Beneficial response to gabapentin portraying with interval change of brain SPECT imaging in a case with failed back surgery syndrome.

WHAT IS KNOWN AND OBJECTIVE: Failed back surgery syndrome (FBSS) is a well-recognized consequence of surgery of the lumbar spine. Here, we present a case with FBSS associated neuropathic pain. CASE SUMMARY: During hospital stay, the patient was stabilized with gabapentin 200 mg twice a day and this was titrated to a dose of 1200 mg per day over the period of 1 week. The treatment produced a substantial reduction in his episodic pain. We assessed regional cerebral blood flow (rCBF) by using brain single photon emission computed tomography (SPECT) scans, which were performed before and after gabapentin treatment 1 week later. The examination of the first SPECT showed decreased uptake in left fronto-temporal-parietal region. The latter one showed much improvement of the above areas. WHAT IS NEW AND CONCLUSION: The gabapentin has beneficial effect in the FBSS associated neuropathic pain. Besides, this case suggests the association between rCBF and pain associated with FBSS, as well as the association of gabapentin and altered blood flow of brain cortex.

Methylprednisolone worsening neuropathic pain in non-traumatic thoracic myelopathy.

Methylprednisolone (MP) is the only neuroprotective medication currently in widespread use for the treatment of spinal cord injury. Increasingly, published studies challenge its clinical effects in view of its serious side-effects including wound infection, pneumonia, sepsis and steroid myopathy. Most cases with spontaneous spinal epidural haematoma (SSEH) need emergency evacuation, and typically show good neurologic recovery. Some patients with SSEH given preoperative or postoperative MP within hours of the onset of symptoms, and have had good motor recovery, although no mention was made of sensory function. Severe, intractable neuropathic pain has not been reported in patients with SSEH. We present a case of SSEH treated with a high-dose MP 16 h after onset of symptoms. Surgical decompression was performed 1 h after MP treatment. Motor recovery was good; however, intractable neuropathic pain developed 5 weeks postoperatively. We discuss the factors contributing to intractable pain. We speculate that the severe, intractable pain might be due to misuse of large-dose steroids in this case of non-traumatic spinal myelopathy, and not because of the injury per se.

Management of primary spontaneous pneumothorax in Chinese children.

OBJECTIVES: To (1) determine the demographics of Chinese children admitted with primary spontaneous pneumothorax, (2) suggest how they may be quantified radiologically, (3) compare the difference in outcomes after their primary management by thoracentesis and chest tube insertion, and (4) review the local experience with surgical intervention for such children. DESIGN: Retrospective, descriptive study. SETTING: Acute tertiary public hospital, Hong Kong. PATIENTS: Consecutive patients younger than 18 years and admitted with primary spontaneous pneumothorax between 1 January 1999 and 30 September 2007. MAIN OUTCOME MEASURES: Hospital stay and risk of recurrence after thoracentesis versus chest tube insertion. RESULTS. Seventy-seven patients with 114 episodes of primary spontaneous pneumothorax were reviewed. They were significantly taller (P<0.001) and thinner (P<0.001) than the population mean percentile. Both the Light index and Collins formula were accurate in quantifying pneumothorax volume, but as the former was simpler and more user-friendly, this was more applicable in children. Thoracentesis resulted in shorter hospital stays (mean, 4.6; standard deviation, 1.9 days) than chest tube insertion (6.9; 3.0 days), but there was no significant difference in the recurrence rates within 6 months (P=1.0), 1 year (P=0.9), and 2 years (P=0.1). Insignificant pneumothorax was treated with observation alone in 16% of the patients. For patients with a clinically significant pneumothorax, thoracentesis and chest tube insertion were successful in 78% and 67%, respectively (P=0.34). The success rate of video-assisted thoracoscopic surgery was 89%, and postoperative recurrence occurred more commonly in patients without a lung bleb. CONCLUSION: Chinese children with primary spontaneous pneumothorax exhibited similar demographic characteristics to Caucasian children. Light index is simple and accurate for quantifying pneumothorax volume in children. Conservative treatment including observation, thoracentesis, and chest tube insertion should suffice for most patients with first episode of primary spontaneous pneumothorax. Early surgery is warranted for any patient who fails conservative treatment, for which video-assisted thoracoscopic surgery is safe and effective.

