Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Autosomal glycogenosis of liver and muscle due to phosphorylase kinase deficiency is caused by mutations in the phosphorylase kinase beta subunit (PHKB)

Glycogen storage disease due to phosphorylase kinase deficiency occurs in several variants that differ in mode of inheritance and tissue- specificity. This heterogeneity is suspected to be largely due to mutations affecting different subunits and isoforms of phosphorylase kinase. The gene of the ubiquitously expressed beta subunit, PHKB, was a candidate for involvement in autosomally transmitted phosphorylase kinase deficiency of liver and muscle. To identify such mutations, the complete PHKB coding sequence was amplified by RT-PCR of RNA isolated from blood samples of patients and analyzed by direct sequencing of PCR products. The characterization of mutations was complemented by PCR of genomic DNA. In one female and four male patients, we identified five independent nonsense mutations (Y418ter; R428ter; Y974H+E975ter; Q656ter in two cases), one single-base insertion in codon N421, one splice-site mutation affecting exon 31, and a large deletion involving the loss of exon 8. Although these severe translation-disrupting mutations occur in constitutively expressed sequences of the only known beta subunit gene of phosphorylase kinase, PHKB, they are associated with a surprisingly mild clinical phenotype, affecting virtually only the liver, and relatively high residual enzyme activity of approximately 10%.      

A somatostatin analogue decreases embryonic loss following superovulation in rats by normalizing insulin-like growth factor-I action in the uterus

This study was designed to determine whether the somatostatin analogue, octreotide, could prevent embryonic loss by normalizing increased uterine insulin-like growth factor-I (IGF-I) action related to hyperoestrogenaemia following superovulation. Superovulated immature and oestradiol-17beta-treated adult rats were infused with 100 or 300 microg/ml of octreotide respectively, or injected daily with 1 or 10 microg of octreotide from day 1 to day 3 of pregnancy. On day 3, embryos were collected from the oviducts and uteri. Uterine luminal fluid was subjected to embryo culture. The amounts of uterine IGF-I and IGF binding proteins (IGFBP) were determined by radioimmunoassay and ligand binding assay respectively. Octreotide infusion normalized uterine IGF-I action following superovulatory and oestradiol-17beta treatment, by reducing IGF-I concentrations and increasing IGFBP concentrations. Octreotide infusion increased the number of normal embryos by 2.7-fold and 1.7-fold in superovulated and oestradiol-17beta- treated rats respectively, and reversed the detrimental effects of uterine luminal fluid on embryonic development caused by superovulatory and oestradiol-17beta treatment. Daily injections with octreotide had similar but reduced effects in all parameters examined in both treatment groups. In conclusion, octreotide may reduce embryonic loss, at least in part, by normalizing IGF-I action following superovulation.      

Development of a novel pulsatile bioreactor for tissue culture

The construction of tissue-engineered parts such as heart valves and arteries requires more than just the seeding of cells onto a biocompatible/biodegradable polymeric scaffold. It is essential that the functionality and mechanical integrity of the cell-seeded scaffold be investigated in vitro prior to in vivo implantation. The correct hemodynamic conditioning would lead to the development of tissues with enhanced mechanical strength and cell viability. Therefore, a bioreactor that can simulate physiological conditions would play an important role in the preparation of tissue-engineered constructs. In this article, we present and discuss the design concepts and criteria, as well as the development, of a multifunctional bioreactor for tissue culture in vitro. The system developed is compact and easily housed in an incubator to maintain sterility of the construct. Moreover, the proposed bioreactor, in addition to mimicking in vivo conditions, is highly flexible, allowing different types of constructs to be exposed to various physiological flow conditions. Initial verification of the hemodynamic parameters using Laser doppler anemometry indicated that the bioreactor performed well and produced the correct physiological conditions.     

Superior outcome of strut allograft-augmented plate fixation for the treatment of periprosthetic fractures around a stable femoral stem

Purpose

This study was designed to compare the outcome of two surgical approaches for treating femoral periprosthetic fractures around a stable femoral stem. The hypothesis was that plate fixation alone might be associated with a higher complication rate due to insufficient mechanical stability. We also considered that the addition of a strut allograft would contribute to fracture healing by means of osteoconduction.

Methods

We retrospectively assessed the outcome of 21 patients who sustained periprosthetic fractures around a total hip replacement system (Vancouver type B1 and type C fractures) and who were treated in our department (January 2006 and August 2011) either by plate fixation alone or by plate fixation and a strut allograft. The mean postoperative follow-up was 23 months (range 9–69 months). Eleven patients were treated by plate fixation alone (Plate Group), and 10 patients were treated by plate fixation and a deep frozen cortical strut allograft (AG Group). Functional outcome was rated by the Harris Hip scoring system. Postoperative radiographs were assessed for evidence of fracture union. Surgical failure was defined as any complication requiring surgical revision.

Results

The 21 patients included 17 females and 4 males. The average age was 79 years (range, 73–88) for the Plate Group and 82 years (range, 53–94) for the AG Group, and the average time to fracture union was 12 weeks (range, 2.5–6 months) and 12.95 weeks (range, 1.5–3) respectively. The overall failure rate was significantly higher in the Plate Group: 5 of them required revision surgery compared to none in the AG Group (p = 0.014).

Conclusion

The results of this analysis indicate that a strut allograft augmentation approach to Vancouver type B1 and type C periprosthetic fractures results in a better outcome than plate fixation alone by apparently adding mechanical stability and enhancing the biological healing process.     

