Effect of aging on the body composition of dialyzed subjects. Comparison with normal subjects.

A bioimpedance analyzer (BIA-CHIP; Akern RJL System) was applied to 366 normal subjects (171 men and 195 women). Each gender group was divided into eight groups, according to age: 20-29 years; 30-39 years; 40-49 years; 50-59 years; 60-69 years; 70-79 years; 80-89 years; and 90-95 years. The same was done with 44 hemodialysis patients (22 men, 22 women), each being evaluated 15 times over a period of 5 years: these were divided into seven groups (seven, because no patient was older than 89) using the same criteria. For each subject, 23 parameters were determined: 5 directly measured (height, weight, resistance, reactance, phase angle) and the others (fat and lean mass, body water, body cell mass, extra and intracellular water, etc.) from appropriate equations. Twenty-four thousand data points were collected and served to form a data bank. Men and women on hemodialysis showed different effects of aging: women normalized their BC at an age > 70 years, whereas men continued to have a muscle mass lower than that of normal subjects until the age of 80. A computerized program (Nutritio) permits fast and reliable evaluation of the nutritional status of hemodialysis patients, each subject being compared with both the similarly aged population (dialyzed or not) or with his or her own data, obtained over time.

Dialysis kinetics of homocysteine and reactive oxygen species.

In patients with chronic renal failure who undergo hemodialysis (HD), the antioxidant system is inadequate to correct the imbalance between the generation and scavenging of reactive oxygen species. To clarify the role of six different membranes on oxidative stress, the authors measured plasma lipid peroxidation and erythrocyte (E) concentrations of several antioxidant enzymes in 30 HD patients: 20 on bicarbonate HD, 4 on paired filtration dialysis, 3 on acetate free biofiltration, and 3 on hemodiafiltration. Before, during, and after the first session of the week (at times 0, 30, 60, and 120 min, end, and 30 min after end of HD), several blood samples were drawn. Plasma (P) homocysteine (HCY), cysteine (CYS), malondialdehyde (MDA), E-glutathione (GSH), glucose-6-phosphodehydrogenase, glutathione reductase (GR), glutathione peroxidase (GP), catalase (CAT), and superoxide dismutase (SOD) were determined. All six membranes (Hemophan [HEMO]; cellulose diacetate [DIAC]; acrylonitrile-69 [AN69]; polymethylmethacrylate [PMMA]; cuprammonium rayon [CURAY]; polysulfone plus hemophan [PS + HEMO]) induced a significant decrease in plasma lipid peroxidation (p < 0.001) and an increase in E-GSH, GR, GR + flavinadenine dinucleotide, GP, and SOD (p < 0.001). Some membranes, however, showed some peculiar effects on reactive oxygen species: HEMO is better than DIAC, as far as P-MDA and P-HCY are concerned; PMMA induces higher changes in E-GR and P-CYS than does HEMO; and patients chronically using PMMA and PS + HEMO membranes show the lowest P-HCY levels both before and after dialytic sessions. Based on these changes, implications as to the effects on vascular disorders could be derived.

Free radicals and oxidative stress challenge dialysis patients: effects of two different membranes.

Patients with end-stage renal disease (ESRD) who undergo hemodialysis manifest pronounced oxidative stress (OS), for the antioxidant system is inadequate to correct the imbalance between generation and scavenging of reactive oxygen species (ROS). To clarify the role of two different membranes on the OS, we measured plasma lipid peroxidation (LPO) and erythrocyte concentration of several antioxidant enzymes on 20 controls and 6 patients on bicarbonate dialysis (BHD). At 7 days intervals, 2 BHD sessions were done on the same 6 hemodialysis patients: the two BHD sessions were similar, except for the membrane used (cuprophan, first study; regenerated cellulose = Bioflux, second study, 7 days later). Before, during, and after each session (0', 30', 60', 120', end, 30' after BHD end), several blood samples were drawn. Lipid peroxidation and erythrocyte glutathione (GSH), superoxide dismutase (SOD), and catalase were spectrophotometrically determined (Bioxytech, France), but for erythrocyte glutathione peroxidase (Gpx) and G-6-PD, Gunzler's and Beutler's methods were used, respectively. Both membranes induce a significant decrease in LPO (p < 0.01) and an increase in erythrocyte SOD (p < 0.05). Bioflux shows some peculiar effects: a significant increase in erythrocyte GSH (p < 0.05) and erythrocyte catalase (p < 0.01) with a gradual increase of erythrocyte SOD and catalase/SOD ratio. Cuprophan, on the contrary, causes a sudden increase in erythrocyte SOD, while erythrocyte catalase decreases. These data support the view that Bioflux induces an OS lower than cuprophan because with the former, increased H2O2 production leads (thanks to catalase and GPx action) to water generation. With cuprophan, instead the reduced SOD/catalase ratio causes a greater H2O2 generation and a lower conversion to water.

