Cerebral radiation necrosis: diagnostic challenge and clinical management.

Cerebral radiation is an indispensable cornerstone in the treatment of many primary and metastatic brain tumors. However, besides its desired therapeutic effect on tumor cells, a significant proportion of patients will experience neurotoxic side effects as the consequence of radiotherapy. Radiation necrosis can result in progressive neurological symptoms and radiographic changes. To differentiate radiation necrosis from progressive tumor based on imaging can pose a diagnostic challenge because the MRI characteristics may be similar in both situations. Therefore, surgical biopsy and pathological confirmation is sometimes necessary to guide further management. Effective treatment options for cerebral radiation necrosis exist and should be offered to symptomatic patients. A better understanding of the cellular and molecular processes underlying the development of radiation necrosis is necessary to prevent and minimize radiation-associated morbidity and to improve treatment strategies.

TITLE: Necrosis cerebral por radiacion: desafio diagnostico y tratamiento clinico.La radioterapia cerebral es una de las piedras angulares del tratamiento de numerosos tumores cerebrales primarios y metastasicos. Pese a ello, aparte de su efecto terapeutico deseado sobre las celulas tumorales, una parte sustancial de los pacientes sufre efectos secundarios de caracter neurotoxico a consecuencia de su aplicacion. La necrosis por radiacion puede provocar sintomas neurologicos y cambios radiograficos progresivos. Diferenciarla de la progresion tumoral en las imagenes puede llegar a ser un verdadero reto, dada la similitud que en ocasiones presentan las caracteristicas de la resonancia magnetica en ambas situaciones. Por esa razon, a veces es necesario recurrir a la biopsia quirurgica y la confirmacion histopatologica para confirmar el diagnostico y orientar el tratamiento. Existen opciones eficaces de tratamiento para la necrosis cerebral por radiacion y los pacientes con sintomas deben recibirlas. Es preciso ampliar el conocimiento sobre los procesos celulares y moleculares que se esconden detras del desarrollo de la necrosis por radiacion si se quiere prevenir y minimizar la morbilidad asociada a ella y mejorar las estrategias terapeuticas disponibles.

Genetic selection of volunteers and concomitant dose adjustment leads to comparable hydralazine/valproate exposure.

WHAT IS KNOWN AND OBJECTIVE: Hydralazine is an inhibitor of DNA methyltransferases, whereas valproate interferes with histone deacetylation. In combination, they show a marked synergism in reducing tumour growth as well as development of metastasis and inducing cell differentiation. Hydralazine is metabolized by the highly polymorphic N-acetyltransferase 2. The current pilot study was performed to analyse the pharmacokinetic parameters of a single dose of hydralazine in 24 h (one tablet with 83 mg for slow acetylators and one tablet with 182 mg for fast acetylators) and three fixed doses of valproate (one tablet of controlled liberation with 700 mg every 8 h) in healthy genetically selected volunteers. Selection was performed based on their NAT2 activity as deduced from their genotype. METHODS: An open label non-randomized single arm study was conducted in two groups of six healthy volunteers of both genders aged 20-45 years with a body mass index 22·2-26·9 which were classified as fast or slow acetylators after genotyping 3 SNPs that cover 99·9% of the NAT2 variants in the Mexican population. Blood samples were collected predose and serially post-dose in an interval of 48 h. Hydralazine and valproate concentrations were determined by ultra-high performance liquid chromatography (UPLC) coupled to tandem mass spectroscopy (MS/MS). RESULTS AND DISCUSSION: The AUC0-48 h and Cmax of hydralazine were almost identical (1410 ± 560 vs. 1446 ± 509 ng h/mL and 93·4 ± 16·7 vs. 112·5 ± 42·1 ng/mL) in both groups with NAT2 genotype-adjusted doses, whereas the multidose parameters of valproate were not significantly affected neither by the selection of the NAT2 genotype (AUC0-48 h 2064 ± 455 vs. 1896 ± 185 µg h/mL; Cmax 96·4 ± 21·1 vs. 88·8 ± 7·2 µg/mL, for the fast and slow acetylators, respectively) nor the co-administration of 83 or 182 mg of hydralazine. WHAT IS NEW AND CONCLUSION: Comparable hydralazine exposures (differences in AUC0-inf of only 7%) were observed in this study with genetic selection of volunteers and concomitant dose adjustment. However, the conclusions have yet to be confirmed with a full-powered 2 × 2 crossover study.

