Chronic stress experience and burnout syndrome have appreciable influence on health-related quality of life in patients with psoriasis.

BACKGROUND: Psoriasis has a negative impact on health-related quality of life (HRQoL) and may favour mental comorbidity. OBJECTIVE: To investigate the contribution of chronic stress and burnout experience to HRQoL and how mental health influences the efficacy of an inpatient rehabilitation measure in psoriasis patients. METHODS: Eighty-four psoriasis patients taking part in a 3-week inpatient rehabilitation measure participated in the study. Severity of psoriasis was assessed with the Psoriasis Area and Severity Index (PASI) and by patients' self-evaluation at the beginning and end of treatment. The following aspects of mental health were explored using validated questionnaires. Symptoms of chronic stress and burnout experience: Trier Inventory for the Assessment of Chronic Stress (TICS) and Shirom Melamed Burnout Measure (SMBM). Symptoms of depression: depression scale of the Patient Health Questionnaire in the German version (PHQ-D). HRQoL: Dermatology Life Quality Index (DLQI) and Short Form Health Survey-8 (SF-8). RESULTS: Linear regression analyses revealed that chronic stress, burnout experience and perceived symptom severity but not clinician-assessed severity of psoriasis had independent negative effects on HRQoL. Patients who achieved a PASI reduction of <75% at discharge from the rehabilitation measure had lower baseline QoL and showed more symptoms of depression, chronic stress and burnout than patients who achieved a PASI improvement of ≥75. CONCLUSION: Chronic stress and burnout have appreciable influence on HRQoL and may adversely affect treatment success in psoriasis patients. Our data underscore the importance of a multidimensional approach in the management of psoriasis.

Mice deficient in the alpha7 neuronal nicotinic acetylcholine receptor lack alpha-bungarotoxin binding sites and hippocampal fast nicotinic currents.

The alpha7 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) is abundantly expressed in hippocampus and is implicated in modulating neurotransmitter release and in binding alpha-bungarotoxin (alpha-BGT). A null mutation for the alpha7 subunit was prepared by deleting the last three exons of the gene. Mice homozygous for the null mutation lack detectable mRNA, but the mice are viable and anatomically normal. Neuropathological examination of the brain revealed normal structure and cell layering, including normal cortical barrel fields; histochemical assessment of the hippocampus was also normal. Autoradiography with [3H]nicotine revealed no detectable abnormalities of high-affinity nicotine binding sites, but there was an absence of high-affinity [125I]alpha-BGT sites. Null mice also lack rapidly desensitizing, methyllycaconitine-sensitive, nicotinic currents that are present in hippocampal neurons. The results of this study indicate that the alpha-BGT binding sites are equivalent to the alpha7-containing nAChRs that mediate fast, desensitizing nicotinic currents in the hippocampus. These mice demonstrate that the alpha7 subunit is not essential for normal development or for apparently normal neurological function, but the mice may prove to have subtle phenotypic abnormalities and will be valuable in defining the functional role of this gene product in vivo.

Immunohistochemical localization of the nicotinic acetylcholine receptor subunit alpha6 to dopaminergic neurons in the substantia nigra and ventral tegmental area.

Participation of the neuronal nicotinic receptor subunit alpha6 in a physiologically relevant receptor has yet to be demonstrated, but its high degree of expression in catecholaminergic nuclei has attracted considerable interest. To investigate the pattern of expression of the alpha6 protein, a subunit specific antibody against the alpha6 subunit was used to immunohistochemically label sections of the adult rat brain. Alpha6 immunoreactivity was found to be present in the substantia nigra, the ventral tegmental area, the locus coeruleus and the medial habenula, and double-labeling for tyrosine hydroxylase demonstrated that the alpha6 protein is present on dopaminergic neurons of the midbrain. A possible role for the alpha6 subunit in nicotinic modulation of dopaminergic transmission is therefore proposed.

Neuronal localization of the cyclophilin A protein in the adult rat brain.

