Elevated endocan levels and its association with clinical severity in Stevens-Johnson Syndrome and toxic epidermal necrolysis.

AIM: The aim of this study was to determine the levels of endocan and other biomarkers of inflammation in the systemic circulation of three groups of patients: 1) biopsy confirmed Stevens Johnson Syndrome, Toxic Epidermal Necrolysis (SJS/TEN) subjects; 2) patients with allergic skin reactions but biopsy negative for SJS/TEN; and 3) normal controls. Besides, this paper aims to investigate the association of endocan levels with the extent of the skin lesions, the presence of purpura, and the degree of acute renal insufficiency, as well as to investigate endocan as a marker of clinical severity by correlating endocan levels with the SCORTEN results (a prognositic score for SJS/TEN). METHODS: Sixteen patients over the age of 18 years who were referred to Loyola University Medical Center with severe allergic skin reactions were recruited over a two-year period from May 2012 to May 2014. A diagnosis of SJS or TEN was confirmed in 7 subjects by skin biopsy. Citrated plasma samples were assayed for endocan, tumor necrosis factor-α (TNFα), vascular endothelial growth factor (VEGF), and C-reactive protein (CRP). The differences between SJS/TEN subjects, biopsy negative subjects, and normal controls (N.=23) were explored using ANOVA and Tukey's post-hoc test. Associations with other clinical variables were identified using linear and logistic regression. RESULTS: Biopsy positive SJS/TEN subjects and biopsy negative subjects had higher endocan levels than normal controls (SJS/TEN: 3.01 ng/mL [IQR: 2.15-8.11]; biopsy negative: 3.96 ng/mL [IQR: 1.54-4.85]; normal controls: 1.79 ng/mL [IQR: 1.67-1.98]; ANOVA P=0.0038). Endocan levels were more strongly associated with SCORTEN in SJS/TEN subjects than in biopsy negative subjects (R2 SJS/TEN=0.5110; biopsy negative=0.0317). SJS/TEN subjects exhibited significantly higher levels of TNF-α compared to normal controls (P=0.0267). The TNF-α levels were significantly lower compared to biopsy negative subjects (P=0.0052). VEGF levels were also elevated among SJS/TEN and biopsy negative subjects compared to normal controls (SJS/TEN: 12.04 pg/mL: [IQR: 7.64-52.7]; biopsy negative: 10.54 pg/mL [IQR: 4.17-6.46]; normal controls: 4.94 pg/mL [IQR: 4.17-6.46]; ANOVA P<0.0001). There was no significant difference in VEGF levels between SJS/TEN and biopsy negative subjects (P=0.7110). Similarly, CRP levels were elevated among SJS/TEN patients and biopsy negative subjects compared to normal controls (SJS/TEN: 32.09 µg/mL [IQR: 31.49-52.08]; biopsy negative: 83.38 µg/mL [IQR: 44.74-145.38]; healthy normal: 1.08 µg/mL [IQR: 0.73-2.03]; ANOVA P<0.0001). There was no significant difference in CRP levels between SJS/TEN and biopsy negative subjects (P=0.2416). CONCLUSION: To our knowledge, this is the first study to evaluate enodcan, a marker of endothelial dysfunction, in the systemic circulation of SJS/TEN patients. Elevated endocan levels were more strongly associated with disease severity among SJS/TEN subjects than among less severe allergic reactions with skin involvement.

Direct observation of counseling on colorectal cancer in rural primary care practices.

To better understand colorectal cancer (CRC) screening practices in primary care, medical students directly observed physician-patient encounters in 38 physician offices. CRC was discussed with 14% of patients >or=50 years of age; 87% of discussions were initiated by the physician. The rate of discussions varied among the practices from 0% to 41% of office visits. Discussions were more common for new patient visits, with younger patients, and in the 24% of offices that utilized flow sheets. The frequency of CRC discussions in physician offices varies widely. More widespread implementation of simple office systems, such as flow sheets, is needed to improve CRC screening rates.

Direct observation of smoking cessation activities in primary care practice.

