Mesospheric Bore Evolution and Instability Dynamics Observed in PMC Turbo Imaging and Rayleigh Lidar Profiling Over Northeastern Canada on 13 July 2018.

Two successive mesospheric bores were observed over northeastern Canada on 13 July 2018 in high-resolution imaging and Rayleigh lidar profiling of polar mesospheric clouds (PMCs) performed aboard the PMC Turbo long-duration balloon experiment. Four wide field-of-view cameras spanning an area of ~75 × 150 km at PMC altitudes captured the two evolutions occurring over ~2 hr and resolved bore and associated instability features as small as ~100 m. The Rayleigh lidar provided PMC backscatter profiling that revealed vertical displacements, evolving brightness distributions, evidence of instability character and depths, and insights into bore formation, ducting, and dissipation. Both bores exhibited variable structure along their phases, suggesting variable gravity wave (GW) source and bore propagation conditions. Both bores also exhibited small-scale instability dynamics at their leading and trailing edges. Those at the leading edges comprised apparent Kelvin-Helmholtz instabilities that were advected downward and rearward beneath the bore descending phases extending into an apparently intensified shear layer. Instabilities at the trailing edges exhibited alignments approximately orthogonal to the bore phases that resembled those seen to accompany GW breaking or intrusions arising in high-resolution modeling of GW instability dynamics. Collectively, PMC Turbo bore imaging and lidar profiling enabled enhanced definition of bore dynamics relative to what has been possible by previous ground-based observations, and a potential to guide new, three-dimensional modeling of bore dynamics. The observed bore evolutions suggest potentially important roles for bores in the deposition of energy and momentum transported into the mesosphere and to higher altitudes by high-frequency GWs achieving large amplitudes.

Phosphorus-enriched hemodialysis for the treatment of patients with severe methanol intoxication.

Severe methanol poisoning requires treatment with prolonged and intensive hemodialytic therapy. Such treatment can engender either the de novo development of hypophosphatemia or the worsening of pre-existing hypophosphatemia. Phosphorus-enriched hemodialysis therapy can prevent the occurrence of this complication. We report three patients with severe methanol poisoning who were treated with phosphorus-enriched hemodialysis. Prevention or treatment of hypophosphatemia was successfully achieved with this dialytic technique.

Cardiovasoactive peptides in hemodialysis patients: diagnostic tools and predictors of outcome: a review of present knowledge and future directions.

The main cardiovasoactive peptides involved in cardiovascular adaptation to renal failure and dialysis are reviewed with a special focus on their possible role in pathophysiology, diagnosis of cardiovascular and fluid volume abnormalities, and prognostic information. The role of vasoactive peptides in cardiovascular stability during hemodialysis (HD) are best seen in sequential HD, where the release of vasoconstrictors is stimulated by volume reduction during ultrafiltration, but is blunted during isovolemic HD, whereas plasma vasodilators increase. Plasma levels of the natriuretic peptides atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are elevated in fluid volume overload and heart failure and decrease during dialysis. Neuropeptide Y (NPY) is elevated in severe volume overload and hypertension and calcitonin gene-related peptide in large-volume overload. Plasma BNP increases with left ventricular failure and improves during dialysis. Activation of the sympathetic nervous system as reflected by increased plasma levels of NPY is associated with poor prognosis. High levels of the natriuretic peptides ANP and BNP are likewise predictors of poor prognosis. Determinations of plasma levels of cardiovasoactive peptides may be helpful in clinical practice to diagnose volume overload and heart failure and to assess the severity of heart failure and of hypertension, as a guide to the choice of dialysis treatment and pharmacotherapy and to monitor treatment. Clinical studies will be needed in HD patients to establish the value of measurement of plasma cardiovasoactive peptides in clinical practice. The research in this field is still in its infancy and promises to be exciting in the future. There appears to be a balance of vasomotor tone and cardiac response to meet any emergency and stress such as intermittent dialysis. Further knowledge will increase our chances for major therapeutic interventions.

