ABSTRACT
BACKGROUND: Response to biologics in psoriasis varies in real-world settings. Serum biomarkers could aid biologic selection and dose modifications to improve patient outcomes while encouraging cost-effective care. OBJECTIVES: To explore the exposure-response relationship for guselkumab (GUS), to define a GUS concentration target for optimal response and to evaluate the potential of serum protein levels as predictive biomarker candidates. METHODS: This is a prospective, multicentric, cohort study in psoriasis patients treated with GUS. Serum GUS trough concentrations (TCs) collected at multiple timepoints were measured using an in-house immunoassay. Next, proximity extension assay technology (Target 96 Inflammation Panel Olink®) was used to measure serum protein levels in a subcohort including 38 GUS patients (week 0 and week 4), six psoriasis patients naive for systemic treatment and four healthy controls. RESULTS: Seventy-five patients participated and 400 samples were collected. Guselkumab TCs and clinical response were correlated at week 4, week 12 and in steady-state (≥20 weeks). Optimal responders (Psoriasis Area and Severity Index [PASI] ≤ 2) had significantly higher TCs than suboptimal responders from week 4 onwards in treatment. An optimal steady-state TC of 1.6 µg/mL was defined. Although TC and absolute PASI were lower and worse, respectively, in patients weighing ≥90 kg, clinical outcomes referred to desirable to excellent PASI ranges. Therefore, we do not recommend systematically higher GUS doses in obese patients. We could not reveal early differentially expressed proteins to distinguish future optimal from suboptimal responders. CONCLUSIONS: We demonstrated an exposure-response relationship for GUS and an optimal steady-state TC of 1.6 µg/mL in real-world psoriasis patients. Hereby, we deliver more evidence that therapeutic drug monitoring poses a promising strategy in optimizing GUS treatment. No biomarker candidates were identified through serum proteomics. We propose protein screening should be repeated in larger cohorts to continue the quest for predictive biomarkers.
Subject(s)
Antibodies, Monoclonal, Humanized , Biomarkers , Proteomics , Psoriasis , Humans , Psoriasis/drug therapy , Psoriasis/blood , Female , Male , Proteomics/methods , Middle Aged , Biomarkers/blood , Prospective Studies , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Aged , Severity of Illness Index , Dose-Response Relationship, DrugABSTRACT
Treating atopic dermatitis (AD) in pregnant or breastfeeding women, and in women and men with AD aspiring to be parents is difficult and characterized by uncertainty, as evidence to inform decision-making on systemic anti-inflammatory treatment is limited. This project mapped consensus across dermatologists, obstetricians and patients in Northwestern Europe to build practical advice for managing AD with systemic anti-inflammatory treatment in men and women of reproductive age. Twenty-one individuals (sixteen dermatologists, two obstetricians and three patients) participated in a two-round Delphi process. Full consensus was reached on 32 statements, partial consensus on four statements and no consensus on four statements. Cyclosporine A was the first-choice long-term systemic AD treatment for women preconception, during pregnancy and when breastfeeding, with short-course prednisolone for flare management. No consensus was reached on second-choice systemics preconception or during pregnancy, although during breastfeeding dupilumab and azathioprine were deemed suitable. It may be appropriate to discuss continuing an existing systemic AD medication with a woman if it provides good disease control and its benefits in pregnancy outweigh its risks. Janus kinase (JAK) inhibitors, methotrexate and mycophenolate mofetil should be avoided by women during preconception, pregnancy and breastfeeding, with medication-specific washout periods advised. For men preconception: cyclosporine A, azathioprine, dupilumab and corticosteroids are appropriate; a 3-month washout prior to conception is desirable for methotrexate and mycophenolate mofetil; there was no consensus on JAK inhibitors. Patient and clinician education on appropriate (and inappropriate) AD treatments for use in pregnancy is vital. A shared-care framework for interdisciplinary management of AD patients is advocated and outlined. This consensus provides interdisciplinary clinical guidance to clinicians who care for patients with AD before, during and after pregnancy. While systemic AD medications are used uncommonly in this patient group, considerations in this article may help patients with severe refractory AD.