OBJECTIVE: Our goals were to determine how often family physicians incorporate smoking cessation efforts into routine office visits and to examine the effect of patient, physician, and office characteristics on the frequency of these efforts. STUDY DESIGN: Data was gathered using direct observation of physician-patient encounters, a survey of physicians, and an on-site examination of office systems for supporting smoking cessation. POPULATION: We included patients seen for routine office visits in 38 primary care physician practices. OUTCOMES MEASURED: The frequency of tobacco discussions among all patients, the extent of these discussions among smokers, and the presence of tobacco-related systems and policies in physicians' offices were measured. RESULTS: Tobacco was discussed during 633 of 2963 encounters (21%; range among practices = 0%-90%). Discussion of tobacco was more common in the 58% of practices that had standard forms for recording smoking status (26% vs 16%; P=.01). Tobacco discussions were more common during new patient visits but occurred less often with older patients and among physicians in practice more than 10 years. Of 244 smokers identified, physicians provided assistance with smoking cessation for 38% (range among practices = 0%-100%). Bupropion and nicotine-replacement therapy were discussed with smokers in 31% and 17% of encounters, respectively. Although 68% of offices had smoking cessation materials for patients, few recorded tobacco use in the "vital signs" section of the patient history or assigned smoking-related tasks to nonphysician personnel. CONCLUSIONS: Smoking cessation practices vary widely in primary care offices. Strategies are needed to assist physicians with incorporating systematic approaches to maximize smoking cessation rates.

How much information about adverse effects of medication do patients want from physicians?

BACKGROUND: Little information exists concerning the amount of information patients expect from physicians as to the risk for an adverse medication reaction. The present study was designed to determine such opinions in a population sample; to correlate results with sex, age, educational level, and previous experience with adverse effects; and to determine whether patients believe physicians should use discretion in the amount of such information given. METHODS: Two thousand five hundred sequential adults visiting outpatient clinics filled out a 12-item questionnaire. Percentages of subjects desiring information about varying degrees of risk and those believing physicians should and should not use discretion in the amount of such information provided were recorded. Results were correlated with demographic variables and previous experience of adverse effects. RESULTS: Among the respondents, 76.2% desired to be told of all possible adverse effects; 13.3% only if an adverse effect occurred 1 in 100 000 times; and 10.2% only if such occurrence was 1 in 100 times; 0.4% were not interested in any information. (Percentages have been rounded and do not total 100.) Percentages were closely similar to those for the same question that restricted opinion to serious adverse effects. Desire for maximum information was significantly correlated with lower educational level (P<.00l) and previous frequent experience with adverse effects (P<.001) and in older women (P<.001). The opinion that the physician should give the same information to all patients was given by 67.6% of the sample, and 73.4% opined that physicians were never justified in withholding any information. CONCLUSION: Most individuals desire from physicians all information concerning possible adverse effects of prescribed medication and do not favor physician discretion in these decisions.

Tube feeding in nursing home residents with severe and irreversible cognitive impairment.

OBJECTIVES: This study was undertaken to determine the degree to which selected demographic and clinical variables are associated with the use of feeding tubes in older nursing home residents with very severe and irreversible cognitive impairment. DESIGN: Descriptive, cross-sectional, population-based study. SETTING: Kansas nursing homes from January 1, 1994, through June 30, 1998. PARTICIPANTS: A total of 4,997 nursing home residents with very severe and irreversible cognitive impairment comprised the study population. Subjects were identified using data in Minimum Data Set (MDS) reports. Those who were included in the study population were over the age of 65, had two consecutive Cognitive Performance Scale scores of 6, were without evidence of significant subsequent improvement, and were not comatose. MEASUREMENTS: The MDS data on each resident were examined to determine subjects' age, ethnicity, gender, Medicaid eligibility, disease diagnoses, physical functioning, and oral/nutritional status, including feeding tube status. The MDS was also used to determine urban versus rural location of the nursing home. The association between the use of feeding tubes and selected demographic and clinical characteristics was then examined using bivariate and logistic regression tests. RESULTS: Of the 4,997 residents in the study population, 577 (11.6%) had feeding tubes. In multivariate analysis, feeding tube use was found to be associated with swallowing problems (odds ratio (OR) 5.4, 95% confidence interval (CI) 4.3-6.8); urban location of nursing home (OR 2.9, 95% CI 2.3-3.5); non-white race (OR 2.7, 95% CI 1.9-3.6); stroke (OR 2.5, 95% CI 2.0-3.1); and absence of dementia (OR 2.5, 95% CI 2.0-3.1). Feeding tubes were also more weakly associated with age <86 years, male gender, dependency for all activities of daily living, and absence of a living will. Feeding tube use was not found to be associated with chewing problems, Medicaid status, or resuscitation status. CONCLUSIONS: Clinical variables including swallowing problems, stroke, and absence of dementia were strongly associated with the use of feeding tubes in this cross-sectional, population-based study. In addition, urban location of nursing home and non-white race were significantly associated with feeding tubes. These findings suggest that feeding tube decisions are strongly influenced by nonclinical factors and invite further investigation.

