A pilot study of streptokinase for acute cerebral infarction

We evaluated intravenous streptokinase in the treatment of cerebralinfarction. Following neurological assessment and cerebral computedtomography (CT), patients aged 40–80 years with symptomsof anterior circulation acute ischaemic stroke were given 1.5M units streptokinase or saline placebo in a double-blind randomizedstudy. Twenty patients (10 streptokinase, 10 placebo), 11 males,9 females, aged 57–79 years, were treated out of 512 consecutiveadmissions to the acute stroke unit over a 2-year period. InitialCT was normal in 11 (6 placebo, 5 streptokinase) and showedearly signs of cerebral infarction in nine (4 placebo, 5 streptokinase).Median times from symptom onset to treatment were 5.2 h (placebo)and 5.8 h (streptokinase). Streptokinase treatment was associatedwith symptomatic symptomatic hypotension in one patient. RepeatCT at 72 h demonstrated intracerebral haematoma in two patientsand haemorrhagic infarction in one patient in the streptokinasegroup; the two cases of haematoma formation were associatedwith neurological deterioration and death. One patient in theplacebo group had evidence of haemorrhagic infarction at 72h. There were three deaths in each treatment group, all withinthe first 14 days. Patients with acute stroke can be evaluatedwith CT and treated with streptokinase within 6 h, but the opportunityfor treatment is currently limited to few patients. Streptokinasetreatment is not without risk, but potential clinical benefitjustifies ongoing multicentre randomized trials.     

DOES GLYCINE ANTAGONISM UNDERLIE THE EXCITATORY EFFECTS OF METHOHEXITONE AND PROPOFOL

We have investigated the pharmacological basis of CNS excitationthat occurs in association with general anaesthesia in mice.Propofol produced sustained clonic movements during anaesthesia.Methohexitone produced intermittent non-rhythmic jerking duringanaesthesia. Ethanol and pento-barbitone produced anaesthesiawithout associated clonic movements. Doses of all anaestheticdrugs were equipotent. Surface EEG recordings showed paroxysmaldischarges consistent with interictal manifestations of corticalseizures with methohexitone or propofol, but not with ethanolor pentobarbitone. Strychnine, a glycine antagonist withouteffects on the cerebral cortex, and bicucul-line, a GABA_A antagonistwith effects on the cerebral cortex, were used in doses thatwere equipotent–0.5 log units less than the ED₁₀ for clonicconvulsions. Strychnine potentiated both excitatory behaviourand EEG paroxysmal discharges when given with methohexitoneor propofol, but not with ethanol or pentobarbitone. Bicucullinedid not affect either behaviour or EEG with any of the anaestheticdrugs. Our data show that methohexitone and propofol producedCNS excitation, while pentobarbitone and ethanol did not. Wepropose that the pharmacological basis of this excitation maybe glycine antagonism occurring in subcortical structures.     

Physical mapping: integrating computational and molecular genetic data

A crucial step beyond the identification of genetic linkage of a disease to a chromosomal region is the production of a physical map that will allow the identification of candidate genes. Although the process of physical map building has been facilitated by the flow of data released by the Human Genome Project, gathering all the information together requires significant effort. In a previous study, we reported linkage between Bipolar Affective Disorder and the chromosomal location 4p15.3–p16.1. In this review we use this example to describe how to collect publicly available sequence, DNA fingerprint, and genetic marker data and integrate these with empirical data to build a large scale high resolution physical map of a region. Methods used to identify new genetic markers and candidate genes within a circumscribed region are also presented.     

Alternans of the ST Segment and T Wave. A Sign of Electrical Instability in Prinzmetal''s Angina

In an effort to determine the incidence of ventricular arrhythmias associated with ST segments alternans, the patterns of ST segment and T-wave electrical alternans (STEA) were analyzed in 93 patients during spontaneous Prinzmetal's angina. Twenty-eight of 93 patients, or 30% (Group I), showed STEA during episodes of ST segment elevation. SIxty-five of 93 patients, or 70% (Group II), showed no alternans during episodes of ST segment elevation. In Group I, ventricular arrhythmias, defined as all ventricular ectopic activity greater than 5 beats per minute and complex Lown grades III to V, occurred during 52 of 55 episodes, or 95%; whereas in Group II, ventricular arrhythmias occurred in only 51 of 125 episodes, or 41% (p less than 0.01). The difference in the incidence of ventricular fibrillation (VF) or ventricular tachycardia (VT) in the two groups was more striking. VT or VF occurred in 20 of 55 in Group I (36%) versus 5 of 125 in Group II (4%). Although there were no significant differences in age or sex between Group I and II patients, there was a significant difference in the magnitude of the maximum ST segment elevation (5 mm in Group I versus 3 mm in Group II, p less than 0.01). This study demonstrates that the occurrence of STEA and T wave alternans frequently heralds the onset of ventricular arrhythmias in Prinzmetal's angina. Both the arrhythmias and the alternans occur during the time of maximal ST segment elevation.     

Meckel's diverticulum

A 31 year-old man was seen with acute gastrointestinal bleeding. Superior mesenteric angiography revealed a vascular blush. This corresponded to an area of narrowing seen on the small bowel series. A diagnosis of malignant neoplasm was made preoperatively. At laparotomy, however, a Meckel's diverticulum with ulceration and stricture formation extending into the ileum was found. The histology showed gastric mucosa with ulceration. This report depicts small bowel narrowing secondary to Meckel's diverticulum.     

Chronic cough with eosinophilic bronchitis: examination for variable airflow obstruction and response to corticosteroid

The purpose of this study was to examine airway responsiveness, sputum cells and the effects of inhaled corticosteroid in the chronic cough syndrome associated with eosinophilic bronchitis. We studied nine consecutive referrals with chronic cough, sputum with >10% eosinophils, normal spirometry, and normal methacholine airway responsiveness. Clinical assessment, sputum analysis, allergy skin tests and a methacholine inhalation test were performed at the first visit. Peak expiratory flow (PEF) was measured twice daily for 1 week followed by an adenosine monophosphate (AMP) inhalation test. Subjects were then treated with inhaled beclomethasone 0.4 mg twice daily for 7 days. Sputum analysis and measurement of methacholine responsiveness were then repeated. Excessive airway narrowing to methacholine was not present in any of the subjects. A methacholine plateau response was present in five subjects. Hyperresponsiveness to AMP was absent in six of the nine subjects, and PEF variability was not increased for eight subjects. Corticosteroid therapy led to a reduction in sputum eosinophil counts from 40.1 (so 21.4)% to 4.0 (4.5)% but there was no significant change in metachromatic cell counts (0.8 so 0.5% vs 0.6 sd 0.6%) or total cell counts. Methacholine responsiveness improved within the normal range in the three subjects in whom it could be determined. Chronic cough associated with eosinophilic airway inflammation can occur in the absence of variable airflow obstruction (asthma) and can improve after treatment with inhaled corticosteroid. This treatment can reduce the level of methacholine responsiveness within the normal range and reduces sputum eosinophils but not mast cells. These results suggest that the occurrence of variable airflow obstruction depends on the baseline level of methacholine responsiveness, the degree of eosinophilic infiltration and the degree to which methacholine responsiveness becomes heightened.     

Computer screening for early detection of melanoma—is there a future?

Computer image analysis in the study of pigmented lesions is critically examined and discussed in the light of the current published data. The potential for objective analysis by computers as a possible screening aid for the inexperienced clinician is discussed. The future for this technology is exciting if handled with care.