Idiopathic CSF rhinorrhoea presenting with tension pneumocephalus and hemiparesis

A case of non-traumatic/non-iatrogenic CSF rhinorrhoea, presenting with tension pneumocephalus and hemiparesis is described. The possible pathological processes involved in this rare case are discussed. Cases in the literature of idiopathic CSF rhinorrhoea and also those of spontaneous pneumocephalus are reviewed.     

Excitotoxic spinal cord injury: behavioral and morphological characteristics of a central pain model

The involvement of tyrosine protein phosphorylation in the regulation of endothelial cell (EC) contraction and barrier function is poorly understood. We have previously shown that myosin light chain (MLC) phosphorylation catalyzed by a novel 214 kDa EC myosin light chain kinase (MLCK) isoform is a key event in EC contraction and barrier dysfunction [Garcia et al. (1995): J Cell Physiol 163:510-522; Garcia et al. (1997): Am J Respir Cell Mol Biol 16:487-491]. In this study, we tested the hypothesis that tyrosine phosphatases participate in the regulation of EC contraction and barrier function via modulation of MLCK activity. The tyrosine phosphatase inhibitor, sodium orthovanadate (vanadate), significantly decreased electrical resistance across bovine EC monolayers and increased albumin permeability consistent with EC barrier impairment. Vanadate significantly increased EC MLC phosphorylation in a time-dependent manner (maximal increase observed at 10 min) and augmented both the MLC phosphorylation and permeability responses produced by thrombin, an agonist which rapidly increases tyrosine kinase activities. The vanadate-mediated increase in MLC phosphorylation was not associated with alterations in either phosphorylase A Ser/Thr phosphatase activities or in cytosolic [Ca2+] but was strongly associated with significant increases in EC MLCK phosphotyrosine content. These data suggest that tyrosine phosphatase activities may participate in EC contractile and barrier responses via the regulation of the tyrosine phosphorylation status of EC MLCK.     

Trypsin-like neutral protease associated with soluble elastin

Isolation of tropoelastin is complicated by the presence of a neutral protease closely associated with tropoelastin that is capable of sequentially degrading tropoelastin to small peptides. Substrate and inhibitor specificities of this neutral protease associated with purified tropoelastin were examined. The enzyme displayed proteolytic activity against casein, and esterase activity was detected when assayed against N-tosyl-L-arginine methyl ester but not against tert-butyl-oxycarbonyl-L-alanine p-nitrophenyl ester. No appreciable elastinolytic activity was detectable against either insoluble sodium dodecyl sulfate treated elastin or maleylated tropoelastin. The enzyme was not inhibited by the chymotrypsin inhibitor toluenesulfonylphenylalanine chloromethyl ketone. The enzyme was inhibited by phenylmethanesulfonyl fluoride and, to various degrees, by metal chelators. Tosyllysyl chloromethyl ketone, epsilon-aminocaproic acid, and Aprotinin (pancreatic trypsin inhibitor--Kunitz type), all inhibitors of trypsin-like enzymes, were very effective inhibitors, as were soybean trypsin inhibitor and human alpha-1-antitrypsin. The data suggest that the tropoelastin-associated enzyme is a neutral serine protease with trypsin-like specificity.     

Gas-liquid chromatographic analysis of synovial fluid. Succinic acid and lactic acid as markers for septic arthritis

Nonvolatile short-chain fatty acids from 80 synovial fluids were quantified by gas-liquid chromatography. Succinic acid was detectable in all 23 septic synovial fluids infected with either gram-positive or gram-negative organisms and in only 5 of 57 nonseptic synovial fluids. Lactic acid was present in all of the effusions but was correlated with septic arthritis only when present in concentrations greater than 250 mg%. Neither short-chain fatty acid was more sensitive than high white blood cell counts (greater than 50,000 mm3) or depressed glucose concentration (less than 40 mg/dl) in diagnosing septic arthritis before antibiotic therapy; however, the detection of succinic acid was helpful in identifying patients with septic arthritis who had been given antibiotic treatment before arthrocentesis. Thus, gas-liquid chromatography, a rapid and sensitive method for the detection of short-chain fatty acids, may complement the currently available methods used to diagnose septic arthritis.     

