bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of moclobemide on the pharmacokinetics of the 5‐HT1B/1D agonist rizatriptan in healthy volunteers
Authors: Van Haarst A. D. , Van Gerven J. M. A. , Cohen A. F. , De Smet M. , Sterrett A. , Birk K. L. , Fisher A. L. , De Puy M. E. , Goldberg M. R. , Musson D. G.
Published: July 2002

Aims
 The new 5‐HT1B/1D agonist rizatriptan (MK‐0462) has recently been registered for the treatment of migraine. Its primary route of metabolism is via monoamine oxidase‐A (MAO‐A). Antidepressants such as the MAO‐A inhibitor moclobemide may be used in patients with chronic headache syndromes. Hence, this study aimed to investigate the interactions between rizatriptan and moclobemide.

Methods
 In a double‐blind, randomized, placebo‐controlled, two‐period cross‐over study 12 healthy, young volunteers (six males, six females) were treated with moclobemide (150 mg twice daily) or placebo for 4 days. On the fourth day, a single dose of rizatriptan (10 mg) was administered, and subsequently blood and urine samples were collected for assay of rizatripan and N‐monodesmethyl rizatriptan. Plasma concentrates of 3,4‐dihydroxyphenylglycol (DHPG), a marker of MAO‐A inhibition, were also assessed. Supine and standing blood pressure were measured regularly.

Results
 Both treatments were well tolerated. During moclobemide, the increase in supine diastolic blood pressure following rizatriptan administration was augmented. Inhibition of MAO by moclobemide was inferred from a persistent decrease in DHPG level (43% on average). When rizatriptan was coadministered with moclobemide, the area under the plasma drug concentration‐time profiles for rizatriptan and its N‐monodesmethyl metabolite increased 2.2‐fold (90% CI, 1.93–2.47) and 5.3‐fold (90% CI, 4.81–5.91), respectively, when compared with placebo. Peak plasma drug concentrations for rizatriptan and its n‐monodesmethyl metabolite increased 1.4‐fold (90% CI, 1.11–1.80) and 2.6‐fold (90% CI, 2.23–3.14), respectively, and half‐lives of both were prolonged.

Conclusions
 Moclobemide inhibited the metabolism of rizatriptan and its active N‐monodesmethyl metabolite through inhibition of MAO‐A. Thus, moclobemide may considerably potentiate rizatriptan action. Concurrent administration of moclobemide and rizatriptan is not recommended.
Bone mineral density and markers of bone turnover in young adult survivors of childhood lymphoblastic leukaemia
Authors: Hoorweg‐Nijman Jantine J. G. , Kardos Gabriella , Roos Jan C. , van Dijk Henrika J. , Netelenbos Coen , Popp‐Snijders Corrie , de Ridder Christine M. , Delemarre‐van de Waal Henriëtte A.
Published: July 2002

OBJECTIVE

In order to determine if a serious disease like childhood acute lymphoblastic leukaemia (ALL) and the treatment necessary to cure the patients has long term effects on bone mass, we assessed bone mineral density (BMD) and several parameters involved in bone formation in a group of young adult survivors of ALL.

DESIGN AND PATIENTS

Fourteen male and ten female survivors, treated for ALL in childhood, were cross‐sectionally studied, at a mean age of 25.1 years (range 20.1–34.9). All patients, except for two, had received cranial irradiation as part of their treatment (mean radiation dose 2460 cGy).

MEASUREMENTS

Height and weight were measured. Bone mineral density (BMD) was assessed using dual energy X‐ray absorptiometry in the lumbar spine, femoral neck, femoral trochanter and at 1/3 distal and ultradistal in the radius. Early morning serum levels of LH, FSH, oestradiol or testosterone, IGF‐1 and IGF‐BP3 were determined as well as several specific markers of bone turnover.

RESULTS

Mean height, expressed as standard deviation score (SDS) was −1.12, significantly reduced. BMD in the lumbar spine, femoral neck and at 1/3 distal and ultradistal in the radius, was significantly lower compared to the reference population (P < 0.05). No correlation was found between the BMD values and the cumulative dose of administered cytotoxic drugs, the age at diagnosis of ALL or the duration of follow‐up. Mean IGF‐1 and IGF‐BP3 SDS‐scores were −1.24 and −0.78 respectively, significantly reduced. GH stimulation tests performed in a subgroup of 9 patients showed an insufficient peak GH response in at least one test in all tested patients. The values of LH, FSH oestradiol or testosterone were within the normal adult range. Serum markers of bone formation and bone resorption were in the normal range, indicating that bone turnover was normal at the time of the study.

CONCLUSIONS

Bone development in patients cured of acute lymphoblastic leukaemia is disturbed, resulting in a significantly reduced bone mineral density. Impaired growth hormone activity, as a long term effect of cranial irradiation, may be one of the underlying causes as well as the illness itself and the administered cytotoxic drugs. Since a reduced bone mineral density predispose patients to osteoporosis, intervention in order to improve bone mass should be considered.
Suppression of endogenous insulin secretion by exogenous insulin in patients with insulinoma
Authors: Kim Chul‐Hee , Park Joong , Shong Young , Hong Sung , Kim Ghi , Lee Ki‐Up
Published: July 2002

OBJECTIVE

Previous studies have demonstrated that endogenous insulin secretion is not suppressed by exogenous insulin in patients with insulinoma. In this study we examined whether insulin secretion in insulinoma patients is suppressed by exogenous insulin during hypoglycaemia.

