Pancreatic necrosis infection due to Lactobacillus paracasei in an immunocompetent patient.

An immunocompetent patient recovering from gallstone-induced pancreatitis had to be readmitted due to abdominal pain, fever, and rapid deterioration. Computed tomography guided needle aspiration established the diagnosis of pancreatic necrosis infection; microbiological investigations revealed monoinfection with Lactobacillus paracasei subspecies tolerans. To our knowledge, this is the first description of a pancreatic necrosis infection due to L. paracasei in an immunocompetent patient without any known risk factors for Lactobacillus infections.

Primary cutaneous nocardiosis in an immune-competent patient.

We present a patient who was hospitalized due to a purulent skin lesion with a surrounding erythematous area in the region of the right paranasal crease accompanied by a swelling of the right eyelid. Initially the diagnosis of a carbuncle caused by an infection with Staphylococcus aureus was supposed. A surgical debridement was performed and an antibiotic therapy was started. Only special microbial investigations requested by the clinician led to the diagnosis of a cutaneous infection with Nocardia brasiliensis. The presented case is remarkable because the nocardia infection was in an immune-competent patient and the patient showed a primary cutaneous nocardiosis without dissemination.

Bilateral contemporaneous posteroventral pallidotomy for the treatment of Parkinson's disease: neuropsychological and neurological side effects. Report of four cases and review of the literature.

The authors report the underestimated cognitive, mood, and behavioral complications in patients who have undergone bilateral contemporaneous pallidotomy, as seen in their early experience with functional neurosurgery for Parkinson's disease (PD) that is accompanied by severe motor fluctuations before pallidal stimulation. Four patients, not suffering from dementia, with advanced (Hoehn and Yahr Stages III-IV), medically untreatable PD featuring severe "on-off" fluctuations underwent bilateral contemporaneous posteroventral pallidotomy (PVP). All patients were evaluated according to the Core Assessment Program for Intracerebral Transplantations (CAPIT) protocol without positron emission tomography scans but with additional neuropsychological cognitive, mood, and behavior testing. For the first 3 to 6 months postoperatively, all patients showed a mean improvement of motor scores on the Unified Parkinson's Disease Rating Scale (UPDRS), in the best "on" (21%) and worst "off" (40%) UPDRS III motor subscale, a mean 30% improvement in the UPDRS II activities of daily living (ADL) subscore, and 60% on the UPDRS IV complications of treatment subscale. Dyskinesia disappeared almost completely, and the mean daily duration of the off time was reduced by an average of 60%. Despite these good results in the CAPIT scores, one patient experienced a partially regressive corticobulbar syndrome with dysphagia, dysarthria, and increased drooling. No emotional lability was found in this patient, but he did demonstrate severe bilateral postoperative pretarsal blepharospasm (apraxia of eyelid opening), which interfered with walking and which required treatment with high-dose subcutaneous injections of botulinum toxin. No patient showed visual field defects or hemiparesis, but postoperative depression, changes in personality, behavior, and executive functions were seen in two individuals. Postoperative abulia was reported by the family of one patient, who lost his preoperative aggressiveness and drive in terms of ADL, speech, business, family life, and hobbies, and became more sleepy and fatigued. One patient reported postoperative mental automatisms, such as compulsive mental counting, and circular thoughts and reasoning during off phases; postoperative depression was found in two patients. However, none of the patients demonstrated these symptoms during intraoperative microelectrode stimulation. These findings are compatible with previous reports on bilateral pallidal lesions. A progressive lowering of UPDRS subscores was seen after 12 months, consistent with the progression of the disease. Bilateral simultaneous pallidotomy may be followed by emotional, behavioral, and cognitive deficits such as depression, obsessive-compulsive disorders, and loss of psychic autoactivation-abulia, as well as disabling corticobulbar dysfunction and apraxia of eyelid opening, in addition to previously described motor and visual field deficits, which make this surgery undesirable even though significant improvement in motor deficits can be achieved.

