Deep brain stimulation in Bassen-Kornzweig syndrome: Still effective after 22 years.

Introduction: Bassen-Kornzweig syndrome or abetalipoproteinemia is a rare autosomal recessive disorder characterized by a malabsorption of dietary fat and fat-soluble vitamins. This deficiency can lead to a variety of symptoms, including hematological (acanthocytosis, bleeding tendency), neurological (tremor, spinocerebellar ataxia), neuromuscular (myopathy), ophthalmological symptoms (retinitis pigmentosa). The thalamic ventral intermediate nucleus (VIM) is a well-established target for deep brain stimulation (DBS) in the treatment of refractory tremor. Research question: We evaluated the clinical long-term follow-up (22 years) after VIM-DBS for refractory tremor in abetalipoproteinemia. We also evaluated the adjustments of stimulation settings and medication balance after DBS procedure. Material and methods: We report a 53-year-old male who suffers from abetalipoproteinemia since the age of 17. He underwent bilateral VIM-DBS to treat his disabling refractory intentional tremor at the age of 31. He still has a very good response to his tremor with limited stimulation adaptations over 22 years. For more than two decades follow-up, the treatment significantly improved his ADL functions and therefore also the QoL. Discussion and conclusion: The VIM target for DBS in the treatment of refractory tremor has been extensively reported in the literature. Thalamic VIM-DBS is a safe and effective treatment for a severe, refractory tremor as a neurological symptom caused by abetalipoproteinemia. It also highlights the importance of a multidisciplinary follow-up, to adjust and optimize the stimulation/medication balance after VIM-DBS surgery.

Can robot-assisted total knee arthroplasty be a cost-effective procedure? A Markov decision analysis.

BACKGROUND: Total knee arthroplasty (TKA) is a frequently and increasingly performed surgery in the treatment of disabling knee osteoarthritis. The rising number of procedures and related revisions pose an increasing economic burden on health care systems. In an attempt to lower the revision rate due to component malalignment and soft tissue imbalance in TKA, robotic assistance (RA) has been introduced in the operating theatre. The primary objective of this study is to provide the results of a theoretical, preliminary cost-effectiveness analysis of RA TKA. METHODS: A Markov state-transition model was designed to model the health status of sixty-seven-year-old patients in need of TKA due to primary osteoarthritis over a twenty-year period following their knee joint replacement. Transitional probabilities and independent variables were extracted from existing literature. RESULTS: The value attributed to the utility both for primary and revision surgery has the biggest impact on the ICER, followed by the rate of successful primary surgery and the cost of RA-technology. Only 2.18% of the samples yielded from the probabilistic sensitivity analysis proved to be cost-effective (threshold set at $50000/QALY). A calculated surgical volume of at least 253 cases per robot per year is needed to prove cost-effective taking the predetermined parameter values into account. CONCLUSION: Based upon transitional probabilities and independent variables derived from existing studies, RA TKA may be cost-effective at a surgical volume of 253 cases per robot per year when compared to conventional TKA.

Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia.

Autosomal recessive progressive external ophthalmoplegia is a mitochondrial disease characterized by accumulation of multiple large-scale deletions of mitochondrial DNA. We previously reported missense mutations in POLG, the gene encoding the mitochondrial DNA polymerase gamma in two nuclear families compatible with autosomal recessive progressive external ophthalmoplegia. Here, we report a novel POLG missense mutation (R627W) in a sporadic patient and we provide genetic support that all these POLG mutations are actually causal and recessive. The novel patient presented with sensory ataxic neuropathy and has the clinical triad of sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO). This is the first finding of a genetic cause of Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoparesis and it implies that this disorder may actually be a variant of autosomal recessive progressive external ophthalmoplegia. Sensory neuropathy is the initial feature in Belgian compound heterozygote autosomal recessive progressive external ophthalmoplegia patients, all carrying the POLG A467T mutation, which occurs at a frequency of 0.6% in the Belgian population.

Glycine antagonist (GV150526) in acute stroke: a multicentre, double-blind placebo-controlled phase II trial.

