Enhancement of recovery from psychiatric illness by methylfolate.
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Biomedical subjects
Publications and source records attributed to A Wilkinson.
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Fine-needle aspiration biopsy (FNAB) was performed in 41 renal transplant patients to assess its value in the diagnosis of the cause of graft dysfunction. The procedure was used on 71 occasions, and in each case a clinical diagnosis was made and compared with the cytological diagnosis made independently by a pathologist. When available, core biopsy histopathology was used to confirm the final diagnosis. Fifty-seven (80%) of the aspirates yielded adequate material. A clinical diagnosis of acute cellular rejection (ACR) was made in 21 patients, 18 (78%) of whom showed confirmatory immune activation on FNAB. The clinical diagnosis of either acute tubular necrosis (ATN) or cyclosporine toxicity was confirmed in 31 (91%) of 34 aspirates. In eight aspirates, the cytological diagnosis was different than that made clinically. Humorally mediated vascular rejection, and lymphocytosis secondary to causes other than rejection, such as viral infection, were considered as possible causes of this discrepancy. Provided that adequate samples are obtained. FNAB is valuable in the clinical management of renal transplant patients. Its accuracy should not be overestimated and the results obtained should be evaluated in the light of the overall clinical picture.
Cytomegalovirus (CMV) infection is an important cause of renal allograft dysfunction and may be difficult to distinguish from acute transplant rejection both clinically and histologically. To establish the early diagnosis of CMV infection, we used immunohistochemical staining with antibodies against CMV early nuclear protein (CMV-A) and histocompatibility leukocyte class II antigen (DR) in renal transplant fine needle aspirates. Fifty-eight aspirates from 27 patients were assessed, 53 for CMV-A and 53 for DR. Positive staining was defined as greater than or equal to 35% stained tubular cells for CMV-A and greater than or equal to 30% stained tubular cells for DR. Clinical diagnoses were made retrospectively without using the information obtained from aspirate diagnoses. CMV-A staining was negative in 44 aspirates, none at the time of CMV infection. CMV-A was positive in nine aspirates, seven during CMV infection (78%, P less than 0.00001 versus CMV-A negative). DR staining was never present in the absence of acute rejection. All aspirates performed during acute rejection had positive DR staining (P less than 0.00001 versus DR negative). Aspirates with acute rejection comprised 80% of all DR-positive aspirates, whereas those with CMV infection included only 13%. The percent CMV-A staining increased with CMV disease progression; DR staining decreased after successful treatment of acute rejection. These data demonstrate that CMV-A staining is associated with CMV infection whereas DR staining is not. DR staining is specifically related to acute rejection. CMV-A and DR staining of fine needle aspirates is a potentially valuable diagnostic tool to distinguish rapidly between CMV infection and acute transplant rejection as the etiology of renal allograft dysfunction.
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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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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.
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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In a study on the influence of age and senile dementia on the mammillary bodies, the medial mammillary nucleus was examined in 15 brains from young (control), normal aged and demented females. Neurone populations, volumes and cell densities were estimated. Individual variation was high in all the groups studied. Normal ageing and dementia were accompanied by a substantial loss of volume but no significant loss of neurones, resulting in a considerable increase in cell density. No significant differences were detectable between the normal aged group and the demented group. These findings are in agreement with other investigators who have found no neuronal loss with age in discrete nuclear structures.
Prekeratin has been isolated from human epidermis using the method of Matoltsy for bovine nose epidermis. Analysis by sedimentation equilibrium indicates that human prekeratin is heterogeneous in solution. The molecular weight range is from about 200 X 10(3) to at least 2 X 10(6). Polyacrylamide gel electrophoresis shows three polypeptide chains of molecular weights 65,000 60,000 and 58,000. A lower than average ratio of polar/apolar amino acid residues suggests that hydrophobic interactions are important for stability.
The purpose of this study was to investigate the influence of schooling and general environmental conditions on the development of memory and cognitive skills in young children. The subjects were 824 5- and 6-year-old children living in jungle villages and in slum settlements of Lima, Peru. Half of the children in both the jungle and city were Mestizo, and half were Quechua Indians. Some 6-year-olds of each cultural group and in each location attended school; others did not. Memory tasks were presented in different modes of representation, that is, verbal, pictorial, and enactive; and cognitive tasks in "concrete" and "abstract" versions. A sample of parents in each group was interviewed concerning environmental conditions. In addition, samples of upper-middle-class children in Lima and poor children in Detroit were tested to assess the generality of the findings. Attendance at school was related to improvement in performance on all tasks. Improvement was equivalent for both locations, both cultural groups, and each social class. Attendance at school also was accompanied by reduced within-group variability on some tasks and by greater differentiation of cognitive processes within children. Location and cultural group interacted differentially by task according to a complex pattern of relations. There were no indications that the organization of memory or cognitive processes differed as a function of social class, age, location, or cultural group. The results were interpreted in terms of children's opportunities to acquire specific memory and cognitive skills from schooling and from their general experience in a particular environment.