Tardive dyskinesia and impaired glucose tolerance

The authors examined the role of impaired glucose metabolism in the pathophysiology of tardive dyskinesia in schizophrenic patients with and without persistent TD. Glucose tolerance and insulin levels were determined in 86 patients with persistent tardive dyskinesia and in 108 patients without tardive dyskinesia. Dyskinesias were assessed by the abnormal involuntary movement scale (AIMS) and extrapyramidal symptoms by the Simpson--Angus rating scale (SARS). Fasting blood glucose levels were significantly lower while the first and second hour glucose levels did not reveal any differences in patients with tardive dyskinesia compared with those without tardive dyskinesia. Insulin levels did not differ in these two groups. Our cross-sectional epidemiological study does not suggest hyperglycemia to be a risk factor for tardive dyskinesia. However, prospective long-term studies with multiple assessment points are needed to clarify the role of glucose metabolism in the development of tardive dyskinesia.     

Lateralising value of neuropsychological protocols for presurgical assessment of temporal lobe epilepsy

PURPOSE: To estimate the value of neuropsychological measurements in determining the side of seizure onset for presurgical assessment in patients with temporal lobe epilepsy. The lateralising value of neuropsychological protocols was evaluated for all patients and in subpopulations depending on surgical outcome with regard to seizure control, speech dominance, neuropathology, and need for intracranial EEG recordings. METHODS: A battery of neuropsychological procedures was carried out preoperatively in 125 patients who underwent left (n = 66) or right (n = 59) temporal lobectomies. Binary logistic regression analysis was performed to find sets of variables that allowed the best prediction of the side of seizure onset (assumed to be the operated-on side). RESULTS: Combinations of noninvasive neuropsychological tests and Wada subscores showed the highest lateralising values: 80.8% for all patients, 79.4% in seizure-free patients, 86.0% in patients not rendered seizure free, 85.7% in left speech patients, 77.8% in non-left speech patients, 89.3% in patients with mesial temporal sclerosis (MTS), 78.1% in non-MTS patients, 80.3% in patients who underwent intracranial EEG recordings, and 77.3% in those who did not. CONCLUSIONS: The lateralising value (80-90%) of neuropsychological protocols appears similar to that of other tests widely accepted for lateralisation (ictal and interictal scalp EEG and neuroimaging). Attention should be paid to neuropsychological results, particularly from the Wada test, during presurgical assessment of temporal lobe epilepsy, as they can provide strong support for findings from other lateralising tests, particularly in patients with presumed MTS or in left-speech patients.     

Hyperventilation-induced high-amplitude rhythmic slowing with altered awareness: a video-EEG comparison with absence seizures

PURPOSE: Hyperventilation-induced high-amplitude rhythmic slowing (HIHARS) in children may be associated with clinical episodes of altered awareness. The presence of automatisms has been proposed as a distinguishing feature that helps to differentiate absence seizures from nonepileptic causes of decreased responsiveness. This retrospective, controlled, video-EEG study compared the clinical characteristics of episodes of HIHARS with loss of awareness with those of absence seizures. METHODS: The database of a tertiary Children's Hospital was searched for patients studied between April 1993 and April 1997 who had at least one episode of HIHARS with loss of awareness. The absence control group was obtained by selecting the next patient, after an HIHARS study subject, who met the following criteria: (a) had at least one absence seizure occurred during hyperventilation in the EEG recording, and (b) had a diagnosis of idiopathic generalized epilepsy. The video-EEG and medical histories of all patients were reviewed and summarized. RESULTS: We reviewed video-EEG recordings of 77 episodes of HIHARS with loss of awareness from 22 children and 107 absence seizures during hyperventilation from 22 children. Eye opening and eyelid flutter were seen more frequently in absence seizures, whereas fidgeting, smiling, and yawning occurred more frequently during HIHARS episodes. Arrest of activity, staring, and oral and manual automatisms were observed in both groups. CONCLUSIONS: Automatisms are common in both HIHARS and absence seizures. Yawning, smiling, and particularly fidgeting occur more commonly and eye opening and eyelid flutter less commonly in HIHARS. However, episodes of HIHARS with loss of awareness clinically mimic absence seizures, and these conditions can be distinguished reliably only by EEG.     

