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Urea and water transport across the toad bladder can be separately activated by low concentrations of vasopressin or 8 Br-cAMP. Employing this method of selective activation, we have determined the reflection coefficient (sigma) of urea and other small molecules under circumstances in which the bladder was transporting urea or water. An osmotic method for the determination of sigma was used, in which the ability of a given solute to retard water efflux from the bladder was compared to that of raffinose (sigma = 1.0) or water (sigma = 0). When urea transport was activated (low concentration of vasopressin), sigma for urea and other solutes was low, (sigma urea, 0.08--0.39; sigma acetamide, 0.55; sigma ethylene glycol, 0.60). When water transport was activated (0.1 mM 8 Br-cAMP) sigma urea approached 1.0 sigma urea also approached 1.0 at high vasopressin concentrations. In a separate series of studies, sigma urea was determined in the presence of 2 x 10(-5) M KMnO4 in the luminal bathing medium. Under these conditions, when urea transport is selectively blocked, sigma urea rose from a value of 0.12 to 0.89. Thus, permanganate appears to "close" the urea transport channel. These findings indicate that the luminal membrane channels for water and solutes differ significantly in their dimensions. The solute channels, limited in number, have relatively large radii. They carry a small fraction (approximately 10%) of total water flow. The water transport channels, on the other hand, have small radii, approximately the size of a water molecule, and exclude solutes as small as urea. [ABSTRACT FROM AUTHOR]

Vsopressin activates a number of transport systems in the toad bladder, including the systems for water, urea, sodium, and other small solutes. Evidence from experiments with selective inhibitors indicates that these transport systems are to a large extent functionally independent. In the present study, we show that the transport systems can be separately activated. Low concentrations of vasopressin (1 mU/ml) activate urea transport with virtually no effect on water transport. This selective effect is due in part to the relatively greater inhibitor action of endogenous prostaglandins on water transport. Low concentrations of 8-bromoadenosine cyclic AMP, on the other hand, activate water, but not urea transport. In additional experiments, we found that varying the ratio of exogenous cyclic AMP to theophylline activated water or urea transport selectively. These studies support the concept of independently controlled systems for water and solute transport, and provide a basis for the study of individual luminal membrane pathways for water and solutes in the accompanying paper. [ABSTRACT FROM AUTHOR]

Abstract Background Lower extremity peripheral arterial disease (PAD) is a marker of widespread atherosclerosis. Individuals with PAD, most of whom do not show typical PAD symptoms ('asymptomatic' patients), are at increased risk of cardiovascular ischaemic events. American College of Cardiology/American Heart Association guidelines recommend that individuals with asymptomatic lower extremity PAD should be identified by measurement of ankle-brachial index (ABI). However, despite its associated risk, PAD remains under-recognised by clinicians and the general population and office-based ABI detection is still poorly-known and under-used in clinical practice. The Prevalence of peripheral Arterial disease in patients with a non-high cardiovascular disease risk, with No overt vascular Diseases nOR diAbetes mellitus (PANDORA) study has a primary aim of assessing the prevalence of lower extremity PAD through ABI measurement, in patients at non-high cardiovascular risk, with no overt cardiovascular diseases (including symptomatic PAD), or diabetes mellitus. Secondary objectives include documenting the prevalence and treatment of cardiovascular risk factors and the characteristics of both patients and physicians as possible determinants for PAD under-diagnosis. Methods/Design PANDORA is a non-interventional, cross-sectional, pan-European study. It includes approximately 1,000 primary care participating sites, across six European countries (Belgium, France, Greece, Italy, The Netherlands, Switzerland). Investigator and patient questionnaires will be used to collect both right and left ABI values at rest, presence of cardiovascular disease risk factors, current pharmacological treatment, and determinants for PAD under-diagnosis. Discussion The PANDORA study will provide important data to estimate the prevalence of asymptomatic PAD in a population otherwise classified at low or intermediate risk on the basis of current risk scores in a primary care setting. Trial registration number Clinical Trials.gov Identifier: NCT00689377.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, is an ongoing pandemic that has affected millions globally. Many infected patients have been noted to have cardiovascular damage. Prior to the development of clinical symptoms, the use of transthoracic echocardiography, specifically with measurements of left ventricular global longitudinal strain (LVGLS), may provide an additional prognostic marker for patients infected with COVID-19. We sought to determine whether patients with COVID-19 and reduced LVGLS have an increased risk for mortality. The mean LVGLS was determined to be significantly lower in the non-survivors compared to the survivors (-11.6 ± 1.8 vs -15.4 ± 0.74, p<0.05). It should be noted, however, that even those that survived were found to have reduced LVGLS (<-18.5%). A multivariate logistic regression analysis was also performed that demonstrated a relationship between reduced LVGLS and an increased risk for mortality. Overall, our data indicate that COVID-19 patients may have subclinical left ventricular dysfunction, and that critically ill patients may have a greater decline in cardiac dysfunction., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Bhatti et al.)