Subject(s)
Cyclosporine , Dermatitis, Atopic , Pregnancy , Male , Humans , Female , Cyclosporine/therapeutic use , Methotrexate/therapeutic use , Breast Feeding , Dermatitis, Atopic/drug therapy , Azathioprine/therapeutic use , Mycophenolic Acid/therapeutic use , Consensus , Anti-Inflammatory Agents/therapeutic useABSTRACT
Adenocarcinomas of the ampulla of Vater represent only 0.2% of all gastrointestinal cancers. Due to the low incidence no large clinical trials evaluating efficacy of treatments are available. Adjuvant therapy is often administered in patients with stage IB or higher. Oxaliplatin is considered as an effective and well tolerated therapeutic option. Adverse events associated with this therapy include cardio-, neuro-, nephrotoxicity and myelosuppression. Previously granulomatous pulmonary and liver manifestations have been described in oxaliplatin-based chemotherapy. In this report peritoneal manifestation of granulomatous disease associated with oxaliplatin is described for the first time. Sarcoidlike reactions may be misinterpreted as tumour progression or metastatic disease, and may consequently result in over-treatment.
Subject(s)
Adenocarcinoma , Ampulla of Vater , Common Bile Duct Neoplasms , Peritoneal Diseases , Humans , Oxaliplatin/adverse effects , Ampulla of Vater/pathology , Adenocarcinoma/pathology , Common Bile Duct Neoplasms/drug therapy , Common Bile Duct Neoplasms/etiology , Common Bile Duct Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
BACKGROUND: Chronic cutaneous pain has a substantial negative impact on quality of life (QoL). Dermo-cosmetics can support therapies for treatment of chronic skin diseases, providing symptomatic relief from chronic cutaneous pain and improved QoL. OBJECTIVES: To assess the global tolerance and efficacy of a dermo-cosmetic spray containing Rhealba® Oat Plantlet and Uncaria tomentosa extracts in reducing cutaneous pain when used as a monotherapy or in association with drug or dermo-cosmetic treatments in patients with an underlying skin pathology. METHODS: Patients aged ≥1 month with a cutaneous pain level ≥3 and an underlying skin pathology were provided with the spray to use up to six times daily for 6-8 weeks. Immediate effect on cutaneous pain and patient satisfaction were assessed after the first application. Global efficacy and tolerance, reduction in symptoms, improvement in QoL, pain reduction and patient overall satisfaction were assessed after 6-8 weeks. RESULTS: Immediately after the first application, significant reductions in cutaneous pain were observed across all age groups (P < 0.0001), with 94% of patients reporting a reduction in pain. After 6-8 weeks, global tolerance was rated 'very good' or 'good' for 97% of patients, and the spray was efficacious in 95% of patients. Patient satisfaction with the efficacy of the spray was 95%. QoL scores improved in 86% and 94% of patients aged ≥12 and <12 years, respectively. Findings were similar across underlying pathology and therapy types (monotherapy or in association with another therapy). CONCLUSIONS: The spray was well-tolerated and efficacious in providing symptom relief in patients with mild-to-moderate cutaneous pain, irrespective of the underlying pathology or therapy type.
Subject(s)
Cat's Claw , Cosmetics , Avena , Child , Humans , Infant, Newborn , Pain/drug therapy , Plant Extracts/therapeutic use , Quality of LifeABSTRACT
BACKGROUND: Chronic spontaneous urticaria (CSU) is characterized by the repeated occurrence of persistent hives and/or angioedema for ≥6 weeks, without specific external stimuli. H1 -antihistamines have long been the standard of care of CSU, but many patients remain uncontrolled even at 4× the approved dose. Add-on therapy with omalizumab has proven effective in clinical trials, but little is known about omalizumab treatment in Belgium. OBJECTIVE: To collect real-world clinical data on omalizumab treatment in adults with CSU in Belgium. METHODS: This was an observational, retrospective chart review of adults with CSU, who initiated omalizumab treatment between August 2014 and December 2016 (maximum 28 months follow-up). RESULTS: In total, 235 patients were included (median time from symptom onset to diagnosis, 5.4 months; median time from diagnosis to commencing omalizumab, 6.7 months). Treatments used before/after commencing omalizumab did not always adhere to guidelines; many patients (26.4%/11.1%) received first-generation H1 -antihistamines, while 20.4% used omalizumab monotherapy after initiating treatment. The mean interval between omalizumab administrations was 4.8 (SD 1.7) weeks; 67.8% of patients had ≥1 interval prolongation and/or shortening. Mean baseline 7-day Urticaria Activity Score (UAS7) was 32.0 (SD 6.05); this improved to 12.6 (SD 11.2) after 1 month of omalizumab. About 67.2% of patients reached UAS7 ≤ 6 (well controlled) during the study. A total of 87 patients stopped omalizumab and never restarted before the end of the observation period; the most prevalent reason was remission of symptoms (49.4% of patients), followed by lack of effect (12.6%), lost to follow-up (6.9%) and adverse events (3.4%). Headache was the most common adverse event (n = 8/82). No anaphylaxis was reported. CONCLUSIONS: This study revealed that patients initiated on omalizumab in Belgium had severe CSU at baseline, and showed substantial improvements after 1 month of treatment. Greater adherence to the prescription of guideline-recommended medications is needed for the treatment of CSU.