Management of hypophosphatemia induced by high-flux hemodiafiltration for the treatment of vancomycin toxicity: intravenous phosphorus therapy versus use of a phosphorus-enriched dialysate.

Intensive high-flux hemodiafiltration is often used in the management of vancomycin toxicity. We describe two patients who developed hypophosphatemia as a consequence of this form of therapy. The first patient was treated with an intravenous phosphorus infusion. For the second patient, hypophosphatemia was corrected, during hemodiafiltration, with the use of a phosphorus-enriched dialysate. The latter dialysate was prepared by adding sodium phosphate salts to the "base concentrate" of a dual-concentrate, bicarbonate-based dialysate delivery system. This simple method was more efficient than intravenous therapy in ameliorating the hypophosphatemia secondary to aggressive hemodiafiltration treatment.

Stability of urea and creatinine in spent hemodialysate.

Urea and creatinine levels in spent hemodialysates showed only small declines in spite of incubation at 37 degrees C for 36 hours. In the determination of dialysate-side solute removal, it would seem prudent to keep spent dialysate cold during collection to retard bacterial breakdown of these waste products.

Dying well after discontinuing the life-support treatment of dialysis.

BACKGROUND: Cessation of life-prolonging treatments precedes death in an increasing number of cases, but little attention has been accorded to the quality of dying. OBJECTIVE: To examine the quality of dying following dialysis termination. PATIENTS AND METHODS: A prospective cohort, observational study involved 6 dialysis clinics in the United States and 2 clinics in Canada, and 131 adult patients receiving maintenance dialysis who died after treatment cessation. Sixty percent (n = 79) underwent patient (n = 23) and/or family (n = 76) interviews and follow-up with caretakers. A quality of dying tool quantified duration, pain and suffering, and psychosocial factors. RESULTS: The sample was 59% female, the age was 70.0+/-1.2 years old, the duration of dialysis was 34.0+/-2.8 months, and death occurred 8.2+/-0.7 days after the last dialysis treatment. (Data are given as mean +/- SE.) Thirty-eight percent of the subjects who completed the protocol were judged to have had very good deaths, 47% had good deaths, and 15% had bad deaths. During the last day of life, 81% of the sample did not suffer, although 42% had some pain and an additional 5% had severe pain. According to the psychosocial domain of the quality of dying measure, patients who died at home or with hospice care had better deaths than those who died in a hospital or nursing home. CONCLUSIONS: Most deaths following withdrawal of dialysis were good or very good. The influence of site of death and physician attitudes about decisions to stop life support deserves more research attention. Quality of dying tools can be used to establish benchmarks for the provision of terminal care.

Dialysis discontinuation and palliative care.

Little attention has been accorded to the terminal course and end-of-life care of patients after dialysis discontinuation. This prospective cohort observational study involves six dialysis clinics in the United States and two clinics in Canada. Data were collected on 131 patients who were undergoing maintenance dialysis and died after treatment discontinuation. Seventy-nine of the patients (60%) were prospectively studied until their deaths. Caregivers and families provided information about the symptoms and treatment provided in the final 24 hours of life, and structured interviews were conducted at the time of stopping dialysis with patients and families. The patient population was primarily white (73%), elderly (70 +/- 1.2 years), and diabetic (46%). Three quarters of the subjects had between three and seven comorbid conditions. Pain and agitation were the most common symptoms during the last day of life. Terminal treatment was generally considered to be satisfactory, and most people had good deaths. Although dialysis prolongs life, the integration of palliative medicine into dialysis programs offers opportunities to improve the quality of end-of-life care, especially for those patients who elect to stop treatment. Recommendations include making advance care planning an expectation at all clinics and using quality-of-dying measures to establish benchmarks for the provision of terminal care.

Hemodialysis as a treatment of severe ethanol poisoning.