SUBJECTS AND METHODS

Sixteen insulinoma patients (5 men and 11 women) and 10 normal subjects were studied. Hyperinsulinaemic glucose clamp studies were performed at both euglycaemia (4.5 mmol/l glucose) and hypoglycaemia (2.5 mmol/l glucose).

RESULTS

In normal subjects, plasma C‐peptide levels were suppressed by 66% during the euglycaemic hyperinsulinaemic clamps (P < 0.01). In contrast, in insulinoma patients, plasma C‐peptide levels increased by 25% during the clamps (P < 0.05). In the hypoglycaemic hyperinsulinaemic clamps, plasma C‐peptide levels were nearly completely (91%) suppressed in normal subjects and partially (39%) suppressed in patients with insulinoma (P < 0.01). The decrease in C‐peptide levels during the hypoglycaemic clamps was > 30% in 12 (75%) of 16 insulinoma patients and > 50% in 8 (50%) patients.

CONCLUSIONS

This study demonstrated that in patients with insulinoma, insulin secretion was not suppressed by exogenous insulin during euglycaemia but was suppressed during hypoglycaemia, although the degree of suppression was less than that in normal subjects. Our results suggest that the feedback regulation of insulin secretion by exogenous insulin is partially retained in patients with insulinoma.
Restoration of species‐rich grassland on arable land: assessing the limiting processes using a multi‐site experiment
Authors: Pywell Richard F. , Bullock James M. , Hopkins Alan , Walker Kevin J. , Sparks Tim H. , Burke Mike J.W. , Peel Steve
Published: July 2002

Agricultural intensification has resulted in the reduction and fragmentation of species‐rich grasslands across much of western Europe.

We examined the key ecological processes that limit the creation of diverse grassland communities on ex‐arable land in a multi‐site experiment over a wide variety of soil types and locations throughout lowland Britain.

The results showed it was possible to create and maintain these communities successfully under a hay‐cutting and grazing management regime. Furthermore, there was a high degree of repeatability of the treatment effects across the sites.

Lack of seed of desirable species was the key factor limiting the assembly of diverse grassland communities. Sowing a species‐rich seed mixture of ecologically adapted grassland plants was an effective means of overcoming this limitation. Community assembly by natural colonization from the seed bank and seed rain was a slow and unreliable process. However, there was no evidence to suggest that sowing a species‐poor grass‐dominated seed mixture made the vegetation any less susceptible to colonization by desirable species than allowing natural regeneration to take place.

Deep cultivation caused significant reductions in soil P and K concentrations across the sites. This had a significant beneficial effect on the establishment and persistence of sown forbs in all years. It also resulted in a significant reduction in the number of unsown weedy grasses. However, for both variables these differences were very small after 4 years.

Sowing a nurse crop significantly reduced the number of unsown grass species, but had no beneficial effect on the establishment of desirable species.

Treatments sown with the species‐rich seed mixture following deep cultivation corresponded most closely to the specified target communities defined by the UK National Vegetation Classification. Natural regeneration and treatments sown with the species‐poor seed mixture were much less similar to the target. The sites on circum‐neutral soils achieved the greatest degree of similarity to the target. Those on calcareous and acid soils failed to achieve their targets and most closely resembled the target for neutral soils. This reflected the poor performance of the sown preferential species for these communities.
Femtosecond near‐field scanning optical microscopy
Authors: Nechay B. A. , Siegner U. , Achermann M. , Morier‐Genaud F. , Schertel A. , Keller U.
Published: July 2002

We have developed an instrument for optically measuring carrier dynamics in thin‐film materials with ≈150 nm lateral resolution, ≈250 fs temporal resolution and high sensitivity. This is accomplished by combining an ultrafast pump–probe laser spectroscopic technique with a near‐field scanning optical microscope. A diffraction‐limited pump and near‐field probe configuration is used, with a novel detection system that allows for either two‐colour or degenerate pump and probe photon energies, permitting greater measurement flexibility than that reported in earlier published work. The capabilities of this instrument are proven through near‐field degenerate pump–probe studies of carrier dynamics in GaAs/AlGaAs single quantum well samples locally patterned by focused ion beam (FIB) implantation. We find that lateral carrier diffusion across the nanometre‐scale FIB pattern plays a significant role in the decay of the excited carriers within ≈1 μm of the implanted stripes, an effect which could not have been resolved with a far‐field system.
Growth Hormone‐Releasing Hormone Decreases Voltage‐Gated Potassium Currents in GH4C1 Cells
Authors: Xu R. , Clarke I. J. , Chen S. , Chen C.
Published: July 2002

Abstract

The electrophysiological properties of anterior pituitary somatotropes integrally involve the function of voltage‐gated K+ currents. In this study, we have used GH4C1 cell lines to investigate the effect of human GHRH on voltage‐gated K+ currents. Because of a clear ‘rundown’ of the K+ current with classic whole cell recording (WCR) without ATP in pipette solution, nystatin‐perforated WCR was the major recording configuration used. Using a low Ca2+ (0.5 mM) bath solution containing Co2+ (1 mM) and TTX (1 μM), GH4 cells predominantly exhibited an outward delayed rectifier K+ current (IK). Local application of growth hormone releasing hormone (GHRH) (100 nM) reversibly reduced the amplitude of the K+ currents (to 83% of control). There was no effect of GHRH on the activation curve of the K+ current and no difference observed using 2.5 mM Ca2+ or low Ca2+ (0.5 mM Ca2++1 mM Co2+) bath solutions. Under the condition of low Ca2+ bath solution, the application of apamin (1 μM) or charybdotoxin (1 μM), two specific blockers of the Ca2+‐activated K+ current, did not alter the K+ current or the response to GHRH. This reduction in the K+ current by GHRH was also observed with classic WCR with a pipette solution containing ATP (2 mM). The GHRH‐induced reduction in the K+ current was completely abolished by the presence of GDP‐β‐s (500 μM) in the pipette solution or by addition of PKC inhibitors, calphostin C (100 nM) and chelerythrine (1 μM), in bath solution. Inhibitor for cAMP‐PKA system (Rp‐cAMP and H89) did not affect the K+ current response to GHRH. These results suggest that GHRH reduces the voltage‐gated K+ current in GH4C1 cells, a response that is mediated by G‐proteins and PKC system but not by cAMP‐PKA system. The reduction in the K+ current may partially contribute to the GHRH‐stimulated growth hormone (GH) secretion.
Functional consequences of mutations in the conserved ‘signature sequence’ of the ATP‐binding‐cassette protein MalK
Authors: Schmees Günter , Stein Anke , Hunke Sabine , Landmesser Heidi , Schneider Erwin
Published: July 2002