Subject(s)
Anti-Allergic Agents/therapeutic use , Chronic Urticaria/drug therapy , Omalizumab/therapeutic use , Adult , Belgium , Drug Administration Schedule , Female , Histamine Antagonists/therapeutic use , Humans , Male , Medication Adherence , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
Leber inherited optic neuropathy (LHON) is characterized by subacute bilateral loss of central vision due to dysfunction and loss of retinal ganglion cells (RGCs). Comprehensive visual electrophysiological investigations (including pattern reversal visual evoked potentials, pattern electroretinography and the photopic negative response) performed on 13 patients with acute and chronic LHON indicate early impairment of RGC cell body function and severe axonal dysfunction. Temporal, spatial and chromatic psychophysical tests performed on 7 patients with acute LHON and 4 patients with chronic LHON suggest severe involvement or loss of the midget, parasol and bistratified RGCs associated with all three principal visual pathways.
Subject(s)
Optic Atrophy, Hereditary, Leber/pathology , Retinal Ganglion Cells/pathology , Visual Pathways/pathology , Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Prospective Studies , Young AdultABSTRACT
A 74-year-old woman with known euthyroid multinodular retrosternal goiter necessitated an urgent intubation at home, due to acute respiratory distress evoked by tracheal compression. Extubation after a few days failed, and she underwent an urgent total thyroidectomy. During postoperative extubation the patient developed suddenly unilateral facial flushing and sweating at the left side, without ptosis of the left levator palpebrae superioris. These symptoms persisted during the next 24 hours. The skin at the right side of the face remained uninvolved. In the early postoperative period this appearance recurred at moments of emotions, exercise or heat. Beside this, the patient had a normal recovery. Six weeks later this reaction couldn't be provoked anymore. 'Harlequin' syndrome (unilateral facial flushing and sweating) is caused by a lesion of the controlateral sympathetic chain at the levels T2 and T3. It is unknown if the sweating and vasodilation at the "healthy" side is normal or if it is a reaction of hyperactivity.
Subject(s)
Flushing/etiology , Goiter, Nodular/surgery , Postoperative Complications , Sweating , Thyroidectomy , Aged , Airway Extubation , Airway Obstruction/etiology , Airway Obstruction/therapy , Emotions , Exercise , Female , Goiter, Nodular/complications , Hot Temperature , Humans , Intubation, Gastrointestinal , SyndromeABSTRACT
PURPOSE: The purpose of this study is to describe the phenotype of a family with de novo mutation in the GUCY2D. MATERIALS AND METHODS: Five subjects, including two monozygotic twins, underwent ophthalmic clinical examination while some had autofluorescence imaging (AF) and optical coherence tomography (OCT). Symptomatic individuals underwent electrophysiological testing. The youngest subject (21 years) was also evaluated psychophysically. DNA obtained from the individuals was screened for mutations in GUCY2D. Microsatellite markers were used to determine the haplotype of 17p surrounding the GUCY2D gene. RESULTS: The youngest subject had 6/18 visual acuity, an annulus of hyper-autofluorescence in the perifoveal region, and a subfoveal absence of outer segments on OCT. In the older individuals, severe thinning of inner retina and a patchy loss of photoreceptors and retinal pigment epithelium were observed in the perifoveal region. All three showed generalised cone system dysfunction with preserved rod function on electrophysiology. Psychophysical evaluation was consistent with poor cone function. Screening of the GUCY2D gene revealed the mutation p.R838H in all the affected individuals and was absent in the asymptomatic patients. Haplotyping showed that the mutation originated from the unaffected mother. CONCLUSIONS: Autosomal dominant cone dystrophy due to GUCY2D can occur without a history in the antecedents due to a de novo mutation. This is important to consider in any simplex case with a similar phenotype. The phenotype description of this disorder is expanded with detailed description of the OCT findings. This paper describes the concordance of the phenotypic findings in the monozygotic twins.
