bluuebunny/crossref_metadata_2025 huggingface dataset:
No evidence for accumulation of insulin glargine (LANTUS®): a multiple injection study in patients with Type 1 diabetes
Authors: Heise T. , Bott S. , Rave K. , Dressler A. , Rosskamp R. , Heinemann L.
Published: March 2003

AimsInsulin glargine is a long‐acting insulin analogue that is metabolically active for at least 24 h. We investigated the multiple‐dose pharmacokinetic properties of insulin glargine to determine whether daily injections lead to the accumulation of circulating insulin levels and a corresponding decrease in blood glucose levels in patients with Type 1 diabetes.

MethodsFifteen patients using preprandial insulin lispro (mean age 36 ± 9 years, body mass index 24.6 ± 2.2 kg/m2) completed the study. Each patient’s optimal insulin glargine dose was determined during a dose‐finding phase. After a washout period, patients were treated over 12 days with a constant daily dose of insulin glargine injected in the abdominal subcutaneous adipose tissue at 22:00 h, and with preprandial insulin lispro. Free serum insulin (FSI) and blood glucose concentrations were assessed hourly after the first, fourth, and eleventh injection, after which patients fasted for 24 h and did not use any other insulin preparation.

ResultsThere were no changes in daily insulin doses during the dose‐finding phase (insulin glargine: initial dose 24 ± 6 IU, mean change 0 ± 3 IU; insulin lispro: 18 ± 9 IU, 0 ± 7 IU). The time course of FSI was comparable on the three pharmacokinetic study days. Notably, the trough FSI at the end of the sampling periods was almost identical (day 1, 79 ± 56 pmol/l, day 4, 77 ± 56 pmol/l, day 11, 86 ± 60 pmol/l). No changes occurred in any of the pharmacokinetic parameters studied.

ConclusionsThere is no evidence that insulin glargine accumulates after multiple injections over 12 days. These results indicate that the predetermined dose of insulin glargine will not need to be reduced after commencing treatment because of a risk of accumulation.
Clinical outcome of diabetes patients hospitalized with foot ulcers, Dar es Salaam, Tanzania
Authors: Gulam‐Abbas Z. , Lutale J. K. , Morbach S. , Archibald L. K.
Published: March 2003

Aims To determine the prevalence rate, clinical features, risk factors, and clinical outcome of foot ulcers in diabetes patients admitted to Muhimbili National Hospital, Dar es Salaam, Tanzania.

Methods A prospective cohort study of newly hospitalized, adult diabetes patients with foot ulcers was conducted during January 1997 to December 1998 (study period). Detailed clinical and epidemiological data were recorded for each patient, followed by a comprehensive physical examination. Clinical outcome was documented.

Results Of 627 diabetes patients evaluated during the study period, 92 (15%) had foot ulcers. Of these 92 patients, 30 (33%) were selected for surgery (minor and major amputations); the rest were managed conservatively. Patients who underwent surgery were more likely than those who did not to have gangrene (P < 0.001) or neuropathy (P < 0.01). On stratification by severity of ulcers, patients with Wagner score ≥ 4 were significantly more likely than those < 4 to have neuroischaemic foot lesions (P < 0.001) or delayed presentation to hospital (P < 0.001). The overall mortality rates for amputees and non‐amputees were similar (29%); the highest in‐patient mortality rate (54%) was observed among patients with severe (Wagner grade ≥ 4) ulcers who did not undergo surgery.

Conclusions Diabetic foot ulcers are associated with significant morbidity and mortality in Tanzania. Mortality rates among patients with severe ulcers remain high despite surgery. Thus, surgery undertaken during the less severe stages of ulcers may improve patient outcome. Education of patients should underscore the importance of foot care and consulting a doctor during the early stages of foot ulcer disease.
Adherence to oral hypoglycaemic agents prior to insulin therapy in Type 2 diabetes
Authors: Evans J. M. M. , Donnan P. T. , Morris A. D.
Published: March 2003

Aim To investigate whether patients require insulin as a result of poor adherence to oral hypoglycaemic agents (OHAs) in Type 2 diabetes.

Methods A diabetes information system and a database of drugs dispensed for the study period 1993–1996 were used in Tayside, Scotland (population 400 000). Patients aged over 34 years with Type 2 diabetes who had at least 6 months exclusive therapy with OHAs (sulphonylureas or metformin) prior to insulin treatment were identified. Intended duration of every OHA prescription was calculated from prescription details. Adherence was estimated by dividing total intended duration of OHA therapy by study time for each patient, and compared between those who did and did not convert to insulin.

Results There were 2537 patients on sulphonylureas (51% male, mean age 67 years). There was improved adherence in the 262 patients who commenced insulin, who had mean adherence of 88.3% (95% confidence interval (CI) 85.9–90.6%) compared with the remaining 2275 patients whose mean adherence was 87.4% (95% CI 86.7–88.2%). In a logistic regression analysis, the adjusted odds ratio (OR) for commencing insulin was 1.20 (95% CI 1.07–1.35) for a quartile increase in adherence. There were 1519 patients on metformin (49% male, mean age 64 years). Mean adherence was 79.7% (95% CI 76.4–83.1%) and 83.1% (95% CI 82.0–84.1%) in 169 patients who did and 1350 who did not commence insulin, respectively, with an adjusted OR for a quartile increase in adherence of 0.91 (95% CI 0.78–1.07).

