to be large. CONCLUSIONS: The influence of age and gender on the pharmacokinetics of ziprasidone is not clinically significant.

[Estimation of the incidence of eight malignant tumours in France, on the basis of health insurance's statistics]. / Estimation de l'incidence de huit tumeurs malignes en France à partir des statistiques de l'assurance maladie.

This work has for aim to suggest coefficients of adjustment applicable to the statistics of malignant tumours refunded through the health insurance as long-term diseases. Those coefficients would allow to evaluate the morbidity rate of cancer in the general population in France. To reach this target, we compared the figures of health insurance to those of the registers of cancers in six french departments, after we made the necessary adjustments to make the comparison possible. We showed that, for each cancer, the coefficient of adjustment is equal to the median of the relative differences that we noticed between the figures of the registers and those of the health insurance. We calculated the adjustment coefficients for bladder cancers (1.07), colon-rectum cancers (1.36), womb cancers (1), kidney cancers (0.83), lung cancers (1.33), oesophagus cancers (1.56) and prostate cancers (1.37). The comparison between the incidences adjusted on the basis of the figures of the health insurance, the incidences estimated by the Inserm and those released in the literature allowed us to confirm the validity of the coefficient we propose, except for the kidney cancer and the lung cancer by women, for whom we can't make any conclusions. Our work shows that the statistics of health insurance builds up a basis of information that can be used to study the morbidity rate of some malignant tumours in France.

Single- and multiple-dose administration, dosing regimens, and pharmacokinetics of trovafloxacin and alatrofloxacin in humans.

A simplified dosing algorithm for trovafloxacin was evaluated following a single-dose infusion of alatrofloxacin at trovafloxacin equivalent doses of 30, 100, 200, 300 and 400 mg (57 subjects), and multiple doses of 200, 300 and 400 mg (30 subjects). Maximum serum concentration and area under the concentration-time curve for trovafloxacin increased with dose. Trovafloxacin clearance (82-85 ml x h/kg) and volume of distribution (1.3-1.6 l/kg) were independent of dose. Infusion of alatrofloxacin at a trovafloxacin equivalent dose of 300 mg at 1, 2 or 3 mg/ml over 1 h did not alter the pharmacokinetics of trovafloxacin. A plot of the weight-adjusted dose of trovafloxacin in individual subjects against the maximum serum concentration following single and multiple dosing, indicated that the maximum serum concentration increased 1 microg/ml for each 1 mg/kg of trovafloxacin administered. Thus, a prior knowledge of the desired serum concentration will permit appropriate dosing without the use of complex nomograms in patients with normal hepatic function.

Pharmacokinetics and safety of trovafloxacin in healthy male volunteers following administration of single intravenous doses of the prodrug, alatrofloxacin.

Fifteen healthy male volunteers (in four groups) received single 1 h i.v. infusions of alatrofloxacin (CP-116,517) equivalent to 30, 100, 200 or 300 mg of its active metabolite, trovafloxacin (CP-99,219). Blood and urine were sampled over 73 and 72 h, respectively, and plasma levels of alatrofloxacin and serum concentrations of trovafloxacin were determined by HPLC with UV detection. Alatrofloxacin was not detectable in plasma samples collected after the end of infusion, indicating rapid conversion to trovafloxacin. Maximum serum concentrations of trovafloxacin were achieved at the end of the infusions. Mean maximum plasma trovafloxacin concentrations for the four alatrofloxacin doses were 0.4, 1.8, 2.3 and 4.3 mg/L. The mean area under the concentration-time curve increased proportionally with the dose. The elimination half-life (T(1/2)) for trovafloxacin was independent of the dose and the mean T(1/2)s for the 100, 200 and 300 mg equivalent doses of alatrofloxacin were 10.4, 12.3 and 10.8 h. Approximately 10% of the equivalent dose was recovered as unchanged trovafloxacin in the urine. No clinical adverse or laboratory reactions were associated with i.v. administration of alatrofloxacin and its conversion to trovafloxacin. These results indicate that alatrofloxacin is rapidly converted to trovafloxacin and that the pharmacokinetic parameters for this new fluoroquinolone after i.v. administration of its parent compound are similar to those reported after oral administration of equivalent trovafloxacin doses.

Sertraline. Chronopharmacokinetics and the effect of coadministration with food.

Two nonblinded single-dose randomised 3-way crossover studies were conducted in healthy male volunteers to determine the effect of the time of administration (morning vs evening) and the effect of food on the pharmacokinetics of sertraline tablets. There were no significant treatment effects on the mean area under the plasma concentration-time curve (AUC), mean peak plasma sertraline concentration (Cmax), mean time to reach Cmax (tmax), mean terminal elimination half-life, or the mean elimination rate constant in either study. The results of these 2 studies show that the bioavailability and elimination of sertraline tablets are not influenced by the time of administration or administration with or without food. Thus, sertraline tablets offer the flexibility of morning or evening administration, to patients in the fasting or nonfasting state.

Effect of sertraline on the pharmacokinetics and protein binding of diazepam in healthy volunteers.