Subject(s)
Guanylate Cyclase/genetics , Mutation , Receptors, Cell Surface/genetics , Retinal Cone Photoreceptor Cells/pathology , Retinal Degeneration , Adult , Aged , Electroretinography , Female , Fluorescein Angiography , Humans , Male , Middle Aged , Phenotype , Photoreceptor Cells, Vertebrate , Psychophysics , Retinal Degeneration/genetics , Retinal Degeneration/pathology , Retinal Degeneration/physiopathology , Tomography, Optical Coherence , Visual Acuity , Young AdultABSTRACT
BACKGROUND: The objective of this study was to study the long-term outcome of adjustable gastric banding in the treatment of morbid obesity. In Europe, the preference for gastric band has declined in favor of Roux-Y-gastric bypass. METHODS: This is a follow-up of a prospective study on a large cohort of patients after laparoscopic gastric banding (LAGB) for morbid obesity. RESULTS: Complete data were collected on 656 patients (88%) from a cohort of 745 patients. After a median follow-up of 95 months (range 60-155), the mean BMI dropped from 41.0 ± 7.3 to 33.2 ± 7.1 kg/m², with a 46.2 ± 36.5% excess weight loss (EWL). A more than 50% EWL was achieved in 44% of patients. The band was still in place in 77.1% of patients; conversion to gastric bypass after band removal was carried out in 98 (14.9%) patients, while a simple removal was done in only 52 (7.9%) patients. Band removal was more likely in women and patients with a higher BMI. CONCLUSIONS: After LAGB, band removal was necessary for complications or insufficient weight loss in 24% of patients. Nearly half of the patients achieved a more than 50% EWL, but in 88%, a more than 10% EWL was observed. LAGB can achieve an acceptable weight loss in some patients, but the failure in one out of four patients does not allow proposing it as a first-line option for the treatment of obesity.
Subject(s)
Gastroplasty/methods , Adult , Esophagitis/epidemiology , Female , Humans , Laparoscopy , Male , Middle Aged , Obesity, Morbid/surgery , Postoperative Complications/epidemiology , Prospective Studies , Treatment Outcome , Weight LossABSTRACT
We investigated the relationship between clinical, laboratory and genetic markers and outcome measures in 159 patients with recent onset of inflammatory arthritis (IA). The majority of patients were managed in community-based rheumatology practice. Median duration of arthritis at baseline was 3 months with median follow-up of 4.0 years (range 0-10). Markers of disease activity and 1987 ACR criteria for rheumatoid arthritis (RA) were estimated every 6 months for the first 2 years and annually thereafter. Presence of shared epitopes (SE) was established by PCR-based method. Main outcome variables were attainment of remission and presence of erosions on X-rays of hands and feet at 3 years. Remission was seen in 34.3% of patients and was independently related to age 60 and older (odds ratio (OR) 3.2; 95% confidence interval (CI), 1.2-8.7) and inversely to the presence of rheumatoid factor (RF) (OR 8.3; 95% CI, 3.2-21.3 for persistent arthritis). Patients with two SE were likely to have persistent arthritis (P=0.006), but this was not significant when corrected for RF. Independent predictors for erosions at 3 years were RF (OR 7.5; 95% CI, 1.9-29.5) and area under the curve for number of swollen joints (OR 1.08; 95% CI, 1.02-1.16). SE status was not predictive of erosions at 3 years (OR 1.6; 95% CI, 0.7-3.7). In univariate analysis, patients possessing DERAA motif on DRB1 were less likely to have erosive disease than without this motif at 4 years (OR 0.21; 95% CI, 0.0-0.9, P=0.037) but this finding was partly explained by adjusting for RF (adjusted OR 0.24; 95% CI 0.04-1.37). In this study of recent onset IA, active disease and RF were associated with poor outcome. Whilst SE did not predict erosive disease, patients with DERAA motif may be protected against erosions whilst the presence of two SE alleles suggests persistence of arthritis.