The alphavbeta6 integrin is a highly specific immunohistochemical marker for cholangiocarcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are common primary hepatic malignancies. Their immunohistological differentiation using specific markers is pivotal for treatment and prognosis. We found alphavbeta6 integrin strongly upregulated in biliary fibrosis, but its expression in primary and secondary liver tumours is unknown. Here, we aimed to evaluate the diagnostic applicability of alphavbeta6 integrin in differentiating primary liver cancers. METHODS: Expression of alphavbeta6 integrin was evaluated in liver tissues from patients with CC, HCC, fibrolamellar HCC, combined CC/HCC, hepatic metastases of colorectal and pancreatic carcinomas, primary sclerosing cholangitis (PSC), and in human primary and tumour-derived liver cell lines by immunohisto- and cytochemistry, and by TaqMan PCR. Diagnostic performance of the beta6 subunit was compared with CK7, CK20, and HepPar 1. RESULTS: In CC cells beta6 mRNA levels were induced 125-fold compared to primary cholangiocytes, while it was completely absent in hepatoma cells. In human tissues, beta6 transcripts were more than 100-fold upregulated in CC compared to normal liver. By immunohistochemistry, 88% of CC, 50% of PSC, 13% of colorectal carcinoma metastases, and 80% of pancreatic carcinoma metastases presented alphavbeta6, whereas all HCC, combined CC/HCC and fibrolamellar HCC stained negative. Specificity of beta6 immunohistochemistry for CC (100%) surpassed all other tested markers and sensitivity was equal to CK7 (86% vs. 90%). CONCLUSION: The alphavbeta6 integrin is strongly expressed in human CC but not in HCC and therefore can be considered as a specific immunohistochemical marker in the differential diagnosis of primary liver tumours.

Ciprofloxacin-related acute severe myalgia necessitating emergency care treatment: a case report and review of the literature.

OBJECTIVE: To report a case of an uncommon and up to date unpublished peracute and overwhelming muscle pain following administration of ciprofloxacin. CASE SUMMARY: A 58-year-old male developed fulminating musculoskeletal pain associated with third-time exposure to ciprofloxacin administered for treatment of chronic otitis media. Symptoms resolved slowly after intense combined analgetic therapy and cessation of ciprofloxacin therapy. 24 h after ciprofloxacin discontinuation the symptoms had completely disappeared and no more analgetic treatment was needed. Laboratory values, especially muscle enzymes, did not reveal any pathological pattern. The patient's past medical history highlighted reproducible side effects with both systemic and local administration of ciprofloxacin including milder symptoms of the musculoskeletal system. DISCUSSION: Common side effects of fluoroquinolones include gastrointestinal, central nervous and allergic reactions, but also more uncommon reactions such as tendonitis and rhabdomyolysis. In our case, there had been no signs of rhabdomyolysis. Besides an elevated IgE level no clinical signs of a true anaphylactic reaction associated with release of mast cell mediators had been observed. A pharmacokinetic interaction between ciprofloxacin and the patient's comedication carbamazepine is unlikely to be the responsible mechanism, since fluoroquinolones inhibit cytochrome P450 isoenzyme CYP1A2 but not CYP3A4 which metabolizes carbamazepine. CONCLUSION: To our knowledge, this is the first report describing fulminating musculoskeletal pain following administration of ciprofloxacin without any signs of rhabdomyolysis. Physicians should notice that there is a variety of adverse reactions of this usually well-tolerated agent and they should be aware of unusual complaints of their patients who receive fluoroquinolone treatment.

Cine magnetic resonance imaging of the small bowel: comparison of different oral contrast media.

PURPOSE: To evaluate several substances regarding small bowel distension and contrast on balanced steady-state free precession (bSSFP) cine magnetic resonance (MR) images. MATERIAL AND METHODS: Luminal contrast was evaluated in 24 volunteers after oral application of two different contrast agent groups leading to either bright lumen (pineapple, blueberry juice) or dark lumen (tap water, orange juice) on T1-weighted images. Bowel distension was evaluated in 30 patients ingesting either methylcellulose or mannitol solution for limiting intestinal absorption. Fifteen patients with duodeno-jejunal intubation served as the control. Quantitative evaluation included measurement of luminal signal intensities and diameters of four bowel segments, qualitative evaluation assessed luminal contrast and distension on a five-point scale. RESULTS: Quantitative and qualitative evaluation of the four contrast agents revealed no significant differences regarding luminal contrast on bSSFP images. Quantitative evaluation revealed significantly lower (P<0.05) small bowel distension for three out of four segments (qualitative evaluation: two out of four segments) for methylcellulose in comparison to the control. Mannitol was found to be equal to the control. CONCLUSION: Oral ingestion of tap water or orange juice in combination with mannitol is recommended for cine MR imaging of the small bowel regarding luminal contrast and small bowel distension on bSSFP sequences.