Do different dialytic techniques have different atherosclerotic and antioxidant activities?

To compare the chronic effect of several dialytic techniques (bicarbonate dialysis, BHD; acetate free biofiltration, AFB; hemodiafiltration, HDF; paired filtration dialysis, PFD) on atherosclerosis and antioxidant activity, three different indices were created. The first (atherosclerotic index = AI) is formed using the sum of three plasma substances: MDA, Hcy, and Cys (malondialdehyde, homocysteine, cysteine). The second (antioxidant activity index = AOAI) is the sum of five erythrocyte (E) parameters: E-GSH, GPx, CAT, SOD, GR (E-glutathione, E-glutathione peroxidase, E-catalase, E-superoxide dismutase, E-glutathione reductase). The third (defense index = DI) is derived from the previous two: (AOAI - AI). The indices were so expressed as AI in mmol/L, AOAI in U/g hemoglobin (Hb), and DI in arbitrary units. These indices were calculated in 20 controls and 51 chronic HD patients (26 female, 25 male) before, during, and after the first session of the week. HD patients were divided according to their dialytic technique: BHD, n = 35; AFB, n = 5 patients; HDF, n = 7 patients; or PFD = 4 patients. All patients had been treated with a given technique for at least 12 months, before entering the study. As expected, HD patients had AI values higher than controls, both before and after the session, with a mean value of 541 (before) and 331 (after), whereas controls had a mean value of 205. The AOAI was lower than controls, both before and after the session, the mean value being 1,122 (before) and 1,582 (after), that of controls being 2,424. In all cases, PFD gave the best "acute" results; at the end of a PFD session, near normal values of AI, AOAI, and DI (defensive index = AOAI - AI) were obtained.

Role of cellulosic and noncellulosic membranes in hyperhomocysteinemia and oxidative stress.

Hyperhomocysteinemia is an independent risk factor for cardiovascular morbidity and mortality in end-stage renal disease (ESRD) with an increased relative risk (RR) of 1% per micromol/L in total homocysteine concentration. In ESRD patients who undergo hemodialysis (HD), the antioxidant system is largely inadequate in correcting the imbalance between generation and scavenging of reactive oxygen species (ROS). To clarify the role of several cellulosic (CMs) and noncellulosic of synthetic membranes (NCMs) upon hyperhomocysteinemia and the oxidative stress, we measured plasma (P) homocysteine (t-HCY), plasma lipid peroxidation (LPO), and erythrocyte (E) concentration of several antioxidant enzymes in 20 normal subjects, in 35 HD patients treated with CMs, and in 29 patients treated with NCMs. Before, during, and after the first session of the week (at times 0', 120', end, 30' after HD end), blood samples were drawn. Plasma (P) homocysteine (t-HCY), cysteine (CYS), malondialdehyde (MDA), erythrocyte (E)-glutathione (GSH), glucose-6-phosphodehydrogenase (G6PD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and superoxide-dismutase (SOD) were determined. The dialytic procedure significantly decreased the three plasma parameters, but none normalized (as a mean). The E-enzymes scavenging ROS (lower than normal before session) increased throughout the session, but the normal range of activity was never reached. Different membranes have shown different effects. When these effects on P and E spaces were pooled, we were able to classify the membranes as follows. In a general sense, cellulosic membranes are less effective than synthetic membranes both on lipoperoxides (LPO) and antioxidant activity (AOA). Among synthetic membranes, PMMA is the best membrane both for plasma values and lesser enzymatic derangement during the session. A practical system for classifying the anti-atherosclerotic action and antioxidant activity of dialytic membranes is proposed.