Cyclophilin A is a small, soluble protein which binds the immunosuppressive drug cyclosporin A. Cyclophilin A is a peptidyl-prolyl isomerase and is widely expressed in a multitude of tissues, but is present in highest concentration in the brain. A role for this protein in the maturation and folding of neuron-specific membrane proteins has been hypothesized. Immunohistochemical staining for cyclophilin A was used to determine whether cyclophilin A is present in neurons, and whether there is variation in the level of expression with respect to brain regions and cell types. The specificity of the antibody used was demonstrated by Western blot analysis and cyclosporin affinity purification. Immunohistochemical staining of sections of adult rat brain showed labelled neurons throughout the neuraxis. The intensity of the immunostaining observed was roughly equivalent to neuronal cell density and was restricted to gray matter. On a cellular level, staining was present in cytosol and nuclei and extended into neuronal processes. Fluorescent double-labelling experiments on hippocampal cell cultures revealed that all cells labelled with the cyclophilin A antibody also showed staining for the neuron-specific marker for microtubule-associated protein (MAP)2, and could, therefore, be identified as neurons. Immunoreactivity in these neurons is present in punctate, spinelike structures along dendrites. Cyclophilin A immunoreactivity was undetectable in glial fibrillary acidic protein (GFAP)-positive cells. The pattern of cyclophilin. A expression is consistent with a role of cyclophilin A in neuronal protein maturation and folding in vivo.

Adherence and arrhythmic mortality in the cardiac arrhythmia suppression trial (CAST).

Patient adherence to therapy is essential to assess treatment efficacy, particularly in clinical trials. Active treatment usually is expected to benefit patients. The healthy adherer effect, the association or greater adherence to all health-promoting behaviors, including medication and overall concern for health, explains the improved survival of more adherent patients in both active and placebo medication groups of several clinical trials. The Cardiac Arrhythmia Suppression Trial (CAST), a placebo-controlled double-blind clinical trial of post-myocardial infarction (MI) patients with asymptomatic ventricular arrhythmias, in which active medication (encainide or flecainide) led to increased mortality, provided an opportunity to examine the relationship of adherence to survival from a different perspective. We consider whether adherence to active treatment was related to arrhythmic mortality and whether a healthy adherer effect might counteract the effect of treatment on mortality among patients taking active medication. Adherence (average pill count) at the first follow-up visit did not differ in the active treatment (92.2%, standard deviation (SD) = 11.97, n = 574) and placebo (90.8%, SD = 13.66, n = 579) groups. In a Cox proportional hazard regression model, medication adherence predicted arrhythmic mortality among the active (P < 0.0062) but not the placebo medication group. The effect of adherence on arrhythmic mortality was significant beyond the effects of ejection fraction, race, spouse, smoking status, diuretic medication, and history of MI. A 10% increase in adherence led to more than a threefold increase of risk of arrhythmic death. The design of the CAST, which included a titration phase, may have tended to select relatively adherent patients since only those whose arrhythmias were suppressed with active medication were randomized into the trial. The data do not support a strong healthy adherer effect in the CAST. There was no evidence in this study that a healthy adherer effect counterbalanced the effect of the active medication.

Optimal bowel preparation for flexible sigmoidoscopy--are two enemas better than one?

Recommendations regarding optimal bowel preparation for fiberoptic flexible sigmoidoscopy remain anecdotal and inconclusive. We prospectively evaluated three commonly recommended regimens for administering hypertonic phosphate enemas to subjects undergoing 60-cm fiberoptic flexible sigmoidoscopy for routine indications. Patients were randomly assigned to one of three hypertonic phosphate enema regimens. Group A received one enema 1 hour before fiberoptic flexible sigmoidoscopy, group B received two enemas 1 hour before, and group C received one enema 3 hours before and a second enema 1 hour before fiberoptic flexible sigmoidoscopy. Adequacy of bowel preparation was graded as excellent, adequate, or poor. Results revealed no statistically significant difference in the adequacy of bowel preparation between the three regimens, all resulting in adequate or excellent preparation in approximately 80% of patients. We recommend the use of one hypertonic phosphate enema 1 hour before routine fiberoptic flexible sigmoidoscopy. Implementation of this recommendation is efficacious, convenient for patients, and cost-effective.