Isoniazid is not a lead compound for its pyridyl ring derivatives, isonicotinoyl amides, hydrazides, and hydrazones: a critical review.

The relationships between structure, disintegration and antituberculotic in vitro activity were studied for over 200 derivatives of isonicotinic acid hydrazide (isoniazid, INH). Conclusive evidence reflects that many compounds do not withstand the in vitro conditions. A pH dependant partial hydrolysis to INH occurs in the case of hydrazones, in analogy to well-known benzoic acid esters. Hydrazides and amides are cleaved into isonicotinic acid. In general, antimycobacterial potencies drop against INH except for two outliers probably with additional unspecific toxicity of their residues. Analyzing the complexity and heterogeneity of molecular events, trends linked to hydrolysis are found when structural features are clustered. Hammett sigma constants correlate to pK(a) values possessing a twofold descriptive meaning: (i) the cardinal increase of partial positive charge of the reaction center towards nucleophilic water attack and (ii) the ionization crucial for mycobacterial cell permeation through porins or lipid barriers. We review the literature concluding that many so-called "novel leads" are nothing else than precursors of an INH-based scaffold. In addition, INH ring-substitution or analogous backbones never achieve the efficiency of INH, itself a prodrug, which accumulates in Mycobacterium tuberculosis in form of its intrabacterial active principle(s) to which it is an optimal transport vehicle, evidencing that INH is not a promising lead compound at all.

Multisphere default spectra--solution spectrum and dosemeter response implications.

Initial calibration of a multisphere spectroscopy system has been completed at Los Alamos National Laboratory using four standard calibration scenarios. Spectrum unfolding was performed using three methods of constructing the default spectrum: simple parameter models, Monte Carlo calculations and physical measurement. Comparisons of the resulting spectra for each solution method are presented. Implications of the spectral solutions upon dosemeter characterisation are addressed.

Rhesus monkey placental transgene expression after lentiviral gene transfer into preimplantation embryos.

Transgenic mice have provided invaluable information about gene function and regulation. However, because of marked differences between rodents and primates, some areas of human biology such as early embryonic development, aging, and maternal-fetal interactions would be best studied in a nonhuman primate model. Here, we report that gene transfer into rhesus monkey (Macaca mulatta) preimplantation embryos gives rise to transgenic placentas that express a reporter transgene (eGFP). Blastocysts resulting from culture of in vitro fertilized ova were transduced with a self-inactivating lentiviral vector and transferred into recipient females. One twin and one singleton pregnancy were produced from a single stimulation cycle, and one live rhesus monkey was born from each pregnancy. Placentas from all conceptuses showed expression of the transgene as detected by reverse transcription-PCR, ribonuclease protection assay, direct epifluorescence, immunohistochemistry, and Western blot analysis. Integration in somatic tissues of the offspring was not detected. A maternal immune response to the xenogeneic placental antigen was shown by the presence of anti-GFP antibodies in peripheral blood of the recipient females by day 99 of gestation (term = 165 days). These results demonstrate that transgene expression during gestation is compatible with successful pregnancy in nonhuman primates and provides an approach that could be broadly applicable to the development of novel models for primate biomedical research.

Pregnancy and live birth from nonsurgical transfer of in vivo- and in vitro-produced blastocysts in the rhesus monkey.

Embryo transfer in the rhesus monkey has been historically limited to transfer of cleavage stage embryos. In order to allow genetic manipulation of rhesus embryos in vitro, without using invasive surgical techniques, it is important to explore the transfer of morula and blastocyst stage embryos. Embryos were produced by in vitro fertilization from gonadotropin-stimulated monkeys, or were obtained by nonsurgical uterine flushing of naturally mated or artificially inseminated females. Nonsurgical transfer was accomplished by inserting a metal guide through the cervix into the uterus, after which a hollow cell sampler was inserted over the guide. The guide was removed and a catheter was inserted containing one to five embryos. Several pregnancies resulted from in vitro- and in vivo-derived blastocysts, and two pregnancies were carried to term resulting in one live birth. Blood samples were collected regularly to monitor plasma levels of chorionic gonadotropin, luteinizing hormone, and progesterone. The recipients received progesterone as a subcutaneous implant or daily injections from the day of transfer. The approach described in this study provides the opportunity to explore transgenic and chimeric models in the monkey by the development of noninvasive methods to transfer late-stage embryos that have been manipulated in vitro.

