Penetration of fusidic acid into human brain tissue and cerebrospinal fluid

Summary Penetration of fusidic acid into brain tissue in six patients and cerebrospinal fluid in seven patients was determined. Tissue samples, taken during surgery revealed drug levels at about 7% of simultaneous serum concentrations. In contrast, cerebrospinal fluid concentrations were below 1% of serum levels. Since serum- and tissue levels of fusidic acid were far above the minimal inhibitory concentration (MICs) of staphylococci and streptococci, and since it has a long serum half-life of about 10 hours, it is a promising candidate for prophylaxis in neurosurgery.     

Production and clearance of lactate from brain tissue, cerebrospinal fluid, and serum following experimental brain injury

Lactate dynamics in the brain, cerebrospinal fluid (CSF), and serum were studied in 20 chloralose-anesthetized cats following fluid-percussion trauma. Brain lactate and brain tissue pH were measured by hydrogen-1 and phophorus-31 magnetic resonance spectroscopy. The CSF, arterial, and cerebrovenous serum lactate levels as well as serum glucose concentration were quantified. In the six sham-operated control animals, brain, CSF, cerebrovenous, and arterial lactate levels as well as brain pH remained at normal values. In the five animals in the mild-trauma group (1.6 atm), brain and CSF lactate levels were moderately elevated, although the brain pH and serum lactate content remained at control values. Severe trauma (3.1 atm) in nine cats produced an 82% increase in the brain lactate index and a reduction in brain tissue pH (7.02 +/- 0.02 to 6.95 +/- 0.02; mean +/- standard error of the mean), indicating brain tissue acidosis caused by excessive lactate accumulation. Brain lactate levels reached a peak 1 1/2 hours after severe trauma, then steadily decreased to normal levels by 8 hours posttrauma. Maximum increases of CSF and arterial lactate levels (from 1.4 +/- 0.2 to 4.1 +/- 0.4 and from 1.6 +/- 0.2 to 4.1 to 0.6 mmol/liter, respectively) were observed 15 minutes after trauma, and the values decreased during the next 2 hours. The response was biphasic, with a secondary rise observed in both CSF and serum lactate levels during the remaining 4 hours of the experiment. The difference between the arterial and venous lactate levels (A-Vlact) gradually increased and reached a peak 2 hours postinjury (from -0.05 +/- 0.10 to -0.41 +/- 0.09 mmol/liter). The results of this study show that the production of lactate in brain tissue, CSF, and blood increased in proportion to the severity of the injury. The observation that lactate levels in blood and CSF are maximum immediately following impact while brain lactate and A-Vlact are gradually increasing suggests that the brain-tissue production of lactate fails to account for the rapid appearance of lactate in CSF and blood. It is speculated that the initial elevation of CSF lactate values reflects the systemic response of trauma, and the secondary rise of CSF lactate levels following severe trauma is due to slow seepage of lactate produced by brain tissue into the CSF space. These studies are the first to describe the temporal profile of brain lactate production and eventual clearance by CSF and blood in fluid-percussion injury.(ABSTRACT TRUNCATED AT 400 WORDS)     

Remodeling of cerebrospinal fluid lipoprotein particles after human traumatic brain injury

The association between possession of the APOE epsilon4 allele and unfavourable outcome after traumatic brain injury (TBI) suggests that the apolipoprotein E protein (apoE) plays a key role in the response of the human brain to injury. ApoE is known to regulate cholesterol metabolism in the periphery through its action as a ligand for receptor mediated uptake of lipoprotein particles (Lps). Greater understanding of cholesterol metabolism in the human central nervous system may identify novel treatment strategies applicable to acute brain injury. We report findings from the analysis of lipoproteins in the cerebrospinal fluid (CSF) of patients with TBI and non-injured controls, testing the hypothesis that remodeling of CSF lipoproteins reflects the response of the brain to TBI. CSF Lps were isolated from the CSF of controls and patients with severe TBI by size exclusion chromatography, and the lipoprotein fractions analysed for cholesterol, phospholipid, apoAI, and apoE. There was a marked decrease in apoE containing Lps in the TBI CSF compared to controls (p=0.002). After TBI there was no significant decrease in apoAI containing CSF Lps (CSF LpAI), but the apoAI resided on smaller sized particles than in control CSF. There was a population of very small sized Lps in TBI CSF, which were associated with the increased cholesterol (p=0.0001) and phospholipid (p=0.040) seen after TBI. The dramatic loss of apoE containing Lps from the CSF, and the substantial increase in CSF cholesterol, support the concept that apoE and cholesterol metabolism are intimately linked in the context of acute brain injury. Treatment strategies targeting CNS lipid transport, required for neuronal sprouting and synaptogenesis, may be applicable to traumatic brain injury.     

