Biomedical subjects
Publications and source records attributed to D R Wilson.
The authors outline the history and activities of a Patients' Rights and Ethics Committee established by a major psychiatric hospital. In this context they discuss the impact of contemporary issues, the need to re-emphasize rights that have been established, and various factors influencing the approach and effectiveness of such a Committee.
The calcium content of the central one third of the skeleton was measured using neutron activation analysis in 109 patients with idiopathic calcium nephrolithiasis. The bone mineral content (calcium bone index or CaBI, corrected for body size) was significantly decreased by 5.2% in 20- to 60-year-old patients with calcium nephrolithiasis (p less than 0.01). Under age 50 the decrease was more marked in 64 males (7.1%; p less than 0.02) than in 21 females (4.1%; p = NS). There was a significant negative correlation of CaBI with fasting urine calcium/creatinine ratio (r = 0.39; p less than 0.01), but no correlation with age or indices of parathyroid function. The decrease in bone mineral content did not appear to be progressive. The decrease in CaBI indicates negative calcium balance, either in the past or at present, in patients with calcium nephrolithiasis and does not favour increased intestinal absorption as a primary cause. The lack of correlation of CaBI with parameters of parathyroid function does not support a primary renal loss of calcium. The results suggest that increased bone turnover may be an important component of disordered calcium metabolism in patients with calcium nephrolithiasis.
Explore the source record for details and available documents.
Blood supply and drainage of the outer medulla of the rat kidney were studied by scanning electron microscopy of vascular casts, using both arterial (n = 10) and venous (n = 10) injections of resin. Both outer and inner stripes of the outer medulla were supplied through different arterial capillary networks arising from efferent arterioles and arterial (descending) vasa recta. In contrast to previous studies using silicone rubber and light microscopy, a rich arterial capillary network supplying the outer stripe was demonstrated. Capillaries in the outer stripe and outer part of the inner stripe drained into venous vasa recta between vascular bundles, while capillaries in the inner part of the inner stripe drained into venous vasa recta within the bundles. The results indicate that each zone in the outer medulla is supplied through separate capillary networks. The demonstration of a rich capillary network in the outer stripe of the outer medulla suggests that the predilection of this zone for tubular necrosis with ischemic or toxic injury is not related to a sparse capillary blood supply.
Zein cDNA clones were used to study the organization of zein genes within the genome of the inbred maize W64A. When individual clones for the two larger molecular-weight classes of zein proteins (Mr = 22,000; Mr = 19,000) were used as probes for Southern blot hybridizations of genomic DNA, multiple restriction fragments were found to hybridize. Reconstruction analyses using moderately stringent criteria were used to estimate a total of 70-80 zein sequences within the genome of this inbred maize. The hybridization patterns suggest that zein sequences are clustered within the same restriction fragment. When criteria permitting less cross-hybridization of homologous sequences (Tm - 10 degrees C) were used, the banding pattern changed, with some of the bands being reduced in intensity or eliminated entirely. Therefore, by control of hybridization criteria, particular zein genes may be more readily distinguished in a Southern blot analysis. The Southern blot hybridization pattern for the Mr = 15,000 zein was less complex. Only a single major band was found, with sufficient hybridization intensity for two or three genes. Genomic Southern analyses of other inbred maizes and related grasses showed similarly complex hybridization patterns with cDNA probes for the 19,000- and 22,000-molecular-weight zeins, suggesting that these sequences have been conserved over evolutionary time. The zein multigene family may therefore have arisen by gene duplication before divergence of the maize, teosinte, and Tripsacum species from a common ancestor.
