Women of the West

"It is quiet disappointing to find among the ommisions names of sufficient importance have been included in…Also out of eighteen women of Washington mentioned in Mrs.Elmendorf's article on that subject, ten fail to be included…

Octahydrocyclopenta[c]pyridine Scaffold – Enantioselective Synthesis and Indole Annulation

An optically active hexahydrocyclopenta[c]pyridine derivative with quaternary stereocenter was prepared as a new heterocyclic scaffold. Key reaction was the Pd‐catalyzed asymmetric allylic alkylation of a piperidine‐based β‐oxoester, which proceeded in very good yield with high level of enantioselectivity (90 %, 95 % ee). The α‐allyl moiety was transformed into a 1,4‐diketone by Pd‐catalyzed Wacker oxidation with molecular oxygen (89 %). This intermediate was cyclized in an intramolecular aldol reaction furnishing the cyclopentenone motif (86 %). Hydrogenation of the C–C double bond gave the cis‐annulated octahydrocyclopenta[c]pyridine (86 %), which was submitted to Fischer indolization (85 %). Although two regioisomers could be expected, only the angular constitution was observed. Relative and absolute configurations were established by X‐ray crystallography of a para‐iodo benzamide derivative. The utility of the title compound as scaffold is further highlighted by a number of synthetically useful transformations, for instance formation of carboxamides, sulfonamides, ureas and reductive aminations with aldehydes

Hand eczema:interventions & contact allergies

Handeczeem is een veelvoorkomende huidaandoening met een prevalentie tot 10%. De behandeling van handeczeem is echter meer gebaseerd op ervaring dan op wetenschappelijk bewijs. Dit proefschrift bevat een Cochrane review die de verschillende behandelopties voor handeczeem bespreekt. Hormoonzalven zijn de meest voorkomende behandeloptie. Alitretinoïne is de best onderzochte optie en zeer geschikt voor patiënten met hyperkeratotisch handeczeem. Echter, de verschillende studies waren te divers om een behandeloptie aan te bevelen ten opzichte van de andere. Dit proefschrift bevat ook een studie over ciclosporine in de dagelijkse praktijk, waar met behulp van drug survival naar de behandeling is gekeken. Ciclosporine werd voor verscheidene maanden gebruikt en was in het bijzonder geschikt voor patiënten met blaasje handeczeem. In het tweede deel van het proefschrift worden contactallergieën als oorzaak van handeczeem bestudeerd. Patiënten met blaasjes handeczeem hadden vaker een contact allergie, terwijl er minder contact allergieën werden gevonden bij patiënten met hyperkeratotisch handeczeem of vingertopeczeem. Daarnaast benadrukt de thesis het belang van blootstelling aan contactallergenen op het werk, wanneer er gedacht wordt aan een arbeidsgerelateerd eczeem. Ook werd ascaridole, een afbraakproduct van theeboomolie bestudeerd. Allergieonderzoek doen met een pure stof, zoals ascaridole, blijkt beter te zijn dan allergieonderzoek met een complex mengsel van stoffen zoals theeboomolie.Ten slotte wordt alle kennis die in het proefschrift verzameld is, gebundeld in een behandelalgoritme wat de arts in de dagelijkse praktijk handvaten biedt om handeczeempatiënten te behandelen.Hand eczema is a common condition with a prevalence up to 10%. Nowadays, the treatment of hand eczema is more experience-based than evidence-based. This thesis features a Cochrane review which includes all RCT on interventions for hand eczema. Topical corticosteroids are the mainstream treatment and oral alitretinoin is the most investigated option, which is especially beneficial for patients with hyperkeratotic hand eczema. However, the studies included in the Cochrane review were to divers to recommend one treatment over the other. A daily-life study featured in this thesis concluded that cyclosporine is a valuable treatment option for patients with recurrent vesicular hand eczema and cyclosporine can be used for several months. In the second part of the thesis we focus on allergic contact dermatis as cause of hand eczema. The relation between a contact allergy and different types of hand eczema was studied. Patients with recurrent vesicular hand eczema were more likely to have an allergy, while patients with hyperkeratotic hand eczema and pulpitis had less often contact allergies. Moreover, the thesis emphasizes the importance of investigation the work area and workplace products in case of an occupational related eczema. Besides, ascaridole (a degradation product of tea tree oil) is studied. In conclusion, patch testing distinct components, such as ascaridole, is preferred over patch testing complex mixtures, such as tea tree oil.Finally, we provide a treatment algorithm for patients with hand eczema which clinicians can use in daily practice

The Aristocratic West

"'The Aristocratic West' is a series of interpretive sketches of the West in general, including chapters on Salt Lake City, Oregon and Washington, New Mexico and Arizona, Reno, and San Francisco… Mrs. Gerould is an entertaining, but not altogether convincing writer. Her very extravagant praise of what she is fond of, and her equally severe criticism of what she is disinterested in do not indicate a deep knowledge of her subject, but rather the superficial gleanings of the traveler which she admits herself to be.

