The rotating contact glass holder

A rotating contact lens holder for the three-mirror Goldmann lens permits circular examination of the fundus or chamber angle without having to change the position of the fingers on the edge of the lens. The contact lens holder consists of an outer polygonal ring hold by the thumber and index finger. An inner rotating ring holds the contact lens. Continuous rotation of the contact lens is performed with the free middle Finger. This device permits circular examination of the retina without interruption of fixation. The instrument improves not only the speed but also the reliability of the examination.     

Increased salt retention and hypertension from non-steroidal agents in the elderly

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.      

Imaging of thoracic aortic dissection

Acute thoracic aortic dissection has a high mortality if untreated, so the diagnosis must be rapidly made if mortality is to be lowered significantly. Multiple imaging techniques are often used. This retrospective study from 1988 to 1993 assesses the usefulness in diagnosis of chest X-rays, computed tomography (CT) scanning, aortography, magnetic resonance imaging (MRI), trans-thoracic (TTE) and trans-oesophageal (TOE) echocardiography. Forty-two patients with a final clinical diagnosis of dissection were studied. The diagnosis was confirmed in 16 (13 at surgery and three at autopsy). Three died with dissection given as the only cause for death. Chest X-ray abnormalities were seen in all 19 patients with surgery or death from dissection, with a widened mediastinum and/or dilated aorta being present in 17. In the group of 16 patients with surgery or autopsy proof, CT scans found dissections in 9 of 12 patients studied and correctly classified the type in only five. Aortography was performed in five, with accurate depiction of dissection and type in all. TTE found dissections in three of eight patients imaged by this method. MRI and TOE were performed each on two patients, with accurate depiction of dissection and type in each. Because of the relatively low sensitivity of CT scanning in defining aortic dissections Westmead Hospital is currently assessing the use of TOE as the prime imaging modality prior to surgical intervention.     

Sentinel Bleeding After Pancreaticoduodenectomy: A Disregarded Sign

Introduction Delayed massive hemorrhage induced by pancreatic fistula after pancreaticoduodenectomy is a rare but life-threatening complication. The purpose of this study was to analyze the clinical course of patients with late hemorrhage, with or without sentinel bleeding, to better define treatment options in the future. Material and Methods From April 1998 to December 2006, 189 pancreaticoduodenectomies were performed. Eleven patients, including two patients referred from other hospitals, were treated with delayed massive hemorrhage occurring 5 days or more after pancreaticoduodenectomy. Sentinel bleeding was defined as minor blood loss via surgical drains or the gastrointestinal tract with an asymptomatic interval until development of hemorrhagic shock. The clinical data of patients with bleeding episodes were analyzed retrospectively. Results Eight of the 11 patients had sentinel bleeding, and seven of them had it at least 6 h before acute deterioration. Seven out of 11 patients died, five out of eight with sentinel bleeding. No differences could be detected between patients with or without sentinel bleeding before delayed massive hemorrhage. The only difference found was that non-surviving patients were significantly older than surviving patients. Delayed massive hemorrhage is a common cause of death after pancreaticoduodenostomy complicated by pancreatic fistula formation. The observation of sentinel bleeding should lead to emergency angiography and dependent from the result to emergency relaparotomy to increase the likelihood of survival.     

A double mutant [N543H+2393del9] allele in the LDL receptor gene in familial hypercholesterolemia: effect on plasma cholesterol levels and cardiovascular disease

Familial hypercholesterolemia is a genetic disorder caused by mutations in the LDL receptor gene. During a survey of mutations of LDL receptor gene in Spanish FH patients we found two mutations in the same allele: a missense N543H mutation in exon 11 and a 9bp inframe deletion (2393del9) located in exon 17. This double mutant allele was founded in 10 out of 458 unrelated patients: one homozygous FH [N543H+2393del9] + [N543H+2393del9], one compound heterozygote [N543H+2393del9] + [W-18X+E256K] and 8 heterozygotes. Flow cytometric analysis showed a defective LDL binding (20% of normal value) and internalization (23%) in lymphocytes from the homozygous patient; furthermore, studies of mitogen-stimulated lymphocytes demonstrated that the ability of LDL to support cell proliferation was impaired. Unexpectedly, not all carriers of the double mutant allele develop hypercholesterolemia and, furthermore, cholesterol-lowering treatment of the homozygous patient resulted in a 58% LDL cholesterol reduction. In conclusion, the phenotypic expression in the homozygous and heterozygous patients presented here, as well as the LDL-receptor residual activity, allowed the classification of this mutation as mild extending the group of mild mutations found at homozygosity.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Metrics and tools for consistent cohort discovery and financial analyses post-transition to ICD-10-CM