A 64-year-old woman presented with coma and shock due to severe ethanol intoxication. Her initial, markedly elevated blood alcohol level of 136.5 mM fell only by 16% after a 4-hour period of conservative treatment consisting of mechanical respiration and the administration of intravenous fluids, vasopressors and inotropics. Subsequent hemodialysis rapidly reduced her blood ethanol concentrations to less threatening levels, with prompt restoration of her consciousness. Hemodialysis may be life-saving and should be considered in patients with severe ethanol intoxication.

Preparation of ethanol-enriched, bicarbonate-based hemodialysates.

We describe a method to produce bicarbonate-based dialysates containing approximately 100 mg/dl ethanol by introducing the alcohol into one of the dialysate concentrate solutions geared for the production of bicarbonate-based dialysates.

Daily hemodialysis: dialysis for the next century.

There are currently over 150 patients receiving daily hemodialysis in over 12 centers worldwide. The experiences of over 200 daily hemodialysis patients spanning 30 years have been reviewed. The reports uniformly describe subjective and objective improvements. There are decreased symptoms during and after dialysis, improved functional status, and better quality-of-life ratings. There are improved nutritional indices, improved blood pressure with fewer blood pressure medications, and improved hematocrit with reduced transfusion or eythropoietin requirements. There also appear to be economic advantages, related to the significant reductions in the need for recombinant human erythropoietin and blood pressure medications. Early data suggest that there may be a significant decrease in days of hospitalization for very ill patients as well. This is important clinically and financially when the global costs of caring for dialysis patients are considered. Substantial issues remain before daily hemodialysis will be widely accepted. These include logistical problems (additional time for transportation, set up and disinfection), economic problems (increased supply costs or labor associated with more frequent treatments), and medical problems (deficiency syndromes and blood access). Technological improvements are close to overcoming many of the recognized problems, although additional payor education, research into deficiency syndromes, and an even greater focus on creating natural arterio-venous fistulae all need to occur before daily hemodialysis is more widely accepted. We are convinced, however, that daily dialysis will be increasingly used in the next century because it is more physiologic, makes many patients feel much better, produces better outcomes, and decreases overall cost for end-stage renal disease patients compared with current dialysis regimes.

Pregnancy in chronic dialysis: a review and analysis of the literature.

UNLABELLED: Pregnancy is uncommon in end-stage renal failure, particularly in patients requiring dialysis. We reviewed the literature from 1965 to date, seeking an optimal way of dialyzing pregnant women after encountering one such patient METHODS: We searched the English literature by cross-referencing "pregnancy" with "hemo-" or "peritoneal dialysis" and "renal failure". Eighty-six pregnancies worldwide were found to which we added one case of our own. Various independent factors were studied against gestational age at delivery using uni- and multivariate analysis. These factors included mother's age, previous delivery, diagnoses of renal disease, dialysis duration prior to pregnancy, gestational age at onset of dialysis, dialysis type, level of hemoglobin during pregnancy, BUN and creatinine targets, BUN/creatinine ratio, dialysis intensity at the beginning and end of pregnancy, influence of erythropoietin and dialysis complications. RESULTS: Of the 87 pregnancies, 12% resulted in stillbirths, 9% of neonates died prior to discharge. The mean gestational age at delivery was 32 +/- 5 weeks, and the mean birth weight 1604 +/- 652 g. Two congenital abnormalities and one twin pregnancy were reported. 48% of deliveries were premature. Pre-eclampsia was reported in 11%, and worsening hypertension in 17%. CAPD was used in 25 and hemodialysis in 62 patients. Fetal survival was similar in both cases (72% vs 82%), although incidence of various dialysis complications differed. The conventional dialysis goals of a low target BUN level and hemoglobin for pregnant patients were not factors in predicting fetal outcome. The number of hemodialyses/week were negatively correlated (R = -0.35, P = 0.061), but the hours of dialysis positively correlated (R = 0.42, p = 0.035) to gestational age. Fetal survival was independently influenced by creatinine level [564 micromol/L when baby survived vs 788 micromol/L when baby died (p = 0.021)], BUN/creatinine ratio (50 vs 30, p = 0.053), and hours of dialysis (5.6 hrs vs 3.6 hrs, p = 0.013). There was no relation of either frequency or volume of peritoneal dialysis exchanges to gestational age or fetal survival. CONCLUSIONS: Greater attention to a high intake of protein (>1.5 g/kg) and higher dose of hemodialysis, achieved by longer, every other day dialysis, may be the optimal approach to pregnant patients on hemodialysis. Our first attempt to define the goal of hemodialysis is to keep the predialysis creatinine below 600 mmol/L and the protein intake high enough so the predialysis BUN level is >25 mmol/L. There are no clear guidelines on how to best perform CAPD.

