Diagnosis of cytomegalovirus infection in renal allografts using fine needle aspiration biopsy.
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Biomedical subjects
Publications and source records attributed to A Wilkinson.
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Rapid tissue diagnosis during acute events associated with renal transplantation is often necessary to permit immediate decisions regarding initiation or modification of therapy. To achieve this, we performed frozen section analyses with cryoprotected alcoholic Bouin's-fixed tissue, which permits evaluation within 2.5 hours. During a 30-month period, 200 allograft biopsies were performed; 68 frozen sections were obtained when deemed necessary by the clinical team. We compared frozen-section diagnoses with those following regular evaluation of the biopsy specimen. Agreement in diagnoses occurred in 61 (88.4%) of 69 specimens. Acute rejection was the dominant diagnosis (n = 39); others were acute tubular necrosis, cyclosporine toxicity, chronic rejection, and infection. Major misdiagnoses included acute vascular processes (three capillary and/or venous thromboses and one vascular inflammation); acute cellular rejection was missed in two cases, reflecting a sampling error. Secondary diagnoses not of immediate therapeutic importance were detected in seven frozen sections and missed in nine. These included chronic glomerulopathies, nephrosclerosis, and mild chronic rejection. Although acute vascular phenomena may be difficult to recognize in frozen sections, we conclude that allograft biopsy frozen-section analysis is a valuable part of the care of transplant recipients.
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Age-associated changes in the structure and function of the neurohypophysis may contribute to the decreased ability to conserve water in older animals. We investigated the neurohypophyses of 6 and 28-month-old male mice using radioimmunoassay and quantitative morphological techniques. The dry-weight and volume of the neurohypophysis increased significantly with age but the quantity of vasopressin in the gland remained constant. Oxytocin levels decreased with age. A quantitative morphological analysis was performed on the compartments of the neurohypophysis from male mice of 6 and 28 months of age which were either normally hydrated, osmotically loaded, or osmotically loaded and rehydrated. The absolute volumes of the axon endings, swellings, their constituent organelles and the axon terminals containing degenerating subcellular components were determined. The design of the analysis allowed us to examine both age-related changes and statistical interactions between the age of the animal and the behaviour of a variable during the osmotic loading/rehydration phase of the experiment. There was a significant age-related reduction in the volume of the neurohypophysis occupied by the endings and swellings. The diameters of the neurosecretory granules found in the endings were significantly smaller than those in the swellings in both age groups but the size difference was greater in the young animals. Dehydration and subsequent rehydration of old male mice leads to extensive re-modelling of the neurohypophysial compartments and subcellular organelles to the configuration found in the adult animal.
We prospectively assessed renal function in a group of 29 renal transplant patients receiving cyclosporine (CsA) in order to determine the course of their renal function over time and the relationship between different markers of glomerular function. We measured serum creatinine, DPTA, and creatinine clearances, and urinary albumin excretion. The clinical course of 24 patients (83%) permitted repeat studies over a period of 32 +/- 1 (SEM) months, and in these patients DTPA clearance, creatinine clearance, and the serum creatinine concentration did not vary with time. Five of the patients (17%) lost their grafts and returned to dialysis. On initial evaluation patients who lost their grafts had a lower DPTA clearance than those whose function was maintained (29 +/- 3 v 46 +/- 2 mL/min/1.73 m2 body surface area [BSA], respectively, P less than 0.005) and all of them had a DTPA clearance of less than 40 mL/min/1.73 m2 BSA. There was an inverse correlation between the log of the urinary albumin excretion and the DTPA clearance (n = 33, r = -0.59, P less than 0.001), a direct correlation with the serum creatinine concentration (N = 33, r = 0.89, P less than 0.0001), but no correlation with time after transplantation. Thus, despite the continued use of CsA, renal function over time was stable in patients who underwent repeated studies, as was the relationship between the DTPA clearance and the clinically used markers of transplant function, the serum creatinine concentration, and the creatinine clearance.
A disconcertingly wide variation exists in the literature as to the accuracy of duplex Doppler sonography in the detection of acute renal transplant rejection. Sensitivities range from 9% to 76%. In an attempt to explain the disparity of results, we undertook a double-blind prospective study of the accuracy of duplex Doppler ultrasound in the detection of acute rejection in renal transplants. We scanned 49 consecutive patients with a total of 65 biopsies; 46 biopsies in 33 consecutive patients were included in our study. In our population, the prevalence of acute rejection was 61% (28/46). Using a resistive index (RI) cutoff of greater than 0.90 based on the main renal artery flow pattern, the sensitivity of our test was 43%, with a 67% specificity. The positive predictive value was 67%. Our results are contrasted and compared with the published data from other groups in a critical survey of the literature. We conclude that duplex Doppler sonography alone is inadequate to evaluate acute rejection in renal transplants.
