Serum concentration and protein binding of thioridazine and its metabolites in patients with chronic alcoholism

Summary The blood chemistry and clinical pharmacokinetics of thioridazine and its metabolites, side-chain sulphoxide, side-chain sulphone and ring sulphoxide, were studied in 31 alcoholics and were compared with values in 17 thioridazine-treated controls without alcoholism. Pathological blood chemistry values, including abnormal liver function and protein concentrations, were common among the alcoholics. In relation to dosage, the majority had a low serum concentration of thioridazine and at a given concentration of thioridazine they had high serum concentrations of its metabolites. Positive intercorrelations were found between pathological liver function tests, prolonged serum half-life and increased serum concentration of thioridazine. The free fractions of thioridazine, side-chain sulphoxide and ring sulphoxide were significantly higher and those of the side-chain sulphone lower in the alcoholics than in the controls. The free fractions of side-chain and ring sulphoxide were significantly increased in patients with a low concentration of ₁-acid glycoprotein.     

Transplacental passage and breast milk concentrations of hydralazine

Summary The concentrations of real and apparent (= real hydralazine + acid-labile hydrazones) hydralazine in maternal and umbilical plasma obtained at delivery of 6 women treated with hydralazine and atenolol for pregnancy hypertension were measured by gas chromatography. In one of the patients, the concentrations of the same substances were subsequently measured in breast milk. Apparent hydralazine reached higher levels in umbilical than in maternal blood. The concentration of real hydralazine seemed to be at least as high in the fetus as in the mother. On the other hand, even though the fraction of real (i.e. presumably active) hydralazine was greater in milk than in plasma, the total concentration was smaller, and the estimated dose per milk feed of 75ml would not exceed 0.013mg. Thus, hydralazine treatment of the pregnant woman would expose her fetus to effective concentrations of the drug, but breast feeding would not result in a clinically relevant concentration in the infant.     

Plasma concentrations of valproate during maintenance therapy in epileptic children

Summary A total of 20 children with various types of epilepsy were treated with valproate, 11 with monotherapy and 9 with valproate in combination with phenobarbitone, phenytoin, or carbamazepine. Valproate was given either every 8 or 12 h. At least two different dose levels were tried in each patient. The pharmacokinetics of valproate during the interval between doses was determined using a gas chromatographic technique. The clinical effect of the treatment was assessed by interviewing the parents.The plasma concentrations showed considerable fluctuation during the intervals between doses. The mean increase from pre-administration to peak level was 82% when the dose interval was 12 h, and 62% when it was 8 h. The mean plasma half-life of valproate, using a one-compartment model, was 10.9±1.3 h (mean±SD). The plasma half-life of valproate was decreased when the drug was combined with the other anti-epileptics. The calculated area under the concentration versus time curve was linearly related to dose, both in a single patient on four dose levels and when different patients were compared. The clinical effect of valproate monotherapy was best in patients with absences, usually good in myoclonus and less favourable in other types of epilepsy. For children with absences, the optimal dose range of valproate was between 20 and 40 mg/kg/24 h. In comparison, the myoclonic types of epilepsy needed a slightly higher dose level, between 30 and 60 mg/kg/24 h. In the latter group a therapeutic window seems to exist, since patients below and above the suggested dose levels were not well-controlled. Therapeutic monitoring of valproate does not appear meaningful when the drug is used as monotherapy. However, in combination therapy, determination of the plasma levels of all anti-convulsants used may be helpful. The large fluctuations of valproate during a dose interval must be taken into consideration when the clinical effects are analysed.Supported by the Swedish Medical Research Council (Project No. 522), Stiftelsen Margarethahemmet, and Sällskapet Barnavård     

The influence of different technique factors on image quality of lumbar spine radiographs as evaluated by established CEC image criteria

In this study we have investigated the image quality of lumbar spine radiographs taken after recording technical and physical parameters. Two technical parameters were altered, tube voltage (70 kV and 90 kV for the anteroposterior (AP) projection and 77 kV and 95 kV for the lateral projection) and sensitivity of the film-screen system (sensitivity class 400 and 600). In total, 85 images were included in the study. Entrance surface dose (ESD) was measured using thermoluminescent dosemeters. The mean value of ESD for the different technique groups varied between 1.9 mGy (90 kV, sensitivity class 400) and 4.6 mGy (70 kV, sensitivity class 400) for the AP projection, and between 6.4 mGy (95 kV, sensitivity class 600) and 20.4 mGy (70 kV, sensitivity class 400) for the lateral projection. Image criteria given in the "European Guidelines on Quality Criteria for Radiographic Images" were used to assess image quality. Two evaluation methods have been employed. A straightforward scoring of fulfilled image criteria, and visual grading analysis using the structures defined in the image criteria. The latter method provided a sharper distinction between groups of images taken using different radiographic techniques. The average number of fulfilled image criteria for the AP projections varied between 0.74 (90 kV, sensitivity class 400) and 0.87 (70 kV, sensitivity class 400). For the lateral projection this number varied between 0.79 (95 kV, sensitivity class 600) and 0.84 (77 kV, sensitivity class 600). This study shows that image criteria are useful tools in clinical studies of image quality.     