Is neuropeptide Y a contributor to volume-induced hypertension?

Hypertension often occurs with fluid overload. The most common mechanism is considered to be mediated by increased cardiac output. Hemodialysis (HD) patients frequently have large amounts of fluid overload. Neuropeptide Y (NPY) is activated by stress and contributes to hypertension and heart failure. We speculated that NPY may be released by the stress of fluid overload and, by its vasoconstrictor effect, may contribute to hypertension and heart failure. Plasma levels of NPY and other vasoconstrictors were studied in 20 HD patients with varying degrees of fluid overload, and the relationship of NPY plasma levels to blood pressure was analyzed. The plasma concentrations of NPY correlated with the degree of fluid overload (r = 0.89; P < 0.0001) and the mean arterial blood pressure (r = 0.85; P < 0.0001). Seven patients had fluid overload of greater than 6% of body weight. They had higher blood pressures and higher plasma concentrations of NPY than 13 HD patients with less than 5% of fluid retention (systolic blood pressure, 179+/-8.2 v 145+/-3.7 mm Hg, P = 0.007; NPY, 61+/-4.6 v 26.8+/-2.7 pmol/L, P < 0.001). In stepwise multiple regression analysis, NPY alone explained blood pressure elevation when analyzed with fluid overload and angiotensin II, renin, noradrenaline, and adrenaline levels. We hypothesized that fluid overload in dialysis patients is a stress-inducing state that activates the sympathetic nervous system and releases the vasoconstrictor NPY. The resulting inappropriate vasoconstriction may contribute to volume-induced hypertension and heart failure in a vicious cycle. We conclude that determination of plasma NPY levels may be useful as a marker of the clinical threat of overhydration.

On the success, cost and efficiency of modern medicine: an international comparison.

OBJECTIVE: To study the success and cost of modern medicine in industrialized, rich countries from 1980 to 1990. DESIGN: Cost per capita and per cent of gross domestic product (GDP) spent on health was related to: (i) mortality in six diseases amenable to treatment by modern medicine; (ii) the sum of those six diseases (avoidable disease); (iii) death due to other, unavoidable diseases; (iv) maternal and infant mortality; (v) life expectancy at birth; (vi) renal dialysis and transplantation rates. Efficiency was studied by comparing a country's avoidable mortality rates multiplied by expenses, to the mean for all countries. RESULTS: During the 10 years, avoidable death rate decreased 38% but unavoidable death rate only 10%. Life expectancy increased 3%. Cost per capita increased 107% but health expenditures, as per cent of GDP only 10%. There was a reasonable correlation between expenses and avoidable mortality but none between expenses and unavoidable death rate. In 1990 avoidable mortality was lowest in Canada, and highest in Japan. Cost was lowest in New Zealand, and highest in the USA. The efficiency index was highest for Australia, and lowest in the USA. CONCLUSION: Modern medicine as we have studied it is successful. Avoidable death rate shows a steep uninterrupted decline over the last 50 years while unavoidable death rate shows only small decreases. Cost as per cent of GDP has increased only moderately. There is a correlation between expenses and mortality from avoidable but not from unavoidable diseases, and a large variation in efficiency.

On the influence of sample size on the prognostic accuracy and reproducibility of renal transplant biopsy.