Postoperative treatment of glioblastoma with BNCT at the petten irradiation facility (EORTC protocol 11,961).

The boron neutron capture therapy is based on the reaction occurring between the isotope 10B and thermal neutrons. A low energy neutron is captured by the nucleus and it disintegrates into two densely ionising particles, Li nucleus and He nucleus (alpha particle), with high biological effectiveness. On the basis of comprehensive preclinical investigations in the frame of the European Collaboration with Na2B12H11SH (BSH), as boron delivery agent, the first European phase I, clinical trial was designed at the only available epithermal beam in Europe, at the High Flux Reactor, Petten, in the Netherlands. The goal of this study is to establish the safe BNCT dose for cranial tumors under defined conditions. BNCT is applied as postoperative radiotherapy in 4 fractions, after removal of the tumor for a group of patients suffering from glioblastoma, who would have no benefit from conventional treatment, but have sufficient life expectancy to detect late radiation morbidity due to BNCT. The starting dose is set at 80% of the dose where neurological effects occurred in preclinical large animal experiments following a single fraction. The radiation dose will be escalated, by constant boron concentration in blood, in 4 steps for cohorts of ten patients, after an observation period of at least 6 months after the end of BNCT of the last patient of a cohort. The adverse events on healthy tissues due to BSH and due to the radiotherapy will be analysed in order to establish the maximal tolerated dose and dose limiting toxicity. Besides of the primary aim of this study the survival will be recorded. The first patient was treated in October 1997, and further four patients have been irradiated to-date. The protocol design proved to be well applicable, establishing the basis for scientific evaluation, for performance of safe patient treatment in a very complex situation and for opening the possibility to perform further clinical research work on BNCT.

Efficiency and safety of bilateral contemporaneous pallidal stimulation (deep brain stimulation) in levodopa-responsive patients with Parkinson's disease with severe motor fluctuations: a 2-year follow-up review.

OBJECT: The aim of this study was to evaluate the long-term safety and efficacy of bilateral contemporaneous deep brain stimulation (DBS) in patients who have levodopa-responsive parkinsonism with untreatable motor fluctuations. Bilateral pallidotomy carries a high risk of corticobulbar and cognitive dysfunction. Deep brain stimulation offers new alternatives with major advantages such as reversibility of effects, minimal permanent lesions, and adaptability to individual needs, changes in medication, side effects, and evolution of the disease. METHODS: Patients in whom levodopa-responsive parkinsonism with untreatable severe motor fluctuations has been clinically diagnosed underwent bilateral pallidal magnetic resonance image-guided electrode implantation while receiving a local anesthetic. Pre- and postoperative evaluations at 3-month intervals included Unified Parkinson's Disease Rating Scale (UPDRS) scoring, Hoehn and Yahr staging, 24-hour self-assessments, and neuropsychological examinations. Six patients with a mean age of 55 years (mean 42-67 years), a mean duration of disease of 15.5 years (range 12-21 years), a mean "on/off' Hoehn and Yahr stage score of 3/4.2 (range 3-5), and a mean "off' time of 40% (range 20-50%) underwent bilateral contemporaneous pallidal DBS, with a minimum follow-up period lasting 24 months (range 24-30 months). The mean dose of levodopa in these patients could not be changed significantly after the procedure and pergolide was added after 12 months in five patients because of recurring fluctuations despite adjustments in stimulation parameters. All but two patients had no fluctuations until 9 months. Two of the patients reported barely perceptible fluctuations at 12 months and two at 15 months; however, two patients remain without fluctuations at 2 years. The mean improvements in the UPDRS motor score in the off time and the activities of daily living (ADL) score were more than 50%; the mean off time decreased from 40 to 10%, and the mean dyskinesia and complication of treatment scores were reduced to one-third until pergolide was introduced at 12 months. No significant improvement in "on" scores was observed. A slight worsening after 1 year was observed and three patients developed levodopa- and stimulation-resistant gait ignition failure and minimal fluctuations at 1 year. Side effects, which were controlled by modulation of stimulation, included dysarthria, dystonia, and confusion. CONCLUSIONS: Bilateral pallidal DBS is safe and efficient in patients who have levodopa-responsive parkinsonism with severe fluctuations. Major improvements in motor score, ADL score, and off time persisted beyond 2 years after the operation, but signs of decreased efficacy started to be seen after 12 months.

