Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME).

This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure.

Plant-derived vaccine protects target animals against a viral disease.

The successful expression of animal or human virus epitopes on the surface of plant viruses has recently been demonstrated. These chimeric virus particles (CVPs) could represent a cost-effective and safe alternative to conventional animal cell-based vaccines. We report the insertion of oligonucleotides coding for a short linear epitope from the VP2 capsid protein of mink enteritis virus (MEV) into an infectious cDNA clone of cowpea mosaic virus and the successful expression of the epitope on the surface of CVPs when propagated in the black-eyed bean, Vigna unguiculata. The efficacy of the CVPs was established by the demonstration that one subcutaneous injection of 1 mg of the CVPs in mink conferred protection against clinical disease and virtually abolished shedding of virus after challenge with virulent MEV, demonstrating the potential utility of plant CVPs as the basis for vaccine development. The epitope used occurs in three different virus species-MEV, canine parvovirus, and feline panleukopenia virus- and thus the same vaccine could be used in three economically important viral hosts-mink, dogs, and cats, respectively.

Hyperbilirubinemia results in reduced oxidative injury in neonatal Gunn rats exposed to hyperoxia.

Bilirubin is a potent antioxidant in vitro. To determine whether bilirubin also is an antioxidant in vivo, we studied markers of oxidative injury in the Gunn rat model exposed to hyperoxia. Homozygous jaundiced males were mated with heterozygous nonjaundiced females to obtain both jaundiced and nonjaundiced pups within a litter. Once delivered, the pups and their mother were placed in air (21% O2) or hyperoxia (> 95% O2) for 3 d. Both jaundiced and nonjaundiced pups were removed from the chambers daily. Animals were sacrificed and blood was drawn for determination of serum bilirubin, blood thiobarbituric acid-reactive substances (TBARS) by fluorescence assay, serum hydroperoxides, and serum protein oxidation. Tissues (liver, lung, and brain) were assayed for lipid peroxides (TBARS, conjugated dienes [CD], loss of polyunsaturated fatty acid content [PUFA]). We also measured a wide range of serum antioxidants including superoxide dismutase, catalase, glutathione, vitamins A, C, and E, and uric acid. Blood TBARS were significantly decreased in the jaundiced pups compared to the nonjaundiced pups on day 3 of hyperoxia, and blood TBARS were inversely correlated to serum bilirubin on day 3 of hyperoxia (R2 +/- .89). Similar decreases in serum lipid hydroperoxides and serum protein carbonyl content were detected in the jaundiced pups as compared to their nonjaundiced littermates. Other serum antioxidants were not increased in jaundiced animals compared to nonjaundiced animals. Relative lung weight was lower in jaundiced pups exposed to hyperoxia compared to similarly exposed nonjaundiced pups, suggesting a reduction in hyperoxia-induced lung edema. We detected no significant effects of bilirubin on parameters of lipid peroxidation in solid tissues. We conclude that serum bilirubin protects against serum oxidative damage in the first days of life in neonatal Gunn rats exposed to hyperoxia. We speculate that bilirubin is a functionally important transitional antioxidant in the circulation of human neonates and that it may be involved in modulation of injury due to hyperoxia.

Disposable jet nebulizers. How reliable are they?

We studied the frequency of malfunction, variability in rate of nebulization, and effect of this variability on aerosol particle size of eight disposable jet nebulizer models produced by six manufacturers. Four of eight models showed visual signs of malfunction, including spraying of large, individually visible droplets, leaking of nebulizer solution, and air leaks that completely prevented nebulization. Variability of nebulization rate within specific models ranged from 57 to 129 percent. The model with the largest variability of nebulization rate was also associated with an unacceptably large variability in particle size. In contrast, two models with smaller variability in nebulization rate had greater consistency of particle size. These results indicate poor quality control by some manufacturers in the disposable nebulizer industry. The data suggest that purchasing agents should consider reliability as well as cost before selecting a specific nebulizer model and that their evaluation should include physical testing of multiple units of each model under consideration.

Endometritis following vaginal delivery.