Pulmonary oxygen transfer, defined by PaO2/FIO2, and radiologic presence of atelectasis were measured pre-, intra-, and postoperatively to postoperative day 9 in elective cardiac aortocoronary bypass surgical patients, who were randomly allocated either to receive 18 h PEEP while on the ventilator followed by 12 h of nasal continuous positive airway pressure (nasal CPAP) or to be control subjects. The two groups were comparable in age, sex, forced expiratory volume in 1 sec (FEV1), the ratio of FEV1 over forced vital capacity (FVC), time on pump, units of blood transfused, New York Heart Association grading, and cardiac performance indices. The PaO2/FIO2 was significantly (p less than .05) better from half an hour after extubation until 24 h postextubation in the nasal CPAP group, but was decreased for the remainder of the study in both groups. Incidence of atelectasis/consolidation was not different in both groups during the study period. We conclude that nasal CPAP is well tolerated as a treatment of hypoxemia in the immediate postoperative period of aortocoronary bypass patients. CPAP does not change the course of postoperative atelectasis.
Transient voice change associated with endotracheal intubation has generally been attributed to vocal fold trauma. To assess the role of altered vocal fold function in transient voice change, a study was designed to evaluate the audioacoustic, endoscopic, and laryngostroboscopic characteristics of the postintubation voice. Vocal function of 10 patients undergoing short-term outpatient surgical procedures using general anesthesia and endotracheal intubation were studied preoperatively and postoperatively. A second group of 10 patients that did not have surgery or general anesthesia was used as an age-matched control. Fundamental frequency, frequency perturbation, electroglottography, endoscopy (including laryngeal stroboscopy), and subjective speech analysis by experienced listeners were used to assess vocal function. No consistent differences in fundamental frequency were observed, although patient-to-patient variation was marked. Statistically significant increases in cycle-to-cycle fundamental frequency variation (jitter) were found postoperatively in the majority of the postintubation patients (P less than 0.05). Electroglottography, laryngeal endoscopy, and stroboscopic laryngoscopy did not demonstrate consistent changes in glottic mucosal function. Listener judgments characterized the postintubation voice change by decreased intensity, increased roughness, and lowered affect without consistent changes in pitch. The perception of decreased affect in the voices (characterized by reduction in pitch variation, vocal stress, and increases in pause times) was a strong perceptual marker for change in the post-intubation voice. Objective measures of laryngeal function suggest that the glottic contribution to postintubation voice change is minimal and that this dysphonia is probably multifactorial.
This study was undertaken to assess the significance of diastolic flow reversal seen on duplex Doppler sonograms of patients with renal transplant dysfunction. Earlier studies have evaluated the causes of increased vascular resistance in renal transplants. None, however, have investigated specifically the subset of patients in whom impedance in the renal microcirculation has increased to the degree that retrograde arterial flow is present. In our series, 533 consecutive scans in 270 patients were reviewed. The patients were referred for evaluation of renal transplant dysfunction during a 25-month period. Doppler samples were obtained from main, segmental, and, when possible, arcuate arteries. An episode of reversed diastolic flow was identified in nine patients. Correlation was made with clinical, laboratory, histologic (biopsy in six patients, nephrectomy in three patients), and imaging studies (DTPA scintigraphy in seven patients, angiography in one patient). On the basis of histologic and nephrectomy results, we determined that among the nine patients, four had acute tubular necrosis, three had acute rejection, and two had renal vein thrombosis. One of these patients had both severe rejection and renal vein thrombosis. One additional patient had neither biopsy nor nephrectomy and was not included in the diagnostic groups listed here. Our study suggests that reversed diastolic flow is not specific for either acute rejection or acute tubular necrosis. Reversal of diastolic flow, however, is a poor prognostic sign; nephrectomy was imminent in three of the nine patients. Furthermore, two (22%) patients had renal vein thrombosis, whereas renal vein thrombosis was not found in any of the 261 patients without reversed diastolic flow. Duplex Doppler examinations with reversed diastolic flow should suggest renal vein thrombosis.
1. Six hundred twenty kidney transplants have been performed at UCLA since 1984. Rather than 1 rigid immune suppression protocol for all patients, an individualized approach has been taken since the advent of OKT3 in 1987. Since then, the 1-year cadaver graft and patient survival rates have been 87% and 97%, respectively, for both primary and repeat transplants, including various categories of high-risk recipients. 2. Delayed graft function, HLA matching, and percent prior sensitization were major determinants of graft survival. Race, age, and diabetes were not significant determinants of graft outcome. 3. Small children had a 94% 1-year graft survival rate following cadaver transplantation. Sequential immune suppression, the use of large kidneys, and careful perioperative fluid management to prevent graft thrombosis may be responsible for the graft survival rate. 4. Long-term (1 year) results continue to show deterioration in graft survival. Many patients are hypertensive and hypercholesterolemic. Many children are noncompliant with medications.
