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Biomedical subjects

P Lang

Publications and source records attributed to P Lang.

At least 325 records · Page 18Linked to original sources

[Demonstration of complex dysregulation of anti-cytomegalovirus T-cellular immunity in Kaposi's sarcoma following renal transplantation].

An increased incidence of Kaposi's sarcoma is well known in renal transplant recipients in whom it may represent up to 3 p. 100 of all de novo tumours. This sarcoma has a close relationship with the potential oncogenicity of the cytomegalovirus (CMV) and with chronic immunological deficiency. Anti-CMV immunity is based on the integrity of cytotoxic cellular functions such as those of cytotoxic T lymphocytes (CTL), "natural killers" cells, and K cells which function in the antibody-dependent cell cytotoxicity (ADCC) system. Two cases of Kaposi's sarcoma were observed out of a total of 700 renal transplant recipients; they underwent the following investigations: lymphocyte sub-group counts by murine monoclonal antibodies, lymphocyte proliferation to lectins and allogenic cells, NK activity and generation of specific auxiliary and cytotoxic anti-CMV cells. Both cases of Kaposi's sarcoma were seropositive for CMV and seronegative for LAV. In one case, an abnormal number of peripheral OKT9 + lymphocytes (normally a thymocytic marker) was observed with small numbers of OKT4/OKT8, a reduced proliferative response to mitogens and allogenic cells. All these in vitro changes persisted despite reduction of immunosuppressive therapy and clinical improvement. A clinical and biological cure was only obtained after withdrawal of immunosuppressive therapy and return to haemodialysis. In the second case of Kaposi's sarcoma, the initial biochemical changes were minimal and a clinical cure was obtained by decreasing the immunosuppressive therapy. These two cases illustrate the complex dysregulation of the immune system in Kaposi's sarcoma.

Adult↗

[Anomalies of coagulation and thromboembolic complications of nephrotic syndromes].

Thrombo-embolic events remain one of the most serious complications in patients with nephrotic syndrome (NS). A causal relationship between coagulation abnormalities and the occurrence of thrombosis in NS has been searched. Several studies have demonstrated multiples abnormalities in the coagulation factors and platelets; however those studies did not provide adequate explanations for the thrombotic tendency of NS. This thrombotic tendency could be related to deficiency in natural coagulation inhibitors. Plasma ATIII level has been reported to be decreased both in some adults and children. Protein C is found normal or high in NS whereas protein S is increased. Nevertheless a possible decrease in functional protein S cannot be excluded.

Blood Coagulation Disorders↗

Anomalous origin of left coronary artery from pulmonary artery. Ligation versus establishment of a two coronary artery system.

Between 1959 and 1985, 24 patients (mean age 38 months, range 15 days to 13 years) with anomalous origin of the left coronary artery from the pulmonary artery as an isolated lesion were treated surgically at Children's Hospital, Boston. In 11 cases a left coronary-to-aortic tunnel was created with a pulmonary artery baffle (Takeuchi) with no deaths either early or late over a mean follow-up period of 18 1/2 months. Late complications of this procedure include moderate aortic regurgitation (one), supravalvular pulmonary stenosis (two-one required a second operation), obstructed baffle (one-asymptomatic). In 11 cases of coronary ligation or ostial closure there was a 27% early mortality and a 25% late mortality over a mean follow-up period of 10 1/2 years. Late complications include residual shunt (three-two required a second operation), severe mitral regurgitation (one), and recurrence of angina (one). Two patients had other procedures. Both early and late deaths occurred in the group who had congestive heart failure and who had simple ligation. Five infants who had profoundly depressed ventricular function and moderate to severe mitral regurgitation, together with widespread Q waves on electrocardiogram, showed a dramatic improvement in ventricular function after the Takeuchi procedure. The Takeuchi procedure is a simple and effective means of establishing a two coronary artery system in the child with anomalous origin of the left coronary artery from the pulmonary artery. This procedure is particularly recommended over coronary ligation in patients in congestive heart failure.

Adolescent↗

Creation and maintenance of an adequate interatrial communication in left atrioventricular valve atresia or stenosis.

