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Biomedical subjects

M J Flanigan

Publications and source records attributed to M J Flanigan.

At least 19 recordsLinked to original sources

Clinical performance measures: the changing status of peritoneal dialysis.

BACKGROUND: The Peritoneal Dialysis-Clinical Performance Measures Project (PD-CPM) characterizes peritoneal dialysis within the U.S. Current survey results are reported and compared to those of previous years. METHODS: Prevalence data from random national samples of adult peritoneal dialysis (PD) patients participating in the United States End-Stage Renal Disease (ESRD) program have been collected annually since 1995. RESULTS: In 1995, 79% of the respondents used continuous ambulatory peritoneal dialysis (CAPD) rather than automated peritoneal dialysis (APD). The mean hematocrit (Hct) of PD patients was 32% and only 66% of individuals had a measurement of dialysis adequacy reported. The mean weekly Kt/Vurea (wKt/V) and weekly creatinine clearance (wCCr) reported for CAPD patients in 1995 were 1.9 and 67 L/1.73 m2/week, respectively. In 2000 the median age of PD patients was 55 years and 63% were white. The leading cause of ESRD was diabetes mellitus (34%) and 54% of adult PD patients performed some form of APD rather than CAPD. Age, sex, size, hematocrit, peritoneal permeability, dialysis adequacy, residual renal function and nutritional indices did not differ between APD and CAPD patients. The mean hemoglobin (Hb) for the 2000 PD-CPM population was 11.6 +/- 1.4 g/dL (mean +/- 1 SD) and 11% of patients had an average Hb below 10 g/dL. The average serum albumin was 3.5 +/- 0.5 g/dL by the bromcresol green method and 56% of subjects had an average serum albumin equal to or above 3.5 g/dL (or 3.2 g/dL by bromcresol purple). In 2000 85% of patients had a dialysis adequacy measurement reported and the mean calculated wKt/V and wCCr were 2.3 +/- 0.6 and 72.7 +/- 24.9 liters/1.73 m2/week for CAPD patients and 2.3 +/- 0.6 and 71.6 +/- 25.1 L/1.73 m2/week for APD patients. PD subjects had a mean body weight of 76 +/- 19 kg and body mass index (BMI) of 27.5 +/- 6.4 kg/m2. The protein equivalent of nitrogen appearance (nPNA) of these patients was 0.95 +/- 0.31 g/kg/day, their normalized creatinine appearance rate (nCAR) equaled 17 +/- 6.5 mg/kg/day, resulting in a percent lean body mass (%LBM) of 64 +/- 17% of actual body weight. Serum albumin correlated in a positive fashion with BMI, nPNA, nCAR and %LBM, but not with wCCr. CONCLUSIONS: The majority of indicator variables monitored by the PD-CPM have improved since 1995. PD patients have higher hemoglobins and a greater proportion of patients meet the criteria for adequate dialysis. Serum albumin values, however, remain marginal and unchanged over the five-year project. Furthermore, serum albumin values fail to correlate with the intensity of renal replacement therapy and are not strongly correlated with alternative estimates of nutritional status.

Adult↗

A whole-genome assembly of Drosophila.

We report on the quality of a whole-genome assembly of Drosophila melanogaster and the nature of the computer algorithms that accomplished it. Three independent external data sources essentially agree with and support the assembly's sequence and ordering of contigs across the euchromatic portion of the genome. In addition, there are isolated contigs that we believe represent nonrepetitive pockets within the heterochromatin of the centromeres. Comparison with a previously sequenced 2.9- megabase region indicates that sequencing accuracy within nonrepetitive segments is greater than 99. 99% without manual curation. As such, this initial reconstruction of the Drosophila sequence should be of substantial value to the scientific community.

Algorithms↗

Role of sodium in hemodialysis.

