Needs of forensic psychiatric patients with schizophrenia in five European countries.

AIMS: The purpose was to compare the frequency of needs of patients with schizophrenia in forensic services across five European countries as assessed by both the patients and their care staff. METHODS: Patients with schizophrenia and a history of significant interpersonal violence were recruited from forensic psychiatric services in Austria, Germany, Italy, Poland and England. Participants' needs were assessed using the Camberwell Assessment of Needs-Forensic Version (CANFOR). Multiple linear regression analyses were used to identify predictors of numbers of needs. RESULTS: In this sample, (n = 221) the most commonly reported need according to patients (71.0%) and staff (82.8%) was the management of psychotic symptoms. A need for information was mentioned by about 45% of staff and patients. Staff members reported a significantly higher number of total needs than patients (mean 6.9 vs. 6.2). In contrast, staff members reported a significantly lower number of unmet needs than patients (mean 2.0 vs. 2.5). Numbers of total needs and met needs differed between countries. Unmet needs as reported by patients showed positive associations with the absence of comorbid personality disorder, with higher positive symptom scores and lifetime suicide or self-harm history. Significant predictors of unmet needs according to staff were absence of comorbid personality disorder and higher positive as well as negative symptom scores according to PANSS. CONCLUSIONS: Staff rated a significantly higher number of total needs than patients, while patients rated more unmet needs. This indicates that patients' self-assessments of needs yield important information for providing sufficient help and support.

Imbalances in protein homeostasis caused by mutant desmin.

AIMS: We investigated newly generated immortalized heterozygous and homozygous R349P desmin knock-in myoblasts in conjunction with the corresponding desminopathy mice as models for desminopathies to analyse major protein quality control processes in response to the presence of R349P mutant desmin. METHODS: We used hetero- and homozygous R349P desmin knock-in mice for analyses and for crossbreeding with p53 knock-out mice to generate immortalized R349P desmin knock-in skeletal muscle myoblasts and myotubes. Skeletal muscle sections and cultured muscle cells were investigated by indirect immunofluorescence microscopy, proteasomal activity measurements and immunoblotting addressing autophagy rate, chaperone-assisted selective autophagy and heat shock protein levels. Muscle sections were further analysed by transmission and immunogold electron microscopy. RESULTS: We demonstrate that mutant desmin (i) increases proteasomal activity, (ii) stimulates macroautophagy, (iii) dysregulates the chaperone assisted selective autophagy and (iv) elevates the protein levels of αB-crystallin and Hsp27. Both αB-crystallin and Hsp27 as well as Hsp90 displayed translocation patterns from Z-discs as well as Z-I junctions, respectively, to the level of sarcomeric I-bands in dominant and recessive desminopathies. CONCLUSIONS: Our findings demonstrate that the presence of R349P mutant desmin causes a general imbalance in skeletal muscle protein homeostasis via aberrant activity of all major protein quality control systems. The augmented activity of these systems and the subcellular shift of essential heat shock proteins may deleteriously contribute to the previously observed increased turnover of desmin itself and desmin-binding partners, which triggers progressive dysfunction of the extrasarcomeric cytoskeleton and the myofibrillar apparatus in the course of the development of desminopathies.

kW-class direct diode laser for sheet metal cutting based on DWDM of pump modules by use of ultra-steep dielectric filters.

A direct diode laser was built with > 800 W output power at 940 nm to 980 nm. The radiation is coupled into a 100 µm fiber and the NA ex fiber is 0.17. The laser system is based on pump modules that are wavelength stabilized by VBGs. Dense and coarse wavelength multiplexing are realized with commercially available ultra-steep dielectric filters. The electro-optical efficiency is above 30%. Based on a detailed analysis of losses, an improved e-o-efficiency in the range of 40% to 45% is expected in the near future. System performance and reliability were demonstrated with sheet metal cutting tests on stainless steel with a thickness of 4.2 mm.

Neonatal abstinence syndrome in European and North American neonates: differences in clinical characteristics derived from a prospective randomized trial.