Determination of the glial fibrillary acidic protein in human cerebrospinal fluid and in cyst fluid of brain tumors

Summary The glial fibrillary acidic protein (GFAP) have been quantitatively determinated in over 200 samples of liquid content of brain tumours and in cerebrospinal fluid (CSF) of cases with various tumours of the cerebral nervous system. For establishing the GFAP value, the rocket radioimmunoelectrophoresis was used. The studies were performed in three series of patients. The GFAP value of fluids from 26 cysts of both neoplastic and non-neoplastic type had a wide range of 0,6 g/ml to 40 g/ml. Significant elevation of GFAP was usually recorded in fluid from cysts of anaplastic tumour with astroglial differentiation. In this series of 24 cases with various brain tumours, the GFAP value of the CSF ranged from 0,2 g/ml to 50 g/ml. In gliomas, as in astrocytoma and glioblastoma, these values were on a higher level, of over 4 g/ml. In other tumours and in cerebral lesions of other aetiology, the GFAP values were lower, below 3 g/ml and 0,3 g/ml respectively.In another series of 32 patients with brain tumour treated surgically, a significant increase of GFAP (to 30 g/ml) was noted in the CSF during the first week after operation, and that was always associated with an increase of the total protein of the CSF. During the second and third week after operation, when the total protein of the CSF was reduced to a normal level, the values of GFAP were still elevated, first of all in those cases of astrocytoma and glioblastoma which were not radically excised. These findings suggest that investigation of GFAP in the CSF of patients with brain tumour may be helpfull in diagnosis and prognosis.Presented at the XV Congress of the Polish Society of Neurosurgeons Szczecin/Poland, September 27–29, 1985.     

Concentrations of albendazole in serum,cerebrospinal fluid and hydatidous brain cyst

A young girl with cerebral echinococcosis was treated with albendazole (13 mg/kg/d, p.o.). The concentrations of albendazole sulphoxide were determined in serum, cerebrospinal fluid and hydatidous cyst over a month. The mean ratios of concentration were: CSF/serum=50%, cyst/serum=40%, cyst/CSF=80%.     

Pseudocholinesterase activity in human cerebrospinal fluid

Pseudocholinesterase (PCHE) activity and dibucaine numbers (DN) in the cerebrospinal fluid (CSF) and plasma of 10 ASA physical status 1 and 2 patients were measured using a kinetic method. CSF had a mean PCHE activity of 0.018 +/- 0.013 unit/ml with a DN of 59 +/- 4. Whereas, PCHE activity and DN in the plasma were 0.960 +/- 0.12 units/ml and 84 +/- 3, respectively. We also measured PCHE activity and DN in the CSF and plasma of 4 patients in whom there was a recent history of intraventricular bleeding. These patients had a CSF PCHE activity of 0.340 +/- 0.07 units/ml (DN = 78 +/- 3) and a plasma PCHE activity of 0.950 +/- 0.10 units/ml (DN = 82 +/- 2). Our data show that there is a low activity of PCHE in CSF, 1/20-1/100th that of plasma. Our data also show that PCHE activity increased to 1/4 to 1/2 that of plasma in CSF of patients with bleeding into CSF.     

Proteome study of human cerebrospinal fluid following traumatic brain injury indicates fibrin(ogen) degradation products as trauma-associated markers

Traumatic brain injury (TBI), like other central nervous system pathologies, causes changes in the composition of cerebrospinal fluid (CSF). Consequently analysis of the CSF components is important to better understand the pathological processes involved in such diseases. The aim of this work was to identify specific markers of severe TBI. Proteomic analysis including two-dimensional gel electrophoresis combined with mass spectrometry analysis was used to compare the CSF protein profile of severe TBI patients and controls. Proteins (alpha 1 antitrypsin, haptoglobin 1 alpha1, alpha2, and beta) belonging to the acute phase response showed an increased expression in severe TBI patients. Two other proteins, identified as proteolytic degradation products of the carboxyl-terminal portion of the fibrinogen beta, were present only in TBI patients. The presence of these markers could correlate with a post-traumatic local increase in fibrinolysis as well as to an inflammatory event following CNS tissue injury.     

