Biomedical subjects

R Risser

Publications and source records attributed to R Risser.

At least 37 records · Page 2Linked to original sources

PubMed1992

Intraoperative albumin administration affects the outcome of cadaver renal transplantation.

The prognostic significance of early malfunction or delayed function after cadaveric renal transplantation is controversial. This study examines the influence of intraoperative management in 438 cadaveric renal transplant recipients on seven posttransplant outcome measures: (1) time of onset of urine output, (2) urine volume, (3) renal function, (4) incidence of delayed function, (5) never-functioning kidney, (6) graft survival, and (7) patient survival. Delayed function, defined as the need for hemodialysis during the first posttransplant week, decreased from 46% in 1982 to 15% in 1990 and was associated with a 25% lower 1-year graft survival rate and a mortality rate of 10% at 3 months, compared with 3% when immediate function was present. The most important factors influencing the outcome were cold ischemia time (P = 0.007), intraoperative administration of albumin (P = 0.0027), duration of surgery (P = 0.020), and recipient age (P = 0.041). A high albumin dose (1.2-1.6 g/kg bodyweight) induced urine output within 30 min in 75% of patients and induced larger urine volumes (7.3 L/24 hr), as compared with the effects of a low dose (0-0.4 g/kg), which induced urine output within 30 min in 39% and only 3.7 L/24 hr. Serum creatinine at 1 week was 3.4 and 5.8 mg/dl for the high and low albumin doses, respectively (P less than 0.0001). Similarly, mean glomerular filtration rates at 1 and 7 days were 33 and 21 ml/min, compared with 47 and 28 ml/min, for the high and low albumin doses, respectively (P less than 0.01). The incidence of delayed function and of never-functioning kidneys declined from 34% and 9% for the low dose to 12% and 1% for the high dose, respectively. Finally, with increasing albumin dose, the graft survival rate at 1 year improved from 59 to 78% (P less than 0.002), and the patient mortality rate at 3 months dropped from 6% to 2%. For albumin dose intervals between the high (1.2-1.6 g/kg) and low (0-0.4 g/kg), the effect on all seven outcome measures was intermediate, generally describing a linear relationship. Weighted least-squares analysis of the relationship of delayed function with high vs. low doses of albumin, mannitol, furosemide, and volumes of crystalloid solutions showed significance only for the albumin effect. High-dose albumin infusion likely produces intravascular volume expansion and achieves a prompt restoration of blood flow, minimizes hypoxic injury, and helps preserve renal tissue. The possibility of other beneficial effects of albumin unrelated to intravascular volume also exists.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1992

Interference established in mice by infection with Friend murine leukemia virus.

Retroviral interference is manifested in chronically infected cells as a decrease in susceptibility to superinfection by virions using the same cellular receptor. The pattern of interference reflects the cellular receptor specificity of the chronically infecting retrovirus and is mediated by the viral envelope glycoprotein, which is postulated to bind competitively all cellular receptors available for viral attachment. We established retroviral interference in mice by infecting them with Friend murine leukemia virus and them measured susceptibility to superinfection by challenging the mice with the erythroproliferative spleen focus-forming virus. Infection of approximately 10% of nucleated splenocytes rendered mice 1% as susceptible to superinfection as untreated controls. The magnitude of this effect was the same in mice incapable of producing neutralizing antibodies or genetically deficient for T cells. The results indicated that retroviral interference in vivo was established rapidly with infection of a fraction of the host cell population and that the decrease in susceptibility to superinfection occurred without a detectable contribution by immunologic factors.

Animals↗

PubMed1992

Effect of maternal hypertension on neonatal neutropenia and risk of nosocomial infection.

