On S. Seygert, V. Kunzmann, N. Schwertfeger, H. C. Koch, A. Faulstich: Determinants of lumbar CSF protein concentration.
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Albumins↗
Biomedical subjects
P Adam
Publications and source records attributed to P Adam.
Complete proteinogram of cerebrospinal fluid and its contribution to the diagnostics of inflammatory and autoimmune diseases of the central nervous system.
Complete evaluation of cerebrospinal fluid proteinogram represents a routine request of the clinician in the analysis of CSF in the Czech Republic. It comprises the measurement of concentrations of acute phase proteins (CRP, orosomucoid, haptoglobin, transferrin, prealbumin), immunoglobulins (IgG, IgA, IgM), compressive markers (albumin, fibrinogen), markers of CNS tissue destruction (apolipoproteins A-I, A-II, Apo B), complement components (C3, C4), alpha-1-microglobulin, beta-2-microglobulin, and proteinase inhibitors (alpha-1-antitrypsin, antithrombin III). Therefore, 19 CSF proteins of precisely verified clinical relevance are routine parameters for the assessment of the functional state of the blood-CSF barrier, presence of the intrathecal synthesis of immunoglobulins, inflammatory changes and verification of CNS tissue destruction. Evidence of these clinically relevant and independent parameters enabled the detection of the presence of autoimmune and neuroinfective diseases of CNS, even in clinical cases where the basic CSF parameters do not express relevant changes, or they are of a bordering or non-specific character. Clinically typical and the most significant abnormalities in the CSF proteinogram represent themselves a new access to a contemporary CSF analysis. Despite the fact that assessment of CSF proteins and their analysis is quite a difficult field in laboratory medicine, it is now routinely requested and routinely performed in the Czech Republic.
Autoimmune Diseases of the Nervous System↗
Studies on the nonmevalonate pathway to terpenes: the role of the GcpE (IspG) protein.
Recombinant Escherichia coli cells engineered for the expression of the xylB gene in conjunction with genes of the nonmevalonate pathway were supplied with (13)C-labeled 1-deoxy-D-xylulose. Cell extracts were analyzed directly by NMR spectroscopy. (13)C-labeled 2C-methyl-D-erythritol 2,4-cyclodiphosphate was detected at high levels in cells expressing xylB, ispC, ispD, ispE, and ispF. The additional expression of the gcpE gene afforded 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate as an intermediate of the nonmevalonate pathway. Hypothetical mechanisms involving conserved cysteine residues are proposed for the enzymatic conversion of 2C-methyl-D-erythritol 2,4-cyclodiphosphate into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate catalyzed by the GcpE protein.
Amino Acid Sequence↗
Biosynthesis of thiophenes in Tagetes patula.
The biosynthesis of 5-(3-buten-1-ynyl)-2,2'-bithiophene was studied in root cultures of Tagetes patula. Organ cultures were grown with [U-13C(6)]glucose or [1-13C]glucose. The bithiopene and amino acids from cell protein were isolated and analysed by quantitative NMR spectroscopy. Retrobiosynthetic analysis establish acetyl-CoA or a closely related compound (e.g. malonyl-CoA) as building blocks and their orientations in the bithiophene. The data confirm a previously suggested biosynthetic route via long-chain fatty acids and polyacetylenes. However, a polyketide-like biosynthesis via a carbocyclic intermediate cannot be excluded.
Asteraceae↗
Cerebrospinal fluid.
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Cerebrospinal Fluid↗
Studies on the nonmevalonate pathway of terpene biosynthesis. The role of 2C-methyl-D-erythritol 2,4-cyclodiphosphate in plants.
