A Selenourea-Thiourea Brønsted Acid Catalyst Facilitates Asymmetric Conjugate Additions of Amines to α,ß-Unsaturated Esters.

ß-Amino esters are obtained with high levels of enantioselectivity via the conjugate addition of cyclic amines to unactivated α,ß-unsaturated esters. A related strategy enables the kinetic resolution of racemic cyclic 2-arylamines, using benzyl acrylate as the resolving agent. Reactions are facilitated by an unprecedented selenourea-thiourea organocatalyst. As elucidated by DFT calculations and 13C kinetic isotope effect studies, the rate-limiting and enantiodetermining step of the reaction is the protonation of a zwitterionic intermediate by the catalyst. This represents a rare case in which a thiourea compound functions as an asymmetric Brønsted acid catalyst.

Localized Pemphigus Foliaceus: Diverse Presentations, Treatment, and Review of the Literature.

The clinical presentation of localized pemphigus foliaceus (PF) often involves photo exposed areas. We describe five cases of localized PF, two of which were rare locations for the disease in non-photo exposed areas, namely the genitalia and back. Patients were treated with topical corticosteroids and calcineurin inhibitors as well as systemic treatment with corticosteroids and dapsone. Each patient responded to treatment, with two achieving remission. No relapses occurred in any of these cases over a mean follow-up time of 3.7 years. A review of the English literature using MEDLINE® yielded 18 reported cases of localized PF. Most occurred in photo exposed areas such as the nose, cheeks, scalp, and other areas of the face. Two patients progressed to generalized involvement without treatment. Treatment regimens had much variation and included both topical and systemic agents. Localized PF is rare, and our findings suggest it may be controlled with topical therapy and systemic dapsone.

A Fatal Case of Lisinopril-Induced Acute Necrotizing Pancreatitis.

Angiotensin-converting enzyme inhibitors (ACE-I), such as lisinopril, are used as first-line therapy in the treatment of hypertension, heart failure with reduced ejection fraction, and proteinuric chronic kidney disease due to their beneficial effects on reducing morbidity and mortality. Commonly cited adverse effects of lisinopril include hyperkalemia, acute kidney injury, and angioedema, and while uncommon, there have been reports of lisinopril-induced necrotizing pancreatitis in the literature. The true incidence of drug-induced pancreatitis is unknown since establishing a causal relationship between medication's adverse effects and disease occurrence is difficult; however, there are validated tools such as the Adverse Drug Reaction Probability Scale that can aid in determining causality. Here, we present a case of a 63-year-old man with a history of hypertension who was being treated with lisinopril for eight months and developed a fatal case of lisinopril-induced severe necrotizing pancreatitis.

Combination Therapy of Plasma Exchange and Rituximab to Treat Cicatricial Pemphigoid and Bullous Pemphigoid.

The pemphigoid group of subepidermal autoimmune blistering diseases can affect both cutaneous and mucosal tissues. Therapy of this group of diseases, including cicatricial pemphigoid (CP) and bullous pemphigoid (BP), consists of systemic steroids and immunomodulatory agents. Recalcitrant cases have typically been treated with plasmapheresis or rituximab individually. This report describes two patients with severe, rapidly progressive CP and BP refractory to high-dosage systemic steroids and immunomodulatory agents. Both patients were treated with a combination of plasmapheresis and rituximab. In addition to these cases, one retrospective study showed the effectiveness of other immunosuppressants in combination with plasmapheresis in 17 patients with pemphigus refractory to corticosteroids and immunosuppressants alone. No major adverse events occurred in the study. Similar studies employing immunoadsorption and rituximab with various combinations of intravenous immune globulin (IVIg), corticosteroids, and other conventional immunosuppressants have shown promising results in other autoimmune blistering diseases. The successful response in the patients described here, as well as those described in the literature who underwent similar management, provides a possible combination treatment option for patients with severe, recalcitrant pemphigoid. A further trial with a larger group of pemphigoid patients is warranted.

Superlative Artistic Abilities in a Patient With Post-traumatic Brain Injury.

This case describes a patient who exhibits newfound superlative abilities in painting, music, philosophy, culinary, and performing arts after a traumatic brain injury (TBI) involving the frontal and temporal lobes. Such a dramatic change in de novo artistic behavior after brain injury is rare but has been reported in other patients with frontotemporal dementia, as well as other neurological diseases. Previous studies have shown that mild frontal cortical dysfunction likely plays a role in facilitating creative endeavors and that artistic circuitry is distributed throughout the brain. The neuronal reorganization which occurs after injuries enhances synapse formation and neural plasticity, which may contribute to the acceleration of artistic output after brain injury. This is likely an underdiagnosed phenomenon and a deeper understanding is required to allow clinicians to more effectively recognize and nurture newfound creativity in the setting of brain damage.