GV150526 is a novel glycine antagonist at the NMDA receptor complex. It is a potent neuroprotective agent in animal models of acute stroke including permanent middle cerebral artery occlusion in the rat. GV150526 was very well tolerated in early human studies. The purpose of this randomised, double-blind, multicentre, placebo-controlled trial was to assess the safety and population pharmacokinetics of GV150526 in patients with a clinical diagnosis of acute stroke. Exploratory assessment of efficacy, quality of life and resource utilisation was also undertaken. Upon clinical diagnosis of acute stroke within 12 h of onset of symptoms, patients were treated with a loading dose of 800 mg GV150526 (or placebo), followed by 5 maintenance doses of 400 mg GV150526 (or placebo) given every 12 h over 3 days. Following observation of asymptomatic hyperbilirubinaemia, the maintenance dose was reduced mid-study to 200 mg. CT/MRI scanning was not mandatory prior to treatment. The study treated 128 patients (38 with GV 800 mg/400 mg, 48 with GV 800 mg/200 mg and 42 with placebo). Fewer patients with mild stroke (NIH scores < or =5) were enrolled in the GV150526-treated groups than in the placebo group (placebo 38%, GV 800 mg/400 mg 18%, GV 800 mg/200 mg 15%). There was also an imbalance in the proportion of patients with haemorrhagic strokes (placebo 5%, GV 800 mg/400 mg 3%, GV 800 mg/200 mg 15%). Mortality at 1 month was unbalanced between treatment groups, being 10, 18 and 17% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively (no significant difference). Similarly, adverse events, though consistent with an acute stroke population, appeared more often in the GV 800 mg/200 mg group. Functional outcomes at 1 month also showed imbalances, the percentage of patients with a Barthel Index score of > or =95 at 1 month being 52, 39 and 27% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively. These results probably reflect a prognostically significant baseline difference between the groups rather than the effect of GV150526. GV150526 was generally well tolerated in patients with a clinical diagnosis of acute stroke and formal efficacy studies were considered justified.

Reboxetine versus imipramine in the treatment of elderly patients with depressive disorders: a double-blind randomised trial.

BACKGROUND: Depression in older people is often unrecognised and untreated or under-treated. Antidepressant treatment may itself exacerbate a pre-existing illness, interact with concomitant medications or produce undesirable cognitive and sedative side effects. Newer antidepressants may offer advantages in terms of a lesser burden of adverse effects. METHODS: The comparative tolerability of the unique selective noradrenaline reuptake inhibitor (selective NRI) reboxetine (4-6 mg/day; n = 176) and that of imipramine (50-100 mg/day; n = 171) was assessed in an elderly ( > 65 years) cohort of depressed or dysthymic patients in an 8-week, double-blind, multicentre trial. Comparative efficacy was also assessed. RESULTS: Overall, 68% of patients in the reboxetine group experienced adverse events compared with 71% in the imipramine group. Reboxetine-treated patients were less likely to develop hypotension and related symptoms (7% vs. imipramine 16%) or cardiovascular disorders (12.5% vs. imipramine 21.1%), while those treated with imipramine were less likely to experience insomnia (6.3% vs. 2.9%). Adverse events were more often assessed as related to treatment (43%) and moderate to severe in intensity (73%) with imipramine than with reboxetine (33% and 65%, respectively). Furthermore, there were fewer serious adverse events in the reboxetine-treated group (P = 0.019). The reduction in the Hamilton Rating Scale for Depression (HAM-D) was comparable between the treatment groups in the total population. At the last assessment, the majority of patients in both treatment groups were assessed as normal to borderline or mildly ill using the Clinical Global Impression (CGI) scale. In a subanalysis of the dysthymic patients a modest but significant difference in favour of imipramine was observed for both HAM-D and CGI assessments. This may have been a reflection of a trend towards more severe depressive symptoms at baseline in the reboxetine group. CONCLUSIONS: Reboxetine is as effective as imipramine in the treatment of depression in elderly patients but is at least as well tolerated with a lower risk of hypotension and related symptoms, fewer serious adverse events, adverse event-related withdrawals and treatment-related adverse events.

The complete DNA sequence and the genetic organization of the short unique region (US) of the bovine herpesvirus type 1 (ST strain).

