Genetic and biochemical background of chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency syndrome caused by a profound defect in the oxygen metabolic burst machinery. Activity of NADPH oxidase is absent or profoundly diminished, as at least one of its components (gp91(phox), p22(phox), p47(phox) and p67(phox)) is lacking or non-functional. This review explains the molecular basis of NADPH oxidase dysfunction by the effects of mutations in genes coding for particular oxidase components. Among the four types of CGD, the most common is X-linked CGD (approximately 65%), with defects in the CYBB gene encoding gp91(phox). A wide spectrum of mutations has been described in the CYBB gene with no predominant genotype. The second most common subtype of CGD caused by NCF1 mutation accounts for 30% of CGD patients and is inherited in an autosomal recessive manner, with predominance of a homozygotous deltaGT deletion in the genotype. The other two CGD subtypes having an autosomal recessive pattern together account for no more than 10% of CGD cases. A strategy for the molecular diagnostics in CGD patients is proposed and principles of genetic counseling are discussed here.     

Knowledge and Attitudes of Health Care Professionals and Laypeople in Relation to Brain Death Diagnosis and Organ Donation in Hungary: A Questionnaire Study

ObjectivesThe aim of the present work was to assess the knowledge and attitudes of different health care workers and laypeople toward the donation and transplantation procedure.Subjects and methodsA survey consisting of questions regarding brain death diagnosis, legal organization or organ donation, and the transplantation procedure were sent to participants: 56 intensive care unit (ICU) doctors, 76 ICU nurses, 188 sixth-year medical students, and 320 general practitioners (GPs). Laypeople were also asked to complete the survey.ResultsThe majority of participants reported being aware of legal regulations for organ donation in Hungary (88.5%). Roughly 25% of GPs and 60% of laypeople were unaware of the opt-out system effective in the country. Less than one-third of ICU physicians (26.9%) and nurses (34.7%) were able to list the organs that may be transplanted from a deceased donor; GPs (22.4%) and medical students (20%) performed even worse on this item. The willingness of ICU specialists (57%) and ICU nurses (45%) to support donating their own organs was moderate.ConclusionsThe results of this survey indicate a need for graduate and postgraduate education and regular teaching programs regarding organ donation and transplantation. More active use of modern media is proposed to improve public awareness and acceptance of organ donation.     

Association of photobiomodulation therapy (PBMT) and exercises programs in pain and functional capacity of patients with knee osteoarthritis (KOA): a systematic review of randomized trials

Lasers in Medical Science - Knee osteoarthritis (KOA) is a common degenerative disease in which several treatments and treatment associations have been investigated. This review analyzed the...     

Parathyroid Carcinoma: A Single-Institution Experience with an Emphasis on Histopathological Features

Parathyroid carcinoma (PC) is a rare malignancy that poses a diagnostic challenge on histologic examination. We analyzed various clinicopathologic features of PC. Pathology reports and slides were reviewed to evaluate the diagnostic histopathologic features of archived cases of PC from the years of 2004–2018. The study cohort comprised twenty cases of PC. The median age was 49 years (range 21–73 years) with equal gender distribution (M:F = 1:1). Most patients presented with symptoms of hypercalcemia (n = 7, 54%). Serum calcium and serum parathyroid hormone were elevated in all but one patient. The right inferior parathyroid was commonly involved (n = 8/14, 57%). The mean tumor size was 2.4 cm (range 0.8–3.5 cm). On frozen section examination, PC was diagnosed in 8 out of 9 cases. Vascular (n = 19/20, 95%) and soft tissue invasion (n = 10/20, 50%) were the most common characteristic histologic findings. Capsular invasion was identified in all cases. Perineural invasion or metastasis at presentation was absent in all cases. Other histological features noted were intratumoral fibrous bands (70%), nodular growth pattern (70%), moderate nuclear atypia (30%), prominent nucleoli (20%), and necrosis (20%). Regional lymph nodes were negative for metastatic disease in all cases (n = 10). Eight out of 16 patients received adjuvant radiotherapy. Follow-up was available in 16 cases (median 21.5 months). Two patients died of disease. Vascular and soft tissue invasion are the most common diagnostic histologic features of PC. Capsular invasion is important to distinguish PC from its benign counterparts. Intraoperative frozen section examination can be used for accurate diagnosis and surgical management.     

How Stigma Toward Anal Sexuality Promotes Concealment and Impedes Health-Seeking Behavior in the U.S. Among Cisgender Men Who Have Sex with Men

Archives of Sexual Behavior - Gay, bisexual, and other men who have sex with men (MSM) experience alarming HIV disparities alongside sub-optimal engagement in HIV interventions. Among MSM, stigma...     

