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Biomedical subjects

E Herbst

Publications and source records attributed to E Herbst.

18 recordsLinked to original sources
PubMed1995

[Collagenous sprue].

HISTORY AND FINDINGS: A 45-year-old man with type I diabetes mellitus was admitted to hospital because of colicky abdominal pain and 5-6 watery stools daily. Upper gastrointestinal endoscopy showed nearly total atrophy of the villi in the duodenum and jejunum suggesting coeliac disease. However, gluten-free diet for 2 weeks brought no improvement. Another examination of the biopsy 6 weeks after the first endoscopy revealed extensive collagen deposition in the lamina propria of the small intestine, giving the diagnosis of collagenous sprue. TREATMENT AND COURSE: Parenteral nutrition, lactulose, cisapride, cholestyramine, doxycycline, paromomycin, vancomycin and octreotide failed to affect the loss of fluid from the gut which 12 weeks after admission had increased to 221 daily. However, it was stopped after prednisolone was administered (100mg daily). 7 months after starting the steroid treatment the collagen layer had disappeared and the villous atrophy had partially regressed. Over the next 6 months the prednisolone dosage was decreased to 10 mg daily. Shortly thereafter a perimembranous glomerulonephritis occurred, with proteinuria (up to 60 g/d) and oedema. It regressed to 6 g/d when the steroid dose was increased and cyclosporin, 0.5 g/d, had been added. On maintenance dosage of cyclosporin the histological and clinical remission of the collagenous sprue has now lasted for over 2 years. CONCLUSIONS: This case suggests that steroid administration is an effective treatment of collagenous sprue. The presence of diabetes and other immune-related diseases in this case also suggests that an immunological mechanism may play a causative role in collagenous sprue.

Anti-Inflammatory Agents↗
PubMed1995

Cancer vaccines: the interleukin 2 dosage effect.

Cancer vaccines genetically engineered to produce interleukin 2 have been investigated intensively in a series of animal models and are at the point of entering into clinical trials. In this study we demonstrate a strong correlation between the rate of interleukin 2 production and the protection efficiency of murine S91 melanoma cell (clone M-3) vaccines. Best immunization is achieved with vaccines producing medium interleukin 2 levels of 1000-3000 units per 10(5) cells per day. Reduced interleukin 2 production evokes a corresponding decline in the number of successfully treated animals. Unexpectedly, when interleukin 2 expression is raised to high levels of 5000-7500 units per 10(5) cells per day, protection is completely absent because of impaired generation of tumor-specific cytotoxic T lymphocytes. In comparison, granulocyte-macrophage colony-stimulating factor as immunomodulator induces substantial immunization even at a moderate level of secretion and protects all animals at the maximal obtainable level of secretion. Our findings demonstrate the importance of the interleukin 2 level produced by genetically modified tumor cells and may have substantial impact for the clinical application of cancer vaccines.

Animals↗
PubMed1995

Tumor vaccines: effects and fate of IL-2 transfected murine melanoma cells in vivo.

We have previously demonstrated the general usefulness of the adenovirus-enhanced transferrinfection (AVET) in the generation of IL-2 producing tumor vaccines. By optimizing different parameters of the transfection protocol we were able to transform the poorly immunogenic M-3 mouse melanoma cell line into a potent immunogen. A long-lasting immunity was demonstrated after administration of the IL-2 releasing vaccine, since immunized animals successfully rejected native M-3 melanoma cells even after a period of more than 6 months. We also demonstrated that in vivo administration of such a vaccine is safe since transmission of the transfected IL-2 gene in host organs was not detected. IL-2 production ceased 2 days after injection because the engineered cells were destroyed. However, RT-PCR analysis of the site of vaccine injection suggests that IL-2 exerts its effects not only directly but also by inducing a set of other immunomodulator cytokines in situ that are probably indispensable in inducing a host response. We conclude that AVET of IL-2 into tumor cells is a safe and efficient method for the generation of tumor vaccines.

Adenoviridae↗
PubMed1995

Tuberous sclerosis complex with end-stage renal failure.

Renal angiomyolipoma is common in the tuberous sclerosis complex (TSC), the classic features of which are facial angiofibroma, seizures, and mental retardation. We report a family with three affected members demonstrating the wide spectrum of TSC-associated lesions ranging from asymptomatic findings to life-threatening complications. The predominant symptoms of the index patient were hypertension and mild renal insufficiency at age 48, resulting in end-stage renal failure at age 63 due to giant bilateral angiomyolipoma of the kidneys. The two TSC-affected siblings had died years previously, one from pulmonary lymphangioleiomyomatosis and the other during an epileptic state; the latter had situs inversus totalis as another remarkable finding. The diagnosis of TSC may be overlooked if CNS symptoms are absent and if cutaneous lesions are masked by cosmetic procedures, as occurred in the index case. Chronic renal failure due to angiomyolipoma is not widely known to clinical nephrologists, but develops in approximately 15% of TSC patients. Displacement of functional renal parenchyma by abnormal tissue appears to be the major pathogenetic mechanism leading to end-stage renal failure. Angiomyolipomas can be diagnosed from this characteristic sonographic pattern and the demonstration of fatty tissue in CT or MRI. Multiple renal cysts are also common in TSC. Therefore TSC should be considered in the differential diagnosis of polycystic kidney disease.

Angiomyolipoma↗
PubMed1989

Stimulation of rat sciatic nerve regeneration with pulsed electromagnetic fields.

