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Biomedical subjects

R E Falk

Publications and source records attributed to R E Falk.

At least 37 records · Page 2Linked to original sources
PubMed1992

Screening for Down syndrome with the femur length/biparietal diameter ratio: a new twist of the data.

OBJECTIVE: The purpose of this study was to determine the value of discordant morphometric measurements as identifiers of Down syndrome by evaluating the relationship of biparietal diameter, femur length, biparietal diameter/femur length ratio, and cephalic index between a group of fetuses with trisomy 21 and a control population. STUDY DESIGN: Biometric measurements from 48 fetuses with trisomy were reviewed and compared with 107 normal fetuses of similar gestational age. Data were analyzed in 2-week gestational age intervals to determine the effect of gestational age on ultrasonographic detection of Down syndrome. Outcome measures were subject to least-squares linear regression and the t test for analysis. RESULTS: A positive relationship between abnormal morphometric measurements and fetuses with Down syndrome was detected but only during specific weeks of pregnancy. CONCLUSION: Although it appears that biometric measurements may be useful for Down syndrome, further study is needed before its widespread introduction into clinical practice.

Down Syndrome↗
PubMed1990

Acrocephalospondylosyndactyly--a possible new syndrome: analysis of the vertebral and intervertebral components.

Apert-Crouzon syndrome (formerly ACS type 2; 10130) is now considered a subset of autosomal dominant Apert acrocephalosyndactyly type 1 (10120), with features of craniosynostoisis, syndactyly of all extremities, maxillary hypoplasia, "parrot-beaked" nose, hypertelorism, exophthalmos, external strabismus, and short upper lip. We report a 3 1/2-month-old infant with features of Apert syndrome, plus thoracic vertebral anomalies radiographically similar to those seen in spondylothoracic dysplasia, a condition in which block thoracic vertebrae with widely open neural arches and a fan-shaped thoracic cage are found. Our patient also had flared metaphyseal ends of humeri, dislocated radii with immobile elbows, an unusual tail-like protuberance in the coccygeal area, and a solid cartilaginous tracheal wall. To date, in ongoing reviews of radiographs of other patients with acrocephalosyndactyly or acrocephalopolysyndactyly complexes and of relevant literature, we have not identified other patients with these findings. The vertebrae and intervertebral discs of the patient in this report, three patients with Jarcho-Levin syndrome, and one with Apert syndrome were measured from anteroposterior chest radiographs; the findings clearly distinguish the condition in our patient from Jarcho-Levin syndrome or Apert syndrome.

Abnormalities, Multiple↗
PubMed1990

Linkage of an autosomal dominant clefting syndrome (Van der Woude) to loci on chromosome Iq.

Van der Woude syndrome (VWS) is an autosomal dominant disorder in which affected individuals have one or more of the following manifestations: cleft lip, cleft palate, hypodontia, or paramedian lower-lip pits. VWS is a well-characterized example of a single-gene abnormality that disturbs normal craniofacial morphogenesis. As a first step in identifying genes involved in human development, we used a candidate-gene-and-region approach to look for a linkage to VWS. Six families with 3 or more generations of affected individuals were studied. Evidence for linkage (theta = 0.02, lod score = 9.09) was found between the renin (REN) gene on 1q and VWS. Other linked loci included CR1, D1S58, and D1S53. The genes for laminin B2 (LAMB2), a basement-membrane protein, and for decay-accelerating factor (DAF) were studied as possible candidate genes on 1q. Recombinants between VWS and both LAMB2 and DAF excluded these genes from a causal role in the etiology of VWS for the families studied in this report. Multipoint linkage analysis indicated that the VWS locus was flanked by REN and D1S65 at a lod score of 10.83. This tight linkage with renin and other nearby loci provides a first step in identifying the molecular abnormality underlying this disturbance of human development.

Chromosomes, Human, Pair 1↗
PubMed1989

Analysis of the effect of liposome encapsulation on the vesicant properties, acute and cardiac toxicities, and antitumor efficacy of doxorubicin.