The binding‐protein‐dependent maltose‐transport system of enterobacteria, a member of the ATP‐binding‐cassette (ABC) transporter superfamily, is composed of two integral membrane proteins, MalF and MalG, and two copies of an ATPase subunit, MalK, which hydrolyze ATP, thus energizing the translocation process. Isolated MalK displays spontaneous ATPase activity, whereas in the assembled MalFGK2 complex, reconstituted in liposomes, ATP hydrolysis requires stimulation by the substrate‐loaded extracellular maltose‐binding protein, MalE. The ATPase domains of ABC transporters, including MalK, share a unique sequence motif (‘LSGGQ’, ‘signature sequence’ or ‘linker peptide’) with as yet unknown function. To elucidate its role in the transport process, we investigated the consequences of mutations affecting two highly conserved residues (G137, Q140) in the MalK–ATPase of Salmonella typhimurium, by biochemical means. Residues corresponding to Q140 in other ABC proteins have not yet been studied. All mutant alleles (G137→ A, V, T; Q140→ L, K, N) fail to restore a functional transport complex in vivo. In addition, the mutations increase the repressing activity of MalK on other maltose‐regulated genes when compared with wild‐type MalK. Purified variants of G137 have lost the ability to hydrolyze ATP but still display nucleotide‐binding activity, albeit with reduced affinity. Binding of MgATP results in similar protection against trypsin, as observed with wild‐type, indicating no major change in protein structure. In contrast, the variants of Q140 differ in their properties, depending on the chemical nature of the replacement residue. MalKQ140L fails to hydrolyze ATP and exhibits a strong intrinsic resistance to trypsin in the absence of MgATP, suggesting a drastically altered conformation. In contrast, the purified mutant proteins Q140K and Q140N display ATPase activities and MgATP‐induced changes in the tryptic cleavage pattern similar to those of wild‐type. However, mutant transport complexes containing the Q140K or Q140N variants, when studied in proteoliposomes, are severely impaired in MalE‐maltose‐stimulated ATPase activity. These results are discussed with respect to the crystal structure of the homologous HisP protein [Hung, L.‐W., Wang, I.X., Nikaido, K., Liu, P.‐Q., Ames, G.F.‐L. & Kim, S.‐H. (1998) Nature (London)396, 703–707] and are interpreted in favor of a role of the signature sequence in activating the hydrolyzing activity of MalK upon substrate‐initiated conformational changes in MalF/MalG.
Bacterial invasion of corneal epithelial cells
Authors: MRepSc V Vallas , McOptom F Stapleton , PhD M D P Willcox
Published: July 2002

Purpose: The normal ocular surface is frequently colonized by commensal Gram‐positive species. Gram‐negative bacteria are often implicated in corneal infection and inflammation, particularly in association with soft contact lens wear. The aim of this study was to elucidate possible mechanisms of virulence in ocular bacteria.

Methods: The susceptibility of a human corneal epithelial cell line to bacterial invasion and association was evaluated using the gentamicin exclusion assay. Organisms tested included isolates from corneal ulcers, corneal inflammation and ocular sites in asymptomatic individuals.

Results: The commensal, non‐pathogenic bacterium Staphylococcus epidermidis and some pathogenic strains of Serratia marcescens did not invade corneal epithelial cells. In contrast, pathogenic strains of Pseudomonas aeruginosa associated with and invaded corneal epithelial cells.

Conclusions: The increased association of P. aeruginosa, compared to other bacterial types, might be a reason for the more frequent association of this bacterium with contact‐lens‐associated microbial keratitis.
Radiation oncology in Australia: Workforce, workloads and equipment 1986–1999
Authors: Wigg David R , Morgan Graeme W
Published: July 2002