The authors reviewed 158 cases of endometritis complicating vaginal delivery. The diagnostic criteria included fever over 100F with uterine tenderness and/or foul lochia. The mean temperature at diagnosis was 102.2F, and only 21 (13%) had temperature less than 100.9F. The majority of patients did not have traditional risk factors. Endometritis was characterized as generally early in onset (84% within 7 days) and usually mild in course (5.0% had bacteremia, 93.7% responded to initial antibiotics). Yet a small group (1.9%) developed documented pelvic abscess, fulminant peritonitis, or suspected septic pelvic thrombophlebitis.

Famotidine-associated mental status changes.

A 77-year-old man who had taken ranitidine for several years for dyspepsia was prescribed alternative therapy with famotidine 20 mg twice/day. He subsequently developed mental status changes, with confusion, disorientation, and nightmares. The symptoms dissipated after he discontinued famotidine for 2 days. He rechallenged himself and experienced return of the symptoms shortly thereafter, with additional visual hallucinations. His therapy was changed to lansoprazole, and his symptoms again disappeared and have not recurred. Case reports of central nervous system effects with other histamine2 antagonists have been published. Eight cases occurred with famotidine, all of which were in hospitalized patients receiving intravenous famotidine. We believe this is the first report of mental status changes in an ambulatory patient taking oral famotidine. The elderly may be particularly susceptible to such changes.

Sources of carbon monoxide (CO) in biological systems and applications of CO detection technologies.

Carbon monoxide is produced from a variety of sources in biological systems. Heme oxygenase and heme oxygenase-like activity is the predominant source in mammals, and may be equally important in plants and lower animals. The enzyme appears to be ubiquitous, highly conserved throughout phylogeny, and tightly regulated during development. This and other evidence suggests that heme oxygenase has an important physiological role, of which CO production may be a part. Other minor sources of CO include the oxidation of organic molecules. This includes the following: (1) auto-oxidation of phenols, flavenoids, and halomethanes; (2) photo-oxidation of organic compounds; and (3) lipid peroxidation of membrane lipids. No longer thought of as a waste product only, recent studies suggest that in the central nervous system cellular CO production can influence cGMP levels through effects on soluble guanylyl cyclase activity. Cellular CO production may also be linked to cell-cell interactions, and may be important in the cell's response to environmental changes. Whether CO will have a place similar to nitric oxide in cellular metabolism is still unclear, but it is apparent that these metabolic relationships will become increasingly complex. Cellular heme oxygenase activity results in the equimolar production of CO and bilirubin for each molecule of heme degraded. The CO thus formed diffuses into the blood, is carried via hemoglobin, and is excreted in the lungs. Therefore, CO production can be assessed clinically by measuring the rate of total body CO excretion, blood COHb levels, and end-tidal CO concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of heme oxygenase after oral vs intraperitoneal administration of chromium porphyrins.

The effects of chromium porphyrins on suckling rat heme oxygenase activity were compared following oral vs intraperitoneal dosing. Chromium protoporphyrin (CrPP), chromium mesoporphyrin (CrMP), or chromium deuteroporphyrin 2,4 bis glycol (CrBG) were administered at 40 mumol/kg to 2-week old suckling rats either orally or intraperitoneally. Six hours after intraperitoneal dosing, CrPP and CrMP had significantly reduced hepatic and splenic heme oxygenase activity by more than 55%. CrBG effectively reduced hepatic heme oxygenase activity by 42%. More importantly, only CrMP was an effective inhibitor of hepatic heme oxygenase activity 6 hr after oral administration. In the first reported comparison of chromium porphyrin efficacy in vivo, our data suggest that chromium porphyrins, and particularly CrMP, may be effective in chemopreventive strategies for the treatment of neonatal jaundice.

EEG sleep, lithium transport, dexamethasone suppression, and monoamine oxidase activity in borderline personality disorder.