Bullous dermatitis artefacta

Bullous dermatitis artefacta is a psychodermatologic disorder in patients who mimic skin disease by inflicting themselves blisters. The diagnosis is often apparent at first visit. The diagnosis should never be immediately revealed to the patient. Instead a serious, yet limited, workup is advised, while developing a trustful patient-doctor relation. The strategy is to give the patient the impression you know it was self-inflicted, but leaving an escape for clearance by trivial causes imagined by the patient such as avoiding drinking coffee (narrow escape). In refractory cases, when confrontation becomes unavoidable, dual approach by dermatologist and psychiatrist is necessary.</p

Efficacy and safety of dupilumab in patients with severe chronic hand eczema with inadequate response or intolerance to alitretinoin:a randomized, double-blind, placebo-controlled phase IIb proof-of-concept study

BACKGROUND: Effective treatment options for patients with chronic hand eczema (CHE) are scarce. Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis and has shown promising results on hand eczema in other studies.OBJECTIVE: To evaluate the efficacy and safety of dupilumab in adult patients with severe CHE (subtypes recurrent vesicular HE or chronic fissured HE) with an inadequate response/intolerance to alitretinoin, or when alitretinoin is medically inadvisable.METHODS: In this 16-weeks, randomized, double-blind, placebo-controlled, proof-of-concept phase IIb trial, patients with severe CHE were randomized 2:1 to dupilumab 300mg or placebo subcutaneously every two weeks. Patients visited the outpatient clinic at initiation of the study drug, and every 4 weeks until 16 weeks of treatment. The primary end point was the proportion of patients achieving at least 75% improvement on the Hand Eczema Severity Index score (HECSI-75) at week 16. Adverse events were monitored during each visit. The study was registered on ClinicalTrials.gov (identifier NCT04512339).RESULTS: In total, 30 patients were randomized, and 29 patients received the assigned study drug (dupilumab N = 20, placebo N = 9). At week 16, more patients achieved HECSI-75 in the dupilumab group than in the placebo group (95.0% [95% confidence interval (CI), 73.1%; 99.7.0%] versus 33.3% [95% CI, 9.0%; 69.1%]). Dupilumab also showed greater least square mean percentage change from baseline to week 16 in peak pruritus numerical rating scale than placebo (-66.5 ±10.7 [95% CI, -88.6; -44.5] versus -25.3 ±17.0 [95% CI, -60.1; 9.4]). Adverse events were similar between dupilumab and placebo groups and were mostly mild. There were no serious adverse events, nor did any of the adverse events lead to discontinuation of the study drug.CONCLUSION: Dupilumab was efficacious and well tolerated. Larger studies of longer duration, are needed to provide more evidence on the efficacy of dupilumab in CHE. Moreover, larger studies could also enable comparisons between clinical subtypes or etiological diagnoses.</p

Efficacy and safety of dupilumab in patients with severe chronic hand eczema with inadequate response or intolerance to alitretinoin:a randomized, double-blind, placebo-controlled phase IIb proof-of-concept study

BACKGROUND: Effective treatment options for patients with chronic hand eczema (CHE) are scarce. Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis and has shown promising results on hand eczema in other studies.OBJECTIVE: To evaluate the efficacy and safety of dupilumab in adult patients with severe CHE (subtypes recurrent vesicular HE or chronic fissured HE) with an inadequate response/intolerance to alitretinoin, or when alitretinoin is medically inadvisable.METHODS: In this 16-weeks, randomized, double-blind, placebo-controlled, proof-of-concept phase IIb trial, patients with severe CHE were randomized 2:1 to dupilumab 300mg or placebo subcutaneously every two weeks. Patients visited the outpatient clinic at initiation of the study drug, and every 4 weeks until 16 weeks of treatment. The primary end point was the proportion of patients achieving at least 75% improvement on the Hand Eczema Severity Index score (HECSI-75) at week 16. Adverse events were monitored during each visit. The study was registered on ClinicalTrials.gov (identifier NCT04512339).RESULTS: In total, 30 patients were randomized, and 29 patients received the assigned study drug (dupilumab N = 20, placebo N = 9). At week 16, more patients achieved HECSI-75 in the dupilumab group than in the placebo group (95.0% [95% confidence interval (CI), 73.1%; 99.7.0%] versus 33.3% [95% CI, 9.0%; 69.1%]). Dupilumab also showed greater least square mean percentage change from baseline to week 16 in peak pruritus numerical rating scale than placebo (-66.5 ±10.7 [95% CI, -88.6; -44.5] versus -25.3 ±17.0 [95% CI, -60.1; 9.4]). Adverse events were similar between dupilumab and placebo groups and were mostly mild. There were no serious adverse events, nor did any of the adverse events lead to discontinuation of the study drug.CONCLUSION: Dupilumab was efficacious and well tolerated. Larger studies of longer duration, are needed to provide more evidence on the efficacy of dupilumab in CHE. Moreover, larger studies could also enable comparisons between clinical subtypes or etiological diagnoses.</p

Manganese toxicity and tolerance in cowpea (Vigna unguiculata L. Walp.) : the role of the leaf apoplast

[no abstract