Regular national surveys of all public and private radiation oncology facilities in Australia have been carried out between 1986 and 1999. Workforce data recorded were numbers of radiation oncologists and trainees, radiation therapists, medical physicists and physics technicians, nursing staff, data managers, social workers and clerical staff. Workloads included treatments with megavoltage beams (linear accelerators, cobalt‐60), orthovoltage/superficial X‐rays, brachytherapy, total body irradiation and stereotactic radiosurgery. Major equipment recorded included numbers of megavoltage and orthovoltage/superficial X‐ray machines, planning simulators, computerized dosimetry systems and brachytherapy equipment. The use of radiotherapy beds and the public–private mix of treatments were also documented. Data were assembled for Australia based on each individual state. Within Australia the number of public and private treatment facilities has increased by 44% from 18 in 1986 to 26 in 1999. The population has increased by 16.4%, cancer incidence by 51.8% and megavoltage workloads (fields) by 102%. The number of radiation therapists and physicists and the number of linear accelerators have, in general, increased with the growth in workloads. The number of radiation oncologists has increased by 60% from 4.5 full‐time equivalent (FTE) radiation oncologists per million population in 1986 to 7.2 per million in 1999. There is currently a deficit of at least 40 radiation oncologists to be able to treat the 50% of newly diagnosed cancer patients requiring radiotherapy. In addition, a significant deficiency exists in numbers of radiation therapists, nursing staff, data managers, social workers and clerical staff. Clearly the demands for medical physicists has increased but the data are insufficient to comment on deficiencies. Despite the increases in workloads the proportion of patients with cancer receiving radiotherapy remains below 40%. A positive correlation has been shown between the proportion of newly diagnosed cancer patients treated and the number of FTE radiation oncologists, the number of megavoltage machines and number of radiation therapists. This was shown for Australia as a whole, for each state and for the years 1986 to 1999. This was also the case when total megavoltage fields was used as the dependent variable. Multiple regression analysis using the same independent variables confirmed these positive correlations. It is concluded that the low treatment rate with radiation oncology for cancer patients in Australia is due mainly to the lack of resource allocation. The stated commitment of governments and health departments to a 50% treatment rate can only become a reality if there is a concerted effort to increase the numbers of radiation oncologists, radiation therapists, megavoltage machines and support staff. Otherwise at least one in every 10 newly diagnosed cancer patients will continue to be denied adequate and equitable access to radiotherapy – in 1999 that total figure was 9400 persons.
Breast radiotherapy: An Australasian survey of current treatment techniques
Authors: Delaney Geoff , Blakey David , Drummond Roslyn , Kenny Lizbeth , Centre Radiation Oncology Advisory Group to the National Breast Can
Published: July 2002

Prior to the dissemination of evidence‐based quality assurance guidelines, the Australian National Breast Cancer Centre Radiation Oncology Group conducted a process survey of breast radiotherapy treatment delivery throughout Australia. A process survey was conducted in August/September 1998. This survey comprised questions enquiring about treatment positioning, immobilization devices used, planning strategies, simulation and dose computation methods, treatment prescribing and quality assurance. The survey was sent to 123 Australian fellows of the Royal Australian and New Zealand College of Radiologists (RANZCR) and to the six directors of New Zealand radiation oncology departments. Fifty‐eight questionnaires were returned of which 38 were received from individuals and 20 represented a reply from a department with a routine breast radiotherapy protocol (representing an average of 4.5 radiation oncologists per reply). The study identified great consistency between departments with respect to dose and fractionation for breast tangents. The study also identified some areas of treatment planning and delivery that varied between individuals or departments. These mainly reflected a lack of evidence in some areas of radiotherapy treatment delivery. The circulation of quality assurance guidelines will perhaps improve consistency of radiotherapy techniques in which studies have identified that technique changes improve outcome. This study identified that these areas include the taking of simulation and port films and the use of off‐axis dosimetry. Further studies are required for areas of radiotherapy treatment delivery that have little evidence for or against their implementation.
Breast conservation in BRCA1 or BRCA2 mutation carriers with early stage breast cancer
Authors: Phillips Kelly Anne , McKay Michael J
Published: July 2002

The role of breast conservation therapy (limited surgery and irradiation of the breast with/without axilla) in the approximately 5% of breast cancer patients who harbour a germline mutation in BRCA1 or BRCA2, is a largely unexplored area and is seen by some as controversial. The relatively high cumulative risk of second primary cancers in such patients and concern about a possible decreased ability of mutation carriers to repair DNA damage caused by radiation has fuelled this controversy. Published studies of breast conservation therapy in carriers of a mutation in BRCA1 or BRCA2 are reviewed, with particular attention to their methodology. These studies have not demonstrated any increase in radiation sensitivity of normal tissues in mutation carriers, either in terms of increased early or late toxicity or tumourigenesis. Likewise, tumour sensitivity to radiotherapy, which might be expected based on the known functions of the BRCA1 and BRCA2 genes, has not been documented to date in mutation carriers. Further, methodologically rigorous studies of large numbers of breast cancer patients who carry a mutation in BRCA1 or BRCA2 are required to fully elucidate these issues.
Prognostic factors in muscle‐invasive bladder cancer treated with radiotherapy: an immunohistochemical study
Authors: Osen  , FossÅ  , Majak  , RØtterud  , Berner
Published: July 2002

Objective

 To determine the prognostic role of p53, Ki‐67 and p21 for patients with muscle‐invasive bladder cancer treated with curative intent by radiotherapy.

Patients and methods

 The study included 131 patients (24 women and 107 men, median age 72 years, range 40–86) with transitional cell carcinoma (T2‐T4) treated with external definitive pelvic radiotherapy between 1985 and 1994. Paraffin‐embedded pretreatment biopsies from the patients were examined for the presence of p53, p21 and Ki‐67, detected by immunohistochemistry, and related to tumour stage, grade and patient survival.

Results

 The expression of p53 protein correlated positively with the detection of Ki‐67 (P<0.05) but did not correlate with p21. None of the immunohistochemical variables (p53, p21 or Ki‐67) correlated with T category and only Ki‐67 correlated with histological grade. Patients with >5% p21 expression tended to live longer than those with <5% (P=0.09). In a multivariate analysis, the T category (T2/T3 vs. T4), histological grade (2 vs. 3) and p21 expression (≤5% vs. >5%) were independent prognostic factors for overall survival.