Tissue cultures from cerebrospinal fluid specimens in the study of human brain tumors.

The authors report a study in which 109 cerebrospinal fluid (CSF) specimens from patients with varying neurological disorders were incubated in tissue culture medium for 1, 3, and sometimes 7 days. Strict criteria for malignancy were applied to cells found at these intervals. In 35 patients with verified central nervous system neoplasms, eight cases had malignant cells and 11 others had "doubtful" cells by tissue-culture analysis. Thirty-three of these cases were also examined with standard millipore cytological techniques: six had malignant cells and four had "doubtful" cells. Of 50 cases with inflammatory or other non-neoplastic conditions, cells were cultured in 13. None was considered malignant by our criteria. Tissue culture of CSF has several potential benefits. Even with stringent criteria, it is possible to demonstrate the presence of unequivocally malignant cells in CSF by tissue culture. The systemic application of such criteria may eventually increase the positive identification of malignancies. Further, since these cells are growing, the degree of malignancy may be more accurately determined by a study of growth in culture. Such a study could not be done by conventional methods. Finally, tissue culture can help to guide therapy in certain instances in which a surgical biopsy cannot be obtained.     

Penetration of cefazolin,ceftriaxone, cefoperazone,and ceftazidime into human gallbladder tissue and bile

Forty patients underwent elective cholecystectomy following administration of a single intravenous dose of cefazolin, ceftriaxone, cefoperazone, or ceftazidime. Mean gallbladder bile concentrations of cefoperazone (398.8 g/ml and ceftriaxone (153.4 g/ml) were significantly higher than those of cefazolin (12.3 g/ml) and ceftazidime (3.08 g/ml) (p<0.008). Mean gallbladder tissue levels of cefazolin (30.1 g/g), ceftriaxone (50.5 g/g), and cefoperazone (91.0 g/g) exceeded that of ceftazidime (7.25 g/g) (p<0.001). When adjusted for known in vitro activity against biliary pathogens, these data suggest that cefoperazone and ceftriaxone are superior to ceftazidime and cefazolin for prophylaxis in elective biliary surgery.

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Resumen Las nuevas cefalosporinas de tercera generación poseen actividad contra una variedad de bacterias, incluso la mayoría de los patógenos biliares comunes. Hemos realizado un estudio prospectivo sobre el grado de penetración de la cefazolina, la ceftriaxona, la cefoperazona, y la ceftazidima en el tejido y la bilis de la vesícula biliar en pacientes sometidos a colecistectomía electiva.Cuarenta pacientes recibieron una dosis única de la cefalosporina dentro de la hora anterior a la colecistectomía. Las concentraciones medias en la bilis de la vesícula biliar fueron significativamente mayores para la cefoperazona (398.8g/ml) y la ceftriaxona (153.4g/ml) que para la cefazolina (12.3g/ml) y la ceftazidima (3.08g/ml) (p<0.008). Los niveles medios en el tejido de la vesícula biliar fueron superiores para la cefalozina (30.1g/g), la ceftriaxona (50.5g/g), y la cefoperazona (91.0g/g que para la ceftazidima (7.25g/g) (p<0.001). Al ajustar estos datos contra valores conocidos de actividad in vitro contra patógenos biliares, aparece que la cefoperazona y la ceftriaxona son superiores a la ceftazidima y la cefazolina en cuanto a profilaxis en cirugía biliar electiva.

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Résumé Quarante patients ont été cholécystectomisés après administration intraveineuse d'une dose unique de céfazoline, de ceftriaxone, de céfapérazone ou de ceftazidine. La concentration moyenne de la bile vésiculaire en céfopérazone (398.8g/ml) et en ceftriaxone (153.4g/ml) était significativement plus élevée que la concentration en céfazoline (12.3g/ml) et en ceftazidine (3.08g/ml) (p<0.008). Les concentrations tissulaires vésiculaires moyennes de céfazoline (30.1g/g), de ceftriaxone (50.5g/g), et de céfopérazone (91.0g/g) étaient plus importantes que la concentration de ceftazidine (7.25g/g) (p<0.001). Lorsque ces antibiotiques sont sensibles in vitro contre des germes pathogènes, nos résultats suggèrent que le céfopérazone et la ceftriaxone sont meilleurs que la ceftazidine et la céfazoline dans la prophylaxie antibiotique de la chirurgie biliaire élective.

