A homozygous missense variant in the WRN gene segregating in a family with progressive pulmonary failure with recurrent spontaneous pneumothorax and interstitial lung disease

Interstitial lung disease (ILD) is a condition affecting the lung parenchyma by inflammation and fibrosis and can be caused by various exposures, connective tissue diseases (CTD), and genetic disorders. In this report, a family with five patients having progressive respiratory failure that begins with coughing in adolescence, followed by dyspnea and recurrent spontaneous pneumothorax, and death in early adulthood is presented. The patients were diagnosed to have ILD through clinical and radiological evaluations. Molecular genetic analyses of the family provided two homozygous rare variants in the WRN and SFXN5 genes, co-segregating with the phenotype. The network analyses pointed out that the variant in the WRN, rather than that in the SFXN5 gene, could be the main factor in the existence of the ILD phenotype, putatively through the altered DNA repair and telomere maintenance pathways. In silico analyses suggested that the variant could affect the exonuclease activity or the stability of the WRN protein. Moreover, the adolescent-onset pulmonary phenotype described in the case has not been reported in Werner Syndrome, the only disease known to be associated with biallelic WRN pathogenic variants. Thus, the present phenotype could be either a very atypical presentation of Werner syndrome or a new clinical entity associated with the WRN gene.     

Effect of low level laser therapy and zoledronate on the viability and ALP activity of Saos-2 cells

A limited number of clinical studies indicate the supportive role of low level laser therapy (LLLT) on medical and/or surgical approaches carried out in treatment modalities for bisphosphonate related necrosis of jaws (BRONJ), the most common side effect of bisphosphonates used to inhibit bone resorption. The purpose of this study was to investigate the effects of LLLT on cell proliferation and alkaline phosphatase (ALP) activity of human osteoblast-like cells (Saos-2) treated with different doses of zoledronate, the most potent bisphosphonate. Saos-2 cells were treated with different concentrations of zoledronate and were irradiated with diode laser (wavelength 808 nm, 10 s, 0.25 or 0.50 W). Cell numbers and ALP activity of the cells were determined. LLLT mildly increased the proliferation rate or ALP activity, while zoledronate reduced both. When applied together, LLLT lessened the detrimental effects of zoledronate and improved cell function and/or proliferation. Based on the results of this study, it was concluded that LLLT has biostimulative effects on Saos-2 cells, even after treatment with zoledronate. LLLT may serve as a useful supportive method for BRONJ treatment through enhancement of healing by osteoblasts.     

A neonate with homozygous protein C deficiency with a homozygous Arg178Trp mutation

Homozygous protein C deficiency affects approximately 1/400,000 to 1/1,000,000 live births. Homozygous protein C deficiency is associated with catastrophic and fatal purpura fulminans-like or thrombotic complications and disseminated intravascular coagulation. In the present patient, genetic study revealed Arg178Trp, a mutation found widely in European population; but this is the first case of homozygous Arg178Trp mutation who suffered from catastrophic purpura fulminans phenotype.     

Does Helicobacter pylori infection play a role in lung cancer?

BACKGROUND: Helicobacter pylori infection is a world-wide common disease and leads to many gastrointestinal and respiratory illnesses. It is suggested that one of these respiratory illnesses is lung cancer. METHODS: Forty-three patients with non-small cell lung cancer and 28 control subjects have been included to this study. H. pylori status of the patients and controls was determined by immunoblot for the detection of IgG (RIDA Blot Helicobacter). All subjects were examined to evaluate the presence of VacA and CagA gene. RESULTS: Seropositivity of anti H. pylori IgG was significantly higher in cancer patients than in control groups, 40 (93%) and 12 (42%), respectively (P<0.01). Although both VacA and CagA seropositivity was high in lung cancer patients, only VacA positivity was statistically significant when compared with control subjects, 35 (81%) and 11 (42%), respectively (P<0.05). CONCLUSION: H. pylori infection may be associated with development of lung cancer.     