Conclusion

 Further investigation is warranted in patients with muscle‐invasive bladder cancer undergoing different types of treatment. p21 seems to play an independent prognostic role in these patients, in addition to T category and grade.
Evaluation of an on‐call diabetes service in a large teaching hospital
Authors: Perros P. , Frier B. M.
Published: July 2002

Aims To assess prospectively the activity and effectiveness of a diabetes specialist on‐call service.

Methods All requests for specialist advice received by the doctor on‐call for diabetes in a large teaching hospital were recorded and analysed over a period of 3 weeks.

Results The total number of calls was 135 (mean 45 per week) of which 48.1% were outside normal working hours. Requests for advice from surgical and medical ward staff accounted for 43% of calls, the remainder were from staff in the maternity ward (12.6%), staff in other hospitals in the city (3.7%), general practitioners (13.3%) and patients (27.4%). The time spent by the on‐call doctor for diabetes responding to calls was a mean of 8.6 h per week. The number of acute admissions prevented by this service was estimated to be 11 (3.6 per week).

Conclusions Open access to specialist advice provided by a doctor with expertise in diabetes is an effective adjunct to the delivery of diabetes care in the setting of a large teaching hospital.
Tinea barbae associated with erythema nodosum in an immunocompetent man
Authors: Foti C , Diaferio A , Daddabbo M , Angelini G
Published: July 2002

We describe the case of a 45‐year‐old man with atopy who developed marked inflammatory lesions on the bearded area of the face caused by Tricophyton rubrum, an anthropophilic fungus not frequently correlated with kerion of the face. After starting therapy with griseofulvin, he developed typical lesions of erythema nodosum on both legs. We discuss how these lesions could be correlated with the kerion of the face.
Improved computing scheme for measuring eye alignment with Purkinje images I and IV
Authors: Barry J. C. , Backes A. , Pongs U. M. , Kirschkamp T. , Dunne M. C. M.
Published: July 2002

This study introduces an improved computing scheme for determining eye rotation from Purkinje images I and IV. The original computing scheme systematically underestimated eye rotation. Paraxial raytracing calculations revealed that this error resulted from failure to account for the fact that Purkinje images I and IV fall al different distances behind the cornea. The error could be overcome with a correction factor derived from paraxial raytracing calculations. A series of experiments were carried out to test the validity of this correction factor; involving exact raytracing calculations as well as measurements on physical model eyes and human eyes. The influence on the correction factor of ocular surface asphericity, accommodation, age and ocular component variations were examined. The new method was also compared to Hirschberg's technique, which makes use of Purkinje image I alone, as a means of screening for strabismus.
Therapeutic Plasma Exchange in Treatment of Adrenoleukodystrophy
Authors: Bambauer Rolf , Schiel Ralf , Cordes Heinz , Latza Reinhard
Published: July 2002

Abstract: Adrenoleukodystrophy (ALD) is an X‐linked disorder of metabolism of very long‐chain fatty acids (VLCFA) with a frequency of up to 1:20,000 in males. VLCFA C 24:0 and C 26:0 accumulate in the cholesterolester and ganglioside fraction in plasma and red cells. Symptoms of ALD are ataxia, loss of visual and auditory functions, and cerebral convulsions. Presently, no sure therapeutic approaches are established. Efforts were reported by dietary regimens with VLCFA‐restriction and glyceroltrioleate and glyceroltrierucate intake. In the present trial, we report on a 58‐year‐old white male suffering from progressive ALD with spastic paraparesis. He has a positive family history back to the 18th century. In this patient, although maximum dietary therapy was applied over a period of 60 months, no normalization of VLCFA C24:0 and C26:0 was reached, and neurological disorders were progressive. As a result, therapeutic plasma exchange (TPE) was applied from 1990 to 1994. Then, for more selective adsorption of VLCFA, dextran‐sulfate adsorption (Liposorber, Kaneka, Osaka, Japan) until 1996, and after that, immunoadsorption (Therasorb, Baxter, Munchen, Germany) were used. During these periods (total, 101 months), VLCFA C 24:0 and C 26:0 levels were reduced by 55% and 50% (p < 0.001). The patient experienced a significant improvement in performance and general well‐being. No further progression of neuronal disorders was documented. This anecdotal data suggest a very beneficial effect of TPE in treatment of progressive ALD.
Development of a Rapid Blood Transfusion System with the Capability of Blood Purification
Authors: Omokawa Susumu , Notoya Takeshi , Kumagai Mikako , Takeda Goro
Published: July 2002

Abstract: Blood is usually irradiated by x‐ray to prevent graft‐versus‐host‐disease. However, plasma potassium levels of irradiated blood are rapidly increased during preservation in irradiated blood. The objectives of this study were to develop a rapid blood transfusion system for which irradiated blood can be used and to evaluate the capability of blood purification of the system. Packed red blood cells (RBC) were irradiated (15 Gy x‐ray) at 21 days and preserved until 42 days after collection. A blood mixture of RBC and plasma was perfused through a dialyzer at 25, 50, 100, and 200 ml/min. Dialysate was perfused at 100, 100, 500, and 500 ml/min, respectively. Preperfusion levels of sodium, 121; potassium, 35; and chlorine, 76 mEq/L were changed to sodium, 144 to 146; potassium 2.5 to 3.0; and chlorine, 105 to 110 mEq/L, which were comparable with the levels in dialysate after perfusion for 25, 50, and 100 ml/min perfusion groups. For the 200 ml/min perfusion group, potassium was 5.3 mEq/L after perfusion which was slightly higher than other groups, but 84% of the potassium was removed by the system. Citrate levels were significantly decreased to 3.4, 28, 31, and 81 mg/dl for the 25, 50, 100, and 200 ml/min groups, respectively, after perfusions. The rapid transfusion system composed of the dialyzer and the blood pumps was effective in the removal of potassium and in the normalization of electrolytes. Irradiated blood with high levels of potassium can be safely and effectively used for this system in cases requiring massive rapid blood transfusion.
MONONEURITIS MULTIPLEX ASSOCIATED WITH POSITIVITY FOR LUPUS ANTICOAGULANT (LA)
Authors: Logullo F. , Di Bella P. , Morresi S. , Manicone M. , Cappelli M. , Danieli M.G.
Published: July 2002