BACKGROUND: Due to the steady increase of substance-dependent pregnant women the neonatal abstinence syndrome has become an increasingly important issue in neonatology. The present study investigates site-specific differences of detailed symptoms and treatment of neonatal abstinence syndrome within the context of an international multicenter clinical trial. METHODS: Site specific neonatal data analyses from a prospective randomized, double-blind, double-dummy clinical trial (MOTHER study) was performed. A standardized NAS rating and treatment protocol was applied, while non-pharmacological care of NAS symptoms differed across the sites. RESULTS: Urban US neonates exhibited most neurological symptoms (p<0.001) while in Europe autonomous, respiratory and gastrointestinal symptoms were found significantly more often compared to urban and/or rural US (p<0.05). Methadone produced significantly greater scores than buprenorphine in neurological, behavioural and respiratory symptoms regardless of the sites (ps<0.05). NAS treatment rates in all site clusters were similar for methadone-exposed neonates, while in Europe significantly more buprenorphine-exposed neonates were treated (p=0.001) than in US site clusters. Urban US neonates had significantly higher NAS scores (p<0.01) compared to rural US and European neonates, and needed significantly higher morphine doses (p<0.05) with longer treatment duration. Birth weight, length and head circumference did not differ significantly among the site clusters, but APGAR scores were significantly higher in European (p<0.01) neonates. CONCLUSION: In addition to intrauterine medication exposure other aspects such as different addiction severity of the mothers, different treatment modalities including rooming-in as well as the frequency of NAS ratings may be influencing the course of NAS.

Modified direct anterior approach in minimally invasive hip hemiarthroplasty in a geriatric population: a feasibility study and description of the technique.

INTRODUCTION: The direct anterior approach (DAA) is generally accepted method for minimal invasive arthroplasty of the hip. As good results for total hip arthroplasty are already published, there is a lack of evidence for the implantation of bipolar hip hemiarthroplasty (BHH) in elderly patients with osteoporosis after femoral neck fracture. MATERIALS AND METHODS: For hip arthroplasty using a direct anterior approach (DAA) in elderly patients with femoral neck fractures, a number of modifications of the original technique are being described. The modified DAA considers in particular the co-morbidity and the bone quality of the geriatric patient population. A consecutive series of 16 hemiarthroplasties using this technique is presented. In all 16 cases, the BHH was implanted in modified DAA technique. Mobility measured by 4-item Barthel Index, pain via visual analogue scale (VAS), duration of surgery, external length of incision and blood loss were evaluated. RESULTS: There was no major operative complication during the procedures. The pain level decreased from 7 (preoperatively) to 0 at postoperative day 40. The Barthel Index increased from 5 at first postoperative day to 40 at day 40. Early postoperative mobilisation is efficiently accelerated. Mean operating time was 71 min; the medium skin incision length was 8 cm. The mean haemoglobin level decreased from 118 g/dl preoperatively to 101 g/dl at first postoperative day. CONCLUSION: The described modifications of the DAA help to implant a BHH gently in elderly patients with increasing risk of complications like iatrogenic fractures, wound or prosthesis infections and haematoma. This will hopefully lead to a faster rehabilitation and lower mortality rate for patients with femoral neck fractures in the future.

[Intermediate and long-term outcome after total joint replacement for hallux rigidus : a retrospective analysis]. / Mittel- und langfristige Ergebnisse nach endoprothetischer Versorgung des Hallux rigidus : Eine retrospektive Analyse.

BACKGROUND: The treatment options for advanced hallux rigidus include arthrodesis, excision arthroplasty (Keller-Brandes) and joint arthroplasty and based on the literature, arthrodesis still appears to be the gold standard. In recent years, technical advances and higher patient demands have led to an increasing use of total joint replacement but comparative data on patient satisfaction and clinical outcome of different forms of treatment are rare. MATERIAL AND METHODS: Between 1995 and 2005 a total of 27 patients were treated with 28 joint replacements of the first metatarsophalangeal joint (MTPJ) in a surgical practice (Bio-Action Great Toe Implant, OsteoMed, Addison, TX). The mean age of the patients was 63.7 years. In a retrospective analysis patients were examined clinically and radiologically after a mean follow-up period of 8.8 years and asked about their satisfaction with surgical results using a questionnaire. RESULTS: After joint replacement 15 patients (53.6%) were free of pain, 8 (28.6%) reported marked improvement, 12 (42.9%) had no limitations in any activity and another 5 (17.9%) had no restrictions in activities of daily life. The maximum walking distance was improved in 21 patients (75%) and walking on rough ground in 24 (85.7%). Of the patients 11 (39.3%) had a good range of motion in the MTPJ, 13 (46.4%) reported a slight restriction, 24 (85.7%) were satisfied or very satisfied with the postoperative result and 22 stated that they would undergo joint replacement again. The results of the Wilcoxon test showed a significant increase in postoperative modified American Orthopaedic Foot and Ankle Society (AOFAS) scores compared with preoperative scores. There was loosening of the phalangeal component in 3 patients (11%), and 2 had to undergo revision. CONCLUSIONS: Many recent studies reported good to excellent long-term results of arthrodesis of the MTPJ for stage III and IV hallux rigidus. The results of this study suggest that similar results can be achieved by an experienced foot surgeon with total joint replacement in strictly selected patients.