2C-methyl-D-erythritol 2,4-cyclodiphosphate was recently shown to be formed from 2C-methyl-D-erythritol 4-phosphate by the consecutive action of IspD, IspE, and IspF proteins in the nonmevalonate pathway of terpenoid biosynthesis. To complement previous work with radiolabelled precursors, we have now demonstrated that [U-13C5]2C-methyl-D-erythritol 4-phosphate affords [U-13C5]2C-methyl-D-erythritol 2,4-cyclodiphosphate in isolated chromoplasts of Capsicum annuum and Narcissus pseudonarcissus. Moreover, chromoplasts are shown to efficiently convert 2C-methyl-D-erythritol 4-phosphate as well as 2C-methyl-D-erythritol 2,4-cyclodiphosphate into the carotene precursor phytoene. The bulk of the kinetic data collected in competition experiments with radiolabeled substrates is consistent with the notion that the cyclodiphosphate is an obligatory intermediate in the nonmevalonate pathway to terpenes. Studies with [2,2'-13C2]2C-methyl-D-erythritol 2,4-cyclodiphosphate afforded phytoene characterized by pairs of jointly transferred 13C atoms in the positions 17/1, 18/5, 19/9, and 20/13 and, at a lower abundance, in positions 16/1, 4/5, 8/9, and 12/13. A detailed scheme is presented for correlating the observed partial scrambling of label with the known lack of fidelity of the isopentenyl diphosphate/dimethylethyl diphosphate isomerase.
Capsicum↗
Transferrin in patients with multiple sclerosis: a comparison among various subgroups of multiple sclerosis patients.
OBJECTIVES: To compare cerebrospinal fluid (CSF) and serum transferrin (Tf) concentrations, transferrin quotient and index in various subgroups of MS patients. MATERIAL AND METHODS: CSF and serum transferrin concentrations, transferrin quotient QTf (i.e. CSF transferrin/serum transferrin x 10(3)) and index (QTf/Qalbumin) were determined in a group of 51 patients with clinically definite or probable multiple sclerosis (MS). Patients were subdivided according to the disease form (relapsing-remitting = RR, secondary progressive = SP, primary progressive = PP; patients with RR form were further subdivided into those in the attack and those in remission), disease severity (EDSS 0-5.5, EDSS 6.0-10.0), its treatment (non-treated - including patients treated with vitamins and/ or vasodilators only, treated - i.e. glucocorticoids and/or immunosuppressants and/or (exceptionally) beta-interferon), disease duration (0-2 years, >2-10 years, > 10 years) and sex. Correlation of transferrin values with age was also performed. RESULTS: Serum transferrin was somewhat lower and significantly more frequently subnormal in PP patients in comparison with the SP form and the RR form in remission. Transferrin index was significantly higher in the PP form than in the RR as well as the SP form. Transferrin quotient was significantly more frequently subnormal in patients in remission compared to those in the attack of the RR disease. CSF transferrin as well as transferrin quotient were more frequently subnormal in patients with short disease duration (0-2 years) than in patients with longer disease duration; these parameters, however, correlated also significantly with age. CSF transferrin and transferrin quotient were higher in male than in female patients. CONCLUSION: The authors conclude that evaluation of transferrin in MS patients - along with albumin - may help to differentiate among various MS subgroups, since there are significant differences among RR, SP and PP forms. For this purpose, however, other CSF protein fractions should be evaluated in parallel in order to obtain more complex information and to establish a panel of examinations enabling multiple statistical analyses. Transferrin evaluation in MS may also be of significant theoretical interest, since transferrin is known to be involved in the regulation of iron metabolism and it may have a protective role against the oxidative stress. Moreover, transferrin is a growth factor important for proliferation of activated T lymphocytes. By means of the use of transferrin quotient and especially transferrin index, it may be possible to estimate the proportion of intra-CNS-synthesized transferrin and/or rate of specific transferrin transport across the blood-CSF barrier. Further studies are, however, needed for such an evaluation.
Age Factors↗
Once weekly fluconazole is effective in children in the treatment of tinea capitis: a prospective, multicentre study.
