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Biomedical subjects

F S Wright

Publications and source records attributed to F S Wright.

At least 37 records · Page 2Linked to original sources
PubMed1990

Cerebral electrical potentials evoked by balloon distention of the human esophagus.

UNLABELLED: Cerebral evoked potentials provide a technique for evaluation of central nervous processing of information derived from a variety of sensory modalities. Evoked potentials associated with balloon distention of the smooth muscle esophagus were studied in 14 adult volunteers. Stimulation was applied via repeated inflation and deflation of a balloon attached to a pressure pump that cycled at 0.2 Hz. Cortical electrical responses were recorded from scalp electrodes at Cz, Cz', and Pz of the international 10-20 System for electroencephalographic recording. The recording electrodes were referenced to Fpz and averaged over a 1-s period for 100 repetitions. Latencies, amplitudes, and waveforms of the evoked potentials were compared with controls consisting of pump on/balloon detached, auditory masking, and conventional somatosensory posterior tibial nerve stimulation. Polyphasic evoked potentials were obtained in all subjects, and maximum positive deflections occurring with latencies of 202-396 ms. Maximal amplitudes ranged from 2.5-8.3 microV. Latencies and amplitudes of the evoked responses were highly reproducible in each subject with considerable variation among subjects. CONCLUSIONS: (a) Reproducible evoked potentials with distinctive waveforms can be recorded in response to esophageal balloon distention in humans; (2) long latency of the evoked potentials suggests involvement of nonmyelinated visceral afferent pathways; (3) the evoked potentials are probably specific to mechanical stimulation rather than being nonspecific arousal responses; and (4) the results support this as a promising new method for investigation of the neurobiology of gastrointestinal sensation in humans that may help clarify pathological conditions of the irritable esophagus syndrome and esophagus-related chest pain.

Adult↗
PubMed1990

Luminal calcium regulates potassium transport by the renal distal tubule.

We examined the effect of changes in lumen calcium concentration on net potassium transport by distal tubules in anesthetized rats. Tubules were perfused with a control solution that resembled interstitial fluid but lacked calcium. Experimental solutions were prepared by adding varying amounts of CaCl2 to the control solution to produce solutions with free ionic calcium concentration ([Ca2+]) of 0.2, 0.4, and 0.8 mM. In paired comparisons 0.2 mM Ca2+ did not affect net potassium transport, whereas 0.4 and 0.8 mM Ca2+ each reduced potassium secretion by approximately 30%. Unidirectional potassium fluxes using 86Rb as a tracer for potassium and transepithelial voltage (VTE) were measured to characterize further the effect of calcium on potassium transport. Presence of 0.8 mM Ca2+ in the lumen did not affect unidirectional absorptive potassium flux; therefore, the decrease in net potassium flux was accounted for entirely by a decrease in unidirectional secretory potassium flux. The lumen negative VTE measured in the late distal tubule decreased during perfusion with 0.8 mM Ca2+. These results are consistent with the hypothesis that increases in lumen (extracellular) calcium concentration in the range normally present in the distal tubule reduce net potassium secretion by decreasing the electrochemical gradient for potassium secretion.

Animals↗
PubMed1990

Episodic symptoms mistaken for seizures in the neurologically impaired child.

We found neurologically impaired children studied by time-locked video-EEG to have episodes of abnormal behaviors which had been mistaken for epileptic seizures. Recognition that other neurologically abnormal phenomena can closely mimic epilepsy is important for prevention of erroneous diagnoses of epilepsy, and thus overtreatment, in this patient population.

Adolescent↗
PubMed1989

Chlorothiazide effect on feedback-mediated control of glomerular filtration rate.