Neonatal neutropenia occurs in approximately 50% of newborns delivered by women with pregnancy-induced hypertension. It is thought to be transient, independent of birth weight and gestational age, and unassociated with significant risks, including infection. It recently was suggested that neonatal neutropenia occurs primarily in smaller, younger neonates, is related to the severity of pregnancy-induced hypertension, and importantly, may be associated with an increased risk for nosocomial infection. We examined these points in a large inborn population in consecutive years, performing retrospective (n = 110, 1989) and prospective (n = 151, 1990) studies in low birth weight (less than or equal to 2200 g) neonates delivered by women with pregnancy-induced hypertension. Overall, 40% to 50% of neonates studied developed neonatal neutropenia, and they were younger and smaller (P less than .01) than non-neutropenic neonates. In the prospective study, neutropenic neonates were more likely to have mothers with severe pregnancy-induced hypertension (P less than .001), and the incidence of neonatal neutropenia was primarily among neonates less than 30 weeks of gestation and less than 1500 g birth weight, approximately 80% vs 35% to 45% in older, larger neonates or infants (P less than .001). Although nosocomial infection occurred more frequently among the group of neutropenic neonates in the prospective study (P less than .02), the incidence was similar to that in matched non-neutropenic controls delivered of normotensive women. Thrombocytopenia (less than 100,000/mm3) was not more frequent in neutropenic neonates.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗

PubMed1992

A retrovirus that expresses v-abl and c-myc oncogenes rapidly induces plasmacytomas.

ABL-MYC, a murine retrovirus that encodes the v-abl and c-myc oncogenes, was constructed from Abelson murine leukemia virus (A-MuLV) in order to assess the biological consequences of co-expression of these genes in lymphoid cells. When inoculated into mice this retrovirus induced plasmacytomas in up to 100% of infected mice and less frequently induced pre-B lymphomas. Both tumor types contained genome-length proviruses in one or a few chromosomal locations, were mono- or oligoclonal as judged by immunoglobulin gene rearrangement and had unrearranged endogenous c-myc loci. The type of tumor induced depended upon the age and strain of mouse, and whether helper virus was present in the inoculated virus pool. ABL-MYC induced plasmacytomas with or without helper virus, with or without pretreatment of the mice with pristane, and in strains of mice resistant to pristane-induced plasmacytomas. Pristane treatment prior to ABL-MYC infection shortened the latent period of plasmacytomagenesis and produced mostly IgM-secreting tumors rather than IgA-secreting tumors, which predominantly arose in the absence of pristane. Control viruses for ABL-MYC with either a deletion in v-abl or a frameshift mutation in c-myc caused predominantly monocyte/macrophage tumors and pre-B-cell lymphomas respectively. Histopathological analysis of ABL-MYC-infected mice showed foci of transformed plasma cells as early as 14 days after infection. These results indicate that v-abl and c-myc act synergistically to transform mature B cells with high efficiency.

Animals↗

PubMed1991

Induction of plasmacytomas secreting antigen-specific monoclonal antibodies with a retrovirus expressing v-abl and c-myc.

ABL-MYC, a recombinant murine retrovirus that expresses v-abl and c-myc, rapidly induces transplantable mono- or oligoclonal plasmacytomas in BALB/c mice. To determine if the targets for transformation of this retrovirus are antigen-committed B lymphocytes and to explore this system as an alternative technique for producing antigen-specific monoclonal antibodies, plasmacytomas were induced in mice that had been immunized with two different types of immunogens, hen egg white lysozyme and sheep red blood cells. The majority of these plasmacytomas secreted immunogen-specific antibodies. Plasmacytomas induced in unimmunized mice did not react with hen egg white lysozyme or sheep red blood cells. The specific antibodies were comparable in concentration, specificity, and affinity to monoclonal antibodies obtained with conventional hybridoma technology, but, in addition to IgGs and IgMs, they included specific IgA antibodies, which are rare among splenic-derived hybridomas. Our results demonstrate that a principal target for ABL-MYC is an antigen-committed B lymphocyte. In addition this procedure provides an alternative method for the production of monoclonal antibodies, without a requirement for hetero-caryon formation by cell fusion techniques.

Animals↗

PubMed1991

Thymic targets for Abelson murine leukemia virus are early gamma/delta T lymphocytes.

