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Biomedical subjects

D Keren

Publications and source records attributed to D Keren.

At least 19 recordsLinked to original sources
PubMed2005

Statin escape phenomenon: Does it really exist?

BACKGROUND: The normalization of blood lipid profile has become an accepted method of primary and secondary prevention of vascular disease, with statins being the most popular group of medicines prescribed to lower cholesterol and LDL cholesterol levels. The failure of statins, administered in an appropriate dose, to maintain the optimal level of LDL cholesterol is a rare phenomenon, and is still not well understood in patients compliant for both medication and diet. The entity of "statin escape phenomenon", proposed to explain the failure of statins in some of these patients, has not been studied or characterized extensively, and reports of its prevalence are scarce. METHODS: Patients with hyperlipidemia type 2a or 2b who had been treated with statins for at least 1 year and who were followed up in the lipid clinic on a regular basis every 3-4 months were included in this study. The charts of patients whose LDL cholesterol levels were elevated by 15% or more while receiving the same treatment were analyzed, and patients with putative statin escape phenomenon were included in the study and further characterized. RESULTS: Forty-five of 358 statin-treated patients demonstrated a 15% increase in LDL cholesterol levels, leading to suspicion of statin escape phenomenon. However, a strict exclusion analysis left only two patients without evident potential triggers for the observed elevation in LDL cholesterol. CONCLUSIONS: Whether a statin escape phenomenon really exists is still not certain, but if it does exist, it is probably an uncommon event with a low prevalence.

Journal Article↗
PubMed2005

Do forceps biopsies truthfully reflect the nature of endoscopically uncovered polypoid lesions of the colon?

BACKGROUND: Total excision of colonic polyps is not always attainable and in some patients it is clinically contraindicated. Also, a resected polyp may be lost at any step between its endoscopic removal and its embedding in paraffin. The aim of this study was to compare the histological features of colonic polyps as analysed by the study of biopsy-forceps obtained samples with those assessed on scrutinizing the totally resected growths. PATIENTS AND METHODS: This prospective study included a cohort of 59 patients in whom, in the course of an elective colonoscopy, a total excision of a 6 mm-sized or larger polyp was called for. Sizeable biopsies were obtained by means of an Olympus Multibyte forceps prior to the total polypectomy. Subsequent to the study of the polypectomy specimens, the forceps biopsy samples were submitted for histological examination. The pathologists were blinded as to the source of the tissue they were studying. The diagnoses rendered by evaluating the biopsy samples and polypectomy specimens of each patient were contrasted with each other. RESULTS: Major discrepancies between the histological features of the fragments captured by the biopsy-forceps and the factual nature of the totally removed polyps were uncovered in 11 (18.6%) of 59 cases. Intriguingly, the grade of the tumours was underrated in all the 11 cases, as judged by contrasting the tentative diagnoses of the forceps-biopsies with the decisive diagnoses of the polypectomies. Importantly, 2 adenocarcinomas would have been missed by just looking at the forceps-retrieved sample. CONCLUSIONS: In our experience, a discordance of 18.6% is to be expected between the diagnoses rendered after examining forceps-biopsies of and totally excised colonic polyps. Nevertheless, it is advisable to procure biopsies prior to the excision of the growths, because on those occasions in which patients' growths cannot be removed or have not been retrieved for one reason or another, a small forceps-captured tissue sample correctly reflects the characteristics of the polyp in 81.4% of the cases. Finally, the biopsies may be discarded in the event that total removal was successful.

Adult↗
PubMed2000

In-field validation of automatic blood pressure measuring devices.