Sodium chloride is the most abundant salt in extracellular fluid. In normal individuals, the tonicity exerted by dissolved sodium chloride determines plasma osmolality and indirectly determines intracellular tonicity and cell volume. Uremic patients retain nitrogenous wastes and have an elevated plasma osmolality. While urea exhibits osmotic activity in serum, no sustained gradient can be established across cell boundaries because it readily diffuses through cell membranes. Thus, sodium remains the major indicator of body tonicity and determines the distribution of water across the intracellular-extracellular boundary, subsequent cell volume, thirst, and, among patients with renal insufficiency, systemic blood pressure. As a result of highly conserved plasma tonicity control systems, uremic subjects demonstrate remarkable stability of their serum sodium. Dialysate is a synthetic interstitial fluid capable of reconstituting extracellular fluid composition through urea extraction and extremely efficient solute and solvent (salt and water) transfer to the patient. Subtle transdialyzer gradients deliver and remove large quantities of trace elements, solvent, and solute to patients, creating a variety of dialysis "disequilibrium" syndromes manifest as cellular and systemic distress. Every dialysis patient uses dialysate, and the most abundant chemicals in dialysate are salt and water. Despite its universal use, no consensus on dialysate composition or tonicity exists. This can only be explained if we believe that dialysate composition is best determined by matching unique dialysis delivery system characteristics to specific patient requirements. Such a paradigm treats dialysate as a drug and the dialysis system as a delivery device. Understanding the therapeutic and toxic profiles of this drug (dialysate) and its delivery device (the dialyzer) is important to safe, effective, goal-directed modifications of therapy. This article explores some of the historical rationale behind choosing specific dialysate tonicities.

Humans↗

1997 Peritoneal Dialysis-Core Indicators Study: Dialysis Adequacy and Nutritional Indicators Report.

The 1997 Peritoneal Dialysis-Core Indicators Study: Dialysis Adequacy and Nutritional Indicators Report documents the current status of peritoneal dialysis within the United States. A national random sample of adult peritoneal dialysis (PD) patients participating in the United States End Stage Renal Disease (ESRD) program was surveyed. PD subjects were large, with a mean body weight of 76 +/- 18.9 kg (mean +/- 1 SD) and a body mass index (BMI) of 27 +/- 6.4. The dialysis prescriptions documented achieved a mean weekly Kt/Vurea (wKt/V) and weekly creatinine clearance (wCrCl) of 2. 45 +/- 2.29 and 65.5 +/- 35.2 L/wk/1.73m2, respectively. The serum albumin of these patients was 3.5 +/- 0.48 g/dL, their normalized protein equivalent of nitrogen appearance (nPNA) 1.0 +/- 0.63 g/kg/d, and their normalized creatinine appearance rate (nCAR) 14 +/- 6.0 mg/kg/d. Serum albumin correlated meagerly but in a positive fashion with BMI, nPNA, and nCAR, and negatively with wCrCl. Among adult US PD patients, serum albumin values appear to correlate poorly with alternative measures of nutritional status and are inversely related to the intensity of renal replacement therapy. The presumptive dietary protein intake (nPNA) and creatinine appearance rate (nCAR) derived for PD patients do correlate in a positive fashion with dialysis delivery, at least up to a wCrCl of 60 to 80 L/wk/1.73 m2 and wKt/V = 2.1, but their values suggest that 30% to 50% of PD patients have marginal nutritional status.

Adolescent↗

Cycler adequacy and prescription data in a national cohort sample: the 1997 core indicators report. Health Care Financing Administration Peritoneal Dialysis Core Indicators Study Group.

BACKGROUND: The Health Care Financing Administration Peritoneal Dialysis Core Indicator Project obtains data yearly in four areas of patient care: dialysis adequacy, anemia, blood pressure, and nutrition. METHODS: Adequacy and dialysis prescription data were obtained using a standardized data abstraction form from a random sample of adult U.S. peritoneal dialysis patients who were alive on December 31, 1996. RESULTS: For the cohort receiving cycler dialysis, 22% were unable to meet the National Kidney Foundation Dialysis Outcome Quality Initiatives (NKF-DOQI) dialysis adequacy guidelines because they did not have at least one adequacy measure during the six-month period of observation. Thirty-six percent of patients met NKF-DOQI guidelines for weekly Kt/V urea, 33% met guidelines for weekly creatinine clearance (CCr), and 24% met guidelines for both urea and creatinine clearances. The mean weekly adequacy values were 2.24 +/- 0.56 for Kt/V urea and 67.5 +/- 24.4 liter/1.73 m2 for CCr, and the median values were 2.20 and 62.25 liter/1.73 m2, respectively. The mean prescribed 24-hour volume was 12,040 +/- 3255 ml, and the median prescribed volume was 11,783 ml. Only 60% of patients were prescribed at least one daytime dwell. By logistic regression analysis, risk factors for an inadequate dose of dialysis included being in the highest quartile of body surface area (odds ratio = 3.3 for CCr and 3.4 for Kt/V urea) and a duration of dialysis greater than two years (odds ratio = 4.2 for CCr and 2.1 for Kt/V urea). CONCLUSION: There is much room for improvement in providing an adequate dose of dialysis to cycler patients. Practitioners should be more aggressive in increasing dwell volumes, adding daytime dwells, and adjusting nighttime dwell times in order to compensate for the loss of residual renal function over time. These changes can only be accomplished if practitioners measure periodically the dose of dialysis as outlined in the NKF-DOQI guidelines.