The use of nicotine patches with minimal intervention.

BACKGROUND: This paper describes a natural, prospective, open-label study designed to evaluate the impact of free nicotine patches with minimal support for smoking cessation. METHODS: Surveys were administered to 223 participants who received nicotine patches from the American Lung Association. All participants received a 6-week supply of 15-mg/16-h transdermal nicotine patches, a self-help book Freedom from Smoking, and information about area smoking cessation classes. Follow-up telephone surveys were administered 6 weeks after the patches were distributed. Abstinence was measured through self-report exclusively. RESULTS: The overall quit rate at 6-weeks was 21% (47/223). Among nonquitters, the mean number of cigarettes smoked per day dropped from 25 at baseline to 14 at 6 weeks. There was a significant difference in the average number of patches used by quitters and nonquitters (26 versus 11, P < 0.001). CONCLUSIONS: Nicotine patches with minimal support can be effective in smoking cessation and smoking reduction. The availability of patches may have motivated participants to quit. Efforts to increase access to and use of nicotine patches may result in increased attempts to quit and successful quitting.

Dose-Response Study of Vigabatrin as add-on therapy in patients with uncontrolled complex partial seizures.

PURPOSE: This placebo-controlled, randomized, double-blind, multicenter study examined the efficacy and safety of three daily doses of vigabatrin (VGB; 1, 3, or 6 g) as add-on therapy in 174 patients with previously uncontrolled complex partial seizures with or without secondary generalization. METHODS: A 12-week pretreatment assessment period was followed by drug therapy with a 6-week titration period and a 12-week maintenance phase. RESULTS: VGB doses of 3 and 6 g/day reduced median monthly frequency of seizures by 4.3 and 4.5 seizures, respectively, compared with 0.2 seizures for placebo (p = 0.0001). The percentages of patients classified as therapeutic successes (> or =50% reduction in seizure frequency) were 7% for placebo and 24, 51, and 54% for patients taking daily VGB doses of 1, 3, and 6 g, respectively; the comparison with placebo was significant for all treatment groups. The linear trend for dose response was highly significant (p< or =0.0001) for both median monthly seizure frequency and therapeutic success. Vigabatrin was well tolerated, causing no clinically significant changes in laboratory parameters, brain magnetic resonance imaging, evoked potentials, cognitive function, or psychosocial tests. Fatigue, drowsiness, and dizziness were the most common treatment-related adverse events in all treatment groups. Dropouts due to adverse events were higher in the 6-g/day group. CONCLUSIONS: VGB was significantly more effective than placebo as add-on therapy in reducing seizure frequency. VGB at 3 and 6 g/day produced the best efficacy: however, adverse events may limit the use of the 6-g/day dose in some patients.

Early retinal and renal abnormalities in diabetes.

The integrity of the blood-retinal and blood-glomerular vascular barriers were investigated simultaneously in diabetic individuals to determine whether or not the early forms of diabetic retinopathy and nephropathy are temporally related. The blood-retinal barrier was assessed by the technique of vitreous fluorophotometry. Twenty-four hour urinary excretion of albumin was determined by radioimmunoassay before fluorescein measurement. Posterior vitreous fluorescein leakage was greater in the study cohort than in the control population after diabetes had been present 11-20 years (p < 0.05) and 21 years or more (p < 0.01). Albumin excretion was also increased in the diabetic subjects (p < 0.001) and correlated to duration of diabetes (r = 0.51, p < 0.005). Hypertension raised midvitreous fluorescein levels (p < 0.05), but it had no effect on posterior vitreous values. Hypertension was an independent predictive factor for urinary albumin excretion (p < 0.05). Partial correlation analysis showed that vitreous fluorescence and urinary protein were not significantly correlated when controlled for duration of diabetes and for age. Early proteinuria did not predict retinal vascular leakage, nor did increased fluorescein leakage predict renal decompensation in the diabetic subjects. The data suggest that during the early stages of retinal and renal abnormalities associated with insulin-dependent diabetes, the eye and kidney follow different temporal courses to abnormal function.

