Increased prevalence of HCV and hepatic decompensation in adults with psoriasis: a population-based study in the United Kingdom.

BACKGROUND: The hepatitis C virus (HCV) is a major cause of global morbidity and mortality, with conflicting evidence regarding a possible association with psoriasis. OBJECTIVE: To determine the prevalence of HCV in psoriasis patients, compared to controls, and to determine the incidence of hepatic decompensation in HCV+ psoriasis patients compared to HCV+ controls. METHODS: Cross-sectional and cohort studies were conducted in The Health Improvement Network (THIN). RESULTS: In fully adjusted models, a statistically significant increase in prevalence was seen in the adults with psoriasis (OR: 1.24, 95% CI 1.10-1.40). A "dose-response" of HCV prevalence with increasing psoriasis severity was not observed. HCV+ patients with psoriasis had a non-statistically significant increased incidence of hepatic decompensation compared to HCV+ individuals without psoriasis (aHR: 1.58, 95% CI: 0.90-2.77). The risk was highest and statistically significant, in those with moderate-to-severe psoriasis (aHR: 21.51, 95% CI: 7.58-61.03). CONCLUSIONS: These results demonstrate a higher prevalence of HCV in adults with psoriasis and a higher rate of hepatic decompensation in HCV+ individuals with moderate-severe psoriasis.

Patient satisfaction with treatments for moderate-to-severe plaque psoriasis in clinical practice.

BACKGROUND: Treatment satisfaction among patients with moderate-to-severe psoriasis has not been studied and compared across treatments using a validated instrument. OBJECTIVES: To assess patient-reported satisfaction with systemic and phototherapy treatments for moderate-to-severe psoriasis in clinical practice and to correlate satisfaction with disease severity and quality-of-life measures. METHODS: This was a cross-sectional study of 1182 patients with moderate-to-severe psoriasis in the Dermatology Clinical Effectiveness Research Network in the U.S.A. Patients receiving either topical therapies only; monotherapy with oral systemic therapies, biologics or narrowband ultraviolet B phototherapy; or combination therapy with biologics and methotrexate completed the Treatment Satisfaction Questionnaire for Medication version II. RESULTS: Median unadjusted overall satisfaction scores were highest for patients receiving biologic monotherapies, biologic-methotrexate combinations, or phototherapy (83.3); scores were lowest for those receiving topical therapies only or acitretin (66.7). In fully adjusted models, compared with patients receiving methotrexate monotherapy, those receiving adalimumab, etanercept, ustekinumab, phototherapy or adalimumab with methotrexate had significantly higher median overall satisfaction scores by 7.2-8.3 points, while those receiving topical therapies only had significantly lower overall satisfaction by 8.9 points. Adjusted convenience scores were lowest for patients receiving topical therapies only or infliximab. Modest but significant correlations were found between the overall satisfaction subscale and both the Psoriasis Area and Severity Index (ρ = -0.36, P < 0.001) and the Dermatology Life Quality Index (ρ = -0.47, P < 0.001). CONCLUSIONS: Discernible differences were found in treatment satisfaction among therapies, particularly regarding treatment effectiveness and convenience. Further application of treatment satisfaction measures may inform treatment decisions and guideline development.

Mechanisms of Ca2+ overload induced by extracellular H2O2 in quiescent isolated rat cardiomyocytes.

Rat cardiomyocytes were exposed to H2O2 (1-100 micromol/L) for 10 min with washout for 10 min. Intracellular Ca2+ concentration ([Ca2+]i) was measured using fluo-3. [Ca2+]i increased with 100 micromol/L H2O2 and further increased during washout, causing irreversible contracture in one-half of the cells. The increase in [Ca2+]i with 10 micromol/L H2O2 was modest with few cells showing irreversible contracture and attenuated by caffeine, and [Ca2+]i gradually decreased during washout and this decrease was accelerated by a calcium-free solution, while 1 micromol/L H2O2 did not have any effects on [Ca2+]i or cell viability. Ca2+ overload caused during exposure to 100 micromol/L H2O2 was attenuated by caffeine with improved cellular viability but not by chelerythrine, KB-R7943 or nifedipine. With 100 micromol/L H2O2 calcium-free solution attenuated the increase during exposure and washout while KB-R7943 or chelerythrine partly attenuated further increase during washout but not improved cell viability, but chelerythrine did not have additional effect on calcium-free treatment. Catalase abolished the effects of H2O2. We concluded that the increased [Ca2+]i during exposure to 100 micromol/L H2O2 was caused both by release of Ca2+ from the intracellular store sites including the sarcoplasmic reticulum and by influx through route(s) other than the voltage-dependent Ca2+ channels or Na+/Ca2+ exchanger, although the Na+/Ca2+ exchanger or protein kinase C-mediated mechanism was partly responsible for a further increase during washout.

