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Background.Tertiary hyperparathyroidism continues to cause significant morbidity in patients with chronic renal failure. This is frequently resistant to medical management and may ultimately require a surgical parathyroidectomy. Recent studies have reported upon the technique of percutaneous ethanol ablation for both primary and tertiary hyperparathyroidism. In this study we report on a 5 year experience using ethanol injection and compare the results with surgical parathyroidectomy. [ABSTRACT FROM PUBLISHER]

Introduction: Iron deficiency is commonly encountered in haemodialysis (HD) patients and may be overcome by i.v. therapy. We have examined the percentage hypochromic red cells (%HRC) for predicting response to i.v. iron in subjects with a low serum ferritin. [ABSTRACT FROM PUBLISHER]

Aim.To investigate the relationship between serum albumin and extracellular fluid volume, as measured by multifrequency bioelectrical impedance, in stable patients treated by CAPD.Method.Fifty-nine stable CAPD patients were assessed. Serum albumin (bromocresol green) and CRP, age, dialysate to plasma (D/P) creatinine ratio, normalized protein catabolic rate (nPCR), daily urine and peritoneal protein losses, and extracellular fluid volume (Vecf) were measured in each patient. Vecf was calculated as a percentage of actual body weight (Vecf% ABW), of lean body mass derived from anthropometry (Vecf% LBM) and of total body water (Vecf% Vtbw). Comparisons between those with a normal serum albumin (37 g/l) and those with a low serum albumin (<37 g/l) were made by Mann-Whitney U test. Correlations with serum albumin were sought by Pearson's test. [ABSTRACT FROM PUBLISHER]

Arthrogryposis multiplex congenita (AMC) is considered a rare disorder resulting in multiple congenital contractures in two or more areas. Considerable literature is available on managing the contractures during an affected child's development but little information is available to those managing these ongoing issues in adulthood. Due to the heterogeneity etiological factors and presentation of AMC, and the small sample sizes of previous studies, it has been difficult to generalize results to the adult population. This current study presents the several steps taken to create an international AMC database for adults to populate with their own data over time. The methods included a scoping review of the literature for valid and reliable outcome measures used for AMC, a Delphi methodology to create the database with a team of clinicians, researchers and patients, a Beta testing of the database, and a final launch of the Adult AMC Registry. This registry includes 48 nonstandardized questions and 12 standardized questionnaires. It takes 35-45 min for a participant to complete. A shorter version will be created for participants to complete for years 2 and 3, followed by this longer version every 4 years. The protocol for referring English-speaking patients and access to the registry is provided. Data will be reviewed every year to ensure quality. The registry will be maintained for a minimum of 10 years and data will be comprehensively analyzed every 5 years. Our goal is to have 500 adults with AMC from around the world as participants., (© 2019 Wiley Periodicals, Inc.)

Arthrogryposis multiplex congenita (AMC) has been described and defined in thousands of articles, but the terminology used has been inconsistent in clinical and research communities. A definition of AMC was recently developed using a modified Delphi consensus method involving 25 experts in the field of AMC from 8 countries. Participants included health care professionals, researchers, and individuals with AMC. An annotation of the definition provides more in-depth explanations of the different sentences of the AMC definition and is useful to complement the proposed definition. The aim of this study was to provide an annotation of the proposed consensus-based AMC definition. For the annotation process, 17 experts in AMC representing 10 disciplines across 7 countries participated. A paragraph was developed for each sentence of the definition using an iterative process involving multiple authors with varied and complementary expertise, ensuring all points of view were taken into consideration. The annotated definition provides an overview of the different topics related to AMC and is intended for all stakeholders, including youth and adults with AMC, their families, and clinicians and researchers, with the hopes of unifying the understanding of AMC in the international community., (© 2019 The Authors American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals, Inc.)

Background: Essential genes are critical for the development of all organisms and are associated with many human diseases. These genes have been a difficult category to study prior to the availability of balanced lethal strains. Despite the power of targeted mutagenesis, there are limitations in identifying mutations in essential genes. In this paper, we describe the identification of coding regions for essential genes mutated using forward genetic screens in Caenorhabditis elegans. The lethal mutations described here were isolated and maintained by a wild-type allele on a rescuing duplication., Results: We applied whole genome sequencing to identify the causative molecular lesion resulting in lethality in existing C. elegans mutant strains. These strains are balanced and can be easily maintained for subsequent characterization. Our method can be effectively used to analyze mutations in a large number of essential genes. We describe here the identification of 64 essential genes in a region of chromosome I covered by the duplication sDp2. Of these, 42 are nonsense mutations, six are splice signal mutations, one deletion, and 15 are non-synonymous mutations. Many of the essential genes in this region function in cell cycle, transcriptional regulation, and RNA processing., Conclusions: The essential genes identified here are represented by mutant strains, many of which have more than one mutant allele. The genetic resource can be utilized to further our understanding of essential gene function and will be applicable to the study of C. elegans development, conserved cellular function, and ultimately lead to improved human health.