Conclusion Despite suboptimal adherence to OHAs in Type 2 diabetes, this is not associated with subsequent requirement for insulin.

Diabet. Med. 19, 685–688 (2002)
The pathogenesis and management of painful diabetic neuropathy: a review
Authors: Spruce M. C. , Potter J. , Coppini D. V.
Published: March 2003

Painful diabetic neuropathy has always been a challenging complication of diabetes mellitus. Emerging theories suggest that early dysaesthesia associated with painful neuropathy may act as a marker for the development of the ‘at risk’ foot, allowing preventative clinical strategies to be undertaken. The mechanisms of neuropathic pain are complex. The authors’ intentions are to help members of the diabetes care team better understand and appreciate the diverse symptoms reported by patients. The various treatments available for painful neuropathy are discussed in detail. Robust comparative studies on such treatments are, however, unavailable and the authors have designed a logical approach to management based on best current evidence and their own clinical experience.
The relationship between birth weight and maternal glycated haemoglobin (HbA1c) concentration in pregnancies complicated by Type 1 diabetes
Authors: Penney G. C. , Mair G. , Pearson D. W. M.
Published: March 2003

Aim  To examine the relationships between maternal HbA1c concentration at different time points and birth weight in pregnancies complicated by pre‐existing Type 1 diabetes.

Methods  A comprehensive audit dataset was collected prospectively on all deliveries in Scotland to women with pre‐existing Type 1 diabetes occurring between 1 April 1998 and 31 March 1999. Data items included HbA1c concentrations prior to conception and in each of the three trimesters of pregnancy, and birth weight. Relationships between standardized birth weight and HbA1c concentrations at each of the four time points were examined using correlation analysis.

Results  Standardized birth weight (Z scores) could be calculated for 203 of 208 singleton liveborn infants. HbA1c concentrations, standardized to correct for assay differences among hospitals, at different time points were available for between 134 (pre‐pregnancy) and 192 (third trimester) cases. Standardized birth weight, relative to a reference population, showed a unimodal distribution, shifted to the right (mean, +1.57 sd). There was a significant negative correlation between pre‐pregnancy HbA1c and birth weight (Spearman's R, −0.208; P = 0.016). There were no statistically significant correlations for other time points.

Conclusions  Standardized birth weight scores of the infants of diabetic mothers are higher than those of a reference population. There is no simple relationship between maternal glycaemic status and birth weight, but there appears to be a paradoxical inverse relationship between pre‐pregnancy glycaemic control and standardized birth weight.
A pilot study of the beneficial effects of amantadine in the treatment of painful diabetic peripheral neuropathy
Authors: Amin P. , Sturrock N. D. C.
Published: March 2003

Background  Current symptomatic treatments for painful peripheral neuropathy in diabetes have variable efficacy in individual patients. Amongst other chemical transmitters involved in pain reception, the N‐methyl‐D‐aspartate (NMDA) subtype of excitatory amino acid receptor is involved in nociception. Amantadine was recently shown to act as a non‐competitive antagonist of NMDA and may be effective in the treatment of neuropathic pain in patients with cancer. We have looked at the benefit of amantadine infusion in diabetic patients with painful peripheral neuropathy.

Methods  Seventeen patients with diabetes (nine men) completed this double‐blind randomized crossover placebo‐controlled trial of intravenous amantadine. The average age was 58.4 (sd 11) years, with duration of diabetes of 21.1 (8.7) years and duration of painful peripheral neuropathy symptoms of 29.1 (24) months. All analgesics except paracetamol were stopped for 4 weeks prior to the study. Infusions were carried out on a weekly basis with amantadine being administered intravenously as a single 200‐mg infusion. The Neuropathy Symptom Score (NSS), together with visual analogue scales, were used to assess current pain intensity (VAS‐P) pre‐therapy and 1 week later VAS‐P was repeated together with a visual analogue scale used to assess relief in pain (VAS‐R) and the Physicians Global Evaluation (PGE) score used to assess response to therapy.

Results  Pre‐therapy, the NSS was 6.8 (6.3–7.4) at baseline, remaining unchanged at 6.6 (5.8–7.4) after placebo (P = 0.33), but fell to 4.6 (3.4–5.8) after amantadine (P = 0.003 vs. baseline and P = 0.02 vs. placebo). The baseline perception of pain was scored as 7.8 cm (7.3–8.3), with no difference following placebo, at 8.2 cm (7.7–8.6) (P = 0.34), but following amantadine it fell to 6.2 cm (4.9–7.8) (P = 0.01 compared with pre‐therapy, P = 0.003 compared with placebo). The perception of relief from pain following placebo was only 0.2 (−0.2 to +0.6) but following amantadine was 10‐fold better at 1.9 (0.8–3.1) (P = 0.016). The PGE assessment of pain relief was −0.3 (−0.5 to 0) for placebo and following amantadine was 0.8 (0.1–1.5) (P = 0.006).

Conclusions  Our study has shown that intravenous amantadine is beneficial in reducing the pain of painful peripheral neuropathy, with an effect sustained for at least 1 week after an infusion.
Do plasminogen activator inhibitor (PAI‐1) or tissue plasminogen activator PAI‐1 complexes predict complications in Type 1 diabetes: The Pittsburgh Epidemiology of Diabetes Complications Study
Authors: Bosnyak Z. , Forrest K. Y.‐Z. , Maser R. E. , Becker D. , Orchard T. J.
Published: March 2003

Aims  To examine the predictive power of plasminogen activator inhibitor‐1 (PAI‐1) and the complexes it forms with tissue plasminogen activator (tPA–PAI‐1) for the two major Type 1 diabetes (T1D) complications (coronary artery disease (CAD) and overt nephropathy) in the context of standard risk factors.

