心脏神经官能症误诊为冠心病27例分析

对我院2002-01～2005-01心脏神经官能症误诊为冠心病27例分析如下。 1 临床资料 1．1 一般资料 本组男8例，女19例。28-40岁19例，40～60岁6例，60岁以上2例。发病至确诊时间为7d～3a。发病有明显诱因18例，其中因工作学习紧张10O例，不良精神刺激因素6例，医源性因素2例，无明显诱因9例。本组均有心悸症状，表现程度不同，胸闷、胸痛21例，心前区不适6例，呼吸困难18例，头晕、头痛12例，睡眠障碍15例，体检偶有期前收缩2例。     

Knowledge about asthma and COPD: associations with sick leave, health complaints, functional limitations, adaptation, and perceived control

We sought to investigate associations between knowledge about the disease and sick leave, health complaints, functional limitations, adaptation and perceived control. Patients with asthma (n = 101) and COPD (n = 64) underwent lung function tests and completed questionnaires. In addition, all were asked the question: ‘what is the diagnosis of your disease?’, with the response categories: ‘asthma’ and ‘COPD (chronic bronchitis or emphysema)’. Thirty-five percent of the asthma patients and 30% of the COPD patients did not know their correct diagnosis. Sick leave was not associated with knowledge about the disease in asthma and COPD. In asthma, much knowledge about management of the disease was associated with better adaptation (P = 0.01) and less perceived control over health by external factors (P = 0.02). Knowing the correct diagnosis was associated with less control over health by powerful others (P = 0.02). For COPD, more knowledge about management of the disease was associated with better adaptation (P = 0.02) and less control over health by internal factors (P = 0.01). Knowing the correct diagnosis was associated with less control over dyspnea at work (P = 0.01).     

Carcinoid tumors of the intestines: developments in the Netherlands for diagnosis and palliative treatment

Carcinoid tumours in the intestine are slowly growing neuroendocrine tumours. Patients as a rule report symptoms of the carcinoid syndrome: attacks of diarrhoea and of flushing. When the earliest symptoms manifest themselves, metastases are already present, virtually always localized in the liver. At a late stage, heart failure may occur, difficult to treat and caused by fibrosis of the tricuspid valve in the presence of protractedly raised blood serotonin levels. To diagnose carcinoid tumours, use is made of radioactive substances binding to hormone receptors such as 131I-MIBG and 111-In-octreotide. When multiple metastases exist, only palliative treatment is possible. The drugs used are the somatostatin analog octreotide, interferon alpha, radioactive MIBG and non-radioactive MIBG; these drugs may also be used in combination. The therapies mentioned have approximately the same effect: symptoms improve in 60-80%, while 30-50% show a biochemical response, i.e. decrease of the number of breakdown products in the urine of the hormones produced by the tumour; tumour size decreases in 0-12%.     

Efficient rescue of infectious bursal disease virus from cloned cDNA: evidence for involvement of the 3'-terminal sequence in genome replication

To study the mechanism of replication of infectious bursal disease virus (IBDV), and to determine factors on the IBDV RNA which are involved in viral replication, we used cloned full-length cDNA of both the A- and B-segments to generate infectious IBDV. Infectious IBDV was rescued from plasmids that contained full-length IBDV cDNA behind a T7 promoter, by transfecting these plasmids into cells which were infected with a recombinant Fowlpox virus that expressed T7 RNA polymerase. By using the cDNA transfection system we evaluated the effect of the length of the 3' terminus of the A-segment plus strand of IBDV. Although wild-type IBDV predominantly contains four cytosines at the 3' terminus, no difference in virus yield was found when virus was rescued from cDNAs containing three to six adjacent cytosines. When the 3' terminus was shorter than three cytosines the efficiency to generate infectious IBDV from cDNA was reduced, but IBDV could still be recovered reproducibly. The rescued viruses from cDNAs containing 3'-terminal deletions appeared to have a restored 3'-terminal sequence. The missing nucleotides are probably restored by using complementary bases of a stem-loop structure as template.     

Head injury in the severely injured: long-term follow-up in 157 patients

Ninety-two patients with head injury in the context of multiple injury were followed up 5 years after injury. Severe disability in this group of patients was nearly always due to brain/spinal cord injury, rather than musculoskeletal injury. A substantial number of patients with mild or moderate head injuries had significant persisting disability 5 years after injury.     

Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis

Gaucher disease (GD), an inherited macrophage glycosphingolipidosis, manifests with an extraordinary variety of phenotypes that show imperfect correlation with mutations in the GBA gene. In addition to the classic manifestations, patients suffer from increased susceptibility to hematologic and nonhematologic malignancies. The mechanism(s) underlying malignancy in GD is not known, but is postulated to be secondary to macrophage dysfunction and immune dysregulation arising from lysosomal accumulation of glucocerebroside. However, there is weak correlation between GD/cancer phenotype and the systemic burden of glucocerebroside-laden macrophages. Therefore, we hypothesized that genetic modifier(s) may underlie the GD/cancer phenotype. In the present study, the genetic basis of GD/T-cell acute lymphoblastic lymphoma in 2 affected siblings was deciphered through genomic analysis. GBA gene sequencing revealed homozygosity for a novel mutation, D137N. Whole-exome capture and massively parallel sequencing combined with homozygosity mapping identified a homozygous novel mutation in the MSH6 gene that leads to constitutional mismatch repair deficiency syndrome and increased cancer risk. Enzyme studies demonstrated that the D137N mutation in GBA is a pathogenic mutation, and immunohistochemistry confirmed the absence of the MSH6 protein. Therefore, precise phenotype annotation followed by individual genome analysis has the potential to identify genetic modifiers of GD, facilitate personalized management, and provide novel insights into disease pathophysiology.     

