Identifying functional cortical plasticity after spinal tumour resection using navigated transcranial magnetic stimulation.

Our aim was to investigate the effectiveness of navigated transcranial magnetic stimulation (nTMS) brain mapping to characterise preoperative motor impairment caused by an intradural extramedullary (IDEM) tumour and postoperative cortical functional reorganisation. Preoperative and 1-year follow-up clinical, radiological and nTMS data from a case of thoracic spinal meningioma that underwent surgical resection of the lesion were collected and compared. A 67-year-old patient presented with severe progressive thoracic myelopathy (hypertonic paraparesis, clonus, insensate urinary retention) secondary to an IDEM tumour. Initial nTMS assessment showed bilateral upper limb representation with no positive responses for both lower limbs. He underwent successful surgical resection for his IDEM (meningioma WHO grade 1). At 1-year follow-up, the patient's gait was improved and his bladder function normalised. nTMS documented positive responses for both upper and lower limbs and a decrease in the area (right side: 1.01 vs 0.39cm2; left side: 1.92 vs 0.81cm2) and volume (right side: 344.2 vs 42.4uVcm2; left side: 467.1 vs 119uVcm2) of cortical activation for both upper limbs, suggesting a functional reorganisation of the motor areas after tumour resection. nTMS motor mapping and derived metrics can characterise preoperative motor deficit and cortical plasticity during follow-up after IDEM resection.

Excited-state quantum phase transitions in the anharmonic Lipkin-Meshkov-Glick model: Dynamical aspects.

The standard Lipkin-Meshkov-Glick (LMG) model undergoes a second-order ground-state quantum phase transition (QPT) and an excited-state quantum phase transition (ESQPT). The inclusion of an anharmonic term in the LMG Hamiltonian gives rise to a second ESQPT that alters the static properties of the model [Gamito et al., Phys. Rev. E 106, 044125 (2022)2470-004510.1103/PhysRevE.106.044125]. In the present work, the dynamical implications associated to this new ESQPT are analyzed. For that purpose, a quantum quench protocol is defined on the system Hamiltonian that takes an initial state, usually the ground state, into a complex excited state that evolves on time. The impact of the new ESQPT on the time evolution of the survival probability and the local density of states after the quantum quench, as well as on the Loschmidt echoes and the microcanonical out-of-time-order correlator (OTOC) are discussed. The anharmonity-induced ESQPT, despite having a different physical origin, has dynamical consequences similar to those observed in the ESQPT already present in the standard LMG model.

Excited-state quantum phase transitions in the anharmonic Lipkin-Meshkov-Glick model: Static aspects.

The basic Lipkin-Meshkov-Glick model displays a second-order ground-state quantum phase transition and an excited-state quantum phase transition (ESQPT). The inclusion of an anharmonic term in the Hamiltonian implies a second ESQPT of a different nature. We characterize this ESQPT using the mean field limit of the model. The alternative ESQPT, associated with the changes in the boundary of the finite Hilbert space of the system, can be properly described using the order parameter of the ground-state quantum phase transition, the energy gap between adjacent states, the participation ratio, and the quantum fidelity susceptibility.

A haplotype of cyclooxygenase-2 gene is associated with idiopathic pulmonary fibrosis.

BACKGROUND: Cyclooxygenase-2, a key regulatory enzyme in the synthesis of the antifibrotic agent prostaglandin E2, is downregulated in lung tissue from patients with idiopathic pulmonary fibrosis. OBJECTIVE: To investigate the association between COX2.3050 (G --> C), COX2.8473 (C --> T) and COX2.926 (G --> C) single nucleotide polymorphisms (SNP) and the susceptibility to idiopathic pulmonary fibrosis and the progression of the disease. DESIGN: Genetic polymorphisms were analyzed in 121 out of 225 available control subjects and in all of 174 patients with idiopathic pulmonary fibrosis by real time polymerase chain reaction. Logistic regression analysis of covariance and chi-squares test were used for statistical analysis. RESULTS: While analysis of disease development did not find any significant association with single SNP genotype, a haplotype analysis revealed a strong association between the disease development and one haplotype [GC] at loci COX2.3050 and COX2.8473, and suggested a recessive genetic effect of this haplotype. Further analysis concluded that subjects having two copies of [GC] haplotype, or equivalently (GG/CC) genotype at the two SNPs, had an increased risk after adjusting for age and sex. Due to the interaction, this elevated risk increased slowly with age, and the estimated odds ratio (OR) decreased with age from OR = 1.4 at age 30 to OR = 1 at age 74 and OR = 0.96 at age SO. The OR was significantly greater than 1 up to age 66, and not significant for age older than 66. Therefore, the recessive effect of [GC] haplotype increased the risk of IPF of subjects younger than 66 years, but its effect diminished for seniors older than 66. One hundred and forty-nine patients with idiopathic pulmonary fibrosis were followed up for 33.7 +/- 2.1 months. Further analysis of disease progressions, defined by the changes in pulmonary function tests, did not reveal any association with either SNP genotypes or haplotypes. CONCLUSIONS: The carriage of double homozygote (GG/CC) at the SNP loci of COX2.3050 and COX2.8473 polymorphisms may increase the susceptibility to idiopathic pulmonary fibrosis, by approximately 1.4 folds at age 30 and by a smaller fold greater than 1 up to age 66 years, but not the progression of the disease. These findings may help to improve our understanding of idiopathic pulmonary fibrosis pathogenesis and may lead to the development of new therapeutic strategies.