In an open, multicentre evaluation carried out in Brazil, Canada and South Africa we have demonstrated that fluconazole 8 mg kg-1 once weekly is effective in tinea capitis caused by Trichophyton and Microsporum species. There were 61 children, aged (mean +/- SE) 5.0 +/- 0.3 years; weight (mean +/- 5.6) 20.0 +/- 0.9 kg; 41 males, 20 females; one Asian, 57 Black, one Caucasian and two Hispanic. The organisms were Trichophyton violaceum (33 patients), T. tonsurans (11) and Microsporum canis (17). The extent of tinea capitis at pretherapy was: mild (18 patients), moderate (30) and severe (13). Patients with tinea capitis due to Trichophyton species were initially treated for 8 weeks with an extra 4 weeks of fluconazole if clinically indicated. All 44 patients with tinea capitis due to Trichophyton species were completely cured (clinically and mycologically) when evaluated 8 weeks after completion of active treatment, following 8 weeks of once weekly dosing in 35 patients and 12 weeks of once weekly dosing in nine patients. In Microsporum canis tinea capitis, an extra 4 weeks was administered at week 12 in patients where it was clinically indicated at the time. Sixteen of 17 patients with M. canis tinea capitis were completely cured (clinically and mycologically) when evaluated 8 weeks following the end of treatment when given for 8, 12 and 16 weeks in 12, one and three patients, respectively. Overall, complete cure (clinical and mycological) occurred in 60 of 61 patients at follow-up 8 weeks from the end of therapy. The duration of once weekly fluconazole in the 60 patients was 8 weeks (47 patients), 12 weeks (10 patients) and 16 weeks (three patients), respectively. Clinical adverse effects consisted of a mild, reversible gastrointestinal complaint in three (4.9%) of 61 children. A laboratory abnormality with elevated liver function tests was observed in one (5.9%) of 17 patients; this was asymptomatic, and reversible. No patient discontinued therapy. The data suggest that once weekly fluconazole dosing is effective, safe and associated with high compliance when used to treat tinea capitis.
Antifungal Agents↗
Intrathecal narcotics are associated with prolonged second-stage labor and increased oxytocin use.
BACKGROUND: Safe and effective labor analgesia is an important part of obstetric care. Intrathecally injected narcotics (ITN) are an effective alternative to epidural anesthesia, and are perceived less likely to interfere with the course and outcome of labor. Data on their effects, however, are sparse and contradictory. METHODS: Our retrospective study compared labor length, oxytocin use, delivery type, maternal side effects, and neonatal outcomes among women who received ITN (n=100) and a group who received intravenous narcotics or no analgesia during labor (n=100). We randomly sampled medical records with stratification for parity and collected data through systematic chart review. RESULTS: Women receiving ITN were more likely to be white. They experienced longer second-stage labors (73 minutes vs 40 minutes, P=.000) and used oxytocin twice as often. These differences remained significant after controlling for potential confounding factors. ITN use was also associated with a trend toward more cesarean sections (7% vs 1%, P=.06). More of the women receiving ITN required urinary catheterization (25% vs 5%, P=.000) and experienced significant pruritus (10% vs 0%, P=.001). Neonatal outcomes were similar for both groups. CONCLUSIONS: In our retrospective study, ITN use was associated with a significant prolongation of second-stage labor, which may be clinically relevant for women having their first child. ITN were also associated with increased oxytocin use and a trend toward more cesarean births. Whether these relationships are causal or a proxy for more difficult labors is a question for future prospective studies.
Adult↗
Experience and hopes for telehealth in Tokelau.
The two key factors affecting healthcare in Tokelau are its small population and its great isolation. Both of these make telehealth a critical issue for the development of health services and it is hard to see how the services can develop to a modern standard without a larger component of telemedicine. The Tokelau islands consist of three roughly equal atolls usually served by 1-2 doctors who deal with all aspects of medical care. There is a small hospital on each atoll and each is staffed by a Nurse manager, two staff nurses and some nurse aides. There is a need for a communication facility for the nurse on the atoll(s) without a doctor to consult with a doctor about medical cases; doctors to consult each other; and for doctors to consult outside specialists about the management of cases. Distance education for health care staff is another perceived need. The current communications systems are still basic and although there is a PeaceSat terminal on each atoll it has largely failed to provide the above communication needs and most is still done by the costly telephone system. Recently ITC has been made a priority for the health department.
Health Priorities↗
The effect of physical activity on absorption and metabolism of an orally applied drug (pentoxifylline).
STUDY OBJECTIVE: In this study the effect of physical activity on absorption and metabolism of a therapeutic drug was investigated by comparing plasma concentrations and metabolism of pentoxifylline during rest and after standardized physical activity. METHODS AND PATIENTS: After an oral dose of 600 mg pentoxifylline plasma concentrations of the drug and its metabolite 1 were monitored in nine healthy volunteers during five hours with the persons at rest and in a second experiment after ability-adapted standardized bicycle ergonometry. MAIN RESULTS: In six of nine test persons exercise led to significant higher plasma concentrations of the drug at 2 hours after application (+77%; p <0.01) compared to the concentrations in the same persons at rest. Reductive metabolism of pentoxifylline decreased in all test persons after physical activity giving 19% lower maximal concentrations of metabolite 1 (p = 0.06, not significant) and a 16% lower area under the concentration time curve (p <0.02). CONCLUSIONS: Our results indicate that physical activity can influence absorption and metabolism of a drug.