Numerous studies have demonstrated that liposomal encapsulation decreases the life-threatening chronic and acute toxicities of doxorubicin in the face of unaltered or improved antitumor activity. Minimal attention has been paid to the encapsulation effect on the lesser toxicities of the drug, specifically the vesicant properties. In this report we assess the effect of the encapsulation of doxorubicin in an egg-yolk phosphatidylcholine (EPC) cholesterol liposome on the drug's topical toxicity. In addition, to ensure acceptable activity and reduction in toxicity comparable with those of previously assessed formulations, the cardiac and acute toxicities and antitumor activity of the liposomal doxorubicin complex were also investigated. Antitumor efficacy was assessed using the metastatic murine P815 mastocytoma model. Equivalent doses of free and encapsulated doxorubicin possessed the same antitumor activity in the prolongation of animal survival in 14-day survival studies conducted to assess the effect of liposomal encapsulation on the acute toxicity of this drug. The LD50 of liposomal doxorubicin was found to be 40 mg/kg, 53% higher than that of free doxorubicin (26 mg/kg). Histologic examination of cardiac sections taken from DBA/2J mice 7 days after a single i.v. injection of free or liposomal doxorubicin (25 mg/kg) revealed that the liposomal preparation was much less cardiotoxic. In animals receiving the free drug, edema, monocytic infiltration, and cell necrosis were evident. In contrast, those receiving the liposomal preparation demonstrated slight cellular edema but showed no evidence of cellular necrosis. To assess vesicant properties, DBA/2J mice were given a single s.c. injection (0.2 ml) of free or liposomal doxorubicin (2 mg/ml). Those receiving the free drug immediately developed erythema and edema at the injection site, which progressed to ulceration. Those receiving the liposomal complex developed slight erythema and edema but did not ulcerate at any time. All signs of irritation in this group had subsided 3 weeks postinjection. In summary, the liposomal complex used eliminated the vesicant properties of doxorubicin as well as significantly decreasing its cardiac and acute toxicities in the face of unaltered antitumor activity.

Animals↗
PubMed1989

Increase of serum interleukin 2 receptor level in thermally injured patients.

Serum concentrations of receptor for the T cell growth factor interleukin 2 (IL-2R) were compared to the capacity of activated T cells to express surface IL-2R in patients with major burns. In immunosuppressed patients the numbers of cells expressing IL-2R were transiently (survivors) or permanently (nonsurvivors) reduced (up to 50 and 90%, respectively). In contrast, the levels of soluble IL-2R in patients' sera were significantly (P less than 0.001-0.05) elevated throughout the postburn period. Within 24 hr postinjury, over 90% of patients demonstrated 400-3500 U/ml of serum IL-2R compared with 120-340 U/ml in normal controls. Soluble IL-2R, when patients became immunosuppressed, further increased to 4445 +/- 962 U/ml in nonsurvivors and to 2031 +/- 578 U/ml in survivors, and demonstrated a significant capacity to inhibit the activity of exogenous IL-2. In survivors the levels of serum IL-2R declined at discharge, to 1009 +/- 104 U/ml. Thus, in thermally injured patients, soluble IL-2 receptor concentrations are elevated, and could interfere with IL-2-mediated immune interactions.

Adolescent↗
PubMed1988

Interleukin-2 secretion and transmembrane signalling in burned patients.

IL2 secretion in response to the T-cell mitogen Staphylococcal protein A (SPA) is significantly decreased in patients with major burns (n = 10, greater than 20% total body surface area) up to 50 days postburn in comparison with normal control (greater than 2 to 10 U/ml and 16 to 36 U/ml, respectively). Activation of protein kinase C (PK-C) and changes in [Ca++]i are both normally implicated in the production of IL2. Bypassing the requirements for mitogen-induced increases in [Ca++]i, using the cation ionophore A23187, or activating PK-C with the phorbol ester 12-o-tetradecanoyl-phorbol-13-acetate (TPA), failed to significantly restore SPA-induced IL2 production in cell cultures from burned patients. The combination of A23187 and TPA significantly (p less than 0.005-0.001) enhanced IL2 secretion in patients' cell cultures (range, 20 to greater than 64 U/ml). However, the levels of IL2 from the burned patients' cultures remained significantly lower (p less than 0.05) than those in control cultures exposed to TPA and A23187 (range, 256 to greater than 600 U/ml). Therefore, the burn-related defect in mitogen-induced IL2 secretion is only partially bypassed with cation ionophores and phorbol esters. This suggests that the abnormality in IL2 production may not be solely related to changes in PK-C activation and in [Ca++]i but may reside in other than transmembrane signalling mechanisms required for IL2 production.