Preventing Macrovascular Disease in Patients with Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (DM) is associated with an increased risk for both micro-and macrovascular complications, and cardiovascular diseases (CVD) are the most common causes of death in these patients, accounting for almost 70% of the deaths. Given the high prevalence of the condition and the expected global increase in the prevalence of type 2 DM, a case is made for prevention of these serious complications in order to reduce the individual morbidity and the economic burden on society. In this review we present the knowledge of how macrovascular disease in patients with type 2 DM may be prevented, and suggest possible strategies for doing so. A thorough search of the published literature was conducted and we first present relevant epidemiological studies demonstrating the impact of important risk factors for CVD in DM, such as dyslipidemia, hyperglycemia, hypertension, smoking, familial premature coronary heart disease and some non-classical risk factors such as hyperinsulinemia, insulin resistance, endothelial dysfunction and inflammation. Secondly, we review the results from published randomized controlled clinical trials and meta-analysis of these, evaluate the findings and suggest strategies for preventing CVD in patients with type 2 DM using non-pharmacological and pharmacological approaches. Present knowledge indicates that most patients with type 2 DM either have manifest CVD or have a high risk for future cardiovascular events, men with DM have a 2- to 4-fold; and women with DM a 3- to 5-fold increased risk for cardiovascular death compared with non-diabetic individuals. Care of patients with type 2 DM should include yearly risk assessment by the use of published risk equations or risk charts. On the background of this assessment, an individual risk reducing strategy should be tailored to each patient’s need, including the treatment of hyperglycemia, hypertension and dyslipidemia together with the use of aspirin (acetylsalicylic acid) and ACE inhibitors. Such measures can reduce the risk of cardiovascular events in patients with type 2 DM.     

SonoWand, an ultrasound-based neuronavigation system

OBJECTIVE: We have integrated a neuronavigation system into an ultrasound scanner and developed a single-rack system that enables the surgeon to perform frameless and armless stereotactic neuronavigation using intraoperative three-dimensional ultrasound data as well as preoperative magnetic resonance or computed tomographic images. The purpose of this article is to describe our two-rack prototype and present the results of our work on image quality enhancement. DESCRIPTION OF INSTRUMENTATION: The system consists of a high-end ultrasound scanner, a modest-cost computer, and an optical positioning/digitizer system. Special technical and clinical efforts have been made to achieve high image quality. A special interface between the ultrasound instrument and the navigation computer ensures rapid transfer of digital three-dimensional data with no loss of image quality. OPERATIVE TECHNIQUE: The positioning system tracks the position and orientation of the patient, the ultrasound probe, the pointer, and various surgical instruments. This makes it possible to update the three-dimensional map during surgery and navigate by ultrasound data in a similar manner as with magnetic resonance data. METHODS: The two-rack prototype has been used for clinical testing since November 1997 at the University Hospital in Trondheim. EXPERIENCE AND RESULTS: The image quality improvements have enabled us, in most cases, to extract information from ultrasound with clinical value similar to that of preoperative magnetic resonance imaging. The overall clinical accuracy of the ultrasound-based navigation system is expected to be comparable to or better than that of a magnetic resonance imaging-based system. CONCLUSION: The SonoWand system enables neuronavigation through direct use of intraoperative three-dimensional ultrasound. Further research will be necessary to explore the potential clinical value and the limitations of this technology.     

Subjective xerostomia in long-term surviving children and adolescents after pediatric bone marrow transplantation

BACKGROUND: The aim of the present investigation was to evaluate whether the subjective symptoms of dry mouth in long-term-surviving pediatric bone marrow transplant (BMT) patients are associated with low unstimulated salivary secretion rates (USSR) and with stimulated whole salivary secretion rates (SSSR). METHODS: Fifty-three patients surviving > or =2 years after pediatric allogeneic BMT were included. USSR, SSSR, and the change in salivary secretion rates since the previous year were estimated. A questionnaire regarding subjective symptoms of xerostomia was answered. RESULTS: The mean USSR and SSSR were 0.24+/-0.17 and 0.90 +/- 0.58 ml/min, respectively. Salivary gland dysfunction, defined as USSR < or =0.1 ml/min or SSSR < or =0.5 ml/min, was present in 35% of the patients. Seventy-nine percent of the patients expressed one or more symptom of dry mouth, and 49% gave at least two answers indicating dry mouth. The number of complaints increased with age at examination (P<0.05). Both USSR (P<0.01) and SSSR (P<0.01) were inversely correlated to the total number of complaints of xerostomia. A reduction in SSSR compared with the year before was correlated to two or more complaints of xerostomia (P<0.01). The presence of dry mouth at night or on awakening was indicative of both low USSR (P<0.01) and SSSR (P<0.001). Patients reporting dryness during the day had significantly lower SSSR (P<0.05). CONCLUSION: The expression of subjective complaints of xerostomia among long-term surviving pediatric BMT patients is correlated to salivary gland dysfunction and age. It is very important to identify these patients with salivary gland dysfunction to relieve their symptoms and prevent secondary complications.     

