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Biomedical subjects

R B Freeman

Publications and source records attributed to R B Freeman.

At least 91 records · Page 5Linked to original sources

Specificities of antibodies eluted from human cadaveric renal allografts. Multiple mechanisms of renal allograft injury.

The purpose of the present experiments was to evaluate the role of circulating antibodies in the rejection of human renal allografts and to study the apparent target(s) for antibody binding. Eluates obtained from surgical biopsy and nephrectomy specimens of rejecting, cadaveric human renal allografts were tested for antibodies directed to structural antigens of normal kidney and for cytotoxic antibody activity against mononuclear cell populations. By indirect immunofluorescence 23 of 35 eluates contained immunoglobulin that bound to normal kidney. Staining was in smooth muscle only in 10 patients, in smooth muscle and other structures such as tubular basement membranes, proximal cells, or brush border in 9 patients, and in structures other than smooth muscle in 4 patients. All 16 eluates tested contained antibodies cytotoxic for cells derived from a panel of normal volunteers. Six were cytotoxic to T cells and 10 to B cell and monocyte-enriched preparations. Absorption of eluates with pooled buffy coat cells, platelet concentrates and packed, cultured B cells removed antibodies reactive with vascular wall smooth muscle and endothelium, but not antibodies to tubular basement membranes, proximal or distal tubular cells, brush border, or other structures of kidney sections. Two of five eluates containing antikidney antibodies were found to bind to rat kidneys in vivo. These results suggest that circulating antibodies participate in cadaveric renal allograft destruction and demonstrate that they can be recovered directly from the allograft. Moreover, the data indicate that there are different antibody populations involved: some clearly directed to allo-specific differences and others that are apparently kidney-specific.

Antibody Specificity↗

The role of urinary tract infection in chronic renal failure.

The importance of bacterial infection as a major cause of progressive renal failure has become less prominent as long-term studies have failed to show progressive renal disease in bacteriuric humans. Functional or anatomic abnormalities of the urinary tract are necessary to perpetuate infection and cause renal scars and renal failure. In children, the most common abnormality is reflux. Sterile reflux that extends into the renal collecting ducts may cause scars previously called atrophic pyelonephritis. This entity is now referred to as reflux nephropathy. Other predisposing factors may lead to end-stage disease in a small proportion of bacteriuric patients. The most common are obstructive uropathy and calculus disease. Bacteriuria is difficult to eradicate in maintenance hemodialysis patients and may require bilateral nephrectomy. In transplant recipients, bacteriuria is common and has been associated with rejection and loss of allograft.

Adult↗

Lymphocyte populations in maintenance hemodialysis patients - reassessment and analysis of B cell subtypes.

Maintenance hemodialysis patients are known to be lymphopenic, and it was previously felt that T and B cells were equally and moderately depressed. With modification of the B cell technique, however, we have shown that MHD patients have a relatively more pronounced depression of B cells, with decreased proportions and markedly reduced total numbers. B cells bearing specific immunoglobulin types are all proportionally reduced. This marked B cell deficiency could be responsible for the increased rate of some infections in MHD subjects. Its relationship to azotemia, malnutrition, toxic or deficiency states, or dialysis itself is unknown, and the stages of cellular maturation or interaction which are affected have not been identified.

Adult↗

Carcinoma of the oral tongue: a study of patient selection and treatment results.

Retrospective review of 118 primarily treated cancers of the oral tongue was done to study patient selection and to search for improved treatment strategies. Small surface lesions were treated by local excision (LE); most small lesions invading muscle of the tongue without lymph node metastases were treated by radiation alone (RA) while larger lesions and those with palpable nodes were treated by preoperative radiation and surgery (R + S). Ultimate control of the primary tumor and lymph nodes after initial treatment and surgical salvage was high for the lesions by LE (91%), the T1N0 lesions treated by RA (88%) and for the TxN+ lesions treated by R + S (57%). Improved treatment strategies are suggested for T2N0 lesions treated by RA because of poor tumor control (53%) and a high rate of radiation complications (25%), and for T3N0 lesions because so many of these patients died from causes other than cancer within two years. Second primary cancers were most common in those patients with a good prognosis.

Aged↗

Insulin action and binding in isolated hepatocytes from fasted, streptozotocin-diabetic, and older, spontaneously obese rats.