Adult↗
PubMed1988

The peripheral nerve allograft: a dose-response curve in the rat immunosuppressed with cyclosporin A.

The potential use of peripheral nerve allografts would significantly improve the reconstructive potential for patients with major peripheral nerve deficits. This study evaluated the response of the nerve allograft recipient treated with varying dosages of cyclosporin A (CsA) to determine the minimal effective dosage necessary to prevent nerve graft rejection. Lewis rats (RT1l) were the recipients of syngeneic nerve grafts from identical Lewis donors or allogeneic nerve grafts from ACI (RT1a) donors. Nerve grafts were inlaid next to the intact sciatic nerve of the recipient. The immunologic responsiveness of the recipient animal's lymphocytes to a donor-specific antigenic challenge was assessed by the mixed lymphocyte reaction (MLR). In addition, nerve grafts were evaluated histologically. Animals were monitored for cyclosporin A toxicity. It was found that cyclosporin A (5 mg/kg per day) was effective in rendering the recipient animals unresponsive by mixed lymphocyte reaction at 10, 20, and 40 days after engraftment. This dosage was similarly effective in preventing histologic changes characteristic of nerve allograft rejection. This dosage regimen was nontoxic to the animals. Our study ascertained a minimal nontoxic dosage of cyclosporin A that effectively prevented nerve allograft rejection across a major histocompatibility disparity in rats.

Animals↗
PubMed1988

The stimulating effect of a cytosol extract from regenerating liver on isolated hepatocytes and the positive role of insulin.

Several kinds of damage induce a regenerative response in the liver. Partial hepatectomy is a well known method, suitable for studying liver regeneration and factor/s involved in it. The presence of the so called Hepatic Stimulator Substance has been demonstrated in the cytosol obtained from regenerating hepatocytes, and it has been partially characterized, from a molecular point of view. Mainly, it stimulates liver regeneration and Tritiated Thymidine incorporation in cultured hepatocytes as demonstrated in this paper (Control Hepatocytes: 8447 +/- 660.4 cpm, (mean +/- sd), Test Hepatocytes: 16974 +/- 2720.9 cpm; Index of Stimulation: 2.01). Furthermore, the stimulating activity of HSS is increased by the presence, in the culture media, of insulin which has been proved to have a positive role in liver regeneration (Control Hepatocytes: 8889 +/- 367.3 cpm; Test Hepatocytes: 21588.5 +/- 1232.4 cpm; Index of Stimulation: 2.42, p less than 0.05). These data seem to suggest that liver is probably the site of production/activity and action of factor/s that stimulate/s liver regeneration; but other substances exist, such as insulin, which play a permissive role.

Animals↗
PubMed1988

The peripheral nerve allograft: an assessment of regeneration across nerve allografts in rats immunosuppressed with cyclosporin A.

Lewis rats (RT1(1] were the recipients of 3-cm nerve grafts from syngeneic Lewis donors or allogeneic ACI (RT1a) donors. Microneurosurgical repair of the nerve graft to the transected sciatic nerve of the recipient animal was performed with 10-0 epineurial sutures. Recipients were randomly allocated to cyclosporin A (CsA) immunosuppressed or untreated groups. Cyclosporin A was administered in the minimal effective dosage to prevent nerve allograft rejection across this major histocompatibility disparity (5 mg/kg per day). Nerve regeneration across the nerve grafts was assessed by sciatic function index (SFI) and toe spread index (TSI) determinations serially and by electrophysiologic, histologic, and morphologic assessments 14 weeks after engraftment. Sciatic nerve regeneration across allogeneic nerve grafts in cyclosporin A immunosuppressed recipients was significantly superior compared to the untreated controls (p less than 0.008) and not significantly different from that across the syngeneic control animals.

Animals↗
PubMed1987

Prenatal diagnosis of tuberous sclerosis: the use of fetal echocardiography.