Comparison of the hepatitis B virus core, surface and polymerase gene substitution rates in chronically infected patients

For phylogenetic comparison of hepatitis B virus (HBV) isolates, often a region of the HBV surface gene is analysed. Because the surface gene completely overlaps the polymerase gene, its evolution is constrained, and it may not be the best choice for genetic comparison of HBV isolates. Analysing serial sample pairs of 33 chronically HBV-infected, untreated patients, with a cumulative follow-up of 184 years, the synonymous and nonsynonymous substitution rates of a part of the overlapping HBV surface and polymerase genes were compared to those of a nonoverlapping part of the HBV core gene. The substitution rate of the HBV core gene was higher (8.15 × 10(-4) vs 4.57 × 10(-4) substitutions/site/year) than that of the surface gene. The difference was mainly due to a significantly lower synonymous substitution rate in the surface gene, with dN/dS ratios of 0.412 in the core gene and 0.986 in the surface gene. Contrary to the core gene, the number of substitutions in the surface gene was higher in low viraemic hosts, who control HBV infection by suppressing replication. The number of substitutions in the core gene correlated more strongly with the duration of follow-up. The overlapping HBV surface and polymerase genes experience strong negative selection, which limits the number of substitutions. Because the HBV core gene reflects the duration of infection more accurately, it is more suitable for the analysis of short-term viral evolution and of hepatitis B transmission chains.     

Recent progress in the development of subtype selective nicotinic acetylcholine receptor ligands

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand gated ion channels, which are found at the neuromuscular junction and in the central and peripheral nervous systems. The channels can be assembled from fourteen known subunits. The exact combination and function of all the channels are still not determined but in the CNS certain combinations have been identified which appear to modulate the release of specific neurotransmitters. Non-specific nAChR agonists like nicotine and epibatidine, have been shown to have interesting pharmacology but their clinical value is limited by their undesirable side effects. Selective ligands for different receptor subtypes have been reported and these compounds are probably the best tools for determining the function of the subtypes. The expectation is that some receptor subtype selective nAChR ligands will be clinically useful for the treatment of a broad range of CNS disorders. The development of stable cell lines functionally expressing specific combinations of subunits has greatly improved our understanding of ligand specificity. There have also been advances in the modelling of the ligand binding site, thanks to the discovery of a homologous snail ACh binding protein the X-ray structure of which was determined in 2001. These techniques should lead to rapid advances in the development of truly subtype selective ligands. In this review we describe recent progress in the area and describe the first 1000 fold selective low molecular weight ligands from the AstraZeneca group. We also comment on the first subtype specific channel modulators.     

Musculoskeletal recovery 5 years after severe injury: long term problems are common

Five years after severe injury (ISS>15), usually involving several body regions, 158 patients were assessed regarding their musculo-skeletal recovery. An earlier paper in this journal about this study 'Injury 29 (1998) 55' showed that when considering the main body regions causing long term disability, 45% were due to bony injuries to the extremities, pelvis and shoulder girdle. We analysed these body areas regarding the degrees of disability and pain and also for problems with activities of daily living, work, sport and mobility. All patients with unstable pelvic fractures had moderate or severe persisting disability and chronic pain. Functional problems with activities of daily living, work, sport and mobility were reported in 28, 86, 100 and 100% of patients, respectively. Patients with stable pelvic fractures had persisting disability in 54% of cases, which was mild in 42% and moderate or severe in 12% of patients. In patients with stable pelvic fractures 54% had chronic pain, which was mild in 24% of patients and moderate or severe in 30% of patients. Functional problems with mobility, work and sport were reported in 38, 19 and 19% of patients, respectively. Patients with shoulder girdle injuries had persisting disability in 48% of cases which was mild in 24% and moderate or severe in 24% of patients. In patients with shoulder girdle injuries 45% had chronic pain, which was mild in 14% and moderate or severe in 31% of patients. Functional problems with activities of daily living, work, sport and mobility were reported in 38, 28, 38 and 38% of patients respectively. Patients with upper limb fractures had persisting disability in 66% of cases which was mild in 34% of patients and moderate or severe in 32% of patients. Chronic pain was present in 62% of these cases, which was mild in 32% and moderate or severe in 34% of patients. Functional problems with activities of daily living, work, sport and mobility were reported in 31, 45, 48 and 66% of patients, respectively. Patients with lower limb fractures had persisting disability in 84% of cases, which was mild in 16% and moderate or severe in 68% of patients. Chronic pain was present in 80% of these cases, which was mild in 24% and moderate or severe in 56% of patients. Functional problems with activities of daily living, work, sport and mobility were reported in 40, 56, 64 and 76% of patients, respectively. Patients with multiple extremity injuries or combinations of pelvic and lower extremity or shoulder girdle and upper extremity injuries were much more likely to have continuing disability compared with those sustaining single bone injuries of that limb. This high disability rate reflecting treatment in 1989-1990, raises the question of whether our present policy of earlier and better fixation and rehabilitation of fractures in severely injured patients (ISS>15) can improve these results.