We examined the effect of chlorothiazide (CTZ) on the tubuloglomerular (TG) feedback system in anesthetized Sprague-Dawley rats. During infusion of CTZ (0.25 mg.kg body wt-1.min-1) we found that whole kidney glomerular filtration rate (GFR) decreased by 19% (1.0 +/- 0.1 vs. 0.8 +/- 0.1 ml/min; P less than 0.005). To asses the activity of the TG feedback system during CTZ administration we compared measurements of single-nephron (SN)GFR from tubule fluid sampled separately at proximal and distal sites. During CTZ administration, distally measured SNGFR decreased significantly by 16% (27.3 +/- 1.3 vs. 22.9 +/- 1.1 nl/min; P less than 0.025), whereas proximally measured SNGFR was unchanged. Thus the difference in SNGFR between proximal and distal determination increased during CTZ infusion (4.7 +/- 0.7 vs. 7.7 +/- 0.7 nl/min; P less than 0.025), indicating that CTZ suppresses GFR by TG feedback. Na, K, and Cl concentrations measured in the late proximal tubule fluid during control and CTZ infusions were similar. In early distal tubule fluid samples K and Cl concentrations were unaffected by CTZ infusion, whereas Na concentrations increased by 32% (47.9 +/- 2.7 vs. 63.1 +/- 2.4 mM; P less than 0.001). Proximal tubule microperfusion with 1.0 mM CTZ decreased transport rates of Na and water by approximately 40%, whereas the transport rate of Cl was not affected. In conclusion our results indicate that CTZ reduces GFR by activating TG feedback. The mechanism by which this occurs is in part due to an increase in the strength of the signal.

Absorption↗
PubMed1989

Adaptation of the distal convoluted tubule of the rat. Structural and functional effects of dietary salt intake and chronic diuretic infusion.

We studied the effects of dietary NaCl intake on the renal distal tubule by feeding rats high or low NaCl chow or by chronically infusing furosemide. Furosemide-treated animals were offered saline as drinking fluid to replace urinary losses. Effects of naCl intake were evaluated using free-flow micropuncture, in vivo microperfusion, and morphometric techniques. Dietary NaCl restriction did not affect NaCl delivery to the early distal tubule but markedly increased the capacity of the distal convoluted tubule to transport Na and Cl. Chronic furosemide infusion increased NaCl delivery to the early distal tubule and also increased the rates of Na and Cl transport above the rates observed in low NaCl diet rats. When compared with high NaCl intake alone, chronic furosemide infusion with saline ingestion increased the fractional volume of distal convoluted tubule cells by nearly 100%, whereas dietary NaCl restriction had no effect. The results are consistent with the hypotheses that (a) chronic NaCl restriction increases the transport ability of the distal convoluted tubule independent of changes in tubule structure, (b) high rates of ion delivery to the distal nephron cause tubule hypertrophy, and (c) tubule hypertrophy is associated with increases in ion transport capacity. They indicate that the distal tubule adapts functionally and structurally to perturbations in dietary Na and Cl intake.

Adaptation, Physiological↗
PubMed1989

Sleep, epilepsy, and the EEG in infancy and childhood.

Each of the major epileptic syndromes that occur in infants and children demonstrates relationships to sleep and wakefulness that are particular to that syndrome. These relationships include activation or suppression of clinical seizures during certain portions of the sleep-wake cycle, differences in symptomatology of the seizures or in seizure type, alterations in distribution or morphology of epileptiform waveforms, and changes in duration and composition of sleep stages. Knowledge of the interactions between sleep and seizures helps to increase understanding of the physiological mechanisms underlying epilepsy, as well as to improve clinical diagnosis.

Child↗
PubMed1987

Carbamazepine plasma concentration. Relationship to cognitive impairment.

Neuropsychological function was assessed before and after carbamazepine monotherapy in children with newly diagnosed complex partial epilepsy. Simultaneous video-electroencephalographic monitoring examined the influence of subclinical abnormal electrical discharges on performance. Total and unbound plasma carbamazepine concentrations were examined in relation to changes in performance at low (carbamazepine level, less than or equal to 32 mumol/L [less than or equal to 7.5 mg/L]) and moderate (carbamazepine level, greater than 34 mumol/L [greater than 8.0 mg/L]) drug levels. The data suggest a mild beneficial effect of carbamazepine on speeded eye-hand coordination and, at low drug levels, more rapid processing of items in memory. Efficiency of learning new information and memory-scanning rate displayed a concentration-dependent relationship with carbamazepine level, with poor performance significantly associated with higher carbamazepine plasma concentrations. Carbamazepine free levels were equivalent to total levels in predicting cognitive side effects.

Carbamazepine↗
PubMed1987

Activated T cells in type I Charcot-Marie-Tooth disease: evidence for immunologic heterogeneity.

