Vitamin K status of preterm infants with a prolonged prothrombin time

AIM: To investigate the vitamin K status of preterm infants who have a prolonged prothrombin time (PT) in the first month of life. METHODS: Measures of vitamin K status were assessed in 21 preterm infants who were found to have an abnormal PT, despite 0.2-0.5 mg vitamin K(1) prophylaxis at birth. RESULTS: All infants had normal or supraphysiological vitamin K(1) concentrations and undetectable or, in one infant, insignificant PIVKA-II, indicating adequate vitamin K status. CONCLUSION: In preterm infants born at <32 wk gestation who received > or = 0.2 mg vitamin K(1) after delivery, a prolonged PT in the first month of life is unlikely to be due to vitamin K deficiency.     

Clozapine augmented with risperidone in the treatment of schizophrenia: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: The authors evaluated the efficacy and safety of augmenting clozapine with risperidone in patients with treatment-resistant schizophrenia. METHOD: In a randomized, double-blind, placebo-controlled 12-week trial, 40 patients unresponsive or partially responsive to clozapine monotherapy received a steady dose of clozapine combined with either placebo (N=20) or up to 6 mg/day of risperidone (N=20). Patient psychopathology was assessed at 2-week intervals with the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS), among other measures. Movement disorders were assessed with the Simpson-Angus Rating Scale. RESULTS: From baseline to week 6 and week 12, mean BPRS total and positive symptom subscale scores were reduced significantly in both groups, but the reductions were significantly greater with clozapine/risperidone treatment. Reductions in SANS scores were also significantly greater with clozapine/risperidone treatment than with clozapine/placebo. The adverse event profile for clozapine/risperidone treatment was similar to that for clozapine/placebo. Simpson-Angus Rating Scale scores were lower with clozapine/risperidone treatment throughout the trial but increased to approach those of clozapine/placebo treatment at week 12. Clozapine/risperidone treatment did not induce additional weight gain, agranulocytosis, or seizures compared with clozapine/placebo treatment. CONCLUSIONS: In patients with a suboptimal response to clozapine, the addition of risperidone improved overall symptoms and positive and negative symptoms of schizophrenia. The combination appears to be safe and well tolerated. Augmentation of clozapine with risperidone may provide additional clinical benefit for patients who are nonresponsive or only partially responsive to clozapine alone.     

Sensorimotor gating, orienting and social perception in schizophrenia

Basic neurocognition and social cognition appear to influence the social impairments of persons with schizophrenia. This study examined relationships between two very basic automatic processes (i.e., sensorimotor gating and orienting) and social perception in schizophrenic patients. Thirty outpatients with schizophrenia completed psychophysiological measures of sensorimotor gating (prepulse inhibition, PPI), orienting (prepulse facilitation, PPF), and social perception (the Half Profile of Nonverbal Sensitivity, Half PONS). A median split was used to divide patients into poor and good gaters and poor and good orienters. Analyses revealed that patients with good PPI scored significantly higher on the Half PONS than patients with poor PPI. PPI showed a significant correlation (r=-0.54) with Half PONS performance, indicating that schizophrenia patients who were better able to gate out competing stimuli (i.e., less startle) were also better at detecting relevant social cues. Orienting (PPF) and social perception were not related. This study is the first to our knowledge to demonstrate an association between sensorimotor gating and social perception. The findings are consistent with other studies that have demonstrated relationships between basic neurocognition and social cognition. By showing a link between sensorimotor gating and social perception, this study supports social cognition's potential role as a mediator of the relationship between neurocognition and social functioning in schizophrenia.     

Recombinant human erythropoietin as an adjunct to radiation therapy and cisplatin for stage IIB-IVA carcinoma of the cervix: a Southwest Oncology Group study

OBJECTIVE: The survival of cervix cancer patients is associated with their hemoglobin (Hgb) level during radiotherapy. The Southwest Oncology Group (SWOG) conducted a phase II trial to determine whether recombinant human erythropoietin (rHuEPO) safely corrects anemia during chemoradiotherapy for cervix cancer. METHODS: Patients had stage IIB-IVA cervix cancer and a Hgb between 8.0 and 12.5 g/dl. All patients received rHuEPO thrice weekly and oral iron starting 10-15 days before their 5-week course of whole pelvic irradiation and weekly cisplatin followed by intracavitary brachytherapy. RESULTS: Fifty-three patients from 26 institutions received the protocol treatment. The mean Hgb was 10.4 +/- 1.3 g/dl on the first day of rHuEPO administration (baseline), 11.0 +/- 1.6 g/dl on the first day of chemoradiotherapy, 11.6 +/- 1.9 g/dl at the midpoint of chemoradiotherapy, and 11.8 +/- 2.2 g/dl at the end of chemoradiotherapy. The target Hgb level of 12.5 g/dl was achieved in 40% of patients (95% CI 26-56%) by the midpoint of Chemoradiotheraphy. Change in Hgb was associated with baseline serum iron (P = 0.008) and transferrin saturation (P = 0.05) levels, but not with baseline Hgb or serum ferritin, or patient age. Seven patients developed deep vein thrombosis. Two-year progression-free survival (PFS) was 43% and overall survival (OS) was 51%. Survival was significantly associated with Hgb level at the end of chemoradiotherapy, but not with the baseline Hgb level. CONCLUSIONS: rHuEPO and iron gradually increased Hgb levels in anemic women with local advanced cervix cancer during chemoradiotherapy. There was a higher than expected incidence of deep vein thrombosis. The progression-free and overall survival rates were lower than reported for women with normal Hgb levels.     