The method for rapid evaluation of automatic blood pressure (BP) measurement devices (READ) is based on numerous BP measurements at rest and during a standardised postural challenge in a small number of subjects with a wide range of BPs. The present study proposes additional parameters of the READ for in-field validation of automatic BP measurement devices. BP measurements were done in supine position for 10 min followed by head-up tilt for 30 min and again supine for 10 min. BPs were determined simultaneously by automatic (AU) and mercury sphygmomanometric (MS) measurements on the same arm. The BP differences DeltaBP:AU-MS were calculated. Three units of the Colin BP-8800 and the Datex-Engstrom Cardiocaptrade mark II were evaluated. Based on DeltaBP(AU-MS), the grade of accuracy, aberration patterns and correlates of accuracy were assessed for each unit. Per unit, an average of 121 measurements were done, every BP category being met in >/=20 MS measurements. In general, the AU systolic BP values were higher than MS systolic BP values (mean systolic DeltaBP = 1.26 +/- 17.1 mm Hg) and AU diastolic BP values were lower than MS diastolic BP values (mean diastolic DeltaBP = -12.31 +/- 7.8 mm Hg). All units classified into category D of the British Hypertension Society grading system and exhibited inconsistent aberration patterns, making design of correction formulas impractical. Inaccuracy of the instruments was independent on mode of measurement, posture, magnitude of the BP and heart rate, early or late measurements from beginning of the head-up tilt test, and prolonged use of the unit. The READ permitted to identify rapidly the degree of accuracy of automatic BP measuring devices. Identification of the aberration pattern of an instrument could be the basis for calculating equations for correction of the measured BP. Further studies will show which parameters of the READ may expose specific defects of the instruments. Journal of Human Hypertension (2000) 14, 37-42.

Adult↗
PubMed2000

Accuracy of the OMRON M4 automatic blood pressure measuring device.

Despite widespread use of the automatic blood pressure (BP) measuring device OMRON M4, there is little formal validation on its accuracy. A study was conducted to assess the accuracy of the OMRON M4 compared with the true indirect BP measured by mercury sphygmomanometer (MS). A rapid method for the evaluation of automatic blood pressure measurement devices (READ) was applied for this study. The READ is based on numerous BP measurements at rest and during a standardised postural challenge in a small number of subjects who exhibit a wide range of BPs. Blood pressure measurements were done in supine position for 10 min followed by head-up tilt for 30 min and again supine for 10 min. The automatic device (AU) and the MS were connected to one arm-cuff by means of a T connector. A stethoscope with dual sets of ear-pieces was used for duplicate MS measurements (MS1 and MS2). The MS1, MS2 and AU measurements were taken simultaneously in a blinded manner. Three units of the automatic instrument were evaluated. An average of 111 measurements per unit were performed, every BP category being present in >/=15 MS measurements. The differences between MS1 and MS2 measurements (DeltaBP: MS1-MS2) were utilized to assess the consistency of true indirect BP and the differences between AU and MS measurements (DeltaBP:AU-MS2) were utilized to assess the accuracy of the AU. The following characteristics of the OMRON M4 were assessed: (1) grade of accuracy, (2) aberration pattern, (3) consistency of the aberration-pattern, and (4) correlation between levels of BP and DeltaBP: AU-MS. For MS paired readings, 92-100% of systolic and 99-100% of diastolic readings fell within 5 mm Hg difference range, that is consistent with a British Hypertension Society grade A of both. For AU compared to MS2, 29-64% of systolic and 73-94% of diastolic readings fell within 5 mm Hg and 49-86% of systolic and 86-99% of diastolic readings fell within 10 mm Hg and the devices qualified C, D and C, respectively. All devices exhibited irregular and inconsistent aberration patterns, making the design of correction formulas impractical. In conclusion, the OMRON M4 device did not meet the requirements of the British Hypertension Society and, therefore, cannot be recommended for clinical use.

Adult↗
PubMed2000

Pulsatile venous insufficiency in severe tricuspid regurgitation: does pulsatility protect against complications of venous disease?