Molecular analysis has shown that the majority of Abelson murine leukemia virus (Ab-MuLV)-induced primary thymomas represent transformed gamma/delta thymocytes. Many of these thymomas are of monoclonal origin as judged by provirus integration pattern and contain rearranged genes encoding T-cell receptor (TCR) gamma and delta chains but germ-line immunoglobulin heavy-chain genes. Some of the monoclonal tumors contain multiple rearranged alleles encoding TCR gamma, delta, and beta chains. Further, one Ab-MuLV thymoma cell line contained germ-line-configuration TCR gamma- and delta-chain genes, which became rearranged after in vitro propagation. Clones of this cell line were observed to rearrange these genes after intrathymic passage. Also, some subclones of this cell line underwent rearrangement of their immunoglobulin heavy-chain genes in culture. These observations suggest that the thymic targets for Ab-MuLV transformation are early gamma/delta thymocytes, some of which continue to rearrange their TCR gamma- and delta-chain genes.

Abelson murine leukemia virus↗

PubMed1991

Prognosis of ovarian cancer developing in the residual ovary.

Elective oophorectomy at the time of hysterectomy for benign disease in women during their fifth decade is an important issue for both gynecologist and patient. It has been suggested that cancer developing in the residual ovary has a worse prognosis than the national average (L. McGowan, Obstet. Gynecol. 69, 386, 1987). In an effort to corroborate such finding, 36 women with epithelial ovarian cancer developing in the residual ovary after prior hysterectomy were compared to a group of 121 patients with epithelial ovarian cancer and no previous surgery. Analysis was made of age, stage at diagnosis, feasibility of cytoreductive surgery, and survival in both groups. Only age distribution was found to be significantly different between the two groups of patients (P less than 0.001). Neither FIGO staging or quality of cytoreductive surgery showed a statistically significant difference between both groups. At 3 years, 41% of the subjects with cancer in the residual ovary were alive, compared to 42% in the group without previous hysterectomy. The corresponding figures for 5-year survival are 34 and 27%, respectively (P = 0.939). On the basis of our findings we conclude that the overall prognosis for patients with ovarian cancer developing in the residual ovary does not appear to be any worse than that reported for ovarian cancer in general.

Adult↗

PubMed1991

Correlation of squamous cell carcinoma antigen levels and treatment response in cervical cancer.

Squamous cell carcinoma antigen (SCC) was measured by serum radioimmunoassay in 82 patients with primary (55) or recurrent (27) squamous carcinoma of the cervix, to determine correlation with the clinical presence of tumor and response to radiation and chemotherapy. Sixty-seven percent of those with newly diagnosed cancer and eighty-one percent of those presenting with recurrence had values above 2.5 ng/ml. In the newly diagnosed patients, 17% of those with stage I and 80% of those with stages II and above had abnormal values. Mean titers for stages I through IV were 2, 9, 19, and 144 ng/ml, respectively, confirming an association with tumor burden. Twenty-four patients underwent radiation therapy; eighteen of these had elevated pretreatment levels and were assessed for response. Titers accurately predicted regression and progression in all cases. Thirty patients received chemotherapy; twenty-seven of them had elevated pretreatment levels and were evaluable for response correlation. Titers predicted response in 96% of cases. An additional group of 20 patients successfully treated and with no evidence of disease was followed with SCC levels every 3 months. In 19 of these 20 patients (95%), the marker accurately predicted the status of disease. In 2 of these patients, who recurred while on the study, the SCC level increased before the tumor became clinically apparent. We conclude that SCC levels are useful in evaluating the response of primary and recurrent squamous cell carcinoma of the cervix to radiation and chemotherapy.

Carcinoma, Squamous Cell↗

PubMed1991

Intraobserver and interobserver reliability in assessment of neonatal cranial ultrasounds.