Mouse alpha-fetoprotein-specific DNA-based immunotherapy of hepatocellular carcinoma leads to tumor regression in mice.

BACKGROUND & AIMS: alpha-Fetoprotein (AFP) is a tumor-associated protein that is frequently expressed at high levels in hepatocellular carcinoma (HCC). The aim of the study was to characterize self-reactive cytotoxic T lymphocytes (CTLs) directed against murine AFP (mAFP) after DNA-based immunization in mice. METHODS: To study CTL responses, mAFP-expressing recombinant vaccinia viruses were generated. An HCC tumor model was established in C57L/J mice by injection of syngeneic endogenously mAFP-expressing Hepa1-6 cells. RESULTS: Gene gun and intramuscular coimmunizations of DNA expression vectors encoding mAFP with plasmids encoding murine interleukin (IL)-12, granulocyte-macrophage colony-stimulating factor, or IL-18 induced weak CTL activity against mAFP in different mouse strains. Some mice developed anti-mAFP antibody responses, suggesting breaking of immunologic ignorance. No hepatocyte damage was detectable despite low-level endogenous hepatic mAFP expression. Therapeutic immunizations of mice bearing mAFP-expressing murine HCCs induced partial regression of tumors. A significant survival benefit was observed in mice immunized with mAFP expression vector DNA but not in untreated mice or in mice immunized with mock/cytokine plasmid DNA. CONCLUSIONS: The data show that AFP may be used as a potential self tumor antigen to induce CTL and CD4(+) T cell-mediated regression of AFP-expressing HCC by DNA-based immunization.

Increased norepinephrine levels during catheterization in patients with spinal cord injury.

The hypothesis for this study was that catecholamine levels increase during urinary catheterization in human patients with spinal cord injury. Catecholamine levels, blood pressure, and pulse were measured prospectively in 40 subjects at baseline and during urinary catheterization. Results showed a significant increase in norepinephrine levels from baseline 245 +/- 240 pg (standard deviation (SD)) to 314 +/- 311 pg (SD) during catheterization (P = 0.018, Wilcoxon's). Results also showed a nonsignificant increase in epinephrine levels from baseline (56 +/- 70 pg, SD) to catheterization (84 +/- 125 pg, SD; P = 0.35, Wilcoxon's). Systolic blood pressure increased from 114 to 124 mm Hg (P = 0.004, paired t test). Diastolic blood pressure increased from 75 to 78 mm Hg (P = 0.11, paired t test). There was no significant change in diastolic blood pressure or pulse (P = 0.11 and P = 0.29, respectively, paired t test). In conclusion, norepinephrine levels increased during catheterization in patients with spinal cord injury. Knowledge of catecholamine levels in this process may assist in determining both pathophysiology and potential pharmacologic treatment options in future studies.

Treatment of plantar fasciitis by iontophoresis of 0.4% dexamethasone. A randomized, double-blind, placebo-controlled study.

Plantar fasciitis is a common problem in running sports. This study was undertaken to determine whether iontophoresis of dexamethasone in conjunction with other traditional modalities provides more immediate pain relief than traditional modalities alone. Forty affected feet were randomly assigned to one of two groups. Group I feet were treated with traditional modalities and placebo iontophoresis. Group II feet received the traditional modalities plus iontophoresis of dexamethasone. Both groups were treated six times over 2 weeks. The subjects' clinical course was assessed using the Maryland Foot Score. At the conclusion of treatment, Group II patients had significantly greater improvement than Group I patients (increase on Maryland Foot Score of 6.8 +/- 5.6 for Group II and 3.1 +/- 4.1 for Group I). However, at followup 1 month after completion of treatment there was no significant difference between groups (increase of 5.6 +/- 8.0 for Group I and 7.4 +/- 6.3 for Group II). These results suggest that although traditional modalities alone are ultimately effective, iontophoresis in conjunction with traditional modalities provides immediate reduction in symptoms. Based on these results, iontophoresis of dexamethasone for plantar fasciitis should be considered when more immediate results are needed (i.e., performance athletes and active patients.