Prior observations showed that the consequences of venous hypertension depend not only on the magnitude of the venous pressure but also on the efficiency of compensatory mechanisms that protect against the effects of excessive pressures on the microcirculation. Pulsatile venous insufficiency (PVI) associated with severe tricuspid regurgitation (TR) provides the opportunity to investigate the effect of the pulsatile shear stress on the outcome of venous insufficiency. The authors conducted a study to assess the flow characteristics and clinical outcome of PVI associated with TR. Five patients were evaluated, presenting venous insufficiency associated with ectasia, varices, and visible systolic pulsations of the leg veins. Characteristics of the venous flow were assessed by duplex ultrasound. In two patients, flow in the distal calf veins was evaluated by power Doppler sonography, and the supine-to-sitting leukocyte trapping was calculated. Results of the latter measurements were compared with measurements in five control patients who presented chronic nonpulsatile venous insufficiency. A survey of complications of PVI was conducted. On follow-up for 6 to 15 years (average 9.4 years) none of the patients developed venous thrombosis, phlebitis, or cutaneous ulcer. Flow in the distal calf vessels was increased in PVI (12-20 vessels/field) as compared with nonpulsatile venous insufficiency (0-7 vessels/field). Leukocyte trapping in the upright position was diminished in PVI (0.8-3%) as compared with nonpulsatile venous insufficiency (7-22%). In conclusion, PVI is characterized by increased flow in the distal calf veins, diminished leukocyte trapping, and a benign clinical course. These data are in agreement with experimental studies showing that pulsatile shear stress enhances secretion of cytokines by venous endothelial cells and, consequently, counteracts a predisposition to platelet aggregation, hypercoagulability, and white cell adhesion and promotes healing of leg ulcers.

Acute Disease↗
PubMed2000

Treatment of refractory, symptomatic, hepatitis C virus related mixed cryoglobulinemia with ribavirin and interferon-alpha.

OBJECTIVE: To assess the benefit of interferon-alpha/ribavirin combination therapy in hepatitis C virus (HCV) infected patients with symptomatic mixed cryoglobulinemia (MC) who failed to respond to treatment with interferon-alpha (IFN-alpha). METHODS: Nine patients (mean age 57 +/- 14 yrs) with type II symptomatic MC who failed to respond to IFN-alpha monotherapy were re-treated with combination treatment of IFN-alpha 3 times weekly and ribavirin 15 mg/kg daily for 6 months. Five of 9 patients had previously received additional treatment during IFN-alpha monotherapy. Clinical and laboratory evaluations (including cryocrit level) were performed weekly for the first month and monthly thereafter. RESULTS: Baseline mean alanine aminotransferase (ALT) and cryocrit levels were 119 +/- 97 IU/l and 7.9% +/- 10%, respectively. All patients were HCV-RNA positive and 5 had cirrhosis. At the end of therapy, mean ALT level was 84 +/- 79 IU/l (p = 0.02), while normal ALT levels were observed in 4 of 9 patients (44%). However, complete virological response was achieved in only 2 patients (22%). Cryoglobulin became undetectable within 6 weeks of therapy in 7 patients (78%) and decreased significantly in 2 others (p = 0.008). A substantial improvement in MC related symptoms (arthralgia/arthritis, proteinuria, skin vasculitis) was achieved in all patients within 10 weeks of combination therapy, although polyneuropathy related symptoms were relatively resistant to treatment. CONCLUSION: Symptomatic, refractory HCV related MC should be considered as an indication for combination therapy with IFN-alpha and ribavirin. Improvement in MC related symptoms can be achieved even without complete biochemical or virological response.

Adult↗
PubMed1999

Myeloma ascites--a favorable outcome with cyclophosphamide therapy.