Background and Aims: The pathogenesis of acute cholangitis (AC) occurs with biliary obstruction followed by bacterial growth in the bile duct. The leading cause of AC is obstructing gallstones. There have been conflicting theories about the optimal timing for cholecystectomy following AC. The aim of this study is to assess the impact of early cholecystectomy on the 30-day readmission rate, 30-day mortality, 90-day readmission rate and the length of hospital stay., Methods: This retrospective study was performed between January 2015 and January 2021 in a high-volume tertiary referral teaching hospital. Included patients were 18 years or older with a definitive diagnosis of acute gallstone cholangitis who underwent endoscopic retrograde cholangiopancreatography (ERCP) with complete clearance of the bile duct as an index procedure. We divided the patients into two groups: patients who underwent ERCP alone and those who underwent ERCP with laparoscopic cholecystectomy (LC) on the same admission (ERCP+LC). Data were extracted from electronic medical records. The primary endpoint of the study was the 30-day readmission rate., Results: A total of 114 patients with AC met the inclusion criteria of the study. The ERCP+LC group had significantly lower rates of 30-day readmission (2.2% vs 42.6%, p<0.001), 90-day readmission (2.2% vs 30.9%, p<0.001) and 30-day mortality (2.2% vs 16.2%, p=0.017) when compared with the ERCP group. In a multivariate logistic regression analysis, patients in the ERCP+LC group had 90% lower odds of 30-day readmission compared with patients who did not undergo LC during admission (OR=0.1, 95% CI (0.032 to 0.313), p<0.001)., Conclusion: Performing LC on same day admission was associated with a decrease in 30-day and 90-day readmission rate as well as 30-day mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Atrial fibrillation is currently managed with a variety of rate controlling and antiarrhythmic agents. Often, magnesium is used as adjunctive therapy, however, the benefit it provides in managing Afib with RVR has been debated. This study aimed to determine if IV MgSO4 administration in conjunction with standard therapy provides any synergistic effect in acute and prolonged control of Afib with RVR., Methods: This was a retrospective study involving ninety patients with episodes of Afib with RVR during their hospitalization. The treatment group included those that had received magnesium (n=32) along with standard management and the control group (n=58) received only standard management. Heart rates at different time intervals were collected. Dose dependent effects of IV MgSO4 on heart rates were also evaluated., Results: Patients that received magnesium had a lower mean heart rate (85 BPM versus 96 BPM, P<0.05) 24 hours after onset of the episode. Also, in the last 16 hours of observation, it appeared that administration of higher levels of magnesium resulted in statistically lower heart rates. In the group of patients that received 2 grams of magnesium, the mean heart rate at 8 hours was 103.4 beats/min and 84.8 beats/min at 24 hours (p<0.01). This same trend was not seen in patients that received 1 gram of magnesium or in the control group., Conclusions: Overall, the use of IV MgSO4 as an adjunctive treatment permitted normalization of the heart rate progressively that continued to at least 24 hours.

