Occupational generalized urticaria and anaphylaxis after inhalation of cefuroxime in a nurse

We present the case of a 53 years old nonatopic female nurse who experienced repeated anaphylactic reactions at work without involvement in drug‐specific tasks such as crushing of tablets or preparation of injections. The causal allergen was not identified until a further severe anaphylactic reaction occurred after oral use of cefuroxime during a respiratory infection. Sensitization to cefuroxime was demonstrated by specific IgE, basophil activation test and skin prick test. An inhalation challenge with a dosimeter induced generalized urticaria after a cumulative dose of about 10 μg of the drug, but no asthmatic reaction. Complete exposure cessation was initiated and a 1‐year follow‐up was without further allergic reactions. We conclude that work‐related systemic allergic reactions to β‐lactam antibiotics may occur in nurses after inhalation of low doses and without perceived association with drug‐specific tasks like handling of antibiotics.

     

Expanding the spectrum of PTH1R mutations in patients with primary failure of tooth eruption

Objectives

Primary failure of tooth eruption (PFE) is a rare autosomal-dominant disease characterized by severe lateral open bite as a consequence of incomplete eruption of posterior teeth. Heterozygous mutations in the parathyroid hormone 1 receptor (PTH1R) gene have been shown to cause PFE likely due to protein haploinsufficiency. To further expand on the mutational spectrum of PFE-associated mutations, we report here on the sequencing results of the PTH1R gene in 70 index PFE cases.

Materials and methods

Sanger sequencing of the PTH1R coding exons and their immediate flanking intronic sequences was performed with DNA samples from 70 index PFE cases.

Results

We identified a total of 30 unique variants, of which 12 were classified as pathogenic based on their deleterious consequences on PTH1R protein while 16 changes were characterized as unclassified variants with as yet unknown effects on disease pathology. The remaining two variants represent common polymorphisms.

Conclusions

Our data significantly increase the number of presently known unique PFE-causing PTH1R mutations and provide a series of variants with unclear pathogenicity which will require further in vitro assaying to determine their effects on protein structure and function.

Clinical relevance

Management of PTH1R-associated PFE is problematic, in particular when teeth are exposed to orthodontic force. Therefore, upon clinical suspicion of PFE, molecular DNA testing is indicated to support decision making for further treatment options.     

Pumpless extracorporeal lung assist using an arterio-venous shunt. Applications and limitations

We report the use of a pumpless extracorporeal lung assist (PECLA) in 70 patients with severe pulmonary failure of various causes. The device was used under rescue conditions in patients with preserved cardiac function. By establishing a shunt between femoral artery and vein using the arterio-venous pressure gradient as the driving force for the blood flow through the oxygenator, PECLA proved to be extremely effective in terms of oxygenation and carbon dioxide removal.     

Clinical comparison of the efficacy and tolerability of once daily Canesten with twice daily Nizoral (clotrimazole 1% cream vs. ketoconazole 2% cream) during a 28-day topical treatment of interdigital tinea pedis

The effects of two topical cream formulations containing clotrimazole 1% and ketoconazole 2%, respectively, were clinically compared in a double-blind, randomized manner for a 28-day therapy of interdigital tinea pedis in 106 treated patients. Ketoconazole was to be used twice daily whereas clotrimazole was administered only once daily. The primary response criterion defined as the number of patients with cure or improvement after 28 treatment days was comparable with 62.0% vs. 64.0% (clotrimazole vs. ketoconazole) for the full analysis set of 100 (50 vs. 50) patients. The mycological response revealed a negative culture and microscopy in 53.1% vs. 52.1% of the patients after 14, in 76.0% vs. 79.2% after 28, and in 83.7% vs. 76.9% after 56 days of observation, indicating a possibly better long-term efficacy of clotrimazole. The development of the overall score of tinea-related signs and symptoms did not show relevant differences between the two drugs and continuously decreased from 11+/-5 in both groups at baseline to 2+/-2 vs. 2+/-1 at day 56. As to the remission and improvement rates of single symptoms, better results were obtained under clotrimazole than under ketoconazole particularly for pruritus (97.8 vs. 89.6%) and burning/stinging (97.5 vs. 89.4%) which both are perceived as most bothersome by the patients. Furthermore, both substances appeared as comparably safe and well tolerable (8 vs. 7 adverse events with only 1 vs. 3 drug related). In conclusion, a successful therapy of tinea pedis can be achieved with both clotrimazole and ketoconazole within 28 days of treatment and once-daily clotrimazole is equally effective as twice-daily ketoconazole with favourable influences on the most irritating symptoms of the disease. Mycological and reliable clinical cure cannot be observed during two weeks after start of treatment.     

Bioactive asterosaponins from the starfish Culcita novaeguineae

Two new sulfated steroidal pentaglycosides（asterosaponins）,novaeguinosides Ⅰ（2） and （Ⅱ）2,along with the known regularoside B（1）were isolated from the starfish Culcita novaeguineae.Their structures were elucidated by extensive NMR techniques as well as chemical evidence.     

Testosterone-mediated increase in 5 alpha-dihydrotestosterone content, nuclear androgen receptor levels, and cell division in an androgen-independent prostate carcinoma of Noble rats

An androgen-independent, transplantable prostate carcinoma line (AIT), originally derived from the dorsolateral prostate (DLP) of Noble rat, was implanted into orchiectomized Noble rats and its response to androgen stimulation was studied and compared to that of the regenerating DLP tissue in sexually ablated rats. AIT tumors carried in castrated hosts displayed a high basal level of proliferative activity (mitotic index (MI), 15.0 +/- 0.5) while DLP tissue in untreated castrates exhibited no proliferative activity. Following androgen stimulation by testosterone capsule implantation into host rats, the AIT responded with a marked increase in cell proliferation; MI values doubled to 30.0 +/- 2.9 on Day 5 following androgen stimulation. This androgen-induced increase in MI values was coincident with elevations in nuclear androgen receptor (20-fold increase) and 5 alpha-dihydrotestosterone content (3-fold increase) in the tumor. However, by Day 10 following androgen treatment, indices of cell proliferation in the AIT declined to pre-androgen-stimulated levels (MI, 14.8 +/- 1.9) despite the continued elevations in nuclear androgen receptor and tissue 5 alpha-dihydrotestosterone contents. Parallel changes in MI were also observed in the normal regenerating DLP following androgen stimulation. MI values in this tissue increased from nondetectable levels to 38.1 +/- 4.7 on Day 5 but declined to relatively low levels (4.5 +/- 0.9) by Day 10 following androgen replacement. Taken together these findings led us to conclude that the AIT carried in castrates is capable of responding to testosterone in a manner similar to that observed for androgen-stimulated DLP of sexually ablated rats. Thus, in both the neoplastic and regenerating tissues, the initial response to androgen is characterized by a marked enhancement of cell proliferation which was correlated with an increase in androgen receptor and 5 alpha-dihydrotestosterone content. However, like its tissue of origin, the AIT possesses mechanisms which act to limit androgen-induced cell division despite continued elevations in key parameters of androgen activation.