A 71-year-old woman with multiple myeloma (MM) in remission was admitted for evaluation of recent abdominal distension and was diagnosed as having massive myeloma ascites. The fluid was characterized by a total nucleated cell count of 6,600/mm3 (67% plasma cells), with a plasma cell CD38+ phenotype. Chemical analysis of the fluid showed lactate dehydrogenase of 122 IU/L, total protein of 2.9 g/dL, albumin of 2.4 g/dL, diastase of 38 IU/dL, cholesterol of 46 mg/dL, and C-reactive protein of 3 g/dL. The serum-ascites albumin gradient (SAAG) was low (0.9). Electrophoresis of the ascitic fluid showed a monoclonal spike in the gamma region and immunoelectrophoresis confirmed the presence of lambda light chains similar to those seen in the urine. Further analysis of the ascitic fluid showed markedly elevated levels of beta2 microglobulin (11,161 microg/L) and interleukin-6 (146 pg/ml compared to serum level of 4.3 pg/ml). There was evidence of intraabdominal masses that completely resolved with continuous high-dose cyclophosphamide (750 mg/m2/day for four days) followed by clinical improvement and disappearance of the ascites. We stress the value of complete fluid characterization and intensive chemotherapy to achieve a favorable outcome.

ADP-ribosyl Cyclase↗
PubMed1999

Rapid estimation of the accuracy of automatic blood pressure measuring devices (READ).

We propose a rapid method for the evaluation of automatic blood pressure measurement devices (READ) in response to the claim to simplify the validation of those devices. The READ is based on numerous blood pressure (BP) measurements at rest and during a standardised postural challenge in a small number of subjects who exhibit a wide range of BPs. Automatic (AU) and mercury sphygmomanometric (MS) brachial BP were measured simultaneously in a blinded manner. An average of 30 measurements per patient were done in 10-min while in a supine position, followed by 30 min in head-up tilt and again supine for 10 min. Two Collin-8800 automated oscillometric devices were tested with the aid of the READ in 15 adults. The consistency of the MS standard was demonstrated by duplicate MS measurements showing minimal inter-observer differences consistent with class A of the British Hypertension Society (BHS) grading system. AU-to-MS differences of 447 measurements were mean systolic deltaBP = 1.1 +/- 11.4 mm Hg and mean diastolic deltaBP = -13.36 +/- 8.9 mm Hg, classifying into category D of the BHS. Both tested instruments, each subject, each phase of the tilt test (supine I, tilt, supine II) and each mode of measurement (at 5-min intervals or continuously) equally qualified as 'D'. We conclude that the READ permitted us to identify quickly and at low expense a grossly inaccurate automatic BP measuring device. Further studies will show whether the READ can be efficient as a pre-validation test, post-validation test, and for assessment of ambulatory BP measuring devices.

Adult↗
PubMed1997

The capnography-tilt test for the diagnosis of hyperventilation syncope.

We describe the capnography tilt test (CTT) for the diagnosis of hyperventilation syncope. The CTT is a 10-min supine, 30-min head-up tilt test with simultaneous monitoring of end-tidal PCO2 (ETPCO2). Hyperventilation (HV) was defined as ETPCO2 < or = 25 mmHg. Hyperventilation syncope (HV syncope) was defined as loss of consciousness with ETPCO2 < or = 25 mmHg and no significant drop in blood pressure. Four groups of patients had the CTT: group I (n = 14), patients presenting with syncope who during a prior tilt test had lost consciousness without concomitant fall in blood pressure; group II (n = 50), syncope, primary evaluation, no prior tilt test done; group III (n = 20), generalized anxiety disorder, no syncope; group IV (n = 80), arterial hypertension, no syncope. Hyperventilation was found in 11/14 patients in group I, 5/50 in group II, 7/20 in group III, and none in group IV; HV syncope was diagnosed in seven patients, all in group I. None of the parameters measured in the evaluation, including ETPCO2, predicted HV syncope on tilting. The mechanisms of resting HV and HV during tilt are not well understood. We confirm the existence of HV syncope. The tilt test should probably be used to screen patients presenting with syncope, with the CTT reserved for patients who lose consciousness during the tilt test without an associated fall in blood pressure, as HV is not always clinically obvious.

