Wiedemann‐Rautenstrauch (neonatal progeroid) syndrome: New case with normal telomere length in skin fibroblasts

Wiedemann‐Rautenstrauch (neonatal progeroid) syndrome is an autosomal recessive condition with characteristic appearance of premature aging present at birth (aged face, natal teeth, and wrinkled skin). Other features of the syndrome are generalized lipoatrophy with specific fat accumulation in the lateral suprabuttock region, hypotrichosis, macrocephaly (pseudohydrocephalus), and mental retardation. We report on a new case that demonstrates all typical features of the syndrome. The girl is now 16 years and 10 months old and has had follow‐up from birth. We measured terminal restriction fragment (TRF) length to evaluate whether the patient's premature aging process is accompanied by shortening of telomere length in her cultured fibroblasts. Mean TRF of 13.5 kb found in our patient's fibroblasts is not shortened as compared to that of normal fibroblasts. Our results differ from those observed in Hutchinson‐Gilford progeria. © 2001 Wiley‐Liss, Inc.     

Atypical hyperplastic lesions of the female breast. A long-term follow-up study

A total of 10,542 breast biopsy specimens obtained between 1950 and 1968 were studied. Examples of atypical "ductal" (ADH) and atypical lobular hyperplasia (ALH), defined as having only some features of carcinoma in situ (CIS), were diagnosed in 3.6% of these specimens. In the same series, CIS was diagnosed in 1.7% of biopsy specimens excluding those with invasive cancer. The subsequent risk of invasive breast carcinoma after ALH or ADH was 4-5 times that of the general population. Follow-up was 90% successful and extended 17 years after biopsy. History of breast cancer in a mother, sister, or daughter doubled the risk of subsequent invasive carcinoma development (to 8 times for ALH and 10 times for ADH). The authors conclude that among the epithelial hyperplastic lesions of the human breast, a minority may be recognized by their resemblance to CIS which have a clinically significant elevation of subsequent breast cancer risk. This risk is one-half that of CIS.     

Anti-SARS-CoV-2 activity of targeted kinase inhibitors: Repurposing clinically available drugs for COVID-19 therapy

Coronavirus disease 2019 (COVID-19) remains a major public health concern, and vaccine unavailability, hesitancy, or failure underscore the need for discovery of efficacious antiviral drug therapies. Numerous approved drugs target protein kinases associated with viral life cycle and symptoms of infection. Repurposing of kinase inhibitors is appealing as they have been vetted for safety and are more accessible for COVID-19 treatment. However, an understanding of drug mechanism is needed to improve our understanding of the factors involved in pathogenesis. We tested the in vitro activity of three kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including inhibitors of AXL kinase, a host cell factor that contributes to successful SARS-CoV-2 infection. Using multiple cell-based assays and approaches, gilteritinib, nintedanib, and imatinib were thoroughly evaluated for activity against SARS-CoV-2 variants. Each drug exhibited antiviral activity, but with stark differences in potency, suggesting differences in host dependency for kinase targets. Importantly, for gilteritinib, the amount of compound needed to achieve 90% infection inhibition, at least in part involving blockade of spike protein-mediated viral entry and at concentrations not inducing phospholipidosis (PLD), approached a clinically achievable concentration. Knockout of AXL, a target of gilteritinib and nintedanib, impaired SARS-CoV-2 variant infectivity, supporting a role for AXL in SARS-CoV-2 infection and supporting further investigation of drug-mediated AXL inhibition as a COVID-19 treatment. This study supports further evaluation of AXL-targeting kinase inhibitors as potential antiviral agents and treatments for COVID-19. Additional mechanistic studies are needed to determine underlying differences in virus response.     

Relationship between peritoneal equilibration test and surface tension of peritoneal effluent in CAPD patients

Surface phenomena resulting from interactions between molecules occur commonly in nature. Peritoneal effluent is a mixture of organic and inorganic substances both macro- and micromolecular. Surfactants present in dialysate affect its surface properties. Among them are: proteins, phospholipids, fatty acids. Our aim in this study was to investigate relationships between peritoneal membrane solute transport characteristics and surface tension of peritoneal effluent. The study was conducted in 40 CAPD patients who were stable, without peritonitis (24 M, 16F), age 51.5 +/- 15.8 (range 30-79) mean CAPD duration 26.4 +/- 20.6 months (range 4-72). Standard peritoneal equilibration test (sPET) was done in all patients. Dialysate surface tension (ST) values after 4 hours dewell were determined using Wilhelmy Plate method. Mean ST values of individual dialysate sample based on 10 measurements were calculated. According to the PET values patients were divided into two groups: group 1 (high/high average transporters, n = 26) and group 2 (low average/low transporters, n = 14). Patients in group 1 had significantly lower ST of dialysate than patients in group 2 (51.2 +/- 4.8 vs 57.9 +/- 1.4 mN/m), p<0.01. The lowest values of ST (48.5 +/- 5 mN/m) were found in patients classified as high transporters (n = 8). Correlation's: significant negative correlation was found between ST and D4/P4 for creatinine (r = -0.45, p<0.005) and significant positive correlation between ST and D4/DO for glucose (r = 0.48, p = 0.003). We conclude that there are significant relationships between peritoneal transport status and surface tension of peritoneal effluent. High transporters have significantly higher concentrations of surfactants in dialysis effluent.     