Background and Objectives: Patients with ESRD have an increased incidence of coronary events with a relatively higher risk for mortality after acute myocardial infarction (AMI). We evaluated whether it is safer to delay dialysis in AMI or if delay poses separate risks., Design, Setting, Participants, & Measurements: We conducted a retrospective review of 131 long-term hemodialysis patients who had AMI and were admitted between 1997 and 2005 at three New York City municipal hospitals. Patients were separated into three groups on the basis of time between cardiac symptoms and first dialysis (<24 h, 24 to 48 h, and >48 h)., Results: A total of 17 (13%) patients died, 10 (59%) of whom had either hypotension or an arrhythmia during their first cardiac care unit dialysis. Although these groups were comparable in acuity and cardiac status, there were no findings of increased morbidity (26, 36, and 20%, respectively) or mortality (11, 18, and 13%, respectively), despite differences in the timing of each group's dialysis. We found that previous cardiac disease, predialysis K+, DeltaK+ after dialysis, and APACHE scores were significantly higher in patients with peridialysis morbidity., Conclusions: We conclude that there is no increased morbidity with early dialysis in AMI, but rather close attention needs to be paid to the rate of decrease in serum potassium in patients with ESRD and their level of acuity when undergoing dialysis.

Intravenous labetolol, a nonselective alpha- and beta-blocking drug, is commonly used to treat severe hypertension. Nonselective beta-blockers can cause hyperkalemia, especially in patients with renal failure. One series reported 3 renal transplant patients who had hyperkalemia after labetolol infusion, but none of these patients developed any serious complication. We report a case of life-threatening hyperkalemia (serum [K+] 9.9 mEq/l) with ventricular tachycardia and hypotension in a patient on maintenance hemodialysis who received labetolol for a hypertensive emergency. Physicians should be aware of this potentially lethal complication, which is easily preventable., (Copyright 2001 S. Karger AG, Basel)

It is commonly believed that the electrolyte pattern in the patients with chronic renal failure (CRF) is associated with high anion gap (AG) and low serum bicarbonate (HCO3). However it was seen in many clinical studies that the AG is normal or only minimally increased in such patients. It is also known that organic cations, in particular guanidines, also increase in the serum of patients with CRF. We thus postulated that the relatively small increase in AG could be, in part, explained by the coexistent increase in unmeasured cations. If this is true, one may expect that the serum osmolality measured directly will be higher than the estimated one, leading to an osmolar gap (OG). Previous studies have shown that indeed OG exists in patients with CRF. We proceeded to determine SMA-7, AG, and OG simultaneously in ambulatory, undialyzed CRF patients with serum creatinine between 4 and 12 mg/dL. These investigations were also done on nine patients, after dialysis, who went on to have dialysis. The patients were divided into the normal AG (AG < or = 14) and a high AG (AG > 14) groups. There was no correlation of serum bicarbonate with degree of renal dysfunction. Serum AG influenced HCO3 only in the patients with high AG group (bicarbonate = 23.85-0.69 (deltaAG), r2 = 0.45). In patients with normal anion gap there was a good correlation between deltaAG and OG (deltaAG = 3.4-0.15 OG, r = 0.46, r2 = 0.21, p < 0.05). Thus serum bicarbonate appears to be controlled by both AG and OG. Following dialysis, OG decreased from 15.5 +/- 1.06 to 6.08 +/- 1.71, p < 0.01. We conclude that OG must be made up of unmeasured cations of low molecular weight as it normalizes the AG, and gets cleared after dialysis. These low molecular weight substances could be guanidines, such as guanidosuccinic acid and methylguanidine, which are increased by one hundred fold in CRF.

