Minnesota Multiphasic Personality Inventory (MMPI) cluster groups among chronically ill patients: Relationship to illness adjustment and treatment outcome

Cluster analysis of the MMPI has been utilized widely in the chronic low back pain literature to try to identify reliable patient subtypes predictive of treatment outcome. We extended this methodology to patients with heterogeneous chronic medical conditions by replicating prototypic MMPI cluster group profiles and by relating cluster groups to clinical baseline and outcome data. Subjects were two independent samples (n=254 and n=263) of chronically ill patients admitted to an inpatient medicine/psychiatry unit. Using a four-cluster solution, similar cluster profile groups were replicated in both samples. Consistent differences emerged between cluster groups on functional impairment, psychiatric diagnoses, depression, and psychosomatic symptoms. Cluster group membership also predicted changes in functional impairment and depression six months after treatment. Results are discussed in terms of similarities between chronic low back pain and chronic illness and tailoring treatment to different patient types.This research was supported in part by a grant from the Henry J. Kaiser Family Foundation.     

Development of capture assays for different modifications of human low-density lipoprotein

Antibodies to malondialdehyde (MDA)-modified low-density lipoprotein (LDL), copper-oxidized LDL (oxLDL), Nepsilon(carboxymethyl) lysine (CML)-modified LDL, and advanced glycosylation end product (AGE)-modified LDL were obtained by immunization of rabbits with in vitro-modified human LDL preparations. After absorption of apolipoprotein B (ApoB) antibodies, we obtained antibodies specific for each modified lipoprotein with unique patterns of reactivity. MDA-LDL antibodies reacted strongly with MDA-LDL and also with oxLDL. CML-LDL antibodies reacted strongly with CML-LDL and also AGE-LDL. oxLDL antibodies reacted with oxLDL but not with MDA-LDL, and AGE-LDL antibodies reacted with AGE-LDL but not with CML-LDL. Capture assays were set with each antiserum, and we tested their ability to capture ApoB-containing lipoproteins isolated from precipitated immune complexes (IC) and from the supernatants remaining after IC precipitation (free lipoproteins). All antibodies captured lipoproteins contained in IC more effectively than free lipoproteins. Analysis of lipoproteins in IC by gas chromatography-mass spectrometry showed that they contained MDA-LDL and CML-LDL in significantly higher concentrations than free lipoproteins. A significant correlation (r=0.706, P<0.019) was obtained between the MDA concentrations determined by chemical analysis and by the capture assay of lipoproteins present in IC. In conclusion, we have developed capture assays for different LDL modifications in human ApoB/E lipoprotein-rich fractions isolated from precipitated IC. This approach obviates the interference of IC in previously reported modified LDL assays and allows determination of the degree of modification of LDL with greater accuracy.     

Rapid differentiation of the major causative agents of bacterial meningitis by use of frequency-pulsed electron capture gas-liquid chromatography: analysis of amines.

The major causative agents of bacterial meningitis (Haemophilus influenzae serogroup B, Neisseria meningitidis serogroups B and C, Klebsiella pneumoniae, Steptococcus pneumoniae, and two types of Escherichia coli) were cultured in a chemically defined medium, and selected strains were further studied in Todd-Hewitt medium. After acidic extraction of the spent media with chloroform, a basic extraction was made with chloroform to obtain amines. A third extraction was performed on re-acidified Todd-Hewitt medium with ethyl ether to obtain hydroxyacids. The extracts were derivatized with heptafluorobutyric anhydride-ethanol to form electron-capturing derivatives, and the derivatives were analyzed on a frequency-pulsed electron capture gas-liquid chromatograph (FPEC-GLC) equipped with a PEP-2 computer. The data obtained from the study showed that amines were produced by these organisms that formed characteristic patterns. Different serotypes of K. pneumoniae and the two serogroups of N. meningitidis produced different types of FPEC-GLC profiles within serotypes. E. coli produced several hydroxy acids on Todd-Hewitt medium that made it unique among the organisms studied. The methods used are practical and the techniques have potential for use in clinical laboratories and hospitals as a valuable aid for the rapid identification of the major causative agents of bacterial meningitis.     

Pentoxifylline treatment of mice with chronic pulmonary tuberculosis accelerates the development of destructive pathology

It is well established in animal models that production of the cytokine tumour necrosis factor-alpha (TNF-alpha) is essential to the proper expression of acquired specific resistance following infection with Mycobacterium tuberculosis. This gives rise to an apparent state of chronic disease which over the next 100-200 days is characterized by slowly worsening pathological changes in the lung. To determine whether continued TNF-alpha production was harmful during this phase mice were treated with a TNF-alpha inhibitor, pentoxifylline. It was observed that although this therapy did not alter the numbers of bacteria recovered from the lungs of the infected mice, tissue damage within the lung was accelerated. These data thus demonstrate that production of TNF-alpha, already known to be important during the early expression of resistance to tuberculosis, remains important and beneficial during the chronic stage of the disease.     

Immunohistochemical analysis of MCT1, MCT2 and MCT4 expression in rat plantaris muscle

All three forms of recombinant low voltage-activated T-type Ca²⁺ channels (Ca_v3.1, Ca_v3.2 and Ca_v3.3) exhibit a small, though clearly evident, window T-type Ca²⁺ current ( I _Twindow) which is also present in native channels from different neuronal types. In thalamocortical (TC) and nucleus reticularis thalami (NRT) neurones, and possibly in neocortical cells, an I _Twindow-mediated bistability is the key cellular mechanism underlying the expression of the slow (< 1 Hz) sleep oscillation, one of the fundamental EEG rhythms of non-REM sleep. As the I _Twindow-mediated bistability may also represent one of the cellular mechanisms underlying the expression of high frequency burst firing in awake conditions, I _Twindow is of critical importance in neuronal population dynamics associated with different behavioural states.     