Reversal of advanced liver fibrosis in rabbits with Schistosomiasis japonica.

Advanced liver fibrosis is generally considered to be irreversible. We studied the reversibility of marked liver fibrosis in rabbits infected with Schistosoma japonicum. We determined liver collagen content, collagen biosynthesis, and collagenase activity using serial biopsy specimens obtained 20, 40, and 60 weeks after infection. Reversibility of this process was investigated in rabbits cured of infection at 21 weeks; control rabbits not cured of infection were also studied. At 20 weeks, liver collagen content was 16-fold greater than normal, with accumulation of collagen types I, III, and V. Synthesis of collagen within fibrotic liver slices was 10-fold greater than normal. Liver collagenolytic activity for a type I substrate was 19-fold greater than normal. After parasitologic cure, a striking morphologic reversal of fibrosis occurred during the subsequent 40 weeks, with the return of liver collagen content to three-fold greater than normal and a 75% decrease in synthetic rates compared with those at 20 weeks (P < 0.01). Collagenolytic activity remained elevated to the same degree noted at 20 weeks. A similar but lesser resolution of fibrosis also occurred in untreated control rabbits, coincident with a spontaneous decrease in new egg deposition known to occur in this model system. We conclude that advanced liver fibrosis in S. japonicum-infected rabbits is slowly reversible after cure or senescence of the infection. A possible mechanism for this reversal is persistently increased collagenolysis as collagen synthesis diminishes.

The tilt test: effect of diabetes mellitus and antihypertensive medication on normal values.

The Tilt Test is a commonly used clinical tool for the assessment of volume depletion. Most of the data pertaining to the normal limits of the Tilt Test were determined by studying normal, healthy volunteers. Patients presenting with possible volume depletion, however, may have medical conditions (e.g., diabetes) or be taking medication (e.g., antihypertensives) that may affect the cardiovascular response to the Tilt Test. One hundred thirty-three euvolemic, asymptomatic outpatients (34 diabetics, 20 patients on beta blockers, 31 patients on diuretics, 28 patients on diuretics plus beta blockers, and 20 patients on clonidine hydrochloride) underwent Tilt testing. The readings obtained from each subgroup were compared to 33 sex- and age-matched controls who had no medical problems and were on no medications. No significant differences among the groups could be determined. We conclude that in otherwise euvolemic, asymptomatic patients, neither diabetes mellitus nor the specific antihypertensives studied interfere with the normal response to the Tilt Test.

Combustible colonic gas levels during flexible sigmoidoscopy and colonoscopy.

To what extent the standard preparation for sigmoidoscopy (phosphosoda enemas) makes the bowel safe for electrocautery is unknown. Sixty patients were prospectively evaluated to compare the presence of the combustible gases hydrogen and methane during colonoscopy and flexible sigmoidoscopy. Thirty patients underwent flexible sigmoidoscopy after phosphosoda enema preparation, and 30 patients underwent colonoscopy after a polyethylene glycol solution preparation. During colonoscopy, the concentrations of hydrogen and methane remained below combustible levels in all patients. Even segments of colon with significant fecal matter present did not have combustible levels of these two gases. However, at flexible sigmoidoscopy, combustible levels of hydrogen and methane were measured in 3 of 30 (10%) patients. Due to the risk of explosion, electrocautery should not be performed during routine flexible sigmoidoscopy after the standard phosphosoda enema preparation.

Follow-up of hot biopsy forceps treatment of diminutive colonic polyps.

