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J Jakobsen

Publications and source records attributed to J Jakobsen.

At least 19 recordsLinked to original sources

Differential effect of p75 neurotrophin receptor on expression of pro-apoptotic proteins c-jun, p38 and caspase-3 in dorsal root ganglion cells after axotomy in experimental diabetes.

We have hypothesized that p75 neurotrophin receptor (p75(NTR))-mediated activation of the pro-apoptotic proteins c-jun, p38 and caspase-3 underlies the neuronal cell loss in dorsal root ganglia (DRG) neurons after axotomy in normal mice, and that this activation is exaggerated in experimental diabetes. To test this hypothesized relationship, we compared the expression of pro-apoptotic proteins in fifth lumbar DRG (L5DRG) neurons of wildtype Balb/c (p75+/+) mice and p75(NTR) knockout (p75-/-) mice, assigned to either non-diabetic control groups or to diabetic (1 month) groups, all with a unilateral sciatic nerve crush produced 10 days before tissue preparation. The absolute number of L5DRG neurons expressing immunoreactivities (IR) for phosphorylated c-jun (P-c-jun-IR), phosphorylated p-38 (P-p38-IR) and cleaved caspase-3 (caspase-3-IR) were estimated in semi-thick sections using the optical fractionator. Nerve crush increased the numbers of P-c-jun-IR and caspase-3-IR neurons in all four groups. On the crush side, diabetes did not exaggerate the increase of P-c-jun-IR or caspase-3-IR neurons in p75+/+ mice, whereas in p75-/- mice diabetes reduced the increase of P-c-jun-IR neurons. Also, in p75-/- mice there was fewer caspase-3-IR cells on the intact and crushed side in comparison with p75+/+ mice independent of the presence of diabetes. This study demonstrates that (1) diabetes of 1 month's duration does not potentiate the expression of three pro-apoptotic markers p38, caspase-3 and P-c-jun neither in intact neurons nor after nerve crush, and that (2) p75(NTR) is required for activation of the pro-apoptosis signal caspase-3 after nerve crush in both diabetic and non-diabetic mice.

Animals↗

Teenage girls and elderly women living in northern Europe have low winter vitamin D status.

OBJECTIVE: To determine the vitamin D status (serum 25-hydroxyvitamin D; S-25OHD) in adolescent girls and elderly community-dwelling women living in four countries of northern Europe and to explain differences in S-25OHD concentrations between and within the countries. DESIGN: A cross-sectional observational study conducted in a standardised way during February-March. S-25OHD was analysed by high-performance liquid chromatography. Vitamin D and calcium intake was calculated using a standardised food composition database. SETTING: Denmark, Finland, Ireland, and Poland. SUBJECTS: A total of 199 girls (mean (s.d.) age 12.6 (0.5) y) and 221 women (mean (s.d.) age 71.8 (1.4) y). RESULTS: The median (inter quartiles) concentration of S-25OHD was 29.4 (20.3, 38.3) nmol/l for the girls and 40.7 (28.0, 54.2) nmol/l for the women. S-25OHD below 25 nmol/l was found in 37% of the girls and 17% of the women, and S-25OHD below 50 nmol/l was found in 92% of the girls and 37% of the women. Positive significant determinants for S-25OHD in girls were use of vitamin D supplements, and in women sun habits, dietary vitamin D intake, use of vitamin D and calcium supplements. Body mass index and smoking were negative determinants in women. For women predictors could explain the differences between countries (P(country) = 0.09, R(2) = 0.39), but for girls the difference remained significant even after including predictors (P(country) = 0.03, R(2) = 0.15). CONCLUSION: Vitamin D status is low in northern Europe during winter. More than one-third of the adolescent girls have vitamin D status below 25 nmol/l and almost all are below 50 nmol/l. Two-thirds of the elderly community-dwelling women have vitamin D status below 50 nmol/l. Use of vitamin D supplements is a significant positive determinant for S-25OHD for both girls and women (P = 0.001). SPONSORSHIP: The European Fifth Framework Programme (Contract No. QLK1-CT-2000-00623).

Age Factors↗

Presence of Epstein-Barr virus and human herpesvirus 6B DNA in multiple sclerosis patients: associations with disease activity.