Kidney Autotransplantation: Between the Past and the Future

Purpose of Review

The practice of kidney autotransplantation (KAT) has become an increasingly favorable approach in the treatment of certain renovascular, ureteral, and malignant pathologies. Current KAT literature describes conventional open procedures, which are associated with substantial risks. We sought to compare previously reported outcomes, evaluate common surgical indications, and assess associated risks and benefits of current KAT methods. A thorough evaluation and review of the literature was performed with the keywords “autologous transplantation” and “kidney.”

Recent Findings

Early outcomes of robotic KAT are encouraging and have been associated with fewer complications and shorter hospital stay, but require robotic technique proficiency.

Summary

KAT is an important method to manage selected complex urological pathologies. Robotic KAT is promising. Nevertheless, future studies should utilize larger patient cohorts to better assess the risks and benefits of KAT and to further validate this approach.

     

Visual internal urethrotomy for management of urethral strictures in boys: a comparison of short-term outcome of holmium laser versus cold knife

Purpose

To compare efficacy and safety of visual internal urethrotomy (VIU) using holmium laser (Ho:YAG) (group A) versus cold knife (group B) in children with urethral strictures. It may be the first comparative study on this issue in children.

Methods

This study compared Ho:YAG group, which was evaluated prospectively from January 2014 till January 2016, versus cold knife group, which was a historical control performed from March 2008 till February 2010. Children ≤ 13 years old with urethral strictures ≤ 1.5 cm were included successively. Recurrent cases, congenital obstructions and cases with complete arrest of dye in voiding cystourethrography were excluded. Scar tissue was incised at twelve o’clock. Outcome was compared using Student’s t, Mann–Whitney, Chi-square or Fisher exact tests as appropriate.

Results

Each group included 21 patients. Mean age was 6.27 ± 3.23 (2–13) years old. Mean stricture length was 1.02 versus 1 cm in group A versus B, respectively (p = 0.862). Ten cases of penile/bulbous strictures and another 11 cases of membranous strictures were found in each group. There was no significant difference between both groups in preoperative data. Success rate for initial VIU was 66.7% in group A versus 38% in group B (p = 0.064). This was associated with significantly higher Q_max in group A (mean 16.52 vs 12.09 ml/s; p = 0.03). Success rate after two trials of VIU was 76.2% for group A and 47.61% for group B (p = 0.057). No complications were reported in both groups.

Conclusion

Laser VIU has a higher success rate than cold knife VIU for urethral strictures ≤ 1.5 cm in children with significantly higher Q_max. Both are easy to perform, low invasive and safe.

     

Treatment of Melasma with Intralesional Tranexamic Acid Versus Cryotherapy

Background Melasma is a relatively common, acquired facial skin disorder of hyperpigmentation. Though it occurs in both sexes, nearly 90% of patients are female. It manifests as hyperpigmented macules and patches distributed symmetrically on the face, neck, and, rarely, the upper limbs. OBJECTIVE: The aim of this study was to evaluate and compare the clinical efficacy and adverse effects of intralesional injection of tranexamic acid (TA) versus cryotherapy in the treatment of melasma.MethodsPatients were divided into two groups: Group A and Group B. Group A comprised 28 patients aged 27 to 50 years. They received localized intralesional injections of TA. According to Wood’s light examination, patients were divided into two subtypes; 13 patients with mainly dermal-type melasma and 15 patients with mainly mixed-type melasma. Family history was obtained in 12 patients. Group B comprised 28 patients aged 29 to 46 years were included. They were treated with cryotherapy. According to Wood’s light examination, the patients were divided into two subtypes of melasma; 8 patients with mainly dermal-type melasma and 10 patients with mainly mixed-type melasma.ResultsThere were no statistically significant differences between Group A and Group B according to contraception, sun exposure, and family history. There was a statistically significant difference between Group A and Group B according to previous treatment. There was no statistically significant difference between the two groups according to drug allergy. There were no statistically significant differences according to systemic disease or general examination.ConclusionIntralesional tranexamic acid is a safe and effective method for the treatment of melasma with no risk of PIH, thrombosis, or bleeding; however, more sessions with longer follow-up periods are recommended, as the final response may take several months to occur. Cryotherapy was neither safe nor effective due to the risk of PIH.     

Radiological impact assessment to the environment due to waste from disposal of porcelain

The present study aimed to assess the radiological parameters from gamma rays due to the uncontrolled disposal of porcelain waste to the environment. Qualitative and quantitative identification of radionuclides in the investigated samples was carried out by means of a high-purity germanium (HPGe) detector. The average activity concentrations of the local porcelain samples were measured as 208.28?Bq/kg for ²²⁶Ra, 125.73?Bq/kg for ²³⁸U, 84.94?Bq/kg for ²³²Th and 1033.61?Bq/kg for ⁴⁰K, respectively. The imported samples had an average activity of 240.57?Bq/kg for ²²⁶Ra, 135.56?Bq/kg for ²³⁸U, 115.74?Bq/kg for ²³²Th and 1312.49?Bq/kg for ⁴⁰K, respectively. Radiological parameters and the radium equivalent Ra_eq for the investigated samples were calculated. The external and internal hazard indices, representative level index (I_γ), alpha index (I_α), and the exemption level (I_x), were estimated to be higher than the recommended value (unity), while the average activity concentrations for the studied samples were higher than recommended levels. In conclusion, we are concerned that disposal of porcelain in the environment might be a significant hazard.