Insulin binding and basal and insulin-stimulated uptake of alpha-aminoisobutyric acid were measured in isolated hepatocytes from young control rats as well as from older spontaneously obese, 72h-starved, and nonketotic streptozotocin-diabetic rats. Isolated hepatocytes from older spontaneously obese rats are similar to those from younger smaller rats in size, maximal insulin responsiveness, the dose-response relationship for insulin-stimulated aminoisobutyrate uptake, and the number and affinity of insulin receptors. Hepatocytes from 72h-fasted rats have similar numbers of insulin receptors per cell as cells from young control animals, but are significantly smaller, have an enhanced basal rate of aminoisobutyrate uptake, and are insulin resistant with regard to maximal insulin-stimulated uptake of aminoisobutyrate at 0.1mm-aminoisobutyrate. Because of the decreased maximal response to insulin, the concentration of insulin that elicits a half-maximal response of aminoisobutyrate uptake is decreased. Hepatocytes from diabetic animals, like those from starved rats, have significantly greater basal rates of aminoisobutyrate uptake; whereas the maximal absolute insulin response is the same as control cells, the percentage response is smaller. These cells bind significantly more insulin than do control cells. The increase in insulin binding is reflected in a shift to the left of the dose-response curve for insulin-stimulated uptake of aminoisobutyrate. These studies indicate that there is no insulin resistance with regard to uptake of aminoisobutyrate in hepatocytes from older obese rats. Furthermore, the insulin resistance observed in hepatocytes from starved rats occurs despite an increase in the number of receptors per unit surface area and cannot be explained by alterations in the interaction between insulin and its receptor. The enhanced insulin binding per unit surface area, however, is reflected in the shift to the left of the dose-response curve for insulin. This is also true for hepatocytes from diabetic animals, in which insulin binding per cell is increased.

Age Factors↗

Delayed-alternation performance after selective lesions within the prefrontal cortex of the cat.

On the basis of new neuroanatomical findings on relationships between subregions of the mediodorsal thalamic nucleus and the prefrontal cortex of the cat, it was attempted to investigate the relative importance of prefrontal subfields with the aim of obtaining evidence in favor of a functional inequality of different prefrontal subfields. Four areas, named presylvian (PRS), proreal (PR), dorsomedial (DM), and orbito-insular (OI) sectors, were ablated successfully in 30 adult animals. Performance of a 10-sec delayed-alternation task was compared pre- and postoperatively. Furthermore, most of the cats had to learn an extension of this task postoperatively, using a 20-sec delay period, and lastly, these animals were subjected to an extinction test. Significant performance differences were obtained between cats of different groups in all three tasks. Lesions of subregion PR, and even more of subregion PRS, led to severe behavioral deterioration, whereas lesions of subregion OI were without effect, when compared with the behavior of a sham-operated control group. PRS-cats, furthermore, showed motor disturbances during the first postoperative week. The results obtained suggest that it is possible to subdivide the cat's prefrontal cortex functionally. In addition, it is hypothesized that behavioral changes in cats of groups PRS and PR are due to an inability to use kinesthetic information properly.

Animals↗

Results of conservation surgery for cancers of the supraglottis and pyriform sinus.

A retrospective review of patients treated by surgery and/or radiation for carcinoma of the supraglottic larynx and the pyriform sinus was accomplished for the period 1964-1974. This patient population reflects the 10-year period following earlier experience with conservation surgery at this institution, and, thus, updates the current status of treatment for these cancers. Endpoints examined included survival, control, pattern of failure, the influence of nodal metastasis, and voice preservation. Of 160 patients treated for supraglottic laryngeal carcinoma, 119 received conservation surgery (subtotal supraglottic laryngectomy, SSL, or partial laryngopharyngectomy, PLP); 21 patients received total laryngectomy; and 20 others received palliative radiation. The 3-year actuarial survivals for these groups were 67%, 43% and 30%, respectively. Voice was preserved in 85% of the patients treated by conservation surgery, in 70% of those treated by radiation alone, and, of course, in none of the patients receiving total laryngectomy. There were 175 patients treated for carcinoma of the pyriform sinus; 85 received PLP; 57, total laryngopharyngectomy (TLP); and 33, palliative radiation. Acturial 3-year survival was 59% for the PLP-treated group, 36% for the TLP-treated group and 11% for the palliation group. Voice was preserved in 52% of the patients treated by conservation surgery, in 6% of those treated by radiation alone, and in none of those patients treated by total laryngectomy. Comparison of this data with that in other published reports indicates that, for selected patients, conservation surgery is as effective in controlling disease as is radical surgery. Furthermore, it is possible to preserve speaking ability in a significant number of patients having carcinoma of the supraglottic larynx or pyriform sinus.

Carcinoma, Squamous Cell↗

A regional end-stage renal disease program: twelve years' experience.

As of 31 December 1978, 558 patients with end-stage renal disease had been treated with transplantation (150), home dialysis (109), and center dialysis (299). Three hundred twenty-eight patients survived--194 (59%) in center, 51 (15%) at home, and 83 (25%) with functioning grafts. The number and age of new patients continue to increase. Significantly more deaths occur among center dialysis patients than among transplant recipients or home patients. Cadaveric donors provide 71% of transplanted kidneys. The increase in new and older patients without a commensurate increase in cadaver organs results in a declining transplantation rate. Home dialysis training has not decreased. Home dialysis and transplantation can treat about 50% of all new patients. Equilibrium in the end-stage renal disease population will occur when 632 patients per million are receiving treatment. Of these, about 500 will be on center dialysis and will need about 100 stations per million population.

Cadaver↗

Epidemiology of cytomegalovirus infection in end stage renal disease.