Robotic three-dimensional positioning of a stimulation electrode in the brain.

Functional stereotactic cerebral operations are currently performed with straight electrodes. After physiological exploration, correction of the initial target is frequently necessary and requires multiple penetrations of the brain. This paper describes a robotic three-dimensional electrode probe that can reach targets located within a cylindrical volume from a single approach trajectory. It has been mounted on the neurosurgical robot Minerva, and includes a string electrode, which can protrude out of the side window of a straight cannula and offers a high intrinsic accuracy of 0.25 mm. A simple man-machine interface allows the surgeon to select reference and target points and to activate the probe from a graphics workstation. This paper also analyzes the accuracy of the probe as well as of the whole operating system, food gelatin being used to simulate brain matter.

Exogenous inositol and genes responsible for inositol transport are required for mating and sporulation in Shizosaccharomyces pombe.

Fission yeast, Schizosaccharomyces pombe, is a natural inositol auxotroph. We show here that the amount of exogenous inositol added to the medium is critical for the control of its life cycle. Above growth-limiting concentrations inositol stimulates mating and sporulation in minimal medium. The effect of inositol is also observed on yeast-extract-medium plates. We selected a mutant, IM49, which mates and sporulates only poorly and show that it is defective in inositol transport. Its defect is in a gene (itr2) coding for a putative 12 membrane-spanning protein. The polypeptide contains the two sugar-transport motifs typical for hexose transporters and shows good homology to the two Saccharomyces cerevisiae inositol transporters. The itr2 gene is essential for cell growth and its mRNA level is repressed by glucose. Mutant IM49 is also complemented by a multicopy suppressor gene (itr1) which codes for a putative hexose transporter with unknown substrate specifity.

Dynamic MRI of cerebrospinal fluid flow in endoscopic percutaneous ventriculostomy.

Endoscopic percutaneous ventriculostomy (EPV) is a new technique to restore the flow of the cerebrospinal fluid (CSF) to the basal cistern in patients with non-communicating hydrocephalus (NCH). Cardiac gated MRI techniques have been applied to demonstrate normal and abnormal CSF flow in humans. The aim of this study was to evaluate the ability of a new multislice spin echo dynamic MRI technique and amplitude and phase reconstruction to demonstrate the impairment of CSF flow through the aqueduct preoperatively and to assess the patency of the ventriculostomy after surgery. Thirteen patients with NCH were studied with dynamic MRI before and after EPV using multiple sagittal multislice gated SE acquisitions to demonstrate the CSF flow. Nine patients were clinically improved by EPS, two remained unchanged and two deteriorated. The permeability of the ventriculostomy was confirmed in all patients. We think that MRI flow studies are useful to demonstrate the site of impairment of CSF flow and its aetiology preoperatively, and to assess the permeability of the ventriculostomy after surgery in a non invasive way.

Recurrent nocardial brain abscesses treated by repeated stereotactic aspirations.

A case of a 61-year-old diabetic patient who had a new onset simple partial seizure is presented. Past medical history was remarkable for pulmonary sarcoidosis for which the patient was on chronic steroid therapy. Computed tomography scan demonstrated a postcentral abscess which was aspirated under stereotactic guidance. Nocardia asteroides was identified. The patient was placed on intravenous trimethoprim and sulfamethoxazole. He required two further stereotactic aspirations of recrudescences until symptoms resolved. The use of repeated stereotactic aspiration in place of an open surgical procedure is advocated for the treatment of nocardial abscesses.

Pharmacokinetics of Na2B12H11SH (BSH) in patients with malignant brain tumours as prerequisite for a phase I clinical trial of boron neutron capture.

