Search PubMed⌕ Search

Biomedical subjects

C Berger

Publications and source records attributed to C Berger.

At least 217 records · Page 12Linked to original sources

Phototoxic liposomes coupled to an antibody that alone cannot modulate its cell-surface antigen kill selected target cells.

Molecules such as antibodies that bind to cell surfaces can be used to deliver cytotoxic drugs to selected cells. To be effective the drug must usually be taken into the cells by endocytosis. In this study a T-cell line (CCRF-CEM) was effectively killed by liposomes carrying a photosensitizer and bearing the antibody OKT4 (anti-CD4). The unconjugated antibody does not induce antigenic modulation in the target cells, an indication of the absence of endocytosis, and would therefore not normally have been selected as an agent for drug delivery. It cannot, however, be concluded with certainty that the conjugates act at the cell surface and several alternative explanations of their efficacy are offered.

Animals↗

Photopheresis for the treatment of cutaneous T cell lymphoma.

We investigated the use of extracorporeal chemotherapy (photopheresis) in eight patients with cutaneous T cell lymphoma. Initially described by Edelson et al. for the treatment of erythrodermic cutaneous T cell lymphoma, we have expanded the treatment to include patients with extensive patch/plaque disease as well as tumor-stage disease. Four of five patients with erythrodermic stage disease had either a complete or a partial clinical remission with photopheresis alone. One patient with extensive patch/plaque disease continued to have a partial clinical remission of 7 months' duration with photopheresis alone. Of the two patients with tumor-stage disease, one remained without evidence of clinical disease at 10 months with photopheresis alone, whereas the second patient had a partial clinical remission of 5 months with a combination of local radiation therapy followed by monthly photopheresis. The skin biopsy specimen obtained from the patient with tumor-stage disease in complete clinical remission did not show cutaneous T cell lymphoma. We conclude that photopheresis is an effective modality alone or in combination with adjunctive therapy for erythroderma, extensive patch/plaque disease, and some tumor-stage disease.

Adult↗

Treatment of thrombocytosis in myeloproliferative disorders with interferon alpha-2a.

In an open prospective pilot trial, we tested the effect of recombinant interferon alpha-2 a (rIFN alpha-2 a) on thrombocytosis in myeloproliferative disorders (MPD). Since October 1986, 13 patients with MPD (4 with chronic granulocytic leukemia, 4 with polycythemia vera, 3 with essential thrombocythemia and 2 with myeloid metaplasia) were treated with rIFN alpha-2 a. Platelet counts decreased in all treated patients within 2 to 10 weeks from a median value of 1,050 x 10(9)/l (range 610-1,940 x 10(9)/l) to 340 x 10(9)/l (range 230-495 x 10(9)/l). The response was dose-dependent. In 11 patients we observed a simultaneous reduction of the white blood cell count. Six patients still continue the IFN alpha-2 a therapy. In 7 treatment was discontinued, because of chronic side effects in 3, and because of noncompliance in one. In these patients, thrombocytosis recurred after discontinuation of the therapy. These results show that rIFN alpha-2 a is effective in controlling thrombocytosis in MPD. However, the long-term benefit of interferon in these disorders remains to be established.

Adult↗

Maternal hemoglobin F levels may have an adverse effect on neonatal birth weight in pregnancies with sickle cell disease.

A total of 26 patients with sickle cell disease were followed up through 32 pregnancies. There was no correlation between days in hospital or number of painful crises and either birth weight or birth weight percentile. The number of dense irreversibly sickled and least deformable cells was negatively correlated with birth weight percentile (r = -0.63, p less than 0.01). Patients' initial hemoglobin levels were positively correlated with birth weight percentile (r = 0.52, p less than 0.004). Hemoglobin F, on the other hand, was significantly inversely correlated with birth weight percentile. Nine pregnancies with small-for-gestational-age infants had an average hemoglobin level of 9.1% +/- 4.5%. In contrast, patients who were delivered of appropriate-for-gestational-age infants (23 pregnancies) had an average hemoglobin F level of 3.6% +/- 2.9% (p less than 0.01). We conclude that total hemoglobin levels and dense cells are correlated with birth weight percentile; moreover, the higher the maternal hemoglobin F levels the higher the risk of small-for-gestational-age infants. We speculate that although high hemoglobin levels may be beneficial to the fetus, high maternal hemoglobin F levels could increase the desaturation of non-F cells and induce placental obstruction.