Since primary cytomegalovirus (CMV) infection is a cause of morbidity among renal transplant recipients, we undertook a prospective study of our maintenance hemodialysis patients and personnel to determine whether these sources posed a risk for transmission of CMV. Our study of 85 patients and 49 personnel showed that CMV was detected in eight nontransplanted, older dialysis patients and 13 patients who had lost their allograft. In spite of the presence of CMV on the unit, no patient or staff member developed primary infection from interpersonal transmission or from transfused frozen red blood cells. All primary infections in renal transplant patients could be accounted for by acquisition from the transplanted kidney, thus eliminating the dialysis unit or frozen blood as a risk to either patients or personnel.

Antibodies, Viral↗

Voice preservation in treatment of carcinoma of the pyriform sinus.

A retrospective analysis of 175 patients having a histopathologic diagnosis of epidermoid carcinoma of the pyriform sinus presenting between January 1, 1964 and December 31, 1973 was undertaken to establish the effectiveness of conservation surgery in preserving voice. Patients were treated by three separate methods: 1. preoperative radiation therapy, partial laryngopharyngectomy and radical neck dissection (PLP and RND) (N = 85); 2. preoperative radiation therapy, total laryngopharyngectomy and radical neck dissection (TLP and RND), (N = 57); and 3. palliation, which consisted of palliative radiation therapy alone or combinations of radiation therapy and chemotherapy or palliative surgery (N = 33). Of the 85 patients treated with the expectation of cancer cure and voice preservation (PLP and RND), 44 or 52% actually had their voice preserved. Of course, in none of the patients treated by TLP and RND was voice preserved, but 2 of the 33 patients treated palliatively retained ability to speak. Overall, 46 of 175 patients (26%) with carcinoma of the pyriform sinus were afforded voice preservation. The ability to preserve voice is correlated with stage and an analysis of operative complications is presented.

Carcinoma, Squamous Cell↗

Carcinoma of the supraglottic larynx.

Retrospective review of 160 patients with carcinoma of the supraglottic larynx was accomplished for the period 1964 to 1974. The majority were treated by low dose preoperative radiation and conservation surgery and the rest by preoperative radiation and total laryngectomy or radiation alone. Relapse-free and actuarial 5 year survival for all patients was 71% and 45%, respectively. Of primary and neck failures, 85% occurred within 2 years. Primary, nodal, and distant failures occurred in 11%, 21%, and 14% of all patients, respectively. Of 40 T and/or N failures, 33 (83%) occurred in the neck and three T and six N failures (23%) were surgically salvaged. Voice was preserved in 71% of the patients. Major complications were noted in 16% and minor complications in 26% of surgically managed patients; operative mortality was 4%. The presence of microscopic lymph node metastases best predicted those who would later develop T and/or N failure and distant metastases. Second primary tumors occurred in 26% and the leading cause of death was tumor.

Adult↗

Cytomegalovirus infection blocks the beneficial effect of pretransplant blood transfusion on renal allograft survival.

Two factors which have gained attention as possible contributors to success of renal allografts are freedom from infection with cytomegalovirus (CMV) after transplant and administration of multiple blood transfusions pretransplant. In order to determine the interrelationship of these two variables, we analyzed 55 recipients of well matched (at least two antigens) cadaveric kidneys. In this study, absence of CMV infection and receipt of multiple transfusions both provided favorable outcomes. When patients were grouped by both factors, those who were free of infection and received multiple transfusions did significantly better than any other combination. Infection with CMV decreased the frequency of allograft survival in multiply transfused patients to a point intermediate between the above group and those who had not been multiply transfused. Since CMV infection can be predicted by measurements made pretransplant, and since up to one-quarter of CMV infection which develops post-transplant is transmitted with the allograft, administration of multiple transfusion to all patients and the use of donors who are free of latent CMV infection for CMV antibody-negative potential recipients should increase allograft success. For those potential recipients who already have latent CMV infection, further study will be necessary to determine what stimuli can be given pretransplant to prevent the interference with the beneficial effect of multiple transfusion.

Blood Transfusion↗

Experimental renal infection: acute and chronic studies of histology and function.

Experimental renal infections have resulted in histologic lesions of acute and chronic pyelonephritis, but in most studies the urinary tract has been "traumatized" to induce persistent infection. Sequential functional alterations have been measured infrequently. The present studies were designed to separate the functional and histological changes caused by high pressure sterile reflux from reflux with pathogenic organisms. Reproducible disruption of the pelvic epithelium with extravasation of solution into the parenchyma and vasculature occurred with reflux of 2.0 ml of solution but not with 1.0 ml. Reflux with 2.0 ml of sterile broth failed to cause permanent histologic changes, but reflux with broth containing organisms resulted in minor inflammatory changes. There was no decrease in renal function in either group. In long-term studies, no histologic changes in the cortex or medulla were noted 21 weeks after reflux of 1.0 ml of broth containing organisms; however, there was failure of functional maturation in the infected animals commensurate with their growth, as compared to the shams and controls (P = 0.03). Sterile reflux did not cause cortical scars or changes in renal function, but persistent parenchymal infection was associated with arrest of functional growth.

Agglutination↗