The disposition of Na2B12H11SH (BSH) in patients with malignant glioma has been investigated, in preparation for a Phase I clinical trial of boron neutron capture therapy. BSH was found to possess a linear disposition over the dosage interval investigated (up to 75 mg/kg). A bi-phasic blood pharmacokinetics was observed. Tumour-to-blood ratios showed variations between patients between 0.08 and 5.1. The data allow the definition of amount of BSH and timing of infusion for a Phase I clinical trial protocol.

Appropriateness of indications for surgery of lumbar disc hernia and spinal stenosis.

STUDY DESIGN: This prospective study examines the appropriateness of indications for surgery of herniated intervertebral disc and spinal stenosis in patients undergoing surgery in a university hospital setting. OBJECTIVE: To evaluate the appropriateness of surgery using explicit criteria developed by an expert panel in the United States. SUMMARY OF BACKGROUND DATA: The use of surgery for herniated intervertebral disc and spinal stenosis varies widely within and among countries. It has been postulated that the main reason for treatment failure is poor selection of candidates for the procedure. METHODS: The authors prospectively evaluated appropriateness of surgical indications for herniated lumbar intervertebral disc or spinal stenosis in 328 consecutive patients undergoing the operation in two university neurosurgery departments. Outcome was measured 1 year after surgery by a standardized interview. RESULTS: Indications for surgery were considered to be appropriate or equivocal in 202 (62%) patients and inappropriate in 126 (38%). Among the 126 inappropriate procedures, 66 were so rated because of insufficient activity restriction before the procedure. One year after surgery, 74% of the patients perceived the results of the operation as good or very good. CONCLUSIONS: Appropriateness as measured by the criteria established by the American panel identified a large percentage of day-to-day practice in the two surgical units as inappropriate. However, use of criteria that include new findings about lack of efficacy of bed rest probably would lower this percentage. Criteria of appropriateness of medical and surgical procedures, developed through the panel process, need to be updated regularly.

Transfer of information between angiographic films and CT images: a technique to control the drawing of target volumes.

BACKGROUND AND PURPOSE: This work was undertaken to improve the definition of target volumes for radiosurgery using the angiographic and CT data. MATERIALS AND METHODS: The basis of this new method is to combine both imaging modalities and to compare them in each representation, i.e. to plot the volume obtained by angiography on CT images and also the contours defined by the CT on angiographic films. To obtain the angiographic volume, the radiographs are taken at several incidence angles. The X-ray sources position and the position of the films are determined using rectangular markers, then the intersection of all the loci of the target volume are calculated. RESULTS: Verifications with a phantom show the accuracy of the procedure and the benefit obtained by increasing the number of angles of incidence in the angiographic imaging. The centre of gravity of the experimental target could be localized to an accuracy of better than 0.4 mm. The method was used in 11 clinical cases with excellent clinical results. CONCLUSIONS: The method can be easily applied and improves the delineation of target volumes in radiosurgery. CT data counterbalances the relative weakness of angiography concerning the three-dimensional geometry. Angiography adds useful information on the blood flow that is not shown in CT. Almost all the presented clinical cases benefit from the technique described here.

[Stereotaxic radiotherapy of brain metastases: experiences in Lausanne]. / Radiothérapie stéréotaxique des métastases cérébrales: expérience lausannoise.

We report the first series of patients treated by stereotactic radiation therapy for brain metastases in Switzerland. From August 1993 to December 1994, 19 patients were treated using a linear accelerator adapted for stereotactic treatment set-up. Most of the patients received combined treatment including external irradiation. The crude overall control rate for brain metastases was 79%. Median survival was 12.2 months. Overall survival at one year was 50 +/- 12%. These data compare reasonably well with the reported median survival of 3-6 months using external cranial irradiation alone. There was no "late toxicity". The data thus indicate that stereotactic radiation therapy combined with external whole brain irradiation appears to increase life expectancy and quality of life in a selected cohort of patients.

Amiloride toxicity in the fission yeast Schizosaccharomyces pombe is released by thiamine and mutations in the thiamine-repressible gene car1.