A double-blind, placebo-controlled study of vigabatrin three g/day in patients with uncontrolled complex partial seizures. Vigabatrin Protocol 024 Investigative Cohort.

This study compared the efficacy and tolerability of vigabatrin 3/day as add-on therapy with that of placebo in patients with focal epilepsy whose complex partial seizures were difficult to control with established antiepilepsy drug therapy. We enrolled 203 patients; 182 (90 placebo; 92 vigabatrin) received drug therapy under double-blind conditions. We increased the daily dosage to 2.5 g/day during a 4-week titration segment and maintained it at 3 g/day during the 12-week maintenance segment. By analyses we found a statistically significant lower frequency of seizures (complex seizures plus partial seizures secondarily generalized) at the end of the study for patients receiving vigabatrin than for those receiving placebo. The median monthly frequency was reduced by three seizures per 28 days in the placebo group (baseline, 8.3; end of study, 7.5) (p = 0.0002). Therapeutic success (a 50% reduction from baseline in mean monthly seizure frequency) was attained in 40 of the vigabatrin patients (43%) compared with 17 of those treated with placebo (19%) (p < 0.001). Vigabatrin significantly increased the mean number of seizure-free days per 28 days (2.2 days) compared with placebo (0.5 days) (p = 0.0024). Mean trough serum vigabatrin concentration during therapy was 8.6 +/- 7.7 micrograms/ml. The oral clearance of vigabatrin was determined to be 7.8 L/hr, and the elimination half-life was 8.4 hours. No clinically important changes in MRI, evoked potential, or other laboratory tests were noted during vigabatrin treatment. The results of this study indicate that 3 g/day vigabatrin is more effective than placebo as add-on therapy. Vigabatrin was well tolerated, compliance was high with twice-daily administration, and therapy did not result in clinically relevant drug interactions.

Retinal sensitivity in acute hypoglycemia.

We measured retinal threshold sensitivity via automated computerized static perimetry in predetermined meridians in euglycemic diabetic subjects and in the same subjects during insulin-induced hypoglycemia. During periods of reduced blood glucose levels, decreased retinal sensitivity, most marked in temporal meridians, was observed.

Ageing parameters of the ocular lens by scanning fluorophotometry.

A Beer-Lambert analysis of fluorophotometric scans of ocular lenses has been carried out. It is shown that an assumption of a single flourophor allows us to calculate the distribution of this fluorophor along the central lens axis. For the great majority of lenses in our study, covering a wide range of ages, our results are in essential agreement with published results on excised lenses. For a small subset of lenses in the study the assumption of a single fluorophor is found to be unsatisfactory. In these cases a reasonable symmetry assumption allows us to estimate the distribution of an additional agent which removes light from the entering or exiting beams without contributing to the fluorescence. The fact that this agent is restricted to the lens nucleus and that it occurs in lenses in which nuclear changes are clinically evident suggests that it is an expression of nuclear cataract.

Fluorophotometric measurement of human tear turnover rate.

Measurement of tear turnover rate using an automated scanning fluorophotometer (FluorotronR) was compared to Schirmer test results without anesthesia in young adults with no known ocular disorder. After the instillation of fluorescein, tear film fluorescence, expressed as fluorescein concentration equivalent, decreased exponentially in a linear fashion with time. The mean tear turnover rate was 30% per minute. Contact lens wearers had higher mean tear turnover rates when compared with non-contact lens wearers, but differences were not statistically significant. Half of tested eyes demonstrated total wetting of Schirmer Tear Test StripsR. Higher mean tear turnover rates were associated with complete wetting of the Schirmer test strips. There was no significant correlation between Schirmer paper wetting of less than 30 mm and fluorescein turnover rate.

Delayed retinal effects of the frequency-doubled YAG laser (532 nm).

