Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP/HUS). Description of a series of 35 patients

Subsequent to the implementation of a severity marker stamp in case notes, an audit was performed in 86 admissions with acute asthma to a specialist centre over a 12 month period. Compared to previous audit the documentation of severity markers was significantly better (PEFR: 52% vs 83% p = 0.001, Respiratory rate: 44% vs 81% p = 0.001, ABG: 72% vs 80% p = 0.04, air entry: 58% vs 86% p = 0.001, speech: 27% vs 86% p = 0.001, exhaustion: 4% vs 86% p = 0.001). In contrast to the previous audit where no patient received FiO2 > 0.35, 66% of the cases in the repeat audit received FiO2 0.60 (p = 0.001). The mean duration of admission was five days and showed highest partial correlation (r = 0.6) to the time in hours for the pulse to fall to 80/min. Multiple linear regression showed that this was the only variable best predicting the duration of admission (R2 = 0.3). Admission pulse rate (p = 0.04) and serum K+ (p = 0.04) best discriminated between patients admitted for over and under five days. Logistic regression identified only the admission pulse as significant in calculating the odds of the patient staying in the hospital for > 5 days.     

Nonoperative management of esophageal perforations. Is it justified?

OBJECTIVE: Experiences obtained with nonoperative treatment (NOT), i.e. total prohibition of per oral food intake for a minimum of 7 days, administration of combinations of broad-spectrum antibiotics, and parenteral hyperalimentation, are described in the management of esophageal perforations. SUMMARY BACKGROUND DATA: The place, value, and indication of NOT in the management of esophageal perforation has not yet been unequivocally defined. As a result, contradictory data have been published regarding the outcome of NOT. METHODS: During the past 15 years (1979 to 1994), 20 of 86 patients (23.3%) with esophageal perforation have been treated nonoperatively from the outset. In this group, perforations were located to the upper, middle, and lower third of the esophagus in 50%, 30%, and 20%, respectively. In the operative management group (OT)--in which conservative (drainage, endeprothesis), reconstructive (suture, reinforced suture), and radical (resection) surgical methods were applied--lesions were preponderantly located in the lower one third of the esophagus (56.1%--37/66). As to the interval between the perforation and the onset of treatment, 14 patients had been diagnosed within 24 hours, whereas in 6 cases treatment had been begun beyond 24 hours. RESULTS: NOT could be successfully carried out in 16 patients; the decision to use NOT had to be revised in 4 other cases (Table 1). Two patients were lost; the mortality rate was 10% (2 of 20). The rate of complications was lower in the NOT group (20%, or 4 of 20) than in the OT group (50%, or 33 of 66). CONCLUSIONS: NOT can be suggested for the treatment of intramural perforations. In the case of transmural perforation, this approach should be taken into consideration if the esophageal lesion is circumscribed, is not in neoplastic tissue, is not in the abdominal cavity, and is not accompanied by simultaneous obstructive esophageal disease; in addition, symptoms and signs of septicemia should be absent.     

Fibrinolytic variables and cardiovascular prognosis in patients with stable angina pectoris treated with verapamil or metoprolol. Results from the Angina Prognosis study in Stockholm

BACKGROUND: Disturbed fibrinolytic function may influence the progression of coronary atherosclerosis and contribute to thrombotic cardiovascular (CV) events. METHODS AND RESULTS: In the Angina Prognosis Study in Stockholm (APSIS), patients with stable angina pectoris were studied prospectively during double-blind treatment with metoprolol or verapamil. Various measures of fibrinolytic function were studied in 631 (of 809) patients. During a median follow-up time of 3.2 years (2132 patient-years), 32 patients suffered a CV death, 21 had a nonfatal myocardial infarction (MI), and 77 underwent revascularization. Plasma levels of tissue plasminogen activator (TPA) activity and antigen (ag), plasminogen activator inhibitor (PAI-1) activity at test, and TPA responses to exercise were determined at baseline and after 1 month's treatment and were related to subsequent fatal and nonfatal CV events. Univariate Cox regression analysis revealed that elevated levels of TPA-ag at rest (P < .05), high PAI-1 activity (P < .05), and low TPA-ag responses to exercise (P < .05) were associated with increased risk of subsequent CV death. After adjustment for baseline risk factors, TPA-ag independently predicted CV death or MI. In addition, PAI-1 activity independently predicted CV death or MI in male patients. Verapamil treatment was associated with a 10% decrease of TPA-ag levels and metoprolol treatment with a 2% increase (P < .001 for treatment difference). CONCLUSIONS: Plasma TPA-ag levels at rest, and among male patients PAI-1 activity as well, independently predict subsequent CV death or MI in patients with stable angina pectoris.     

The activity of acid phosphatase and its isoenzymes in patients with food poisonings

Changes in the activity of acid phosphatase (AP) and its isoenzymes (tartrate-insensitive AP and formalin-insensitive AP) were investigated in patients with food poisoning in the course of the disease. The activity of AP and its isoenzymes in the serum started to grow in early convalescence and reached maximum in late convalescence. Total activity of AP in food toxic infections consists primarily of the activity of its platelet fraction. AP activity may serve as an additional criterion to predict vascular platelet involvement of hemostasis.     

Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB), a neural member of the EGF family of differentiation factors, is implicated in neurite formation

Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB) was identified by combining binding assays with immunological screens in the chicken nervous system as a novel member of the EGF family of differentiation factors. cDNA cloning indicates that CALEB is a multidomain protein that consists of an NH2-terminal glycosylation region, a leucine-proline-rich segment, an acidic box, a single EGF-like domain, a transmembrane, and a short cytoplasmic stretch. In the developing nervous system, CALEB is associated with glial and neuronal surfaces. CALEB is composed of a 140/130-kD doublet, an 80-kD band, and a chondroitinsulfate-containing 200-kD component. The latter two components are expressed in the embryonic nervous system and are downregulated in the adult nervous system. CALEB binds to the extracellular matrix glycoproteins tenascin-C and -R. In vitro antibody perturbation experiments reveal a participation of CALEB in neurite formation in a permissive environment.     

Pharmacokinetic and bioequivalence study of two gemfibrozil preparations

A comparative pharmacokinetic study has been performed in 19 healthy male volunteers in a single-dose, randomized, two way cross-over design with two preparations of gemfibrozil (CAS 25812-30-0) capsules each of them containing 300 mg active ingredient. The test preparation was Innogem 300 mg capsule. The plasma concentration of gemfibrozil was determined by a validated HPLC-UV analytical method. The statistical comparison of individual pharmacokinetic parameters (AUC0-16, AUC0-oc Cmax, tmax) of the two capsule preparations was performed by three-way analysis of variance (ANOVA), Wilcoxon's, Westlake's, Schuirmann's and Hanck-Anderson's method as well as by the calculation of confidence intervals on the ratio of test/reference. The relative bioavailability of the test preparation with respect to the reference preparation in terms of the AUC0-oc was 104.06 +/- 21.61%. No statistically significant difference was found between the pharmacokinetic parameters, calculated from plasma concentration-time curves, indicating that the two preparations were bioequivalent.     

Electrophysiological and Fos immunohistochemical evidence for the excitatory nature of the parafascicular projection to the globus pallidus

Extracellular recordings and immunohistological detection of c-Fos-like immunoreactive proteins were used to determine the synaptic effect of the parafascicular projection to the globus pallidus. Electrical stimulation of the parafascicular neurons induced a single-spike excitatory response with a stable latency of 2.3 ms, suggesting a monosynaptically driven effect. Pharmacological stimulation of the parafascicular nucleus with carbachol increased tonically the pallidal discharge rate by 142%. The discharge rate of the pallidal neurons was described by 37% in parafascicular-lesioned rats. These results demonstrate the excitatory nature and the tonic action of the parafasciculopallidal projection. Carbachol activation of parafascicular neurons also induced the synthesis of c-Fos-like immunoreactive proteins in the pallidal neurons. Control experiments in subthalamic-lesioned rats showed that the parafascicular excitation of the pallidal neurons remained, but both electrophysiological and expression of c-Fos-like immunoreactive proteins were attenuated. This suggests that the direct parafascicular excitation of the pallidal neurons is indirectly reinforced by the previously described parafascicular excitatory input to the subthalamic nucleus. Conversely, the effect of this last input to the subthalamic nucleus is dramatically enhanced in rats with pallidal lesion. Our results demonstrate the complex role of the parafascicular nucleus in activating both the globus pallidus and the subthalamic nucleus, two closely related structures. These results illustrate the integrative capacities of the globus pallidus, whose activity is modulated by multiple afferents.     

The in vivo metabolic pattern of low-grade brain gliomas: a positron emission tomographic study using 18F-fluorodeoxyglucose and 11C-L-methylmethionine

OBJECTIVE: The object of the present study was to identify metabolic differences between low-grade astrocytomas and oligodendrogliomas and to improve their diagnosis and noninvasive assessment, because both types of tumors look very similar from the point of view of clinical and radiological data (as assessed by computed tomography and magnetic resonance imaging). METHODS: Before any aggressive treatment, 22 patients with primary low-grade gliomas (astrocytomas in 12 patients and oligodendrogliomas in 10) were investigated with positron emission tomography for both glucose metabolism (18F-fluorodeoxyglucose) and amino acid uptake (11C-L-methylmethionine). An original software that allows a full metabolic analysis of the tumor region of interest (defined from the T1-weighted magnetic resonance image) and compares tumor tissue uptake tracer concentrations with average healthy tissue values has been implemented for data processing. Heterogeneity of each individual tumor has been taken into account and was expressed in histograms, which provided data about the mean and also extreme and intermediate values of tracer concentrations and the way these values are distributed among the full tumor mass. RESULTS: It has been shown that both tumor types exhibit a glucose hypometabolism (slightly more pronounced with astrocytomas), whereas they strongly differ in methionine uptake, which is high in all oligodendrogliomas and either decreased, normal, or moderately increased in astrocytomas. This latter metabolic difference between both tumor populations may be partially explained by their different cell densities. CONCLUSION: This study suggests that despite similar radiological and clinical presentations, these two kinds of low-grade gliomas are metabolically different and could therefore have specific responses to different therapies. Moreover, their in vivo metabolic follow-up with positron emission tomography should rely on different parameters, depending on their histological type; methionine uptake may be more relevant than glucose metabolism in the follow-up of oligodendrogliomas.     

Regional chemotherapy of liver tumors

In the absence of adequate autogenous vein for tibial artery bypass in limb salvage surgery, the use of prosthetic grafts with a distal anastomotic vein cuff or patch has shown promising results. Here, we describe how the Florester Internal Vessel Occluder (Meadox UK, Bedfordshire, UK) can facilitate the construction of a distal anastomotic vein cuff.