Serum vitamin B6 in schizophrenic and schizoaffective patients with and without tardive dyskinesia

There are several reports regarding the efficacy of vitamin B6 in the treatment of tardive dyskinesia (TD). Vitamin B6 plays a key role in the synthesis of several neurotransmitters, including serotonin, dopamine, norepinephrine, and gamma-aminobutyric acid, all of which have been proposed to be involved in the development of TD. The purpose of this study was to examine whether there are special markers to distinguish long-term neuroleptic exposure patients who have TD from those patients who do not develop this side effect. In view of the pivotal role of vitamin B6 in the synthesis of all neurotransmitters believed to take part in the pathogenesis of TD, we decided to examine whether basal levels of vitamin B6 might explain the difference between these two groups. Such a finding could provide a predictive marker for vulnerable patients. The active metabolite of vitamin B6 is pyridoxal phosphate (PP). Pyridoxal phosphate blood levels were measured in 15 schizophrenic and schizoaffective patients with TD and compared with 15 patients without evidence of TD (matched by sex, age, smoking, and diagnosis). We found that, although patients in the TD group were exposed to neuroleptic drugs for significantly longer periods of time, there were no differences in serum PP levels between the groups. The reports of the effectiveness of vitamin B6 supplementation in the treatment of TD could therefore be explained by the assumption that central nervous system or intracellular vitamin B6 levels, which are involved in the pathogenesis of TD, are not the same as vitamin B6 peripheral serum levels. There is need for further studies, which will clarify the relationship between vitamin B6 and TD.     

Diagnosis and management of cystic duct leakage after laparoscopic cholecystectomy, report of 3 cases

BACKGROUND： Operative complications after laparoscopic cholecystectomy （LC） vary. Abdominal pain and other symptoms caused by fluid accumulation in the operative area are not uncommon. Cystic duct （CD） leakage is one of the main sources of the fluid. This study was to evaluate the procedures used in the diagnosis and management of CD leakage after LC. METHOD： The clinical materials of 3 patients with CD leakage after LC were studied retrospectively.     

Nomograms provide improved accuracy for predicting survival after radical cystectomy.

AIMS: To develop multivariate nomograms that determine the probabilities of all-cause and bladder cancer-specific survival after radical cystectomy and to compare their predictive accuracy to that of American Joint Committee on Cancer (AJCC) staging. METHODS: We used Cox proportional hazards regression analyses to model variables of 731 consecutive patients treated with radical cystectomy and bilateral pelvic lymphadenectomy for bladder transitional cell carcinoma. Variables included age of patient, gender, pathologic stage (pT), pathologic grade, carcinoma in situ, lymphovascular invasion (LVI), lymph node status (pN), neoadjuvant chemotherapy (NACH), adjuvant chemotherapy (ACH), and adjuvant external beam radiotherapy (AXRT). Two hundred bootstrap resamples were used to reduce overfit bias and for internal validation. RESULTS: During a mean follow-up of 36.4 months, 290 of 731 (39.7%) patients died; 196 of 290 patients (67.6%) died of bladder cancer. Actuarial all-cause survival estimates were 56.3% [95% confidence interval (95% CI), 51.8-60.6%] and 42.9% (95% CI, 37.3-48.4%) at 5 and 8 years after cystectomy, respectively. Actuarial cancer-specific survival estimates were 67.3% (62.9-71.3%) and 58.7% (52.7-64.2%) at 5 and 8 years, respectively. The accuracy of a nomogram for prediction of all-cause survival (0.732) that included patient age, pT, pN, LVI, NACH, ACH, and AXRT was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.615). Similarly, the accuracy of a nomogram for prediction of cancer-specific survival that included pT, pN, LVI, NACH, and AXRT (0.791) was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.663). CONCLUSIONS: Multivariate nomograms provide a more accurate and relevant individualized prediction of survival after cystectomy compared with conventional prediction models, thereby allowing for improved patient counseling and treatment selection.     

Amniocentesis after multifetal pregnancy reduction: is it safe?