Mammary angiosarcoma in two patients at either end of the age spectrum.

Angiosarcoma of the breast is rare and has a poor prognosis due to its aggressive nature. This is a report of two patients with mammary angiosarcomas, each with different clinical presentations, and at either end of the age spectrum. One is an 18-year-old woman who presented with a rapidly enlarging breast mass, and the other a 72-year-old woman whose breast mass was found during screening mammography. The radiological features of mammary angiosarcoma are summarised in this report.

Hemichorea associated with gabapentin therapy with hypoperfusion in contralateral basal ganglion - a case of a paraplegic patient with neuropathic pain.

Functional imaging in patients with movement disorders has suggested abnormalities of regional cerebral blood flow (rCBF). We describe a patient with thoracic cord lesion with subsequent severe neuropathic pain. Right hemichorea developed and was related to adjunctive therapy with gabapentin. The patient's hemichorea decreased gradually after cessation of gabapentin. The study of rCBF revealed hypoperfusion in the contralateral basal ganglia compared with the previous study of rCBF. Our patient is the first patient with neuropathic pain, treated with gabapentin who developed hemichorea, in the absence of brain lesions. Imaging studies of rCBF showed a perfusion defect in the contralateral basal ganglion.

Multicentric giant cell tumours in an adolescent with haemophilia.

''Multicentric giant cell tumour (GCTs) of the extremity is prone to be distributed over the age range of 20-40 years, but is rare in haemophilia and in the age before 20. We report a case of a 15-year-old haemophilia boy who presented initially with two radiolucent loci in the right femur and tibia revealed from the X-ray films and then another lesion in the posterior femoral shaft shown from MRI by one year. Differential diagnosis of GCTs should be appraised in various aspects. Radiological diagnostic pitfall was avoided by the pathology disclosed GCTs without malignancy. The early diagnosis of GCTs in haemophilia may be delayed unless appearance of symptoms of pathologic fracture. Coincident multicentric GCTs do occur in haemophilic patients and their incidence might be underestimated, as it might not be judged because immediate symptoms of pain would resolve with appropriate factor replacement."

Glycolytic pathway and hydrogen yield studies of the extreme thermophile Caldicellulosiruptor saccharolyticus.

NMR analysis of (13)C-labelling patterns showed that the Embden-Meyerhof (EM) pathway is the main route for glycolysis in the extreme thermophile Caldicellulosiruptor saccharolyticus. Glucose fermentation via the EM pathway to acetate results in a theoretical yield of 4 mol of hydrogen and 2 mol of acetate per mole of glucose. Previously, approximately 70% of the theoretical maximum hydrogen yield has been reached in batch fermentations. In this study, hydrogen and acetate yields have been determined at different dilution rates during continuous cultivation. The yields were dependent on the growth rate. The highest hydrogen yields of 82 to 90% of theoretical maximum (3.3 to 3.6 mol H(2) per mol glucose) were obtained at low growth rates when a relatively larger part of the consumed glucose is used for maintenance. The hydrogen productivity showed the opposite effect. Both the specific and the volumetric hydrogen production rates were highest at the higher growth rates, reaching values of respectively 30 mmol g(-1) h(-1) and 20 mmol l(-1) h(-1). An industrial process for biohydrogen production will require a bioreactor design, which enables an optimal mix of high productivity and high yield.

Fermentation of resistant rice starch produces propionate reducing serum and hepatic cholesterol in rats.

This study was designed to investigate the effects of different proportions of rice starch and cornstarch on lipid metabolism in rats fed high dietary cholesterol. Male Wistar rats were fed a 10 g/100 g fat diet containing 1 g/100 g cholesterol with 0 (control diet), 15, 30, 45 or 63 g/100 g rice starch with an enzyme resistant starch concentration of 1.26, 1.39, 1.52, 1.65 or 1.80 g/100 g, respectively, for 4 wk. Groups fed diets with < 63 g/100 g rice starch were supplemented with cornstarch to 63 g/100 g. The two kinds of starch had different structures as seen using scanning electron microscopy (SEM). The rice starch was an aggregation (n = 20-60) of smaller granules (3-8 microm in diameter), whereas the cornstarch was composed of larger (5-15 microm in diameter), single granules. The compound rice starch (0.99 kg/L) was larger in size and denser in structure than cornstarch (0.63 kg/L). Serum total cholesterol concentrations in rats fed both the 45 and 63 g/100 g rice starch diets were significantly lower than in all other groups (P < 0.05). The serum propionate concentration in the rats fed 63 g/100 g rice starch diets was significantly higher than that of other groups. Hepatic triglyceride and total cholesterol concentrations in rats fed 63 g/100 g rice starch diets were significantly lower than in the control group. These results suggest that, because the compound rice starch was an aggregation of smaller granules, larger in size and denser in structure than cornstarch, it was digested more slowly and altered lipid metabolism. Resistant rice starch may be fermented to produce propionate, which reduces serum and hepatic cholesterol.