Background: Prediction of which intensive care unit (ICU) patients are likely to develop acute renal failure (ARF) would be useful. However, scoring systems such as APACHE have been disappointing in this regard. We previously developed a bedside formula to predict ARF using only 3 parameters: serum albumin, urine osmolality, and presence of sepsis., Methods: We prospectively evaluated 115 consecutive medical ICU (MICU) patients, comparing the bedside formula to APACHE II AND APACHE III as predictors of ARF or death and looking at nutritional parameters such as iron binding capacity, triceps skin fold, mid-arm circumference, and total lymphocyte count. We then evaluated 123 additional consecutive MICU and 98 consecutive surgical ICU (SICU) patients, comparing the bedside formula to APACHE II., Results: The bedside formula was consistently more accurate than APACHE II in predicting ARF or in-hospital death in MICU patients. However, in SICU neither formula predicted ARF, and APACHE II predicted in-hospital death slightly better. No nutritional parameter other than albumin correlated with ARF., Conclusion: The bedside formula appears superior to APACHE II in predicting ARF or death in MICU but not SICU. This suggests that these two ICU populations are different.

Objective: In view of the limitations of albumin in peritoneal dialysis (PD), we set out to evaluate whether total lymphocyte counts (TLC) could serve as a better prognostic indicator. We were also interested in how these parameters might differ between PD and hemodialysis (HD) patients., Design: In a retrospective study, we reviewed 113 charts from our dialysis unit. All laboratory analyses were performed by the Department of Clinical Pathology of the Nassau County Medical Center, using standard procedures. Intact parathyroid hormone (PTH) was sent out to Nichols Laboratories., Setting: All patients originated from the renal clinic at Nassau County Medical Center, a 612 bed public hospital., Patients: The 38 PD and 75 HD patients selected had been receiving dialysis for at least 12 months and up to 3 years. The PD patients received either continuous ambulatory and/or cycler PD. For the survivors, the averages of their routine chemical analyses were considered their representative values. For the nonsurvivors, the most recent laboratory values prior to their end point were considered., Main Outcome Measures: Mortality or apparent malnutrition leading to transfer to HD represented the end points for PD patients. Mortality alone was used as the end point for HD patients., Results: Within the PD population, serum albumin was not significantly lower in nonsurvivors compared to survivors, while the TLC was significantly lower in nonsurvivors (1277 +/- 146/mm3 vs 2249 +/- 236/mm3, p = 0.0036). The HD population demonstrated a significant difference in both TLC and serum albumin levels between its two prognostic groups; albumin was the better discriminator. Nonsurvivors had a 20% lower serum albumin than did the survivors (27.0 +/- 1.6 g/L vs 34.0 +/- 0.5 g/L, p = 0.0001). Patients on PD had a higher TLC than those on HD (p = 0.0001)., Conclusions: In the HD population, but not in the PD population, both serum albumin and TLC were significantly higher in the group that survived. Serum albumin is a more powerful discriminator of mortality in the HD population, while TLC is a better discriminator of mortality in the PD population. For uncertain reasons, PD patients have a higher TLC than those on HD.

Uncontrolled infection quite often leads to systemic inflammatory reaction syndrome (SIRS) and multiorgan dysfunction (MOD) syndrome. Thirty-five consecutive patients (19 males) fulfilling strict diagnostic criteria for SIRS were enrolled in two multicenter prospective double-blind trials involving new therapies for SIRS. The patients were followed prospectively up to day 28 after the enrollment. In the 35 patients with SIRS, males predominated in the age group below 40 (10/12, 83%) compared to the older group (nine males out of 23, 39%). Out of 16 females presenting with SIRS, only two were below the age of 40. This distribution was statistically different than our general MICU population. The serum albumin in these patients was uniformly low, with a mean of 22.5 gm/L. The bulk of SIRS patients (22/35; 63%) went on to develop acute renal failure (ARF). Although statistically not different, skin and peritoneal infections were more common in ARF group while pulmonary infections in non-ARF group. The majority of blood-cultures grew gram-positive organisms. Resolution of SIRS occurred within first 3 days in greater number of non-ARF survivors than ARF survivors (6/9, 66.7% vs. 6/16, 37.5%). Of the 22 ARF patients, 17 showed improvement in their renal function; the five who did not, died before day 28. The overall mortality (about 32%) was similar in both groups. Patients who developed both ARF and ARDS did not survive. In conclusion. SIRS occurs mostly in elderly patients, almost always in patients with low albumin levels. Premenopausal women seem to be protected. Blood cultures isolated a gram-positive organism in the majority of cases. Improvement in serum creatinine suggests good prognosis. The mortality in ARF and non-ARF groups is similar.

