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Biomedical subjects

E Brewer

Publications and source records attributed to E Brewer.

At least 19 recordsLinked to original sources
PubMed2003

Glomerular filtration rate in children with solid tumors: normative values and a new method for estimation.

Many chemotherapy regimens used in children are nephrotoxic. Accurate dosing of these medications requires that some estimation of glomerular filtration rate (GFR) be performed prior to initiating chemotherapy. However, few studies evaluating normal GFR in children exist. The authors report normal values for GFR for children with nonhematogenous malignancies using a highly accurate method of directly measuring GFR and an equation for estimating absolute GFR in these children. Children with nonhematogenous malignancies with no evidence of renal involvement or prior use of nephrotoxic agents had their GFR measured using an iothalamate infusion methodology. A total of 111 children (males and females) with a mean age = 7.95 years (range 2.8 months-19.5 years) were included in the study. GFR adjusted for body surface area (mL/min/1.73 m(2)) increases in the first 2 years of life and then plateaus at a level comparable to adult values. GFR adjusted for body surface area for males >2 years = 131.3 +/- 22.5, females = 126.8 +/- 24.4 mL/min/1.73 m(2) (p value not significant). Absolute GFR in mL/min can be easily estimated by a simple formula (r(2) =.97) based on the child's weight and serum creatinine: GFR (mL/min) = k sqrt[ ( (agemos+ 6)* wt) / Cr serum ] where agemos is age in months, wt is weight in kg, and k = 1.05 for males and 0.95 for females. The accurate measurement of GFR remains vitally important in the safe and effective treatment of pediatric solid tumors. This study provides a set of normal GFR values for these children and an equation for easy estimate of absolute GFR.

Adolescent↗
PubMed2001

Chronic endothelin-1 blockade reduces sympathetic nerve activity in rabbits with heart failure.

Endothelin-1 (ET-1) is elevated in chronic heart failure (CHF). In this study, we determined the effects of chronic ET-1 blockade on renal sympathetic nerve activity (RSNA) in conscious rabbits with pacing-induced CHF. Rabbits were chronically paced at 320--340 beats/min for 3--4 wk until clinical and hemodynamic signs of CHF were present. Resting RSNA and arterial baroreflex control of RSNA were determined. Responses were determined before and after the ET-1 antagonist L-754,142 (a combined ET(A) and ET(B) receptor antagonist, n = 5) was administered by osmotic minipump infusion (0.5 mg. kg(-1) x h(-1) for 48 h). In addition, five rabbits with CHF were treated with the specific ET(A) receptor antagonist BQ-123. Baseline RSNA (expressed as a percentage of the maximum nerve activity during sodium nitroprusside infusion) was significantly higher (58.3 +/- 4.9 vs. 27.0 +/- 1.0, P < 0.001), whereas baroreflex sensitivity was significantly lower in rabbits with CHF compared with control (3.09 +/- 0.19 vs. 6.04 +/- 0.73, P < 0.001). L-754,142 caused a time-dependent reduction in arterial pressure and RSNA in rabbits with CHF. In addition, BQ-123 caused a reduction in resting RSNA. For both compounds, RSNA returned to near control levels 24 h after removal of the minipump. These data suggest that ET-1 contributes to sympathoexcitation in the CHF state. Enhancement of arterial baroreflex sensitivity may further contribute to sympathoinhibition after ET-1 blockade in heart failure.

Acetamides↗
PubMed1995

Particle size determination by automated microscopical imaging analysis with comparison to laser diffraction.

A rapid and precise microscopical analysis technique for the determination of particle size distribution has been developed. Particle size distribution was determined with a Carl Zeiss Axioplan microscope equipped with a computer-controlled image analysis system. Area and volume measurements were performed on a number of particles and plotted against Feret's diameter to yield a distribution histogram. This technique was then applied to several compounds of pharmaceutical interest, and the resulting histograms were compared with histograms determined with a laser diffraction instrument. The reproducibility of the microscopical determination was good and the agreement between the two determinations was dependent on the crystalline shape.

Crystallization↗
PubMed1991

Production of interleukin 2 and interleukin 4 by immune CD4-CD8+ and their role in the generation of antigen-specific cytotoxic T cells.

