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Biomedical subjects

R Hoppe

Publications and source records attributed to R Hoppe.

At least 19 recordsLinked to original sources

Observations on the effect of chimeric anti-CD4 monoclonal antibody in patients with mycosis fungoides.

Chimeric (murine/human) anti-CD4 monoclonal antibody was infused into seven patients with mycosis fungoides. Successive patients received doses of 10, 20, 40, and 80 mg of antibody twice a week for 3 consecutive weeks. All patients had some clinical improvement, but responses were of relatively short duration. Serum levels of chimeric antibody varied as a function of dose. At the 80-mg dose level, antibody was readily observed in biopsied skin lesions. Although there was coating by antibody of most CD4 positive cells in the blood, there was no significant depletion of CD4 positive cells. Low-level antibody responses against the mouse Ig variable region and human Ig allotypic constant region determinants were observed in several patients, but none were of clinical significance. All but two patients made primary antibody and T-cell proliferative responses to a simultaneously administered foreign protein test antigen. However, there was marked suppression of the mixed lymphocyte reaction. We conclude that at the dose levels studied, a chimeric anti-CD4 monoclonal antibody (1) had some clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) had immediate immunosuppressive effects; and (5) did not induce tolerance to a co-injected antigen.

Adult

The effect of controlled reperfusion in porcine hearts submitted to three hours of cold global ischemia.

At present, many investigations of myocardial function following ischemic insults concentrate on the modalities of reperfusion rather than on the mode of preservation. In this study, we tried to define the effect of reperfusion using warm blood cardioplegia (WBC) after medium-term (3 h) cold global ischemia, as required in cardiac transplantation. Twenty-one porcine hearts were harvested after preservation with cold cardioplegia (St. Thomas Hospital solution) and topical cooling. Normothermic reperfusion with blood was initiated after 3 h of ischemia utilizing a special extracorporeal pump circuit. Twelve hearts served as controls (group A), while substrate-enriched WBC was applied during the initial 20 min of reperfusion in nine hearts (group B). Hearts in both groups were then studied for myocardial function and metabolism under both working and nonworking conditions for a maximum of 180 min. In the nonworking mode, left ventricular dp/dt was significantly higher in group B than in group A at 15 min (2201 +/- 785 mm Hg/sec vs 1515 +/- 732 mm Hg/sec) and at 180 min (1730 +/- 471 mm Hg/sec vs 836 +/- 147 mm Hg/sec; P less than 0.05). After 3 h, lactate production was significantly higher in group A (371 +/- 45 mg/dl) than in group B (108 +/- 44 mg/dl; P less than 0.05). Creatine kinase release into the coronary sinus was also significantly elevated in group A at 15 min (2807 +/- 1478 IU/l vs 1148 +/- 1272 IU/l; P less than 0.05). Similarly, the hemodynamic data obtained under working conditions in group B were superior to those in group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Outcome of the acute glomerular injury in proliferative lupus nephritis.

Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.

Acute Disease

Characterization of splenic structure in Hodgkin disease by using narrow-band filtration of backscattered ultrasound.

A preliminary study was performed to evaluate the effectiveness of narrow-band filtration of backscattered ultrasound for the detection of splenic involvement in patients with Hodgkin disease. Regions of interest were identified in the spleens of 14 normal volunteers and eight Hodgkin disease patients before staging laparotomy. An analysis of the narrow-band-filtered waveforms showed that the mean amplitudes of the filtered ultrasonic signals received correlated with the presence of extensive splenic involvement with Hodgkin disease (defined as more than four grossly visible nodules on cut section) (p = .0004). Conversely, mean amplitudes of unfiltered ultrasonic backscatter, employed in conventional sonographic imaging, did not correlate with splenic involvement (p = .5). Phantom studies were performed to develop a tissue model for the observed phenomena; images of the phantoms and of the involved and uninvolved spleens were made by using techniques involving narrow-band filtration of backscattered ultrasound. Our results indicate that narrow-band-filtered sonography holds promise for detecting lymphomatous involvement of the spleen, although larger studies, with equipment allowing real-time implementation of narrow-band filtering, are needed.

Acoustics

Suppression of anti-mouse immunoglobulin antibodies in subhuman primates receiving murine monoclonal antibodies against T cell antigens.

Murine monoclonal antibodies stimulate the production of human anti-mouse immunoglobulin antibodies (AMIA) when administered to patients. This limits their long-term usefulness as therapeutic and diagnostic agents. We report the use of three maneuvers to suppress AMIA against T cell-specific monoclonal antibodies in cynomolgus monkeys. Twelve monkeys received daily i.v. infusions of 1 mg each of anti-Leu-2a, -3a, and -5 on days 1 through 10. One group (control) received no suppressive regimen. The second group received cyclosporine, 12.5 mg/kg daily on days -7 to +14. The third group (PI) were passively immunized with 0.4 ml of hyperimmune monkey AMIA serum on days -7, -1, 2, 4, 6, and 8. The fourth group (TLI) received 1700 rad fractionated total lymphoid irradiation ending on day -1. The animals treated with TLI were markedly delayed in the onset of AMIA, which was suppressed to less than 1% of the control group. The AMIA specific for the constant region of animals receiving PI was also suppressed to one-third of control. The majority of the AMIA in all the animals was anti-idiotypic and wholly anti-idiotypic in the TLI animals.

Animals

The smoking problem.

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Developing Countries

A profile of the self-poisoner in Michigan.

We reviewed the charts of all patients (160) ages 15 and older discharged in 1981 from the four hospitals in Lansing, Michigan with a diagnosis of overdose. Females predominated (65 per cent) and the median age was 27 years. The most common reason for intentional self-poisoning was "significant-other" conflict (54.5 per cent), followed by family conflict and financial problems. Benzodiazepines were most commonly used followed by acetylsalicylic acid and ethanol.

Adolescent

Cardiac allograft survival in rhesus primates treated with combined total lymphoid irradiation and rabbit antithymocyte globulin.

Eighteen abdominal heterotopic cardiac allografts were performed in outbred rhesus primates. For immunosuppression seven animals received six 100-rad/day total lymphoid irradiation (TLI) doses the week preceding transplant and three 3-mg/kg i.m. rabbit antithymocyte globulin (RATG) doses on postoperative days -1, 0, and +1; five animals were given this RATG dose but no irradiation; three were given TLI alone; and three were given no immunosuppressive therapy. Circulating T lymphocyte counts were monitored in all animals (rosettes). Graft survival in the combined TLI-RATG therapy group (169 +/- 15 days) was significantly greater than in untreated (11 +/- 1 days), RATG alone (22 +/- 12 days), or TLI alone (38 +/- 6 days) treated animals (P less than 0.001, 0.0001, and 0.001, respectively). The animals receiving combined TLI-RATG therapy also achieved significantly greater and more prolonged T lymphopenia than that obtained in the other three groups. Six of seven cardiac allografts placed in animals receiving TLI-RATG therapy were removed electively before cessation of electrical activity; however, in four of these rejection pathology was noted. Thus, it seems that combined TLI-RATG therapy may be of benefit in the management of transplant recipients, but its use will probably not abolish these patients' requirements for immunosuppressive maintenance measures.

Animals