Adolescent↗
PubMed1997

Severe reversible cardiomyopathy associated with systemic vasculitis in primary Sjögren's syndrome.

A 40y old woman with primary Sjögren's syndrome developed elevated purpura, peripheral neuropathy, muscular tenderness, abdominal pain, heart failure, and convulsive spells. The hallmarks of this disease were high titers of anti-Ro antibodies and low complement levels in the serum, leukocytoclastic small vessel vasculitis in the cutaneous biopsy specimen, and a life threatening clinical course. Echocardiography revealed left ventricular hypokinesis with low ejection fraction, which is unlike the more common features of cardiomyopathy complicating Sjögren's syndrome. The rapidly deteriorating heart failure and other systemic complications remitted on pulse corticosteroid and cyclophosphamide therapy. The pathogenesis of heart failure, which appeared concurrently with vasculitis and was reversed on immunosuppressive therapy, is explained in the context of the systemic disease. Leukocytoclastic vasculitis might be at the origin of this rare variant of acute, severe but reversible cardiomyopathy in pSS.

Adult↗
PubMed1996

Hypotensive reactions on passive head-up tilt testing of hypertensive patients.

With the aid of a protracted passive postural test, the rate of occurrence and the variants of orthostatic hypotensive reactions in hypertensive patients were studied. Three hundred and eighty-two consecutive tilt tests in 161 hypertensive patients, 89.4% of whom were taking antihypertensive medications, were reviewed. Orthostatic hypotensive reactions were recognized in 33.8% of examinations. Thirty-one hypotensive episodes (8.1%) were associated with symptoms of cerebral ischemia, resulting in termination of the tilt test at a median of 5 min from onset (range 1-30 min). A survey of possible risk markers of symptomatic hypotensive reactions during tilt showed that increasing age was associated with significantly increased risk (P < 0.001), while gender, office blood pressure (BP), diabetes mellitus, ischemic heart disease, anxiety, history of syncope, and treatment with antihypertensive drugs were not. Asymptomatic orthostatic hypotension early in the course of the tilt test was a weak predictor of symptomatic hypotensive reactions later during the test (positive predictive value 17.4-33.3%). Among the 31 symptomatic hypotensive reactions, 10 were typical cases of orthostatic hypotension, four were typical vasovagal reactions, and 17 episodes were difficult to classify. The implications of symptomatic hypotensive reactions triggered by protracted head-up tilt in hypertensive patients are unknown and can only be elucidated in longitudinal studies.

Adolescent↗
PubMed1990

Long-term maintenance of the adult pattern of liver-specific expression for P-450b, P-450e, albumin and alpha-fetoprotein genes in intrasplenically transplanted hepatocytes.

Hepatocytes isolated from livers of Fischer 344 rats and transplanted into the spleens of rats from the same strain survived for at least 15 mo in the absence of immunosuppressive drugs. Hepatocytes attached themselves only in the red pulp of the spleen, most commonly in clumps without a discernible structure. Throughout the 15-mo period, intrasplenically transplanted hepatocytes expressed cytochrome P-450b, P-450e and albumin messenger RNAs, whereas alpha-fetoprotein messenger RNA was not expressed. In addition, the relative expression of albumin and P-450 genes was similar to that in liver. For example, albumin messenger RNA was expressed to higher levels than P-450b or e messenger RNAs. Northern blots hybridized with oligonucleotides specific for P-450b or P-450e showed that, as in liver, both P-450b and P-450e genes were induced in response to phenobarbital. Quantitative slot-blot hybridizations performed at 15 days and 1, 6, and 15 mo after hepatocyte transplantation revealed that cytochrome P-450b and P-450e messenger RNAs were induced about 20- to 30-fold by a single dose of phenobarbital. This level of induction was also similar to that observed in liver. Hence, intrasplenically transplanted hepatocytes represent a unique system in which hepatocytes, cultured in an extrahepatic in vivo environment, maintain for at least 15 mo a pattern of expression for these four liver genes similar to that in the adult liver. Moreover, these studies suggest that neither the organization of liver into acini nor a specific zonal sinusoidal microenvironment is necessary for adult hepatocytes to respond to phenobarbital with induction of P-450b and P-450e genes.