Administration, Oral↗
Unusual maxillofacial injury caused by a model airplane.
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Cheek↗
Intermittent short duration therapy with fluconazole is effective for tinea capitis.
We have demonstrated in an open multicentre investigation that oral fluconazole 6 mg/kg daily for 2 weeks, followed, if clinically indicated four weeks from the start of therapy, by an extra week of treatment at the same dosage, may be effective and safe in the treatment of tinea capitis. Of a total of 48 patients, there were 42 evaluable children < 18 years old (19 boys, 23 girls; mean age 6.2 years, range 1.5-16). The causative organisms were Trichophyton tonsurans (38 subjects) and T. violaceum (four). In the 42 evaluable patients, a 2-week course of fluconazole was administered in 21, with the remainder requiring 1 additional week of therapy. At follow-up 12 weeks from the start of therapy, mycological and clinical cure was recorded in 37 of the 42 evaluable patients (88.1%, 95% confidence interval 83.1-93.1%). The treatment was well tolerated, with no clinical adverse effects. This regimen appears to be effective and safe, and is associated with high compliance. The preliminary results of the investigation need to be evaluated in a larger sample of patients, and in tinea capitis caused by zoophilic species.
Adolescent↗
Itraconazole oral solution for the treatment of tinea capitis using the pulse regimen.
A 7-year-old boy with Trichophyton tonsurans tinea capitis was cured following the administration of itraconazole oral solution. He had difficulty swallowing tablets or capsules, so the availability of the oral solution was particularly advantageous. The itraconazole was given once daily in a fasting state at a dosage of 3 mg/kg/day as a pulse lasting 1 week. The first two pulses were separated by 2 weeks and the second and third pulse by 3 weeks. The decision whether or not to administer the third pulse was guided by the presence of clinical symptoms and signs of tinea capitis just prior to the scheduled administration. The availability of the oral solution will enable more young children to be considered for treatment of tinea capitis with itraconazole than was possible when only tablets or capsules were available.
Administration, Oral↗
[Therapeutic effect of Myolastan on increased muscle tone of various etiologies].
The authors tested in 101 patients the clinical effect of Myolastan (tetrazepam), generic name 1,4, benzodiazepine (BZD), in indications with increased muscular tonus of varying etiology. The drug has a balanced affinity to central and peripheral benzodiazepine receptors, it enhances the presynaptic inhibition of GABAergig neurones at the peripheral and supraspinal level. Clinical experience has shown that a decline of the increased muscular tonus in the affected segment mitigates subjective complaints, in particular pain, if the dosage and time of administration are adjusted for every individual patient. A favourable effect was proved during clinical administration to a heterogeneous group of patients which reflects the spectrum of our ambulatory patients with a locally increase muscle tonus. In addition to vertebrogenic complaints, non-discogenic and discogenic (proved by MR or CT), the group of patients comprised also some with multiple sclerosis. In the latter a favourable effect was recorded in 50%. The effect on spasticity in these patients was comparable with other drugs used by the patients before administration of Myolastan. The heterogeneous group of the remaining patients to whom Myolastan was administered suggests its possible further indications, without the possibility of significant conclusions. Possible side-effects could be eliminated by the administration of low doses in the evening or at night. Myolastan extends the range of drugs which have an impact on an increased muscular tonus.
Anti-Anxiety Agents↗
Treatment of tinea capitis with itraconazole capsule pulse therapy.