Fetal echocardiography was used to identify a cardiac rhabdomyoma in the second trimester. The combination of this finding with a maternal history of Tuberous Sclerosis allowed the patient and her family to make a more educated decision regarding termination of the pregnancy. Post mortem examination of the fetus confirmed the prenatal findings. This case report demonstrates the importance of ultrasound evaluation of the fetus at risk of recurrence of a genetic syndrome in which one or more anatomical defects might be seen.

Adolescent↗
PubMed1987

Impaired expression of interleukin-2 receptor (IL2R) in the immunosuppressed burned patient: reversal by exogenous IL2.

The capability of exogenous recombinant Interleukin 2 (rIL2) to increase expression of the IL2 receptor (IL2R), and to augment the in vitro proliferative response of lymphocytes from immunosuppressed burned patients (5-80% full-thickness burns) was examined. Throughout the postburn period the percentage of IL2R-bearing cells in Concanavalin A-activated cultures of patients' peripheral blood mononuclear cells (PBMC) was measured by direct immunofluorescence with monoclonal anti-IL2R antibodies. Mitogen-induced IL2R expression was decreased by 40-90% in cultures of patients' PBMC, parallel to their reduced alloreactivity. During this period of immunosuppression supplementation of the mitogen-activated cultures with recombinant IL2 (20 U/ml) significantly increased the number of IL2R-expressing cells in all patients studied. However, IL2-induced enhancement of blastogenesis in the MLR was observed only with the patients who, in mitogen-activated cultures, sustained numbers of IL2R-endowed cells at least 50% of their baseline (the level within the first 24 hours postburn). Also, unstimulated PBMC of the same responding patients demonstrated a restoration of proliferation in the presence of rIL2. These patients were survivors. Thus the proliferative response correlated well with the number of Con A- but not rIL2-induced IL2R-expressing cells. These results suggest that in burned patients, IL2 up-regulates its receptors, but they may represent low-affinity nonfunctional receptors. Thus thermal injury appears to affect expression of functional (high-affinity) receptors.

Adolescent↗
PubMed1987

16, 16 Dimethyl prostaglandin E2 prevents the development of fulminant hepatitis and blocks the induction of monocyte/macrophage procoagulant activity after murine hepatitis virus strain 3 infection.

16, 16 Dimethyl prostaglandin E2 (dmPGE2), a known cytoprotective agent, was examined for its ability to alter the course of fulminant hepatitis in an experimental model of fulminant viral hepatitis, murine hepatitis murine hepatitis type 3 (MHV-3). Fully susceptible BALB/cJ mice, infected with 100 50% lethal doses (LD50) of MHV-3 developed histologic and biochemical evidence of fulminant hepatitis, as evidenced by massive hepatic necrosis with hypoglycemia, metabolic acidosis, and a markedly elevated serum alanine aminotransferase (ALT) (mean, 1,402 +/- 619 IU/liter). In contrast, animals treated with dmPGE2 either before or after infection (up to 48 h) demonstrated a marked reduction in both histologic and biochemical evidence of liver damage as characterized by normal blood glucose, total CO2, and ALT determinations (mean ALT, 63 +/- 40 IU/liter). Treatment of infected mice with PGF2 alpha demonstrated no cytoprotective effects. High titers of infectious virus were recovered from the livers of both dmPGE2-treated and -untreated animals throughout the course of infection. In a parallel in vitro study, dmPGE2 (10(-4)-10(-8) M) demonstrated a similar cytoprotective effect on monolayers of isolated cultured hepatocytes from fully susceptible BALB/cJ mice infected at a multiplicity of infection of 0.1, 1.0, and 10.0. In addition, splenic macrophages recovered from infected and untreated BALB/cJ mice demonstrated a marked augmentation in procoagulant activity (PCA) from a basal 10 +/- 5 mU/10(6) splenic macrophages to a maximum of 615 +/- 102 mU/10(6) splenic macrophages, whereas no increase in macrophage PCA was detected in infected animals treated with dmPGE2. These results suggest that dmPGE2, without detectably altering viral replication or infectivity in vivo, confers a marked cytoprotective effect on hepatocytes both in vivo and in vitro, and prevents the induction of macrophage PCA in vivo in fully susceptible BALB/cJ mice after murine hepatitis virus type 3 infection.

16,16-Dimethylprostaglandin E2↗