EORTC QLQ-C30 assessment in Turkish patients with hematological malignancies

We aimed to evaluate the prevalences of self-reported anxiety and depression symptoms in hematological malignancy patients and to determine the association between the presence of these disorders and the results of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30). One hundred and forty patients with a diagnosis of a hematological malignancy completed the Hospital Anxiety and Depression Scale (HADS) and the General Health Questionnaire. Patients with higher anxiety scores were more frequently inpatients, had higher EORTC general symptom scores, and they had lower cognitive, emotional, social functioning and global quality of life (QoL) scores (all p values <0.05). Patients with higher depression scores had more frequently active disease and were inpatients; they had higher mean Eastern Cooperative Oncology Group performance scores, EORTC gastrointestinal system and general symptom scores, and significantly lower physical, role, emotional, social and cognitive functioning and global QoL scores (all p values <0.01). During follow-up, it was observed that survival curves of patients with active disease who had higher HADS depression scores tended to be shorter than those with lower scores (p = 0.1). Anxiety and depression are frequent in hematological malignancy patients and associated with poor QoL and performance status. In addition, the presence of self-reported depression might have a predictive value for poor prognosis.     

High-dose thiotepa,melphalan and carboplatin (TMCb) followed by autologous stem cell transplantation in patients with advanced breast cancer: a retrospective evaluation

This study was conducted to evaluate the efficacy of high-dose thiotepa, melphalan and carboplatin (TMCb) regimen in 27 patients undergoing autologous stem cell transplantation (ASCT) for metastatic breast cancer. A total of 27 patients with stage IV breast cancer underwent ASCT following thiotepa (500 mg/m(2)), melphalan (100 mg/m(2)) and carboplatin (1200-1350 mg/m(2)). Of 27 patients, 17 had refractory relapse, eight had responding relapse, and two had no evidence of disease (NED) at the time of transplant. In all, 11 patients had only bone disease, nine had bone plus visceral disease, three had only visceral disease, and two had locoregional recurrent disease. The median time from diagnosis to transplant was 1081 days (range 180-2341). Staging for evaluation of response was performed 4-6 months after transplantation. Five patients were not evaluable (NE) for response because of NED at transplant (n=2) or early death due to transplant-related complications (n=3) (two of viral pneumonia and one of regimen-related toxicity) occurring at a median of 4 days (range 11-46) post-transplant. One of the two patients who was NED at the time of transplant is still NED on day 760 post-transplant. Seven of 15 refractory (47%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft-tissue disease with at least improvement in bone lesions. Of 27 patients (37%),(10) are alive and progression-free, a median of 582 days (range 410-1380) after treatment, 6/17 (35%) with refractory disease and 4/10 (40%) with responsive disease. The probability of progression-free survival (PFS) for all patients was 0.50. The probabilities of PFS at 2 years for patients with refractory (n=17) and responsive (n=10) disease were 0.42 and 0.60, respectively. PFS at 2 years for the 14 patients who were NED or achieved CR/PR(*) following-HDC was 0.67. PFS at 2 years for patients who did not achieve CR/PR(*) following-DHC was 0.33. These preliminary data suggest that high-dose TMCb followed by autologous stem cell transplantation is an effective regimen for patients with advanced breast cancer and may be comparable to some previously used regimens.     

Comparison of SPECT findings and neuropsychological sequelae in carbon monoxide and organophosphate poisoning

Abnormal regional cerebral blood flow in patients with acute carbon monoxide (CO) and organophosphate (OP) poisoning was examined using (99m)Tc-hexamethylpropylene amine oxime (HMPAO) brain single photon emission computed tomography (SPECT) in fourteen patients. We evaluated the predictive significance of acute phase brain SPECT findings for long-term neuropsychological sequelae. Changes were found in the frontal, temporal, parietal lobes within the first week after both types of poisoning. The distribution of the hypoperfused cerebral areas as demonstrated by (99m)Tc-HMPAO imaging was similar in the two groups during the acute phase. Neuropsychological sequelae developed in five patients poisoned with OP and six with CO. Patients who had SPECT findings heterogeneously or in the temporal or frontal lobes displayed disorientation. Those with fronto-parietal and frontal lobe changes displayed mental confusion. Parkinsonism also was observed in patients with parieto-occipital, parietal and frontal lobe lesions. The distribution of these lesions appears to predict the long term sequelae of these poisonings, though additional studies with larger numbers of patients are needed to confirm the role of SPECT imaging in both OP and CO poisonings.