OBJECTIVE: To assess the presence of Epstein-Barr virus (EBV) and human herpesvirus 6B (HHV-6B) DNA in saliva and plasma from multiple sclerosis (MS) patients enrolled in a randomized, double-blind, placebo-controlled valacyclovir treatment study. METHODS: DNA was prepared following ultracentrifugation of saliva and plasma. EBV and HHV-6B DNAs were determined by real-time polymerase chain reaction. RESULTS: EBV and HHV-6B DNAs were detected in 41% and 65% of saliva samples, respectively. In patients treated with valacyclovir, the percentage of saliva samples with EBV was significantly reduced (9%; P = 0.000017), whereas the frequency of HHV-6B positive samples was unchanged (57%; P = 0.38). Longitudinal studies demonstrated a time-dependent reduction in the frequency of saliva samples containing EBV following valacyclovir treatment. In contrast, plasma contained EBV and HHV-6B DNAs in 17% and 25% of the samples, respectively, and these numbers were not significantly reduced following valacylovir treatment (13% and 16%, respectively), nor were they different from those of healthy controls (6% and 39%, respectively). Patients with high disease activity had a significantly higher frequency of EBV (P = 0.018) and HHV-6B (P = 0.023) positive samples than did patients with low disease activity. The presence of EBV and HHV-6B was strongly correlated in plasma (P < 0.00000001), but not in saliva (P = 0.41). CONCLUSION: MS patients express EBV and HHV-6B in both saliva and plasma, but only the expression of EBV in saliva is significantly reduced following valacyclovir treatment. Although EBV and HHV-6B DNAs can be detected in plasma from healthy individuals, the co-expression of both these viruses in MS patients is highly significant and further associated with clinical activity. The observations of viral DNA in plasma are consistent with an underlying immunologic defect in MS.

Acyclovir↗

Vitamin and mineral intake of twelve adolescent male Kalenjin runners in western Kenya.

OBJECTIVE: To determine whether the diet of adolescent male Kalenjin runners in a boarding school setting was adequate compared to FAO/WHO recommendations. DESIGN: A cross-sectional design study. SETTING: Marakwet High School in western Kenya. SUBJECTS: A study of twelve adolescent male Kalenjin runners was carried out to determine their micronutrient intake. MAIN OUTCOME MEASURES: Over a two-week period, samples of the main eaten food were collected for analysis of micronutrient distribution and a daily 24 recall interview performed to determine additional food intake. RESULTS: The estimated intakes were compared to recommended or suggested adequate daily intake (RSDI) by FAO/WHO. For vitamin A, pyridoxine, folic acid, vitamin B12, vitamin C, and vitamin E, the intakes represented only 17%, 82%, 56%, 55%, 95%, and 65% of RSDI, respectively. In contrast, the intakes of thiamine. riboflavin, and niacin all met RSDI by 208%, 107%, and 131%, respectively. Similarly, the intakes of magnesium, iron, and zinc were 272%, 404%, and 122% of RSDI, respectively, while calcium and selenium were below, 47% and 49%, respectively. The daily intakes of phosphorous, copper, and chromium were estimated to 4214 mg, 1309 microg, and 79 microg, respectively. CONCLUSION: Total daily micronutrient intake of the twelve Kalenjin runners was far from adequate compared to FAO/WHO daily recommended and suggested adequate intake.

Adolescent↗

The role of the p75 neurotrophin receptor in the morphology of dorsal root ganglion cells in streptozotocin diabetic mice: effects of sciatic nerve crush.