Methods  Observational prospective study of 454 participants with childhood onset (< 17 years) T1D, aged 18+ years at baseline. PAI‐1 and tPA–PAI‐1 were determined using ELISA methodology. Follow‐up (6 years) was limited to 382 individuals for CAD and 294 individuals for overt nephropathy, after excluding baseline cases. Total, HDL and LDL‐cholesterol, triglycerides, HbA1, blood pressure, body mass index (BMI), waist–hip ratio (WHR), leucocyte count, Beck depression score and fibrinogen were also examined.

Results  The 56 incident cases of CAD had marginally lower PAI‐1 and higher tPA–PAI‐1 levels compared with those free of CAD. However, marginally higher PAI‐1 and significantly higher tPA–PAI‐1 (P = 0.04) levels were seen in those who developed nephropathy. After controlling for age, both PAI‐1 and tPA–PAI‐1 showed significant negative correlations with HDL‐cholesterol, and positive correlations with triglycerides, WHR, HbA1 and fibrinogen. tPA–PAI‐1 was also positively correlated with total and LDL‐cholesterol. In multivariate analyses, neither PAI‐1 nor tPA–PAI‐1 was an independent predictor of CAD or overt nephropathy.

Conclusions  These results suggest little association between PAI‐1 and later CAD in patients with T1D. However, tPA–PAI‐1 complexes may be involved in the pathogenesis of overt nephropathy.
Elevational diversity gradients, biogeography and the structure of montane mammal communities in the intermountain region of North America
Authors: Rickart Eric A.
Published: March 2003

1 Distribution data were assembled for non‐volant small mammals along elevational gradients on mountain ranges in the western U.S.A. Elevational distributions in the species‐rich Uinta Mountains were compared to those on smaller mountain ranges with varying degrees of historical isolation from the Uintas.

2 For mountain ranges supporting the richest faunas, species richness is highest over a broad low‐ to mid‐elevation zone and declines at both lower and higher elevations. Patterns on other mountain ranges are similar but reflect lower overall species richness.

3 A basic relationship between elevational and geographical distribution is apparent in the occurrence patterns of mammals on regional mountains. Faunas on mountains that have had low levels of historical isolation appear to be influenced by immigration rather than extinction. Species restricted to high elevations in the Uintas are poorly represented on historically isolated mountains and form a portion of local faunas shaped by extinction. Species occurring at lower elevations in the Uintas have better representation on isolated mountains and apparently maintain populations through immigration.

4 Several widespread species show substantial variation in maximum elevation records on different mountain ranges. This involves (1) an upward shift in habitat zones on small, isolated mountain ranges, allowing greater access by low‐elevation species, and (2) expansion of certain low‐ and mid‐elevation species into habitats normally occupied by absent high‐elevation taxa.

5 Results indicate that montane mammal faunas of the intermountain region have been shaped by broad‐scale historical processes, unique regional geography and local ecological dynamics. Parallel examples among mammals of the Philippine Islands suggest that such patterns may characterize many insular faunas.
Latitude, elevation and body mass variation in Andean passerine birds
Authors: Blackburn Tim M. , Ruggiero Adriana
Published: March 2003

Relationships between body mass and latitude, and body mass and elevation are examined in the assemblage of Andean passerine birds.

Across species, body mass is positively correlated with the mid‐point of the species elevational distribution, but there is no significant relationship between body mass and latitudinal range mid‐point.

When the assemblage is separated into Andean endemic and non‐endemic species, the former group shows a significant positive relationship between body mass and elevation, and the latter a significant positive relationship between body mass and latitude (‘Bergmann’s rule’). Andean endemic species exhibit Bergmann’s rule once elevation is controlled for using multiple regression.

These relationships are not a consequence of the phylogenetic non‐independence of species. All the effects shown are very weak, with latitude and elevation explaining only a few per cent of the variation in body mass. Relationships are strongest when phylogenetically controlled analyses are performed just within genera.

The implications of these results for the mechanistic understanding of Bergmann’s rule are discussed.
The influence of resprouting forest canopy species on richness in Southern Cape forests, South Africa
Authors: Kruger L. M. , Midgley J. J.
Published: March 2003

We investigated the relationship between species richness and numbers and types of individuals and species present in forests with different physiognomies in the southern Cape Province, South Africa. Data were collected from three different ‘plot’ types: 400 m2, canopy‐scaled (plot length is directly proportional to canopy height) and per 100 individuals closest to a point. Plots were designed to control for the effect of scale on local richness. Canopy species richness was inversely proportional to the abundance of resprouting species. The strength of the relationship between the abundance of resprouters and canopy species richness increased progressively from the 400 m2 plots to the canopy‐scaled plots and finally to the plots of 100 individuals. Resprouter abundance decreased, while canopy species richness increased, with increasing canopy height. Resprouters are able to retain their in situ position in the forests for longer periods of time than do reseeders. This reduces individual and species turnover, thus reducing species richness in resprouter‐dominated forests.
The validity of twin studies
Authors: Evans David M. , Martin Nicholas G.
Published: March 2003

