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.     

Case report: unilateral haematocolpos in uterine duplication associated with renal agenesis

A case of unilateral haematocolpos correctly diagnosed by ultrasound is described in a 13 year old girl known to have a solitary kidney. The association of renal agenesis with Müllerian abnormalities is well recognised and in this case the ultrasound findings ensured that the correct surgical management was undertaken.     

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.     

Mandibular lingual releasing approach.

The mandibular lingual releasing approach to oral cavity and oropharyngeal tumors provides excellent visualization for resection while integrity of the mandibular arch is preserved. A lingual floor-of-mouth flap is created, which allows delivery of these structures directly into the neck without lip splitting, mandibulotomy, or mandibulectomy. The procedure was carried out on 15 patients between 1987 and 1991, with followup ranging from 2 to 50 months. Nine patients had received previous radiation, whereas planned postoperative radiation was administered to five patients. The visualization afforded by this technique was very good, in that 12 patients had clear margins of resection. Three patients had close margins; recurrent disease developed in one of these patients 18 months later. Twelve of the patients were able to maintain their weight with an oral diet alone. Four postoperative fistulae occurred, three of these were in patients who had not been previously irradiated. The single fistula that did not spontaneously heal occurred in a patient who had received previous radiation and was also on long-term corticosteroids. Mandibular osteoradionecrosis developed in two patients who received postoperative radiation. The complication rate after previous radiation is acceptable; however, there is risk of mandibular osteoradionecrosis after high-dose postoperative radiation.     

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.     

Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography.

The role of cerebral ischemia in the pathophysiology of traumatic brain injury is unclear. Cerebral blood flow (CBF) measurements with 133Xe have thus far revealed ischemia in a substantial number of patients only when performed between 4 and 12 hours postinjury. But these studies cannot be performed sooner after injury, they cannot be done in patients with intracranial hematomas still in place, and they cannot detect focal ischemia. Therefore, the authors performed CBF measurements in 35 comatose head-injured patients using stable xenon-enhanced computerized tomography (CT), simultaneously with the initial CT scan (at a mean (+/- standard error of the mean) interval of 3.1 +/- 2.1 hours after injury). Seven patients with diffuse cerebral swelling had significantly lower flows in all brain regions measured as compared to patients without swelling or with focal contusions; in four of the seven, cerebral ischemia (CBF less than or equal to 18 ml/100 gm.min-1) was present. Acute intracranial hematomas were associated with decreased CBF and regional ischemia in the ipsilateral hemisphere, but did not disproportionately impair brain-stem blood flow. Overall, global or regional ischemia was found in 11 patients (31.4%). There was no correlation between the presence of hypoxia or hypertension before resuscitation and the occurrence of ischemia, neither could ischemia be attributed to low pCO2. Ischemia was significantly associated with early mortality (p less than 0.02), whereas normal or high CBF values were not predictive of favorable short-term outcome. These data support the hypothesis that ischemia is an important secondary injury mechanism after traumatic brain injury, and that trauma may share pathophysiological mechanisms with stroke in a large number of cases; this may have important implications for the use of hyperventilation and antihypertensive drugs in the acute management of severely head-injured patients, and may lead to testing of drugs that are effective or have shown promise in the treatment of ischemic stroke.