Small doses of droperidol do not present relevant torsadogenic actions: a double-blind,ondansetron-controlled study

AIM

Drugs used for postoperative nausea and vomiting prophylaxis are believed to provoke torsadogenic changes in cardiac repolarization. The aim of this study was to assess the effect of small doses of droperidol on the parameters of cardiac repolarization, including the QT_c interval and transmural dispersion of repolarization.

METHODS

A total of 75 patients were randomly allocated to receive 0.625 or 1.25 mg droperidol or 8 mg ondansetron. The QT_c interval was calculated using Bazett''s formula and the Framingham correction. The transmural dispersion of repolarization was determined as T_peak–T_end time.

RESULTS

Transient QT prolongation, corrected with both formulae, followed 1.25 mg of droperidol 10 min after administration. No change in the QT_c value was observed in the other groups. When corrected with Bazett''s formula, QT_c was prolonged above 480 ms in two patients receiving 1.25 mg droperidol (at the 10^th and 20^th minute of the study) and in one receiving ondansetron. No patients developed a QT_cB prolongation over 500 ms. No increase above 480 ms was observed relative to the Framingham correction method. There were no significant differences in the T_peak–T_end time either between or within the groups.

CONCLUSION

In men without cardiovascular disorders small doses (1.25 mg) of droperidol prophylaxis induced transient QT_c prolongation without changes in transmural dispersion of repolarization. The apparently low risk of the drug applies only in low risk male patients with a low pro-QT_c score.     

Tumour in left atrium diagnosed 6 years after ablation of pulmonary vein ostia and inferior right atrial isthmus: thrombus or myxoma?

We present a case of the left atrial myxoma 6 years after atrial fibrillation ablation. The initial diagnosis of the mass revealed on echocardiography was a thrombus. Failure of anticoagulant treatment and transesophageal echocardiography led to diagnosis of myxoma, confirmed intraoperatively and histologically.     

A 59 year-old patient with acute anterolateral myocardial infarction, complicated by cardiogenic shock, with chest wall deformity caused by Heine-Medin disease

We report a case of a 59 year-old patient in a condition of acute myocardial infarction with ST elevation, in a cardiogenic shock, with multiple cardiac arrests in mechanism of ventricular fibrillation with a significant chest wall deformity caused by Heine-Medin disease in childhood. To our knowledge, this is the first case report of a patient in critical condition with a considerable pectus deformity after poliomyelitis who needed to undergo cardiovascular angioplasty. Although severe patient's condition and numerous difficulties during percutaneous coronary intervention, therapy was successful.     

Bone graft incorporation after revision hip arthroplasty in patients with rheumatoid arthritis, seventy eight revisions using bone allografts with or without metal reinforcements

Purpose

The aim of the study was to assess bone graft incorporation after revision hip arthroplasty in patients with rheumatoid arthritis (RA).

Methods

We report an acetabular reconstruction using impacted, morselized, frozen, radiation sterilized bone allografts in 71 patients suffering from RA. There were sixty-six women and five men at a mean age of 57.5 years. Reconstruction was performed in 78 revision total hip arthroplasties (THAs) for aseptic loosening of acetabular component. The mean follow-up was five years and four months. In 38 cases, a revision was done with use of reinforcement devices.

Results

In four revised hips (10 %) without reinforcement implants, resorption of the allografts was noticed. All Mueller rings and 50 % of unscrews cages (Link, Howmedica) were revised because of aseptic loosening and bone graft resorption. In all of 17 hips with the Burch-Schneider cage, no measurable migration or bone allografts resorption occurred. There were no major general complications.

Conclusions

Acetabular reconstruction with use of morselized, frozen, radiation sterilized bone allografts and the Burch-Schneider cage can be highly successful in managing massive deficiency of acetabular bone stock in revision hip arthroplasty in RA patients.