AIMS/HYPOTHESIS: Neuronal dorsal root ganglion (DRG) cells seem to be vulnerable in diabetes. The aim of this study was to determine whether the p75 neurotrophin receptor stimulates perikaryal shrinkage and neuronal death, and further accelerates neuronal DRG cell loss after axotomy in a mouse model of diabetes. METHODS: Nine non-diabetic BALB/c p75(+/+) mice, seven diabetic BALB/c p75(+/+) mice, nine non-diabetic p75(-/-) mice and nine diabetic p75(-/-) mice received a unilateral sciatic nerve crush 1 to 2 days after streptozotocin treatment. Tissues were fixed 28 days later by vascular perfusion, and the volume and number of the fifth lumbar DRG neurons were obtained using assumption-free stereological techniques. RESULTS: In diabetic p75(+/+) mice there was a 9% reduction in the perikaryal volume of the DRG A cells ( p<0.05) and a 10% reduction in the perikaryal volume of the DRG B cells ( p<0.05) on the non-crushed side compared with in non-diabetic p75(+/+) mice. However, neuronal cell number was not reduced. Conversely, no perikaryal shrinkage of A cells or B cells occurred on the non-crushed side in diabetic p75(-/-) mice, and no neuronal cell loss was observed. Following nerve crush, there was a loss of B cells in non-diabetic p75(+/+) mice (37+/-6%) and in diabetic p75(+/+) mice (36+/-4%). In non-diabetic p75(-/-) mice, no neuronal cell loss occurred after crush, whereas in diabetic p75(-/-) mice the loss of B cells (14+/-4%) was small but significant ( p<0.02). CONCLUSIONS/INTERPRETATION: In experimental diabetes the p75 neurotrophin receptor is involved in neuronal DRG cell body shrinkage without loss of neuronal DRG cells. Following sciatic nerve crush, DRG cell loss is not accelerated in diabetic p75(+/+) mice.

Animals↗

Effect of a high-protein, high-salt diet on calcium and bone metabolism in postmenopausal women stratified by hormone replacement therapy use.

The objective of this study was to investigate the influence of a high-sodium, high-protein diet on bone metabolism in postmenopausal women (aged 49-60 y) stratified by hormone replacement therapy (HRT) use. In a crossover trial, 18 women (n = 8 HRT users (+HRT) and n = 10 nonusers (-HRT)) were randomly assigned to a diet high in protein (90 g/day) and sodium (180 mmol/day) (calciuric diet) or a diet moderate in protein (70 g/day) and low in sodium (65 mmol/day) for 4 weeks followed by crossover to alternative dietary regimen for a further 4 weeks. The calciuric diet significantly (P < 0.05) increased urinary sodium, calcium and nitrogen in both groups. While the calciuric diet increased urinary N-telopeptide crosslinks of collagen (by approximately 25%, P = 0.003) in the -HRT group, it had no effect in the +HRT group. It appears that postmenopausal HRT use attenuates the increase in a marker of bone resorption associated with a calciuric diet.

Bone and Bones↗

Para-aminobenzoic acid (PABA) used as a marker for completeness of 24 hour urine: effects of age and dosage scheduling.

OBJECTIVE: To examine the age dependency of the urinary para-aminobenzoic acid (PABA) excretion, and if a delayed PABA excretion can be overcome by advancing intake schedule; and to examine the recovery of PABA in fractionated urinary samples collected during 24 h after single and repeated doses of PABA. DESIGN: Cross-over study with subjects randomized to start with recommended schedule of PABA administration (80 mg at 08:00, 12:00 and 18:00; PABA18) and then an advanced schedule (80 mg at 08:00, 12:00 and 15:00; PABA15) or vice versa. One subgroup of eight subjects collected individual urine specimens for 24 h after a morning dose of 80 mg of PABA, and another subgroup of 10 subjects collected individual urine specimens for 24 h after ingestion of 80 mg of PABA three times at mealtimes. SUBJECTS: Employees and relatives from the Danish Food Administration. SETTING: Ninety-nine healthy volunteers (61 females and 38 males) aged 30-91 y. RESULTS: Linear regressions for PABA15 and PABA18 demonstrate significantly less recovery with age (PABA15: r(2)=0.1784, P=0.0002; PABA18: r(2)=0.1273, P=0.0019). Linear regression of DeltaPABA (PABA15-PABA18) with age showed the best fit line to be horizontal (slope -0.0066, P=0.89; 95% CI -0.1046, 0.0915) and with a Y-intercept not significantly different from 0 (1.575; 95% CI -4.176, 7.326). In this population the lower limit for complete 24 h urine collection was 79.2%. After a single dosage of 80 mg PABA 70-85% was recovered after 8 h. Within 16 h after ingestion of 240 mg PABA at recommended hours the lowest acceptable recovery (78.1%) was reached. CONCLUSION: There is a gradual decline of PABA recovery with age that cannot be overcome by advancing the dosage schedule. Because of a lower delimiting PABA recovery for the elderly, some 24 h collections in this age group will be rejected unjustly (false-negatives). Also, with the currently recommended dosage schedule (PABA taken with the main meals) the risk of false-positive 24 h urine collections prevails. With refinement of the PABA test procedure, ie employing a specific analytical method and age-dependent cut-off values, the test may achieve a higher specificity and sensitivity.