Genetic mechanisms of age regulation of human blood coagulation factor IX.

Blood coagulation capacity increases with age in healthy individuals. Through extensive longitudinal analyses of human factor IX gene expression in transgenic mice, two essential age-regulatory elements, AE5' and AE3', have been identified. These elements are required and together are sufficient for normal age regulation of factor IX expression. AE5', a PEA-3 related element present in the 5' upstream region of the gene encoding factor IX, is responsible for age-stable expression of the gene. AE3', in the middle of the 3' untranslated region, is responsible for age-associated elevation in messenger RNA levels. In a concerted manner, AE5' and AE3' recapitulate natural patterns of the advancing age-associated increase in factor IX gene expression.

Neuropsychologic implications in erotomania: two case studies.

OBJECTIVE: To explore neuroanatomic substrates and cognitive factors associated with erotomania through neuropsychologic test data and neurologic studies. BACKGROUND: Erotomania is a delusional disorder that has been examined and conceptualized both clinically and psychodynamically. It is believed that neuroanatomic and neuropsychologic correlates can provide important insights into the causes of erotomania. METHOD: Two patients with erotomania and the results of their neuropsychologic testing were examined, and neurologic studies also were examined for one of the patients. These data were compared with case studies from the literature. RESULTS: Neuropsychologic test results suggested that erotomania may be associated with deficits in cognitive flexibility and associative learning that are mediated by frontal-subcortical systems, and with deficits in verbal and visuospatial skills. Neurologic studies suggested abnormalities in temporal areas. CONCLUSIONS: Visuospatial-functioning deficits or limbic lesions, particularly in the temporal lobes, in combination with isolative and ambivalent romantic experiences, may contribute to misinterpretations in erotomania, and deficits in cognitive flexibility may contribute to the maintenance of the delusional belief.

Deamination and Dimroth rearrangement of deoxyadenosine-styrene oxide adducts in DNA.

In reactions between styrene oxide and the ring nitrogen at the 1-position of deoxyadenosine, the epoxide is opened at both the alpha- (benzylic) and beta-carbons. The 1-substituted nucleosides formed are unstable and subsequently undergo either Dimroth rearrangement to give N6-substituted deoxyadenosines or deamination to give 1-substituted deoxyinosines. alphaN6-Substituted compounds are also formed from direct reaction at the exocyclic nitrogen. Kinetic experiments revealed that relative rates of deamination of 1-substituted deoxyadenosine-styrene oxides and 1-substituted adenosine-styrene oxides were similar. However, the rate of Dimroth rearrangement in beta1-substituted adenosine-styrene oxides was approximately 2.3-fold greater than that of beta1-substituted deoxyadenosine-styrene oxides and approximately 1.5-fold greater in alpha1-substituted adenosine-styrene oxides relative to alpha1-substituted deoxyadenosine-styrene oxides. Analysis of the products formed from reactions of styrene oxide with [3H]deoxyadenosine and [3H]deoxyadenosine incorporated into native and denatured DNA showed that the double-helical DNA structure reduced the levels of adducts formed 5-fold relative to denatured DNA but did not present a complete barrier to formation of either N6-substituted deoxyadenosine- or 1-substituted deoxyinosine-styrene oxide adducts in native DNA. Additionally, in denatured and native DNA the product distributions were altered in favor of formation of beta1-substituted deoxyinosine-styrene oxide adducts with respect to reactions of the nucleoside. The ratio of retained to inverted configuration of alphaN6-substituted products was higher in DNA than in nucleoside reactions. These experiments indicate that in addition to the N6-position, the ring nitrogen at the 1-position of deoxyadenosine is available, to some extent, for reaction in native DNA. In styrene oxide-DNA reactions, formation of 1-substituted adenines can lead to deaminated products where both Watson-Crick hydrogen-bonding sites are disrupted.

Assessment of extrapyramidal symptoms during acute neuroleptic treatment.