The possible role of the tubuloglomerular feedback (TGF) mechanism in the altered glomerular hemodynamics and tubular reabsorption which occur with prolonged (24-hr) ureteral obstruction and the changes in renal interstitial hydrostatic and oncotic pressure which may modulate TGF sensitivity were examined. The proximal tubule stop-flow pressure (PSF) response to increased distal tubular flow rates (TGF activity) was determined in rats with sham operation, 24-hr unilateral ureteral obstruction (UUO), or 24-hr bilateral ureteral obstruction (BUO), both before and for 2 hr after relief of obstruction. Subcapsular hydrostatic pressure, lymph flow and oncotic pressure, clearance and excretory data were measured in the second series of animals. During and after release of UUO, TGF sensitivity was increased, as indicated by the marked decrease in the loop perfusion rate at which 50% of the maximum decrease in PSF occurred (the turning point of TGF activation). Interstitial oncotic pressure but not hydrostatic pressure was significantly increased in UUO kidneys. In BUO rats, the turning point for TGF activation was slightly higher than the controls and the change in PSF with maximum loop perfusion rates was reduced, indicating a blunting of the TGF response before and particularly during postobstructive diuresis after release of BUO. Interstitial hydrostatic and oncotic pressures were both slightly increased resulting in no changes in net interstitial Starling forces. We conclude that enhanced TGF sensitivity after release of prolonged UUO, associated with increased interstitial oncotic pressure, may play a role in preventing postobstructive diuresis, while the blunting of TGF sensitivity after BUO may contribute to this phenomenon.
Changes in mitochondrial (Mito) calcium (Ca++) and Mito respiration have been demonstrated 24 hr after a renal ischemic insult. The Ca++ accumulation has been suggested to contribute to impaired Mito function; alternatively, the Mito Ca++ accumulation could be a late event resulting from cell death. The present aim was, therefore, to determine the sequence of changes in Mito function in ischemic acute renal failure (ARF) induced by 45 min of bilateral renal pedicle clamping in the rat. Animals were studied at the end of clamping, 1, 4, and 24 hr after reflow. By 24 hr, the serum creatinine level had risen progressively to almost ten times control values and fractional excretion of sodium and water were increased. Mito respiration (state 3, adenosine diphosphate-stimulated; acceptor control ratio, state 3/state 4; and uncoupled, FCCP) was severely depressed immediately after 45 min of clamping but improved significantly at 1 and 4 hr after reflow although remaining below sham-operated controls. At 24 hr, when ischemic ARF was established, Mito respiration was again severely depressed. Mito Ca++ was increased slightly but significantly at the end of clamping and increased progressively at 1, 4, and 24 hr after reflow. The Mito Ca++ accumulation was not only demonstrated to occur very early after the ischemic insult, but was relatively selective since it was not associated with Mito Mg++ accumulation. Moreover, the increased Mito Ca++ during reperfusion (1, 4, and 24 hr) demonstrated a significant correlation with the decreased state 3 respiration and the rising serum creatinine level (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Objective measurements of blood flow changes following UV irradiation in the skin of human volunteers have been made with the noninvasive technique of laser Doppler velocimetry (LDV). This optical procedure allowed perfusion (number of red cells X velocity) alterations in the cutaneous microcirculation to be monitored after exposure of the skin to UVA and UVB + UVC radiation. Response curves were obtained in 6 subjects following irradiation at 4 times the minimal UVB + UVC erythema dose (MED). Measurements were made on control (untreated) skin and on skin pretreated with a sunscreen lotion. It was found that: (1) the lotion vehicle had no protective effect, (2) the active sunscreen constituent (2-ethylhexylcinnamate, 5%) was significantly protective, and (3) the presence of bergapten (5-methoxypsoralen, 30 ppm) did not enhance or diminish the cinnamate protective effect. LDV measurements in 5 subjects were also taken during and subsequent to 5 daily exposures to 1 MED of UVB + UVC radiation. Control and pretreated skin sites were again studied and similar protective effects were observed. However, on subsequent reexposure of these sites to 4 MED of UVB + UVC, 14 days after the first of the 5 single MED doses, no significant change in skin blood perfusion was detected at either control or pretreated sites. In a separate series of experiments, LDV data were collected after UVA radiation exposures up to 15 J/cm2. No changes in microcirculation perfusion were detected in any of the situations considered. All LDV measurements were made with 2 instruments of slightly different design and were compared to subjective assessments of erythema performed by a single observer. The results suggest that LDV has significant potential as a means to quantify (1) UV exposures in excess of the MED and (2) the inhibition of UV-induced changes in microcirculatory flow by chemical protectants.