INTRODUCTION: The minimal specimen size necessary for accurate interpretation of a renal biopsy has not been identified. We attempted such a determination by three different analyses of a collection of biopsies performed in renal transplants. METHODS: First, we studied the influence of three lesions (glomerulosclerosis, arteriolar hyalinosis, interstitial fibrosis/tubular atrophy) in 199 baseline biopsies, obtained at time of transplantation, on transplant outcome. Secondly, we compared the results from the three lesions in baseline biopsy with those from 114 subsequent core biopsies in the same patients. Thirdly, we compared the two baseline biopsies obtained in 118 paired kidneys in cadaver transplantation where both kidneys were used. RESULTS: For statistically significant prediction of outcome from glomerulosclerosis, we found that a specimen containing at least 25 glomeruli was needed in the baseline biopsy. Arteriolar hyalinosis predicted outcome independent of sample size, but became less important than percentage glomerulosclerosis in predicting outcome if only samples containing more than 25 glomeruli were considered. Interstitial fibrosis/tubular atrophy did not predict the outcome of a kidney, independent of sample size. When comparing baseline with subsequent core biopsies, or with paired baseline biopsies, at least 14 glomeruli were necessary to allow even moderate reproducibility of glomerulosclerosis (Cohen's kappa > 0.25) and to allow statistical significance (P < 0.05). The reproducibility of arteriolar hyalinosis was not dependent on sample size but was reproducible in 80% of paired baseline biopsies, and in 67% of the comparison of the baseline with core biopsy. Both precision and significance was lost if sample numbers were reduced by including only larger samples. There was no reproducibility in any study of interstitial fibrosis/tubular atrophy when comparing either baseline with subsequent biopsy, or paired baseline biopsies. SUMMARY: Much larger biopsy samples are necessary than has generally been assumed in order for glomerulosclerosis rates to be reproducible or predictive of outcome. Arteriolar hyalinosis is prognostically important and shows good reproducibility independent of sample size. Interstitial fibrosis/tubular atrophy appear useless as predictors, being of no prognostic importance and lacking reproducibility. Our finding clarifies some of the discrepancies found by different investigators regarding the importance of renal biopsy in predicting prognosis. Preliminary, our data indicate that samples containing fewer than 25 glomeruli are unreliable in determining outcome based on glomerulosclerosis. The importance of our findings which are based only on chronic lesions, with respect to acute changes, is unknown.

Hemodialysis versus peritoneal dialysis: a comparison of adjusted mortality rates.

Although kidney transplantation is the preferred treatment method for patients with ESRD, most patients are placed on dialysis either while awaiting transplantation or as their only therapy. The question of which dialytic method provides the best patient survival remains unresolved. Survival analyses comparing hemodialysis and continuous ambulatory peritoneal dialysis/continuous cyclic peritoneal dialysis (CAPD/CCPD), a newer and less costly dialytic modality, have yielded conflicting results. Using data obtained from the Canadian Organ Replacement Register, we compared mortality rates between hemodialysis and CAPD/CCPD among 11,970 ESRD patients who initiated treatment between 1990 and 1994 and were followed-up for a maximum of 5 years. Factors controlled for include age, primary renal diagnosis, center size, and predialysis comorbid conditions. The mortality rate ratio (RR) for CAPD/CCPD relative to hemodialysis, as estimated by Poisson regression, was 0.73 (95% confidence interval: 0.68 to 0.78). No such relationship was found when an intent-to-treat Cox regression model was fit. Decreased covariable-adjusted mortality for CAPD/CCPD held within all subgroups defined by age and diabetes status, although the RRs increased with age and diabetes prevalence. The increased mortality on hemodialysis compared with CAPD/CCPD was concentrated in the first 2 years of follow-up. Although continuous peritoneal dialysis was associated with significantly lower mortality rates relative to hemodialysis after adjusting for known prognostic factors, the potential impact of unmeasured patient characteristics must be considered. Notwithstanding, we present evidence that CAPD/CCPD, a newer and less costly method of renal replacement therapy, is not associated with increased mortality rates relative to hemodialysis.