In a population of 141 very elderly subjects, there was a small but significant decline in BUN and creatinine at 3 years, which persisted at 6 years although partially attenuated. A similar pattern of falling BUN and creatinine was seen in the 31 subjects who began the study with mild azotemia. There was no significant change in the subjects' mean Body Mass Index during the 6-year period of observation. The azotemic subjects had a rate of death or dropout from the study similar to that of the entire cohort. Mean systolic blood pressure fell by 5.4 mm Hg (p < 0.05) and diastolic blood pressure by 2.1 mm Hg (p = NS) by 6 years. Users of diuretics or NSAID had a mean BUN and creatinine comparable to those not taking these medications. We conclude that BUN and serum creatinine do not necessarily increase with time in the old old, even in those with mild azotemia, hence, several determinations of these parameters may be needed to ensure accuracy. While renal function in the elderly probably does not improve with time, it may stabilize due to improvement in blood pressure. Use of diuretics and NSAID by functioning elderly individuals is not necessarily associated with worsening azotemia.

Incubation of the toad bladder epithelia with 100 nM 12-O-tetradecanoylphorbol 13-acetate (TPA) for 1, 3 and 5 min decreased cytosolic protein kinase C (PKC) activity to 85, 80 and 75% of control, while membrane-associated PKC activity increased to 127, 140 and 126% of control, respectively. Long-term treatment of epithelial cells with TPA caused downregulation of PKC with a loss of 80% of the enzymic activity. Incubation with vasopressin (AVP) for 2 min decreased cytosolic PKC activity by 20%, whereas the activity in the membrane fraction increased by 33%. PKC translocation did not occur when epithelia were stimulated with [deamino1-D-arginine8]-vasopressin which binds more specifically to the V2 receptor. Staurosporine inhibited PKC activity as well as the effect of AVP on translocation. Phorbol esters decreased the response to AVP on water transport, whereas staurosporine greatly increased the hormonal response. We conclude that TPA induces an intracellular translocation and downregulation of PKC. The translocation of PKC by AVP and the inhibition of AVP-stimulated water flow by TPA suggest a significant negative feedback loop involving PKC to modulate the action of AVP.

In agreement with previous reports, we found that absence of K+ from the serosal bath of the toad urinary bladder substantially impairs vasopressin and cAMP-stimulated water flow. The decreased response to vasopressin appears unrelated to prostaglandin production since inhibition of endogenous prostaglandins by pretreatment with naproxen 10(-5) M failed to prevent the effect seen with K+-free Ringer's. The resistance to vasopressin does not appear to be directly related to epithelial K+ concentrations, in that maneuvers leading to decreased intracellular K+ failed to produce a similar effect. A more likely explanation appears to be that K+-free Ringer's induces an increased cytosolic Ca++ which, in turn, decreases the hydrosmotic effects of vasopressin. Several lines of evidence argue in favor of such an explanation: (a) Increased cytosolic Ca++ had been found in other tissues with low extracellular K+; (b) The resistance to vasopressin decreases with decreased serosal Ca++; (c) The effects of K+-free Ringer's are not additive in situations believed to have increased epithelial Ca++, i.e. replacement of serosal Na+ with choline; (d) The effects of K+-free serosal bathing medium could be both prevented and/or reversed if already established by increasing serosal bath, and presumably intracellular, pH, which is believed to decrease intracellular Ca++.

Patients receiving hemodialysis are particularly susceptible to infection. We report a case of Listeria monocytogenes bacteremia and graft infection developing in a patient receiving hemodialysis. Vancomycin hydrochloride therapy was initiated in anticipation of a staphylococcal infection, and continued as the patient's clinical course improved. Ultimately the arteriovenous graft required excision. Identification of the organism and drug susceptibilities are described. To our knowledge, this is the first case report of both an L monocytogenes arteriovenous graft infection and the use of vancomycin in the treatment of this infection.