Anemia, Sickle Cell↗

Inhibition of antiskin allograft immunity by infusions with syngeneic photoinactivated effector lymphocytes.

Induction of tolerance for skin allotransplantation requires selective suppression of the host response to foreign histocompatibility antigens. This report describes a new approach that employs pretreatment of effector cells with 8-methoxy-psoralen (8-MOP) and ultraviolet A light (UVA) to render the effector cells of graft rejection immunogenic for the syngeneic recipient. Reinfusion of photodamaged cells resulted in an immunosuppressive host response that permitted prolonged retention of histoincompatible skin grafts and specifically inhibited in vitro and in vivo responses that correlate with allograft rejection. Eight days after BALB/c mice received CBA/j skin grafts, their splenocytes served as a source of alloreactive effector cells. The splenocytes were treated with 100 ng/ml 8-MOP and 1 J/cm2 UVA before reinfusion into naive BALB/c recipients. Recipient mice were tested for tolerance to alloantigens in mixed leukocyte culture (MLC), cytotoxicity (CTL), delayed type hypersensitivity assays (DTH), and challenge with a fresh CBA/j graft. Splenocytes from BALB/c recipients of photoinactivated splenocytes containing the effector cells of CBA/j alloantigen rejection proliferated poorly in MLC and generated lower cytotoxic T cell responses to CBA/j alloantigens in comparison with sensitized and naive controls. Splenocytes from these hyporesponsive mice suppressed the MLC and CTL response to alloantigen from sensitized and naive BALB/c mice. In vivo the DTH response was specifically suppressed to the relevant alloantigen in comparison with controls. Moreover, BALB/c mice treated in this fashion retained a CBA/j skin graft for up to 42 d posttransplantation without visual evidence of rejection. These results indicate that the in vivo and in vitro response to alloantigen can be attenuated by pretreating the host with photoinactivated splenocytes containing the effector cells of alloantigen rejection.

Animals↗

Decreased formation of aqueous humour in insulin-dependent diabetic patients.

The rate of aqueous humour formation was measured by fluorophotometry in 34 insulin-dependent diabetic patients and 12 non-diabetic controls to determine whether or not aqueous flow in diabetics differed from that of normal controls, and whether or not aqueous flow among diabetics was correlated with the stage of retinopathy. Diabetic patients were divided into three groups based on the degree of retinopathy; group I without retinopathy, group II with minimal to moderate non-proliferative retinopathy, and group III with proliferative retinopathy. Aqueous flow (mean, SD) in diabetic patients was: 1.55 (0.32) microliter/min in group I, 1.51 (0.47) microliter/min in group II, and 1.26 (0.39) microliter/min in group III. No statistically significant difference was found among these three diabetic groups. Aqueous flow in the non-diabetic controls was 2.18 (0.40) microliter/min, and this was statistically significantly greater than in each of the diabetic groups. Intraocular pressure, age, duration of diabetes, haemoglobin A1C, and blood glucose levels had no significant effect on aqueous flow in diabetic patients.

Adult↗

[Serum immunoglobulin concentrations in patients following bone marrow transplantation and preventive administration of high-dose nonspecific or normal-dose CMV-specific immunoglobulin].

Ten consecutive bone marrow transplant recipients were assigned alternatively to receive either a high dose polyspecific intravenous immunglobulin (HDIVIG) 0.5 g/kg weekly X 14, or a conventional dose of a CMV specific intravenous immunglobulin (CMVIG) 0.1 g/kg every three weeks. Before and after each application we determined the levels of total IgG, IgG subclasses, IgG 1, IgG 2, IgG 3, IgG 4, total IgA and IgM and of specific IgG and IgM antibody concentrations against endotoxin, lipid A, streptococcus A, hemophilus, EBV and CMV. In the HDIVIG, total IgG rose from 11 (median, range 2-11) g/l to 25 (22-32) g/l by day 89, in the CMVIG group, IgG dropped from 11 (10-15) g/l to 9 (6-12) g/l. In the same period the mean levels of IgG subclasses expressed as % of normal plasma pool increased in the HDIVIG group in all subclasses, not in the CMVIG group. The differences were significant, however, only for IgG 1 and IgG 2. IgG-antibodies against CMV, EBV, endotoxin, streptococcus and hemophilus did increase significantly in the HDIVIG group, but not in the CMVIG group. No increase was seen in both groups in lipid A antibodies and in specific IgM antibodies. Each application of CMVIG induced a transient increase of anti-CMV antibodies. We conclude that HDIVIG induces reproducibly an increase of specific and non-specific IgG antibodies. No attempt was made to assess clinical outcome. However, these results provide a rational basis for further therapeutic studies.

