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.     

Congenital esophageal stenosis presenting as noncardiac,esophageal chest pain

Summary A case of a 31-year-old female with congenital esophageal stenosis presenting with symptoms of chest pain caused by esophageal dysmotility is described. The involved segment in congenital esophageal stenosis has a characteristic thickening of the muscularis propria layer, as seen by EUS examination. In these patients, symptoms of dysphagia can be managed with esophageal dilation and noncardiac esophageal chest pain responds to pharmacotherapy with diltiazem.The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official policy or reflecting the views of the Army or the Department of Defense.     

Cell survival and DNA double-strand break repair following X-ray or neutron irradiation of V79 cells

We have investigated the effects of 250kVp X-rays and 2.3 MeV (mean energy) neutrons on the cell survival, DNA double-strand break (dsb) induction and repair (using the Kohn neutral elution technique) in V79 cells. The lethal effects of neutrons were shown to be significantly greater than for a similar dose of X-rays (RBE = 3.55 at 10 per cent survival). However, the RBE for dsb induction, in a dose range of 10-50 Gy, was 1. On investigating the repair of DNA dsb induced by either X-ray or neutron irradiation, clear differences in the pattern of repair were found. Both a fast and a slow component of repair were seen in both cases; the former, however, was reduced following neutron irradiation and, since the amount of slow repair was similar in both cases, this resulted in proportionally more unrejoined breaks after neutrons. These experiments were carried out with elution buffer at pH 9.6; however, when similar experiments were performed at pH 7.2 the results obtained support our earlier findings. We suggest that these differences in DNA dsb repair reflect basic differences in the nature of the lesions induced by high- and low-LET ionizing radiations.     

Does the Prepubertal Duration of Diabetes Influence the Onset of Microvascular Complications?

This study investigated the relationship between the development of diabetic retinopathy and pubertal status at onset of diabetes in 521 Type 1 diabetic patients diagnosed between 1950 and 1985. Pubertal status was based on age at onset (girls ≧ 11 years and boys ≧ 12 years). Retinopathy (all forms) developed in 112 patients (21.5%; 65 background and 47 proliferative retinopathy). For subjects diagnosed in either the prepubertal or postpuberal period, a similar proportion survived without developing retinopathy for any given duration of diabetes (X² = 0.3822, p = 0.54). However, if only the postpubertal duration of diabetes is considered, then the proportion of patients surviving without retinopathy was significantly less for those diagnosed in the prepubertal period (X² = 14.2, p = 0.002). This study suggests that the prepubertal duration of diabetes is an important phase and that the years prior to puberty do contribute to the risk of developing microvascular injury.     

The introduction of a new assessment system in restorative dentistry: the undergraduate and patient experience

In 2000, the University of Bristol Dental School Division of Restorative Dentistry carried out a review of the assessment methods used within the undergraduate programme. Following this review, a number of key recommendations were made and the system of formative assessment within the division was changed. Audits were conducted immediately prior to the introduction of the new system and 2 years after it had been introduced, the results of these audits are presented. There was no change in the number of failed appointments between the initial audit and the second audit. There was a reduction in the number of patients treated by more than one student from 25% to 14% (approximating to 3% if student withdrawal from the course is taken into account). The length of time taken to complete treatment reduced between the two audits with more than half of all patients having their treatment completed within 3 months of their initial examination in the second audit. Ninety-five percent of treatment plans were completed in the second audit compared with only 62% in the first audit. In the second audit, the outstanding 5% of cases were signed off as incomplete for satisfactory reasons by the member of supervisory staff (e.g. patients who had moved away or were discharged due to poor attendance). Student comments were mostly positive, the small number of negative comments related to some students being confused by the paperwork in the new system. The overall process has been an extremely positive experience which has resulted in an assessment system with increased clarity which appears to have reduced the stress levels reported by the undergraduate students on the programme and improved the quality of patient care within restorative dentistry.     

Pro-opiomelanocortin messenger ribonucleic acid and posttranslational processing of beta endorphin in spleen macrophages.

We have previously demonstrated low levels of immunoreactive (ir)-beta-endorphin (beta-EP) and ir-ACTH in a subpopulation of mouse spleen macrophages, which is consistent with an involvement of opioid peptides in modulation of immune responses. Gel chromatography studies suggested the presence of an approximately 3.5,000-molecular weight (mol wt) species, putatively beta-EP, an approximately 11.5,000-mol-wt species, putatively beta-lipotropin, and a higher molecular weight species (putative beta-EP precursor, pro-opiomelanocortin (POMC). In this study we have extended our original findings by demonstrating the presence of messenger RNA for POMC by the use of a complementary DNA probe and Northern blot analysis of extracts of mouse and rat spleen. In addition, using high performance liquid chromatography (HPLC), we have shown that the major endorphin species in mouse spleen macrophages is beta-EP1-31, and that there are smaller amounts of each of the acetylated forms, N-acetyl-beta-EP1-16 (alpha-endorphin), N-acetyl-beta-EP1-17 (gamma-endorphin), N-acetyl-beta-EP1-27, and N-acetyl-beta-EP1-31. We interpret these studies as showing that (a) the spleen is an organ of POMC synthesis and that (b) the predominant COOH-terminal product of macrophage POMC is the opiate-receptor active species beta-EP1-31.     

An assessment of intrarenal hydrostatic pressure measurements in the diagnosis of acute renal allograft rejection

Postoperative intrarenal pressure measurements may be an aid to the diagnosis of acute renal transplant rejection, especially in patients treated with cyclosporine. Serial measurements of intrarenal pressure were made in 38 recipients using a fine-needle technique. Thirty-two intraoperative and 207 postoperative measurements were made, and 39 clinical rejection episodes (23 confirmed by biopsy) monitored. Intraoperative pressures in grafts with immediate function (37.4 +/- 4.0 mmHg, mean +/- SEM) were not significantly different from those with delayed function (30.9 +/- 4.8 mmHg), whereas postoperative pressures were greater (P less than 0.01) in kidneys with acute tubular necrosis (29.4 +/- 1.9 mmHg) than in functioning grafts (20.4 +/- 0.9 mmHg). Pressures recorded during clinical rejection episodes (44.3 +/- 2.3 mmHg) exceeded (P less than 0.001) those during quiescent periods (23.6 +/- 1.0 mmHg). During rejection episodes, higher pressures (P less than 0.01) were recorded from tender or palpably enlarged grafts (52.5 +/- 3.0 mmHg) than in the absence of these signs (36.3 +/- 3.1 mmHg), and patients whose transplants biopsies showed cellular rejection tended to have greater pressures (50.1 +/- 4.1 mmHg) than those with concomitant vasculopathy (36.4 +/- 3.9 mmHg), but the latter did not reach statistical significance. In 7 cases of cyclosporine toxicity the intrarenal pressure was 17.8 +/- 4.2 mmHg. Using a diagnostic cut off point of 40 mmHg, the investigation failed to recognize 26% of acute rejection episodes--and, in the presence of acute tubular necrosis, it wrongly categorized 21% of nonrejectors. While its predictive capacity was limited, the test may occasionally be helpful in the differentiation of cyclosporine toxicity and rejection in functioning kidneys.     

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.