In order to compare the retinal effects of the frequency-doubled YAG laser (532 nm) with those of argon laser, rabbit eyes were exposed to green YAG laser irradiation and processed for light and electron microscopic study at 24 hr, 2 weeks and 4 weeks. Detailed analysis was conducted on tissue exposed to 7.3 and 7.6 millijoules (mj). Response of the photoreceptors and retinal pigmented epithelium to green YAG was very similar to that described for argon laser over the same time period. By 2 weeks post-exposure, there was histologic evidence of partial recovery with absence of damaged, pycnotic photoreceptor nuclei, increased numbers of typical photoreceptor outer segment lamellae and repair of retinal pigmented epithelium. Four weeks after irradiation, normal-appearing photoreceptor nuclei were present although inner photoreceptor segments still showed mitochondrial damage. Outer segments at 4 weeks showed regular lamellar structures. We conclude that the frequency-doubled YAG laser is equivalent to the argon laser with respect to the production of thermal lesions in the retina. Its additional advantages include increased efficiency, portability, reliability and lack of absorption by macular xanthophyll pigment.

Autofluorescence of the crystalline lens in diabetes.

Lenticular autofluorescence in a diabetic population was quantitated by scanning ocular fluorophotometry. Measurements were made through the lens along the optical axis. The profile of the scan from front to rear was characterized by anterior and posterior juxtacortical peaks and a central plateau. Maximum fluorescence values were compared with those of nondiabetic control subjects. Fluorescence increased linearly with age in both populations, but was significantly higher in the diabetic population of all ages. Posterior to anterior fluorescence peak ratios decreased as a parabolic function of age in both populations, but peak ratios were lower in the diabetic population. We conclude that in vivo measurements of lens autofluorescence correlate with premature lenticular senescence in diabetes.

Increased synthesis of glycosaminoglycans of the cornea during fasting and refeeding in rats.

The effect of a 48 hour fast on sulfate incorporation of corneal mucopolysaccharides was investigated in the rat. After fasting for 24 hours, experimental and control rats were injected intraperitoneally with 35S-sulfate. After fasting an additional 24 hours, the rats were sacrificed and incorporation of the label into the acid mucopolysaccharide fraction of the cornea was determined. Incorporation of the label into the acid mucopolysaccharide fraction was significantly increased in the fasted rat cornea. Increased synthesis of corneal sulfated mucopolysaccharides during fasting in the rat contrasts with the well known decreased synthesis in cartilage under the same conditions. These findings suggest that corneal acid mucopolysaccharide synthesis is selectively preserved and/or increased during fasting.

Autofluorescence and light transmission in the aging crystalline lens.

We quantitated blue-green light transmission and autofluorescence of the human crystalline lens in vivo, using an automated scanning fluorophotometer (Fluorotron) coupled with a lens system designed for high resolution of the ocular anterior segment. Lenses were scanned through the dilated pupil along the optical axis, generating a fluorescence profile consisting of anterior and posterior juxtacortical peaks and a central plateau. Fluorescence increased linearly with increasing age. We calculated percent transmission of excitation (410-500 nm) and emission (510-670 nm) as the ratio of posterior to anterior juxtacortical peaks. Light transmission decreased as a parabolic function of age and was correlated with both fluorescence increase and observed lens brunescence.

Anterior retinal cryotherapy in diabetic vitreous hemorrhage.

Recurrent vitreous hemorrhage associated with proliferative retinopathy can occur in eyes that do not satisfactorily respond to argon laser pantretinal photocoagulation. To evaluate the effect of relatively low-risk surgical intervention, we performed peripheral retinal cryopexy on 24 eyes of 23 diabetic patients with proliferative diabetic retinopathy and vitreous hemorrhage. In most cases, cryopexy followed complete or nearly complete panretinal photocoagulation which did not prevent subsequent vitreous hemorrhage. Existing vitreous hemorrhage cleared postoperatively in 23 of 24 eyes. The best corrected visual acuity improved in 15 eyes, remained unchanged in five, and worsened in four. Four postoperative anterior segment complications resolved completely within a short time. One patient, a 68-year-old woman who had had diabetes for 18 years, postoperatively had a macular hole in one eye and macular edema with tractional retinal detachment in the other.