Interaction of cysteine and its derivatives with monolayers of dipalmitoylphosphatidylcholine.

Molecular interactions between l-cysteine (Cys) and its ester derivatives (Cysx); l-cysteine ethyl ester (CE), l-cysteine methyl ester (CM) and N-acetyl l-cysteine (NAC) with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayers were investigated using Langmuir film balance technique. The effect of charge on monolayers made of cysteine and three ester derivatives with DPPC was investigated by working with un-buffered and buffered subphases. Also, the effects of cysteine derivatives interaction with DPPC monolayers were studied measuring the change in the surface tension upon aminoacid injection in the subphase whilst keeping lipid molecular density and lateral packing controlled. Cysteine and its ester derivatives showed interfacial activity reducing the air/water surface tension (πi) by 4 mN m-1. However, ester derivatives were able to insert into preformed DPPC monolayers at much higher surface pressures (Δπ), indicating a preferential interaction of Cysx with DPPC. The results indicate that, although the different derivatives of cysteine presented low surface activity, they were able to favourably interact with DPPC monolayers. Also, compression isotherms experiments in binary mixtures indicate that the more surface active compounds stabilized the gel phase of DPPC. The charge on cysteine and its derivatives did not increase the observed effects.

Severe and recurrent episodes of bronchiolitis obliterans organising pneumonia associated with indolent CD4+ CD8+ T-cell leukaemia.

The present study describes an adult male who has had recurrent episodes of pulmonary infiltrates with severe acute respiratory failure over a period of 10 yrs. Clinical and pathological characteristics revealed bronchiolitis obliterans with organising pneumonia (BOOP) that responded dramatically to prednisone. BOOP is characterised by inflammation of the bronchioles and surrounding tissue in the lungs. It can mimic infectious pneumonia but diagnosis is suspected when there is no response to multiple antibiotic treatment, and blood and sputum cultures are negative for microorganisms. A high proportion of double-positive (DP)-T-cells was detected in peripheral blood and in bronchoalveolar lavage, expressing CD4 and CD8alphabeta heterodimer with memory phenotype. These DP-T-lymphocytes expressed specific homing molecules that could explain their tropism to lung tissue, giving rise to the clinical symptoms. The patient did not present organomegaly, lymphadenopathy, lymphocytosis or other features of malignancy. However, T-cell receptor Vbeta chain analysis indicated clonal rearrangement, and cytogenetic studies displayed chromosomic alterations that were similar to clonal proliferation observed in ataxia-telangiectasia and T-prolymphocytic leukaemia. The findings suggest a smouldering form of lymphoproliferation, the first sign of which was bronchiolitis obliterans organising pneumonia requiring constant corticoid treatment.

Naloxone reverses pattern of obstruction of the distal common bile duct induced by analgesic narcotics in hepatobiliary imaging.

It is widely known that narcotics, such as morphine, cause spasm of the sphincter of Oddi, increasing pressure in the common bile duct. This pharmacologic effect has been applied to hepatobiliary scintigraphy in patients with chronic cholecystitis or cholestasis to reducing the time required for a diagnostic study. However, this feature of narcotics could result in delayed or nonvisualization of the small bowel, simulating a distal common bile duct obstruction, in patients requiring parenteral narcotic analgesics who must undergo hepatobiliary scintigraphy. We report on three patients where administration of intravenous naloxone hydrochloride (Narcan), a narcotic antagonist, was helpful in distinguishing narcotic-induced spasm of the sphincter of Oddi from true obstruction of the common bile duct.

Comparison of methods for identifying early methotrexate-induced hepatotoxicity in patients with rheumatoid arthritis.