Albumins↗
PubMed1989

Induction of P-450IIB genes within the rat liver acinus is not dependent on the chemical inducer or on the acinar organization.

P-450IIB genes (P-450b and P-450e in rat) are induced following treatment with phenobarbital predominantly in hepatocytes located in zones 2 and 3 of the liver acinus. The previous finding of phenobarbital-mediated induction of P-450IIB mRNAs and apoproteins in the same zonal hepatocytes suggests that this differential induction is most likely due to zonal differences in the activation of gene transcription. To determine whether differential P-450IIB gene transcription was dependent on the type of inducer (i.e., inducer specificity) or on the capacity of hepatocytes located in different acinar zones to respond to inducers (i.e. zonal specificity), the pattern of acinar induction was evaluated following treatment with inducers that have diverse physiochemical properties and inductive capacities. The zonal distribution of P-450b and P-450e mRNAs in liver was determined by in situ hybridization after the administration of either phenobarbital, polychlorinated biphenyls, chlordane, or chlorpromazine. Liver sections were hybridized with 3H-labeled RNA transcripts of a P-450e cDNA that recognizes sequences of both P-450b and P-450e mRNAs and the pattern of zonal mRNA induction was measured by quantitative image analysis. Each inducer increased P-450b,e mRNA levels predominantly in hepatocytes of zones 2 and 3 of the hepatic acinus. The P-450b and P-450e apoproteins were induced in the same zonal hepatocytes as the P-450b,e mRNAs as shown by immunofluorescence studies using monoclonal antibodies. Therefore, differential transcriptional induction of the P-450IIB genes in the liver acinus does not seem to be dependent on a specific chemical inducer, but rather is a characteristic capacity of hepatocytes located in different acinar zones. To determine whether the induction of P-450b and P-450e was dependent on the liver tissue organization, hepatocytes were isolated by collagenase perfusion of the liver and transplanted into the spleens of syngeneic rats. Induction of P-450b and P-450e mRNAs and apoproteins, assessed 1 month after transplantation, was evident with each of the chemical inducers. These data suggest that, once hepatocytes have attained the capacity to respond to inducers, the organization of hepatocytes into acini and the sinusoidal microenvironment of the liver are not required for hepatocytes to maintain the ability to respond to inducers with an increase in transcription of P-450IIB genes. Moreover, the splenic hepatocytes demonstrated a heterogeneous pattern of P-450b,e apoprotein induction; this raises the possibility that the acinar organization is also not required for the heterogenous expression of P-450IIB genes.

Animals↗
PubMed1988

Demonstration by in situ hybridization of the zonal modulation of rat liver cytochrome P-450b and P-450e gene expression after phenobarbital.