Changes in medullary circulation may contribute significantly to the pathogenesis of ischemic acute renal failure. The microcirculation of the outer medulla of the rat kidney was studied by morphometry, carbon injection, and scanning electron microscopy of vascular casts after temporary renal ischemia. Morphometry showed a markedly reduced vascular area and an increased tubular epithelial cell area in the outer stripe of the medulla 2 hours after blood reflow. Maximum diminution in vascular area occurred 24-48 hours after reflow, with swollen and later necrotic tubular epithelium compressing the surrounding vascular compartment. Outflow blockade of venous vasa recta in the outer stripe caused congestion of the inner stripe. Carbon injection and scanning electron microscopy of vascular casts confirmed the perfusion defects of the outer stripe. These results suggest that decreased blood reflow to the outer stripe of the medulla secondary to tubular epithelial cell swelling and necrosis plays a significant role in the pathogenesis of ischemic acute renal failure in the rat.
The effect of 8 days skin occlusion on Pityrosporum orbiculare, bacteria, skin PCO2, pH, transepidermal water loss (TEWL), and water content (WC) was studied. P. orbiculare counts increased from a baseline of 2.1 X 10(2)/cm2 to 2.3 X 10(3)/cm2 after 3 days occlusion; bacterial counts increased from 2.9 X 10(3)/cm2 to 1.8 X 10(5)/cm2 after 8 days occlusion. pH increased during occlusion from 5.6 to a maximum at day 3 of 6.7; TEWL increased to a maximum of 11.74 g m-2 h- after 3 days occlusion compared with 4.39 g m-2 h-1 before. P. orbiculare counts, pH, and TEWL were lower at 8 days than at 3 days occlusion. WC and PCO2 remained high after 8 days; relative WC was then 60.6% compared with 52.5% before occlusion; PCO2 was 63.1 mm Hg compared with 53.1 mm Hg before occlusion. The increased levels of these factors may partially explain the higher risk of infection in occluded compared with non-occluded skin.
The complaints of depressed patients were investigated in a private, single-physician family practice clinic. Complaints and visits of depressives were compared to those of age- and sex-matched non-depressed controls over a period of 3 years beginning 18 months prior to the diagnosis of depression. Pain, functional and anxiety complaints signalled the onset and paralleled the course of depression. Somatic complaints were a conspicuous mode of presentation in this family practice. These somatic features are not among the usual diagnostic and research criteria for depression (DSM-III, Feighner Criteria and RDC) although they appear to be a major feature in the natural history of depression.
The distal convoluted tubule is thought to be the principal site of action of thiazide diuretics, but, to our knowledge, there are no studies of their possible effects on collecting duct transport. Microcatheterization of the inner medullary collecting duct (IMCD) was carried out in rats undergoing a modest diuresis, natriuresis, and chloriuresis from hydro-chlorothiazide (2 mg/kg/hr) and in normal controls. Delivery of fluid, sodium, and chloride to the beginning of the IMCD was increased, but not significantly, while the load remaining at the papillary tip (end) of the duct was increased markedly by hydrochlorothiazide. Chloride reabsorption in the IMCD was affected most markedly; the chloride reabsorption between the beginning and end of the duct, as a fraction of the delivered load, was reduced from 70.4 +/- 5.4% in controls to insignificant amounts with hydrochlorothiazide (8.2 +/- 11.5%, P less than 0.001). The fraction of delivered sodium reabsorbed along the collecting duct was decreased from 78.5 +/- 4.9% in controls to 37.2 +/- 12.4% (P less than 0.005) in thiazide-treated rats and fluid reabsorption was decreased from 59.4 +/- 4.0% in controls to 31.9 +/- 5.1% (P less than 0.005). Small but significant potassium secretion into the IMCD occurred with hydrochlorothiazide, probably secondary to the marked increase in potassium delivery to the duct. Increased potassium excretion could account for a maximum of 50% of chloriuresis with hydrochlorothiazide. The observation that thiazide diuretics decrease chloride, sodium, and fluid reabsorption in the medullary collecting duct, like the recently demonstrated inhibitory effect of furosemide on this nephron segment, has significant implications for the rationale for diuretic use.