The DNA sequence of bovine herpesvirus type 1 (BHV-1) ST strain (BHV-1.2 subtype) entire unique short (US) region and part of adjacent flanking sequences of the inverted repeats was determined. The BHV-1 ST US region is 9745 bp in size and has a 70.5% G + C content. Eight potential open reading frames (ORFs) longer than 100 amino acids and designated ORF1 to ORF8 were identified on this sequence. Seven of these had counterparts in the US of herpes simplex type 1 (HSV-1), pseudorabies virus (PRV), and equine herpesvirus type 1 (EHV-1). BHV-1 ORF2 encodes a protein homologous to HSV-1 US2; ORF3 putative protein exhibits homology with HSV-1 US3 (serine-threonine protein kinase); ORF4 encodes a putative glycoprotein homologous to PRV gG (gX) and EHV-1 gG (gX); ORFs 5,6, and 7 encode respectively HSV-1 glycoproteins gD, gl, and gE homologues; and ORF8 codes for a putative homologue of HSV-1 US9. Although BHV-1 ST strain apparently lacks a HSV-1 US1 homologue, the genetic content and the genomic organization of its US region was found to be similar to the general organization already described for HSV-1, EHV-1, PRV, and avian herpesviruses HVT and MDV US regions. In fact, the BHV-1 US region genomic organization is the closest to the general consensus determined from the comparison of known alphaherpesvirus US regions.

[Non-invasive diagnosis of phlebothrombosis of the limbs. Prospective evaluation of mercury gauge plethysmography associated with ultrasonic Doppler]. / Le diagnostic non invasif des phlébothromboses des membres. Evaluation prospective de l'association pléthysmographique à jauge de mercure-Doppler ultrasonique.

Associated ultrasonic Doppler study (D) and plethysmography (P) were evaluated as compared to phlebography in diagnosis of venous thrombosis of the lower limbs (TVP). Probes (5 and 7.5 MHz respectively) were used in D for examination of proximal and calf veins. Plethysmography using a mercury ring gauge (Perivein, ETNA) was considered pathologic if filling volume was less than 1.5 vol% and/or emptying volume less than 40 ml/min/100 ml. One hundred and four patients hospitalized in an internal medicine department for suspected deep venous thrombosis were studied, including 97 for whom phlebography interpretation was unmistakable: 11 calf vein, 28 collector trunk and 42 total limb involvement TVP. In these localizations, D sensitivity was respectively 55, 72 and 100% (mean 85.5%) and that of P 63.5, 68 and 88% (mean 77.7%); association of D or P improved sensitivity: 82, 82 and 100% (mean 91.5%). Specificity was 86.6% for D, a poor 62.5% for P and 93.5% for associated D and P. The results are comparable to those in the literature but disappointing for diagnosis of isolated calf vein TVP. False-negatives in both D and P were due to strong collateral circulation or limited thrombus extension.

Abetalipoproteinemia or Bassen-Kornzweig syndrome. Clinical, biochemical and electrophysiological features of two cases.

The clinical, biochemical and electrophysiologic features of two patients with abetalipoproteinemia, a 17 year old boy and his sister of 14, are reported. They are the second and third reports of this disease in Belgium. Diagnosis was made by the Apo-B deficiency in their serum and the normal levels in their parents'. According to other investigators we revealed in both cases deficiency of other apoproteins, indicating, that the metabolic defect affects all classes of plasma lipoproteins. EMG findings showed axonal neuropathy. Somatosensory evoked potentials demonstrated dorsal column dysfunction. Findings were consistent with the known neuropathology of abetalipoproteinemia and of vitamin E deficiency syndromes. The therapeutic role of vitamin E is discussed.

[Research policy in gerontology: "Advice on programs and tools in gerontological research"]. / Onderzoeksbeleid in de gerontologie: het 'Advies inzake programma en instrumentarium voor gerontologisch onderzoek'.