4-Aminobenzoic Acid↗

Decreased muscle strength and contents of Mg and Na,K-pumps in chronic alcoholics occur independently of liver cirrhosis.

OBJECTIVES: To evaluate the influence of established liver cirrhosis on muscle strength and muscle contents of magnesium (Mg), potassium (K) and sodium, potassium pumps (Na,K-pumps) in chronic alcoholic patients. DESIGN: An open cross-sectional study. SETTING AND SUBJECTS: Forty consecutive chronic alcoholics (18 with cirrhosis and 22 without cirrhosis) admitted to the Department of Hepatology, Aarhus University Hospital, Denmark, or to a collaborating alcoholism treatment centre, and 36 healthy control subjects. MAIN OUTCOME MEASURES: Evaluation of participant's subjective physical ability and measurement of maximum isokinetic muscle strength and muscle mass, as well as measurements of Mg, K and Na,K-pumps in skeletal muscle. RESULTS: Maximum isokinetic muscle strength and muscle mass were equally reduced in patients with and without cirrhosis (P < 0.01 all). In keeping with this, both groups of patients felt equally physically restricted. Muscle Mg was reduced to the same extent in the two groups of patients (by 12 and 9%, P < 0.001, both), whereas the muscle K content was only significantly lower in the cirrhotic patients (10%, P < 0.001). The muscle content of Na,K-pumps was reduced by 14%, (P < 0.01) in the cirrhotic patients and by 8% (P < 0.05) in the noncirrhotic patients. CONCLUSION: Our alcoholic patients complained of physical disability, had reduced skeletal muscle mass, isokinetic muscle strength, content of muscle Mg and content of Na,K-pumps. There was no difference between patients with and without cirrhosis. It appears that it is the heavy alcohol intake, and not the cirrhosis per se, that is responsible for the observed defects.

Adult↗

A population based epidemiological study on myasthenia gravis in Estonia.

OBJECTIVE: To describe the occurrence of myasthenia gravis in the Baltic area. METHODS: Data were obtained from hospital files recorded during the period 1942 to 1996 from neurologists and the patient organisation. Survival data were checked with the Estonian Citizenship and Migration Board. Prevalence was determined on 1 January 1997. A questionnaire on the course of myasthenia gravis was sent to all the prevalent patients. RESULTS: The size of the population surveyed was 1 462 130. The average annual incidence from 1970 to 1996 was 4.0 per million (women, 5.2; men, 2.6). The point prevalence was 99 per million (women, 133; men 59). The incidence in the younger age group (<50 years) was 3.4 per million (women, 4.8; men, 1.9) and in the older age group (>or=50 years), 5.5 (women, 5.9; men, 4.9). The prevalence ratio was twofold higher in the older age group (p<0.0001)-for men (p = 0.034) as well as for women (p<0.001). CONCLUSIONS: Prevalence and incidence values of myasthenia gravis from Estonia are similar to those reported in most studies from Europe and north America. However, there seems to be a higher frequency in the elderly (>or=50 years) in Estonia.

Adolescent↗

A randomized, double-blind, placebo-controlled MRI study of anti-herpes virus therapy in MS.