Intermittent venovenous hemofiltration as a chronic treatment for refractory and intractable heart failure.

Chronic heart failure (HF) is considered to be refractory when persisting despite an intensive drug regimen, or intractable when requiring "artificial" supports. Among them, hemofiltration (HE) has been used frequently, but only on an "acute" basis, to induce fast and safe water removal. Since 1985 the authors have treated refractory and intractable HF first by means of acute CAVH (continuous arteriovenous HE: 11 patients) and then (1988-1992) with IVVH (intermittent venovenous HE), initially done on an "acute" basis (13 patients) and then an a chronic basis (CIVVH): 8 subjects (6M, 2F; mean age, 60.8 years), 3 with RCHF and 5 with ICHF. This report deals with our experience in CIVVH. All patients were in severe failure. During a follow-up period of 63 months (range, 1-17/patient), 82 IVVH treatments (10.2/patient) were carried out, using this schedule: permanent Tesio catheter in superior vena cava, 0.6 m2 filter, double blood pump (blood flow = 80-250 ml/min); transmembrane pressure = 50-150 mmHg; mean ultrafiltration = 19 ml/min; replacement fluid = 8.6 ml/min; and session time = 340 +/- 88 min, according to individual dry weight (bioimpedance system). Six patients died (1-13 months after IVVH began); four of six had ICHF and two of six had RCHF; five of eight patients showed a significant amelioration of functional state, changing from fourth to third, to second and first degree failure, but this was after heart transplantation. In all cases a marked reduction in the drug regimen and in hospitalization was the rule.

The plasma glutathione peroxidase enzyme in hemodialyzed subjects.

The kidney is probably the major site of production of the plasma enzyme glutathione peroxidase (GSHPx-P). For this study, GSHPx-P activity was determined in 40 healthy people, in 34 patients with differing degrees of renal impairment, and in hemodialysis patients from whom blood samples were withdrawn either before or after each session (18 patients) or throughout the dialysis session (27 patients). Hemodialysis patients were treated by means of different techniques (bicarbonate hemodialysis, hemodiafiltration, and acetate free biofiltration), and different membranes (cuprophane, polyacrylonitrite, and polymethylmethacrylate). The following results were obtained: 1) GSHPx-P activity was significantly decreased in renal impairment patients; 2) GSHPx-P activity negatively correlated with serum creatinine values in renal impairment patients (r = -0.55; p < 0.001); and 3) the enzyme activity slightly increased after the session in hemodialysis patients. The following conclusions can be drawn: GSHPx-P activity could be new index of renal function, because it was decreased in patients with renal failure; the decrease in GSHPx-P activity paralleled the severity of renal impairment, and was maximal in hemodialysis patients; GSHPx-P activity was slightly raised at the end of the hemodialysis session, concomitant with other enzyme activities (aspartate transaminase, alanine transaminase, and alkaline phosphatase) and total protein concentration. This seems to be attributable to the process of water loss rather than other hypothetical mechanisms, such as A) enzyme activation by either peroxide generation during blood-membrane contact, or by the removal of a hypothetical inhibitor; and B) de novo synthesis in the residual renal mass or in other sites of production.

Pharmacological data and technical feasibility of intraperitoneal 5-fluorouracil administration.

Via a surgically implanted Tenckhoff catheter, 5-fluorouracil was intraperitoneally administered to patients with malignant disease confined to abdominal space. Treatment was well tolerated without local complications. Peritoneal and plasmatic drug levels were measured, showing that: 1) peritoneal drug levels declined as a first order function; 2) plasmatic levels were very close to those reported for continuous i.v. administration, but peritoneal concentrations were much higher (log 1 to 3); 3) concentration x time product had a peritoneum: plasma ratio ranging from 120 to 1350. The hypothesized role of intraperitoneal 5-fluorouracil administration and the questions still to be answered are summarized.

