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Biomedical subjects

M I Sorkin

Publications and source records attributed to M I Sorkin.

At least 19 recordsLinked to original sources
PubMed1999

Indices of activity of the nitric oxide system in hemodialysis patients.

Arginine deficiency and/or increased levels of circulating nitric oxide (NO) synthesis (NOS) inhibitors can cause reduced NOS, which may contribute to hypertension in patients with end-stage renal disease (ESRD). To test these hypotheses, NO oxidation products (NO(2) + NO(3) = NO(x)) and cyclic guanosine monophosphate (cGMP), the vasodilatory second messenger of NO, were measured in the blood, urine, and dialysate effluent of hemodialysis (HD) patients and compared with the blood and urine of healthy subjects. The subjects ate a controlled low-nitrate diet (approximately 330 micromol/d) for 48 hours before and during blood, dialysis effluent, and 24-hour urine collection. NO(x) output was significantly reduced in HD patients versus controls (552 +/- 51 v 824 +/- 96 micromol/24 h; P < 0.001), whereas cGMP output was not low versus controls. Plasma arginine level was normal and plasma levels of citrulline and the endogenous NOS inhibitor, asymmetric dimethylarginine (ADMA), were markedly elevated in patients with ESRD versus controls. Systolic blood pressure was greater in HD patients compared with controls despite concurrent antihypertensive therapy in most patients with ESRD. These studies suggest NO production is low in patients with ESRD undergoing HD, possibly because of the increased ratio of plasma ADMA to arginine.

Arginine↗
PubMed1999

Nitric oxide production is low in end-stage renal disease patients on peritoneal dialysis.

To test the hypothesis that nitric oxide (NO) deficiency occurs in end-stage renal disease (ESRD), NO oxidation products (NO2 + NO3 = NOx) and cGMP were measured in blood, urine, and dialysate effluent of peritoneal dialysis (PD) patients and compared with blood and urine of healthy subjects. All subjects were on a controlled low-nitrate diet (approximately 330 micromol/day). NOx and cGMP outputs were significantly reduced in PD patients (334 +/- 50 micromol/24 h and 55 +/- 13 nmol/24 h, respectively) vs. controls (823 +/- 101 micromol/24 h and 149 +/- 46 nmol/24 h). Plasma arginine was borderline low, plasma citrulline was elevated and plasma levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine were approximately five time higher in PD patients (2.2 +/- 0.3 microM) vs. controls (0.4 +/- 0.1 microM). Although blood pressure (BP) was not different between groups at the time of study, 10 of 11 PD patients were on medication for hypertension. These studies demonstrate that total NO production is low in ESRD, and with appropriate caution, we conclude that this NO deficiency may contribute to the increased BP that occurs in ESRD.

Adult↗
PubMed1998

Early referral and its impact on emergent first dialyses, health care costs, and outcome.

Early referral (ER) to nephrologists of patients with chronic renal failure was assessed for its impact on the incidence of emergent first dialyses and choice of dialysis modality (hemodialysis [HD] or peritoneal dialysis [PD]), and survival. We reviewed events preceding first dialyses of 238 patients with end-stage renal disease (ESRD) starting dialysis between January 1990 and April 1997, with follow-up extending through November 1997. Patients referred more than 1 month before needing dialysis (early referral [ER]) were compared with patients presenting within 30 days of needing dialysis (late referral [LR]). The need for emergent HD was significantly less among ER (29%) as compared with LR (90%) (P < 0.0001). Initial modality chosen was similar among ER patients (59% for HD v 41% for PD), a finding that contrasts with national percentages, which approximate 85% and 15%, respectively. Whereas most patients had not changed modality at 4 months, significantly more had changed from HD to PD (36 of 160 or 23%) than from PD to HD (7 of 78 or 9%) (P < 0.0001). Despite starting out on HD, ER and LR patients were amenable to ultimately changing to PD. ER and LR groups had similar numbers of Medicaid patients and patients living 1 hour or more distant to tertiary medical care. Furthermore, no difference was observed in the incidence of emergent HD when ER and LR living more than 1 hour away were compared. LR was not associated with lack of insurance or distance from referral site, although these patients more often required emergent HD, with its higher attendant medical care costs. Controlling for age and cause of ESRD, there was no statistically significant difference in long-term survival when ER patients were compared with LR patients or when patients who had received emergent HD were compared with those who had not. Despite the lack of difference in long-term survival, the financial costs of emergent HD alone merit greater promotion of ER and the psychosocial preparation and modality choice it allows.

Adult↗
PubMed1994

Stopping dialysis of an incompetent patient over the family's objection: is it ever ethical and legal?

Decisions to stop dialysis or other life-sustaining treatments for incompetent patients are among the most difficult ethical problems faced by physicians and families. This observation is verified by the large number of court cases and the increasing frequency of ethics consultations on these issues. In such instances, in the absence of an advance directive, the usual practice for physicians is to turn to the patient's family for direction on whether to start, continue, or withdraw the treatment. They do so on the presumption that the family best represents the patient's interests. This presumption may not always be correct. A case is presented in which the family's insistence on continued dialysis was contrary to the patient's previously expressed wishes and the treating physician's assessment of the patient's best interests. It is asserted that, in such situations, after thorough conversation with the family, consultation, documentation, and an unsuccessful attempt to transfer the patient's care to another physician, nephrologists have an ethical obligation and legal right to override the family's decision and to stop dialysis. The ethical obligation is supported by the principles of respect for persons, beneficence, and nonmaleficence. The legal right is grounded in common law and state statutes.