BACKGROUND: Acute administration of traditional neuroleptic drugs is often accompanied by the emergence of extrapyramidal symptoms (EPS). The use of a standardized scale to measure EPS can assist the clinician in assessing the occurrence and severity of these adverse reactions. The current work presents the interrater reliability and validity of the Yale Extrapyramidal Symptom Scale (YESS)--an eight-item, easy-to-administer scale for assessing emergence, severity, and type of side effects that commonly occur during acute treatment. METHOD: Interrater reliability (Study 1) and validity (Study 2) of the scale were studied using two independent samples of acutely psychotic patients treated with neuroleptic drugs. Study 1: Interrater reliability was assessed by comparing the YESS ratings of two clinicians blind to the other's rating and to the patient's drug regimen and dose. Study 2: Validity was studied by examining whether YESS items correlated with other EPS measures (convergent validity) but not with psychotic symptoms that may be confused with EPS (discriminant validity). RESULTS: Interrater agreement between clinicians was good to excellent. YESS items correlated with assessments used to measure symptoms of Parkinson's disease and akathisia and generally showed low nonsignificant correlations with ratings of symptoms of psychosis. CONCLUSION: The current work presents a brief EPS scale for the assessment of commonly occurring neuroleptic-induced extrapyramidal side effects. It was demonstrated that the YESS could be used reliably across clinician raters and that the YESS is a valid measure for assessing EPS during acute treatment.

Resuscitation by extracorporeal lung assist of a patient suffocating after inhalation of sawdust particles.

A 17-yr-old male accidentally inhaled a massive amount of sawdust particles. Severe respiratory distress developed, resulting in subcutaneous emphysema and left pneumothorax. Therefore, sufficient positive-pressure ventilation was inapplicable. Under veno-venous extracorporeal lung assist (ECLA) with an artificial lung, the sawdust particles were removed by broncho-fibroscopy and lung lavage. After 36 h, the patient was weaned from ECLA without further complications.

[Why does the symptom of venous air embolism appear suddenly?].

A glass model of the human heart with the vena cava was made to study the behavior of air entering into a vein by accident. The capacities of the right atrium and ventricle of this model were 50 ml and 130 ml respectively. The superior and inferior venae cavae were irrigated with the running water. Direction of the vena cava, relative posture of the right heart against the vena, flow rate of the water, volume and frequency of air infusion were changed in turn. Migration of the air bubbles was observed. Most of the air injected into the vena cava formed multiple bubbles of various sizes and kept floating in the running water in the vena. Some air bubbles were transferred to the atrium and ventricle and trapped there until they were suddenly washed away. This happened after the air bubbles grew larger to impede the water flow, when the flow rate of water was increased, or when the vena cava was laid horizontal and the atrium and ventricle were positioned higher than the vena cava. Although this hard model is quite different from the contracting human heart, the behavior of the air in the flowing fluid affords us some indication of an explanation of the sudden onset of the symptom of venous air embolism during a surgical operation.

[A method for continuous exposure of blood in vitro and in vivo to light, radiation or gas].

Various medical treatments with extracorporeal circulation have increased the opportunities of exposing blood to light, radiation, or gas. In this paper, several simple methods of exposing blood to these bioactive exogenic agents are introduced. In in vitro method, blood is divided into two cylindrical glass bottles which have openings on both ends. After the bottles are connected with a vinyl tube to make a circuit, they are mounted parallel on the axis of a rotating rod. The air (or laboratory gas) is circulated by a vibration pump incorporated into this gas circuit to equalize the temperature in the two bottles. When the rod is rotated, a thin film of blood is formed over the internal surface of the bottles. This method permits blood to be in contact with the gas inside and to be exposed to light from the outside of the bottle. In in vitro method, blood is divided into two thin-walled, transparent, rectangular bags placed parallel on a tilting board. When the board is tilted intermittently, a thin blood layer is formed in each bag. If the bags are installed with inlet and outlet tubes and connected with blood accesses to either animals or humans, this device will become a circuit for an in vivo study. When one of the two bottles or bags is covered with metal foil to shield it from light or radiation, it can be used as a control. These devices will offer a laboratory method to study the effects of the exposure of blood to some exogenous bioactive agents as well as a new therapeutic method with such agents.

[Emergency cardiopulmonary bypass for cardiopulmonary-cerebral resuscitation].

