Antiproliferative Activity Against MCF‐7 Breast Cancer Cells by Diamino‐Triazaspirodiene Antifolates

Two triazaspirodienes, having similar phenoxy propyloxy side chain, were identified as potent mammalian dihydrofolate reductase inhibitors; one having a 6,5‐spiro bicyclic ring system (IC₅₀ = 2.3 nm ) and the other a 6,6‐spiro bicyclic system (IC₅₀ = 6.9 nm ). They also showed more than 50% antiproliferative activity against the MCF‐7 breast cancer cells at 20 μm . This study demonstrated the potential lead of the diamino‐triazaspirodienes in anticancer chemotherapeutical agents’ discovery.     

Neuropsychological assessment, neuroimaging, and neuropsychiatric evaluation in pediatric and adult patients with sickle cell disease (SCD)

Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD) have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE) may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities.     

The role of low fat diets in the management of gall-bladder disease

This paper presents the results obtained from 87 questionnaires completed by dietitians about the dietary management of gall-biadder disease. Of the patients referred to the dietitians, 86% were referred by surgeons. Of the dietitians that responded 77% thought that there was a role for low fat diets in the management of these patients; 92% would advise a low fat diet to help avoid pain, and 11% would advise a low fat diet to patients with gall-bladder disease who did not have pain, steatorrhoea or obesity.
The paper reviews the available evidence concerning the effect of dietary fat on the gall-bladder; it is concluded that, at present, there is little data to support the therapeutic use of a low fat diet for individuals with gall-stones.     

Alcohol: The Ambiguous Molecule.: By Griffith Edwards. Penguin Books, London. 2000, 230pp. paperback, {pound}7.99. ISBN: 0-14-126666-6.

The title points to society’s contradictory views of alcohol,to the seductiveness of alcoholic beverages and to their potentialfor harm. Professor Edwards, who is the doyen (worldwide) ofstudies on alcohol policies     

Dietary carnitine intake related to skeletal muscle and plasma carnitine concentrations in adult men and women

The purpose of this investigation was to determine if there was any relationship between dietary carnitine intake and the concentrations of carnitine in skeletal muscle and blood plasma in healthy adult men and women. Subjects (14 men, 14 women, fasted 8 h) reported to the Biodynamics Laboratory where they completed a 24-h diet recall questionnaire. Resting muscle biopsy (vastus lateralis) and blood plasma samples were taken and assayed for free, short-chain, and long-chain acyl carnitine concentrations. Dietary carnitine intake was estimated from data on concentrations in food. There was no significant relationship between either protein or carnitine intake with skeletal muscle carnitine concentrations. There was a significant relationship between both dietary carnitine (r = 0.50) and protein (r = 0.48) intake with blood plasma total acid soluble carnitine concentrations (p less than 0.01) in all subjects.     

Surgical staging of gastric carcinoma: sources and consequences of error

Macroscopic 'TNM' staging was performed during 78 consecutive operations for gastric carcinoma and compared with subsequent pathological staging. Surgical assessment was correct for tumour (T) in 60 per cent when depth of invasion was assessed, for nodes (N) in 61 per cent, for liver metastases (M) in 92 per cent but for all aspects in only 21 per cent. Curability (conservatively defined as T1-3, N0-1, M0) was correct in 8 of 18 patients thus assessed at surgery and incurability was pathologically correct in 58 of 60 patients. Despite inaccurate surgical staging, no patient was denied a resection although 10 patients had unduly radical procedures for their stage and 2 had inappropriately conservative procedures for their stage (but without evidence of residual disease). Staging errors did not jeopardize conventional surgical management substantially and use of intra-operative microscopic sampling of nodes would have improved surgical treatment only minimally.     

Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset.

Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP-lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L-dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action.     

Dynamic contrast-enhanced MR imaging assessment of vascularized free fibular grafts

Magnetic resonance (MR) imaging may be a noninvasive method for assessing perfusion of vascularized bone grafts placed for treatment of avascular necrosis. One proximal femur of seven beagles was devascularized, with insertion of a vascularized fibular graft. MR imaging at 1 week (seven dogs) and 6 weeks (five dogs) after surgery included pre- and postcontrast spin-echo sequences, unenhanced twodimensional time-of-flight (TOF) vascular imaging, and dynamic gradient-echo imaging during infusion of gadolinium. Relative signal intensity values of selected regions obtained from the dynamic gradientecho images were plotted as percent enhancement versus time. In the operated hip, MR imaging did not show enhancement in six of seven femoral heads and greater trochanters at 1 week after surgery, with similar results after 6 weeks. MR imaging of fibular grafts 6 weeks after surgery showed an initial rapid increase in enhancement and a subsequent slower increase in five of five dogs, although no enhancement was seen in six of seven dogs at 1 week. These findings contrasted with a rapid initial increase in enhancement followed by slow decline in non-operated hips. Two-dimensional TOP imaging did not show the vascular pedicle of the graft in any dog. Findings of radionuclide bone scanning performed 1 week after surgery were consistent with devascularization of the operated femur and fibular graft. However, tetracycline distribution and histologic findings confirmed the viability of five of five grafts within the devascularized femurs 6 weeks after surgery. Thus, dynamic contrast-enhanced MR imaging at 6 weeks after surgery is valuable for assessing vascular bone graft perfusion, while similar imaging at 1 week may suggest otherwise.     

Subjective perceptions and physiological variables during weaning from mechanical ventilation.

BACKGROUND: As costs related to mechanical ventilation increase, clear indicators of patients' readiness to be weaned are needed. Research has not yet yielded a consensus on physiological variables that are consistent correlates of weaning outcomes. Subjective perceptions rarely have been examined for their contribution to successful weaning. OBJECTIVE: To explore the subjective perceptions of dyspnea, fatigue, and self-efficacy and selected physiological variables in patients being weaned from mechanical ventilation. METHODS: Data were collected prospectively on 68 patients being weaned from mechanical ventilation. Subjective perceptions were measured by using 3 visual analog scales; physiological variables were measured by using the Burns Weaning Assessment Program and a patient profile. Weaning outcomes were recorded 24 hours after data collection. RESULTS: Participants were primarily white women and required mechanical ventilation for a mean of less than 4 days. Participants reported mild dyspnea, moderate fatigue, and high weaning self-efficacy. High PaO2, low PaCO2, stable hemodynamic status, adequate cough and swallow reflexes, no metabolic changes, and no abdominal problems were associated with complete weaning (P = .05). Subjective perceptions were associated with physiological variables but not with weaning outcomes. CONCLUSIONS: Multidimensional assessment of both primary and secondary indicators of readiness to be weaned is necessary for timely, efficient weaning from mechanical ventilation. Primary assessments include physiological variables related to gas exchange, hemodynamic status, diaphragmatic expansion, and airway clearance. Secondary assessments include perceptions related to key physiological variables. Additional research is needed to determine the predictive value of physiological variables and perceptions of dyspnea, fatigue, and self-efficacy.