Adolescent↗

Trends in clinical indicators of care for adult peritoneal dialysis patients in the United States from 1995 to 1997. ESRD Core Indicators Workgroup.

BACKGROUND: This article describes the changes in four core indicator variables: dialysis adequacy, hematocrit, serum albumin, and blood pressure in peritoneal dialysis CAPD and cycler patients over a three-year period. METHODS: A national random sample of adult peritoneal dialysis patients in the United States was drawn each study period. Clinical data abstraction forms were completed by facility staff for patients selected for the sample, returned to the respective network, then forwarded to the Health Care Financing Administration for analysis. RESULTS: The mean weekly Kt/V urea for CAPD patients increased from 1.91 in 1995 to 2.12 in 1997 (P < 0.001) and for cycler patients, from 2.12 in 1996 to 2.24 in 1997 (P < 0.05). The mean weekly creatinine clearance for CAPD patients increased from 61.48 liter/week/1.73 m2 in 1995 to 65.84 liter/week/1.73 m2 in 1997 (P < 0.05). For cycler patients, it increased from 63.37 liter/week/1.73 m2 in 1996 to 67.45 liter/week/1.73 m2 in 1997 (P < 0.05). Despite this increase in adequacy values, less than 40% of peritoneal dialysis patients in 1997 had weekly Kt/V urea or creatinine clearance values that met subsequently published National Kidney Foundation's Dialysis Outcomes Quality Initiative (DOQI) guidelines. These data suggest that the dialysis prescription may not be adequately modified to compensate for increased body weight and for decreased residual renal function as years on dialysis increase. The average hematocrit value increased modestly in both CAPD and cycler patients from 1995 to 1997, and the number of patients with a hematocrit of less than 25% decreased from 6% in 1995 to 1.4% in 1997 (P < 0.001). Both serum albumin values and systolic and diastolic blood pressure values were essentially unchanged during the three-year period of observation. CONCLUSIONS: Despite improvements in dialysis adequacy and hematocrit values, there remains much room for improvement in these core indicator values.

Adolescent↗

Long-term, successful peritoneal dialysis: end-stage renal disease core indicators study data.

The proportion of U.S. dialysis patients using peritoneal dialysis (PD) continues to fall. The reasons for the decline are presumably related to reduced patient recruitment and poor patient retention (technique failure). Yet, the 1998 Peritoneal Dialysis Core Indicators Study (PD-CIS) report suggests that PD provides satisfactory "long-term" renal replacement for many patients, and, further, that this capacity is becoming more obvious and is beginning to mimic center hemodialysis results. Several patient characteristics suggest that the key to successful "long-term" PD involves the delivery of "adequate dialysis" and that increasing attention to PD prescription and dialysis delivery has been accompanied by an improvement in PD technique success.

Female↗

Peritoneal dialysis indices: weekly CrCl and weekly Kt/Vurea are linked.

Peritoneal dialysis uses a biological "membrane," the peritoneum, to control solute movement between the patient and the dialysate. Equilibrium thermodynamic models predict that the movement of small molecules across the peritoneum will be restricted in proportion to their permeability indices, the available membrane surface area, and the solute concentration gradient between plasma water and dialysate. During peritoneal dialysis, the membrane surface area, dialysate flow, and solute concentration gradients are quite similar for small solutes such as creatinine and urea. Hence, the clearances of creatinine and urea should be proportional to one another in a ratio equal to that of their membrane permeabilities; if that ratio is known, a peritoneal creatinine clearance could be derived for any known peritoneal urea clearance, and vice versa. Analysis of patient data supports this hypothesis and suggests that if disparate normalization procedures are avoided, peritoneal dialysis patients without residual renal function will have difficulty consistently attaining the weekly normalized creatinine clearance of > or =60 L/1.73 m2 recommended by the National Kidney Foundation-Dialysis Outcomes Quality Indicators (NKF-DOQI) without achieving a weekly Kt/Vurea of > or =2.5.

Adolescent↗

1996 peritoneal dialysis--core indicators report.