Analytical magnetapheresis of magnetically susceptible particles.

Analytical magnetapheresis is a newly developed technique for analyzing magnetic particles. The magnetically susceptible particles form deposition patterns after flowing through a separation channel in a magnetic field. The separation channel requirements for analytical magnetapheresis are an excellent seal for the carrier flow and ease of disassembly after magnetapheresis. Previously used separation channels often exhibit variable channel leakage and unstable flow velocities. We improved the separation channel assembly to ensure stable, high flow velocities and characterized the system with various magnetically susceptible and labeled particles. Our new separation channel featured silicone sealant with embedded nylon wires and met analytical magnetapheresis requirements. Characterization of this system was performed using several magnetically susceptible particles, and we studied a variety of diamagnetic sample labels with paramagnetic ions and magnetically susceptible particles at different flow-rates and solution pH values. The minimal labeling concentration for complete deposition was determined to be approximately 2.50 x 10(10) ions per particle for test samples at a flow velocity of 0.67 mm s(-1) and a magnetic field gradient of 2.8 T mm(-1). Silicas, yeasts and blood cells were used for these studies. We determined that the minimal difference in magnetic susceptibility (delta(chi)) for successful separation was approximately 2.00 x 10(-6) [SI]. The magnetic susceptibilities of Dynabeads M-450 at several separation distances and flow-rates were determined to be 0.25 [SI], within 2% of values published by other workers. The magnetic susceptibilities of various ion-labeled yeasts and cells were determined and most varied by less than 5% at different flow-rates. The results of this study provide very important references for analytical magnetapheresis applications.

A new chalcone, xanthones, and a xanthonolignoid from Hypericum geminiflorum.

A new prenyl chalcone, gemichalcone C (1), was isolated from the heartwood and root of Hypericum geminiflorum. Three new xanthones-6, 7-dihyroxy-1,3-dimethoxyxanthone (2), 4-hydroxy-1, 2-dimethoxyxanthone (3), and gemixanthone A (4)-and four known xanthones were isolated from the leaves and stems of the same plant.

Multiple copies of PBS2, MHP1 or LRE1 produce glucanase resistance and other cell wall effects in Saccharomyces cerevisiae.

Five sequences were isolated by selection for multiple copy plasmids that conferred resistance to laminarinase, an enzyme that specifically degrades cell wall beta(1-3) glucan linkages. Strains carrying three of these plasmids showed alterations in cell wall glucan labelling. One of these plasmids carried PBS2, a previously identified, non-essential gene which produces a variety of phenotypes and encodes a mitogen-activated protein kinase kinase analogue (Boguslawski and Polazzi, 1987). Cells carrying PBS2 at multiple copy show a small decrease in cell wall beta(1-6) glucans. Measurements of beta(1-3) glucan synthase activity in multi-copy PBS2 cells showed an approximate 30-45% increase in enzyme specific activity while a pbs2 delta disruption strain showed a decrease in glucan synthase activity of approximately 45% relative to control. A pbs2 delta disruption strain was laminarinase super-sensitive and supersensitive to K1 killer toxin while a strain carrying PBS2 at multiple copy was resistant to killer toxin. A second plasmid carried a portion of the MHP1 gene which has been reported to encode a microtubule-interacting protein (Irminger-Finger et al., 1996). The MHP1 gene product is a predicted 1398 amino acid protein and only approximately 80% of the amino portion of this protein is required for laminarinase resistance. Cells carrying the amino portion of MHP1 at multiple copy show a decrease in high molecular weight cell wall beta(1-6) glucans and were killer toxin resistant while a disruption strain was viable and killer toxin super-sensitive. Cells carrying this plasmid showed decreased levels of high molecular weight beta(1-6) glucans and increased glucan synthase activity. The laminarinase resistance conferred by the third plasmid mapped to the previously uncharacterized YCL051W open reading frame and this gene was therefore named LRE1 (laminarinase resistance). The LRE1 gene encodes a non-essential 604 amino acid hydrophilic protein. Unexpectedly, cells carrying LRE1 at multiple copy show no alteration in cell wall glucans or glucan synthase activity. Subcloning experiments demonstrated that the production of these cell wall effects requires the presence of both LRE1 and YCL052C (PBN1), a second open reading frame present on the original plasmid. Cells carrying multiple copies of PBN1 alone show no significant alterations in cell wall glucans or glucan synthase activity, indicating that these effects require the presence of multiple copies of both genes.