Cardiopulmonary bypass (C-P bypass) was performed on two patients who had not responded to conventional cardiopulmonary resuscitation (CPR). The first patient, a 56-y-o male, with bilateral pulmonary thromboembolism repeatedly underwent cardiac massage and electric defibrillation for recurrent ventricular fibrillation. A veno-arterial bypass route was prepared during cardiac massage, and bypass circulation was started 3 hours after the onset of the first ventricular fibrillation. Soon after the initiation of C-P bypass, the physical status and EEG of the patient improved. The patient regained consciousness within a few hours and later underwent open chest pulmonary embolectomy. The second patient, a 44-y-o male, developed refractory cardiogenic shock near the end of aortocoronary bypass graft operation. Under closed chest massage, a femoro-femoral cardiopulmonary bypass operation was started. Soon after the initiation of the bypass circulation and IABP, peripheral circulation improved markedly, and consciousness returned within several hours. Though the first patient finally died from far advanced pulmonary embolism, he was conscious as long as the C-P bypass was continued for two days. In the second patient, the cardiac function gradually improved after the 3rd day. C-P bypass was tapered and discontinued on the 5th day. Emergency veno-arterial bypass for CPR is effective means to maintain life until the cardiopulmonary and cerebral functions are restored. Recent advances in emergency C-P bypass are introduced and a new acronym extracorporeal lung and heart assist, ECLHA, is proposed. Emergency ECLHA with veno-arterial cannulations through percutaneous puncture will become a promising adjunct of cardiopulmonary-cerebral resuscitation in the near future.

[A portable manual sternal compressor for cardiac massage of a patient under transportation--1. Evolution after trials and errors].

Difficulties of external cardiac massage during transportation of a patient on a litter or stretcher prompted us to develop a new portable manual sternal compressor. A seemingly good idea of sternal compression with an inflatable balloon placed between the sternum and a chest band engaged us in a long ordeal of trial and error until we retreated from this preconception. A practical sternal compressor has finally been created by applying two hydraulic pistons, one as a sternal compressor and the other as its push-pull energizer incorporated into a manual lever system. In this paper, one of the serial reports on this new device, all our errors are described lest some one in the future meet the same problems. Details of this new apparatus and the results of our experimental study and clinical application will soon follow this paper.

[A case of acute airway obstruction with sharp sawdust particles, successfully treated by extracorporeal lung assist].

A 17 year-old male accidentally fell into a loading shute filled with sharp particles of sawdust. He aspirated a large amount of sawdust and suffered from acute airway obstruction accompanied by barotrauma, probably due to severe cough and tissue damage from the needle sharp sawdust particles. Ordinary mechanical ventilation was not enough to keep normal gas exchange. To sustain life, a venovenous extracorporeal lung assist, ECLA, with two Kolobow membrane lungs was performed. Under ECLA, the sawdust particles were removed from the airway one by one with a bronchofiber scope taking almost 10 hours. Then the left lung lavage was performed with normal saline to remove finer sawdust. The patient survived these procedures and was weaned from ECLA after 36 hrs. His recovery was uneventful.

[Part I. Theory and computer simulation for cerebrospinal infusion].

A pharmacokinetic one-compartment model for the cerebrospinal infusion for the brain tumor chemotherapy is described together with various parameters used for computer simulation. An antitumor protein, neocarzinostatin (NCS) as a prototype drug, has been utilized since it was found effective against glioblastoma cells at extremely low concentration (less than 5 ng/ml) and it is readily inactivated by serum. A very slow infusion velocity was found necessary for an appropriate dose regimen; for example, 0.25mg of the drug should be infused into CSF for about 40 min to attain a drug level of 8 ng/ml.

In vitro mode of action, pharmacokinetics, and organ specificity of poly (maleic acid-styrene)-conjugated neocarzinostatin, SMANCS.

The organ specificity and pharmacokinetics of SMANCS, poly (maleic acid-styrene)-conjugated neocarzinostatin (NCS), were investigated in rats. The drug activity accumulated primarily in the regional lymph nodes after subcutaneous injection. After intravenous injection, the drug was found in the kidney, lymph nodes, and bladder in very high concentrations, and in lesser concentrations in the bone marrow, lung, small intestine, liver and spleen. The urinary excretion rate and total recovery of the drug after intravenous injection were higher than those after subcutaneous injection. SMANCS, having a molecular weight of 2.5 x 10(4) daltons, was degraded in vivo to NCS (mol. wt. about 1.1 x 10(4)). This was also confirmed in vitro by incubating the drug with cell homogenates. SMANCS caused strand scission of DNA similarly to NCS in lymphoblastoid cells. However, in a cell-free system using colicin E1 plasmid DNA, a high concentration of SMANCS was required to produce DNA degradation detectable by the alkaline sucrose gradient method.