OBJECTIVE: To evaluate the effect of treatment with the antiherpes drug valacyclovir on MRI-evident lesions in patients with relapsing-remitting MS in a phase 2, randomized, double-blind, placebo-controlled study. BACKGROUND: It has been postulated from virologic studies that herpesvirus infection could play a role in the progression of MS. METHODS: Patients were eligible for the study if they had had two or more MS relapses in the 2-year period before enrollment. Seventy patients with Expanded Disability Status Scale scores of 0 to 5.5 were randomly assigned to receive 1 gram of valacyclovir (n = 36) or placebo (n = 34) three times daily for 24 weeks. Patients underwent MRI every fourth week for 32 weeks: twice during pretreatment, six times during treatment, and once after treatment. Scoring of neurologic disability was performed at the start and end of the treatment period. The primary endpoint was the number of new active MRI-evident lesions over 24 weeks of treatment. Secondary endpoints included other MRI measures and clinical endpoints. RESULTS: The mean number of new active lesions +/- SD per patient during 24 weeks of treatment with valacyclovir was 11.9 +/- 17.6 and that during placebo treatment was 14.5 +/- 21.4. A protocol-planned exploratory analysis stratified patients according to baseline activity; this analysis showed that patients with high levels of disease activity in the valacyclovir treatment group (n = 17) developed fewer new active lesions per scan than did those in the placebo treatment group (n = 11). The median number (Q(1), Q(3) range) of active lesions was 2.0 (1.38, 3.96) in the valacyclovir treatment group and 6.5 (2.63, 9.0) in the placebo treatment group. CONCLUSIONS: Valacyclovir treatment did not reduce the formation of active lesions in patients with relapsing-remitting MS who had two or more relapses during the previous 2-year period. In a subgroup of patients with high levels of disease activity who had more than one active MRI-evident lesion during 4 weeks, valacyclovir treatment was associated with a reduced number of new active MRI-evident lesions and with an increase in the number of scans free of new active lesions. The results of the exploratory subgroup analysis provide support for further studies of antiherpes therapy for patients with MS and high levels of MRI-evident disease activity.

Acyclovir↗

Long-term acrylamide intoxication induces atrophy of dorsal root ganglion A-cells and of myelinated sensory axons.

We have examined the effects of acrylamide on primary sensory nerve cell bodies and their myelinated axons in chronic acrylamide intoxication. The numbers and sizes of dorsal root ganglion cell bodies (L5) and myelinated nerve fibers were estimated with sterelogical techniques in severely disabled rats which had been treated with 33.3 mg/kg acrylamide twice a week for 7.5 weeks. There was no loss of dorsal root ganglion cells or myelinated nerve fibers in the roots, the sciatic nerve, sural nerve, and a tibial nerve branch. The mean perikaryal volume of A-cells was reduced by 20% (2P < 0.001) from 50000 microm(3) in controls (CV = 0.13) to 40000 microm(3) (0.12), whereas B-cell volume was unchanged. All size-frequency distribution curves of myelinated axon area of peripheral nerves and sensory roots were shifted to the left towards smaller values in rats exposed to acrylamide. In the L5 sensory root 3 mm from the ganglion, there was a significant reduction of mean cross sectional area of myelinated axons by 14% (2P < 0.05) from 7.6 microm(2) (0.11) in controls to 6.5 microm(2) (0.13) in intoxicated rats. The mean cross sectional area of myelinated sural nerve axons was reduced by 22% (2P < 0.001) from 8.6 microm(2) (0.08) in controls to 6.7 microm(2) (0.17) in intoxicated rats. We conclude that chronic intoxication with acrylamide leads to selective atrophy of type A dorsal root ganglion cell bodies and simultaneous atrophy along their peripheral axons, whereas neuronal B-cell bodies and motor axons are spared. It is suggested that the neuronal atrophy might well represent a defect of neurofilament synthesis and transport.

Acrylamide↗

Predominant neuronal B-cell loss in L5 DRG of p75 receptor-deficient mice.

The significance of the p75 low-affinity neurotrophin receptor, for the maintenance and survival of DRG cells, was studied in p75-deficient mice. Perikarya of the L5 DRG of 12-week-old p75 receptor-deficient mice and healthy Balb C mice were compared using stereological techniques. Following systematic sampling, the optical fractionator and the planar vertical rotator were used to estimate the number and mean volume of the cell bodies of the two neuronal subpopulations. The loss of B-cells was 57% (P < 0.00001), numbers being 7300 (CV = 0.12) in controls and 3100 in p75 receptor-deficient mice (CV = 0.18). Also, A-cells showed a significant loss of 39% (P < 0.0001), numbers being 2600 (CV = 0.12) in control mice and 1500 (CV = 0.16) in p75 receptor-deficient mice. The volume of A-cells was reduced by 30% (P<0.01), from 24.700 microm3 (CV=0.17) perikarya in p75 knock-out mice to 15.100 microm3 (CV=0.17) in controls. B-cell volume did not change significantly. It is concluded that the p75 receptor plays a major role in the survival of DRG cells. The predominant loss of small B-cells indicates that the effect of neurotrophins is dependent upon the presence of the p75 low-affinity receptor.