Induction signals for vancomycin resistance encoded by the vanA gene cluster in Enterococcus faecium.

The induction of vancomycin resistance in enterococci containing the vanA gene cluster is thought to be controlled by a two-component sensor-response regulator system encoded by vanR and vanS. Eight inducing compounds were identified by screening a panel of more than 6,800 antibiotics and synthetic compounds including the three tested glycopeptides (vancomycin, avoparcin, and ristocetin), two other cell wall biosynthesis inhibitors (moenomycin and bacitracin), two cyclic peptide antibiotics (antibiotic AO341 beta and polymyxin B), and a macrocyclic lactone antibiotic (moxidectin). Induction activity by structurally unrelated antibiotics suggests that the induction signal is not a structural feature of vancomycin.

Nikkomycin Z is a specific inhibitor of Saccharomyces cerevisiae chitin synthase isozyme Chs3 in vitro and in vivo.

Nikkomycin Z inhibits chitin synthase in vitro but does not exhibit antifungal activity against many pathogens. Assays of chitin synthase isozymes and growth assays with isozyme mutants were used to demonstrate that nikkomycin Z is a selective inhibitor of chitin synthase 3. The resistance of chitin synthase 2 to nikkomycin Z in vitro is likely responsible for the poor activity of this antibiotic against Saccharomyces cerevisiae.

Identification of a gene encoding a new Ypt/Rab-like monomeric G-protein in Saccharomyces cerevisiae.

A Saccharomyces cerevisiae sequence cloned by serendipity was found to encode a protein that is a new member of the Ypt/Rab monomeric G-protein family. This sequence shows high homology to the yeast genes SEC4 and YPT1 and, like SEC4 and YPT1, is essential for viability. The sequence was localized to chromosome V based upon hybridization to pulse-field gel-separated yeast chromosomes. The sequence has been deposited in the GenBank data library under Accession Number L17070.

The identification of a gene family in the Saccharomyces cerevisiae ergosterol biosynthesis pathway.

The Saccharomyces cerevisiae ERG24 gene, encoding sterol delta 14 reductase (Erg24p), was cloned by selecting strains carrying sequences on a 2 mu-based vector for resistance to the morpholine fungicide, fenpropimorph (Fp). Four distinct plasmid inserts which conferred Fp resistance (FpR) were recovered (plasmids pML99, pML100, pML101 and pM103). Although Fp is reported to inhibit activity of Erg24p and sterol delta 8-delta 7 isomerase (Erg2p; encoded by ERG2), none of the inserts had restriction maps resembling ERG2. In addition, a 2 mu plasmid overexpression of the ERG2 sequence did not produce FpR. Characterization studies were focused on plasmid pML100, because it was the only plasmid to confer FpR consistently when tested in a number of different genetic backgrounds. Tests with a panel of fungicides indicated that pML100 conferred significant resistance only to compounds (Fp, tridemorph, fenpropidin and azasterol) which have a shared site of action, Erg24p. An insertional disruption of pML100 resulted in an obligate anaerobic phenotype, indicating a lesion in sterol biosynthesis. Sterol analysis of the disrupted mutant demonstrated the accumulation of ignosterol, indicating a loss of Erg24p activity. A SphI-XbaI fragment of pML100 was sequenced, revealing the presence of an ORF encoding a 438-amino-acid protein, which is highly similar to those encoded by two previously reported yeast drug sensitivity genes, sts1+ (Schizosaccharomyces pombe) and YGL022 (S. cerevisiae). Analyses of these genes demonstrated that strains carrying disruptions of sts1+ or YGL022 have ergosterol biosynthesis defects in the enzyme, sterol C-24(28) reductase (Erg4p; encoded by ERG4).(ABSTRACT TRUNCATED AT 250 WORDS)

Structure and functional expression of a complementary DNA for porcine growth hormone-releasing hormone receptor.