Peripheral neuropathy is a common complication of systemic necrotizing vasculitis. Vasculitis may also selectively affect the peripheral nervous system (non‐systemic vasculitic neuropathy). We describe two patients affected with overlapping mononeuritis multiplex (MM) associated with LA—positivity in absence of sural nerve biopsy proven involvement of vasa nervorum. Both had livedo reticularis in distal upper and lower limbs. There were no signs of pulmonary, renal, gastrointestinal, ear, nose or throat involvement. Skin biopsy showed a thrombotic microangiopathy. Serological abnormalities were limited to an elevated ESR in one patient and LA—positivity in both. One patient was affected by recurrent brain focal ischemia one year before the onset of MM leading to death. MM associated with LA—positivity has previously been described only in four patients and deserves further investigation to highlight the pathogenetic significance of this association.
THE CONNEXIN 32 NERVE‐SPECIFIC PROMOTER IS DIRECTLY ACTIVATED BY Egr2/Krox20 IN HeLa CELLS
Authors: Musso M. , Balestra P. , Bellone E. , Di Maria E. , Cassandrini D. , Ajmar F. , Mandich P.
Published: July 2002

Connexin 32 (Cx32) belongs to a protein family that forms intercellular channels mediating the exchange of ions and chemical messengers. In the peripheral nervous system (PNS) Cx32 is expressed in Schwann cells and contributes to the homeostasis and structural integrity of myelin. Mutations of this gene determine X‐linked form of Charcot Marie‐Tooth (CMTX) disease. Cx 32 is transcriptionally regulated in a tissue‐specific manner by two different promoters termed P1 and P2. P2, active in Schwann cells, is located 5 kb downstream from the P1 promoter and at 500 bp from the exon 2 that contains the entire coding region.

Previously, by Electrophoretical Mobility Shift Assay (EMSA) we have identified a sequence (‐101/‐93), within P2, specifically recognized by recombinant Egr2. In order to prove the direct involvement of Egr2 in the transcriptional control of the Cx32 gene, we have performed transfection experiments in HeLa cells with a luciferase driven by the P2 promoter in presence or not of a vector expressing Krox20, the mouse homologue of human Egr2. We have found that the construct in which the sequence ‐103/‐93 is mutated is not activated as well as the wild type sequence. Moreover we have detected another upstream sequence (‐236/‐213) recognized by recombinant Egr2 and other transcription factors present in HeLa nuclear extract like SP1. The construct, lacking this sequence and carrying the mutated downstream Egr2 recognition sequence, is not activated at all by Krox20. Taken together these findings strongly suggest the role of Egr2 in the transcriptional control of Connexin 32 through both sequences.

The laboratory is a member of the European CMT Consortium; partially granted by Ministero della Sanit… to PM, MURST and Ateneo to FA.
INCREASED CSF PROTEINS IN CMT1A: ROLE OF ROOT HYPERTROPHY OR SUPERIMPOSED CIDP?
Authors: Pareyson D. , Erbetta A. , Taroni F. , Milani M. , Lauria G. , Ciano C. , Scaioli V. , Morbin M. , Sghirlanzoni A. , Testa D.
Published: July 2002

A 45‐year‐old male patient came to our observation with a clinical picture of slowly progressive wasting and weakness of distal limb muscles, mild distal sensory to all modalities, with pes cavus and hammer toes. His parents were consanguineous and both were affected by Charcot‐Marie‐Tooth disease (CMT). In the patient, disease onset occurred at age 11. Disease course was slowly progressive, but a somewhat sudden worsening had occurred three years before; muscle wasting and weakness were slightly asymmetrical. A previous spinal tap had demonstrated very high levels of CSF proteins (about 300 mg/dl). When admitted to our hospital, a repeat CSF examination revealed even higher protein content (380 mg/dl), raising the hypothesis of CIDP (chronic inflammatory demyelinating polyradiculoneuropathy) superimposed on CMT. Nerve conduction studies showed a diffuse and uniform nerve conduction slowing (10–12 m/s in limb nerves). Molecular analyses demonstrated the common 17p11.2 duplication of CMT1A. We performed nerve biopsy looking for signs of nerve inflammation, and MR scan of lumbar roots searching for evidence of blood‐root barrier disruption and root inflammation (root enhancement). We administered to the patient two courses of high dose intravenous immunoglobulin (IVIg), followed by steroid treatment for some weeks: there was a questionable clinical improvement and CSF protein content slightly decreased (288 mg/dl). Nerve biopsy showed the typical features of CMT1A with diffuse onion‐bulb formations, but neither focal abnormality nor inflammatory infiltrates were observed. MR scan demonstrated very mild enhancement of lumbar nerve roots after gadolinium administration, but the most impressive finding was a striking hypertrophy of the lumbar roots, which were overall much thicker than the cord itself and filled almost completely the spinal canal. Although superimposition of CIDP cannot be excluded, root hypertrophy causing leakage of the blood‐root barrier or even block of the CSF circulation appears the most likely explanation of the incredible rise of CSF protein content in this case.