Patients with left atrioventricular (AV) valve atresia or stenosis were studied retrospectively to determine the incidence of early and late failures of procedures to enlarge an interatrial communication. The 61 patients underwent 80 procedures: 5 balloon atrial septostomies, 12 blade atrial septostomies and 63 surgical septectomies. No balloon septostomy provided adequate long-term palliation. Of 12 blade septostomies, 4 resulted in gradients across the atrial septum of 5 to 8 mm Hg and 8 in gradients 3 mm Hg or less. Results from blade septostomy were unrelated to underlying diagnosis, age, gradient before the procedure, number of previous procedures, pulmonary blood flow or size of the postprocedure defect by balloon sizing, but were related to size of the postoperative defect estimated by echocardiography. Among 8 patients with gradients of 3 mm Hg or less after blade septostomy, 7 were followed 9 +/- 7 months and showed no evidence of restenosis. Of 63 surgical septectomies, 11 (17.5%) were inadequate, and in at least 7 cases the failure was due to restenosis of the defect as documented by serial catheterizations or echocardiograms. Outcome after surgical septectomy was unrelated to underlying diagnosis, age or number of previous procedures, but was related to size of the defect created. Our results reveal improved results in terms of residual gradient for blade septostomy compared with previous studies and the need to follow these patients carefully, even those undergoing surgical septectomy.

Blood Pressure↗

[Immunopathological study of acute interstitial nephropathy induced by clometacin].

Clometacin is an antalgic drug with a chemical structure very similar to that of indomethacin; it is widely used in France. We report evidence for a cell-mediated immune mechanism in the pathogenesis of clometacin-induced acute interstitial nephritis. In the interstitial infiltrate of a female patient presenting with this condition, T cells constituted 75% of the total lymphocyte population. Cytotoxic/suppressor T cells predominated over helper/inducer T cells with a ratio of two to one. IgA-secreting plasmocytes were also present (about 23% of the inflammatory infiltrate). Peripheral blood lymphocyte studies showed that pre-incubation of the patient's cells with clometacin resulted in an increased sensitivity to interleukin 2 and a positive syngeneic mixed lymphocyte culture. This study seems to be relevant to the pathogenesis of acute interstitial nephritis induced by nonsteroidal anti-inflammatory drugs.

Acute Disease↗

Cytotoxic T cell response and thymic hormonal dysfunction in graft-vs-host mice.

As an approach to dissect complex mechanisms that lead to graft-vs-host (GvH)-associated immune disorders, we have compared the splenic cytotoxic T lymphocyte (CTL) response and thymic hormonal function in nonirradiated F1 hybrid mice injected with parental spleen cells. Thymic secretory function was studied by the determination of serum thymulin levels, and the number of thymic epithelial cells containing thymulin as assessed by indirect immunofluorescence with the use of an anti-thymulin monoclonal antibody. In addition, the epithelial cell network was analyzed with an anti-keratin serum, and the general histology pattern was studied by conventional histologic methods. An initial analysis was performed on day 15, which was characterized by CTL suppression mediated by parental suppressor T cells. No thymic abnormalities were detected at this time. By day 45 after GvH induction, active CTL suppression had decreased, and GvH was associated with a progressive decline in thymic hormonal function. Finally, by day 60 and thereafter, F1 GvH mice recovered normal in vitro CTL responsiveness, which contrasted with profound alterations of the epithelial cell network and severely reduced serum thymulin levels. This hormonal dysfunction was shown to be directly associated with a reduction in the number of thymulin-containing cells. Moreover, no anti-thymulin auto-antibodies could be detected. The results are discussed with respect to the role of thymic hormonal dysfunction in the modulation of F1 CTL responses observed during the course of a GvH reaction, and the additional analogy of this GvH model with human immunodeficiency.

Animals↗

Cardiac output estimates in the pediatric intensive care unit using a continuous-wave Doppler computer: validation and limitations of the technique.

We compared the cardiac index obtained by means of a continuous-wave Doppler computer with simultaneous thermodilution measurements in 25 children in the pediatric intensive care unit (40 observations). The aortic diameter was measured at various levels to determine which provided the best measure of cardiac index. The Doppler measurements were performed independently by a physician trained in Doppler cardiography and by a nurse with no experience in echocardiography. Both the nurse and physician obtained high-quality flow velocity recordings in all patients in a mean time of 5 minutes or less. Cardiac index and total systemic vascular resistance measured by means of Doppler and thermodilution techniques were highly correlated (r = 0.86 and r = 0.93, respectively). The highest correlation was obtained when Doppler cardiac index was computed by means of the internal diameter measured at the aortic anulus. There was no significant difference between the nurse's and physician's measurements. We conclude that cardiac index can be accurately determined in the pediatric intensive care unit by means of continuous-wave Doppler computer, even when operated by personnel not trained in Doppler cardiography.