Depressive symptoms as a transdiagnostic mediator of mother-to-infant bonding: Results from a psychiatric mother-baby unit.

Maternal symptoms of depression can interfere with the establishment of healthy mother-infant-bonding, which negatively affects developmental trajectories of the child and maternal wellbeing. However, current evidence about the effects of treatment in severely affected women is still lacking and the transdiagnostic prognostic value of depressive symptoms is not fully clear. Therefore, a naturalistic clinical sample of 140 mother-infant-dyads in inpatient treatment at a mother-baby-unit was analyzed with instruments being administered at admission and before dismissal. Linear mixed effects models were calculated in order to assess the longitudinal influence of scores on the Edingburgh Postpartum Depression Scale (EPDS) on post-partum-bonding measured with the postpartum bonding questionnaire (PBQ). Furthermore, interaction-effects with psychiatric diagnosis of the mothers (depression vs. psychosis) and their partners were assessed. Successful treatment of depressive symptoms was paralleled by a significant decrease of impaired bonding, with only 6.4% of the women having PBQ total scores above cut-off at discharge. Overall, higher scores on the EPDS were associated with a significantly poorer outcome on the PBQ (p = < 0.001), irrespective of diagnosis (p = 0.93). Importantly, there was an interaction effect of EPDS and a psychiatric diagnosis of the partner on the PBQ (p = 0.017). Thus, our results further emphasize the significance of postpartum symptoms of depression for mother-child bonding, which can be effectively improved by comprehensive treatment even in severely affected women. Optimizing treatment and diagnostics as early as possible and enabling access for all women must become a priority.

Clinical characteristics of central European and North American samples of pregnant women screened for opioid agonist treatment.

BACKGROUND: Little comparable information is available regarding clinical characteristics of opioid-dependent women from different countries. In the present study, women from the USA, Canada and a Central European country, Austria, screened for participation in the Maternal Opioid Treatment Human Experimental Research study, were compared with respect to their demographic and addiction histories. METHODS: Pregnant women (n = 1,074) were screened for study participation using uniformed clinical criteria and instruments. The screening results were compared with regard to exclusion, demographics, drug use, and psychosocial and treatment histories. RESULTS: Compared to the screened US and Canadian women, Austrian women were more likely to be younger (p < 0.001), white (p < 0.001), had significantly lower levels of educational attainment (p < 0.001), were less likely to use opioids daily (p < 0.001) and more likely to have been prescribed buprenorphine (p < 0.001). Compared to both rural and urban US groups, the Austrian group was less likely to have legal issues (p < 0.001) and was younger when first prescribed agonist medication (p < 0.001). CONCLUSION: The differences between North American and European groups may offer unique insights concerning treatment and pregnancy outcomes for opioid-dependent pregnant women.

Acoustic monitoring (RFM) of total hip arthroplasty - Results of a cadaver study.