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Air plethysmography has been used to quantitate venous reflux by measuring the average filling rate of the veins (venous filling index; in milliliters per second) on standing from the supine position, the ejection fraction of the calf muscle pump as a result of one tip-toe movement, and the residual volume fraction after 10 tip-toe movements. Thirty normal limbs, 110 limbs with primary varicose veins, 34 limbs with reflux in the deep veins but without occlusion, and 31 limbs with deep venous occlusion, with or without reflux, have been studied. An increase in the incidence of ulceration occurred with increasing values of reflux and decreasing values of the calf muscle pump ejection fraction. A poor ejection fraction was the primary cause of venous ulceration in limbs with minimal reflux. A good ejection fraction, however, significantly reduced the incidence of ulceration in limbs with marked reflux (p less than 0.05). The residual volume fraction, which expresses the combined effect of venous reflux and ejection fraction with rhythmic exercise, showed a good correlation with the incidence of ulceration and the measurements of ambulatory venous pressure (r = 0.81). The air-plethysmographic measurements completely assess the calf muscle pump function and provide an accurate method to identify the predominant hemodynamic factor (ejection fraction, reflux, or both) responsible for the clinical picture of the patient.
The hemodynamic effect of conventional surgery for varicose veins has been evaluated with a new method of air-plethysmography. The functional venous volume of the leg, venous reflux, and calf muscle pump-ejecting capacity have been measured in 42 legs with primary varicose veins. The patients were studied clinically, with Doppler ultrasound, duplex scanning, and phlebography preoperatively. Doppler ultrasound was repeated postoperatively. Air-plethysmography was performed one day before surgery and 8 to 10 days after surgery. A decrease of the functional venous volume of 16% has been observed (p less than 0.001). The abolition of venous reflux has been shown in all the patients. An improvement in the calf muscle pump-ejecting capacity has also been shown, with a 30% increase of the ejection fraction of the calf muscle pump and with a 43% decrease of the residual volume fraction after 10 tiptoe movements (p less than 0.001). The results indicate that this new method of air-plethysmography apart from its diagnostic value offers a new and unique technique for a noninvasive, objective, and quantitative evaluation of the results of established and experimental venous surgery.
Cholinergic input to the anterior segment of the eye was chronically reduced by ciliary ganglionectomy in cats and by treatment with hemicholinium-3 in both rabbits and cats. The parasympathetically denervated cat eyes developed super-sensitivity to the intraocular pressure lowering effects of carbachol and echothiophate. On the other hand, responsiveness to the similar effects of norepinephrine, epinephrine, and isoproterenol was not changed. After both acute and chronic treatment of rabbit eyes with hemicholinium-3, intraocular pressure was markedly lowered, but the facility of aqueous outflow after chronic treatment was not changed. During chronic treatment of cat eyes with hemicholinium-3, intraocular pressure was also lowered. Three days after chronic delivery of this acetylcholine synthesis inhibitor to the eyes of cats, the rate of formation of aqueous humor was reduced by 50 percent. These results suggest that chemical compounds lowering ocular cholinergic input may possess a pharmacological profile useful as an alternative means for the treatment of glaucoma.
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We studied 31 stable renal cadaver kidney transplant patients receiving cyclosporine (CyA) and prednisone for immunosuppression to determine what reduction in true glomerular filtration rate (GFR) was reflected by their mild elevation in plasma creatinine concentration (1.8 +/- 0.11 mg/dL). We measured both the creatinine clearance (60 +/- 4.32 mL/min/1.73 m2) and the true GFR using Technetium 99m-DTPA (44 +/- 2.72 mL/min/1.73 m2). The creatinine clearance overestimated true GRF by a mean of 38%, indicating that this percentage of creatinine reached the urine by tubular secretion rather than glomerular filtration. A similar degree of overestimation was found in a separate group of 14 patients receiving imuran for immunosuppression. In 23 patients receiving CyA in whom the serum creatinine concentration was less than 2.0 mg/dL, the mean DTPA clearance was 49.5 +/- 2.83 mL/min/1.73 m2. In stable renal transplant patients receiving CyA, a serum creatinine concentration at, or close to, the upper limit of the normal range may reflect markedly impaired renal function.
In a prospective randomized multi-centre study, the mortality following internal fixation surgery for fracture of the upper femur was investigated in 538 elderly patients allocated to receive subarachnoid blockade or general (narcotic-relaxant) anaesthesia. The 28-day mortality was 6.6% with subarachnoid, and 5.9% with general, anaesthesia. The difference was not significant (95% confidence limits: -3.5 to +4.8). At 1 year following surgery, the mortality was 20.4%. Increasing age, ischaemic heart disease, cardiac failure, preoperative arrhythmias and poor ASA status were all associated with increases in early and long term mortality. A delay to surgery of more than 24 h from admission was also associated with an increased 28-day mortality. Senile dementia and admission other than from the patient's own home, were factors associated with a poorer long term outcome. From the point of view of mortality, subarachnoid anaesthesia did not appear to confer any advantages over general anaesthesia in non-prosthetic surgery for hip fracture in the elderly.
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