The 1996 Peritoneal Dialysis-Core Indicators Study (PD-CIS) retrospectively reviews a random sample of peritoneal dialysis patients from the United States End-Stage Renal Disease (ESRD) program. Peritoneal dialysis (PD) patients are more likely to have a primary diagnosis of glomerulonephritis, less likely to be of African-American heritage, and are younger than hemodialysis patients. One third of PD patients now perform some form of automated peritoneal dialysis (APD) rather than continuous ambulatory peritoneal dialysis (CAPD). The dialysis prescriptions currently employed do not appear to be based on kinetic principles, and the intensity of dialysis achieved is below the proposed minimal guidelines for 30% of patients. In 1996, the mean dialysis index or wKt/Vurea for CAPD patients was 2.0 +/- 0.5 and was not significantly altered from the 1995 value of 2.1. Eighty-four percent of CAPD patients perform four or fewer exchanges daily, and only 27% of patients have prescriptions using infusion volumes greater than 2 L. Although hematocrits have improved since 1995, 30% of PD patients have a hematocrit below 30%. The mean serum albumin for PD patients is 3.5 g/dL, and 25% of patients have a 6-month average serum albumin value below 3.2 g/dL. In general, the indices monitored as predictive of health and well-being of PD patients afford significant opportunity for improvement.

Adult↗

The effect of uraemia, acidosis, and dialysis treatment on protein metabolism: a longitudinal leucine kinetic study.

BACKGROUND: Uraemia and dialysis are viewed as catabolic processes resulting in malnutrition in chronic renal failure (CRF) patients. To sort out the effects of uraemia, acidosis, and dialysis on protein metabolism, we measured leucine flux in CRF patients before and after initiation of maintenance dialysis. SUBJECTS AND METHODS: Whole-body leucine flux was measured by primed-constant infusion of L[1-(13)C] leucine in nine CRF patients longitudinally; twice before and once after initiation of maintenance dialysis (D). Before dialysis, one leucine flux was measured when the patients were acidotic (A), and the other, when acidosis was corrected with NaHCO, (NA). Five normal subjects underwent one single leucine flux measurement to serve as control (N). Both patients and normal subjects consumed a constant diet for 6 days and leucine flux was measured on the 7th day 12 h post-absorption. Diet for the CRF patients was identical during the three periods. Plasma L[1-(13)C] leucine and L[1-(13)C]KIC were measured by gas chromatography/mass spectrometry and expired 13CO2 by isotope ratio spectrometry. Leucine kinetics were calculated using standard equations. RESULTS: Plasma CO2 levels were 19, 26 and 31 mmol/l in A, NA and D periods respectively. All kinetic results (micromol/kg/h) are presented as means +/- SD in the order of A, NA, D, and N, and CRF values that are statistically different from N are identified (*). The amounts of leucine release from endogenous protein breakdown (Ra or Q) were 101 +/- 12* 95 +/- 9* 113 +/- 22 and 117 +/- 6. Leucine oxidation (C), quantities of leucine irreversibly oxidized to CO2, were 16.5 +/- 5.4, 9.7 +/- 3.7*, 12.3 +/- 3.0*, and 23.2 +/- 3.1. Leucine protein incorporation levels (S) were 85 +/- 10, 85 +/- 8, 101 +/- 19 and 94 +/- 6. The S of 101 in CRF patients at period D was statistically higher than those during A and NA periods. CONCLUSIONS: These data indicate that when acidosis was corrected, CRF patients adapted to lower protein intake by reducing amino-acid oxidation and protein degradation, and maintained protein synthesis at normal levels. Metabolic acidosis impaired the downregulation of amino-acid oxidation. Maintenance dialysis treatment longitudinally restored protein flux to normal and increased protein synthesis. The general notion that uraemia and dialysis are protein catabolic is not supported by this work.

Acidosis↗

Leucine turnover in patients with nephrotic syndrome: evidence suggesting body protein conservation.

