Changes in CSF pressures during experimental acute arterial subdural bleeding in pig

Summary The effects of acute arterial subdural bleeding on cerebrospinal fluid (CSF) pressure and 12 other vital parameters were studied in spontaneously breathing pigs (group 1, n=9) and in mechanically ventilated pigs (group 2, n=18) to analyze quantitatively the bleeding course and the lethal mechanism.Spontaneously breathing animals all succumbed after a mean bleeding volume of 45.6±8.9ml, corresponding to about 50 per cent of the intracranial volume, and a mean bleeding duration of 11.0±2.6 min. Rapid rise in CSF pressures, marked transtentorial pressure gradients, and progressive reductions of cerebral perfusion pressure leading to a permanently iso-electric EEG, apnoea and to a terminal rise in arterial pressure (Cushing response), was the rule in these animals.The mechanically ventilated animals had smaller bleeding volumes (34.3±8.1 ml), but longer bleeding durations (13.8±5.8 min). In this group 7 animals survived. They had no pressure gradients, and only moderate changes in arterial pressure and EEG. The 11 animals that succumbed had marked transtentorial pressure gradients, but smaller increments in arterial pressure than the spontaneously breathing animals.At autopsy, subdurally located blood was found throughout the intracranial and spinal subdural compartments and along the spinal nerve roots in both groups.The results of this study suggest that survival after acute subdural haematoma is influenced by the presence of transtentorial pressure gradients and by the spinal sac acting as a space for expansion. The beneficial effect of artificial ventilation is discussed.This study has been supported by the University of Oslo, The Anders Jahre Foundation for The Advance of Research, and by the Norwegian Society for fighting Cancer.     

Megestrol acetate versus aminoglutethimide for metastatic breast cancer

In this prospective, randomized study the clinical response and toxicity of megestrol acetate (MA) and aminoglutethimide (AG) as second-line treatment in patients with metastatic breast cancer was compared. 176 patients were included, and 150 received treatment greater than 8 weeks and are evaluable for treatment response. The two groups did not differ with regard to prognostic factors. Response rate for the AG and MA groups were 34% and 31% respectively, with duration of response of 13.1 and 13.0 months. Stable disease was obtained in 33% and 35% respectively. No difference was observed in survival. Side effects occurred more frequently in the AG group (42%) than in the MA group (18%).     

Inter- and intraobserver variability in the histopathological diagnosis of medullary carcinoma of the breast,and its prognostic implications

Summary One hundred thirty-one breast carcinomas with medullary features, registered in the Danish Breast Cancer Cooperative Group from 1977–1982, have been histopathologically reviewed by two senior pathologists and classified as typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), and non-medullary carcinoma (NMC). Diagnostic criteria were based on those put forward by Ridolfiet al. and Fisheret al. The procedure was repeated with an interval of about one year by both pathologists. The diagnostic interobserver agreement was 72% with a Kappa of 0.55. The intraobserver agreement was 77% and 63% with Kappa values of 0.64 and 0.44, respectively. To see whether the observed inter- and intraobserver variability had any prognostic implications, diagnostic subgroups for both pathologists were analyzed with Kaplan Meier plots for recurrence-free survival (RFS) and with log rank tests. In the first evaluation pathologist 1 segregated a group of TMC with a significantly better RFS than for the NMC group, and pathologist 2 segregated a group of TMC with a corresponding strong trend. These findings could not, however, be reproduced in the second evaluation. The study indicates that the criteria of TMC and AMC as proposed by Ridolfiet al. need to be sharpened and simplified in order to reduce inter-and intraobserver variability. Larger studies with a control group of infiltrating ductal carcinomas are mandatory to elucidate the clinical importance of the diagnoses of Typical and Atypical Medullary Carcinoma of the breast.     

Phenotypes and spontaneous cell cytotoxicity of mononuclear cells from patients with seronegative spondyloarthropathies: Ankylosing spondylitis,psoriatic arthropathy and pauciarticular juvenile chronic arthritis — Analysis of mononuclear cells from peripheral blood,synovial fluid and synovial membranes

Summary T-cell subpopulations and natural killer (NK) cells from peripheral blood, synovial fluid and synovial membranes from patients with seronegative spondyloarthropathies were investigated. Thirty-four patients with ankylosing spondylitis, sixteen patients with psoriatic arthropathy and six patients with pauciarticular juvenile chronic arthritis were studied. All the patient groups had normal proportions of T4⁺ and T8⁺ cells as well as normal T4/T8 ratios in peripheral blood. In the synovial fluids the T4/T8 ratios were reduced in ankylosing spondylitis and psoriatic arthropathy (p<0.05). Although both the T4 and T8 subpopulations were reduced, the T4/T8 ratios in the synovial membranes of patients with these two disorders tended to be within the normal range of that of peripheral blood. Increased numbers of T-cells in the synovial fluid from patients with ankylosing spondylitis expressed class II MHC antigens. The natural killer cell activity was normal in peripheral blood and synovial fluids of patients with ankylosing spondylitis and psoriatic arthropathy while it tended to be reduced, although not significantly, in pauciarticular juvenile chronic arthritis. Synovial membranes were almost devoid of NK cell activity. The number of Leu 7⁺ cells were reduced in synovial fluid of patients with psoriatic arthropathy (p<0.04), but not as significantly as in the two other patient groups.     

Persistent right umbilical vein: incidence and significance.