Hepatotoxicity may complicate therapy with methotrexate in patients with rheumatoid arthritis. Prevention of cirrhosis may depend upon early identification of liver damage, usually accomplished by serial biopsy. To determine the adequacy of noninvasive methods for identifying hepatotoxicity, 22 sets of data were obtained in patients undergoing therapy with methotrexate for rheumatoid arthritis. Comparisons were made between liver biopsy, hepatocellular enzymes and two noninvasive radioisotopic methods that have been shown to be abnormal in hepatocellular disease: the rate constant of excretion of the 14C-aminopyrine and the time from injection to peak hepatic activity of 99mTc-diisopropylimidodiacetic acid. The hepatocellular enzymes and the time-to-peak-activity of diisopropylimidodiacetic acid were not useful predictors of methotrexate-induced hepatotoxicity. The aminopyrine breath test was abnormal in approximately half the patients with hepatotoxicity but showed poor specificity. Noninvasive methods remain inferior to biopsy for the detection of mild to moderate methotrexate-induced hepatotoxicity in patients with rheumatoid arthritis.

Biotransformation of 4beta-hydroxyeudesmane-1,6-dione by Gliocladium roseum and Exserohilum halodes.

Biotransformation of sesquiterpene 4beta-hydroxyeudesmane-1,6-dione by the filamentous fungi Gliocladium roseum and Exserohilum halodes was achieved. With Exserohilum halodes, only one metabolite was obtained, as a result of the regio- and stereoselective reduction of the keto group at C-1, which is difficult to achieve by chemical means. Five metabolites were produced with Gliocladium roseum, three of which, the 7alpha-hydroxylated, the 7alpha,11- and the 1alpha,8alpha-dihydroxylated derivatives, have not previously been reported. The hydroxylation at C-11 is the main action of this microorganism. These 11-hydroxylated compounds can be chemically transformed into 6beta,12-eudesmanolides.

Synthesis of enantio-manoyl oxides: modifiers of the activity of adenylatecyclase enzyme.

Cyclization of methyl ent-8 alpha-hydroxylabd-13(16),14-dien-18-oate with m-chloroperbenzoic acid gave methyl (13S)-ent-16-hydroxy-8 alpha,13-epoxylabd-14-en-18-oate and its epimer at C-13. Biotransformation of the former (which exhibits antileishmania activity) with Rhizopus nigricans cultures produced the methyl (13S)-ent-11 beta,16-dihydroxy-8 alpha,13-epoxilabd-14-en-18-oate (carbomanoyl, which inhibits the activity of the adenylatecyclase enzyme), methyl (13S)-ent-3 beta,16-dihydroxy-8 alpha,13-epoxilabd-14-en-18-oate, methyl (13S)-ent-3 beta,11 beta,16-trihydroxy-8 alpha,13-epoxilabd-14-en-18-oate and the (14S)-ent-3 beta-hydroxy-14,15-epoxy derivative that cyclized spontaneously to a spiran compound. Biotransformation of methyl (13S)-ent-16-hydroxy-3-oxo-8 alpha,13-epoxilabd-14-en-18-oate with R. nigricans produced ent-11 beta-hydroxylation, reduction of the keto group at C-3 (to give 3S-alcohol) and 14(S),15-epoxidation, which also rearranged to a spiro compound.

Chemical-microbiological synthesis of ent-13-epi-manoyl oxides with biological activities.

The biotransformation of ent-13-epi-3-keto manoyl oxide, which possesses antileishmania activity, with Curvularia lunata produced ent-6 beta-hydroxy, ent-1 alpha-hydroxy, ent-11 beta-hydroxy and delta 1-derivatives, as well as a reduction product a C-3 (S-alcohol) with another hydroxyl group at C-6 (ent-6 beta) or C-11 (ent-11 beta). The ent-6 beta-hydroxy and delta 1-derivatives inhibited growth of the pathogenic protozoa, Leishmania donovani. The biotransformation of ent-12 alpha-acetoxy-3 beta-hydroxy-13-epi-manoyl oxide and ent-3 beta-acetoxy-12 beta-dihydroxy-13-epi-manoyl oxide gave ent-3 eta,12 beta-dihydroxy-13-epi-manoyl oxide and ent-3 beta,6 beta,12 beta-trihydroxy-13-epi-manoyl oxide (trimanoyl). Both products increased the activity of adenylatecyclase.

Sex differences and age-related changes in human serum aminopeptidase A activity.