BACKGROUND: The number of newly diagnosed cases of tinea capitis in children appears to be on the rise, particularly in urban centers. OBJECTIVE: The purpose of this study was to assess the effectiveness, safety, and compliance of itraconazole pulse therapy for tinea capitis. METHODS: Fifty subjects (48 children [less than 18 years of age] and 2 adults) with tinea capitis were treated with pulse itraconazole in a multicenter evaluation. Each pulse lasted 1 week, with 2 weeks between the first two pulses and 3 weeks between the second and third pulses. The decision to administer a second or third pulse was determined by the response of the subject at the time that the next pulse was due. During the 1-week pulse of active therapy, itraconazole (5 mg/kg/day) was dosed as follows: more than 40 kg, 200 mg per day (two capsules per day); 20 to 40 kg, 100 mg per day (one capsule per day); and 10 to 19 kg, 50 mg per day (one half of a capsule per day). The duration of the study was 12 weeks with mycologic evaluation at this time. Subjects who were classified as treatment failures at 12 weeks after the start of therapy were given the option of receiving an additional 1-week pulse of active therapy, with 3 weeks between successive pulses. RESULTS: The causative organisms were Trichophyton tonsurans (41 subjects), T violaceum (7), T. soudanense (1), and T rubrum (1). Thirteen subjects were lost to follow-up, with 37 subjects (35 children and 2 adults) available for evaluation 12 weeks after the start of therapy. At this time, cure (clinical and mycologic) was observed in 30 (81%) of 37 subjects. When the tinea capitis was mild, cure was obtained after one pulse in two subjects and after two pulses in five subjects. With tinea capitis of moderate extent, complete cure was obtained after one pulse in one subject, two pulses in eight subjects, and after three pulses in seven subjects. When tinea capitis was severe, two and three pulses produced complete cure in one and six subjects, respectively. Of the seven subjects whose conditions failed to respond (three subjects with moderate disease and four subjects with severe disease), five subjects chose to receive extra itraconazole. Clinical and mycologic cure was observed after four pulses in four subjects and after five pulses in one subject. There were no associated clinical adverse effects with itraconazole therapy. CONCLUSION: With tinea capitis, itraconazole pulse therapy is effective and safe and is associated with high compliance. The pulse regimen enables the duration of treatment to be individualized, according to the extent of disease and its rate of resolution.
Antifungal Agents↗
Itraconazole oral solution for the treatment of tinea capitis.
Twenty-seven children (12 boys, 15 girls, age range 3-11 years, weight range 10-40 kg) were treated with itraconazole oral solution 10 mg/mL given as pulse therapy for tinea capitis. The dosage regimen was 3 mg/kg per day given once daily in a fasting state with each pulse lasting 1 week. The first two pulses were separated by a 2-week off-drug period, and the second and third pulses had a 3-week period without drug between them. For each patient a second and third pulse were administered if there was clinical evidence of tinea capitis at the time-point when the next pulse was due. The overall severity of tinea capitis at pretherapy was classified as mild, moderate or severe with the aetiology being: Trichophyton tonsurans, 24 patients; T. violaceum, two patients and Microsporum canis, one patient. In 19 evaluable patients, 12 weeks after starting therapy, the numbers of pulses of itraconazole oral solution required to produce complete cure were, according to the severity of disease, mild tinea capitis (one pulse: four patients; two pulses: five), moderate disease (one pulse: two patients; two pulses: two; three pulses: two), and severe disease (three pulses: three patients). One patient with moderate severity tinea capitis was clinically clear after three pulses of therapy but mycological examination was positive. Seven patients were lost to follow-up and one discontinued therapy because of nausea. Itraconazole oral solution 3 mg/kg per day was generally well tolerated. Three children developed gastrointestinal adverse effects which were considered to be minor or 'nuisance' effects. The data from this preliminary report need to be confirmed in a larger group of patients. It remains to be seen whether itraconazole oral solution will become a practical alternative to the antifungal agents available in a liquid preparation for the treatment of tinea capitis.
Administration, Oral↗
Evaluation and management of diabetes insipidus.
Diabetes insipidus is an uncommon condition characterized by polyuria and polydipsia. The symptoms and biochemical changes of this condition result from either a lack of antidiuretic hormone or renal insensitivity to its effect. Failure to produce or release antidiuretic hormone may result from cranial pathology, including trauma and surgery. The renal insensitivity to antidiuretic hormone that occurs in patients with nephrogenic diabetes insipidus may be caused by genetic factors, drugs (especially lithium) or specific disease processes. Patients may compensate for polyuria and nocturia by excessive water intake but show marked decreases in urine specific gravity and osmolality. Patients with severe and uncompensated symptoms develop marked dehydration, neurologic symptoms and encephalopathy. The water deprivation test is useful in diagnosing diabetes insipidus and in differentiating neurogenic from nephrogenic cases. Neurogenic diabetes insipidus may respond to nasal administration of desmopressin. Nephrogenic diabetes insipidus requires good hydration and monitoring of body chemistry. Thiazides and amiloride may relieve symptoms.
Algorithms↗