INTRODUCTION: At present there are no reliable non-traumatic and non- invasive methods to analyse the healing process and loosening status after total hip replacement. Therefore early as well as late loosening of prosthesis and interface component problems are difficult to be found or diagnosed at any time. METHODS: In a cadaver study the potential application of Resonance Frequency Monitoring (RFM) will be evaluated as a non-invasive and non-traumatic method to monitor loosening and interface problems in hip replacement. In a 65 year old female cadaver different stability scenarios for a total hip replacement (shaft, head/modular head and cup, ESKA, Luebeck, Germany) are simulated in cemented and cement less prosthesis and then analysed with RFM. The types of stability vary from secure/press-fit to interface-shaft disruption. RESULTS: The RFM shows in cemented as well as cement less prosthesis significant intra-individual differences in the spectral measurements with a high dynamic (20 dB difference corresponding to the factor 100 (10000%)), regarding the simulated status of stability in the prosthesis system. CONCLUSION: The results of the study demonstrate RFM as a highly sensitive non-invasive and non-traumatic method to support the application of RFM as a hip prosthesis monitoring procedure. The data obtained shows the possibility to use RFM for osteointegration surveillance and early detection of interface problems, but will require further evaluation in clinical and experimental studies.

Recover recovery style from psychosis: a psychometric evaluation of the German version of the Recovery Style Questionnaire (RSQ).

AIMS: The way an individual handles the experience of psychosis, the so-called 'recovery style', has been shown to substantially affect long-term outcomes. The Recovery Style Questionnaire (RSQ) measures this psychological dimension. The aim of this study was to provide a validation of the German version of the RSQ and to raise awareness for recovery-oriented approaches. METHODS: The RSQ was translated into German according to the guidelines of the WHO and patients were administered this questionnaire and measures of internalised stigma, psychotic symptoms, illness concept, empowerment, self-esteem and quality of life. Descriptive statistics were demonstrated to characterise the sample. Reliability was assessed in different forms: internal consistency, test-retest reliability and split-half reliability. Items were evaluated with descriptive data and item-total correlations. Convergent and discriminant validity were shown, and a confirmatory factor analysis was performed. In order to ameliorate the model, a post hoc model modification was done. RESULTS: The sample consisted of 138 patients diagnosed with schizophrenia spectrum disorders (mean age: 35.7 years; 53.6% men; mean duration of illness: 20.6 years) with a mean RSQ overall percentage of 66.12 (s.d. ± 17.43%), mainly representing the categories 'mixed picture' and 'tends towards integration'. The reliability of the RSQ was acceptable with a Cronbach's α of 0.741 and a test-retest coefficient of 0.502. Item-total correlations were not acceptable for 27 of 39 items. Moderate evidence for convergent validity of the RSQ was found. Confirmatory factor analysis revealed that the 13-factor model with 39 items originally proposed was partially poorly replicated in the present sample (χ2 ratio to degrees of freedom (χ2/df) of 1.732, Comparative Fit Index (CFI) of 0.585, Normed Fit Index (NFI) of 0.414, Tucker-Lewis Index (TLI) of 0.508, root mean square error of approximation (RMSEA) of 0.095). The RSQ was modified based on item-total correlations and path coefficients of the single items. The confirmatory factor analysis of the resulting one-factor model with 11 items showed adequate fit to the data (χ2/df of 1.562, CFI of 0.936, NFI of 0.847, TLI of 0.910, RMSEA of 0.083) and demonstrated good model fit. CONCLUSIONS: Despite partially insufficient psychometric data of the original RSQ, the concept of recovery style is beneficial to psychiatric research and clinical practice. The underlying idea is valuable, and the questionnaire needs further development. Therefore, a short version of the RSQ is proposed.

E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis.

Tissue sections of 32 squamous cell carcinomas (SCCs) of the head and neck were investigated for the expression of the epithelium-specific cell adhesion molecule E-cadherin. We found that E-cadherin expression is inversely correlated both with the loss of differentiation of the tumor and with lymph node metastasis. The well-differentiated SCCs expressed E-cadherin, often as strongly as the normal stratified epithelium (12 cases were tested); the moderately differentiated SCCs expressed intermediate amounts of E-cadherin or were heterogeneous (15 cases were analyzed); whereas the poorly differentiated SCCs were all E-cadherin-negative (five cases were investigated). Furthermore, seven of eight infiltrated lymph nodes of SCCs were E-cadherin-negative. These data indicate that the loss of the cell adhesion molecule E-cadherin in fact plays an important role in the progression of human squamous cell carcinomas, i.e., that down-regulation of expression is associated with dedifferentiation and metastasis of the tumor cells in vivo.