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Presented at the Société Internationale de Chirurgie in Sydney, Australia, September, 1987.     

Concentration of antibiotics in renal interstitial fluid: An experimental model

In a new canine experimental model the time concentration relationship of cephalothin in serum, urine, soft tissue interstitial fluid (STIF) and renal interstitial fluid (RIF) were compared simultaneously. Antibiotic concentration in RIF was less than urinary levels but exceeded the serum concentration. Urinary antibiotic concentration does not necessarily reflect concentration in the renal interstitium. This model helps to understand the basic pharmacokinetics of antibiotics in the renal interstitium where pyelonephritis occurs.     

Collagen sponge repair of small cerebrospinal fluid leaks obviates tissue grafts and cerebrospinal fluid diversion after pituitary surgery

OBJECTIVE: Repair of a cerebrospinal fluid (CSF) leak created at the time of transsphenoidal surgery typically involves placement of a fat, fascial, or muscle graft and sellar floor reconstruction. In this report, a simplified repair for small, "weeping" CSF leaks using collagen sponge is described. METHODS: All patients underwent an endonasal transsphenoidal procedure using the operating microscope. At the completion of tumor removal, if a small CSF leak was noted but no obvious large arachnoidal defect was present, a piece of collagen sponge was fashioned to cover the exposed diaphragma sellae. Titanium mesh was then wedged into the intrasellar, extradural space and a larger piece of collagen was placed over the reconstructed sellar floor. Nasal packing was removed within 24 hours. RESULTS: During an 18-month period, 62 consecutive transsphenoidal procedures were performed for tumor removal. Of 20 patients with a small CSF leak (18 pituitary adenomas, 1 Rathke's cleft cyst, and 1 chordoma), all had successful repair with collagen sponge. At follow-up examinations at 1 to 18 months, no patient had required a lumbar drain or had developed meningitis. One other patient had a large intraoperative arachnoidal defect that was unsuccessfully repaired with the collagen sponge technique; in this patient, a second operation was required with a fat graft, sellar floor reconstruction, and lumbar drainage. CONCLUSION: A simplified repair of small CSF leaks after transsphenoidal surgery using a two-layered collagen sponge technique with sellar floor reinforcement is thought to be safe and effective and obviates the need for tissue grafts, fibrin glue, or lumbar drain placement.     

Concentration of rocuronium in cerebrospinal fluid of patients undergoing cerebral aneurysm clipping

Background. This study assessed the concentration of rocuroniumin the cerebrospinal fluid (CSF) of patients undergoing cerebralaneurysm clipping, and investigated whether the mode of administration(single bolus vs continuous infusion) influenced the CSF concentration. Methods. Twenty patients with subarachnoid haemorrhage wererandomly allocated to receive a bolus dose (bolus group), ora bolus followed by a continuous infusion of rocuronium (infusiongroup) (n=10 for each group). Arterial blood and ventricularCSF were sampled 2 h after the rocuronium bolus. Samples wereanalysed by liquid chromatography electrospray ionization-tandemmass spectrometry. Results. Rocuronium could be detected in all the CSF samples.The mean (range) CSF concentration was 2.2 (0.9–4.6) ngml^–1 in the bolus group and 12.4 (2.4–34.6) ng ml^–1in the infusion group; P<0.01. Conclusions. This study demonstrated that rocuronium, normallynot considered to cross the blood–brain barrier, is regularlyfound in the CSF of patients undergoing cerebral clipping; continuousinfusion of the drug led to higher plasma and CSF concentrationsthan after a single bolus dose. Br J Anaesth 2004; 92: 419–21     

Treatment of cerebrospinal fluid and syringosubarachnoid shunt infection with systemic and intrathecal antibiotics

We present a case of a patient with two preexisting Silastic syringosubarachnoid shunt catheters who developed Enterobacter meningitis. The infection was treated successfully with systemic and intrathecal antibiotics without removal of the catheters. With careful sequential clinical and laboratory monitoring, even this type of cerebrospinal fluid shunt infection can be eradicated without catheter removal and replacement.