Intraobserver and interobserver reliability in assessing neonatal cranial ultrasounds for periventricular-intraventricular hemorrhage (PVH-IVH) is not well studied; therefore, studies were designed to address this. For intraobserver reliability 180 cranial ultrasounds (360 hemispheres) were randomly selected from greater than 2000 ultrasounds and read twice by one radiologist in a blinded fashion. Ninety-eight percent were interpreted identically; of the 2% reinterpreted differently, all were initially abnormal but normal on the second reading. The least agreement occurred when interpreting ventricular size. Only four infants (1.1%) were placed in an unfavorable prognostic category (grades III and IV) on the first reading and a favorable prognostic category on the second interpretation (no bleed, grades I and II). To determine interobserver reliability, 20 sonograms were interpreted by eight independent observers representing five institutions. Using the multiple rater kappa kappa statistic, we determined interobserver agreement on overall impression (normal vs. abnormal), presence and extent of PVH-IVH (i.e. grade), presence of residual cyst, and ventricular dilatation. Greatest degree of agreement occurred when determining normal vs. abnormal, residual cyst, no bleed, and grades III and IV PVH-IVH. Poorest agreement occurred when reading grades I and II PVH-IVH and ventricular dilatation. After condensing interpretations of cranial ultrasounds into two prognostic categories, i.e. favorable (no bleed, grades I and II) and unfavorable (grades III and IV), there was excellent agreement among the observers.

Cerebral Hemorrhage↗

PubMed1991

Symptomatic patent ductus arteriosus in very-low-birth-weight infants: 1987-1989.

Symptomatic patent ductus arteriosus (sPDA) may occur in up to 50% of very-low-birth-weight (VLBW, less than or equal to 1500 g) infants. We reported a 16% incidence in 1979-1980 in a totally inborn population, demonstrating the importance of early fluid management. Although survival of VLBW infants, especially those less than 1000 g, has increased, sPDA has not been carefully re-examined. Therefore, we sought to determine if the incidence, morbidity, treatment, or risk factors for sPDA had changed in this population. Between January 1, 1987 and December 31, 1989 all VLBW infants with sPDA surviving greater than 72 h (119/636) were identified and compared to matched controls (n = 70). Incidence and onset of sPDA were 19% and 10 +/- 6 days (+/- S.D.), respectively, the former increasing from 8% to 33% between 1251-1500 g and 500-750 g, respectively (P less than 0.001). Fluid and colloid administration were similar in sPDA and control infants. sPDA was associated with the occurrence of chronic lung disease (18% vs 7%, P = 0.005) and intracranial hemorrhage (53% vs 21%, P less than 0.001). Using stepwise logistic regression analysis we were unable to create a model that accurately predicted sPDA. Medical management and indomethacin were unsuccessful in 66% and 25%, respectively, of infants so treated; 43% required surgical ligation. Although survival of VLBW infants has increased, our incidence of sPDA remains low, with greater than 80% of infants demonstrating spontaneous closure when fluid and colloid administration are judiciously used.

Analysis of Variance↗

PubMed1991

Identification of conserved residues in the human immunodeficiency virus type 1 principal neutralizing determinant that are involved in fusion.

The principal neutralizing determinant of the human immunodeficiency virus type 1 (HIV-1) is located within the V3 loop of the surface glycoprotein gp120. Recently a mutational approach was used to demonstrate that the tip of the V3 loop is involved in cell fusion mediated by the HIV-1 envelope glycoproteins. Here these results are extended by introducing seven additional single amino acid mutations in the V3 loop. Mutations at highly conserved amino acids in the left stem, tip, and right stem of the V3 loop blocked or greatly reduced cell fusion without affecting envelope glycoprotein processing, transport, or binding to the CD4 receptor molecule. This study further characterizes the involvement of the V3 loop in cell fusion mediated by the HIV-1 envelope glycoproteins and identifies residues involved in the fusion reaction.

Amino Acid Sequence↗

PubMed1991

Identification of the principal neutralizing determinant of human immunodeficiency virus type 1 as a fusion domain.