Subject(s)
Arthritis/genetics , Arthritis/immunology , Arthritis/pathology , Arthritis/therapy , Age of Onset , Arthritis/diagnostic imaging , Arthritis/physiopathology , Cohort Studies , Epitopes/blood , Female , Follow-Up Studies , Foot/diagnostic imaging , Foot/pathology , Genetic Markers , HLA-DR Antigens/blood , HLA-DR Antigens/immunology , Hand/diagnostic imaging , Hand/pathology , Humans , Male , Middle Aged , Prospective Studies , Radiography , Remission Induction , Rheumatoid Factor/blood , Risk Factors , Severity of Illness Index , Time FactorsABSTRACT
BACKGROUND: Treatment of bullous pemphigoid (BP) with systemic immunosuppressive agents, in particular with systemic corticosteroids, has many long-term side-effects. A dozen reports were published regarding the efficacy of topical corticosteroids in the treatment of bullous pemphigoid. OBJECTIVE: To evaluate the efficacy of potent class I topical corticosteroids in relation to the affected body surface area (BSA) in patients with bullous pemphigoid and to review the literature. METHODS: An open prospective trial with 10 patients with BP with measurement of the affected BSA. Treatment protocol consisted of three steps: potent class I topical corticosteroid treatment, systemic tetracyclines and systemic corticosteroids. Follow-up period was between 24 and 72 months. RESULTS: Our study suggests a correlation between the success rate of topical corticosteroid treatment and the body surface area initially affected: all patients with an affected BSA of less than 20% healed with topical treatment only. The patients with more than 40% affected BSA needed systemic treatment with steroids. CONCLUSION: Topical class I corticosteroids seem to be effective in healing lesions of BP, especially if less than 20% of the BSA is affected. This study comprises only 10 patients, making further studies necessary to draw definite conclusions.
Subject(s)
Adrenal Cortex Hormones/administration & dosage , Pemphigoid, Bullous/drug therapy , Administration, Topical , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pemphigoid, Bullous/pathologyABSTRACT
AIMS: It has been suggested that WT-1 is helpful in distinguishing a primary ovarian serous carcinoma (OSC) from a primary uterine serous carcinoma (USC). Since both neoplasms are often disseminated at diagnosis and since USC often spreads to the ovary and vice versa, it may be difficult to ascertain the primary site. This is important, since adjuvant therapies for OSC and USC may differ. WT-1 staining patterns also differ between OSC and ovarian endometrioid carcinoma and so it is possible that WT-1 may assist in the distinction of these two neoplasms, which is sometimes problematic, especially with poorly differentiated tumours. This study aims to document the value of WT-1 in these settings. Cases of ovarian borderline serous tumour, primary peritoneal serous carcinoma (PPSC) and uterine endometrioid carcinoma were also studied. METHODS AND RESULTS: Cases of OSC (n = 38), USC (n = 25) (in five of these cases there was also a component of endometrioid adenocarcinoma), ovarian endometrioid carcinoma (n = 13), uterine endometrioid carcinoma (n = 7), ovarian borderline serous tumour (n = 16) and PPSC (n = 6) were stained with WT-1. Cases were scored on a scale of 0-3, depending on the percentage of positive cells. The intensity of staining was scored as weak, moderate or strong. There was positive nuclear staining of 36 of 38 (94.7%) OSC with WT-1. In most OSC (68.4%), >50% of cells stained positively and staining was usually strong. Five of 25 (20%) USC were positive with only two cases exhibiting staining of >50% of cells. All primary ovarian and uterine endometrioid carcinomas were negative. All PPSC were positive, usually with diffuse strong immunoreactivity. Fourteen of 16 borderline serous tumours exhibited positivity with WT-1. CONCLUSIONS: WT-1 is useful in distinguishing OSC (characteristically diffuse strong nuclear positivity) from USC (characteristically negative). However, rarely OSC is negative and occasional cases of USC are positive. WT-1 may also be helpful in differentiating poorly differentiated OSC from poorly differentiated ovarian endometrioid carcinoma.