The kallikrein-kinin and the prostaglandin systems are both important modifiers of vasopressin action. This study examines whether the systems are dependent on one another for their action. Four groups of toad hemibladders were examined. In groups 1 and 2 animals the endogenous prostaglandin system was inhibited. Inhibition of kallikrein by aprotinin caused vasopressin-stimulated water flow to increase further (24.8 +/- 4.9 to 34.5 +/- 4.8 microliters/min) while potentiation of kinins by captropril caused vasopressin-stimulated water flow to decrease (45 +/- 6.3 to 30.5 +/- 5.4 microliters/min). In groups 3 and 4 endogenous kallikrein was inhibited by aprotinin. The addition of prostaglandin E2 caused vasopressin-stimulated water flow to decrease (17.5 +/- 2.7 to 5.71 +/- 1.0 microliter/min) while the inhibition of endogenous prostaglandins caused vasopressin-stimulated water flow to increase (26.7 +/- 3.4 to 39.2 +/- 3.5 microliters/min). Thus, the inhibitory effects of prostaglandins and kinins on vasopressin-stimulated water flow are independent of one another.

Stimulation of urea and water transport by vasopressin (ADH) appears to occur via independent pathways. We examined the effects of altering serosal or mucosal bath pH on transport of water, urea, and sodium. Compared to bladders with a serosal bath pH of 7.4 to 8.0, reducing the serosal bath pH to 6.8 led to a 60% fall in ADH-stimulated osmotic water flow, without decreasing the permeability of urea. Raising the serosal pH to 9.5 had the opposite effect: urea permeability was inhibited by 40% without altering water flow. Exogenous cyclic AMP-stimulated water and urea permeabilities were not dissociated, but were changed in the same direction by alterations in serosal pH: serosal acidification enhanced the effect of exogenous cyclic AMP on both urea and water, whereas the cyclic AMP effect on both was diminished by serosal alkalinization. This was especially marked for urea, suggesting that an alteration in the urea response to cyclic AMP may be particularly important in defining vasopressin-stimulated urea permeability as the serosal bath pH is altered. Mucosal acidification increased short circuit current but decreased both the urea and water response to ADH and 8-bromo-cyclic AMP. The response to cyclic AMP was less consistent. Mucosal alkalinization did not cause significant changes in either basal or stimulated transport. The data demonstrate distinct and separable effects of bath pH alterations on each of the transport systems examined.

Fat and fat-free tissues were determined in hemodialysis patients using either anthropometric measurements or indirectly from total body water (TBW) determined from urea kinetics. A very close correlation between the two methods in determining either fat or fat-free tissue (r greater than 0.8, n = 43) was shown. Twenty-two patients were followed for 2 yr. We found that fat increased while fat-free tissue decreased over that period of time. The latter appears to reflect methodological problems since both fat-free determinations depend upon TBW rather than somatic proteins. This was further confirmed by finding a proportional decrease in TBW with time, while creatinine appearance rate remained unaffected. Adherence to prescribed diet was monitored through diet records and periodic determination of urea N appearance rate during interdialysis periods. Our present studies determined body composition of hemodialysis patients and examined the relative validity of the commonly used methods. We demonstrate that no malnutrition occurs with time in patients adhering to their prescribed diet.

The course of nonoliguric acute renal failure (ARF) in 11 patients was analyzed. The possible etiology of the renal failure was multiple in all cases and did not differ from that seen in oliguric acute tubular necrosis (ATN). Other than the urine volume, which ranged from 510 to 2,325 ml/day, there was no major clinical or biochemical difference between these cases of nonliguric ARF and those described for oliguric ATN. Creatinine clearance, however, was higher than anticipated in oliguric ATN and ranged from 2.8 to 15.0 ml/min. There was a direct relationship between creatinine clearance and daily urine volume. The essential difference between oliguric and nonoliguric renal failure appears to be the lesser degree of renal damage in the nonoliguric form.