Possibilities and limits of automatic detection of pathologic intracranial pressure waves with FFT

Owing to the existence of "reserve spaces" varying individually in extent and expressed by the term compliance, space-consumption intracranial processes do not raise the intracranial pressure (ICP) primarily. Only when this compliance has been exhausted may ICP rise dramatically and may rapidly reach dangerously high levels. It has been shown in the past that "anticipatory" initiation of ICP-reducing measures--i.e. very early in the development of increasing mean ICP--may greatly benefit patient outcome. To recognize an imminent ICP crisis, the available compliance needs to be known. The classical method for determining this latter is the bolus test, which, however, has the disadvantage of being discontinuous and associated with the risk of infection. Another, less invasive and continuous, option is the recognition of pathological intracranial pressure waves. However, recognition of such patterns requires specialized knowledge, that is not widely available. Since, however, knowledge of the compliance is of general importance for intensive care, the idea of developing a PC-based automated system for the identification of pathological waves was followed up. During the course of our basic research effort, we investigated the suitability of the fast Fourier transformation (FFT) algorithm for this purpose. We were able to show that while the FFT is theoretically useful for the detection of pathological intracranial waves, its shortcomings in terms of its sensitivity to extraneous signals (noise) (of considerable importance for biological data handling) and errors in correctly estimating the amplitudes of pathological waves (of great importance for clinical evaluation) make FFT appear less than optimally suitable for this purpose.     

Mechanism-based design of prolactin receptor antagonists

The mechanism of action of two forms of the prolactin (PRL) receptor was studied using analogs of human growth hormone (hGH). At low concentrations (approximately 1 pM), hGH binds and stimulates proliferation of Nb2 cells containing the 391-residue PRL receptor as well as murine lymphoid FDC-P1 cells transfected with the 591-residue hPRL receptor. However, at high concentrations (approximately 70 microM) hGH inhibits proliferation of both these cell lines. Such a "bell-shaped" hormone response curve was observed for hGH stimulation of the hGH receptor (Fuh, G., Cunningham, B.C., Fukunaga, R., Nagata, S., Goeddel, D. V., and Wells, J.A. (1992) Science 256, 1677-1680) and is consistent with the sequential formation of an active hormone-(receptor)2 complex in which hGH binds through a first site (Site 1) to a first receptor and then through a second site (Site 2) to a second receptor. By analogy to hGH activation of the hGH receptor, we find that hGH variants that are mutated in Site 1 or Site 2 are greatly reduced as agonists. Similarly, only Site 2 mutants are potent antagonists of either hGH or hPRL stimulated cell proliferation. These and other data support the notion that hGH and hPRL activate the PRL receptor by sequential dimerization and provide a rational basis for the design of potent antagonists to the prolactin receptor.     

Regulation of phosphatidate phosphatase activity from the yeast Saccharomyces cerevisiae by sphingoid bases

The regulation of Saccharomyces cerevisiae membrane-associated phosphatidate phosphatase (3-sn-phosphatidate phosphohydrolase, EC 3.1.3.4) activity by sphingoid bases was examined using Triton X-100/lipid-mixed micelles. Sphingosine, phytosphingosine, and sphinganine inhibited purified preparations of the 104- and 45-kDa forms of phosphatidate phosphatase in a dose-dependent manner. The structural requirements for the sphingoid base inhibition of phosphatidate phosphatase activity were a free amino group and a long chain hydrocarbon. A detailed kinetic analysis was performed to determine the mechanism of phosphatidate phosphatase inhibition by sphingoid bases. The phosphatidate phosphatase dependence on phosphatidate was cooperative (Hill numbers of approximately 2) in the absence and presence of sphingoid bases. Sphingosine, phytosphingosine, and sphinganine were parabolic competitive inhibitors of phosphatidate phosphatase activity. This indicated that more than one inhibitor molecule contributed to the exclusion of phosphatidate from the enzyme. The aKi values (inhibitor constants) for sphingosine, phytosphingosine, and sphinganine were 1.5, 0.4, and 0.2 mol %, respectively, and the Km value for phosphatidate was 2.2 mol %. The cellular concentrations of free phytosphingosine and sphinganine were 0.16 and 0.53 mol %, respectively, relative to the total phospholipids in S. cerevisiae. The cellular concentrations of phytosphingosine and sphinganine were in the range of the aKi values for these sphingoid bases. These results raised the suggestion that phosphatidate phosphatase activity may be regulated in vivo by sphingoid bases.     

Interhemispheric subdural hematoma in adults: case reports and a review of the literature

The interhemispheric subdural hematoma is a relatively uncommon type of subdural hematoma, especially seen in patients with blood clotting disturbances. When its mass becomes sufficiently large, specific neurological abnormalities such as hemiparesis and signs of the falx syndrome are seen. Treatment can consist of conservative observation or craniotomy and is dictated by the clinical course. Conservative management is the treatment of choice for patients without disturbances of consciousness and for patients with stable clinical conditions. Surgical treatment is necessary in patients with progressive deterioration. Three case reports are presented, as well as a review of 64 cases described in the literature. The salient aspects of this clinical entity are discussed.     

Fibromuscular dysplasia of the internal carotid artery associated with alpha1-antitrypsin deficiency

OBJECTIVE: A deficiency of alpha1-antitrypsin has been implicated in the development of various disorders affecting medium-sized arteries, including intracranial aneurysms, cervicocephalic arterial dissections, and fibromuscular dysplasia (FMD). We performed alpha1-antitrypsin phenotyping in three consecutive patients who underwent bypass surgery for FMD of the extracranial internal carotid artery to test the hypothesis that alpha1-antitrypsin deficiency is a genetic risk factor for the development of FMD. METHODS: The study population consisted of three women (aged 37, 49, and 53 years, respectively) who had bilateral internal carotid artery stenosis caused by FMD. The indications for surgery included ocular or cerebral ischemic symptoms in two patients and progressive stenosis in one patient. The diagnosis of FMD was confirmed by histological examination of the resected segment of artery. The alpha1-antitrypsin phenotype was determined by isoelectric focusing in polyacrylamide gels. RESULTS: Two of the three patients had a heterozygous alpha1-antitrypsin deficiency (PiMZ phenotype). Pathological examination of the resected arterial segment showed typical medial FMD with focal intimal fibroplasia in both patients with the PiMZ phenotype. CONCLUSION: These findings suggest that a heterozygous alpha1-antitrypsin deficiency may be a genetic risk factor for the development of FMD of the internal carotid artery.     

Absence of cyclin D1 protein expression in splenic marginal zone lymphoma

We studied the endoscopic removal of tracheobronchial foreign bodies from 13 patients. Eight patients were treated under local anesthesia and 5 under general anesthesia. Complications included mild bleeding during endoscopic treatment of 3 patients. One patient was placed under general anesthesia because the patient was irritable and because hemorrhage made observation difficult. Laryngeal masks were used in 4 cases, and resulted in no complications. The follow-up courses ranged from 4 months to 12 years and were uneventful for all patients. Use of a fiberoptic bronchoscope in combination with laryngeal masks facilitated the management and removal of tracheobronchial foreign bodies by providing a secure airway and by minimizing the effect on the cardiorespiratory system.