Training enhances vascular relaxation after chemotherapy-induced vasoconstriction

PURPOSE: Although evidence is accumulating that suggests regular moderate physical activity improves physiological and psychological well-being of cancer patients undergoing chemotherapy, the mechanisms involved remain unclear. Therefore, the purpose of this study was to determine if exercise training improves endothelium-dependent vasodilation after exposure to the chemotherapeutic agent 5-fluorouracil (5-FU). METHODS: Rats were injected with N-methyl-N-nitrosourea (MNU) and assigned to either exercise (EX; treadmill running, 20-25 m.min(-1) grade, 30 min.d(-1), 5 d.wk(-1) for 8 wk) or sedentary (SED) groups. After the exercise training period, aortic rings were obtained and used to assess contractile and relaxation characteristics. In addition, endothelial nitric oxide synthase (eNOS) protein content and eNOS enzyme activity was determined. RESULTS: Exercise training resulted in increased maximal endothelium-dependent vasorelaxation to acetylcholine (ACh, 1 x 10(-5) M) (SED, 56 +/- 3%; exercise, 71 +/- 5%; P < 0.05) after norepinephrine-induced (1 x 10(-7) M) vasoconstriction. Exposure of aortic rings from each group to increasing concentrations of 5-FU (7 x 10(-5) x 10 M(-3)) resulted in vasoconstriction. Rings obtained from exercise-trained animals demonstrated enhanced vasorelaxation to ACh (1 x 10(-5) M) after 5-FU-induced vasoconstriction compared with rings obtained from SED animals (P < 0.05). In addition, exercise training enhanced eNOS protein content and eNOS activity. CONCLUSION: Exercise training enhances endothelium-dependent vasorelaxation after 5-FU-induced vasoconstriction, and this may be due, at least in part, to an increase in aortic eNOS protein content and activity. Such exercise-induced adaptations may help alleviate chemotherapy-related fatigue observed in cancer patients.     

Biomechanics and development of the elbow in the young throwing athlete

This article reviews basic concepts in fundamental elbow biomechanics, particularly how they relate to the skeletally immature elbow in throwing athletes. Adult phases of throwing and the forces generated in each phase are compared with the developmental phases of throwing in children. The impact of elevated forces, poor mechanics, and poor coordination are emphasized as they relate to potential areas of injury in the skeletally immature. Finally, concepts in prevention focused on biomechanics are offered.     

Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion

Human marrow stromal cells (MSCs) can be isolated from bone marrow and differentiate into multiple tissues in vitro and in vivo. These properties make them promising tools in cell and gene therapy. The lack of a specific MSC marker and the low frequency of MSCs in bone marrow necessitate their isolation by in vitro expansion prior to clinical use. This may severely reduce MSC proliferative capacity to the point that the residual proliferative potential is insufficient to maintain long-term tissue regeneration upon reinfusion. In this study we determined the effect of in vitro expansion on the replicative capacity of MSCs by correlating their rate of telomere loss during in vitro expansion with their behavior in vivo. We report that even protocols that involve minimal expansion induce a rapid aging of MSCs, with losses equivalent to about half their total replicative lifespan.     

"The lion, the witch and the wardrobe": impact on sibs of individuals with AAT deficiency

Alpha(1)-antitrypsin (AAT) deficiency is a genetic disorder that may cause serious pulmonary or liver impairment in children or adults. Although genetic sequencing of the AAT gene has only been available for 20 years, analysis of the amount and electrophoretic mobility of the AAT protein has allowed clinical phenotyping for more than 40 years. There have been no studies assessing the psychological impact of having a sib affected by AAT deficiency. Twenty-five participants drawn from the Alpha-1 Research Registry completed a questionnaire and semi-structured interview. Respondents were supportive of testing prior to adulthood for AAT status; 18 thought it was a good idea to test a child, three did not know, and four said children should not be tested, primarily citing insurance concerns. Of those 18 who stated it was a good idea, 14 would test at birth. Knowledge of genetics of AAT deficiency was limited; only 44% of respondents understood the inheritance pattern. We recommend: (1) parents and sibs need help in mourning the loss of children with AAT deficiency; young sibs are at risk for trauma and long-term developmental problems. (2) Teams evaluating donors for liver transplantation should be aggressive in ruling out AAT deficiency prior to invasive testing. (3) Testing should be offered to individuals with a family history of AAT deficiency to obtain the health benefits of lifestyle modification and limit the burden of disease discovery in symptomatic relatives. (4) Awareness of liver disease from AAT deficiency should be increased.