Studies with chymotrypsin and RNAase showing a heterooligomeric structure of the glucocorticoid receptor complex from rat liver which is stabilized by a low molecular weight factor.

The glucocorticoid receptor from rat liver displays a differential sensitivity toward digestion by chymotrypsin and RNAase A that is dependent on its activation state. Unactivated (9-10 S) receptor is not digested by these enzymes, while activated 7-8 S receptor is. Chymotrypsin treatment yields an approx. 3 S form, while RNAase treatment yields a 4.9 S form that is distinct from the high-salt 4 S form. To firmly establish that the results are due to specific hydrolytic activities of the particular enzymes, we show that the chymotrypsin effect is inhibited by diisopropylfluorophosphate and not RNAasin, while the reverse is true for RNAase A. We further show that the differential sensitivity toward chymotrypsin is due to the association of a proteinase-resistant, heat-stable low molecular weight factor with the unactivated glucocorticoid receptor. When this factor is removed by warming, dialysis or molecular sieving of the receptor complex, the complex becomes sensitive to chymotrypsin. We also show that moderate chymotrypsin treatment yields a 6-7 S form of the receptor which is composed of, at least, RNA and the 4 S receptor. On the basis of these results, we propose that the 9-10 S receptor is composed of a low molecular weight stabilizing factor whose presence apparently alters the conformation of the complex such that the RNA and the RNA-binding site of the receptor are protected, a chymotrypsin-sensitive factor, RNA and the 4 S receptor itself.

The ability to convert the 4 S glucocorticoid receptor to the 7-8 S form is dependent on both RNA and protein factors.

The DEAE-cellulose-purified 4 S form of the rat liver glucocorticoid receptor can associate with cytosolic factors, as evidenced by an alteration of the sedimentation value of the 7-8 S form. On the basis of sedimentation profile, this form is indistinguishable from the activated, low-salt 7-8 S form isolated from rat liver cytosol. In addition, both the endogenous and reconstituted 7-8 S receptor can bind DNA as the 7-8 S form. In keeping with our reports that the endogenous form of the 7-8 S receptor is sensitive to RNAase digestion, treatment of the cytosol with RNAase prior to mixing with the 4 S receptor prevents the formation of the 7-8 S material. Moreover, warming the cytosol to 50 degrees C prior to mixing with the 4 S receptor also eliminates the ability to form the heavier material. Since RNA is heat-stable, this suggests that other factors may be involved. Treatment of the cytosol with N-ethylmaleimide, a reagent reported to be specific for sulfhydryl groups, also eliminates 7-8 S generating ability. These observations suggest that a protein may be a component of the 7-8 S generating material. This is substantiated by the observation that trypsin or chymotrypsin treatment of the cytosol mitigates the ability of the cytosol to form the 7-8 S material and results in the appearance of a form of the receptor that sediments at approximately 6 S. Protease treatment of partially purified material eliminates the 7-8 S generating activity entirely. We conclude that the 7-8 S form of the receptor can be reconstituted from the 4 S receptor via association with at least two other cytosolic factors, a protein and an RNA.

Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the systemic hemostatic profile.

OBJECTIVES: The study sought to determine the effects of lipid-lowering with pravastatin on the systemic fibrinolytic profile and on thrombus formation under dynamic flow conditions. BACKGROUND: Lowering cholesterol (C) decreases clinical events in coronary artery disease (CAD) patients, but an analysis of the effects of lipid-lowering on the entire hemostatic and thrombotic profile has not been conducted. METHODS: We prospectively studied 93 stable patients with untreated low-density lipoprotein cholesterol (LDL-C) >145 mg/dl. The CAD patients received pravastatin, and non-CAD patients were randomized to pravastatin versus placebo (double-blind). Thrombus formation upon an injured vascular surface was assessed in a substudy of 40 patients with a previously validated ex vivo perfusion chamber system. Systemic hemostatic markers and thrombus formation were evaluated at baseline, three and six months. RESULTS: Placebo produced no changes in either the lipid profile, any of the hemostatic markers, or the ex vivo thrombus formation. Both pravastatin groups (CAD and non-CAD) showed decreased LDL-C by 30% within 6 weeks (188 to 126 mg/dl, p < 0.001 vs. baseline), and decreased plasminogen activator inhibitor-1 at 3- and 6-month follow-up compared to baseline (15% to 18% decrease at 3 months and 21% to 23% at 6 months). For the tissue plasminogen activator antigen, CAD and non-CAD groups showed significant decreases at 6 months compared to baseline (10% and 13%, respectively). No significant changes were observed with treatment in d-dimer, fibrinopeptide A, prothrombin fragment F1.2, factor VIIa, von Willebrand factor, or C-reactive protein. Fibrinogen levels were significantly increased at 6 months compared to baseline, though still below the upper normal limit. In the perfusion chamber substudy, there was a decrease in thrombus area in non-CAD patients treated with pravastatin at both 3 and 6 months compared to baseline (by 21% and 34%, respectively). The CAD patients showed decreases in thrombus formation by 13% at 3 months, and by 16% at 6 months. The change in LDL-C- correlated modestly with the change in thrombus formation (r = 0.49; p < 0.01). CONCLUSIONS: Pravastatin therapy significantly decreased thrombus formation and improved the fibrinolytic profile in patients with and without CAD. These early effects may, in part, explain the benefit rendered in primary and secondary prevention of CAD.