Animals↗

Muscle strength, Na,K-pumps, magnesium and potassium in patients with alcoholic liver cirrhosis -- relation to spironolactone.

OBJECTIVES: To evaluate the muscle strength in relation to muscle contents of magnesium (Mg), potassium (K) and sodium, potassium (Na,K)-pumps in patients with alcoholic cirrhosis. DESIGN: An open cross-sectional study. SETTING AND SUBJECTS: Fifty-one consecutive patients with liver cirrhosis admitted to the Department of Hepatology, Aarhus University Hospital, Denmark, and 28 age- and sex-matched healthy control subjects. MAIN OUTCOME MEASURES: Biopsies of skeletal muscle were performed in patients and controls for measurements of Mg, K, and Na,K-pumps. Furthermore, maximum isokinetic knee extension and skeletal muscle mass were evaluated. RESULTS: Muscle mass, muscle strength, muscle Mg and muscle K were substantially reduced in the patients (P < 0.01, all), and fell with increasing severity of the liver disease reflected in the Child-Pugh (C-P) class. Patients treated with spironolactone for 2 weeks or more, had increased muscle strength, muscle Mg and content of Na,K-pumps, compared with the rest of the patients (P < 0.05, all). In a multivariate analysis of the patients, skeletal muscle mass, muscle Mg and daily alcohol consumption (g) were independent predictors of isokinetic muscle strength (P < 0.05, all). CONCLUSIONS: Patients with alcoholic liver cirrhosis showed considerably reduced muscle strength and muscle Mg was an independent predictor of muscle strength. Surprisingly, in the spironolactone treated patients, muscle weakness was less pronounced, possibly because of the action of spironolactone on muscle Mg, K and Na,K-pump content.

Adult↗

Unidentified bodies/skulls found in Danish waters in the period 1992-1996.

In the period 1992-1996 a total of 89 unidentified bodies/skulls found in Danish waters were investigated at the three University Institutes of Forensic Medicine in Denmark. Males constituted 79% of the total material. Open water was the finding place in half the cases, about one-fourth was found on shore and another fourth in a harbor basin. Totally 73 bodies and one skull were identified. Danes constituted 57% of the material. Almost all non-Danes originated from countries with borders to the waters surrounding Denmark. The cause of death was in 71% stated as presumably/possibly drowning, in 5% as severe lesions (precipitation) and in 25% it could not be solved. The manner of death was in non-Danes most often stated as an accident (56%), and according to this the finding place in non-Danes most frequently was the open water (66%). In Danes suicide predominated (71%) and the finding place in Danes was almost equally distributed among open water, shores and harbors, respectively. Among the totally 74 identified cases, 83% of the total material, an initial suggestion of the identity based on effects found on the body was possible in 43 cases (58%). The final identification was performed by means of forensic dental examination in total 58 cases (78%), in Danes in 93% and in non-Danes in 59%. In the remaining 16 cases one or more of the following contributed to the final identification: information about dental condition, clothing, personal papers, X-ray photos, jewelry, tattoos/scars and fingerprints. The importance of a close collaboration between the police, the forensic pathologist and the forensic dental expert in order to reach a fair number of positive identifications is emphasized.

Adolescent↗

[Cervical lymphatic metastases from occult primary tumor. A nation-wide 20-year study from the Danish society of head and neck oncology].