Intestinal non-Hodgkin's lymphoma: a multicenter prospective clinical study from the German Study Group on Intestinal non-Hodgkin's Lymphoma.

PURPOSE: Intestinal non-Hodgkin's lymphomas are not well characterized. We therefore studied prospectively their clinical features and response to standardized therapy. PATIENTS AND METHODS: Fifty-six patients with primary intestinal lymphoma were included in a prospective, nonrandomized multicenter study. Lymphoma resection was recommended and staging was performed according to the Ann Arbor classification. Patients were scheduled to receive six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy, and at stages EIII to EIV, they received additional involved-field radiotherapy. Corticosteroids were used in patients who could not receive chemotherapy. RESULTS: Thirty-five patients had intestinal T-cell lymphoma (ITCL), 21 patients had intestinal B-cell lymphoma (IBCL; 18 diffuse large-cell lymphomas, two marginal-cell lymphomas, and one follicle-center lymphoma). Thirty-four patients at stages EI to EII (14 ITCL and 20 IBCL) and nine patients at stages EIII to EIV (all ITCL) received chemotherapy. No patient in stages EIII to EIV received radiotherapy, because death occurred in 12 of 14 patients. Two-year cumulative survival in patients with IBCL was 94% (95% CI, 82% to 100%) and higher than in patients with ITCL (28% [95% CI, 13% to 43%]; P <.0001), even when only stages EI to EII were considered (ITCL, 37.5% [95% CI, 16.5% to 58.5%]; P <.0001). IBCL patients compared with ITCL patients were at lower lymphoma stages (P <.01), had higher Karnofsky status (P <.005), had intestinal perforation less often (P <.05), required emergency operation less often (P <.05), received CHOP (P <.05) more often, and reached complete remission (P <.0005) more frequently. CONCLUSION: IBCL patients at stages EI and EII respond well to chemotherapy, but the prognosis and treatment of ITCL patients is unsatisfactory.     

New non-cocaine-containing topical anesthetics compared with tetracaine-adrenaline-cocaine during repair of lacerations

OBJECTIVE: To compare the effectiveness of three new topical anesthetics that do not contain cocaine (prilocaine-phenylephrine, tetracaine-phenylephrine [tetraphen], and tetracaine-lidocaine-phenylephrine) to that of tetracaine-adrenaline-cocaine (TAC) during laceration repair in children. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: The emergency department of an urban children's hospital. PARTICIPANTS: Children 1 year of age or older with a laceration /= 5 years of age using a visual analogue scale (VAS). Suture technicians, research assistants, and parents also scored pain using a seven-point Likert scale. In addition, suture technicians completed an anesthetic effectiveness scale. RESULTS: There was consistently no difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. A statistically significant difference was seen among anesthetics when comparing VAS and Likert scale scores of suture technicians and Likert scale scores of research assistants. Based on post hoc analyses, these statistically significant differences were between TAC and prilocaine-phenylephrine (suture technician VAS and Likert scale) and between TAC and tetracaine-lidocaine-phenyl-ephrine (suture technician Likert scale), but not between TAC and tetraphen. When power analyses were performed using alpha = 0.05 and beta = 0.20, it was possible to detect a difference of 1.2 VAS units for each of the observer groups. Based on anesthetic effectiveness scale scores, the three new topical preparations collectively performed significantly better on the face and scalp than on the extremities (relative risk = 1.83; 95% confidence interval 1.20 < relative risk < 2.79). CONCLUSION: This study demonstrated the effectiveness and safety of three new non-cocaine-containing topical anesthetics. Consistently, there was no statistical difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. Tetraphen offers an effective alternative to TAC during laceration repair in children.     

Diet and the risk of papillary and follicular thyroid carcinoma: a population-based case-control study in Sweden and Norway

A population-based case-control study was conducted in two regions ofSweden and Norway to investigate the association between dietary habits andthe risk of thyroid cancer. The consumption of selected foods was reported ina self-completed food-frequency questionnaire by 246 cases withhistologically confirmed papillary (n = 209) and follicular (n = 37) thyroidcarcinoma, and 440 age- and gender-matched controls. Odds ratios (OR) andtheir 95 percent confidence interval (CI) were calculated as estimates of therelative risk using conditional logistic regression. High consumption ofbutter (OR = 1.6, CI = 1.1-2.5) and cheese (OR = 1.5, CI = 1.0-2.4) wasassociated with increased risks. Residence in areas of endemic goiter inSweden was associated with an elevated risk, especially among women (OR =2.5, CI = 1.3-4.9). High consumption of cruciferous vegetables was associatedwith increased risk only in persons who ever lived in such areas. A decreasedrisk was associated with consumption of iodized salt in northern Norway, andwith use of iodized salt during adolescence among women (OR = 0.6, CI =0.6-1.0). The results of this study suggest a role of diet and environment inthe risk of thyroid cancer.