In the United States, International Classification of Disease Clinical Modification (ICD-9-CM, the ninth revision) diagnosis codes are commonly used to identify patient cohorts and to conduct financial analyses related to disease. In October 2015, the healthcare system of the United States will transition to ICD-10-CM (the tenth revision) diagnosis codes. One challenge posed to clinical researchers and other analysts is conducting diagnosis-related queries across datasets containing both coding schemes. Further, healthcare administrators will manage growth, trends, and strategic planning with these dually-coded datasets. The majority of the ICD-9-CM to ICD-10-CM translations are complex and nonreciprocal, creating convoluted representations and meanings. Similarly, mapping back from ICD-10-CM to ICD-9-CM is equally complex, yet different from mapping forward, as relationships are likewise nonreciprocal. Indeed, 10 of the 21 top clinical categories are complex as 78% of their diagnosis codes are labeled as “convoluted” by our analyses. Analysis and research related to external causes of morbidity, injury, and poisoning will face the greatest challenges due to 41 745 (90%) convolutions and a decrease in the number of codes. We created a web portal tool and translation tables to list all ICD-9-CM diagnosis codes related to the specific input of ICD-10-CM diagnosis codes and their level of complexity: “identity” (reciprocal), “class-to-subclass,” “subclass-to-class,” “convoluted,” or “no mapping.” These tools provide guidance on ambiguous and complex translations to reveal where reports or analyses may be challenging to impossible.Web portal: http://www.lussierlab.org/transition-to-ICD9CM/Tables annotated with levels of translation complexity: http://www.lussierlab.org/publications/ICD10to9     

Physical activity intensity and surrogate markers for cardiovascular health in adolescents

We examined the impact of physical activity (PA) on surrogate markers of cardiovascular health in adolescents. 52 healthy students (28 females, mean age 14.5 ± 0.7 years) were investigated. Microvascular endothelial function was assessed by peripheral arterial tonometry to determine reactive hyperemic index (RHI). Vagal activity was measured using 24 h analysis of heart rate variability [root mean square of successive normal-to-normal intervals (rMSSD)]. Exercise testing was performed to determine peak oxygen uptake ( $ \dot{V}{\text{O}}_{{2{\text{ peak}}}} $ ) and maximum power output. PA was assessed by accelerometry. Linear regression models were performed and adjusted for age, sex, skinfolds, and pubertal status. The cohort was dichotomized into two equally sized activity groups (low vs. high) based on the daily time spent in moderate-to-vigorous PA (MVPA, 3,000–5,200 counts^.min^?1, model 1) and vigorous PA (VPA, >5,200 counts^.min^?1, model 2). MVPA was an independent predictor for rMSSD (β = 0.448, P = 0.010), and VPA was associated with maximum power output (β = 0.248, P = 0.016). In model 1, the high MVPA group exhibited a higher vagal tone (rMSSD 49.2 ± 13.6 vs. 38.1 ± 11.7 ms, P = 0.006) and a lower systolic blood pressure (107.3 ± 9.9 vs. 112.9 ± 8.1 mmHg, P = 0.046). In model 2, the high VPA group had higher maximum power output values (3.9 ± 0.5 vs. 3.4 ± 0.5 W kg^?1, P = 0.012). In both models, no significant differences were observed for RHI and $ \dot{V}{\text{O}}_{{ 2 {\text{ peak}}}} $ . In conclusion, in healthy adolescents, PA was associated with beneficial intensity-dependent effects on vagal tone, systolic blood pressure, and exercise capacity, but not on microvascular endothelial function.     

Erythropoietin production in a primary culture of human renal carcinoma cells maintained in nude mice

The present studies report erythropoietin (Ep) production in primary cultures of a human renal carcinoma from a patient with erythrocytosis that has been serially transplanted to BALB/c nude mice. The levels of erythropoietin in the culture media were estimated using the exhypoxic polycythemic mouse assay (EHPCMA), fetal mouse liver erythroid colony- forming technique (FMLC), and a radioimmunoassay (RIA). The spent culture media of the exponentially growing cells contained less than 10 mU/ml of Ep measured by RIA. However, after the cells became confluent, Ep levels (RIA) in the spent media showed a marked increase to approximately 300 mU/ml. Ep levels estimated using the FMLC and EHPCMA were approximately 2/3 and 1/10, respectively, of those measured by RIA. Rabbit antiserum to highly purified human urinary Ep (70,400 U/mg protein) was utilized for immunocytochemical (peroxidase-antiperoxidase method) localization of Ep in the cultured cells. Very few of the cells in exponential growth exhibited Ep-like immunoreactivity, whereas intense Ep-like immunoreactivity was observed in the cytoplasm of the cells maintained in culture for a prolonged period after reaching confluency. The most intense staining was observed in some of the cells forming domes. The domes developed after the cells reached confluency, and their numbers increased with increasing time in confluent culture, in parallel with the increase in Ep levels in the spent media. This primary cell culture system of a renal cell carcinoma maintained in nude mice, which produces immunologically and biologically active Ep, may provide a useful model for studies of the mechanism of Ep production.