Twenty-one patients who met DSM-III criteria for borderline personality disorder (BPD) and also scored at least 7 on the Diagnostic Interview for Borderlines (DIB) were assessed on four biological markers: electroencephalographic (EEG) sleep, in vitro lithium ratio, platelet monoamine oxidase (MAO), and dexamethasone suppression test (DST). REM latency averaged 58.66 (SD 14.39); platelet MAO averaged 21.74 (SD 10.33); and lithium ratio was 0.357 (SD 0.139) in the BPD patients. All of those values were significantly abnormal. Many patients had abnormalities on three or four measures. These patients in general had multiple Axis I diagnoses from the Diagnostic Interview Schedule (DIS), and these Axis I diagnoses tended to produce patient clusters. Patients with a DIS diagnosis of schizophrenia, mania, hypomania, or schizoaffective mania had elevated lithium, low MAO, and normal EEG sleep, while those patients with coexisting major depression tended to have short rapid eye movement (REM) latency, high REM density, and normal MAO and lithium ratio. Only two patients were nonsuppressors on the DST, confirming recent reports of normal DST results in personality disorders.

Intrarenal Doppler ultrasound studies in normal and acutely obstructed kidneys.

Renal ultrasound examinations and intrarenal arterial Doppler studies were performed on 48 patients with normal renal tracts and 20 patients presenting with acute renal colic resulting from ureteric calculus, 14 of whom had urographic evidence of renal obstruction. The mean resistance index (RI) of the Doppler waveforms obtained on the 14 obstructed kidneys (70.4 +/- 6.22) was significantly higher than the mean RI of the 96 normal kidneys (62.4 +/- 6.43). The mean difference between the RIs of the obstructed kidneys and their contralateral non-obstructed kidneys (8.37 +/- 4.43) was also significantly higher than the differences in RI seen between pairs of normal kidneys (2.70 +/- 1.71). Five out of 14 obstructed kidneys showed no pelvicalyceal dilatation and could not have been shown to be obstructed on conventional sonography. Four of these five had RI changes suggestive of obstruction and thus 13 of 14 obstructed kidneys would have been identified as obstructed by a combination of Doppler and conventional sonographic findings. 10 of the 14 obstructed kidneys were re-examined after passage of a urinary calculus and nine showed a reduction in the RI of the previously obstructed kidneys. The 10th subsequently required ureterolithotomy.

Periodontal regeneration in naturally occurring Class II furcation defects in beagle dogs after guided tissue regeneration with bioabsorbable barriers.

THE EFFICACY OF A BIOABSORBABLE polylactic acid based barrier was evaluated using naturally occurring buccal Class II furcation defects in beagle dogs. Sixteen furcation sites (8 control and 8 experimental) were treated in 6 adult animals. After full thickness flap reflection, exposed furcations and root surfaces were thoroughly root planed. In experimental sites a customized barrier was formed and fitted to cover the defect. Surgical flaps were replaced slightly coronal to the cemento-enamel junction. Animals were sacrificed at 6 months and specimens processed for histologic evaluation. Histologic and histometric analyses were done using 6 micrograms step serial sections in the buccal-lingual plane, corresponding to the buccal-lingual extent of the furcation. Results were: mean total defect experimental sites 1.92 mm; control sites 1.47 mm. Mean new cementum formation experimental sites 1.36 mm (71% of initial defect); control sites 0.25 mm (17% of initial defect). Mean new bone formation experimental sites 1.42 mm (74% of initial defect); control sites 0.20 mm (14% of initial defect). Mean junctional epithelium formation experimental sites 0.42 mm (22% of initial defect); control sites 1.21 mm (82% of initial defect). Statistical analysis demonstrated significant differences in all healing parameters favoring experimental (barrier-treated) sites. In this model, regeneration (new bone, cementum, and periodontal ligament) of 71% of the original defect in experimental sites and only 14% in control sites demonstrated a response that highly favored use of the barrier.

Anthropometry and bilirubin production.

Anthropometric measurements and total bilirubin formation (TBF) estimates were performed on infants born to normal and diabetic mothers. Although we do not exclude the theoretical possibility of a low-frequency occurrence of increased TBF in macrosomic infants of normal mothers, we can conclude that infants of mothers whose diabetes is well managed may have normal TBF.

Developmental biology of heme oxygenase.