[Cercaria dermatitis (swimmer's itch). Case report of cercaria dermatitis caused by Trichobilharzia (Digena, Schistosomatidae)]. / Zerkariendermatitis (swimmer's itch). Fallbericht einer Zerkariendermatitis durch Trichobilharzia (Digena, Schistosomatidae).

A 63-year-old woman developed a pruritic exanthema on the extremities after one hour of work in her garden pond in Planegg, Southern Bavaria. As the appropriate vectors (ducks and snails) were present, we made the tentative diagnosis of cercarial dermatitis (swimmer's itch). By different serological methods (cercarial fluorescent antibody test, cercarial Hüllen reaction, circumoval precipitin test) antibodies against cercariae could be demonstrated in the serum of the patient 14 days later. Cercarial dermatitis appears worldwide, but in Central Europe the disease is often not recognized.

Lipid peroxidation and glutathione metabolism in chronic pancreatitis.

In experimental models of pancreatitis lipid peroxidation products are increased possibly because of an enhanced generation of oxygen radicals. The purpose of this study was to determine whether lipid peroxidation products are increased in pancreatic tissue and serum of patients suffering from chronic or acute pancreatitis. In 20 patients undergoing operative treatment for chronic (n = 11) and acute pancreatitis (n = 9) the levels of malondialdehyde, conjugated dienes, and reduced and oxidized glutathione were determined in resected tissue samples. The excised tissue was examined and evaluated by light microscopy. Shortly before operation the serum concentrations of malondialdehyde, alpha-amylase, and lipase were measured. Pancreatic tissue from eight organ donors who had no abdominal trauma or pancreatic disease served as control. In chronic pancreatitis, conjugated dienes as well as malondialdehyde concentrations in the tissue were significantly elevated. Reduced glutathione was significantly decreased, suggesting glutathione depletion due to oxidative stress. In acute pancreatitis only the tissue and serum malondialdehyde levels were significantly high, whereas conjugated dienes remained within the normal range. Serum malondialdehyde levels correlated significantly with tissue concentrations (r = 0.76; p < 0.05) but not with the clinical course or the enzyme levels. In chronic pancreatitis, the increased tissue levels of lipid peroxidation products and the changes in glutathione metabolism suggest ongoing peroxidation of lipids due to an enhanced generation of oxygen radicals. In hemorrhagic necrotizing pancreatitis, however, oxygen radical-induced lipid peroxidation cannot be proven. Apparently, other pathomechanisms are involved in the development of the severe tissue damage.

Improvement in the long-term stability of an amperometric glucose sensor system by introducing a cellulose membrane of bacterial origin.

Classical amperometric glucose sensors that use cellulose membranes of wood origin (Cuprophan) suffer from the fact that their long-term stability in blood is short; therefore, their clinical use is limited. In the present study, a classical amperometric glucose sensor was covered with a bacterial cellulose (BC) membrane. Its surface in comparison to that of the classical glucose sensor (Cuprophan) and its long-term stability were tested in vitro and in vivo. The surface element composition was approximately 44% oxygen and approximately 56% carbon in both membranes and thus typical for cellulose. BC membranes exhibited fiber structure, whereas cup membranes did not. There was also a qualitative difference in protein adsorption between both membranes on exposure to bovine serum albumin. Treatment with Trogamid of one site of the BC membranes allowed linear glucose detection between 0 and 40 mM. Hemocompatibility of BC membranes was improved in comparison to cup membranes on the basis of complement activation (C3a and C5a). In diluted blood (1:10), the BC-covered sensor exhibited a long-term stability of more than 200 h; in undiluted blood it was stable for about 24 h, which is about 6-7 times longer than the stability of the classical Cup membrane-covered sensor. In in vivo studies, where the BC membrane-covered sensors were connected to the jugular vein of rats, blood glucose levels could be monitored for at least 24 h. In summary, the use of a modified bacterial cellulose membrane to cover the classical amperometric glucose sensor significantly improves the sensor's long-term stability both in vitro and in vivo.

[The role of oxygen radicals in acute pancreatitis. Clinical and experimental results of therapy with free radical scavengers]. / Die Bedeutung der Sauerstoffradikale bei akuter Pankreatitis. Klinische und experimentelle Ergebnisse der Radikalenfängertherapie.