The classical twin study is the most popular method for assessing the relative contribution of genes and environment to traits in human populations. Critics argue that several assumptions of the twin method are unjustified, and therefore results from twin studies are misleading. Specifically, it has been suggested that twins differ in important aspects from singletons, that monozygotic (MZ) and dizygotic (DZ) twins are not matched in their degree of environmental similarity, and that MZ twins are neither matched genetically nor in their prenatal environments. These criticisms are addressed and it is suggested that they do not provide serious impediments to the validity of the twin study.
The future of stock enhancements: lessons for hatchery practice from conservation biology
Authors: Brown Culum , Day Rachel L
Published: March 2003

The world's fish species are under threat from habitat degradation and over‐exploitation. In many instances, attempts to bolster stocks have been made by rearing fish in hatcheries and releasing them into the wild. Fisheries restocking programmes have primarily headed these attempts. However, a substantial number of endangered species recovery programmes also rely on the release of hatchery‐reared individuals to ensure long‐term population viability. Fisheries scientists have known about the behavioural deficits displayed by hatchery‐reared fish and the resultant poor survival rates in the wild for over a century. Whilst there remain considerable gaps in our knowledge about the exact causes of post‐release mortality, or their relative contributions, it is clear that significant improvements could be made by rethinking the ways in which hatchery fish are reared, prepared for release and eventually liberated. We emphasize that the focus of fisheries research must now shift from husbandry to improving post‐release behavioural performance. In this paper we take a leaf out of the conservation biology literature, paying particular attention to the recent developments in reintroduction biology. Conservation reintroduction techniques including environmental enrichment, life‐skills training, and soft release protocols are reviewed and we reflect on their application to fisheries restocking programmes. It emerges that many of the methods examined could be implemented by hatcheries with relative ease and could potentially provide large increases in the probability of survival of hatchery‐reared fish. Several of the necessary measures need not be time‐consuming or expensive and many could be applied at the hatchery level without any further experimentation.
β2‐Glycoprotein I – dependent anticardiolipin antibodies in ischemic stroke
Authors: Fiallo P. , Tomasina C. , Cardo P.P.
Published: March 2003

Our study was undertaken to investigate whether beta2‐glycoprotein I (GPI) is relevant for enhancing anticardiolipin antibody (aCL) binding in stroke patients, in particular view of vascular risk factors and recurrence of previous cerebral ischemic events. One‐hundred and twenty‐one sera from patients with ischemic stroke and 154 control sera from patients with non‐ischemic neurological disorders (n= 43) and healthy subjects (n= 111) were included in the study. All sera were tested for either GPI‐independent aCL and GPI‐dependent aCL. GPI‐independent aCL were detected in two (1.7%) stroke patients. When GPI was added to the assay system, 13 (10.8%) sera were positive. Of the 43 sera in the neurological control group one was positive for both GPI‐independent aCL and GPI‐dependent aCL. Multiple linear regression in the stroke group revealed that GPI‐dependent aCL are marginally associated with sex, prior TIA/strokes and embolism. More importantly, GPI‐dependent aCL were significantly more frequent in stroke patients with a history of prior TIA/strokes compared with patients with a first ischemic stroke (p= 0.029).

The present study demonstrates that aCL in stroke patients are of the GPI‐dependent type and emphasizes the importance of adding GPI in the immunoassay for the optimal detection of aCL. Furthermore, it supports the recommendation of testing aCL in those patients who experience unexplained recurrent cerebral ischemic events.
Magnetic resonance imaging of subacute myelopathy due to cobalamin deficiency
Authors: Masson C. , Colombani J.M. , Dehen H.
Published: March 2003

A 77‐year‐old woman presented with rapidly ascending sensory ataxia. Magnetic resonance imaging (MRI) showed extensive involvement of the dorsal columns of the spinal cord. Hematological data were normal despite severe cobalamin deficiency. The contribution of magnetic resonance imaging in subacute degeneration of the spinal cord is discussed.
Encephalopathy and biopsy‐proven cerebrovascular inflammatory changes in a cocaine abuser
Authors: Díez‐Tejedor E. , Frank A. , Gutiérrez M. , Barreiro P.
Published: March 2003

Cocaine abuse is a well known cause of cerebrovascular complications. An inflammatory vasculopathy hypothesis has been proposed, but the medical literature has only reported a few pathological confirmations. We report a case with a biopsy demonstrating cerebral inflammatory vascular changes that are associated with cocaine abuse. A 21‐year‐old male, a twice weekly cocaine abuser, developed encephalopathy, apraxia and left hemiparesis with hemisensory loss during the first week after his last cocaine intake; postural tremor and dystonia appeared later. Laboratory data were unrevealing. Cerebral angiography showed a lack of vascularization in the left precentral and central arterial groups. A corticomeningeal cerebral biopsy demonstrated perivascular cell collection and transmural lymphomonocytic infiltration of the small cortical vessels. All symptoms improved with corticosteroid treatment, but 4 years later, the patient returned with a worsening of his encephalopathy and a severe memory impairment, emotional lability and apraxia. A cerebral magnetic resonance image (MRI) showed subcortical and periventricular lesions suggesting ischemic damage in small‐size vessel areas as well as cortical atrophy. This new case supports the existence of an encephalopathy associated with vascular inflammatory changes in a cocaine abuser, although more clinical and experimental data are necessary to define its physiopathology.
Does combined levodopa and bromocriptine therapy in Parkinson's disease prevent late motor complications?
Authors: Alarcón F. , Cevallos N. , Lees A.J.
Published: March 2003