Aged↗
PubMed1993

Is ultrasonography useful in predicting catheter loss?

Exit-site infections (ESI) and/or tunnel infections (TI) are common causes of peritoneal catheter loss. Catheter-related infection can be characterized by ultrasonographic examination (UE) of the exit site and the tunnel. This study was done to determine if the UE is useful in predicting catheter loss. Records from 1990 to 1992 of all continuous ambulatory peritoneal dialysis (CAPD) patients with an ESI or TI who had an UE performed were reviewed for causative organism, loss of catheter, and infection resolution. ESI was defined as redness or induration of exit site with or without the presence of drainage. TI was defined as induration or redness along tunnel or incision site with or without the presence of drainage. The presence of a pericatheter sonolucent fluid collection was considered a positive (+) UE, and the absence of fluid a negative (-) UE. Eleven CAPD patients had 12 UE performed within a week of starting antibiotic therapy. Ten were (+) and 2 (-); 7 catheters were removed, all with (+) UE. Of those removed, 6 were due to S. aureus, and 1 due to mycobacterial infection. Of the 3 (+) catheters not removed, 2 infections resolved clinically: both reverted to (-) UE after treatment. We conclude that a (+) UE is a useful predictor of catheter loss.

Abdomen↗
PubMed1991

The effect of body weight on CAPD related infections and catheter loss.

CAPD related infections and catheter loss continue to be the major problems facing the peritoneal dialysis patient. Few risk factors for infections and catheter loss have been identified. We hypothesized that overweight and underweight patients may be at increased risk for infections and catheter related problems. We examined the effect of the patient's weight at the start of peritoneal dialysis on the subsequent peritonitis and catheter infection rates, as well as catheter loss. Weight was expressed as a percentage of ideal body weight (IBW). Those patients who were more than 110% of IBW were considered to be overweight, 90 to 110% of IBW normal and less than 90%, underweight. An equivalent percentage of patients were overweight and underweight at the initiation of peritoneal dialysis (55/228, 24% for both groups). Overweight, normal, and underweight patients had peritonitis rates of 1.0, 0.9, and 0.8 episodes/y and catheter infection rates of 1.1, 1.2, and 0.8 episodes/y, respectively. Despite these similar rates, catheter loss due to infectious complications was greatest in the overweight group and least in the underweight group (p less than 0.05). No obvious explanation for the difference in catheter loss rate was found. Neither S. aureus nor P. aeruginosa infections occurred more frequently in the overweight patients. However, S. aureus infections more often led to catheter loss in the overweight patients. Catheter loss due to catheter leaks and failure to drain was similar in the three groups of patients. We conclude that deviation from ideal body weight at the initiation of dialysis is not a risk factor for CAPD related infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

The effect of the Y-set on catheter infection rates in continuous ambulatory peritoneal dialysis patients.

We hypothesized that catheter infections in continuous ambulatory peritoneal dialysis (CAPD) patients may be reduced with a disconnect system. We examined this theory in 116 CAPD patients over a 2-year period. In CAPD patients who switched to the Y-set (n = 22), the catheter infection rate decreased from one per 13 patient-months to one per 26 patient-months (P = 0.05), whereas the catheter infection rate in matched controls (n = 22) remained unchanged. Patients who began CAPD using the Y-set (n = 36) had catheter infection rates of one per 14 patient-months versus one per 8 patient-months in matched controls (n = 36, P = 0.05). Staphylococcus aureus was the most common cause of catheter infections in both groups of patients. However, Pseudomonas aeruginosa replaced Staphylococcus epidermidis as the second most common cause of catheter infections in the patients using the Y-set. The number of catheters that had to be removed due to catheter infections, mainly those due to S aureus or P aeruginosa, was the same in the Y-set and control groups. We conclude that the Y-set system is associated with reduced numbers of catheter infections, but that catheter loss from catheter infections remains a serious problem.

Adult↗
PubMed1989

Exit-site location does not influence peritoneal catheter infection rate.

Peritoneal catheter infections are a cause of peritonitis, catheter loss, and permanent transfer of continuous ambulatory peritoneal dialysis (CAPD) patients to hemodialysis. Risk factors for catheter infections have not been delineated. We investigated the location of the peritoneal exit-site location as a risk factor for catheter infection and loss. There was no relationship between catheter infection rates and exit location. Catheters exiting on the beltline had a median infection rate of 0.5 episodes/year, as opposed to 1.2 episodes/year for catheters exiting above the beltline and 0.9 episodes/year for catheters exiting below the beltline (ns). The percentage of catheters that became infected and required removal was the same for catheters exiting above, below, or on the beltline. Although we recommend avoiding the beltline for patient comfort, exit-site location is not an important determinant of infection rates or catheter outcome.