Post-mortem examination of a female homicide victim suggested a fracture of the larynx and increased flexibility, without associated hemorrhage, of the hyoid bone. There was a history of domestic violence, which included an allegation of attempted strangulation. Microscopy confirmed a recent fracture of the larynx and showed evidence of a healing fracture in the hyoid bone. Death was due to multiple blunt force trauma, including pressure to the neck. The deceased's partner admitted strangulation and was convicted of murder. The discussion concentrates on causation of laryngo-hyoid fractures and the potential usefulness of microscopy, particularly identifying evidence of previous trauma.

The principal aims of this retrospective study were to assess the prevalence and causes of laryngo-hyoid fractures found in coroners' adult postmortem examinations over a five-year period. In 78 of 1930 cases (4%), there was a fracture of the larynx (thyroid or cricoid cartilage) or hyoid bone. The thyroid cartilage alone was fractured in 38 cases; the hyoid bone alone was fractured in 19 cases; the larynx and hyoid bone were both fractured in 21 cases, including one which involved the cricoid cartilage. There was no evidence of surface injury to the neck in 14.1% of cases. The majority (44/78; 56.4%) involved classical manual or ligature 'pressure to the neck', i.e. hanging (32) or strangulation (12) but a significant minority (35.9%) involved other circumstances: road/rail traffic collision (12; 15.4%); falls (6; 7.7%); assaults involving blunt force trauma to the head and neck (4; 5.1%); incised wounds (3; 3.8%); gunshot wounds (2; 2.6%); and explosion (1; 1.3%). The circumstances of death and cause of fracture(s) were 'unascertained' in four cases (5.1%). Postmortem artefact accounted for two cases (2.6%).

No study has investigated the participation of Ly6C(+) monocytes in the earliest phase of skin infection with the mosquito-borne West Nile virus. In a novel murine model mimicking natural dermal infection, CCL2-dependent bone marrow (BM)-derived monocyte migration, differentiation into Ly6C(+) dendritic cells (DC), and accumulation around dermal deposits of infected fibroblasts by day 1 postinfection were associated with increasing numbers of monocyte-derived TNF/inducible NO synthase-producing DC by day 2 postinfection in draining auricular lymph nodes (ALN). Adoptive transfer demonstrated simultaneous migration of bone marrow-derived Ly6C(lo) monocytes to virus-infected dermis and ALN, where they first become Ly6C(hi) DC within 24 h and then Ly6C(lo) DC by 72 h. DC migration from the infected dermis to the ALN derived exclusively from Ly6C(lo) BM monocytes. This demonstrates that Ly6C(hi) and Ly6C(lo) BM-derived monocytes have different fates in vivo and suggests that BM may be a reservoir of preinflammatory monocytes for rapid deployment as inflammatory DC during virus infection.

A 62-year-old male with no significant medical history developed thromboembolic complications in the lower limbs shortly after an assault which involved punching and kicking to the trunk. Laparotomy revealed intra-abdominal injuries and an abdominal aortic aneurysm. Death from multi-organ failure and sepsis occurred 9 days post-injury. The discussion concentrates on blunt force trauma to the abdominal aorta, specifically on causation, mechanisms of injury and complications.

An 83-year-old man was admitted to hospital with a general decline in health, including deteriorating ability to swallow. He was not managing sufficient oral intake to meet his daily nutritional requirements, so had a percutaneous endoscopic gastrostomy (PEG) tube inserted for long-term feeding. Following the procedure he became shocked, and was unresponsive to aggressive fluid resuscitation. He died approximately 7 h after the PEG tube insertion. A postmortem examination revealed 2.5 litres of blood and bloodstained fluid within the abdominal cavity and a haemorrhagic pancreas. Microscopy of the pancreas showed a defect in a small to medium-sized artery, likely to be a branch of the splenic artery. The cause of death (as per section 1 of the death certificate) was (1a) intra-abdominal haemorrhage, (1b) pancreatic trauma at PEG feeding tube insertion and (1c) dysphagia due to cerebrovascular disease.