Levodopa‐carbidopa (LD) in low dosages adequately controls symptoms in most patients with Parkinson's disease and delays the appearance of fluctuations and dyskinesias. It has been suggested that early combination therapy with bromocriptine and levodopa delays or prevents the onset of late treatment complication associated with LD monotherapy in Parkinson's disease. We have conducted this study to assess the possible benefit of combined therapy compared with levodopa monotherapy. Seventy‐eight previously untreated patients with Parkinson's disease were recruited over a period of 54 months and randomly allocated to either a levodopa‐carbidopa (LD) Group or a levodopa‐carbidopa in combination with low‐dose bromocriptine (LD‐Br) Group. The appearance of motor complications determined the end point of the study. We gradually increased the doses of bromocriptine (2.5–15 mg/d) or levodopa (125–500 mg/d) until the maximum “on” time was reached. In six patients, the doses of levodopa had to be increased up to the optimal dose (625–1000 mg/day). In the last evaluation the on‐time and parkinsonian disability were similar in both treatment groups. We did not find statistically significant differences in the frequency of motor complications when comparing the two groups of treatment. Our study suggests that early combination of levodopa and bromocriptine does not confer any clinical benefit over levodopa alone in treating early Parkinson's disease, nor will it influence the evolution of the disease.
A case of facial diplegia associated with herpes simplex reactivation
Authors: Berry C. , MacKie R.M.
Published: March 2003

Facial nerve palsy is the commonest cranial neuropathy affecting 40/100 000 people in the Western World but is idiopathic in 50–70% of cases. This report describes a case of recurrent facial nerve palsy in association with herpes simplex virus (HSV) reactivation. HSV may be a major cause of racial nerve palsy. Further research is required to clarify this issue in order that targeted treatment strategies can be developed for this common problem.
Unusual neurological manifestations of primary human immunodeficiency virus infection
Authors: Hassin‐Baer Sharon , Steiner Israel , Achiron Anat , Sadeh Menachem , Vonsover Ami , Hassin David
Published: March 2003

The nervous system may be involved during primary human immunodeficiency virus (HIV) infection. Recognized clinical syndromes include meningitis, meningo‐encephalitis, myelopathy, polyneuropathy and rhabdomyolysis. We report three patients with unusual neurological presentations of primary HIV infection: intracranial hypertension, severe encephalopathy characterized by personality changes and regressive behavior, and iumbosacral radiculoneuropathy. In all, the neurological disorder had a benign course and resolved within a few months. Awareness of the large spectrum of neurological manifestations of primary HIV infection can enable early diagnosis and treatment.
Absence of linkage with the neuronal nitric oxide synthase (NOS1) gene in 41 multiplex Swedish MS families
Authors: Xu Chun , Hillert Jan
Published: March 2003

Several genetic factors are likely to play a role in the aetiology of multiple sclerosis (MS), although so far only the HLA gene complex has been clearly identified as important. In addition, several studies support the importance of nitric oxide synthase (NOS) as a component in the pathogenesis of MS. We have investigated the role of the neuronal nitric oxide synthase (NOS1) gene in 41 Swedish multiplex MS families by parametric and nonparametric linkage analysis with two polymorphic intragenic markers. Two‐point lod scores were clearly negative, effectively excluding a role of the NOS1 gene in most models tested. Non‐parametric linkage analysis (NPL), affected pedigree member (APM) analysis and extended transmission disequilibrium test (ETDT) also failed to provide evidence for a susceptibility locus in this gene. Thus, a contribution of the NOS1 gene to the genetic background of MS is unlikely in this population.
High levels of hippocampal cholinergic neurostimulating peptide (HDNP> in the CSF of some patients with Alzhemer's disease
Authors: Tsugu Yasukuni , Ojika Kosei , Matsukawa Noriyuki , Iwase Tamaki , Otsuka Yasushi , Katada Eiichi , Mitake Shigehisa
Published: March 2003

Hippocampal cholinergic neurostimulating peptide (HCNP), originally purified from the hippocampus of young rats, enhances the cholinergic development of rat medial septal nuclei in vitro. This report concerns the determination of the HCNP content of the cerebrospinal fluid (CSF) of 173 clinically, and of 22 clinico‐pathologically defined patients. A radiommunossay was used throughout. The HCNP level was relatively uniform among the clinically defind patients for almost all non‐Alzheimer's patients, the level fell within the range delimited by ± 2 SD of the mean of all patients taken together, and none of them had a level above this range. By contrast, the early‐onset Alzheimer's diseas patients could be divided on the basis of their HCNP level into two groups, one with high levels (markedly above the mean ± 2 SD range), and the other with levels similar to those of the other patients. The analysis of the CSF samples obtained postmortem revealed that Group I Alzheimer‐type dementia (ATD) patients with clinico‐pathologically established diagnoses had a strikingly higher level of HCNP than patients with either Group II ATD or cerebral vascular diseas. These results suggest that HCNP is involved in certain pathophysiological alterations associated with dementia, and that its determination may be useful in patient evaluation.
Brucellar spinal epidural abscess
Authors: Pina M.A. , Ara J.R. , Modrego P.J. , Juyol M.C. , Capablo J.L.
Published: March 2003