A pharmacological and histological examination of the microcirculation of the rat subcutaneous air-pouch: microcirculation of the rat air-pouch

The effects of histamine, 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) on plasma protein extravasation in the rat subcutaneous air-pouch have been studied. Both histamine and 5-HT produced increases in plasma protein extravasation which were inhibited by specific receptor antagonists. Plasma protein extravasation induced by PGE2 was partially inhibited by either a 5-HT receptor antagonist (methysergide) or by a combination of H1 and H2 receptor antagonists (mepyramine and cimetidine). A combination of all three antagonists further reduced plasma protein extravasation. These results suggest that PGE2 increases vascular permeability indirectly via the degranulation of mast cells. This supposition was confirmed by histological evidence of extensive mast cell degranulation following the injection of PGE2 but not following histamine, 5-HT or saline injection. Using a technique of vascular labelling, following the intravenous injection of Monastral blue dye, plasma extravasation induced by histamine, 5-HT or PGE2 was observed to be restricted to post-capillary venules and was not observed in arterioles or capillaries. Electron microscopic examination of the tissue revealed the presence of monastral blue particles trapped between endothelial cells. These findings suggest that the microcirculation of the rat subcutaneous air-pouch behaves in an analogous manner to that of other tissues.     

An investigation into the relationship between salivary cortisol,stress, anxiety and depression

This study examined the relationship between indices of self-reported emotional distress and absolute versus change in cortisol levels. Fifty-four women attending a diagnostic breast clinic completed scales measuring stress, anxiety and depression and provided five saliva samples over the course of a single day for the measurement of cortisol. No significant relationships were evident between absolute cortisol levels and the distress measures. Analysis of the change in cortisol levels revealed a non-linear interaction effect between stress and anxiety and time of day. There was a non-linear relation between time of day and cortisol levels, but the extent of the non-linearity was dependent upon levels of stress and anxiety, not depression. A relationship was apparent between indices of distress and change in cortisol levels, but not absolute levels of the hormone.     

Evaluation of the MicroScan Urinary Combo Panel and API 20E system for identification of glucose-nonfermenting gram-negative bacilli isolated from clinical veterinary materials

Many isolates of glucose-nonfermenting gram-negative bacilli (NFB) cultured from clinical veterinary specimens are not identified because of the large number of identification tests required. We evaluated two commercial identification systems to determine if they could accurately identify NFB isolated from animals. Of 182 strains of NFB, the MicroScan Urinary Combo Panel (MicroScan, Inc., Campbell, Calif.) correctly identified 72%, and the API 20E system (Analytab Products, Plainview, N.Y.) correctly identified 74%. Of the 118 strains of the three most common species of NFB isolated from animals, the MicroScan Urinary Combo Panel identified 86% correctly, and the API 20E system identified 92% correctly. The use of either of these systems could improve the accuracy of identification of NFB from clinical veterinary materials.     

Gentamicin-mediated suppression of Hurler syndrome stop mutations restores a low level of alpha-L-iduronidase activity and reduces lysosomal glycosaminoglycan accumulation

Hurler syndrome is the most severe form of a lysosomal storage disease caused by loss of the enzyme alpha-L-iduronidase (encoded by the IDUA gene), which participates in the degradation of glycosaminoglycans (GAGs) within the lysosome. In some populations, premature stop mutations represent roughly two-thirds of the mutations that cause Hurler syndrome. In this study we investigated whether the aminoglycoside gentamicin can suppress stop mutations within the IDUA gene. We found that a Hurler syndrome fibroblast cell line heterozygous for the IDUA stop mutations Q70X and W402X showed a significant increase in alpha-L-iduronidase activity when cultured in the presence of gentamicin, resulting in the restoration of 2.8% of normal alpha-L-iduronidase activity. Determination of alpha-L-iduronidase protein levels by an immunoquantification assay indicated that gentamicin treatment produced a similar increase in alpha-L-iduronidase protein in Hurler cells. Both the alpha-L-iduronidase activity and protein level resulting from this treatment have previously been correlated with mild Hurler phenotypes. Although Hurler fibroblasts contain a much higher level of GAGs than normal, we found that gentamicin treatment reduced GAG accumulation in Hurler cells to a normal level. We also found that a reduced GAG level could be sustained for at least 2 days after gentamicin treatment was discontinued. The reduction in the GAG level was also reflected in a marked reduction in lysosomal vacuolation. Taken together, these results suggest that the suppression of premature stop mutations may provide an effective treatment for Hurler syndrome patients with premature stop mutations in the IDUA gene.     

Detection of either rapidly cytolytic macrophages or NK cells in "activated" peritoneal exudates depends on the method of analysis and the target cell type

The nature of the cytotoxic cells present in the peritoneal cavity of rats treated with Bacille Calmette-Guérin (BCG) or Corynebacterium parvum was investigated using a 6 hr chromium release assay and a quantitative method of analysis based on consideration of target-cell killing as an enzyme-substrate reaction. When the results of cell-fractionation experiments were evaluated in terms of recovery of total lytic units and when appropriate target cells (such as sarcoma Mc7) were used, the simultaneous presence of both cytotoxic macrophages and NK cells in peritoneal exudates could be readily demonstrated. With certain other target cells different results were obtained. Thus, with normal thymocytes, normal hepatocytes, or myeloma P3NSI as targets, NK cells were preferentially detected, whereas with leukaemias L5178Y, P815, and EL4 as targets, cytotoxic macrophages were preferentially detected. These findings resolve the previously conflicting reports concerning the nature of cytotoxic cells in activated peritoneal exudates.