OBJECTIVE: This report reviews the obstetric outcomes of women with multifetal pregnancy reductions who subsequently underwent elective amniocentesis. STUDY DESIGN: Five hundred eight patients underwent multifetal pregnancy reduction at our institution. Among these, 91 patients underwent subsequent elective amniocentesis. The obstetric outcomes of all 508 patients were followed up. By means of logistic regression we evaluated several variables to determine any association with loss rate: (1) the finishing number of fetuses, (2) the number of fetuses undergoing reduction (starting number of fetuses minus the finishing number of fetuses), (3) the gestational age at reduction, (4) the maternal age at reduction, and (5) the procedure protocol. We observed that the finishing number of fetuses, the number of fetuses removed, and the procedure protocol were significantly associated with pregnancy loss rate. Women who underwent subsequent amniocentesis were compared with those who did not undergo amniocentesis. By means of multivariate conditional likelihood analysis we stratified the two groups according to the previously mentioned significant variables to compare the pregnancy loss rates. RESULTS: Among patients who subsequently underwent elective amniocentesis the total uncorrected pregnancy loss rate was 9.0% and the early premature delivery rate was 4.5%. The number of fetuses removed, the finishing number of fetuses, and the procedure protocol were statistically significantly associated with the loss rate. The adjusted odds ratio relating amniocentesis to the pregnancy loss rate was 0.7 (95% confidence interval, 0.31.5; P =.3.) CONCLUSIONS:The uncorrected rates of pregnancy loss and of early premature delivery among patients with multifetal pregnancy reduction who underwent subsequent amniocentesis were comparable to those of patients with multifetal pregnancy reduction who did not undergo amniocentesis.     

High-level amikacin resistance in Pseudomonas aeruginosa associated with a 3'-phosphotransferase with high affinity for amikacin

This work describes the characterization of the phosphotransferase enzymatic activity responsible for amikacin resistance in two clinical Pseudomona aeruginosa strains, isolated from a hospital that used amikacin as first-line aminoglycoside. Amikacin-resistant P. aeruginosa PA40 and PA43 (MIC: 128 mg/l) were shown to have APH activity with a substrate profile similar to that of APH(3′)-VI. The enzyme from P. aeruginosa PA40 was purified to >70% homogeneity. The K_m of amikacin for this enzyme was 1.4 μM, the V_max/K_m ratio for amikacin was higher than for the other aminoglycosides tested and PCR and DNA sequencing ruled out the presence of aph(3′)-IIps. Amikacin resistance in this strain was, therefore, associated with APH(3′)-VI and the high affinity of this enzyme for amikacin could explain the high-level resistance that we observed.     

Assessment and intervention for attention-deficit/hyperactivity disorder in the schools. Lessons from the MTA study

The MTA experience provides several lessons that may have clinical relevance. First, the MTA study identified six key instruments (see Table 1) that clinicians may want to use, but even on these instruments discrepancies in parent and teacher sources should be expected. We believe that unnoticed or unresolved discrepancies may be important factors contributing to the "disconnect" identified by the Consensus Conference Panel. Based on the MTA experience, we recommend a telephone call to the child's teacher, specifically to inquire about any discrepancy in the "source by domain" summary, as an efficient way to make a meaningful connection "... between developmental or educational (school-based) assessments and health-related (medical practice-based) services" for children with ADHD. Second, evaluation of pharmacologic intervention in the MTA study confirmed that teachers' reports are crucial for documenting efficacy, whereas parent reports are crucial for documenting side effects. Based on the MTA experience, we recommend frequent telephone contact with the teacher specifically to inquire about the peak effects and dissipation of effects of medication that are expected to occur during the school hours as a way to improve "... communication between diagnosticians and those who implement and monitor treatment in the schools."     