Isolation of ribonucleic acid from the unactivated rat liver glucocorticoid receptor.

We have reported that the 7-8S form of the rat liver glucocorticoid receptor is associated with RNA. Whether the unactivated 9-10S form of the glucorticoid receptor is also associated with RNA is less clear. Here we provide evidence that the unactivated 9-10S receptor is indeed associated with RNA. Unactivated 9-10S receptor was partially purified by diethylaminoethyl (DEAE)-cellulose chromatography in the presence of molybdate, an activation inhibitor. This preparation was then bound to BuGR-2, a mouse monoclonal antibody of the immunoglobulin G (IgG)-2 class to the rat liver glucocorticoid receptor, or to nonspecific mouse IgG-2. The antibody-antigen complex was then bound to protein A sepharose and washed to remove extraneous RNA. When the receptor was dissociated from the antibody and the RNA extracted and end-labeled, a distinct band of approximately 170 nucleotide (nt) was found that was specific for the BuGR-2 purified receptor. This band could also be found in DEAE-cellulose receptor that had been isolated from sucrose gradients. The DEAE-cellulose receptor was then cross-linked with formaldehyde before mixing with BuGR-2 in order to permit more vigorous washing of the antigen-antibody complex. In addition to the 170 nt RNA band, another distinct band at approximately 400 nt was seen that was specific to the BuGR-2 derived isolate. These results provide evidence that the 9-10S form of the glucocorticoid receptor from rat liver is associated with RNA.

Treatment of dialysis-related muscle cramps with hypertonic dextrose.

Hypertonic dextrose (50% dextrose in water [D50W]) has been studied as a therapeutic agent to relieve dialysis-related muscle cramps (DMCs). We conducted a double-blind study comparing the effectiveness of 1 mL/kg of D50W with an identical volume of 5% dextrose in water (D5W) administered as an intravenous bolus. Twelve of 36 patients studied experienced DMCs. Thirty-three cramping episodes were studied. Eighteen were treated with D50W and 15 with D5W. Blood glucose levels and blood pressure were measured before infusion and at intervals to one hour. Cramp relief was graded and recorded at the same intervals. Eighty-nine percent of treatments with D50W resulted in complete relief, compared with 40% of treatments. Partial relief was obtained in 5.5% of treatments with D50W, compared with 40% relief with D5W. Twenty percent with D5W did not effect relief. In one treatment with D50W, observations were unsatisfactory to judge relief. There were no important side effects. We have shown D50W to be a safe effective treatment for DMC. Our data suggest that plasma volume contraction is important in the genesis of DMC, and that relief is related to expansion of plasma volume secondary to increased plasma osmolality.

Molecular cloning of major and minor allergens of Alternaria alternata and Cladosporium herbarum.