The V3 loop, located near the middle of the surface envelope glycoprotein gp120, is the major neutralizing domain of human immunodeficiency virus type 1 (HIV-1). Although the majority of the V3 loop is highly variable between different strains of HIV-1, a Gly-Pro-Gly-Arg motif at the tip of the loop is highly conserved. To determine whether this region plays a role in fusion mediated by the HIV-1 envelope glycoproteins, we introduced seven single-amino-acid changes in the V3 loop. The mutant envelope glycoproteins were expressed from an HIV-1 envelope expression vector and analyzed for their ability to induce cell fusion in the absence of virus replication. Our results indicated that single-amino-acid changes in the V3 loop were capable of completely abolishing or greatly reducing the ability of the HIV-1 envelope glycoproteins to induce cell fusion, thereby identifying the V3 loop as a fusion domain of HIV-1. Mutations in the highly conserved tip of the loop or in a nonconserved region flanking the highly conserved tip had no effect on envelope glycoprotein synthesis, processing, transport, or binding to the CD4 receptor molecule. Mutation of the putative disulfide bridge-forming Cys at residue 336 blocked gp160 cleavage and CD4 binding.

Amino Acid Sequence↗

PubMed1991

Verapamil improves the outcome after cadaver renal transplantation.

Because of their favorable effects on renal hemodynamics, calcium antagonists may have a major role in the prevention and management of certain types of acute renal dysfunction. In fact, verapamil (VP) was shown to prevent cyclosporin A (CsA)-induced decreases in RBF in mice and in cadaver renal transplant (CRT) recipients. The study presented here of 59 cadaver renal transplant patients evaluates the outcome from perioperative treatment with VP (N = 30) administered intraoperatively into the renal artery (10 mg) followed by oral administration of 120 mg every 8 to 12 h for 14 days versus no drug (N = 29). Early immunosuppression included azathioprine, corticosteroids, and antilymphocyte globulin with subsequent overlapping with CsA on days 5 and 6. Actuarial graft survival at 1 yr was different when the two groups were compared (P less than 0.05). Estimated graft survival at 1 yr for VP patients was 93.3 compared with 72.4% in control patients. The improved graft survival was most striking in repeat transplants with 90% graft survival at 1 yr for VP recipients versus 37.5% for controls. Compared with controls, VP recipients had significantly improved renal parenchymal diastolic blood flow velocities on the first day after surgery (7.8 versus 5.8 cm/s). By day 7, GFR were greater with VP (44 +/- 29 mL/min) versus controls (28 +/- 22 mL/min). Of VP patients, 67% (18 of 24) had GFR greater than 30 mL/min versus 33% (9 of 26) for control patients. Similarly, on the seventh day, 77% (21 of 30) of VP patients had serum creatinines less than 2.0 mg% versus 34% (10 of 29) for controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Pentafraction-Du Pont versus albumin for resuscitation of a lethal intestinal ischemic shock in rats.

This study compares the effect of pentafraction-Du Pont 6% (PF), albumin 5% (ALB), and Ringer's lactate (RL) on plasma volume (PV) expansion and survival in a lethal intestinal ischemic shock model. Shock was induced by exteriorizing the small intestines and occluding the mesenteric vessels for 75 min. Changes in PV were estimated using hematocrit (Hct). The solutions were administered continuously for 6 hr in volumes to maintain a stable Hct, or 15 ml/100 g body weight (bwt) for PF and ALB and 44 ml/100 g bwt for RL. Hct and bwt were measured hourly during the infusion and at 24 h. Untreated animals in shock developed hemoconcentration (Hct 62%) corresponding to a PV of 41% of baseline preshock level, with 9% (3/35) of the animals surviving 72 hr. RL expanded PV to 87% of preshock level, with a 57% (20/35) 72 hr survival rate and 46% (16/35) surviving greater than 7 days. Only 34% as much ALB was needed to induce a greater PV expansion of 101% with a 72 hr survival rate of 51% (18/35) and 46% (16/35) surviving greater than 7 days. When PF was used, PV expanded to 109% of preshock level with survival rates improving to 80% (28/35) at 72 hr and 71% (25/35) greater than 7 days compared to RL and ALB (P less than 0.05). There were no significant differences in survival rates between RL and ALB treated animals. We conclude that PF improves survival following intestinal ischemic shock compared to ALB and RL. PF is a safe and effective alternative to albumin for resuscitation in this shock model.

Albumins↗

PubMed1991