Numerous studies support the theory that oxygen free radicals (OR) are involved in the development of tissue damage in all forms of experimental acute pancreatitis. OR are generated in an early phase of the disease before tissue damage is detectable by histology. The pathomechanism that leads to this oxidative stress is not fully understood. The efficacy of scavenger treatment was clearly proven in most models of experimental acute pancreatitis. In first clinical trials applying antioxidant treatment with selenium show favorable results in reducing the lipidperoxidation and improving the antioxidant status. However these preliminary results but must be supported in a larger series of patients to allow proper evaluation of patient outcome.

Neurotoxicity of glucocorticoids in the primate brain.

Severe and prolonged physical and psychological stress is known to cause brain damage; long-term torture victims in prison have later developed psychiatric disorders and cerebral cortical atrophy observed in CT scans (Jensen, Genefke, Hyldebrandt, Pedersen, Petersen, and Weile, 1982). In nonhuman primates, we observed degeneration and depletion of the hippocampal neurons in African green monkeys that had been severely abused by cagemates and died with complications of multiple gastric ulcers and adrenal cortical hyperplasia (Uno, Tarara, Else, Suleman and Sapolsky, 1989). In our previous studies the administration of dexamethasone (DEX) (5 mg/kg) to pregnant rhesus monkeys at 132 to 133 days of gestation induced degeneration and depletion of the hippocampal pyramidal and dentate granular neurons in the brains of 135-gestation-day fetuses, and these changes were retained in the brains of fetuses at near term, 165 days of gestation (Uno, Lohmiller, Thieme, Kemnitz, Engle, Roecker, and Farrell, 1990). We also found that implantation of a cortisol pellet in the vicinity of the hippocampus in adult vervet monkeys induced degeneration of the CA3 pyramidal neurons and their dendritic branches (Sapolsky, Uno, Rebert, and Finch, 1990). Thus, hippocampal pyramidal neurons containing a high concentration of glucocorticoid receptors appear to be highly vulnerable to either hypercortisolemia caused by severe stress or to exposure to exogenous glucocorticoids. To study the long-term postnatal sequelae of prenatal brain damage, eight rhesus monkeys were treated with either DEX (5 mg/kg), 5 animals, or vehicle, 3 animals, at 132 to 133 days of gestation. After natural birth, all animals lived with their mothers for 1 year. At 9 months of age, we found that DEX-treated animals had significantly high plasma cortisol at both base and post-stress (isolation) levels compared to age-matched vehicle-treated animals. Magnetic resonance images (MRI) of the brain at 20 months of age showed an approximately 30% reduction in size and segmental volumes of the hippocampus in DEX-treated compared to vehicle-treated animals. Measurements of whole brain volume by MRI showed no significant differences between DEX and vehicle groups. Prenatal administration of a potent glucocorticoid (DEX) induced an irreversible deficiency of the hippocampal neurons and high plasma cortisol at the circadian baseline and post-stress levels in juvenile rhesus monkeys. These results suggest that the hippocampus mediates negative feedback of cortisol release; a lack or deficiency of the hippocampal neurons attenuates this feedback resulting in hypercortisolemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Optimized biosensor for whole blood measurements using a new cellulose based membrane.

We used bacterial cellulose membranes as outer membranes for glucose sensors based upon amperometric detection of glucose oxidase reaction products. We found a long-term stability in 1:10 diluted blood of about 200 h. In comparison a Cuprophan membrane was stable for only 30 h under the same conditions. Comparing the two membranes in undiluted human blood, a similar trend was found in the long-term stability; Cuprophan was stable for only 3-4 h and the glucose sensor with the bacterial cellulose membrane was stable for more than 24 h. In addition, the measuring range of the glucose sensor could be extended up to 170 mM glucose by treating the bacterial cellulose membrane with a polyamide.

Conditions of the toenails.

Athletes are susceptible to developing toenail problems because of the speed or intensity of play (runners), the starting and stopping nature of the sport (tennis, racquetball), and the type of activity and shoes they wear or do not wear (ballet dancers, gymnasts). They may also have other conditions, such as hallux valgus, claw toes, gout, diabetes, arthritis, or fungus infection of the nails, that may influence the decision on the type of treatment recommended. Nail trauma that could result in osteomyelitis; secondary effects of arthritis, such as the development of a mucous cyst; and the infected ingrown toenail are seen frequently in the athlete and can be satisfactorily treated by the orthopedist.