Amiloride (Am) inhibits growth in the fission yeast Schizosaccharomyces pombe. We show that the toxic effect of this drug is relieved by low concentrations of thiamine (Th) and that the pyrimidine moiety of the Th molecule is responsible for growth inhibition release. A putative membrane protein encoded by the car1 gene is the target for Am action. It is responsible for Am sensitivity and is involved in the utilization of Th and its biosynthetic precursor, 4-amino-5-hydroxymethyl-2-methylpyrimidine. Its expression is repressed by Th and is under the genetic control of the genes, thi1, tnr1, tnr2 and tnr3, which have previously been shown to be responsible for the transcriptional control of genes involved in the biosynthesis and dephosphorylation of Th.

Schizosaccharomyces pombe thiamine pyrophosphokinase is encoded by gene tnr3 and is a regulator of thiamine metabolism, phosphate metabolism, mating, and growth.

The Schizosaccharomyces pombe gene tnr3 has been genetically defined as a negative regulator of genes involved in thiamine metabolism (Schweingruber, A. M., Frankhauser, H., Dlugonski, J., Steinmann-Loss, C., and Schweingruber, M. E. (1992) Genetics 130, 445-449). We have isolated and sequenced the gene and show that it codes for a putative protein of 569 amino acids which exhibits, in its carboxyl-terminal half, good homology to Saccharomyces cerevisiae thiamine pyrophosphokinase (TPK). tnr3 mutants have reduced levels of intracellular thiamine diphosphate, show impaired TPK activity, which is enhanced by introducing the tnr3 wild type gene on a plasmid, and can be complemented by the S. cerevisiae TPK-encoding gene TH180. These data strongly suggest that tnr3 encodes S. pombe TPK. We present evidence that TPK also acts as a negative regulator for gene pho1, which is derepressed when cells are starved for phosphate and show that in contrast to wild type cells, tnr3 mutants mate constitutively in response to thiamine, indicating that TPK is also involved in regulation of mating. Disruption of the tnr3 gene is lethal, and a tnr3 mutant expressing only residual TPK activity grows slowly and shows aberrant morphology.

[Postoperative work incapacity, type of work resumed and residual pain following surgical treatment of lumbar herniated disk: prognostic factors]. / Incapacité de travail postopératoire, type de travail repris et douleurs résiduelles après traitement chirurigical de hernie discale lombaire: facteurs pronostiques.

The outcome in 258 patients 3 to 4 years after operation for lumbar disc herniation was studied. The median duration of postoperative work incapacity was 3.5 months; 202 (78%) patients resumed full time work in their previous job; 16 (6%) did not resume work due to lumbar pathology; 193 (75%) were free of pain. Predictive factors for a good professional outcome were a preoperative work incapacity inferior to 4 weeks and, for men only, operation at the L5-S1 level and the absence of daily lifting of heavy weights.

Growth of a mutant defective in a putative phosphoinositide-specific phospholipase C of Schizosaccharomyces pombe is restored by low concentrations of phosphate and inositol.

A mutant (plc1-1) of Schizosaccharomyces pombe unable to grow on a minimal medium containing high amounts of phosphate was selected. On yeast-extract agar its growth is temperature sensitive. Tests in liquid synthetic medium show that growth of the mutant is partially restored by lowering the phosphate and inositol concentrations in the growth medium. The growth defect is fully suppressed by a plasmid encoding a putative protein having the structural features of phosphoinositide-specific phospholipases C (PI-PLC). This protein, of 899 amino-acids, contains the characteristic X and Y domains found in all PI-PLCs of higher and lower eucaryotes and reveals, in addition, an EF-hand motif (putative Ca(2+)-binding site). Like the corresponding enzyme from Saccharomyces cerevisiae, the S. pombe PI-PLC is most similar to the delta form of PI-PLC isoenzymes. The cloned gene integrates at the plc1 site indicating that plc1 codes for a putative PI-PLC. Plc1 physically maps on the left arm of chromosome II between rad11 and mei3.