INTRODUCTION: The management of patients with cervical lymph node metastases from unknown primary tumours is a major challenge in oncology. This study presents data collected from all five oncology centres in Denmark. MATERIALS AND METHODS: Of the 352 consecutive patients with squamous cell or undifferentiated tumours seen from 1975 to 1995, a total of 277 (79%) were treated with radical intent. Most patients received radiotherapy to both sides of the neck as well as elective irradiation of the mucosal sites in nasopharynx, oropharynx, hypopharynx and larynx (81%). Irradiation of the ipsilateral neck only was done in 26 patients (10%). Radical surgery was the only treatment in 23 N1-N2 patients (9%). RESULTS: The five-year estimates of neck control, disease-specific survival and overall survival for radically treated patients were 51%, 48% and 36%, respectively. The emergence of the occult primary was observed in 66 patients (19%). About half of the emerging primaries were within the head and neck region with oropharynx, hypopharynx and oral cavity being the most common sites. Emerging primaries outside the head and neck region were primarily located in the lung (19 patients) and oesophagus (five patients). The most important factor for neck control was nodal stage (5-year estimates 69% [N1], 58% [N2] and 30% [N3]). Other important parameters for neck control and disease-specific survival included haemoglobin, gender and overall treatment time. Patients treated with ipsilateral radiotherapy had a relative risk of recurrence in the head and neck region of 1.9 compared to patients treated at both neck and mucosa. At five years, the estimated control rates were 27% (ipsilateral) and 51% (bilateral; p = 0.05). The 5-year disease-specific survival estimates were 28% and 45%, respectively (p = 0.10). DISCUSSION: Extensive irradiation to both sides of the neck and the mucosa in the entire pharyngeal axis and larynx resulted in significantly fewer loco-regional failures compared to patients treated with ipsilateral techniques, but only a trend towards better survival. Determination of the optimal strategy in terms of loco-regional control, survival and morbidity requires a prospective randomized trial.

Adolescent↗

Cued and non-cued repetitive ballistic movements. A kinematic study in healthy subjects.

Repetitive ballistic movements of the upper limbs were registered in 63 healthy subjects with an optoelectric 3-dimensional infrared computerized system. For evaluation of externally cued movements the arm was moved at maximum speed between two targets. As internally cued movements elbow flexion and extension at maximum speed was performed. At non-cued movements the subject shifted the hand between pronation and supination as fast as possible without further instructions. Movement velocity decreased progressively with increasing age at an annual rate of 0.5-0.6%. Women moved more slowly than men during cued movements, whereas no sex differences were found for non-cued movements. The peak velocity of cued movements remained unchanged during the 20 s performance period, whereas non-cued movements showed signs of fatigue with slowing. In conclusion, the maintenance of velocity during simple repetitive ballistic movements in healthy subjects depends on cueing and on sensory-motor function rather than on cognitive motor processing.

Adult↗

Neuronal cell death in the visual cortex is a prominent feature of the X-linked recessive mitochondrial deafness-dystonia syndrome caused by mutations in the TIMM8a gene.

The Mohr-Tranebjaerg syndrome (MIM 304700) and the Jensen syndrome (MIM 311150) were previously reported as separate X-linked recessive deafness syndromes associated with progressive visual deterioration, dystonia, dementia, and psychiatric abnormalities. In the most extensively studied Norwegian family, the Mohr-Tranebjaerg syndrome was reported to be caused by a one-basepair deletion (151delT) in the deafness/dystonia peptide (DDP) gene at Xq22. This gene has been renamed TIMM8a. We identified a stop mutation (E24X) in the TIMM8a gene segregating with the disease in the original Danish family with the Jensen syndrome, which confirms that the two disorders are allelic conditions. We also report abnormal VEP examinations and neuropathological abnormalities in affected males from the two unrelated families with different mutations. The findings included neuronal cell loss in the optic nerve, retina, striate cortex, basal ganglia, and dorsal roots of the spinal cord. The demonstration of mitochondrial abnormalities in skeletal muscle biopsies in some patients is compatible with the suggestion from recent research that the TIMM8a protein is the human counterpart of an intermembrane mitochondrial transport protein, Tim8p, recently characterized in yeast. The clinical and neuropathological abnormalities associated with mutations in the TIMM8a gene support that this X-linked deafness-dystonia-optic neuropathy syndrome is an example of progressive neurodegeneration due to mutations in a nuclear gene necessary for some, yet unknown mitochondrial transport function. We recommend sequencing the TIMM8a gene, thorough ophthalmological examination, and measuring visual evoked potentials in clinically suspected male patients with either progressive hearing impairment, dystonia, or visual disability in order to establish an early diagnosis and provide appropriate genetic counselling.

Adolescent↗

[Bite wounds and infection prophylaxis. Evidence-based therapeutic recommendations].

Infections are common complications of bite wounds, changing in severity from local cellulitis to life-threatening septicaemia. Treatment recommendations are often contradictory and rarely reflect evidence-based medicine. Risk factors associated with higher rates of infection include localization on the hands, puncture wounds and age older than 50 years. The literature is critically reviewed for evidence-based treatment of bite wounds. The results are discussed with respect to common practice in Denmark.

Age Factors↗