Growth hormone-releasing hormone (GHRH) belongs to the family of gut-neuropeptide hormones which also includes glucagon, secretin and vasoactive intestinal peptide (VIP). All receptors for this peptide hormone family seem to involve similar signal transduction pathways. Upon hormone binding, these receptors interact with guanine nucleotide binding protein 'Gs' and cause the stimulation of adenylate cyclase. The secretin and VIP receptor cDNAs have recently been cloned and found to be homologous to those of calcitonin and parathyroid hormone receptors. Based on cDNA sequences of these receptors, we designed several oligonucleotide primers which were used to amplify two novel porcine pituitary cDNA fragments by the polymerase chain reaction. One novel receptor cDNA fragment was used to screen a porcine pituitary cDNA library and a full-length cDNA encoding a putative porcine GHRH receptor of 451 amino acids was isolated. This putative receptor mRNA is present specifically in porcine anterior pituitary cells and not in eight other porcine tissues as shown by Northern hybridization analysis. The receptor cDNA was subsequently cloned into a mammalian cell expression vector containing the cytomegalovirus promoter. A human kidney tumor cell line (293) stably transfected with this vector was found to express the receptor efficiently and to bind [125I]-GHRH specifically. Furthermore, challenge of the 293 cells expressing the receptor by GHRH leads to efficient stimulation of cytoplasmic cAMP production.

Impeded progression of Friend disease in mice by an inhibitor of retroviral proteases.

The protease of the human immunodeficiency virus type 1 (HIV-1) is essential for the processing of GAG and POL polyproteins and maturation of the virus particles. Using recombinant protease and a truncated GAG polyprotein as substrate, we developed a Western blot assay for the evaluation of inhibitors of the enzyme. Two statine-based inhibitors of the enzyme, KH161 and KH164, were effective in blocking the replication of HIV-1 in acutely infected human T4 lymphoid cells, with potency approaching that of zidovudine (ZDV) when tested in parallel. In chronically infected cells, the production of infectious virus was inhibited by KH161 and KH164, while ZDV was ineffective. Both KH161 and KH164 were also active as antivirals against the replication of murine leukemia virus (MLV) in cultured mouse cells. In an animal model of a murine retroviral disease, KH164 was shown to inhibit in a dose-dependent manner the progression of the disease induced by Friend virus complex (a mixture of Friend MLV and spleen focus-forming virus). The results suggest that the progression of the acquired immune deficiency syndrome (AIDS) may be impeded by inhibitors of HIV-1 protease.

Design and implementation of a particle concentration fluorescence method for the detection of HIV-1 protease inhibitors.

A critical step in the replicative cycle of the human immunodeficiency virus HIV-1 involves the proteolytic processing of the polyprotein products Prgag and Prgag-pol that are encoded by the gag and pol genes in the viral genome. Inhibitors of this processing step have the potential to be important therapeutic agents in the management of acquired immunodeficiency syndrome. Current assays for inhibitors of HIV-1 protease are slow, cumbersome, or susceptible to interference by test compounds. An approach to the generation of a rapid, sensitive assay for HIV-1 protease inhibitors that is devoid of interference problems is to use a capture system which allows for isolation of the products from the reaction mixture prior to signal quantitation. In this paper, we describe a novel method for the detection of HIV-1 protease inhibitors utilizing the concept of particle concentration fluorescence. Our approach involves the use of the HIV-1 protease peptide substrate Ser-Gln-Asn-Tyr-Pro-Ile-Val which has been modified to contain a biotin moiety on one side and a fluorescein reporter molecule on the other side of the scissile Tyr-Pro bond. This substrate is efficiently cleaved by the HIV-1 protease and the reaction can be readily quantitated. Known inhibitors of the protease were readily detected using this new assay. In addition, this approach is compatible with existing instrumentation in use for broad screening and is highly sensitive, accurate, and reproducible.