Cardiac Output↗

Transthoracic intracardiac monitoring lines in pediatric surgical patients: a ten-year experience.

A study of 6,690 transthoracic intracardiac monitoring (TIM) catheters in 5,666 pediatric patients undergoing cardiac surgical procedures during a 10-year period demonstrates the safety of this monitoring method. The utility of TIM catheters in patients undergoing a modified Fontan procedure, those undergoing repair of tetralogy of Fallot, and those with elevated or labile pulmonary resistance is stressed. Right atrial (RA) and left atrial (LA) catheters are particularly safe; they have a low incidence of bleeding complications (RA = 0%, LA = 0.13%) and retention complications (RA = 0.15%, LA = 0.63%). Pulmonary artery (PA) catheters that are introduced through the right ventricular infundibulum have higher complication rates (1.07%); unpredictable hemodynamic compromise occurs in approximately 0.5% of such patients. PA catheters placed through the wall of the atrium have a lower complication rate-approximately equal to that for RA and LA catheters. The benefits of TIM catheters far outweight the associated risks if care is exercised in placing and removing them, and if complications are rapidly recognized and aggressively managed. The continued use of TIM catheters in pediatric cardiac surgical patients is therefore strongly recommended.

Cardiac Catheterization↗

Percutaneous balloon valvotomy of congenital pulmonary stenosis using oversized balloons.

Percutaneous balloon valvotomy was attempted in 27 patients (aged 6 days to 19 years, median 2 years, 11 months) with unoperated typical valvular pulmonary stenosis using a balloon 7 to 60% (mean 30%) larger than the valve anulus. One patient had undergone a previous balloon valvotomy elsewhere. To achieve an oversized dilation diameter in three larger patients, two balloons were inflated side by side. Their "effective dilation diameter" was determined by the diameter of the circle with the same area as that of the oval enveloping the two balloons. A significant reduction of the transvalvular gradient occurred in all patients (mean +/- SD = 74.3 +/- 14.7%, range 33 to 100%). The average gradient of 65.0 +/- 19.0 mm Hg (mean +/- SD) fell to 15.9 +/- 7.6 mm Hg (0 to 30 mm Hg). Twenty-five of 27 patients had a residual transvalvular gradient of less than 25 mm Hg. The calculated valve orifice area increased by an average of 183 +/- 80%. No significant complications occurred. It is concluded that percutaneous balloon valvotomy with a balloon 20 to 40% larger than the valve anulus is the treatment of choice for typical congenital valvular pulmonary stenosis.

Adolescent↗

Comparison of 75SeHCAT retention half-life and fecal content of individual bile acids in patients with chronic diarrheal disorders.

Measurement of the retention of 23-75Se-25-homotaurocholic acid (SeHCAT) has been suggested as a new test for ileal function. We investigated 31 patients with chronic diarrhea, 10 with ileal Crohn's disease and 21 with diarrhea but without ileal disease. The whole-body retention half-life of 1 mu Ci SeHCAT was determined and compared to the fecal content of total and individual bile acids. Patients with ileal disease had increased primary fecal bile acids (chenodeoxycholic acid: mean 6.95 mg/g dry weight, range 3.15-10.6 mg/g; cholic acid: mean 18.15 mg/g, range 10.3-33.9 mg/g) and a short SeHCAT retention (mean 11.9 h, range 2-24 h), whereas patients with intact ileum had normal fecal bile acids and a SeHCAT retention of 85.9 h (range 28-216 h). SeHCAT retention half-life differentiated well between patients with ileal disease and patients with normal ileum, thus indicating the SeHCAT test as a valid investigation method for detection of primary bile acid malabsorption in patients with chronic diarrhea and ileal dysfunction.

Adolescent↗

First-stage palliation of hypoplastic left heart syndrome. The importance of coarctation and shunt size.

After Norwood's initial report of successful first-stage palliation of hypoplastic left heart syndrome in neonates, an improved understanding of both the pathologic anatomy and physiology of this common condition has led to improving surgical results. Twenty-five neonates have been treated by modifications of the Norwood procedure, and the early mortality between January, 1984, and July, 1985, has been 24% (six deaths). Two premature neonates weighing less than 2 kg died, as did two neonates who could not be resuscitated with prostaglandin E1 and had cardiac arrests immediately preoperatively. There have been four late deaths. The frequent occurrence (80%) of a juxtaductal coarctation or coarctation shelf necessitates alteration of surgical technique. Failure to do so will be reflected in an early persistent postoperative metabolic acidosis with an arterial oxygen tension greater than 35 to 40 mm Hg in the operating room or greater than 40 to 45 mm Hg in the intensive care unit. A similar acid-base derangement will be seen if the systemic-to-pulmonary shunt is excessively large. Careful ventilatory and pharmacologic management of the ratio of pulmonary to systemic vascular resistance is an essential part of the perioperative management of these neonates with two parallel competing circulations. Late postoperative catheterization findings have emphasized the importance of a wide atrial septectomy, because restrictive atrial septal defects have developed in a number of children, despite partial surgical atrial septectomy. Central pulmonary artery reconstruction must be carefully performed to avoid distorted hypoplastic pulmonary arteries that would be unsuitable for a second-stage modified Fontan procedure.