Given that aminopeptidase A is primarily responsible for cleaving aspartic acid and converting angiotensin II to angiotensin III, the purpose of the present study was to evaluate the activity of aminopeptidase A by determination of glutamate aminopeptidase activity (GluAP) and aspartate aminopeptidase activity (AspAP) (reported respectively as aminopeptidase A and angiotensinase A activities) in human serum during development and ageing, in an apparently healthy population of 139 male and 148 female subjects. To measure GluAP and AspAP we used glutamyl- and aspartyl-2-naphthylamide as substrates. Significant age-related increases were observed in GluAP activity in males and females and in AspAP activity in females. In males, there were no age-related differences in AspAP activity. A significant correlation was observed between age and GluAP activity in the population analysed as a whole or according to sex. No correlation was demonstrated between age and AspAP activity either in the whole population or according to sex. These results may reflect the evolution of the functional status of susceptible circulating substrates during development and ageing.

Repair of facial nerve after removal of cerebellopontine angle tumors: a comparative study.

The results of repair of 18 facial nerves were examined by means of a modified House-Brackmann grading system. Six were repaired by end-to-end anastomosis and 12 by nerve graft. The reliability of the simplified House-Brackmann grading system was also assessed, using the kappa statistic to analyze the agreement between pairs of observers who examined the function of 40 nerves in 37 patients. Facial nerves studied had been either preserved, repaired or grafted, or divided and treated by faciohypoglossal nerve anastomosis. One nerve was not treated. The grading system proved to be somewhat unreliable, with complete agreement between observers in only 25% of cases. Facial nerve repair produced a fair return of function in just under two-thirds of the cases. The ability of an examiner ignorant of the patient's history to assess from the end result how the nerve had been managed was also estimated. Observers showed little ability to decide correctly on the previous treatment of the nerve when the patient showed moderate dysfunction postoperatively. The implications of these findings for grading systems and for management of the facial nerve in acoustic nerve tumor surgery are discussed.

Progressive posttraumatic myelomalacic myelopathy: treatment with untethering and expansive duraplasty.

Patients with progressive posttraumatic myelomalacic myelopathy (PPMM), or tethered cord syndrome, present with symptoms and signs similar to those observed in case of progressive posttraumatic cystic myelopathy, that is, sensorimotor function deterioration, local and/or radicular pain, increased spasticity, increased autonomic dysreflexia, and sphincter dysfunction. The authors investigated surgical outcomes of untethering combined with expansive duraplasty. Forty patients with PPMM who presented with functional deterioration underwent untethering of the spinal cord and nerve roots with an expansive duraplasty. Meticulous dissections of adhesions on the dorsal and lateral aspects of the spinal cord and nerve roots were performed. Intraoperative ultrasonography was used to detect the presence of a confluent cyst and to assess the success of untethering. After surgery, the patients were treated using a protocol that involved frequent turning for 48 hours and subsequently mobilization. Preoperative magnetic resonance (MR) imaging, with and without administration of a contrast agent, was obtained in all patients, except one patient who underwent immediate and delayed computerized tomography (CT) myelography. The mean follow-up period was 3 years (range 20-57 months) for the 36 patients available for follow-up review. Spinal cord tethering was observed in all patients preoperatively. Trauma was the most common cause of this pathology, accounting for 31 of the 40 cases. Preoperative MR imaging did not demonstrate tumor recurrence in the group of five patients who had undergone an initial operation for tumor excision. The interval between the causative event and the operation was less than 5 years in half of the patients (20 of 40), with the longest interval lasting up to 37 years. Motor function deterioration was the most frequent manifestation; it was present in 31 of 40 patients. Improvements in motor function, autonomic dysreflexia, pain, sphincter dysfunction, and sensory function were found during the most recent follow-up examination in 79%, 75%, 62%, 50%, and 43% of the patients, respectively. Two patients experienced retethering of the spinal cord and one underwent a second operation. Surgical untethering and expansive duraplasty, followed by postoperative position rotation to avoid retethering, provide symptomatic relief for patients with PPMM.

Purification and partial characterization of an antibiotic produced by Myxococcus coralloides.

A strain of Myxococcus coralloides producing an antibiotic capable of inhibiting growth of Gram-positive bacteria was isolated. Antibiotic production occurred during vegetative growth but not during myxospore formation. The antibiotic was extracted from the growth medium with chloroform and purified by adsorption on silicic acid and by preparative silica gel thin-layer chromatography. The purified antibiotic showed a resistance to heat, acid, alkali and proteolytic enzymes. Chromatographic and electrophoretic behavior as well as infrared, ultraviolet and mass spectra are presented.