In this report we investigated the production and role of interleukin (IL)2 and IL4 in the generation of antigen-specific cytotoxic T cells (CTL). We used as our model the ultraviolet-light-induced epithelial tumor 1591, a highly immunogenic regressor tumor which evokes a strong cell-mediated immune response leading to rejection. We show that IL2 and IL4 are differentially required for the development of optimal cytolytic activity to the 1591 tumor in primary and secondary in vitro splenic cultures. First, anti-IL2 receptor monoclonal antibody (mAb) significantly decreased specific cytotoxicity in both primary and secondary splenic mixed lymphocyte-tumor cell culture (MLTC) cultures, but anti-IL4 mAb inhibited the cytotoxic responses only secondary and not primary cultures. Second, when supernatants from MLTC were tested for lymphokine activity, primary cultures produced only IL2 while secondary cultures produced both IL2 and IL4. Splenic cells were then depleted of CD4+ cells by negative selection, or enriched for CD8+ cells by positive selection, and tested for lymphokine production and requirements. CD8+ cells could not generate significant CTL activity in primary cultures, but could in secondary MLTC. The addition of mAb to either IL2 or IL4 significantly inhibited the generation of CTL by CD8+ cells in these secondary MLTC.CD8+ cells were also found to produce both IL2 and IL4 in secondary MLTC by functional and Northern blot analysis. The production of IL2 and IL4 by CD8+ cells occurs during different phases of culture, with IL2 being produced early (days 1 and 2) and IL4 late (days 3-5). In addition, the requirement of CD8+ cells for both IL2 and IL4 is unique for that lymphokine. These results suggest that both IL2 and IL4 are both produced and required by CD8+ cells during secondary MLTC, and suggest an additional cellular source of IL4 production besides CD4+ T cells during antigen-specific CTL responses.

Animals↗
PubMed1990

Generation of a T-cell hybridoma producing a contrasuppressor factor for contact sensitivity.

C3H/HeN mice were immunized to induce contrasuppressor T-cell (Tcs) activity, splenic T cells from these mice were fused with the BW5147 thymoma, and the resulting hybridomas were tested for their ability to produce a contrasuppressor T-cell factor (TcsF). Nine TcsF-producing hybridomas were preliminarily identified by their ability to inhibit the effect of antigen-specific suppressor T-cell factor (TsF) on the adoptive transfer of contact sensitivity. One of these hybrids, AF5.C6, was cloned, the production of a contrasuppressor factor confirmed, and the high-titred TcsF produced by this cloned hybrid characterized. Hybridoma-derived TcsF is antigen-specific and specifically binds its antigen, but does not bear immunoglobulin (Ig) determinants. Thus, hybridoma-derived TcsF is serologically and functionally identical to an antigen-specific contrasuppressor factor for contact sensitivity, whose production from splenocyte cell cultures has previously been described. The generation of a hybridoma secreting a contrasuppressor factor identical to that produced by spleen cells significantly strengthens the hypothesis that the phenomenon of T-cell contrasuppression is mediated by a specific subset of cells whose activity is contrasuppressive. The further advantages of employing T-cell hybridomas for functional, biochemical and molecular genetic analyses of contrasuppression are also discussed.

Animals↗
PubMed1990

A dextromoramide-related fatality.

A 38-year-old man was found in his car suffering from a heart attack. Serum analysis by capillary gas chromatography and mass spectrometry confirmed the presence of dextromoramide (Palfium), methadone, and lidocaine. The serum concentrations at admission to the hospital were: 1.9 micrograms/mL of dextromoramide, 0.4 micrograms/mL of methadone, and 0.4 micrograms/mL of lidocaine. A serum alcohol analysis performed using headspace gas chromatography was negative.

Adult↗
PubMed1989

Stimulation of protein phosphorylations in frog rod outer segments by protein kinase activators. Suppression of light-induced changes in membrane current and cGMP by protein kinase C activators.

Addition of protein kinase C activators to electropermeabilized frog rod photoreceptors enhances the phosphorylation of proteins with molecular masses of 54, 24, 19, 17, 12, and 11 kDa. The latter two correspond to components I and II, which are also phosphorylated by cyclic nucleotide-dependent protein kinase. Stimulation of phosphorylation by the protein kinase C activator oleoylacetylglycerol (OAG) is half-maximal at 7.7 microM OAG and is reduced by the protein kinase C inhibitor H-7. In contrast with earlier observations, no effects of calcium, calmodulin, or insulin on protein phosphorylations are observed. We find evidence for only three protein kinases in rod outer segments: a protein kinase C-like activity, cAMP-dependent protein kinase, and rhodopsin kinase. With the exception of components I and II, the substrate proteins for each kinase are distinct. Treatment of intact rods with OAG decreases the amplitude of the photoresponse and dark levels of cGMP up to 40%, as well as depressing the light-stimulated decrease in cGMP levels. These effects are observed between 0.1 and 1 microM OAG. The data suggest that OAG-sensitive reactions may modulate pathways that support the light response.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

Low grade pelviureteric junction obstruction with normal diuretic renography.