The two moulds, Alternaria alternata and Cladosporium herbarum, are recognized as major causes of fungal allergies. Cloning, sequencing and heterologous expression of the allergens of the two moulds is a necessary step in understanding fungal allergy and in the development of new and improved methods of diagnosis and therapy. The seven new mould allergens presented here represent four new allergen proteins: aldehyde dehydrogenase (ALDH), enolase, YCP4 (previously found as a Saccharomyces cerevisiae protein of unknown function), and the acidic ribosomal protein, P2. Three of them (ALDH, YCP4 and P2) were found to be allergens in both fungi, Alternaria and Cladosporium. All allergens found so far are cytoplasmic proteins and are rather well conserved in evolution even when comparing distant species. Most of the allergens have "household" functions (ALDH, enolase). One allergen (P2) is a homolog of a very highly conserved human lupus erythematodes (LE) antigen. None of the fungal allergens is clearly related to other known non-fungal allergens.

Neuromyelitis optica (Devic's syndrome) and pulmonary tuberculosis.

Neuromyelitis optica and acute necrotic myelopathy occur in association with pulmonary tuberculosis. We studied 8 patients with either neuromyelitis optica (6), acute myelopathy (1), or acute optic neuropathy (1) in close temporal association with pulmonary tuberculosis, but with no evidence for CNS tuberculosis. Neurologic symptoms preceded the use of antituberculosis medication in 5 patients. Different patients showed similar clinical features, suggesting a consistent disease pattern. Autopsy examination (1 patient) revealed extensive spinal cord and optic nerve demyelination. We identified only 5 additional patients seen over the same period with idiopathic neuromyelitis optica, thus suggesting that the close temporal relationship to pulmonary tuberculosis is not coincidental. The syndrome is most likely due to an immune reaction to tuberculosis rather than the use of antituberculosis medication.

A comparison of two techniques for the detection of an antibody in human serum to Chang liver cell surface antigens.

The antibody-dependent cell-mediated cytotoxicity technique (ADCC) and an isotopic antiglobulin technique have been compared for their abilities to detect human serum antibodies to Chang liver cell membrane antigens. The optimal conditions were established for the latter technique, which was found to be superior with respect to reproducibility and sensitivity. Also, unlike ADCC, the isotopic antiglobulin technique was unaffected by other factors, such as immune complexes present in pathological sera.

Pravastatin: an antithrombotic effect independent of the cholesterol-lowering effect.

Lipid-lowering with statins reduces blood thrombogenicity. However, it is unknown whether this is purely due to LDL-cholesterol reduction, or it is related to a statin or agent specific effect. We investigated the relationship between reduction in blood thrombogenicity and the magnitude of low-density lipoprotein cholesterol (LDL-C) during pravastatin therapy. We prospectively followed for 6 months 57 hyperlipidemic patients who initiated therapy with pravastatin, and 36 patients who were randomized into placebo plus diet. Pravastatin-treated patients were grouped according to the LDL-C reduction at 6 months; (i) "adequate LDL-C reduction": LDL-C reduction >30% from baseline or LDL-C<125 mg/dl (n = 38; LDL-C reduction 74 +/- 4 mg/dl; 6-month LDL-C 119 +/- 5 mg/dl); (ii) "inadequate LDL-C reduction": neither of the above criteria (n = 19; LDL-C reduction 31 +/- 5 mg/dl; 6-month LDL-C 158 +/- 6 mg/dl). Placebo patients were divided into those "with LDL-C reduction" (n = 17, mean reduction 21 +/- 5 mg/dl) and those "without LDL reduction" (n = 19). The following parameters were altered at 6 months in both patients with "adequate" and "inadequate" LDL-C reduction: (1) tissue plasminogen activator decreased by 1.4 +/- 0.4 and 1.5 +/- 0.5 ng/ml respectively (p = NS); (2) plasminogen activator inhibitor-1 decreased by 8.7 +/- 2.0 and 10.1 +/- 2.7 ng/ml respectively (p = NS); (3) thrombus formation under dynamic flow conditions decreased by 3.5 +/- 0.9 and 2.8 +/- 1.2 microm2 x 10(3) respectively (p = NS). In contrast, no significant changes from baseline were noted in placebo-treated patients, regardless of their LDL-C reduction category, and multivariate analysis eliminated LDL-C reduction as an independent predictor of reduction in thrombogenicity. Therefore, the reduction in thrombogenicity was not proportional to the magnitude of LDL-C reduction suggesting that a class or agent specific property is primarily responsible for the pro-fibrinolytic/antithrombotic effects observed.