Common recognized variability in the familial peripheral neuropathy, type I Charcot-Marie-Tooth disease (CMT I), led to an examination of cell-mediated immune responses in 23 CMT I patients. Increased numbers of activated T cells were found in the peripheral blood of 14 (61%) patients using fluorescent monoclonal Ta1 antibody as quantitated by flow cytometry. Altered immunoregulation was also suggested by increased levels of prostaglandin-mediated lymphocyte suppression. In the other nine CMT I patients, immune responses were normal. Lack of a relationship between Ta1 expression and CMT clinical symptoms, but with consistency within six CMT families, support the concept of immunologic heterogeneity in type I CMT with a possible genetic component.

Adolescent↗
PubMed1987

Modification of tubuloglomerular feedback signal by dietary protein.

Compared with the effects of a 6% protein diet, feeding rats a 40% protein diet for 10 days increases glomerular filtration rate and decreases the activity of the tubuloglomerular (TG) feedback control system. The decrease in TG feedback activity results from an increase in the threshold at which the loop of Henle flow rate initiates feedback responses. To determine whether this protein-dependent shift in the TG feedback response curve is caused by changes in either the signal or the sensing mechanism in the feedback pathway, we used micropuncture and microperfusion techniques to study the TG feedback system of rats fed high- or low-protein (40 or 6% casein) diets for approximately 7-10 days. Compared with the rats fed the low-protein diet, in the high-protein group distally measured single nephron glomerular filtration rate was 17% higher, and Na and Cl concentrations in early distal tubule fluid were 30-50% lower. Early distal osmolality was not different in the two groups. TG feedback responses assessed by changes in stop-flow pressure during perfusion of the distal nephron with NaCl solutions did not differ between diet groups. We conclude that the sensing mechanism in the TG feedback system is not altered by this manipulation of dietary protein, whereas the signal eliciting the TG feedback response is affected. Because rats fed a high-protein diet have higher rates of Na and Cl absorption between the late proximal and early distal tubules than do rats fed a low-protein diet, early distal Na and Cl concentrations are reduced, and the signal for TG feedback is diminished in rats fed the high-protein diet.

Animals↗
PubMed1987

Thiazide-sensitive sodium chloride cotransport in early distal tubule.

At least two pathways mediate sodium absorption across the luminal membrane of the renal distal tubule. One pathway is a conductive channel and the other appears to be a coupled Na-Cl cotransport pathway. The distal tubule comprises three segments: the distal convoluted tubule, the connecting tubule, and the initial collecting duct. To provide information about cellular locations of the proposed sodium transport pathways, we perfused early (14-38% of whole distal length) and late (61-83% of whole distal length) segments of whole distal tubules separately in vivo in anesthetized rats. When perfused with a solution that resembles fluid normally arriving at the distal tubule (75 mM Na, 68 mM Cl), rates of sodium absorption were similar in early and late segments (early 68 +/- 29.6, late 67 +/- 27.5 pmol X min-1 X mm-1). When perfused with a solution that resembles interstitial fluid (148 mM Na, 110 mM Cl), sodium transport was significantly higher in early than in late segments (276 +/- 28.4 vs. 113 +/- 29.7 pmol X min-1 X mm-1). Chlorothiazide (10(-3) M), which blocks sodium and chloride absorption in whole distal tubules, reduced sodium and chloride transport to zero in early distal tubules but had no significant effect in late distal tubules. Removing all chloride from perfusion solutions reduced sodium transport in early but not late distal segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Chloride-dependent potassium secretion in early and late renal distal tubules.

Potassium transport by subsegments of the rat surface distal tubule was studied using a modified in vivo microperfusion method. The nephron segments between 14 and 38% and between 62 and 83% of total distal length distance between macula densa region and confluence of tubule with another) were perfused separately. The first of these two segments is composed primarily of distal convoluted tubule (DCT) cells; the more distal segment is made up primarily by initial collecting tubule (ICT) epithelium. Experiments were performed to measure potassium secretion via two pathways: a diffusion mechanism driven by a favorable electrochemical gradient for potassium, and a cotransport mechanism activated when lumen chloride concentration is low. In a first series of experiments, both the DCT and the ICT secreted potassium when perfused with an artificial control solution resembling fluid normally present at the beginning of the distal tubule. Absolute rates of potassium secretion were higher in the ICT than in the DCT. Decreasing lumen Cl concentration stimulated potassium secretion more in the ICT than in the DCT. In a second series of experiments, the subsegments were perfused with a solution in which ion concentrations were raised to levels found in interstitial fluid. Under these circumstances, potassium secretion was lower in both segments. Decreasing lumen Cl concentration resulted in higher rates of potassium secretion in the DCT than those seen in the first series with low chloride; rates of potassium secretion in the ICT were as high as in the first series.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Mechanisms of sodium, potassium and chloride transport by the renal distal tubule.