Partly supported by a grant from the Italian Ministry of Health.
Prompted Voiding for Nighttime Incontinence in Nursing Homes: Is it Effective?
Authors: Ouslander Joseph G. , Ai‐Samarrai Nahia , Schnelle John F.
Published: July 2002

OBJECTIVES: To determine whether prompted voiding (PV) is effective for nighttime urinary incontinence in nursing home (NH) residents and whether residents who respond well to daytime PV also respond well at night.

DESIGN: Prospective case series.

SETTING: Four community NHs.

PARTICIPANTS: Sixty‐one long‐stay incontinent NH residents of mean age 88 years, 75% female.

MEASUREMENTS: The percentage of hourly checks for wetness and the appropriate toileting rate (continent voids divided by total voids) were measured during 3 days (7 a.m.–7 p.m.) of PV, and for an average of 5 nights (7 p.m.–7 a.m.), during which a modified PV protocol, designed to be minimally disruptive to sleep, was carried out.

RESULTS: Fourteen residents (23%) responded well to daytime PV, with average wetness and appropriate toileting rates of 5% and 73%, respectively. In the group as a whole, nighttime PV was not effective, with wetness and appropriate toileting rates of 49% and 18%, respectively. Among those who responded well to daytime PV, wetness rates during nighttime PV remained significantly higher than during the day (24% vs 5%; P = .000), and nighttime appropriate toileting rates were significantly lower (39% vs 73%; P = .002). The poor response rate at night was primarily observed between 10 p.m. and 6 a.m.

CONCLUSIONS: In this sample of incontinent NH residents, nighttime PV, even when carried out so as to minimize sleep disruption, was not an effective intervention. Although residents who responded well to daytime PV responded better to nighttime PV than those who did not respond to daytime PV, their wetness rates remained relatively high and their appropriate toileting rates were low. These data suggest that routine nighttime toileting programs should not be carried out for the majority of incontinent NH residents. Instead, individualized care based on resident's preferences, willingness to toilet at night, and sleep patterns should be emphasized. J Am Geriatr Soc 49:706–709, 2001.
Plasma levels after peroral and topical ibuprofen and effects upon low pH‐induced cutaneous and muscle pain
Authors: Steen Astrid E. , Reeh Peter W. , Geisslinger Gerd , Steen Kay H.
Published: July 2002

Cutaneous applications are gaining popularity in the treatment of cutaneous pain and of painful disorders in joints and muscle. The low pH‐pain model in human skin has previously been able to demonstrate the effects of NSAIDs in dose‐dependent manner and to establish time‐effect relationships. We examined the analgesic action of ibuprofen after cutaneous application and compared the effects with oral administration. The two studies (with n = 12 subjects each) were performed in a double‐blind, randomized fashion with a 1‐week cross‐over interval. In study 1 volunteers received intradermal infusions with phosphate buffered saline solution of pH 5.2 and received either 800 mg ibuprofen per os and topical placebo, or 4 g of a 5% commercial ibuprofen gel topically applied and oral placebo capsules, respectively. In study 2 the same protocol was applied with painful intramuscular infusion of stronger, isotonic phosphate buffer (pH 5.2). The flow rate of the pH‐infusion was individually adjusted to induce pain with a magnitude of 20% on a visual analogue scale (ranging from ‘no’ (0%) to ‘unbearable pain’ (100%)). Ibuprofen (S‐, R‐) plasma levels after oral administrations were measured with HPLC, and after topical applications, by gas chromatography combined with mass spectroscopy to determine plasma levels in the range of ng/ml. In the cutaneous model pain ratings decreased to zero after topical verum gel within 45 min of the observation period of 55 min. Pain reduction after peroral ibuprofen was of the same magnitude, but was achieved within only 30 min. In the muscle model, the commercial ibuprofen gel did not reduce the pain in the acidic muscle. The peroral ibuprofen was less effective in the muscle compared to the skin pain model, although there was a significant progressive pain reduction within 55 min. Reasons for the differential susceptibility of cutaneous vs muscular acidosis pain to ibuprofen remain to be established.
Leaf Phenology and Seasonal Carbon Gain in the Invasive Plant, Bunias orientalis L.
Authors: Zotz G. , Franke M. , Woitke M.
Published: July 2002

Abstract: In two potentially competing herbaceous plants, the invasive Bunias orientalis L. (Brassicaceae) and the native Picris hieracioides L. (Asteraceae), seasonal changes in leaf CO2 gas exchange and plant growth were studied over an entire growing season from February 1998 to December 1998 in two experimental fields. The study was motivated by the hypothesis that pre‐adaptive phenological displacement of alien species relative to the native flora may be an important reason for the observed expansion of B. orientalis in central Europe. We quantified the importance of phenological differences for annual carbon gain in both species by estimating total leaf carbon gain from the results of leaf CO2 exchange and changes in plant leaf area. Bunias orientalis achieved almost half of its annual carbon gain in the time between early September and December, when competition for light by other species, like P. hieracioides, is low. Our quantitative approach corroborates the notion that the phenological shift of a relatively poor competitor, such as B. orientalis, could be of great importance for the success as an invasive species.
The Phylogeny of the Families Lecanoraceae and Bacidiaceae (Lichenized Ascomycota) Inferred from Nuclear SSU rDNA Sequences
Authors: Ekman S. , Wedin M.
Published: July 2002