Although the hot biopsy technique is widely used to treat diminutive colon polyps, there is concern over its efficacy and safety. Our study involved 39 patients undergoing routine colonoscopy in whom 62 diminutive polyps were found in the rectosigmoid. These lesions were treated with hot biopsy forceps in the standard manner. Flexible sigmoidoscopy was repeated 1 and 2 weeks later with the original treatment sites being identified. Eleven of the 62 sites (17%) revealed persistent viable polyp remnants, indicating incomplete treatment. In terms of safety, there were no clinical complications in this small study and most post-biopsy ulcers were healed by 2 weeks. This study shows that the hot biopsy technique may be unreliable in eradicating diminutive colon polyps.

Validation of the digital rectal examination as an estimate of anal sphincter squeeze pressure.

Although digital examination is commonly used to assess anal sphincter tone and maximal squeeze pressure, the accuracy of this test has never been adequately validated. A total of 27 patients with a spectrum of subjectively assessed anal sphincter tones were studied. Simultaneous subjective (digital) and objective (manometric) determinations of maximal anal squeeze pressures were made. Subjective digital assessment revealed the following: three patients, absent squeeze pressure (grade 0); two patients, markedly reduced (grade +1); six patients, reduced (grade +2); and the remaining 16 patients had normal maximal squeeze pressure (grade +3). Simultaneous objective anal sphincter pressure measurements, when compared with these subjective values, revealed a correlation coefficient of 0.97 (p less than 0.05). Therefore, the clinician can reliably use the digital rectal examination to judge anal sphincter strength.

Can clinicians accurately assess esophageal dilation without fluoroscopy?

This study questioned whether clinicians could determine the success of esophageal dilation accurately without the aid of fluoroscopy. Twenty patients were enrolled with the diagnosis of distal esophageal stenosis, including benign peptic stricture (17), Schatski's ring (2), and squamous cell carcinoma of the esophagus (1). Dilation attempts using only Maloney dilators were monitored fluoroscopically by the principle investigator, the physician and patient being unaware of the findings. Physicians then predicted whether or not their dilations were successful, and they examined various features to determine their usefulness in predicting successful dilation. They were able to predict successful dilation accurately in 97% of the cases studied; however, their predictions of unsuccessful dilation were correct only 60% of the time. Features helpful in predicting passage included easy passage of the dilator (98%) and the patient feeling the dilator in the stomach (95%). Excessive resistance suggesting unsuccessful passage was an unreliable feature and was often due to the dilator curling in the stomach. When Maloney dilators are used to dilate simple distal strictures, if the physician predicts successful passage, he is reliably accurate without the use of fluoroscopy; however, if unsuccessful passage is suspected, fluoroscopy must be used for confirmation.

Colonic lavage solution (polyethylene glycol electrolyte lavage solution) as a treatment for chronic constipation: a double-blind, placebo-controlled study.

The purpose of this study was to demonstrate that polyethylene glycol electrolyte lavage solution (PEG-ELS), a colonic lavage solution presently used for gut cleansing in preparation for colonic procedures, can be an effective agent in the treatment of chronic constipation. Thirty-two patients with chronic constipation completed a controlled, double-blind, randomized, cross-over study. Each patient was given two containers, marked A and B, one containing PEG-ELS and the other a placebo. They drank a specified amount (8 or 16 oz) of solution A for five consecutive days. Daily number of bowel movements and stool consistency were recorded. Group I (patients 1-16) drank 8 oz of solution per day; group II (patients 17-32) drank 16 oz of solution per day. Mean stool frequency and mean stool consistency were calculated per 5-day testing period for each treatment group (8 oz placebo, 8 oz PEG-ELS, 16 oz placebo, 16 oz PEG-ELS). Two-factor analysis of variance results confirmed that PEG-ELS was superior to placebo with regard to mean stool frequency (7.75 +/- 4.55 vs. 4.88 +/- 2.62, p less than 0.01) and mean stool consistency (2.56 +/- 1.17 vs. 1.91 +/- 0.94, p less than 0.05). Furthermore, PEG-ELS 16 oz per day was superior to all other groups with regard to the measured variables. Side effects from the PEG-ELS were infrequent and tolerable. Our results indicate that PEG-ELS may be an effective alternative therapy in the treatment of chronic constipation. The proper dosage is probably between 8 and 16 oz per day.