Pharmacologic data and technical feasibility of intraperitoneal doxorubicin administration.

Seventy intraperitoneal administrations of doxorubicin were performed in 12 patients with malignant disease in the abdominopelvic space. Peritoneal and hematologic drug levels were measured by fluorimetric assay. A first-order decline in the peritoneal level was determined (T 1/2 96 +/- 18 min), with a mean drug absorption of 84% in 4 h (range 40-96%) and a mean ratio of a peak dialysate/peak serum level of 111 (range 12-390). Gastrointestinal toxicity was common and peritoneal phlogosis occurred twice. The doxorubicin level and the time of peritoneal exposure seem to be critical factors for major local toxicity. At a moderate concentration doxorubicin can be intraperitoneally administered, but its usefulness is probably confined to patients with minimal abdominal disease.

Different buffers for hemodiafiltration: a controlled study.

Hemodiafiltration (HDF) is usually performed using a dialytic solution (D) containing acetate (A) or bicarbonate (B) and a replacement fluid (RF) containing lactate (L). To clarify the role of buffers in HDF, 11 patients underwent different study periods, each three months long: bicarbonate hemodialysis (BHD = Baseline period); HDF with (A) in D and (L) in RF (first period of HDF); HDF with (A) in D and (B) in RF (second HDF); HDF with (B) in D and (L) in RF (third HDF); HDF with (B) in D and (B) in RF (fourth HDF = BHDF). HDF achieved: 1) an increase in dialytic efficiency (kt/V, 1.28), reducing the time-session (197 min); 2) an improvement in acid-base status (pre-dialytic values in BHDF: pH 7.36; pCO2 39.8 mmHg; HCO3- 21.8 mM/L); 3) better "dry weight" gain (reached in 92.8% of HDF and in 81% of BHD sessions); 4) a significant decrease, in dialytic side-effects (mainly during the third and fourth periods). On the whole, BHDF (HDF done using only bicarbonate buffer) represents an easy and safe technique, leading to better cardiovascular stability than BHD and HDF without bicarbonate buffer.

Geographic tongue. Report of a case showing significant reduction in lingual tactile sensitivity.

A case of a 25-year-old white adult female with geographic tongue is reported. A decrease in lingual tactile sensitivity was indicated to exist as measured through mechanical vibration. This decreased lingual sensitivity remained constant over a 10-week interval, even though the patient developed an overall healthier general outlook during this period. The overt symptoms accompanying this condition also changed from day to day, but appeared to have little or no effect on the overall decreased lingual tactile sensitivity.

Oral vibrotactile assessment procedures: modifications.

An ongoing process to develop oral vibrotactile instrumentation that can be standardized and used in practical assessment of the oral tactile sensory system was reported in The International Journal of Orofacial Myology in March, 1990, by Fucci, Petrosino, and Harris. The material presented in the present article reflects the current research and future direction that the development of this instrumentation is taking. Potential benefits of this instrumentation for individuals working in the area of orofacial myofunctional disorders are suggested.

Listener ratings of the intelligibility of tracheoesophageal speech in noise.

The purpose of this investigation was to determine the extent to which listener ratings of the intelligibility of tracheoesophageal puncture (TEP) speech vary as a function of different signal-to-noise ratios. Fifty college students, 25 men and 25 women (Median age = 19.7 years) participated in the study. They were instructed to assign numbers to audio-recorded speech samples in each of nine signal-to-noise ratio conditions (+65 dB, +20 dB, +15 dB, +10 dB, +5 dB, 0 dB, -5 dB, -10 dB, and -15 dB) in two separate magnitude estimation scaling tasks. During Task 1 the subjects rated the intelligibility of a TEP speech sample. In Task 2 the subjects rated the intelligibility of a normal speech sample. The results indicated that as the levels of background noise increased, listener ratings of intelligibility decreased (F 8,392 = 37.84; p < or = .0001).