The authors report a case of fatal peritonitis due to small bowel perforation in a 21-month-old female child. Necropsy excluded natural disease and a thorough Coronial investigation concluded that an accidental fall onto a "doorstop" caused the bowel injury. The investigative findings are presented; the discussion address issues of diagnosis and causation/mechanism of injury.

Objective: To transform a pharmaceutical mathematics course to a self-paced instructional format using Web-accessed databases for student practice and examination preparation., Design: The existing pharmaceutical mathematics course was modified from a lecture style with midsemester and final examinations to a self-paced format in which students had multiple opportunities to complete online, nongraded self-assessments as well as in-class module examinations., Assessment: Grades and course evaluations were compared between students taking the class in lecture format with midsemester and final examinations and students taking the class in the self-paced instructional format. The number of times it took students to pass examinations was also analyzed., Conclusions: Based on instructor assessment and student feedback, the course succeeded in giving students who were proficient in pharmaceutical mathematics a chance to progress quickly and students who were less skillful the opportunity to receive instruction at their own pace and develop mathematical competence.

Amplified fragment length polymorphism (AFLP) was applied to 35 and 34 isolates, respectively, of Salmonella enterica serovar Typhimurium phage types DT 9 and DT 135, using eight primer pair combinations. Eight and 17 AFLP types were observed in DT 9 and DT 135, respectively. DT 9 is rare in the UK and common in Australia, but one AFLP form dominated with 28 isolates, comprising 22 of 25 UK isolates, four of five Australian isolates, one Jamaican and one Spanish isolate. Of the others, two UK isolates are closely related to the major form, two from elsewhere are in the major cluster and three isolates from different countries are in a separate cluster. For DT 135, two closely related AFLP types of seven and 11 isolates form the major cluster, which also includes 11 isolates, mostly in single-isolate AFLP types, while five isolates from different countries form a well-separated minor cluster. For both DTs all isolates are grouped together if only the phage type specific bands identified earlier are used, confirming their value for molecular-based 'phage typing'. Polymorphic markers identified in this study could also be used for subtyping within both phage types. The value of AFLP is in locating DNA fragments useful for typing, but implementation of a replacement typing scheme would probably involve multiplex PCR or microarray technologies.

We assessed the relationship of certain clinical variables (including bradykinin [BK] release and dialysis membrane) to initial mean arterial pressure (MAP) reduction in 47 patients requiring continuous renal replacement therapy (CRRT) in an intensive care unit. The pretreatment MAP was 84 +/- 14 mm Hg for the group as a whole. The initial MAP reduction was 11.5 (7-20) mm Hg, occurring 4 to 8 min after connection. MAP reduction was 9 (6-15) mm Hg with polyacryonitrile (PAN) membranes versus 14 (5-19) mm Hg with polysulfone (PS) (not significant). There were positive correlations between MAP reduction and BK concentration at 3 (BK3; r = 0.58, p < 0.01) and 6 (BK6; r = 0.67, p < 0.001) min with PAN but not with PS. A greater reduction in MAP was seen in patients who were not receiving inotropic support (Mann-Whitney test, p < 0.01). BK3 and BK6 values for the PAN and PS groups were not significantly different. However, BK concentrations greater than 1,000 pg/ml were only seen with PAN (6 patients, MAP reduction 27 [17-31] mm Hg). There were positive (albumin) and negative (age; acute physiology, age, and chronic health evaluation score; C-reactive protein [CRP]; calcium) correlations with BK3/BK6 in the PAN and PS groups, some of which (albumin, CRP) reached statistical significance. In summary, MAP reduction at the start of CRRT correlates with BK concentration. The similarity of response with PAN and PS suggests an importance for other clinical factors. In this study, hemodynamic instability was more likely in patients with evidence of a less severe inflammatory or septic illness.

Two examples of hereditary nephropathy within the context of clinical syndromes are described. Emphasis is put on the ability to make a renal diagnosis without renal biopsy and the benefits of screening relatives once a diagnosis is achieved. A variant of Alport's syndrome with associated macrothrombocytic thrombocytopenia, known as Epstein's syndrome, is reported. In addition siblings with Alström's syndrome characterized by pigmentary retinal degeneration (causing blindness in early childhood), progressive sensorineural hearing loss, and progressive renal failure are reported. Both cases had previously presented for non-renal pathology in advance of the onset of symptomatic renal failure and may have benefited from appropriate screening.