Certolizumab-induced lichenoid eruption in a patient with rheumatoid arthritis.

Certolizumab is a monoclonal antibody against tumour necrosis factor-alpha (TNF-α) commonly used in rheumatologic conditions such as rheumatoid arthritis. Skin rashes are an uncommon side effect with few cases of lichenoid drug eruption reported in the literature. We describe a patient with rheumatoid arthritis who presented 6 weeks after initiating certolizumab pegol. Physical examination showed pink-to-violaceous papules on her upper and lower extremities. Biopsy confirmed a lichenoid drug eruption. The medication was discontinued and she was treated with topical steroids and a calcineurin inhibitor, with resolution of her lesions. Clinicians should be cognizant of such adverse reactions to TNF-α inhibitors and keep drug-induced lichenoid eruptions on the differential. Lichenoid eruptions induced by certolizumab pegol may affect the skin and/or mucous membranes. While most cases occur within weeks to months of starting therapy, eruptions may occur years after treatment initiation, underscoring the importance of a thorough review of medications.

Spironolactone-Induced Lichenoid Drug Reaction and Subsequent Diffuse Eruptive Squamous Cell Carcinomas Successfully Treated With Systemic Methotrexate.

Antihypertensive agents such as spironolactone have been reported to cause lichenoid drug eruptions. Eruptive keratoacanthomas (KA), considered to be well-differentiated squamous cell carcinoma (SCC), may develop in the setting of such lichenoid reactions. Thus, definitive treatment is imperative. This case report describes a patient on spironolactone who developed a lichenoid drug eruption followed by eruptive KAs and SCC. The treatment approach used systemic methotrexate. While most treatment regimens for widespread eruptive KA/SCC employ intralesional methotrexate, this case demonstrated the utility of its systemic counterpart. This may have also facilitated the resolution of the patient's lichenoid eruption. There are only three other reports in the literature describing a spironolactone-induced lichenoid drug eruption. Further investigations are needed to evaluate the adverse cutaneous effects of spironolactone as well as the efficacy of systemic methotrexate in treating patients with a significant number of SCCs arising from lichenoid drug eruptions.

Emphysematous Cholecystitis Secondary to Fusobacterium nucleatum.

Fusobacterium nucleatum may be implicated in cases of emphysematous cholecystitis (EC) and carries a high mortality risk, especially in individuals with heart disease, renal insufficiency, and underlying malignancy. Fusobacterium infections are rarely detected in the setting of cholecystitis possibly due to the difficulty with properly culturing the bacteria. We describe a case of a patient with EC in whom blood cultures were positive for growth of F. nucleatum in one of two samples. The patient was treated with empiric antibiotic therapy consisting of metronidazole and cefepime. In patients with EC and negative cultures, it is possible that they may have an undetected infection with fusobacteria, which carries a high mortality risk. As such, clinicians should maintain a high degree of suspicion of obligate anaerobic infection in patients who have negative blood culture for growth in the setting of EC and consider continuation of adequate antimicrobial coverage.

Identification of a strong and specific antichlamydial N-acylhydrazone.

Sexually transmitted Chlamydia trachomatis is an extremely common infection and often leads to serious complications including infertility and pelvic inflammatory syndrome. Several broad-spectrum antibiotics are currently used to treat C. trachomatis. Although effective, they also kill beneficial vaginal lactobacilli. Two N-acylhydrazones, CF0001 and CF0002, have been shown previously to inhibit chlamydial growth without toxicity to human cells and Lactobacillus spp. Of particular significance, the rate of random mutation leading to resistance of these inhibitors appears to be extremely low. Here, we report three analogs of CF0001 and CF0002 with significantly stronger inhibitory effects on chlamydiae. Even though the new compounds (termed SF1, SF2 and SF3) displayed slightly decreased inhibition efficiencies for a rare Chlamydia variant selected for CF0001 resistance (Chlamydia muridarum MCR), they completely overcame the resistance when used at concentrations of 75-100 µM. Importantly, SF1, SF2 and SF3 did not shown any toxic effect on lactobacilli, whereas SF3 was also well tolerated by human host cells. An effort to isolate SF3-resistant variants was unsuccessful. By comparison, variants resistant to rifampin or spectinomycin were obtained from smaller numbers of chlamydiae. Our findings suggest that SF3 utilizes an antichlamydial mechanism similar to that of CF0001 and CF0002, and will be more difficult for chlamydiae to develop resistance to, potentially making it a more effective antichlamydial agent.