OBJECTIVES: To conduct a prospective evaluation of the incidence and neonatal outcome of fetuses with persistent right umbilical vein. This condition had traditionally been considered to be extremely rare and to be associated with a very poor neonatal prognosis, but later evidence has raised some doubts about the veracity of these contentions. METHODS: Between August 1995 and November 1998, 8950 low-risk patients were prospectively evaluated at two medical centers. The sonographic diagnosis of a persistent right umbilical vein was made in a transverse section of the fetal abdomen when the portal vein was curved toward the stomach, and the fetal gall bladder was located medially to the umbilical vein. RESULTS: Persistent right umbilical vein was detected in 17 fetuses during the study. Four of them had additional malformations, of which three had been detected antenatally. CONCLUSIONS: We established that the incidence of persistent right umbilical vein in a low-risk population is 1 : 526. We believe that the sonographic finding of this anomaly is an indication for conducting targeted fetal sonography and echocardiography. When the persistent right umbilical vein is connected to the portal system and other anomalies are ruled out, the prognosis can generally be expected to be favorable.     

Hyperosmolarity selectively enhances IgE-receptor-mediated histamine release from human basophils

Increased osmotic pressure has been reported to cause non-cytotoxic histamine release (HR) from human basophils, as well as a potentation of HR induced by anti-IgE. In this study, the effects of hyperosmolar Na–K-acetate (300–600 mOsm/kg H₂O) on HR was studied in washed human blood cells from newborns, adult volunteers and patients with severe atopic dermatitis. These three patient groups represesented 3 very distinct populations with respect to total plasma IgE content, medians were <0.2 IU/ml, 20.5 IU/ml and 2508 IU/ml, respectively. Increasing osmolarity to 500 mOsm/kg H₂O caused little HR in the absence of other stimuli, whereas at 600 mOsm/kg H₂O a significant increase in spontaneous HR was seen. The HR induced by anti-IgE and Concanavalin A, acting through the IgE-receptor, was increased approximately twofold at 500 mOsM/kg H₂O. Responses were highly correlated to results at 300 mOsm/kg H₂O. The use of 600 mOsm/kg H₂O buffers caused a further increase in most, but not all blood samples. The potentiation of IgE-receptor-mediated HR when using hyperosmolar media was clearly independent of plasma IgE contents, and did not change the concentration-response to anti-IgE. In contrast, HR induced by the IgE-receptor-independent stimuli, Formyl-met-leu-phe and calcium ionophore A 23187, were not enhanced at all by incrased osmotic pressure. We conclude, that hyperosomolar media selectively enhance IgE-receptor-mediated HR. The use of hyperosmolar media may therefore be beneficial in a diagnostic application of washed blood HR assays use in allergy diagnosis.     

The effect of quinidine on the analgesic effect of codeine

Summary We have studied the hypoalgesic effect of codeine (100 mg) after blocking the hepatic O-demethylation of codeine to morphine via the sparteine oxygenase (CYP2D6) by quinidine (200 mg). The study was performed in 16 extensive metabolizers of sparteine, using a double-blind, randomized, four-way, cross-over design. The treatments given at 3 h intervals during the four sessions were placebo/placebo, quinidine/placebo, placebo/codeine, and quinidine/codeine. We measured pin-prick pain and pain tolerance thresholds to high energy argon laser stimuli before and 1, 2, and 3 h after codeine or placebo.After codeine and placebo, the peak plasma concentration of morphine was 6–62 (median 18) nmol·.l^–1. When quinidine pre-treatment was given, no morphine could be detected (<4 nmol·l^–1) after codeine. The pin-prick pain thresholds were significantly increased after placebo/codeine, but not after quinidine/codeine compared with placebo/placebo. Both placebo/codeine and quinidine/codeine increased pain tolerance thresholds significantly. Quinidine/codeine and quinidine/placebo did not differ significantly for either pin-prick or tolerance pain thresholds.These results are compatible with local CYP2D6 mediated formation of morphine in the brain, not being blocked by quinidine. Alternatively, a hypoalgesic effect of quinidine might have confounded the results.     

Cerebrospinal fluid cholinesterases in aging and in dementia of the Alzheimer type

Protein concentration and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were assayed in the cerebrospinal fluid (CSF) of 26 healthy normal subjects (20-86 years old), 27 patients with dementia of the Alzheimer type (DAT), and 10 patients with dementia of the Alzheimer type with extrapyramidal signs (EDAT). In normal subjects, there was an age-related increase in CSF protein and AChE activity and a significant correlation (p less than 0.001) between CSF protein and BChE activity. In the DAT and EDAT groups, CSF AChE activities (mean +/- SD = 17.5 +/- 3.6 and 15.3 +/- 4.4 nmol/min/ml, respectively) were significantly lower (p less than 0.05) than in 13 age-matched control subjects (21.5 +/- 5.6 nmol/min/ml). In contrast, neither CSF protein concentration, BChE activity, nor the ratio of AChE/BChE differed significantly between groups. In patients with DAT, CSF AChE activity was significantly lower (p less than 0.05) in subjects with an early onset compared to those with a late onset (16.4 +/- 3.4 and 19.7 +/- 2.8 nmol/min/ml, respectively), and activity in the latter group did not differ significantly from control values. CSF AChE activity was not related to dementia severity and did not change significantly over an 18-month period. Although these results confirm a cholinergic deficit in patients with DAT, the considerable overlap of CSF AChE activity between groups and the nonsignificant correlation between AChE activity and dementia severity limit the usefulness of CSF AChE as a diagnostic marker of this disorder.