The John Charnley Award. Prophylaxis of fat and bone marrow embolism in cemented total hip arthroplasty

The efficiency of a new cementing technique developed to prevent the risk of intraoperative pulmonary embolism was assessed. Seventy patients with coxarthrosis entered into a prospective, randomized clinical trial. In the control group of 35 cases the total hip replacement was cemented conventionally. In the second group a proximal drainage placed along the Linea aspera, and a distal drainage placed in the diaphysis, created a vacuum in the medullary cavity of the femur during the insertion of the stem. The operation was performed with the patient under blood gas analysis and hemodynamic and transesophageal echocardiography monitoring. Severe transatrial embolic events were observed during the insertion of the femoral component in 94% of the cases of the control group and in 14% of the cases of the vacuum group; the difference is statistically significant. A significant decrease of arterial partial pressure of O2 (-40.8 mm Hg) and increase of the pulmonary shunt values (+28.3%) occurred 5 minutes after the observation of embolic events in the cases operated on conventionally, but these parameters showed minimal changes in the vacuum group. The rise of intramedullary pressure in the femur is the most decisive pathogenic factor of pulmonary embolism during total hip arthroplasty. The logical prophylactic measure to prevent intravasation of fat and bone marrow is to create sufficient drainage. The cohorted investigation showed the value of the vacuum cementing technique for a substantial reduction of intraoperative embolism and pulmonary impairment.     

Interrupted noise exposures: threshold shift dynamics and permanent effects

A parametric study of the reduction of threshold shift (toughening phenomena) that takes place during the course of an interrupted noise exposure is described. 266 chinchillas randomly assigned to one of 32 experimental groups were exposed to one of the following: a 400-Hz narrow-band impact noise having a center frequency of 0.5, 1.0, 2.0, 4.0, or 8.0 kHz and peak sound-pressure levels of 109, 115, 121, or 127 dB. The impacts were presented for 5 d, 24 h/d or for 20 d, 6 h/d. corresponding pairs of exposures had equal energy. Group mean noise effects were estimated from pure-tone threshold obtained form inferior colliculus evoked potentials and from surface preparation histology. The threshold shift (TS) toughening phenomena is shown to occur in response to all stimuli that produce a TS and at all audiometric test frequencies. The amount of toughening, which is limited to less than 35 dB, varies with noise frequency and intensity. Based on group mean data the auditory system is not protected from the permanent effects of an interrupted noise exposure as a result of the toughening effect but rather differences in permanent effects between the 5- and 20-d exposures are attributed to the spreading of the exposure energy over an extended period of time.     

Domain swapping in G-protein coupled receptor dimers

Computer simulations were performed on models of the beta2-adrenergic receptor dimer, including 5,6-domain swapped dimers which have been proposed as the active, high affinity form (here the dimer interface lies between helices 5 and 6). The calculations suggest that the domain swapped dimer is a high energy structure in both the apo dimer and in the presence of propranolol. In the presence of agonist the energy of the domain swapped dimer is significantly lowered. Analysis of the dimer structure suggests that the agonist-induced conformational change optimizes the helix-helix interactions at the 5-6 interface. An antagonist on the other hand has little effect on these interactions. These observations are consistent with the hypothesis that the agonist functions by shifting the equilibrium in favour of the domain swapped dimer. Indirect support for the domain swapping hypothesis was obtained from the correlated mutations amongst the external residues of the known beta2-adrenergic receptors. These occur mainly at the 5-6 interface at precisely the locations predicted by the simulations; site-directed mutagenesis data in support of a functional role for these lipid-facing correlated residues is presented. The article includes a review of the experimental evidence for G-protein coupled receptor dimerization. Many other aspects of G-protein coupled receptor activation are discussed in terms of this domain swapping hypothesis