Detection and surveillance of colorectal cancer.

Colorectal cancer is the second most common cause of cancer in the United States. The overall mortality rate approaches 60%. However, the detection of early lesions results in a mortality rate of 20% or less. Therefore, if improvement in survival is to occur, increased efforts need to be focused not only on primary prevention but also on early detection of malignant lesions and the eradication of potentially malignant lesions. There is no universal consensus as to how this can be accomplished. The purpose of this article is to serve as a guideline, providing a practical basis for improving early detection and management of colorectal cancer and its precursors.

Columnar mucosa in the proximal esophagus.

Twelve cases of columnar mucosa occurring in the proximal esophagus are described. This lesion is more common than previously recognized and is frequently overlooked at endoscopy, possibly due to inadequate examination of the proximal esophagus. This lesion has a typical and easily recognized endoscopic appearance. Biopsy of the lesion confirms the presence of columnar mucosa, usually with parietal cells (11 of 12 cases). It does not appear to be related to Barrett's epithelium and may represent either a congenital rest or a response to recurrent trauma. Current evidence would seem to support a congenital origin.

Appendicitis as an unusual cause of progressive sigmoid narrowing.

Although the presentation of appendicitis is usually straight-forward, unusual manifestations can delay diagnosis. To emphasize this, we describe a patient who developed progressive sigmoid narrowing with only nonspecific abdominal complaints over a period of months. Eventually, we came upon a pelvic abscess from a ruptured appendix. Clinicians must be ever vigilant for appendicitis and its complications.

Enzymatic digestion of esophageal meat impaction. A study of Adolph's Meat Tenderizer.

While a solution of Adolph's Meat Tenderizer (AMT) is commonly used to treat esophageal meat impaction, few studies describe its clinical effects. We examined AMT with regard to (1) its papain activity; (2) its ability to digest meat cubes in vitro; and (3) its effect on rabbit esophageal mucosa. A standard papain assay was developed against which the activity of AMT was compared. Proteolytic activity was detected in AMT only when the papain activators, 0.02 M cysteine and 0.008 M EDTA, were added to the system. Meat cubes incubated in AMT solution exhibited no evidence of digestion as determined by protein release or change in sample weight. A solution of AMT had no adverse effect on normal esophageal mucosa in rabbits, but significantly increased esophagitis when infused onto previously inflamed mucosa. We conclude that AMT solution has no inherent capacity to digest or to reduce the size of an impacted meat bolus, and may, in fact, worsen existing esophagitis.

Long-term treatment of hypertension with methyldopa. VII. Effectiveness among patients treated for seven or more years.

Experience with 25 hypertensive patients who had received methyldopa for 7 years or more as part of a multiclinic retrospective study is described. Methyldopa proved highly effective and usually well tolerated for long-term management of essential hypertension.

Comparison of the Menghini, Klatskin and Tru-Cut needles in diagnosing cirrhosis.

The Menghini, Klatskin and Tru-cut needles were used to obtain multiple biopsies from cirrhotic livers at autopsy. Comparison of specimens showed that Tru-Cut biopsies were the longest and least fragmented, produced the greatest diagnostic accuracy and fewest false negative diagnoses of cirrhosis. Pending further evaluation of its safety, the Tru-Cut needle seems the instrument of choice for the biopsy diagnosis of cirrhosis.

Hemobilia secondary to metastatic liver disease.

Hemobilia has previously been reported only in association with primary hepatic tumors. A patient with metastatic liver disease is described who presented with melena, abdominal pain, and jaundice. Bleeding from the ampullary papilla was observed at endoscopy. Jaundice resulted from biliary obstruction by blood clots containing foci of tumor cells identical to those of the hemorrhagic hepatic tumor nodules. Hemobilia from metastatic liver disease may occur more commonly than reported.