Variations in the low levels of cyclin D1/BCL1 have prognostic value in chronic lymphocytic leukemia

Cyclin D1 (CyD1)/BCL1 (PRAD1) is expressed at high levels in almost all cases of mantle cell leukemia/lymphoma (MCL) and in rare cases of chronic lymphocytic leukemia (CLL). The CyD1/BCL1 protein plays an important role in the progression of cells through the G1 phase of cell cycle. Most of the CyD1/BCL1 protein expression studies are performed using immunohistochemistry. We used a sensitive solid-phase radioimmunoassay (RIA) to quantify CyD1 protein expression in 199 patients with CLL. Of these 137 patients were previously untreated with the rest having had standard chemotherapeutic regimens including alkylating agents and fludarabine before being referred to our center. Median white cell count in these patients was 49x10(3) /microl (range 3.0-438.5x10(3)/microl), hemoglobin level 13.1 g/dl (range 5.2-17.3 g/dl), platelet count 157x10(3) /microl (range 10-377x10(3) /microl), age 58 (range 26-89), and beta2-microglobulin 2.75 mg/dl (range 1.1-14.3). The median radioactivity (CPM) of mononuclear cells obtained from 56 normal individuals was assigned a value of 1. There was no significant variation in CyD1 levels among normal individuals (SD=0. 12). While most CyD1 levels in MCL varied from 6.5 to 15.6, the median CyD1/BCL1 in CLL was 1.4 with 75th percentile under 2.12. Rare CLL cases (3.5%) showed levels between 4 and 8.83. When divided into two groups at the median level, patients with higher CyD1/BCL1 expression had shorter survival (P = 0.03). This remained true when applied only to the previously untreated patients (P=0.05). Despite the relatively low expression, the CyD1/BCL1 levels in univariate analysis were as good or better predictors of survival than Binet (P = 0.03) or Rai (P = 0.05) staging. Furthermore, CyD1/BCL1 levels correlated with serum beta2-microglobulin (P = 0.001), white blood cell count (P = 0.004) and hemoglobin levels at the time of collection (P = 0.0003) but not with lymphocyte count, platelet count or age. The data demonstrate that CyD1/BCL1 is likely to play a significant role in the biology of CLL and can be used as a prognostic indicator. Further studies to clarify the role of CyD1 in the biology of CLL and its value as a prognostic indicator at the time of diagnosis are encouraged.     

Role of pHyde novel gene product as an intrinsic factor for apoptotic pathway in prostate cancer

Induction of apoptotic cell death mechanism can be regulated by internal factor(s), such as by gene product(s) that directly upregulate the apoptosis pathway or indirectly by down-regulating the anti-apoptosis gene. This homeostasis is a normal phenomenon in a biological system disturbed by cancer. It is thus important to find any gene functioning as an upregulator for the apoptosis pathway that may have a potential application in the context of cancer gene therapy. We have cloned a novel rat gene, denoted as pHyde, that fulfilled this objective. Internally, this pHyde gene product renders the stable transfectant of rat prostatic cancer cell lines more susceptible to apoptosis even without any external inducer. By using an external agent, such as 5-fluoro-2'-deoxyuridine (FdUr), apoptotic responses of the stable transfectants are even higher, suggesting that both intrinsic and extrinsic factors work synergistically. The pHyde gene product was termed an intrinsic factor, whereas FdUr was considered an extrinsic factor for the apoptosis in rat prostate cancer model.     

Evaluation of individual subjects in the analog classroom setting: I. Examples of graphical and statistical procedures for within-subject ranking of responses to different delivery patterns of methylphenidate.

In this article, we describe graphical and statistical methods developed to evaluate the response patterns of individual children with attention deficit hyperactivity disorder (ADHD) to different conditions of treatment with stimulant medication. We used data from an investigation of drug delivery patterns to demonstrate these methods. Thirty-one children with ADHD participated in a double-blind crossover study of four conditions (three patterns of delivery of methylphenidate and a placebo control). In each condition, the children were evaluated across an 11-hour (7:00 a.m. to 6:00 p.m.) laboratory school day, and ratings of classroom behavior were obtained at regular intervals across the day. Graphical procedures were developed to display, for each individual, time courses of multiple measures of behavior taken across each double-blind test day. Expert clinicians judged these graphs and used this information to rank-order the test days from best to worst. A within-subject variant of Kendall's W was used to evaluate, for each subject, whether the rankings of these multidimensional graphs were reliable (concordant) across judges. A generalized kappa statistic was used to evaluate, for each condition, the reliability of the judges' rankings across subjects. Friedman's analysis of variance of ranks was used to evaluate, for the study, whether the conditions differed in terms of the average (consensus) rank assigned by the judges.