We report five patients with normal diuretic renograms who underwent Whitaker pressure perfusion testing. They were found to have normal pressure at low flow rates (2-4 ml/min) and an abnormally elevated pressure at high flow rates (8-10 ml/min). Because of persistent symptoms, two patients underwent surgery, while the other three have been followed up. Our findings indicate that a negative diuretic renogram in a well hydrated patient with good renal function may not rule out low grade obstruction. Renal pelvic perfusion at low flow rates as well as high flow rates is recommended to determine better the function of the pelviureteric junction.

Adolescent↗
PubMed1986

Flurbiprofen in the treatment of juvenile rheumatoid arthritis.

Thirty-four patients with juvenile rheumatoid arthritis, who were treated with flurbiprofen at a maximum dose of 4 mg/kg/day, had statistically significant decreases from baseline in 6 arthritis indices after 12 weeks of treatment. Improvements were seen in the number of tender joints, the severity of swelling and tenderness, the time of walk 50 feet, the duration of morning stiffness and the circumference of the left knee. The most frequently observed side effect was fecal occult blood (25% of patients); however, there was no other evidence of gastrointestinal (GI) bleeding in these patients. One patient was prematurely discontinued from the study for severe headache and abdominal pain. Most side effects were mild and related to the GI tract.

Abdomen↗
PubMed1985

Use of cyclosporine in pediatric renal transplant recipients.

Cyclosporine and prednisone were used in combination to produce immunosuppression in 18 pediatric recipients of renal allografts. Ten children received cadaveric kidneys and eight received kidneys from living related donors. With a mean follow-up of 16.5 months (range 7 to 33 months), the patient survival rate is 100% (18 of 18) and the graft survival rate is 83% (15 of 18). Two grafts were lost for nonimmunologic reasons. Currently the group mean (+/- SE) serum creatinine concentration is 1.22 +/- 0.11 mg/dl and creatinine clearance is 69.3 +/- 4.79 ml/min/1.73 m2. Cyclosporine nephrotoxicity has not caused irreversible allograft injury nor led to graft loss in this population. The incidence of treated rejection episodes has been 39% (seven of 18). Only 39% (seven of 18) of children have required hospital readmissions since the initial transplant discharge. There have been no opportunistic infections. In the 15 children with functioning grafts, some linear growth has occurred in 10 of 11 prepubertal and two of four postpubertal patients. Cyclosporine and prednisone have constituted a safe, efficacious immunosuppressive regimen for pediatric renal allograft recipients. Longer follow-up will be necessary to confirm whether these advantages persist beyond 2 years.

Adolescent↗
PubMed1983

The influence on pretransplant blood transfusions from random donors on immune parameters affecting cadaveric allograft survival.

The number of pretransplant blood transfusions (BT) from random donors influences the recipient's immune response status and suppressor cell number and function, as well as allograft survival. The 54% one-year survival rate for 104 cadaveric renal allograft recipients treated with azathioprine and prednisone was divisible into two groups: 74.5% in 51 patients receiving greater than 5 BT and 34% for 53 patients with less than 5 BT (P less than 0.02). Transfusions enhanced the benefit of HLA A, B, and DR compatibility on graft survival: 33 recipients of well-matched grafts (less than 2 A, B, and 0-1 DR mismatches) had a one-year survival rate of 94% when pretreated with greater than 5 BT, compared with 38% when receiving less than 5 BT (P less than 0.05). The graft survival of 73% (36/49) displayed by patients determined preoperatively to be weak immune responders was significantly better than the 36% survival (20/55) demonstrated by strong immune responders (P less than 0.01). The transfusion history correlated with immune responder status: 76% (39/51) of patients receiving greater than 5 BT were weak immune responders, whereas 81% (43/53) of patients receiving less than 5 BT were strong immune responders (P less than 0.001). Ninety-two percent (12/13) of patients with greater than 5 BT, but only 58% (10/17) of patients with less than 5 BT, had a normal number of OKT8+ T suppressor cells. Only 1 X 10(5) mononuclear cells from patients with greater than 5 BT rather than 4 X 10(5) cells from patients with less than 5 BT caused 50% suppression of a third-party MLC. Thus, patients receiving greater than 5 BT are more likely to display weak immune responses, normal numbers of OKT8 cells, strong suppressor function in vitro, and prolonged allograft survival.

Antibodies, Monoclonal↗