The various physiological processes that constitute liver function are compartmentalized within the hepatic acinus. The molecular mechanisms modulating the development and maintenance of this hepatocyte heterogeneity have not been defined. The objective of this study was to determine whether transcriptional or posttranscriptional zonal modulation of cytochromes P-450b,e gene expression was responsible for the heterogeneous induction of the P-450 proteins, which is observed after phenobarbital (PB) administration. The exact localization in liver tissue of hepatocytes responding to PB with induction of either P-450b,e mRNA or proteins was established by in situ hybridization and by immunofluorescence, respectively. As demonstrated by quantitative assessment of autoradiographs of approximately 20 hepatocytes located between a terminal portal venule and a hepatic venule, PB induced the P-450b,e mRNA up to sixfold in the 12-15 hepatocytes located closer to the hepatic venules (zones 2 and 3). In contrast, there was only a twofold induction in the 4-6 hepatocytes surrounding the terminal portal venules (zone 1). Quantitative immunofluorescence using an MAb showed that the acinar distribution of PB-induced P-450b,e proteins was similar to that of the mRNA. This combined approach indicated that, most likely, an increased rate of transcription of cytochromes P-450b,e genes in hepatocytes of zones 2 and 3 concomitantly, with a relative lack of activation, or repression, of these genes in hepatocytes of zone 1, were responsible for the heterogeneous phenotype observed after PB administration. Therefore, modulation of gene expression among hepatocytes of the liver acinus is one mechanism by which the functional heterogeneity of hepatocytes is attained. Experiments in which the induction of cytochromes P-450b,e genes was studied after administration of either PB or para-hydroxyphenobarbital, a main hepatic metabolite of PB, suggested that the species involved in the inductive process is the parent PB molecule rather than para-hydroxyphenobarbital.

Animals↗
PubMed1986

Gangliosides GM1 and GD1b are antigens for IgM M-protein in a patient with motor neuron disease.

We studied a patient with an IgM M-protein and lower motor neuron disease to identify the antigens to which the M-protein bound. Gangliosides from peripheral nerve and spinal cord were separated by high-performance thin-layer chromatography and immunostained with the patient's serum. The serum IgM immunostained two gangliosides identified as GM1 and GD1b, and immunostaining was specific for the M-protein light chain type. IgM-binding to the two gangliosides was detectable by ELISA at serum dilutions of greater than 1:10,000, and the M-protein was selectively immunoabsorbed by liposomes containing GM1 or GD1b. The IgM M-protein also bound to asialo-GM1, indicating reactivity to the galactosyl(beta 1-3)N-acetylgalactosaminyl moiety shared by GM1, GD1b, and asialo-GM1.

Antigens↗
PubMed1984

Safety and antigenicity of typhoid-Shigella sonnei vaccine (strain 5076-1C).

The form-1 antigen of Shigella sonnei was transferred to the avirulent Salmonella typhi strain 21a and the resulting 5076-1C transconjugate strain was tested for safety and immunogenicity as a candidate oral vaccine. The transconjugant strain was shown to be well tolerated and safe in 19 human volunteers who were fed from 1 X 10(7) to 1 X 10(10) organisms. Only two of 10 volunteers tested had developed a rise in antibody titer to the lipopolysaccharide of the hybrid 5076-1C strain.

Administration, Oral↗
PubMed1981

Porcine xenograft valve failure in children: an immunologic response.

Thirty-six children underwent placement of either an intracardiac porcine xenograft valve (n = 17) or an extracardiac porcine xenograft-valve conduit (n = 20). Eleven of 17 patients with intracardiac porcine valves and only one of patients with 20 extracardiac porcine valved conduits had severe hemodynamic valvular changes (p less than 0.01). Twelve of 17 of the intracardiac xenograft patients had symptoms: eight had congestive heart failure, one had angina and three had exercise intolerance. The only extracardiac conduit patient with hemodynamic changes had congestive heart failure. Calcification was noted in 11 of 18 intracardiac porcine valves and in none of the extracardiac valved conduits. Pathologic valve material was available in nine of 18 intracardiac porcine valve patients and disclosed extensive ingrowth of host tissue in eight valves, histiocytic infiltrates in all nine valves, plasma cell infiltrates in three valves and positive immunofluorescence for immunoglobulin in all three valves. Three of 17 patients with intracardiac porcine xenograft valves had increased plasma immunoglobulins and one patient had bone marrow plasmocytosis. Our data suggest that children have a high incidence of early xenograft dysfunction only when intracardiac porcine valve replacement is performed. The infiltration of plasma cells and histiocytes and the immunoglobulin response in children with intracardiac glutaraldehyde-preserved porcine valves suggest the xenograft dysfunction may in part be due to an immunologic reaction.

Adolescent↗