Abstract: The phylogeny of the families Lecanoraceae and Bacidiaceae (Lecanorales, Ascomycota) was investigated using 29 nuclear small subunit ribosomal DNA sequences, 9 of which were newly determined. The data set contained 368 variable characters, 234 of which were parsimony‐informative. Phylogenetic estimations were performed with maximum parsimony and maximum likelihood optimality criteria. In the most parsimonious and most likely reconstructions, the Bacidiaceae sensu Hafellner 1988 forms a monophyletic group and the Lecanoraceae sensu Hafellner a paraphyletic group. The genera Tephromela and Scoliciosporum appear to belong outside these families. However, the hypothesis that the Lecanoraceae sensu Hafellner is monophyletic cannot be rejected, as indicated by a Kishino‐Hasegawa test. Three hypotheses were rejected by Kishino‐Hasegawa tests, viz. (1) that the Lecanoraceae and Bacidiaceae together form a monophyletic group; (2) that both the Lecanoraceae (incl. Scoliciosporum) and Bacidiaceae (incl. Tephromela) are monophyletic; and (3) that the ascus apex anatomy reflects phylogeny. The suborder Lecanorineae is paraphyletic unless the Stereocaulaceae and Cladoniaceae are included. One or both of the Bacidia and Lecanora types of ascus have probably evolved at least twice.
In Situ and in Vitro Binding of Natriuretic Peptide Hormones in Tradescantia multiflora
Authors: Suwastika I. N. , Toop T. , Irving H. R. , Gehring C. A.
Published: July 2002

Abstract: An increasing body of evidence suggests that in plants, as in vertebrates, biologically active natriuretic peptide (NP) hormones play an important role in the regulation of the osmotic and ionic balance. The evidence includes isolation and immunoaffinity purification of biologically active natriuretic peptide analogues (irPNP) from ivy that promoted stomatal opening and specifically, rapidly and transiently increased cGMP levels in root conductive tissue. In this study we demonstrate that I125‐rat atrial natriuretic peptide (rANP) binds to plasma membranes from leaf and stem tissue of Tradescantia multiflora and importantly, both unlabelled rANP and irPNP can competitively displace that binding. In addition, tissue section autoradiography reveals specific in situ binding of I125‐rANP to leaf and stem tissue. The findings are consistent with the presence of a biologically active NP system in plants and suggest that NPs signal through a dedicated receptor system.
Allozyme Diversity in Populations of Cymbidium goeringii (Orchidaceae)
Authors: Chung Mi Yoon , Chung Myong Gi
Published: July 2002

Abstract: Using 14 allozyme loci, we investigated levels of genetic diversity within populations, and degree of genetic divergence among 24 populations of Cymbidium goeringii (Orchidaceae) in Korea and Japan. Cymbidium goeringii maintains high levels of genetic diversity both at population (mean expected heterozygosity, He = 0.238) and species levels (0.260). Means of He found in 24 populations were not significantly different from each other. About 90 % of the total variation in the species is common to all populations (mean GST = 0.108). No unique allele was found in any population. The indirect estimate of gene flow based on the mean GST was high (Nm = 2.06). Nei's genetic identities for pairs of populations had high values (mean = 0.974 [SD = 0.013]). The Mantel‐Z test showed a significant correlation between genetic distance and geographic distance. However, the mean GST value between 17 populations in Korea and seven Japanese populations was relatively low (0.029), even though the land connection between the southern Korean peninsula and southern Japanese archipelagos has not existed since the middle Pleistocene. Large numbers of small seeds of C. goeringii might travel long distances by wind from populations to populations both in Korea and Japan, increasing genetic diversity within populations and maintaining low genetic differentiation among populations.
Guided-wave optical wavelength demultiplexer using an asymmetric Y junction
Authors: Negami T. , Haga H. , Yamamoto S.
Published: July 2002

An optical wavelength demultiplexer using an asymmetric Y junction is numerically analyzed and the experimental results are reported. This demultiplexer utilizes both the mode splitting characteristic of an asymmetric Y junction and the waveguide dispersion of channel waveguides. Analysis shows that the device with step-index profile has more than 20 dB isolation for wavelengths with 6.5% separation from the center wavelength. The fabricated device composed of two-step ion exchanged soda-lime glass waveguides coated asymmetrically with Corning 7059 glass thin film separated the lights of 0.63 and 0.84 μm wavelengths.
Effect of quasibound-state lifetime on the oscillation power of resonant tunneling diodes
Authors: Brown E. R. , Parker C. D. , Sollner T. C. L. G.
Published: July 2002

A new equivalent circuit is derived for the double-barrier resonant tunneling diode. An essential feature of this circuit is the addition of an inductance in series with the differential conductance G of the device. The magnitude of the inductance is τN/G where τN is the lifetime of the (Nth) quasibound state through which all of the conduction current is assumed to flow. This circuit model is used to derive values of theoretical oscillator power that are in much better agreement with experimental results than theoretical predictions made without the inductance. The conclusion is drawn that the response of the double-barrier structure to a time varying potential is consistent with the coherent picture of resonant tunneling.
Optimization of the efficiency in gyrotron backward-wave oscillator via a tapered axial magnetic field
Authors: Ganguly A. K. , Ahn S.
Published: July 2002

The efficiency of a gyrotron backward-wave oscillator (gyro-BWO) in the presence of a tapered axial guide magnetic field is calculated from a three-dimensional self-consistent theory. The saturation efficiency has a low value in the range 10–15% when the external magnetic field is uniform. However, the efficiency can be enhanced to over 30% by a small taper in the magnetic field. Numerical results are shown for operation in the TE11 mode of a cylindrical waveguide.