Cutaneous temporal resolution values for "sophisticated" and "naive" subjects.

Temporal resolution values for the tactile sensory modality were obtained for two loci, the tongue and the thenar eminence of the right hand, using a two-pulse mechanical stimulus. Two groups of 11 females each, participated in this study. One group was "sophisticated" in terms of educational background and training in experimental procedure. The other group was "naive" in terms of educational background and training in experimental procedure. Analysis showed that both the tongue and hand responded similarly to the fusion task but that there was a significant difference in fusion thresholds for both structures between the sophisticated and the naive groups. The sophisticated subjects showed more acute fusion thresholds for both the tongue and thenar eminence.

Effect of stimulus intensity on lingual vibrotactile fusion thresholds.

Lingual fusion thresholds for a two-pulse stimulus were obtained at a 15-dB sensation level and a 35-dB sensation level for 15 subjects (18 to 22 yr.). The 35-dB sensation level provided better temporal resolution thresholds as well as less variable responses.

Temporal resolution of the aging tactile sensory system.

Oral and nonoral tactile fusion thresholds were obtained for 39 subjects ranging in age from 12 to 76 yr. Regression analysis of the data indicated a trend for fusion thresholds to become poorer with age. Further statistical testing indicated mean threshold and variability differences between subjects when they were placed into four groups according to age.

Lingual vibrotactile sensation magnitudes: comparison of suprathreshold responses for three different age ranges.

Vibrotactile magnitude scaling was performed on three different age groups of six normal subjects each. The psychophysical method of magnitude production was used for the scaling of vibratory stimuli applied to the anterior dorsal surface of the tongue. The older subjects produced shallower upper-slope functions than the younger subjects and also showed greater response variability. Behavioral, anatomical, and physiological factors are discussed.

Stability of magnitude production scales for oral and nonoral vibrotactile mechanoreceptive systems.

The stability of oral and nonoral vibrotactile magnitude scales produced by the method of magnitude production was investigated for 11 adult subjects. Each subject was tested over four sessions separated by 1-wk. intervals. Data analyses included correlations across trials of power function slopes as well as individual adjustments of intensity. Analysis showed a lack of stability over time for the slope functions obtained on the thenar eminence but moderate stability for the functions obtained on the tongue. Individual adjustments on intensity showed consistently high correlations across trials and structures. It was concluded that the subjects' responses were guided by the imposed experimental variables and that each individual's scaling was not necessarily reflected by the correlations based on power function slopes established over the four trials.

Sensation magnitude scales for vibrotactile stimulation of the tongue and thenar eminence.

This study represents the first attempt to generate magnitude-estimation and magnitude-balance functions for the human tongue. Vibrotactile magnitude scales for the tongue and thenar eminence of the hand were investigated for nine adult subjects. The methods of magnitude estimation and magnitude production were used to obtain magnitude-balance functions for both structures. The magnitude-estimation task resulted in magnitude functions for the tongue which were similar in slope value to those found for the thenar eminence. The magnitude-production task also gave magnitude functions which were similar in slope value for the two structures.

Differences in lingual vibrotactile thresholds of sensitivity using adjusted vs fixed methods of vibrator probe-contactor alignment.

The purpose of this study was to compare lingual vibrotactile thresholds of sensitivity obtained using individual subject adjustments of vibrator probe-contractor to lingual surface, with thresholds obtained using a fixed vibrator probe-contactor position across 30 subjects ranging in age from 18 to 26 yr. (M age = 20 yr.). Analysis showed minor (less than 5 dB SPL) differences in lingual vibrotactile thresholds of sensitivity between the two methods of vibrator probe-contactor alignment. For research purposes, the vibrator probe-contactor assembly should be adjusted to each individual's lingual surface, but for clinical-behavioral purposes, it might be sensible to use a fixed vibrator probe-contactor position across subjects, especially when performing research on young children, older adults, and the communicatively handicapped.