Spinal epidural abscesses account for approximately one of every 10,000 admissions to tertiary hospitals. The midthoracic vertebrae are the most frequently affected, whilst the cervical spine is involved in fewer patients. Staphylococcus aureus is identified as the cause in most cases of epidural abscess; other bacteria responsible include Gram‐negative bacteria, Streptococcus species and Brucella species. We report the case of a patient with cervical spondylodiscitis at level C4‐C5 and an epidural abscess which was compressing the spinal cord and the retropharyngeal space. The previous symptoms of brucellosis were atypical. We discuss the clinical manifestations, diagnosis, treatment and prognosis of the case.
Cytochrome P4502D6 (debrisoquine 4‐hydroxylase) and Parkinson's disease in Chinese and Caucasians
Authors: Ho Shu‐Leong , Kung Michelle H.W. , Li Leonard S.W. , Lauder Ian J. , Ramsden David B.
Published: March 2003

Four polymorphic sites (C/T188 C/T2938, G/C4268, G/A1934) in the cytochrome P4502D6 (debrisoquine 4‐hydroxylase) gene were investigated for their association with sporadic Parkinson's disease (PD). Three mutant allels (C/T188, C/T2938 and G/C4268) result in amino acid changes which could alter the substrate specificity or alter its ability to metabolize their substrates; the fourth (G/A1934) causes a loss of enzyme activity. The study was carried out in two ethnically homogenous populations: Chinese (123 PD patients, 124 controls); and Caucasian (95 PD patients, 62 controls). Haplotype status, which took into account amino acid changes at three polymorphic sites, was deduced from genotyping results in order to investigate whether substrate specificity was important rather than loss of enzyme activity. There was no gender difference in the distribution of the alleles in either race. There was, however, significant association among the three polymorphic sites (C/T188, C/T2938, C/C4268) in both ethnic groups. T/T188:C/C2938:C/C4268 is the most common genotype in the Chinese population, in contrast to C/C188:C/T2938:C/G4268 (followed by C/C188:C/C2938:G/G4268) in Caucasians. All 69 of the sub‐group of Chinese patients tested were homozygous for the wild‐type allele at the G/A1934 polymorphic site. Neither the CYP2D6 allele nor haplotype was associated with PD in either ethnic group.
Dural puncture and corticotherapy as risks factors for cerebral venous sinus thrombosis
Authors: Milhaud D. , Heroum C. , Charif M. , Saulnier P. , Pages M. , Blard J. M.
Published: March 2003

Dural puncture with corticosteroid could be a predisposing factor for cerebral venous thrombosis (CVT ). A 35‐year‐old woman using oral contraception was treated with corticosteroid epidural infiltration for L5 radiculalgia. The following day a postural headache developed and accidental dural puncture was suspected. Four days later, she presented with fever and consciousness impairment requiring mechanical ventilation. Magnetic resonance angiography (MRA) confirmed thrombosis of the superior sagittal sinus. Recanalization was observed three weeks later and the patient fully recovered. Blood tests for thrombophilia showed a moderate decrease in the C protein level (chronometric activity 44%, N = 65–130). CVT has been reported after spinal anaesthesia or peridural anaesthesia with accidental puncture. After dural puncture the decrease of cerebrospinal fluid pressure induces a rostrocaudal sagging effect with traumatic damage to the fragile venous endothelial wall, and may trigger a venous vasodilatation with resultant stasis. CVT has also been described in patients after lumbar puncture and oral corticoid treatment for multiple sclerosis and after corticosteroid intrathecal infiltration. Therefore, corticosteroids can be considered as a potential additional procoagulant stimuli.
Phosphoglycerate kinase deficiency in two brothers with McArdle‐like clinical symptoms
Authors: Aasly J. , van Diggelen O. P. , Boer A. M. , Brønstad G.
Published: March 2003

Phosphoglycerate kinase (PGK) catalyses the transfer of the acylphosphate group of 1,3‐diphosphoglycerate to ADP with formation of 3‐phosphoglycerate and ATP in the terminal stage of the glycolytic pathway. Two young brothers are presented who both experienced muscle pain, cramps and stiffness shortly after beginning heavy exercise. After these episodes they noticed that the urine was dark brown, indicating rhabdomyolysis and myoglobinuria. The neurological examinations were without remarks. There was no lactate increase in the ischaemic forearm exercise test. Both had very low PGK levels in muscle, erythrocytes, leukocytes and fibroblasts.

This is the first family with more than one affected case of PGK deficiency and exercise‐induced stiffness, myalgia and rhabdomyolysis. The clinical manifestations may resemble myophosphorylase deficiency (McArdle’s disease: glycogenosis Type V) and muscle phosphofructokinase deficiency (Tarui’s disease: glycogenosis Type VII). PGK deficiency is inherited as an X‐linked trait and may show other features such as mental retardation and/or haemolytic anaemia.
Neurological complications of drug abuse: pathophysiological mechanisms
Authors: Neiman J. , Haapaniemi H. M. , Hillbom M.
Published: March 2003