The regulation of heme oxygenase activity in the developing neonate is essential to the control of bilirubin production as well as intracellular heme and hemoprotein metabolism. The coordinated activity of the microsomal enzymes, heme oxygenase and NADPH-cytochrome c (P450) reductase, and the cytosolic enzyme biliverdin reductase is responsible for the degradation of heme. The complete reaction sequence requires oxygen and NADPH, and produces bilirubin and carbon monoxide in equimolar amounts. Although heme oxygenase expresses a rather broad range of substrate affinities, the oxidative degradation of heme is exclusively alpha-specific. Heme oxygenase is found in several tissues, with significant activity levels in the liver, spleen, and erythropoeitic tissue. Heme oxygenase activity is inducible by heme and other metalloporphyrins, hormones, starvation, stress, toxins, and xenobiotics. Heme oxygenase induction is generally considered to be the result of an increased protein synthesis and gene transcription. This hypothesis is supported by recent studies of the heme oxygenase gene that identified inducer element binding sites responsive to metal administration, heat shock, and nutrient availability. In the developing fetus and neonate, hepatic heme oxygenase activity and mRNA levels are elevated above that of the adult. This suggests that the elevated heme catabolism observed in neonates may be associated with an increased transcription of the heme oxygenase gene. The apparent induction of hepatic heme oxygenase during the neonatal period is probably the result of tissue-specific and time-dependent transcriptional regulating factors including potentially hormones and heme. Several metalloporphyrins, such as the tin and zinc porphyrin complexes, inhibit heme oxygenase activity and thus have therapeutic potential for the treatment of neonatal jaundice. Recent studies suggest that the meso- and bis-glycol derivatives of these metalloporphyrins may be more potent inhibitors of heme oxygenase activity in vitro and in vivo than the protoporphyrin structures. As structural analogues of heme, however, these compounds may also have other less desirable effects on the regulation of heme and hemoprotein metabolism, particularly in the developing neonate.

External and middle ear effects on infant hearing screening test results.

This study investigated the relationship between external and middle ear factors and hearing screening results by automated auditory brain stem response (ABR) and transient-evoked otoacoustic emissions (EOAEs). The ears of 200 healthy newborns aged 5 to 48 hours underwent screening by ABR and EOAE, followed by otoscopic examination. The pass rates for ABR and EOAE were 91% and 58.5%, respectively. On otoscopic examination, 28% (112/400) ears had occluding vernix obscuring the view of the tympanic membrane. Cleaning of vernix was successfully performed in all but 2 ears that had occluding vernix. Cleaning of vernix significantly increased the pass rates of all 400 ears for ABR and EOAE to 96% and 69%. Decreased tympanic membrane mobility was found in 22.7% (90/396) of ears that were evaluated otoscopically. Decreased tympanic membrane mobility had a significant effect on EOAE screening; only 33.4% of ears passed EOAE testing. Decreased tympanic membrane mobility did not significantly affect pass rates for ABR screening; 95% of these ears passed the automated ABR screen. Implications for newborn hearing screening are discussed.

Spatial and temporal bacterial quality of a lowland agricultural stream in northeast Scotland.

Stream water concentrations of the faecal coliform group of sanitary indicator bacteria were monitored in the Newmills Burn, a small agriculturally intensive tributary of the River Don in Aberdeenshire. The results indicated that during its passage through the catchment, stream water became significantly contaminated with faecal coliform bacteria from the main agricultural land use inputs of livestock grazing and organic waste applications. Point sources of faecal coliform bacteria in terms of farmyard runoff, however, also appeared to be important in contributing to the spatial pattern of contamination. Significant temporal variation was observed in response to the hydrological behaviour of the catchment. Higher flows and more frequent washout of stored bacteria in winter and spring months led to lower faecal coliform concentrations than were detected during the summer. Maximum faecal coliform concentrations were measured during rainfall events and the varying responses associated with these helped to identify the importance of different sources of bacteria in the catchment and the mechanisms transferring them. The overall impact on the water quality of the Newmills Burn was considered as having a potentially serious threat to the health of downstream recreational users of the River Don, as well as to the large proportion of the local population who rely on private water supplies.