Subject(s)
Biomarkers, Tumor/analysis , Cystadenocarcinoma, Serous/pathology , Ovarian Neoplasms/pathology , Uterine Neoplasms/pathology , WT1 Proteins/metabolism , Carcinoma, Endometrioid/metabolism , Carcinoma, Endometrioid/pathology , Cystadenocarcinoma, Serous/metabolism , Female , Humans , Immunohistochemistry , Ovarian Neoplasms/metabolism , Uterine Neoplasms/metabolismABSTRACT
BACKGROUND: Kawasaki's disease may have numerous atypical forms and these must be recognized in order to avoid delay of treatment. We report a case of psoriasis, first pustular and then guttate, occurring during Kawasaki's disease, and discuss a common pathophysiological mechanism. CASE-REPORT: A 3 year-old boy was seen for a febrile exanthema suggestive of Kawasaki disease (bilateral conjunctivitis, red and fissured lips, palmoplantar erythema, scarlet fever-like rash and perineal desquamation) associated with pustular lesions. A biopsy specimen of a pustular area showed histological features consistent with the diagnosis of pustular psoriasis. No coronary abnormality was found. The child was treated with intravenous immunoglobulins (2 g/kg) and oral aspirin (60 mg/kg/d). All the symptoms disappeared and immediate follow-up was marked by the appearance of guttate psoriasis. DISCUSSION: Onset of psoriatic lesions during Kawasaki disease has been reported in 12 cases, either in acute phase or in immediate follow-up. Coronary complications have been found in 4 of 5 cases with acute psoriasis, suggesting a severe prognosis for this association. The hypothesis of a common pathophysiological mechanism is discussed with the intervention of a bacterial toxin acting as a superantigen and resulting in an strong activation of T-cells that leads to keratinocyte activation. The psoriatic lesions could hence be considered as a form of Köbner's phenomenon.
Subject(s)
Exanthema/etiology , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/pathology , Psoriasis/etiology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/therapeutic use , Buttocks/pathology , Child, Preschool , Exanthema/pathology , Humans , Immunoglobulins, Intravenous/therapeutic use , Male , Psoriasis/pathology , Treatment OutcomeABSTRACT
OBJECTIVE: To assess the intrarater and interrater reliability among rheumatologists of a standardised protocol for measurement of shoulder movements using a gravity inclinometer. METHODS: After instruction, six rheumatologists independently assessed eight movements of the shoulder, including total and glenohumeral flexion, total and glenohumeral abduction, external rotation in neutral and in abduction, internal rotation in abduction and hand behind back, in random order in six patients with shoulder pain and stiffness according to a 6x6 Latin square design using a standardised protocol. These assessments were then repeated. Analysis of variance was used to partition total variability into components of variance in order to calculate intraclass correlation coefficients (ICCs). RESULTS: The intrarater and interrater reliability of different shoulder movements varied widely. The movement of hand behind back and total shoulder flexion yielded the highest ICC scores for both intrarater reliability (0.91 and 0.83, respectively) and interrater reliability (0.80 and 0.72, respectively). Low ICC scores were found for the movements of glenohumeral abduction, external rotation in abduction, and internal rotation in abduction (intrarater ICCs 0.35, 0.43, and 0.32, respectively), and external rotation in neutral, external rotation in abduction, and internal rotation in abduction (interrater ICCs 0.29, 0.11, and 0.06, respectively). CONCLUSIONS: The measurement of shoulder movements using a standardised protocol by rheumatologists produced variable intrarater and interrater reliability. Reasonable reliability was obtained only for the movement of hand behind back and total shoulder flexion.
Subject(s)
Clinical Competence/standards , Range of Motion, Articular/physiology , Rheumatology/standards , Shoulder Joint/physiology , Aged , Aged, 80 and over , Analysis of Variance , Humans , Male , Middle Aged , Observer Variation , Physical Examination/standards , Reproducibility of Results , Shoulder Pain/physiopathologyABSTRACT
The spectral sensitivities of middle- (M-) and long- (L-) wavelength-sensitive cones have been measured in dichromats of known genotype: M-cone sensitivities in nine protanopes, and L-cone sensitivities in 20 deuteranopes. We have used these dichromat cone spectral sensitivities, along with new luminous efficiency determinations, and existing spectral sensitivity and color matching data from normal trichromats, to derive estimates of the human M- and L-cone spectral sensitivities for 2 and 10 degrees dia. central targets, and an estimate of the photopic luminosity function [V(lambda)] for 2 degrees dia. targets, which we refer to as V(2)*(lambda). These new estimates are consistent with dichromatic and trichromatic spectral sensitivities and color matches.