Drug abuse is associated with a variety of neurological complications. The use of certain recreational drugs shows a marked temporal association with the onset of both haemorrhagic and ischaemic strokes, the majority of which develop within minutes to 1 h after the administration of the index drug. Delayed onset of stroke has also been observed. Acute, severe elevation of blood pressure, cardiac dysrhythmias, cerebral vasospasm, vasculitis, embolization due to infective endocarditis or dilated cardiomyopathy, embolization due to foreign material injected with the diluents under non‐sterile conditions and ‘street drug’ contaminants with cardiovascular effects have been suggested as possible underlying mechanisms. Rupture of aneurysms and arteriovenous malformations have been detected in up to half of the patients with haemorrhagic stroke due to cocaine abuse. The less common findings reported have included a mycotic cerebrovascular aneurysm in a patient with infective endocarditis and haemorrhagic stroke. In addition to stroke, cocaine seems to provoke vascular headache. Seizures precipitated by recreational drug abuse are usually caused by acute intoxication in contrast to the withdrawal seizures encountered in subjects with alcohol abuse. Movement disorders and cerebral atrophy correlating with the duration of abuse have been described. Snorting of organic solvents may cause encephalopathy. Cases of spongiform leukoencephalopathy in heroin addicts have also been reported. Peripheral neuropathy is occasionally precipitated by drug poisoning after intravenous administration. Impurities of the drug, risky administration techniques, and the use of mixtures of various drugs, frequently with simultaneous alcohol drinking, should be taken into account when assessing the background of the adverse event as well as the overall lifestyle of the addicted subjects.
Ataxic form of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
Authors: Yato M. , Ohkoshi N. , Sato A. , Shoji S. , Kusunoki S.
Published: March 2003

We reported a 64‐year‐old male with an eight‐month history of gait disturbance and sensory impairment. The patient initially noticed unsteadiness of gait and numbness in his feet, and these symptoms progressed until he was unable to walk without assistance five months later. Vibratory sensation and position sense were markedly diminished, and deep tendon reflexes were absent in all extremities. Motor conduction velocities were slow with prolonged distal latencies, and sensory nerve action potentials (SNAP) were not elicited. Sural nerve biopsy revealed a mild loss of myelinated fibres and segmental demyelination. Cerebrospinal fluid showed normal cell count with protein 526 mg/dL. Anti‐GM1, anti‐GM2 and anti‐GA1 antibodies in serum were positive. We diagnosed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) presenting ataxia. Steroid therapy provided immediate improvement of symptoms and signs. This case suggests that CIDP should be considered as one of the potential causes of ataxic neuropathy.
Impaired interleukin‐2 response of mononuclear cells in Guillain–Barré syndrome
Authors: Yoshii F. , Shinohara Y.
Published: March 2003

We studied the production of and response to interleukin‐2 (IL‐2) by cultured peripheral blood mononuclear cells (PBMC) and the soluble IL‐2 receptor levels in 10 patients with GBS (eight men and two women) aged 23–67 years. The first blood sample was obtained within seven days of the onset of neuropathic symptoms, and blood samples were collected serially after treatment with plasma exchange. PBMC from GBS patients were found to produce little IL‐2 and to have a low response to IL‐2 soon after the onset, but marked improvement was seen within one month, concomitantly with improvement of neuropathic symptoms. Serum soluble IL‐2 receptor levels were increased at the onset, but gradually decreased thereafter. Our findings suggest that primary immune response in acute‐stage GBS may be downregulated via a decrease in the function of PBMC that had previously been activated by interacting with the antigen.
Musicogenic epilepsy with ictal single photon emission computed tomography (SPECT): could these cases contribute to our knowledge of music processing?
Authors: Genç B. O. , Genç E. , Taştekin G. , İihan N.
Published: March 2003

Musicogenic epilepsy has a strong correlation with the temporal lobe with a right‐sided preponderance. We report the case of a 48‐year‐old woman whose seizures began at the age of 32 years. Her prenatal, natal and childhood histories were unremarkable and her family history was negative for epilepsy. She had typical complex partial seizures with chewing automatisms. Cranial computed tomography, magnetic resonance imaging (MRI) and interictal SPECT showed no abnormality. Interictal EEG showed paroxysmal bitemporal sharp wave discharges predominant on the right side. Ictal EEG showed a combination of high voltage sharp and slow sharp waves and spikes that originated from the right temporal leads and then became generalized. Ictal activity on EEG started 4–5 min after the music stimulus. For the ictal SPECT study, i.v. injection of 20 mCi of HMPAO was administered approximately 30 s after the ictal activity started. Ictal SPECT demonstrated a right anterior and mesial temporal hyperperfusion. These results seem to support the dominant role of the right temporal lobe and the possible relation of mesial temporal structures to the affective content of music in musicogenic epilepsy.
Interest in genetic testing in pallido‐ponto‐nigral degeneration (PPND): a family with frontotemporal dementia with Parkinsonism linked to chromosome 17
Authors: McRae C. A. , Diem G. , Yamazaki T. G. , Mitek A. , Wszolek Z. K.
Published: March 2003

The specific mutation on the tau gene responsible for a neurodegenerative disease known as pallido‐ponto‐nigral degeneration (PPND) was recently located. PPND family members are at risk for an autosomal dominant form of frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP‐17). This study investigated whether individuals in this family would consider presymptomatic genetic testing. Surveys were sent to 66 at‐risk individuals in the family; replies were received from 20 (30%). Family members were asked if they would consider having testing now or in the future, and to indicate their reasons for and against proceeding with testing. Fifty per cent (n=10) of those who were at risk and who responded indicated they would consider testing now, and 55% (n=11) would think about it in the future. The most frequently cited reasons to proceed with testing were to ‘collaborate with research’ (70%) and to ‘know if my children are at risk’ (45%). The most frequently cited reason not to pursue testing was ‘I can enjoy my life more fully by not knowing’ (50%). Results suggest that interest in determining whether they will manifest PPND is generally low among at‐risk members of this family, despite wide support and participation in other research studies.
Visual cortex excitability in migraine before and after valproate prophylaxis: a pilot study using TMS
Authors: Mulleners W. M. , Chronicle E. P. , Vredeveld J. W. , Koehler P. J.
Published: March 2003

We examined the effect of standard migraine prophylaxis with sodium valproate on repeated measures of occipital excitability using transcranial magnetic stimulation (TMS). We predicted that, comparing pre‐ and post‐treatment assessments, a reduction in clinical migraine parameters would be paralleled by a decrease in excitability measurements.