Adult↗

[Effect of calcium antagonists and beta receptor blockers on coronary vessel diameter].

32 patients in an early state of coronary sclerosis were investigated in connection with diagnostic angiography. 8 patients received 2 mg gallopamil (G) and for every 12 patients 0.1 mg/kg propranolol (P), respectively, 0.12 mg/kg Atenolol (A). All medications were injected intravenously over 4 min. The angiograms were repeated in identical projections before (control) as well as 5, 10, 15, and 20 min after G and 2, 4, 6...up to 20 min after P and A. All angiograms were analyzed using a quantitative computerized contour detection system. 10 min after infusion of G 34 measured coronary segments showed a significant (p less than 0.05) medium dilation of 21 +/- 4.3% and after a further 10 min an insignificant increase in coronary diameter was observed up to 25 +/- 4%. After infusion of P and A a distinct vasoconstriction could be seen. Especially P showed a decrease in diameter of almost 25% in small coronary segments (less than 2.0 mm diameter). The dilatative effect of G i.v. seems to be important in the therapy of acute ischemic situations, for instance, for unstable angina, acute myocardial infarction, or during PTCA. The acute coronary vasoconstriction after infusion of P and A should be considered when used in acute ischemic events.

Angina Pectoris↗

[Ambulatory therapy with amphotericin B].

Therapy of systemic fungal infection with amphotericin B (AmB) must be continued for several months and is usually performed on an inpatient basis because of the risk of drug toxicity. Between 1983 and 1987 we treated 14 outpatients with a total of 164 AmB infusions. Side effects were generally mild and easy to control. Progressive impairment of renal function led to dose reduction and interruption of therapy in only one patient. Ambulatory therapy with AmB is feasible in an outpatient unit with adequate experience, and a significant reduction of treatment costs can result. Outpatient therapy is an acceptable alternative to inpatient treatment. Patients with malignant diseases under palliative therapy will profit most from the reduced duration of hospital stay.

Adolescent↗

[A Candida krusei epidemic in a hematology department].

Candida krusei is a rarely isolated opportunistic yeast which we observed in 12 immunocompromised patients over a four-month period. Epidemiologic investigations identified the source of the organism in a bottle containing contaminated lemon juice in the hospital kitchen. Since elimination of the source we found the yeast in only 3 additional cases (4% vs. 0.4% of all patients with positive yeast cultures) over 11 months. Upper respiratory tract was the most common site of colonization. 6 of 15 patients developed infections with C. krusei (4 pneumonia, 1 disseminated infection and 1 localized). 4 died from fungal infections. - The importance of infection control institutions for efficient epidemiologic investigation of nosocomial infections is discussed.

Adult↗

Autoreactive B-cell repertoire in mice with chronic graft versus host disease.

A quantitative analysis of the frequencies of autoantibody producing B-cells has been undertaken by producing and analyzing random hybridoma collections generated in fusions with activated B-cells. Activated B-cells were derived from mice injected with LPS and SRBC and normal mice. They were compared to those derived from mice undergoing chronic GVHD. The frequencies of successful fusion events correlate well with the number of activated B-cells used in the fusions, so that it is reasonable to conclude that the hybridoma collections reflect the activated B-cell repertoires in the different animals. The frequencies of hybridomas producing autoantibodies as well as their specificities for self-antigens, were not significantly different between the different collections of hybridomas. Moreover, no difference in VH gene family expression was found in the different collections of autoantibody producing hybridomas. So, the activated autoreactive B-cell repertoires in GVHF1 mice and in normal mice is similar. In contrast to the normal activated autoreactive B-cell repertoires, which make predominantly IgM antibodies, the GVH-activated autoreactive B-cells make predominantly antibodies of the IgG class. Therefore, we conclude that T-cell mediated graft versus host activation does not generally lead to selective expansion of autoreactive B-cells, but appears to play a crucial role in the switch from IgM to IgG production.

Animals↗