Introduction: Iron deficiency is commonly encountered in haemodialysis (HD) patients and may be overcome by i.v. iron therapy. We have examined the percentage hypochromic red cells (%HRC) for predicting response to i.v. iron in subjects with a low serum ferritin., Methods: Prospective study of i.v. iron saccharate (trivalent iron 200 mg/week for 8 weeks) in anaemic (Hb < 10 g/dl) HD patients with serum ferritin < 100 microg/l despite oral iron therapy. Response to i.v. iron was assessed by comparing Hb at 0 and 8 weeks according to %HRC at baseline (0-3%, 4-9%, > or = 10%). Results are mean+/-1 SD., Results: For all subjects (n=82), Hb and ferritin increased between 0 and 8 weeks (8.9+/-1.0 to 10.1+/-1.4, P<0.0001; 55+/-24 to 288+/-126, P<0.0001). Patients were stratified into three groups according to %HRC at baseline (0-3%, 4-9%, > or = 10%). Hb increased significantly in all three groups. The mean increase in Hb was greater (0-3%, 0.6+/-1.2; 4-9%, 1.2+/-1.0; > or = 10%, 1.6+/-1.4; P=0.02) and the proportion of patients showing a > or = 1 g/dl increase in Hb was greater (0-3%, 27%; 4-9%, 57%; > or = 10%, 67%; P=0.02) in those with the largest %HRC pre-treatment., Conclusion: Intravenous iron therapy is effective in improving Hb in anaemic HD patients with a low ferritin. However, the magnitude of this response and the proportion of patients responding is related to the percentage hypochromic red cells prior to treatment.

Scotland and England are part of the United Kingdom but have separate legal systems. These legal differences have a substantial effect on forensic pathology practice, and are probably best appreciated by those pathologists who have worked on both sides of the border. This paper seeks to highlight the differences in forensic pathology practice between Scotland and England, discussing the investigation of death in both countries. It concludes that a knowledge of the Scottish procurator fiscal system of death investigation may be beneficial to those contemplating changes to the coroner system. All three authors have practised forensic pathology in Scotland and England or Wales.

There are structural and functional changes which take place in the kidney with age. These changes have an impact on patient management, particularly with respect to drug therapy. It is unlikely that glomerulonephritis is less common in the elderly, and any apparent difference with respect to younger patients most likely reflects clinical practice rather than any inherent difference in the aged kidney. Tubulointerstitial nephritis may be more common and is most likely linked to drug therapy. The management of end-stage renal failure in the elderly should not be significantly different from that in younger patients and should be based on the capacity for rehabilitation rather than any arbitrary age.

Synthetic membranes are not identical and have specific interactions that may be harmful or beneficial. We have investigated the incidence of hypotension and the outcome of acute renal failure (ARF) in ventilated patients treated by continuous venovenous dialysis with 2 different synthetic membranes. In Study 1, the mean arterial pressure (MAP) and systemic vascular resistance (SVR) were monitored during the first 12 min of dialysis with polyacrylonitrile (PAN). In Study 2, the MAP and survival rates were compared in patients randomly assigned to either PAN or polysulfone. No subjects were receiving angiotensin converting enzyme inhibitors. In Study 1, the MAP decreased due to a reduction in the SVR during the first 6 min of dialysis but returned to the baseline value by 12 min in 22 patients during 27 dialysis treatments. In Study 2, the MAP was lower than the baseline value at 6 min during 233 dialysis treatments in 133 patients randomly assigned to PAN or polysulfone membranes (PAN group, 81.5 +/- 15 to 78.7 +/- 15.6 mm Hg, p = 0.001; and polysulfone group, 81.3 +/- 15.4 to 80.0 +/- 15.7 mm Hg, p = 0.06). Severe reductions in the MAP were seen during 13.2% of the PAN and 7.2% of the polysulfone treatments (chi 2, p = NS). The age, APACHE II score, MAP, inotrope requirement, and primary diagnosis did not differ according to membrane material in a total of 197 consecutive patients (PAN, n = 97; polysulfone, n = 100). Patients survival was 29% (PAN) and 27% (polysulfone). In multivariate analysis, APACHE II score, inotrope requirement, and liver failure were significant determinants of survival. In conclusion, PAN and polysulfone membranes were not different with respect to hypotensive reactions or survival in critically ill patients undergoing continuous venovenous hemodialysis.