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.     

Resuscitation with Recombinant Hemoglobin rHb2.0 in a Rodent Model of Hemorrhagic Shock

Background: Hemoglobin solutions combine volume effect, oxygen-carrying capacity, and vasoactive properties, the latter facilitating restoration of global hemodynamics but endangering microvascular resuscitation. Hemoglobin-evoked vasoconstriction probably is due to nitric oxide scavenging, which can be reduced by genetic modifications of the heme pocket. This study compares resuscitation with a nonhemoglobin colloid and two recombinant hemoglobin solutions with wild-type and reduced nitric oxide-scavenging capacity.

Methods: Twenty-seven awake Syrian golden hamsters fitted with dorsal skinfold chambers underwent a 30 min-hemorrhagic shock (mean arterial pressure [MAP] 30-35 mmHg) and resuscitation with shed blood volume of either 6% dextran 60 (Biophausia, Uppsala, Sweden), recombinant hemoglobin 1.1 (rHb1.1; wild-type nitric oxide-scavenging capacity; 10 g/dl), or recombinant hemoglobin 2.0 (rHb2.0; reduced nitric oxide-scavenging capacity; 10 g/dl; both Baxter Healthcare, Boulder, CO). Macrohemodynamic and laboratory parameters were assessed; microvascular parameters in the skinfold chamber were analyzed by intravital microscopy.

Results: Hemorrhagic shock reduced functional capillary density (FCD) by 70% and caused significant metabolic acidosis. Colloid resuscitation led to incomplete recovery of MAP and FCD. Infusion of rHb1.1 completely restored MAP but not FCD, with the smallest arteriolar diameters found in this group. FCD was restored best by resuscitation with rHb2.0, although MAP was lower than in rHb1.1-treated animals. Metabolic acidosis was resolved by both hemoglobin solutions, but not by dextran.     

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.     

Passive Pneumatic Stabilization Device for Assisting in Reduction of Femoral Shaft Fractures

Abstract During treatment of femoral shaft fractures, not only the actual fracture reduction but also the retention of the achieved reduction is essential. Substantial forces may apply to the bone fragments, due to multidirectional muscular contraction. Furthermore, forces from manipulation of one bone fragment may be transferred over the soft tissues onto the other fragments, thus hindering accurate fracture reduction. Once a sufficient reduction has been achieved, this position must be retained whilst definitive internal fixation is performed. Conventional methods comprise mounting patients on a traction table and applying manual distraction or employing special distraction devices, such as the AO distractor device. These approaches, however, only insufficiently stabilize both main fragments. For example, on the traction table the proximal femoral fragment can pivot around the hip joint thus complicating precise reduction. A novel pneumatic stabilization device to assist surgeons during operative procedures is described. This passive holding device “Passhold” connects to one main fragment through a minimally invasive bone interface and statically locks the fragment’s position. Thereafter, only the other main fragment is manipulated to achieve reduction. Mutual interference of the reciprocal fragment positions, due to soft-tissue force transfer during manipulation, is avoided. The authors examined the stability of the novel retention device on a test rig and proved its functionality under sterile settings using cadaver tests. It is concluded that this device largely facilitates the operative procedure in femoral shaft fractures, is sufficiently stable and ergonomically suitable for intraoperative deployment.     

Erythropoietin accelerates the recovery from extreme hemodilution: a randomized, placebo-controlled study in dogs

Six splenectomized beagles of either sex (13.8 +/- 2.2 kg) were randomly treated either with 500 U/kg recombinant human erythropoietin (rhu-EPO) (verum group, n = 3) or an equivalent volume of the vehicle (placebo group, n = 3). Both solutions were given intravenously for 3 days. At day 4 after onset of treatment, the dogs were anesthetized and subjected to isovolemic hemodilution using 6% Dextran 60 (MW 60,000) down to a hematocrit of 0.10. During the recovery period vehicle or rhu-EPO was given every other day until the hematocrit reached control values. Every day venous blood samples were withdrawn, and the hematocrit as well as the concentrations of hemoglobin and 2,3-diphosphoglycerate were determined. In addition, the platelets and reticulocytes were counted. Treatment with rhu-EPO shortened the time of hematocrit recovery from 20 (placebo) to 11 days (p less than 0.05). The reticulocyte count peaked at day 2 (verum) versus day 5 (placebo). These findings indicate a successful stimulation of red blood cell production after extreme hemodilution in animals treated with erythropoietin. Therefore, rhu-EPO may allow to optimize blood donation programs as well as preoperative hemodilution and yield both, higher amounts of autologous blood and an accelerated reversal of dilutional anemia.     

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.