Acid-Base Imbalance↗

[Study of the protein C-protein S system in glomerulopathies and nephrotic syndrome].

The protein C-protein S natural anticoagulant system was evaluated in 32 patients with proteinuria, 11 without nephrotic syndrome (NS) and 21 with NS of different grade. Antithrombin III (AT III), factors II, VII, X were also measured in the same groups of patients. In addition to plasma levels of these proteins, urinary loss of protein C was evaluated in concentrated urine specimens from 17 of the 21 patients with NS. The protein C antigen level was found to be normal or high in NS, but the difference between the control group and nephrotic patients was statistically significant only in severe NS. For all proteinuric patients, the plasma concentration of protein C correlated positively with the degree of proteinuria, cholesterol level, triglyceride level, and correlated inversely with serum albumin concentration; 17/17 patients with NS exhibited urinary loss of protein C and the degree of protein C excretion correlated positively with the degree of proteinuria. Plasma protein S antigen was measured in only 11 patients with NS and was found to be significatively increased, with a negative correlation with serum albumin concentration. AT III did not differ between the control group and the proteinuric patients with or without NS. Factors II and X were in the normal range for all patients. Factor VII was increased even in mild NS. Thus, the plasma levels of protein C and protein S antigens were normal or increased in patients with NS and this is probably related to an increased liver synthesis rate of these proteins, which is secondary to proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Effector mechanisms of graft rejection].

The rejection of an allograft is a complex phenomenon involving various subsets of immune cells. If the role of humoral immunity and cytotoxic T cells is well demonstrated, helper T cells have also a major effect in some models of allograft destruction. Moreover, Natural Killer cells, Killer cells, monocytes/macrophages, B lymphocytes are also implicated in various stages of graft rejection. The analysis of the clonal repertoire of T lymphocytes, the discovery of the structure and function of the T-cell receptor and finally the genetic control by encoded genes of the immune response may lead to a better comprehensive and therapeutic approach of graft rejection.

Animals↗

Extending the limits for modified Fontan procedures.

During the early development of atriopulmonary anastomotic operations (Fontan-Kreutzer), a number of physiologic and anatomical limits were proposed by the Fontan group as selection criteria. Among 167 consecutive patients undergoing modified Fontan procedures from 1973 through 1985, 109 (65%) patients exceeded one or more of the original selection criteria in areas of age, anomalies of systemic or pulmonary venous connection, pulmonary artery distortion, and pulmonary artery pressure. Twenty-six patients had a mean pulmonary artery pressure greater than 15 mm Hg, with 16 operative survivors (62%). Nineteen patients had anomalies of systemic and/or pulmonary venous connection, and 16 survived (84%). There were 44 patients under the age of 4 years, and 26 survived (59%). Twenty-five patients were older than 15 years, and 23 (92%) survived the Fontan procedure. Pulmonary artery distortion, relating to prior palliative operations, was found in 34 patients. Seventeen of these 34 survived a modified Fontan procedure (50%). Twenty-six patients had a pulmonary arteriolar resistance more than 2 Wood units times square meter, and 14 survived (54%), whereas 81 of 93 with a pulmonary arteriolar resistance of less than 2 U X m2 survived (87%). Multivariate analysis showed that pulmonary arteriolar resistance and pulmonary artery distortion had a significant, negative impact on survival, but age and anomalies of systemic and/or pulmonary venous connection did not. Pulmonary artery pressure was not an independent predictor of outcome. The results show that the original criteria may be exceeded in the areas of age and anomalies of pulmonary or systemic venous connection. Pulmonary artery pressure alone should not contraindicate a Fontan procedure if pulmonary arteriolar resistance is low. Pulmonary artery distortion from a prior palliative operation and elevated pulmonary arteriolar resistance increase the risk of a Fontan procedure.

Adolescent↗