"INTERMED": a method to assess health service needs. II. Results on its validity and clinical use

The validity and clinical use of a recently developed instrument to assess health care needs of patients with a physical illness, called INTERMED, is investigated. The INTERMED combines data reflecting patients' biological, psychological, and social characteristics with information on health care utilization characteristics. An example of a patient population in which such an integral assessment can contribute to the appropriateness of care, are patients with low back pain of degenerative or unknown origin. It supports the validity and the clinical usefulness of the INTERMED when clinically relevant subgroups in this heterogeneous population can be identified and described based on their INTERMED scores. The INTERMED was utilized in a group of patients (N = 108) having low back pain who vary on the chronicity of complaints, functional status, and associated disability. All patients underwent a medical examination and responded to a battery of validated questionnaires assessing biological, psychological, and social aspects of their life. In addition, the patients were assessed by the INTERMED. It was studied whether it proved to be possible to form clinically meaningful groups of patients based on their INTERMED scores; for this, a hierarchical cluster analysis was performed. In order to clinically describe them, the groups of patients were compared with the data from the questionnaires. The cluster analysis on the INTERMED scores revealed three distinguishable groups of patients. Comparison with the questionnaires assessing biological, psychological, and social aspects of disease showed that one group can be characterized as complex patients with chronic complaints and reduced capacity to work who apply for a disability compensation. The other groups differed explicitly with regard to chronicity, but also on other variables. By means of the INTERMED, clinically relevant groups of patients can be identified, which supports its use in clinical practice and its use as a method to describe case mix for scientific or health care policy purposes. In addition, the INTERMED is easy to implement in daily clinical practice and can be of help to ease the operationalization of the biopychosocial model of disease. More information on its validity in different patient populations is necessary.     

Intramuscular inoculation of Sin Nombre hantavirus cDNAs induces cellular and humoral immune responses in BALB/c mice.

To examine whether genetic immunization with Sin Nombre (SN) hantavirus genes could elicit immune responses, nine fragments spanning the envelope glycoprotein genes G1 and G2, and the complete N gene were cloned into a CMV expression vector. To ensure representation of all potential epitopes, adjacent fragments of the glycoprotein genes overlapped one another by 100 nucleotides. Vectors containing the gene fragments were inoculated intramuscularly into BALB/c mice and splenocyte proliferation and western blot-detectable antibodies and neutralization titers were determined. The N gene and seven of the nine M segment-derived cDNAs tested produced significant specific lymphoproliferative responses, and many of the constructs elicited either neutralizing or western blot-detectable antibodies. These promising results encourage the development of infection models for SN virus that will be capable of detecting protective responses.     

Clinical and economic evaluation of benzodiazepines: a value analysis

Benzodiazepines are one of the most frequently prescribed classes of medications in the world. Thought to relieve the symptoms of anxiety, insomnia, epilepsy, and some less common conditions, these medications are supported by a body of clinical trials demonstrating efficacy. However, there is also literature that suggests problems of abuse and dependence, along with some serious adverse effects. The present article utilises a value-analysis strategy to outline the clinical efficacy and economic efficiency of benzodiazepines from a variety of perspectives including those of the patient, physician and manufacturer. Results of this analysis suggest that these medications are effective when used appropriately, but that implementation of appropriate use is difficult. Remedies to this situation are discussed.     

Structure and function of the neuromuscular junction in young adultmdx mice

Summary Dystrophin, the protein product of the gene responsible for X-linked muscular dystrophies, shares structural features with the cytoskeletal proteins spectrin and -actinin. Like spectrin, it is localized at the cytoplasmic surface of the sarcolemma and is particularly concentrated in the subsynaptic region of the neuromuscular junction.Mdx mice have a profound deficiency of dystrophin and develop a necrotizing myopathy in the first weeks of life. Abnormalities of the neuromuscular junction, including a redistribution of postsynaptic molecules and reduction in synaptic folding, are also observed. We have studied these mice to see whether the lack of dystrophin has a specific effect on the structure and function of their neuromuscular junctions.Using a fore-limb muscle from 8 week oldmdx mice we confirm the previously described postsynaptic structural changes and in addition show that many nerve terminals are abnormally complex. We demonstrate that these structural abnormalities are found exclusively at neuromuscular junctions on regenerated muscle fibres. Despite these structural abnormalities, miniature endplate potential frequency, the quantal content of endplate potentials, the amplitude and time course of miniature endplate currents and the number of acetylcholine receptors at the postsynaptic membrane are normal inmdx mice of this age. We conclude that in themdx mouse the absence of dystrophin from the postsynaptic membrane has little direct effect on the function of the neuromuscular junction but that degeneration and regeneration of muscle fibres leads to remodelling of both its pre- and postsynaptic components.     

Malignant transformation of a Hürthle cell tumor: case report and survey of the literature

Hürthle cell carcinoma is a relatively uncommon type of well-differentiated thyroid carcinoma. Its diagnosis has been controversial due to the difficulty in separating Hürthle cell adenoma from Hürthle cell carcinoma, thus the term Hürthle cell tumor is often used to describe both lesions. The present case of anaplastic giant-cell carcinoma in an 81-yr-old woman arose in a Hürthle cell tumor. This case illustrates the propensity of Hürthle cell tumor to undergo "malignant transformation" and argues for a more aggressive approach to such tumors.     

Early mutation of the neu (erbB-2) gene during ethylnitrosourea-induced oncogenesis in the rat Schwann cell lineage.

The development of malignant tumors of the peripheral nervous system (schwannomas) within a defined intracranial section of the rat trigeminal nerve ("trigeminal box") was used as a model to identify genetic alterations typically associated with the process of cell-lineage-specific oncogenesis induced by exposure to N-ethyl-N-nitrosourea on postnatal day 1. All 47 trigeminal schwannomas (and 12 extracranial neurinomas) investigated carried a T.A----A.T transversion mutation at nucleotide 2012 of the neu (erbB-2) gene sequence encoding the transmembrane domain of pg185neu. This mutation was absent in all 18 tumors in the brain and spinal cord (central nervous system) isolated from the same animals. Identical observations were made in cell lines derived from N-ethyl-N-nitrosourea-induced rat schwannomas vs. brain tumors. By asymmetric PCR and mutant-specific Mnl I restriction fragment length analyses, cells carrying the mutant neu allele became detectable and could be localized within the trigeminal box as early as 7 days after the carcinogen pulse. The proliferation rate of the mutant cells strongly exceeded that of the wild-type cells up to the time of maturation of the trigeminal nerve around postnatal day 30 and thereafter to a lesser extent until the appearance of schwannomas. A specific mutation of the neu gene thus represents a very early, probably the first, step in the malignant conversion of immature rat Schwann cells exposed to N-ethyl-N-nitrosourea in vivo and is diagnostic for a subset of proliferative cells at high risk of progressing toward the expression of fully malignant phenotypes. Loss of heterozygosity for the mutant neu allele is a candidate event for a critical second step in the process.