A total of 31 migraine patients enrolled in the study, for assessment prior to and 1 month after commencement of sodium valproate prophylaxis. At each assessment, we used a standardized protocol to stimulate the occipital cortex with a 90‐mm circular (coil A) and 70 mm figure‐of‐eight (coil B) coil. We recorded the threshold stimulation intensity at which subjects just perceived phosphenes. Subjects kept detailed records of headache parameters 1 month before and also during the study period.

Valproate therapy significantly improved headache indexes, as expected. In MA subjects assessed with coil B, phosphene thresholds were significantly higher post‐treatment than pre‐treatment, but those for MO did not change. Modest correlations were observed in MA patients between increase in phosphene threshold and decrease in headache index.

Although preliminary, the findings with coil B lend some support to the notion that effective migraine prophylaxis may be achieved through lowering cortical excitability by γ‐aminobutyric acid (GABA)‐ergic intervention. Further investigation of the effect of sodium valproate or other similarly acting substances on cortical excitability in migraine is warranted.
Incidence and predictors for post‐stroke epilepsy. A prospective controlled trial. The Akershus stroke study
Authors: Lossius M. I. , Rønning O. M. , Mowinckel P. , Gjerstad L.
Published: March 2003

The aim of the study was to assess the incidence and identify predictors for post‐stroke epilepsy (PSE), in particular the possible influence of treatment in a stroke unit (SU). Patients with PSE were identified between 4 weeks and 1 year after the stroke. Different parameters were studied as possible predictors. Twelve patients (2.5%) developed PSE during 12 months. Four of the patients (33%) were treated in an SU and eight of the patients (67%) were treated in general medical wards (GMWs) (P=0.50). Mean age in those with PSE was 75 and 76 in those without (P=0.57). Four out of 363 patients (1.1%) with minor stroke [Scandinavian Stroke Scale (SSS)‐score >30] developed PSE. Seven out of 104 patients (6.3%) with severe stroke developed PSE (P=0.004). In the multivariate analysis SSS‐score scores below 30 was a significant predictor for incidence of PSE (odds ratio=6.1, P=0.003). At 12 months the incidence of PSE was 2.5%. SSS‐score below 30 was a significant predictor for PSE, whilst age and treatment in SU versus GMW were not.
Disturbance in the serum IgG subclass distribution in patients with anti‐Hu positive paraneoplastic neurological syndromes
Authors: Blaes F. , Klotz M. , Funke D. , Strittmatter M. , Kraus J. , Kaps M.
Published: March 2003

Autoantibodies in patients with paraneoplastic neurological syndromes (PNS) have been reported to be predominantly IgG1 and IgG3 isotypes. However, no data are available about the IgG subclass distribution of the total serum IgG in these patients. Therefore, we investigated the IgG subclass distribution (given as percentage of total IgG) in 15 anti‐Hu positive PNS patients, 15 patients with small cell lung cancer (SCLC) without PNS and 23 healthy controls using a commercial enzyme‐linked immunosorbant assay test. Although IgG1 (and to a lower extent IgG3) are the predominant subclasses of the anti‐Hu antibodies, PNS and SCLC showed a significant decrease in IgG1 and a concomitant increase in IgG2 compared with healthy controls (P < 0.05, respectively). In contrast, only SCLC patients, but not PNS patients, had higher IgG3 and IgG4 values compared with controls (P < 0.05, respectively). There was no correlation between IgG subclass levels and the titre or the predominant isotype of the antineuronal antibodies. PNS patients with autonomic disturbances had lower IgG4 levels than PNS patients without autonomic disturbances (P < 0.05). Our study demonstrates a disturbance in the IgG subclass distribution in PNS patients which is partly different from SCLC patients. The isotype regulation of the anti‐Hu antibody seems to be independent from this phenomenon.
A controlled historical cohort study on the post‐concussion syndrome
Authors: Mickevičiene D. , Schrader H. , Nestvold K. , Surkiene D. , Kunickas R. , Stovner L. J. , Sand T.
Published: March 2003

In Lithuania, expectation of chronic symptoms after minor head injury is less than in western countries and possibilities for monetary compensation are minimal. Therefore, an opportunity exists to study the post‐concussion syndrome (PCS) without several confounding factors present in western societies. We sent questionnaires about symptoms attributed to PCS to 200 subjects who had a concussion with loss of consciousness between 35 and 22 months before the study. For each study subject, a sex‐ and age‐matched control person with minor non‐head injury was identified. These controls received similar questionnaires. All the responding post‐concussion patients stated that they had had acute headache after the trauma but this headache had disappeared in 96% of cases within 1 month. Headache and dizziness at the time of the questioning were not significantly more prevalent in the patients with concussion than in the controls, and there was no significant difference concerning subjective cognitive dysfunction. Scores of visual analogue scales of symptoms attributed to PCS showed no significant differences except for depression, alcohol intolerance and worry about brain injury, which were more frequent in the concussion group. No specific effect of the head injury was detected when various definitions and different constellations of core symptoms of PCS were used. These findings question the validity of the PCS as a useful clinical entity.