Atrial natriuretic peptide (ANP) attenuates brain oedema accompanying experimental subarachnoid haemorrhage

Summary The effects of centrally administered atrial natriuretic peptide (ANP) on the brain water and electrolyte contents were investigated in a rodent subarachnoid haemorrhage (SAH) model. SAH caused statistically significant increases in the brain sodium and water contents, while the potassium content did not change significantly, indicating that the brain oedema could be classified as having a primarily vasogenic component. Two g or 5 g of rat ANP administered into the lateral ventricle at the time of SAH induction statistically significantly decreased the water and sodium accumulation measured 90 minutes following SAH. The same treatment did not inhibit development of brain oedema measured 3 hours following SAH. However, when 5 g of ANP was administered intraventricularly at the time of SAH induction and also 90 minutes later, the brain oedema 3 hours following SAH was again reduced statistically significantly. These effects of ANP were found not to be mediated by primary changes in serum osmolality and electrolyte concentrations.The present results confirm that centrally administered ANP may act directly on the central nervous system to inhibit brain water and sodium accumulation in SAH-induced brain oedema. The potentials of influencing the central neuro-endocrine system as a novel way of the treatment of brain oedema are discussed.Supported by Grant OTKA I/3 2728 and ETT T110/ 1990.     

Corneal arcus and life expectancy

In 1964-66, the authors completed the comprehensive medical screening of 1412 persons. Apart from the indicators of health state they also recorded their social and cultural parameters. The diagnoses they registered included AC, which has been covered in literature in rather contradicting ways. They found no data concerning survival; as analysing such a correlation is only possible within the frame-work of a several-decade follow-up study. By the end of the follow-up stage (31:12:1994), after 30 years, 1375 persons had died. Their death certificates and--if there were any--necropsy records have been processed and thoroughly analysed. They examined the occurrence of AC, life duration and survival probability--all in correlation with age, gender, constitution, certain diseases (hypertonia, ostheoarthrosis) and diagnoses at death (ischaemic heart diseases, acute myocardiac infarction, cerebrovascular diseases). They point it out that the occurrence of AC is significantly higher among males, but it increases in strong correlation with age in both sexes. Those who had AC were found to be older at the time of death, but it doesn't mean that AC correlates with better life expectancy--it means that AC occurs at older age. The survival probability of men over 75 was better than that of women. On the whole, AC is unfavourable concerning life expectancy, but the later it occurs, the less it can be used as an indicator of life expectancy. It was found that greater average weight correlated with longer average life duration, while among females the more a person weighed, the less frequent AC became. It was true for each weight group that those with AC had worse life expectancy. Altogether those with no AC were found to suffer from hypertonia significantly more frequently. The life expectancy of those with both AC and hypertonia, however, was always worse than those with hypertonia only, regardless of age and the type of hypertonia. Generally women are in a more favourable position, but in the 'serious' and 'very serious' hypertonia groups there is practically no difference in the survival of the two sexes. The authors have also found that AC has a significant negative prognostical value concerning survival and correlation with ostheoarthrosis, ischaemic heart diseases and cerebrovascular diseases. The correlation of AC with acute myocardiac infarction could not be proved convincingly.     

Trochanteric Osteotomy for Total Hip Arthroplasty: Six Variations and Indications for Their Use

Trochanteric osteotomy of the femur in total hip replacement used to be a simple, stereotyped technique and was declining in frequency of use. Many variations in the technique have evolved recently, including the trochanteric slide and the extended trochanteric osteotomy, which have increased the flexibility and utility of trochanteric osteotomy and the frequency of its application. The authors describe six trochanteric osteotomies and discuss the indications for their use.     

Measurement of lymphocyte activation by a chromatin topo-optical reaction

Summary A rapid inexpensive method is presented for detecting peripheral blood lymphocyte chromatin activation by the neutral red topo-optical reaction, which causes strong and easily measurable birefringence in the lymphocyte nuclei. This reaction can be enhanced by fixing the cells with 150 mM/l NaCl in 70% ethanol and/or by treating the unfixed cellular suspensions with 0.2 M/l HCl to remove histones. In histone-removed preparations, 30 min DNase I treatment almost completely abolished the birefringent reaction, whereas RNase treatment resulted in only 18% loss.Chromatin activation induced by enzyme inhibition increased chromatin birefringence significantly. The same phenomenon could be induced in sensitive subjects' lymphocytes by specific antigens or haptens much more rapidly. The monocytes were not activated to a significant extent. In non-sensitive subjects different kinetics of antigen or hapten-dependent activation and no cytotoxic effects have been observed. Depletion of T-lymphocytes in vivo in SLE patients or by in vitro treatment with 0.5 mM/l KCN as well as with 0.02% trypsin has caused a significant drop in the mean chromatin birefringence. The effect of trypsin was reversible.