Lanthanum fixation by Myxococcus xanthus: cellular location and extracellular polysaccharide observation.

Myxococcus xanthus is a soil bacterium of the myxobacteria group and is abundant in almost all soils. Its role in soil ecology is considered significant. One noteworthy characteristic of the bacterium is that it produces large quantities of extracellular polymeric substances (EPS). It is also known that its biomass has the capacity to fix heavy metals. Here it is reported that M. xanthus was able to accumulate 0.6 mmol of La per g of wet biomass and/or 0.99 mmol per g of dry biomass. Transmission Electron Microscopy (TEM) observation of M. xanthus cells treated with La showed that a substantial amount of this cation was fixed in the EPS and in the cell wall. Smaller amounts were also observed in the cytoplasm. Fixed La appeared as phosphate in all cellular locations. The results given here also show that the use of La enables TEM observation of the M. xanthus EPS as a dense fibrillar net surrounding the cells. This technique is relatively easy and prevents EPS collapse, which occurs frequently during the fixation and dehydration procedures commonly used in preparations for TEM observations. Since antibodies are no longer required, the La stain can be carried out without delaying bacterial cell cultivation or isolation. In addition, the presence of La in cell cytoplasm without cell degeneration suggests that this microorganism could be used as a model in the study of bacteria-lanthanide interactions.

Plasma lipid composition in an elderly population: correlation with dietary fat.

The effects of dietary fat on plasma lipid composition were studied in a population of 51 elderly subjects (19 men, 32 women) who lived in a retirement home in the province of Jaén (southern Spain). Dietary intake of fat was elevated (106 and 115 g/day in men and women respectively), and fatty acid intake consisted of 40% oleic acid, 17% linoleic acid and 0.7% linolenic acid. Cholesterol intake was 506 and 518 mg/day in men and women respectively, whereas the plasma level of cholesterol was approximately 250 mg/dl in both sexes. In men and women, HDL-cholesterol levels were 71.5 and 62.2 mg/dl, and LDL-cholesterol levels were 153.5 and 152.3 mg/dl. The most abundant circulating fatty acid was palmitic acid (25%) in both sexes, followed by oleic (23%) and linoleic acid (15-16%), whereas linolenic acid represented only 0.3% of the plasma fatty acids. To determine whether plasma levels of fatty acids served as reliable biological markers of dietary fatty acid intake, we compared the two sets of values, and found that higher intake was reflected in higher plasma levels, although a significant linear correlation (p < 0.05) was found only for linolenic acid.

Determination of glomerular filtration rate using technetium-99m-DTPA with differing degrees of renal function.

UNLABELLED: Glomerular filtration rate (GFR) is an important index of renal function. Twenty-four-hour creatinine clearance overestimates GFR in patients with poor renal function. Inulin and iothalamate clearances are accepted reference standards for determining GFR but are expensive and laborious. We have previously reported that GFRs obtained by measuring the disappearance of 99mTc-DTPA from ultrafiltered (protein-free) samples of plasma were virtually identical to those obtained by the iothalamate method. However, the subjects used in that study had normal to only moderately decreased renal function. METHODS: The accuracy of measuring GFR by plasma clearance of 99mTc-DTPA was determined in subjects where renal function varied from normal to severely impaired. In all subjects, GFR was established by clearance of 125I-iothalamate from urine and serum and was used as the standard of reference. RESULTS: For subjects with normal to moderately diminished renal function (GFR > 20 ml/min), the correlation between values of GFR obtained by the DTPA and iothalamate methods was high (n = 18, r = 0.966). The difference between the pairs of GFR values obtained by the two methods was not statistically significant (p > 0.1). In patients with severe renal insufficiency (GFR < 20 ml/min), the correlation between the DTPA and iothalamate methods was poor (n = 11, r = 0.236), and the GFR values obtained by the two methods were statistically different (p < 0.01). CONCLUSION: These results suggest that GFR can be determined accurately by plasma clearance of 99mTc-DTPA in all patients except those with severe renal insufficiency.

Production of acid and alkaline phosphatases by Myxococcus coralloides.

Acid and alkaline phosphatase of Myxococcus coralloides were examined during vegetative growth in a liquid medium. Two extracellular phosphatases and two cell-bound phosphatases, acid and alkaline in both cases, were produced. The phosphatase production was unaltered by the presence of high concentrations of inorganic phosphate. Both enzymes were produced constitutively. These two hydrolases were released into the growth medium during the exponential growth phase (approximately 10% of total activity). The production of these enzymes was modified by the presence of organic acids and metal ions in the medium.