The 'Planninggroup for Gerontological research' published in february 1981 the 'Research plan in gerontology in the Netherlands'. In this article attention is given to some characteristics of science policy in the Netherlands during the last few years. Some features of the history and methods of working of the Planninggroup are pointed out. Next the main recommendations of the research-plan are stated: The premises on which the programming is based; the considerations to obtain a balance in attention paid to several research-fields; criteria for priority-setting (both scientific and social relevance criteria). Based on symptoms and problems in processes of aging twelve research-fields are chosen. Within these fields principal topics are further developed. The premises and criteria result into the selection of 22 priority research-projects. Recommendations are made for execution of the research-plan. It is suggested to establish a so called 'Gerontology Research Commission'. The task is to coordinate execution of the program within a 5-year period. Ways to execute the research-plan are given. A significant governmental investment in research on aging (100 research-positions in the 5 year period) is needed. In the discussion some consideration is given to the investment in manpower in gerontological research in the Netherlands and the costs of making the research-plan. The relation of the plan with the existing research-situation is stressed.

Influence of diet on in vitro and in vivo rates of fatty acid synthesis in coho salmon [Oncorhynchus kisutch (Walbaum)].

The site and the influence of diet on fatty acid synthesis in juvenile coho salmon were investigated. Tritiated water was used to obtain estimates of the rates of fatty acid synthesis. Liver slices and mesenteric glucose and tritiated water. The rate of fatty acid synthesis averaged 1172 +/- 126 and 40 +/- 8 nmoles tritium incorporated into fatty acids per 2 hours per 100 mg of liver and adipose tissue, respectively. The pattern of [1-14C]acetate incorporation into fatty acids in the liver slices indicated that de novo fatty acid synthesis, rather than chain elongation, was occurring. In vivo rates of fatty acid synthesis in liver were approximately linear for 30 minutes. In vivo rates of fatty acid synthesis averaged 244 +/- 14 and 44 +/- 11 dpm of tritium incorporated into fatty acids per 20 minutes per 100 mg of liver and adipose tissue, respectively. Consumption of a high-fat diet or fasting for 2 days decreased the in vitro and in vivo rates of fatty acid synthesis in fish liver. Refeeding fasted (48 hours) fish with a high-carbohydrate diet for 4 hours increased the rate of hepatic fatty acid synthesis. The major site of fatty acid synthesis in coho salmon appears to be the liver, and dietary alterations influence the rate of fatty acid synthesis in the liver.

Effects of fasting and feeding various diets on hepatic lipogenic enzyme activities in coho salmon (Oncorhynchus kisutch (Walbaum)).

The influence of fasting and diet composition on the time sequence of changes in hepatic lipogenic enzyme activities in coho salmon was investigated. Young coho salmon fed a high-carbohydrate diet for 3 weeks were then fasted for 2, 6, or 23 days. Liver preparations were assayed for fatty acid synthetase, citrate cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities. Fasting the fish for 2 or 6 days did not influence the activities of these enzymes; however, by the end of the 23-day fast the activities of all these enzymes had decreased. Changing the diet of the fish from high-carbohydrate to high-fat had only a minimal influence on the activities of the hepatic lipogenic enzymes after 7 to 14 days. Longer-term studies demonstrated that high-fat diets did eventually depress lipogenic enzyme activities. The effect of fasting and feeding on the level of lipogenic enzyme activities was observed only after several weeks, in contrast to hours in the rat. This may reflect a difference between poikilothermous and homoiothermous animals.

Influence of dietary lipid on lipogenic enzyme activities in coho salmon, Oncorhynchus kisutch (Walbaum).

Coho salmon (Oncorhynchus kisutch), 8 to 18 months of age, were maintained in culture tanks and were fed three semipurified diets. The diets contained 40% of energy from protein and 11.5%, 23%, or 46% of energy from lipid. The body weight gain and food conversion factors were similar among groups of fish fed the diets in each of the three experiments. Wet weight of mesenteric adipose tissue increased with increased amount of lipid in the diet; however, epaxial muscle lipid content was not influenced by the lipid content of the diet. Several hepatic and adipose tissue lipogenic enzymes (fatty acid synthetase, citrate cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-isocitrate dehydrogenase) were assayed. These lipogenic enzymes exhibited high activities in liver and relatively low concentration in adipose tissue of the fish. The activities of all the hepatic lipogenic enzymes assayed, except for NADP-isocitrate dehydrogenase, were depressed as the level of lipid in the diet was increased; however, the activities of these enzymes in mesenteric adipose tissue were not influenced by the diets fed. The results of this study indicate that dietary lipid depresses hepatic lipogenic enzyme activities and that the liver may be a more important site for fatty acid synthesis than is adipose tissue in coho salmon.