Whole-body leucine flux was measured in eight patients with nephrotic syndrome and in five healthy subjects by primed-constant infusion of L-[1-13C leucine]. Plasma enrichment of 13C leucine and 13C alpha-keto-isocaproate (13C KIC) was measured by gas chromatography/mass spectrometry, and expired 13CO2 was measured by isotope ration mass spectrometry. Leucine kinetics, calculated from the primary pool enrichment [13C leucine], showed no difference between the nephrotic patients and the control subjects. Kinetics derived from the reciprocal pool [1-13C KIC] enrichment, however, showed that leucine turnover rates were reduced in the nephrotic patients. The values (mumol/kg per h, means +/- SD) comparing the patients and the control subjects are as follows: rate of leucine release from protein degradation, 99 +/- 6 and 117 +/- 12 (P = 0.007); leucine oxidation rate, 15 +/- 7 and 22 +/- 3 (P = 0.04); rate of leucine incorporation into body protein [S], 84 +/- 10 and 95 +/- 6 (P = 0.04); protein turnover rate, 3.99 +/- 0.49 and 4.72 +/- 0.25 g/kg per d (P = 0.007). Nitrogen balance, measured only in the nephrotic patients, showed a mean positive balance of 0.5 g/d. In the nephrotic and control subjects, protein intake levels were 0.84 +/- 0.16 and 1.17 +/- 0.18 g/kg per d (P = 0.002), respectively, and energy intake levels were 33.3 +/- 8.5 and 33.9 +/- 2.4 kcal/kg per d, respectively. Linear correlations between leucine turnover rates and protein intake were highly significant. This study found that nephrotic patients given a modestly protein-restricted diet were able to maintain positive nitrogen balance. Moreover, leucine flux measurements showed downregulation of protein degradation and amino acid oxidation, reflecting appropriate adaptation to a lower protein intake.

Adult↗

Report from the 1995 Core Indicators for Peritoneal Dialysis Study Group.

The 1995 Peritoneal Dialysis Core Indicators Study was conducted by the Health Care Financing Administration to ascertain standard practices and outcomes in chronic peritoneal dialysis patients. Data from 1,202 patients who did not receive hemodialysis but who were on chronic ambulatory peritoneal dialysis (CAPD) for at least part of the 6-month period between November 1, 1994, and April 30, 1995, are reported. The mean serum albumin level for this cohort was 3.5 g/dL by the bromcresol green method and 3.2 g/dL by the bromcresol purple method. Data sufficient to calculate a weekly Kt/V(urea) or weekly creatinine clearance were available for only 34% of patient submissions. In these patients, the median weekly Kt/V(urea) was 1.7 using a fixed value for V of 0.58 x body weight and was 2.0 using the Watson equation to calculate V; the median weekly creatinine clearance was 60.7 L/wk/1.73 m2. The mean hematocrit for this cohort was 32% and the average weekly recombinant human erythropoietin (rHmEPO) dose was 115 u/kg. Hematocrit values < or = 30% were found in 50% of black patients and 31% of white patients. The average blood pressure among peritoneal dialysis patients was 139/80 mm Hg, with 29% of patients having a systolic blood pressure exceeding 150 mm Hg and 18% a diastolic blood pressure greater than 90 mm Hg. In summary, serum albumin levels were significantly lower in peritoneal dialysis patients than in hemodialysis patients. Approximately one third of peritoneal dialysis patients did not have an adequacy measure obtained during the 6-month observation period. A significant minority of patients had either inadequately treated anemia of chronic renal disease or hypertension. There is an opportunity to substantially improve the medical care provided to chronic peritoneal dialysis patients.

Adolescent↗

Dialysate sodium delivery can alter chronic blood pressure management.

Low dialysate sodium concentrations can reduce postdialysis thirst and serum sodium activity, but patients typically experience dialysis hypotension, fatigue, disequilibrium, and cramps. "High-sodium" hemodialysis minimizes dialysis disequilibrium but increases the serum sodium activity of most patients. Programmed "variable-sodium" dialysis can minimize dialysis discomfort but may also alter the sodium kinetics from those of "high-sodium" dialysis. We designed a cross-over study with random order assignment to determine whether a "variable-sodium" dialysis program could reduce the blood pressure of dialysis patients without increasing dialysis morbidity. Dialysis with a dialysate sodium of 140 mEq/L was compared with dialysis with a programmed exponential decrease of dialysate sodium from 155 mEq/L to 135 mEq/L. Dialysate sodium was then held constant at 135 mEq/L for the final half hour of dialysis. Eighteen patients completed the 7-month study, each receiving 3.5 months of experimental and 3.5 months of standard therapy. Programmed "variable-sodium" dialysis resulted in a reduction in antihypertensive drug use without alterations in predialysis blood pressure, interdialytic weight gain, ultrafiltration tolerance, or the frequency of symptomatic dialysis cramps or hypotension. Patients did, however, have lower postdialysis standing blood pressures and higher postdialysis target weights during programmed "variable-sodium" dialysis.

Adult↗

Impaired bone growth after ileal augmentation cystoplasty.