Catheters, Indwelling↗
PubMed1989

Exacerbation of aluminium encephalopathy after treatment with desferrioxamine.

Two haemodialysis patients with aluminium encephalopathy developed dramatic deteriorations of their neurological symptoms after initiation of desferrioxamine (DFO) therapy. Both patients were treated with relatively large doses of DFO (1 g and 2 g per treatment). In the first case, paranoid delusions, visual hallucinations, seizures and deteriorating speech followed each dialysis treatment with DFO. The second patient experienced increasing confusion, decreasing short-term memory, and deterioration in speech. In both cases the neurological symptoms regressed after decreasing or discontinuing the DFO. These patients demonstrate the potential dangers of using high doses of DFO. The pathogenesis of the exacerbation is not well understood but, may not simply be due to the result of elevated plasma aluminium levels after DFO therapy. We argue in this communication for reducing DFO in patients with aluminium encephalopathy to doses of 1 g three times per week to ensure adequate treatment of aluminium encephalopathy while minimising the risk of exacerbation from overzealous DFO administration.

Aged↗
PubMed1985

Effects of end-stage renal disease and aluminum hydroxide on temazepam kinetics.

The kinetics of temazepam, 30 mg, were evaluated in 11 patients with end-stage renal disease. Age ranged from 18 to 65 years. On two occasions separated by 1 week, single oral 30 mg doses of temazepam were given once with water (TM) and once with 3600 mg aluminum hydroxide gel (TM + AHG). There were no significant differences in the maximum plasma concentration, the time to reach maximum concentration, or elimination rates between TM and TM + AHG dosing. In approximately half the subjects there were secondary temazepam peak concentrations. In the remaining subjects, temazepam elimination was biphasic, with the terminal t1/2 ranging from 11 to 77 hours. There was a lag time before absorption in all subjects. The percent free temazepam in plasma from dialysis subjects ranged from 4.4% to 8.8% (mean = 5.9%). Compared with literature reports of subjects with normal renal function, the maximum plasma concentration was lower and the percent free temazepam was higher in dialysis subjects. When sedation score was plotted against plasma temazepam concentration, there was clockwise hysteresis consistent with tolerance or adaptation to effects of the drug. Thus aluminum hydroxide gel does not affect temazepam absorption. The clinical significance of the low plasma concentrations and high free temazepam fraction in dialysis subjects is uncertain.

Absorption↗
PubMed1985

Effects of end stage renal disease and aluminium hydroxide on triazolam pharmacokinetics.

Triazolam 0.5 mg was administered to 11 dialysis patients and 11 age, weight and sex matched controls. Peak plasma concentrations (Cmax) were higher in control subjects, but there were no other differences between the groups. When dialysis patients took triazolam with 3600 mg aluminum hydroxide suspension, Cmax and AUC were increased into the range observed in control subjects. It appears that triazolam can be used at normal doses in patients with renal dysfunction, without regard to interaction with aluminum hydroxide gel, or to alterations in elimination.

Adolescent↗
PubMed1984

Triazolam protein binding and correlation with alpha-1 acid glycoprotein concentration.

On two occasions separated by a minimum of 1 wk, plasma was obtained from 12 patients (aged 18 to 73 yr) on dialysis after an overnight fast. Samples were assayed for albumin and alpha 1-acid glycoprotein (AGP) concentrations. 14C-Triazolam was added to each sample to a final concentration of 5 ng/ml. Protein binding was determined by equilibrium dialysis. Unbound triazolam ranged from 6.4% to 15.4% (mean = 10.0%). AGP concentrations ranged from 71.8 to 205.1 mg% (mean = 123.4 mg%). Triazolam binding ratio (bound/unbound concentration) correlated with AGP concentration (r2 = 0.69) but not with albumin concentration, age, or sex. This correlation was verified by adding AGP in varying amounts to control plasma.

Adolescent↗
PubMed1983

Peritoneal access and related complications in continuous ambulatory peritoneal dialysis.

Over a four-year period, 50 patients underwent continuous ambulatory peritoneal dialysis. After 24 months, 48 percent of the patients continued to receive continuous ambulatory peritoneal dialysis treatment (including those who underwent continuous ambulatory peritoneal dialysis with bottled solutions from 1977 to 1978). Using solutions in plastic bags, 63 percent of patients continued to undergo continuous ambulatory peritoneal dialysis after 24 months. The mortality rate at 24 months was 23 percent overall and 15 percent for those using plastic bags. There was an overall average of 2.4 episodes of peritonitis a year per patient and 1.3 episodes a year per patient from 1979 through 1980, when only the technique with plastic bags was used. The number of days a patient was hospitalized averaged 48 per year, and 37 days per year in 1979 and 1980. Fifty-five percent of catheters remained functional at 24 months. Other complications included 15 hernias, 15 skin and tunnel infections, 12 leaks, and five cuff extrusions. Improved catheters and further reductions in the incidence of peritonitis will most likely result in a decreased number of patients who withdraw from continuous ambulatory peritoneal dialysis therapy.

Adolescent↗