A new score for the evaluation of palpable breast masses in women under age 40

BACKGROUND: The purpose of this study was to develop a rapid and accurate diagnostic test for palpable breast masses in women under age 40. METHODS: Masses were evaluated utilitzing a modified triple test score (MTTS), which assigned scores of 1 point for benign, 2 points for suspicious, or 3 points for malignant findings from physical examination, ultrasonography, and fine needle aspiration. The MTTS was the sum of the three scores and was correlated with biopsy or follow-up. RESULTS: Among 113 masses, 100 scored 3 points, 8 scored 4 points; all were benign. Three scored 5 points; 1 was malignant. Two scored >or=6 points: both were malignant. CONCLUSIONS: The MTTS has 100% diagnostic accuracy when other than 5 points. Masses scoring or=6 points may proceed to definitive therapy. Masses scoring 5 points (3%) require biopsy. This approach avoids open biopsy in the majority of cases, while capturing all malignancies.     

A novel small molecule that directly sensitizes the insulin receptor in vitro and in vivo

Insulin resistance, an important feature of type 2 diabetes, is manifested as attenuated insulin receptor (IR) signaling in response to insulin binding. A drug that promotes the initiation of IR signaling by enhancing IR autophosphorylation should, therefore, be useful for treating type 2 diabetes. This report describes the effect of a small molecule IR sensitizer, TLK16998, on IR signaling. This compound activated the tyrosine kinase domain of the IR beta-subunit at concentrations of 1 micromol/l or less but had no effect on insulin binding to the IR alpha-subunit even at much higher concentrations. TLK16998 alone had no effect on IR signaling in mouse 3T3-L1 adipocytes but, at concentrations as low as 3.2 micromol/l, enhanced the effects of insulin on the phosphorylation of the IR beta-subunit and IR substrate 1, and on the amount of phosphatidylinositol 3-kinase that coimmunoprecipitated with IRS-1. Phosphopeptide mapping revealed that the effect of TLK16998 on the IR was associated with increased tyrosine phosphorylation of the activation loop of the beta-subunit tyrosine kinase domain. TLK16998 also increased the potency of insulin in stimulating 2-deoxy-D-glucose uptake in 3T3-L1 adipocytes, with a detectable effect at 8 micromol/l and a 10-fold increase at 40 micromol/l. In contrast, only small effects were observed on IGF-1-stimulated 2-deoxy-D-glucose uptake. In diabetic mice, TLK16998, at a dose of 10 mg/kg, lowered blood glucose levels for up to 6 h. These results suggest, therefore, that small nonpeptide molecules that directly sensitize the IR may be useful for treating type 2 diabetes.     

Inositol 1,4,5-trisphosphate turnover enzymes--activities and subcellular distribution in hepatocarcinogenesis

The metabolism of inositol 1,4,5-trisphosphate and inositol 1,3,4,5- tetrakisphosphate in homogenates and sub-fractions from normal rat liver and premalignant liver nodules was investigated. The activities of 5-phosphatase, expressed as pmol converted substrate per minute and mg protein, were equal when using the two substrates, and did not differ between normal and nodular homogenates. Subcellular fractions were purified by sequential steps of differential centrifugation and density gradient fractionation procedures. The total phosphatase activity was found to be distributed between cytosol (15%) and membraneous fractions (75%), with most of the enzyme activity residing in the plasma membranes. A doubling of phosphatase specific activity was seen in the nodular low density membrane fraction, containing Golgi apparatus and endosomes, as compared with normal liver. Inositol 1,4,5- trisphosphate 3-kinase activity was found to be exclusively cytosolic. No difference in this enzyme was seen between the two tissue types studied. Vasopressin (0.2 or 2 microM) had no effect either on phosphatase or kinase activity. The compartmentalization of inositol polyphosphate 5-phosphatase activity presents a possible explanation of earlier findings that premalignant liver tissue was able to respond with inositol 1,4,5-trisphosphate, but not inositol 1,3,4,5- tetrakisphosphate formation after agonist stimulation.      

A BPA survey of recently appointed consultants

A postal survey of recently appointed consultant paediatricians was undertaken to determine whether they perceived their training had adequately equipped them for their current job. The response rate was 69% (207/299). After excluding replies from consultants trained outside the UK the analysis was carried out on 167 replies. Trainees held a mean 5.2 posts during general and higher professional training, necessitating a mean 1.8 house moves. Altogether 82% felt moves were beneficial to training but 46% found moves 'very disruptive' to family life. Only 12% of district general hospital and 22% of teaching hospital senior registrars took two research sessions a week. Supervision and training in research was absent or poor for more than 60%; 24% felt major changes and 55% moderate changes were needed to current training. Training in non-clinical skills was particularly in demand and a curriculum for both trainers and trainees with regular appraisals is required. Research at senior registrar level needs review and educational methods improved to achieve better training in a shorter period.