Previous studies have shown that the 24-h unilateral ureteral obstructed kidney (UUO) responds to acute renal denervation after relief of obstruction with an increase in glomerular filtration rate (GFR), renal plasma flow (RPF), natriuresis, and diuresis, while the 24-h bilateral ureteral obstructed kidney (BUO), undergoing postobstructive diuresis after relief of obstruction, shows no response to acute denervation. In the present study, renal tissue norepinephrine (NE) content and concentration were found to be markedly decreased in the BUO kidney suggesting partial renal denervation, while renal NE content was normal in the UUO kidney. The decrease in renal NE content in the BUO kidney was organ specific since myocardial NE was not affected, and was not due to acute uremia, since rats made uremic by 24 h of total intravenous urine reinfusion showed no change in renal NE content. Renal dopamine content was markedly increased in the UUO kidney, perhaps as a result of renal decarboxylation of dopa and failure of excretion, while renal and myocardial epinephrine content were increased in the BUO and urine reinfused groups, both of which were subjected to the stress of acute uremia. The decrease in renal NE content in the kidney undergoing postobstructive diuresis after relief of 24-h BUO probably indicates damage to sympathetic nerve terminals by high intrarenal pressure during BUO and suggests that partial renal denervation could contribute to the functional changes observed in this experimental model.
The effect of furosemide on inner medullary collecting duct chloride reabsorption has not been determined, and the blunting of furosemide action by drugs that inhibit prostaglandin synthesis, while known to occur, has not been examined in detail. The effect of indomethacin and meclofenamate on furosemide diuresis was studied in the rat using clearance and collecting duct microcatheterization methods. Furosemide-treated control animals showed complete inhibition of chloride, sodium, and water reabsorption in the inner medullary collecting duct. Rats given indomethacin or meclofenamate before and during furosemide administration showed marked reduction of the chloriuresis, natriuresis, and diuresis. Reduced delivery of sodium and chloride to the beginning of the inner medullary collecting duct, associated with a decrease in glomerular filtration rate and increased reabsorption in more proximal nephron segments, was largely responsible for the reduced natriuresis and chloriuresis during inhibition of prostaglandin synthesis. In addition, indomethacin increased collecting duct NaCl reabsorption toward normal, but meclofenamate showed no such effect. The results indicate that furosemide inhibits medullary collecting duct reabsorption of chloride, sodium, and water in the rat. The blunting of diuretic action seen with inhibition of prostaglandin synthesis is largely, although not entirely, due to effects of indomethacin and meclofenamate on furosemide action at nephron sites proximal to the collecting duct.
Ischemic ARF is characterized by progressive mitochondrial accumulation of Ca++ which is inversely correlated with the level of oxidative phosphorylation. At least two possibilities exist which would be compatible with these data 1) depressed respiration leads to Ca++ accumulation or 2) increased mitochondrial Ca++ leads to reduced mitochondrial respiration. We favor the latter hypothesis for the reasons outlined above; furthermore, this conclusion is supported by the observations of Lehninger, made some 20 years ago: first, that either oxidative phosphorylation or mitochondrial Ca++ accumulation can be accomplished by intact mitochondria but that these events cannot occur simultaneously and second, that Ca++ accumulation takes precedence over oxidative phosphorylation. Our observation made during post-ischemic reflow that mitochondrial Ca++ accumulation occurs to a significant degree, strongly suggest a potential role for mitochondrial Ca++ overload in the pathogenesis of ARF. Nevertheless, this is not an irreversible pathogenetic process. Clearly, impermeant solutes, vasodilators and Ca++ membrane blockers will alter the natural history of this injury and prevent the severity of the functional defect. A common mechanism of action may involve direct or indirect modification of cellular Ca++ overload in renal vascular and epithelial tissue. The vascular smooth muscle may then revert to a less constricted state with a subsequent more rapid recovery of renal blood flow and that the renal epithelial cell death may be minimized thereby reducing tubular obstruction.
Surveys of nephrologists in Canada indicate that the incidence of analgesic nephropathy has decreased by about 50% in less than a decade in association with the removal of phenacetin from the market and restrictions on the availability analgesic mixtures containing acetaminophen and acetylsalicylic acid. The number of patients presenting with end-stage renal disease attributed to analgesics has shown a similar drop. These decreases have occurred in spite of increased consumption of acetaminophen as a single analgesic. Analgesic nephropathy should not be expected to disappear, however, since there is evidence that the drugs still in use have the potential to cause renal damage.
Explore the source record for details and available documents.
Explore the source record for details and available documents.