A double-blind randomised placebo-controlled study was conducted in healthy male volunteers to determine the effects of sertraline on the pharmacokinetics of diazepam and its primary metabolite, N-demethyldiazepam. The effect of sertraline on the plasma protein binding of diazepam was also studied. Sertraline 50 mg/day titrated over a 10-day period to 200 mg/day or placebo was administered for 32 days. A single intravenous dose of diazepam 10 mg was given before the start, and after 21 days of sertraline or placebo treatment. The pharmacokinetic analyses were based on data from 20 individuals. The systemic clearance of diazepam decreased by 32% (-0.100 ml/min/kg) in the sertraline group compared with a 19% decrease (-0.054 ml/min/kg) in the placebo group (p = 0.0266). However, this small difference (13%) between the 2 groups was not considered meaningful. Other than a prolonged time to maximum plasma concentration for N-demethyldiazepam, no other pharmacokinetic parameters were significantly altered by sertraline. The plasma protein binding of diazepam was unchanged by concomitant administration of sertraline. These results suggest that sertraline at the maximum recommended dosage under steady-state conditions, and demethylsertraline, the principal metabolite of sertraline, are unlikely to exert significant inhibitory effects on the CYP2C19 and CYP3A3/4 hepatic isoenzymes responsible for the metabolism of diazepam. Therefore, it would be expected that sertraline would, similarly, have a minimal effect on the pharmacokinetic profile of other drugs metabolised by these hepatic isoenzymes.

Environmental fibrous zeolite (erionite) exposure and malignant tumors other than mesothelioma.

We studied the mortality in three villages in the Cappadocian region of Central Anatolia, Karain, Tuzköy, and Sarihidir, which were exposed to fibrous zeolite (erionite), a known carcinogen more potent than the amphibole asbestos. Between 1970 and 1994, there were 305 deaths in Karain, and 177 (58%) were cancer related, including 150 (49.2%) malignant pleural mesothelioma, seven (2.3%) malignant peritoneal mesothelioma, and six (1%) gastroesophageal carcinoma. Four deaths (1.3%) from lung cancer included two nonsmoking females. There were three cases (1%) of leukemia and six of other malignancies (1.9%). Between 1980 and 1994, there were 519 deaths in Tuzköy (T) and Sarihidir (S) (T = 432, S = 87). Of these, 257 were cancer related, and included 120 cases of malignant pleural mesothelioma and 64 cases of malignant peritoneal mesothelioma. Intraabdominal carcinoma was noted in 29 patients and 14 patients had lung cancer (four of whom were nonsmoking women). There were five cases of gastroesophageal cancer, five deaths due to leukemia, and 16 cases of various malignancies. These mortality figures support the hypothesis that erionite fibers cause cancer other than mesothelioma and lung cancer. Mineralogic analyses of the tissues should be performed to demonstrate this relationship.

Pharmacokinetics of fluconazole in renal failure.

Fluconazole (FLU) is a widely used antifungal agent. The multiple-dose pharmacokinetics of FLU in renal impairment have not been previously investigated. The following groups were studied: volunteers with creatinine clearances (CLcr, > 50 mL/min) of 107 mL/min, given a loading dose of 400 mg and a daily dose of 200 mg/day for 9 days (Group 1); subjects with CLcr between 21 and 50 mL/min with a mean of 38 mL/min, given a loading dose of 200 mg and a maintenance dose of 100 mg/day for 9 days (Group 2); subjects with CLcr between 11 and 20 mL/min with a mean of 14.8 ml/min, given a loading dose of 100 mg and a maintenance dose of 50 mg/day for 9 days (Group 3); and subjects on hemodialysis (three times per week) receiving a loading dose of 200 mg and then 100 mg after each of four dialysis sessions (Group 4) (N = 10 per group). After the administration of the loading dose on Day 1, the mean area under the curve (AUC) (0-24) measurements were approximately proportional to the dose of FLU and independent of renal function. After 10 days of FLU dosing, the mean renal clearance of FLU decreased as CLcr decreased for Groups 1 to 3, and the Day 10 mean half-lives were inversely related to mean CLcr (36.7 h in Group 1, 84.5 h in Group 2, and 101.9 h in Group 3). The mean AUC (0-24) on Day 10 was similar for Group 1 compared with Group 2, despite a reduction in the maintenance dose by 50%. (ABSTRACT TRUNCATED AT 250 WORDS)

Carbon monoxide poisoning related to the use of steam coal in poorly ventilated bucket stoves.

During the years 1986 to 1990, an increasing number of cases of acute carbon monoxide (CO) poisoning were encountered in the Emergency Department Hacettepe University Hospital in Ankara, Turkey. Between January 1 and March 31, 1991, all the patients presenting with complaints compatible with CO poisoning were evaluated; the diagnosis was confirmed in 55 of the 5795 people who attended the Emergency Department during this period. In all cases the source of CO intoxication was determined. Among these patients, nausea or vomiting and headaches were the most common complaints (occurring in 100% and 85%, respectively). At least transient impairment of alertness was observed in 29% of cases. The carboxyhaemoglobin levels ranged from 3.80 to 48.1% (median 14.2%). Two comatose patients who developed a non-cardiogenic pulmonary oedema required mechanical ventilation. One of them was discharged from the hospital with mild cerebral disability. Another patient developed an acute myocardial infarction. In all the cases in this series, the source of CO poisoning was identified as improper combustion of recently marketed steam coal in inadequately ventilated bucket stoves.