The distal tubule contributes importantly to renal sodium and chloride reabsorption and potassium secretion. Changes in various factors acting from the luminal or basolateral side of the distal tubule can alter rates of net ion transport. Experiments were designed to examine some of the factors of luminal fluid that can alter sodium, chloride and potassium transport rates. This was accomplished by employing in vivo microperfusion techniques to change luminal sodium, potassium and chloride concentrations and fluid flow rate independent of any effects on systemic homeostatic mechanisms. Results of these experiments indicate that increasing the rate of fluid flow in the distal tubule, within the physiologic range, stimulates potassium secretion, even when sodium concentration does not change. Low sodium concentrations inhibit net potassium secretion only when they are below those that have been measured in this segment under physiologic conditions. Potassium secretion rates increase significantly when the luminal chloride concentration is reduced, an effect that can be dissociated from changes in transepithelial voltage. Sodium absorption is limited by low luminal chloride concentration and chloride absorption is limited by low luminal sodium concentration. These results and others have led us to postulate that at least four different pathways mediate Na, K and Cl transport across the luminal membrane of distal tubule cells. Two pathways permit diffusive movement of cations, one an amiloride inhibitable channel for sodium, the other a barium inhibitable channel for potassium. Two other pathways appear to mediate coupled K-Cl secretion and Na-Cl absorption across the apical membrane of distal tubule cells. A new model of apical membrane transport pathways in the distal tubule is presented.

Absorption↗
PubMed1986

Calcium transport by the proximal tubule.

Taken together the results of these in vivo microperfusion experiments indicate that calcium absorption by the proximal tubule depends on more than one transport mechanism. We have observed that net calcium flux is affected by changes in calcium ion activity (even with constant total calcium concentration) and in transepithelial voltage. This sensitivity of calcium flux to changes in electrochemical driving force points to a diffusional component of calcium transport. Ng et al. (1984) have recently concluded that simple diffusion accounts for the majority of calcium absorption by superficial proximal convoluted tubules of the rabbit. The pathway for this diffusional component may involve paracellular channels. The permeability of this pathway appears to be as high for calcium as it is for sodium, potassium and chloride. Calcium flux is also affected by changes in osmotic water flow. The effect of changes in volume flow on calcium transport occurs even in the absence of concentration changes in bulk solutions. Thus, it does not appear to be the result of changes in passive driving forces secondary to dilution or concentration of tubule fluid. At present we are not able to distinguish between two other possible mechanisms: solute polarization in a microscopic unstirred fluid layer adjacent to the cell membrane, or true entrainment of calcium in the stream of osmotically driven water flow (solvent drag). Either mechanism could provide an additional component of total calcium transport independent of changes in bulk phase ion concentrations and electrical driving forces. A third component of total calcium absorption appears to involve active transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1986

Control by drugs of renal potassium handling.

This review has focused on the influence of several diuretic drugs on potassium handling by the kidney. One class of drugs (loop diuretics) acts by directly inhibiting a potassium absorptive mechanism in the luminal membrane of cells of the thick ascending limb of Henle's loop. Two other groups of diuretics affect potassium transport indirectly by inhibiting salt and water absorption upstream from the potassium secretory site in the late distal tubule: carbonic anhydrase inhibitors act in the proximal tubule; thiazides act in the early distal tubule. The subsequent increase in lumen flow rate then stimulates net potassium secretion by the distal tubule. A fourth class of drugs (spironolactone) acts by antagonizing the response of the distal tubule to aldosterone. These drugs decrease the ability of aldosterone to stimulate distal potassium secretion. Finally, a fifth group of drugs (potassium-sparing diuretics) decreases potassium secretion by increasing the luminal membrane voltage and thus decreasing the electrochemical gradient for potassium exit from the cell.

Acetazolamide↗