PURPOSE: We evaluated how ileal augmentation cystoplasty predisposes growing animals to hyperchloremic acidosis and abnormal skeletal development. MATERIALS AND METHODS: Weanling female Wistar rats weighing 35 to 50 gm. underwent ileal augmentation cystoplasty or sham operation consisting of a similar ileal resection and closure (ileoileostomy). Both groups were stressed with 1% ammonium chloride loading. Serial bone densitometry measurements, weight and blood gas studies were performed in an 8-week growth period. Femur bone ashing and mineral analysis, arterial blood gas studies and serum bone mineral determinations (calcium, magnesium and phosphorus) were obtained at study conclusion. RESULTS: Augmented and control animals had similar serum calcium, phosphorus and magnesium concentrations. In augmented animals metabolic acidosis developed with respiratory compensation and decreased mean serum bicarbonate plus or minus standard deviation compared to controls (18.34 +/- 3.23 versus 21.76 +/- 2.46 mEq./l., p <0.003). Growth curves of both groups were similar, although augmented animals had shorter femur lengths than controls (p <0.04). Bone density results were mixed. Whole body bone density was decreased (p <0.05), while bone ash and mineral content (except phosphorus) were not. When rats with augmentation cystoplasty given 1% ammonium chloride were fed an equal molar diet of sodium bicarbonate, metabolic acidosis and bone mineral density normalized to control values. CONCLUSIONS: Acid challenged weanling rats that underwent ileal augmentation cystoplasty demonstrated decreased bone mineral density and growth compared to controls. These changes were prevented by bicarbonate replacement.

Acidosis↗

Regional hemodialysis anticoagulation: hypertonic tri-sodium citrate or anticoagulant citrate dextrose-A.

Regional citrate anticoagulation should be a simple process of substituting hypertonic (1.6 mol/L) citrate for heparin and adjusting the infusion to obtain an arterial activated clotting time of 150 to 200 seconds. Serious, documented complications of citrate anticoagulation involve citrate intoxication during isolated ultrafiltration; hyperaluminemia, hyperammonemia, and hypernatremia during sorbent dialysis; and profound alkalosis, paresthesias, arrhythmia, and cardiac arrest during bicarbonate dialysis. We suspected that some of these complications could be avoided by using anticoagulant citrate dextrose-A (ACD) rather than hypertonic tri-sodium citrate (TSC) as the anticoagulant. In a cross-over study with random assignment order eight adults underwent mid-week dialyses with ACD (0.113 mol/L citrate) and TSC (1.6 mol/L citrate) regional citrate anticoagulation. Predialysis to postdialysis changes in Na (mEq/L), Ca (mg/dL), ionized Ca (mg/dL), pH, and HCO3 (mEq/L) are listed below. [Table in journal] Using continuous blood flow and avoiding isolated ultrafiltration and sorbent dialysis should prevent the delivery system complications of regional citrate anticoagulation. During this evaluation isotonic and hypertonic citrate resulted in similar serum sodium changes, and standard dialysate effectively reversed the citrate/calcium interaction of both hypertonic and isotonic citrate infusions to restore homeostasis without a separate calcium infusion. The combination of TSC and bicarbonate dialysate does produce a profound metabolic alkalosis, which is lessened by using ACD. In general, regional citrate anticoagulation is simplified by using standard dialysate with a hypertonic rather than an isotonic citrate infusion, and dangerous complications are further evaded by adjusting the dialysate bicarbonate to 25 to 30 mmol/L or substituting a mixture of citric acid and TSC (ACD) for TSC.

Adult↗

The influence of ipsapirone, a 5-HT1A agonist, on sleep patterns of healthy subjects.

Ipsapirone is a new pyrimidinylpiperazine ligand specific for 5-HT1A receptors, with potential therapeutic use in affective disorders. Because 5-HT is involved in the regulation of sleep, we investigated the effect of ipsapirone hydrochloride on sleep patterns in 18 normal, healthy subjects of both sexes. Compared to placebo, ipsapirone 5 mg administered by mouth three times daily for 14 days decreased rapid eye movement (REM) sleep duration and, by the tenth day of treatment, began to reduce slow wave sleep (SWS) duration. The decrease in REM sleep occurred in the first 3 h of sleep. The latency to REM sleep was increased from the first night following ipsapirone administration, remained increased throughout the 14 days of administration, and fell to equal latency on placebo immediately administration ended. Subjective assessments of sleep revealed no differences between ipsapirone and placebo. Our experiments confirm a role of 5-HT1A receptors in sleep. The effects of ipsapirone on the sleep patterns of patients with affective disorders still need to be determined.

Adult↗