Subject(s)
Color Perception/genetics , Color Vision Defects/genetics , Retinal Cone Photoreceptor Cells/physiopathology , Adult , Algorithms , Case-Control Studies , Color Vision Defects/physiopathology , Genotype , Humans , Photometry , Retinal Pigments/genetics , Retinal Pigments/physiology , X Chromosome/geneticsABSTRACT
Tritanopic color matches (i.e. matches that depend on the middle- (M) and long- (L), but not short- (S) wavelength-sensitive cones) were made between two half-fields: one illuminated by either a 405 or a 436 nm Hg spectral line; the other by a light of variable wavelength and radiance. Our purpose was to test between rival M- and L-cone spectral sensitivities, which should predict the tritanopic matches. The observers were tritanopes, in whom functioning S-cones are lacking, or normal trichromats, in whom artificial tritanopia was induced by a strong, violet adapting field. The wavelengths found to match the 405 and 436 nm lights agreed poorly with those predicted by the cone spectral sensitivities of Smith and Pokorny (1975) [Vision Research, 15, 161], while the 405 nm matching wavelength agreed poorly with that predicted by Stockman, MacLeod and Johnson (1993) [Journal of the Optical Society of America, A10, 2491]. Both matching wavelengths agreed well, however, with the predictions of the Stockman and Sharpe (2000) [Vision Research] M- and L-cone spectral sensitivities, which lie within the range of measured matches.
Subject(s)
Color Perception/physiology , Color Vision Defects/physiopathology , Retinal Cone Photoreceptor Cells/physiology , Color Vision Defects/genetics , Female , Genotype , Humans , Male , Retinal Pigments/physiologyABSTRACT
Bullous pyoderma gangrenosum is an atypical, more superficial variety of the classical pyoderma and is often associated with myeloproliferative disorders. We present the case of a patient who presented initially with subcutaneous nodules and who developed bullous lesions afterwards. Histological evaluation showed the presence of neutrophilic infiltrates in both lesions. A few months after the diagnosis of bullous pyoderma gangrenosum, an underlying leukemia was revealed. Our case illustrates the importance of regular blood and bone marrow examinations in patients with atypical bullous pyoderma gangrenosum, resulting in a rapid diagnosis of the underlying disease.
Subject(s)
Leukemia, Myeloid, Acute/complications , Pyoderma Gangrenosum/complications , Female , Humans , Leukemia, Myeloid, Acute/pathology , Middle Aged , Pyoderma Gangrenosum/pathology , Skin/pathologyABSTRACT
Anatomical and physiological studies of the mammalian retina have revealed two primary pathways available for the transmission of rod signals to the ganglion cells: one via ON rod bipolars, amacrine II cells, and ON and OFF cone bipolars, which is exquisitely designed for the transmission of single-photon absorption events; and a second via rod-cone gap junctions, and ON and OFF cone bipolars, which is designed for the transmission of multiple photon-absorption events at higher light levels. Psychophysical and electroretinographic (ERG) studies in normal observers and in two rare types of observer, who are devoid of either rod or cone function, support an analogous duality in the human visual system, the clearest signature of which is a loss of flicker visibility and ERG amplitude at frequencies near 15 Hz that results from destructive interference between sensitive 'slow' and insensitive 'fast' rod signals. The slow rod signal is most probably derived from the ON rod bipolar pathway and the fast signal from the rod-cone gap junction and cone pathways. Evidence has emerged recently for a third, insensitive rod pathway between rods and OFF cone bipolars, but it has so far only been observed clearly in rodents.
Subject(s)
Retinal Rod Photoreceptor Cells/physiology , Vision, Ocular/physiology , Visual Pathways/physiology , Electrophysiology , Humans , Psychophysics/methodsABSTRACT
We used two methods to estimate short-wave (S) cone spectral sensitivity. Firstly, we measured S-cone thresholds centrally and peripherally in five trichromats, and in three blue-cone monochromats, who lack functioning middle-wave (M) and long-wave (L) cones. Secondly, we analyzed standard color-matching data. Both methods yielded equivalent results, on the basis of which we propose new S-cone spectral sensitivity functions. At short and middle-wavelengths, our measurements are consistent with the color matching data of Stiles and Burch (1955, Optica Acta, 2, 168-181; 1959, Optica Acta, 6, 1-26), and other psychophysically measured functions, such as pi 3 (Stiles, 1953, Coloquio sobre problemas opticos de la vision, 1, 65-103). At longer wavelengths, S-cone sensitivity has previously been over-estimated.