Prevalence of carpal tunnel syndrome and median mononeuropathy among dentists.

BACKGROUND: The authors undertook a study to determine the prevalence in dentists of abnormal sensory nerve conduction and/or symptoms of carpal tunnel syndrome, or CTS, the most common nerve entrapment syndrome. METHODS: In a cross-sectional study, dentists (n = 1,079) were screened during the American Dental Association's Annual Health Screening Program in 1997 and 1998 by means of standard electrodiagnostic measures in the dominant hand and a self-reported symptom questionnaire. The authors diagnosed a median mononeuropathy from a 0.5- or 0.8-millisecond, or ms, prolongation of the median sensory-evoked peak latency compared to the ulnar latency. They diagnosed CTS if the subject also had accompanying symptoms of numbness, tingling or pain. RESULTS: Thirteen percent of screened dentists were diagnosed with a median mononeuropathy (using a 0.5-ms prolongation as the criterion), but only 32 percent of these had symptoms consistent with CTS (4.8 percent overall). When the 0.8-ms prolongation was used as the electrodiagnostic criterion, only 2.9 percent (overall) were diagnosed with CTS. People with diabetes, rheumatoid arthritis and obesity were more likely to have a median mononeuropathy. CONCLUSIONS: The prevalence of symptoms consistent with CTS in the dominant hand among dentists was higher than the prevalence in the general population. However, when electrodiagnostic confirmation is added, the prevalence of CTS was nearly the same as that among the general population. CLINICAL IMPLICATIONS: Early recognition of CTS can lead to more effective management. Education regarding ergonomic risk factors can be an effective preventive measure.

Periodontal healing after guided tissue regeneration with Atrisorb barriers in beagle dogs.

Periodontal healing after use of Atrisorb barrier material (polylactic acid) for guided tissue regeneration was studied in the premolar and molar teeth of six beagle dogs. Defects studied were surgically induced or were caused by naturally occurring periodontitis. Barriers fragmented and became displaced in 2 to 5 weeks after application. Granulation tissue was sometimes present between the barrier and root surface at 10 days to 4 weeks. Several sites were surgically reentered at 4 months, and new bone covered 60% to 100% of the formerly exposed furcations and root surfaces. Sites obtained for histologic evaluation 9 to 12 months after the baseline surgery showed new connective tissue attachment, cementum, and alveolar bone. Histomorphometric analyses quantitated these tissue changes, and new connective tissue attachment covered 72% of surgically exposed root surfaces and 77% of periodontitis-exposed root surfaces. It was concluded that new periodontal supporting tissues became reconstituted on root and furcation surfaces after use of the Atrisorb barrier material for GTR.

A negative herniogram does not exclude the presence of a hernia.

A retrospective review of 63 consecutive herniograms over a 3-year period was performed to assess the reliability in diagnosis of occult hernias. In all, 26 hernias were diagnosed in 23 patients, of which 13 were confirmed at operation. However, there were three false-positive results. Of the 38 negative herniograms, four proceeded to surgery with three positive hernia findings. We therefore found false-positive and false-negative rates of 18.7% and 7.9%, respectively. All of the false-positive results were in patients with a history of pain as the presenting complaint, while all of the patients with false-negative results had presented with a history of both pain and jump but no clinically detectable hernia. Our experience of this investigation is not as encouraging as others have reported.

Medication nonadherence--Part I: The health and humanistic consequences.

Nonadherence is a significant medical problem in the United States, leading to excessive morbidity, mortality, and medical costs. In this first installment of a two-part article, the authors review the literature and discuss the effects of the problem, with particular reference to patients with congestive heart failure.

Medication nonadherence: Part II--A pilot study in patients with congestive heart failure.

Nonadherence is a significant medical problem in the United States, leading to excessive morbidity, mortality, and medical costs. In the conclusion to this two-part article, the authors describe a pilot study involving 311 patients taking an angiotensin-converting enzyme inhibitor that evaluates the principal factors for nonadherence to pharmaceutical therapy in patients with congestive heart failure.