Diagnoses of chronic beryllium disease within cohorts of sarcoidosis patients.

An increase in chronic beryllium disease (CBD) has been suggested due to higher industrial use of beryllium alloys. Since occupational CBD is a perfect phenocopy of sarcoidosis, it might be misdiagnosed as sarcoidosis. In the current it was hypothesised that CBD exists in cohorts of sarcoidosis patients. In a prospective case study, sarcoidosis patients were evaluated for potential beryllium exposure. In those patients in whom beryllium exposure was confirmed and beryllium hypersensitivity demonstrated, the diagnosis of sarcoidosis was rejected and corrected to CBD. In 84 patients seen for re-evaluation or making a diagnosis of sarcoidosis, beryllium exposure was recognised and a diagnosis of CBD was made in 34 out of 84 patients. The time lag between clinical diagnosis of sarcoidosis and the final diagnosis of CBD ranged 0-18 yrs (median 3 yrs) and the mean (range) age at time of diagnosis of CBD was 43.9(25-80) yrs. Beryllium-contaminated workplaces causing disease encompassed a wide spectrum of industries and technical trades in which beryllium-exposure is generally not perceived as a health hazard. In conclusion, chronic beryllium disease still belongs to the spectrum of differential diagnoses of granulomatous disorders.     

Intravenous cidofovir treatment for recalcitrant warts in the setting of a patient with myelodysplastic syndrome

Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.     

Colorectal tumor screening in women with a past history of breast, uterine, or ovarian malignancies

Epidemiologic studies have shown that women who have successfully recovered from breast, uterine, or ovarian cancer have about twice the expected risk of developing colorectal cancer. These high-risk women were entered, therefore, into a large bowel screening program based on fecal occult blood detection, flexible sigmoidoscopy, and colonoscopy, when appropriate. The study group consisted of 183 women and the results were compared with 252 comparison subjects of similar age and ethnic origin. Neoplastic lesions, adenomatous polyps, or cancer were 2.5 times more frequent in the study group. However, for the largest group, women with a past history of breast cancer, the relative risk, adjusted for a family history of gastrointestinal cancer, was 3.0 (P = 0.03). This pilot study confirms the value of continuing to screen these patients, especially those with a positive family history of gastrointestinal malignancies. However, for psychological and administrative reasons, it may be better that their colon screening be integrated into a combined colon, breast, and gynecologic tumor follow-up, and not be part of a separate service.     

Testing for recovery of thyroid function after withdrawal of long-term suppression therapy

Many persons are given thyroid hormone for long periods without sufficient justification. We selected 45 patients whose chart reviews did not demonstrate a clear need for thyroid replacement. Thyroid hormone was withdrawn and blood samples taken for free thyroxine index and TSH levels at 2, 4, 6, and 8 weeks after thyroid withdrawal. At 8 weeks, 30 of the 45 were normal. A single TSH test 8 weeks after thyroid withdrawal appears to be the most efficient way to separate euthyroid from hypothyroid patients.     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.     

Late side-effects with cosmetic relevance following soft X-ray therapy of cutaneous neoplasias

Background Cosmetic changes are to be expected after radiotherapy for skin tumours. Objectives This study aimed to answer the questions: How frequent are cosmetic changes after soft X‐ray therapy? Do treatment parameters, tumour thickness, localization and size of the irradiated field have a major influence? Were patients irritated by the visual appearance of the irradiated field? Methods In total, 2474 examinations of 1149 irradiated fields were performed. Results Hypopigmentation was found in 64.7% of examinations more than 90 days after therapy, teleangiectases in 43.1%, erythema in 24.8%, and hyperpigmentation in 16.8%. The frequency of hypopigmentation, teleangiectases and hyperpigmentation increased with time from X‐ray exposure; more than 4 years after therapy hypopigmentation was diagnosed in 91.8% and teleangiectases in 82.2% of examinations. Total dose, the time–dose–fractionation factor (TDF), field size and dose per fraction were significantly related to the frequency of cosmetic changes. Incidence rates of cosmetic changes differed by less than 15% if different treatment conditions were compared: thicker vs. thinner tumours, larger vs. smaller fields, higher vs. lower total doses, doses per fraction, and TDF. Frequencies of hypopigmentation, teleangiectases, erythema and hyperpigmentation differed by more than 15% between some localizations on the head. Women reported irritation by the visual appearance of the irradiated field in 12.6% of 1116 interviews, and men in 4.4% of 1284 interviews. Conclusions Cosmetic changes after soft X‐ray therapy are relatively frequent. Treatment parameters, tumour thickness and field size have only a minor influence. Few patients, but more women than men, were irritated by the visual appearance of the irradiated field.     

HYPOKALEMIA IN THE ELDERLY: IS IT ALWAYS DIURETIC-INDUCED?

SUMMARY Serum potassium was measured within 24 hours in 156 patients (48 male, 108 female) with an average age of 81.9 years admitted to the unit with acute illness. Of the 156 patients, 88 (56.4%) were taking diuretics (none was on ACE inhibitors); 20 patients (12.8%) were also on digoxin therapy. In all, 24 patients (16%) had hypokalaemia and 3 (2%) hyperkalaemia. Hypokalaemia was seen in patients associated with acute illness. There was no significant difference between the diuretic and non-diuretic groups. Monitoring of serum potassium is not routinely indicated to detect hypokalaemia in patients on diuretic therapy except in those with severe hepatic or renal impairment or those on digoxin.