The effects of pulsed electromagnetic fields (PEMF) on rat sciatic nerve regeneration after a crush lesion were determined. The rats were placed between a pair of Helmholtz coils and exposed to PEMF of frequency 2 Hz and magnetic flux density of 0.3 mT. A 4 h/day treatment for 3-6 days increased the rate of nerve regeneration by 22%. This stimulatory effect was independent of the orientation of the coils. Exposure times of 1 h/day-10 h/day were equally effective in stimulating nerve regeneration. Rats exposed to PEMF for 4 h/day for 7 days before crush, followed by 3 days after crush without PEMF, also showed significantly increased regeneration. This pre-exposure 'conditioning' effect suggests that PEMF influences regeneration indirectly.

Animals↗
PubMed1986

The bone growth chamber for quantification of electrically induced osteogenesis.

A dividable titanium implant was inserted in the tibial metaphysis of rabbits, which permitted a numerical evaluation of ingrowing bone. The implant on the test side was used as cathode and was connected to a subcutaneously located stimulator delivering constant current of either 5 microA, 20 microA, or 50 microA. A corresponding control implant was inserted in the other tibia of the same animal and treated likewise, but was not connected to the stimulator. Distally to each implant, a platinum-iridium screw was inserted into the cortex and connected on the test side to the stimulator to serve as the anode. The results showed a 2.4-fold increase in bone formation with 5 microA. In the 20-microA group, there was 2.6-fold more bone in the test chambers. Direct current (DC) stimulation with 50 microA caused a clear decrease of bone volume, with an average of 48% less bone in the test implants. The results indicate that 5 and 20 microA direct current enhance bone ingrowth into a titanium implant that is used as a cathode. The osteogenesis seemed to be more pronounced in the case where the chamber was used as a cathode compared to earlier experiments in which the cathode was placed at a distance of 5 mm from the implant.

Animals↗
PubMed1985

Effects of direct currents on bone growth into delrin implants.

The delrin Bone Growth Chamber (BGC) which is a dividable implant, was inserted in its assembled form in the tibial metaphysis of the rabbit. The BGC allows a numerical estimation of the bone growth into the implant, based on microradiography and microdensitometry that permits evaluation of direct current (DC) effects on bone regeneration. A test chamber was inserted in one tibia and was stimulated with either 5, 20 or 50 microA for three weeks, while on the contralateral side of the same animal, a control implant was inserted under identical conditions as the test, but was not stimulated. The results showed a significant increase of bone growth with 20 and 50 microA and a tendency towards more bone formation with 5 microA.

Animals↗
PubMed1984

Direct current influence on bone formation in titanium implants.

A dividable, titanium implant was inserted bilaterally in assembled form in the tibial metaphyses of adult rabbits. A titanium cathode was placed 5 mm proximal and a platinum-iridium anode 5 mm distally. The chamber on one side served as a non-stimulated control: on the other side the electrodes were connected to a constant current generator. Ten animals were treated with 5 microA, ten with 20 microA and ten with 50 microA. After three weeks the implants were removed, taken apart and the bone which had grown into two central canals of the chamber was collected for macroradiographic and computer-based numerical analysis. DC-stimulation with 50 microA did not result in any measurable increase of bone formation in the test implants compared to the controls. After stimulation with 5 or 20 microA, on the other hand, there was a statistically significant increase of osteogenesis, in spite of the fact that the electrodes were situated at some distance from the implant.

Animals↗
PubMed1977

Cryopreservation of blood mononuclear leukocytes and stem cells suspended in a large fluid volume. A preclinical model for a blood stem cell bank.

It was the purpose of this study to establish and evaluate a freezing-and-thawing method for preservation of hemopoietic stem cells from the peripheral blood. Blood leukocytes collected by means of an IBM Blood-Cell-Separator were frozen in plastic bags using 10% DMSO and controlled cooling rates. Thawing was performed rapidly, and DMSO was diluted and removed prior to the in-vitro and in-vivo assays. The mean recovery of mononuclear cells collected from 82 leukaphereses was 86%. To assess the recovery of cryopreserved hemopoietic stem cells, the soft agar culture method adapted for the dog was used. There was no significant difference in the CFUc recovery per 1 X 10(6) mononuclear cells or in per leukapheresis after different cryopreservation times (1--6 and 7--27 months). To evaluate the hemopoietic repopulation capability of cryopreserved blood stem cells, leukapheresis-derived leukocytes were transfused into 1200 R whole body x-irradiated dogs. The hemopoietic repopulation pattern at day 10 after transfusion of comparable numbers of fresh or frozen leukocytes was not significantly different, as measured in bone marrow smears and sections and by granulocyte concentration in the peripheral blood.

Animals↗
PubMed1976

Regeneration of blood-forming organs after autologous leukocyte transfusion in lethally irradiated dogs. II. Distribution and cellularity of the marrow in irradiated and transfused animals.

Dogs were given transfusions of cryopreserved autologous mononuclear blood leukocytes after 1200 roentgens (R) (midline dose) whole-body x-irradiation. Bone marrow repopulation was studied by means of histomorphological methods at days 9 and 10 after transfusion of an average of 3 X 10(9), 7 X 10(9), 13 X 10(9), and 31 X 10(9) cells. The return of marrow cellularity to normal values was related to the number of cells transfused. With low cell doses (3 X 10(9) and 7 X 10(9)), the marrow regeneration at 10 days was focal. There were groups of cells (colonies) showing either erythropoiesis, myelopoiesis, or megakaryocytopoiesis in the osteal niches of the trabecular bones. Frequently such niches were seen showing complete cellular recovery next to niches with complete aplasia. With higher cell doses, all niches showed hemopoietic regeneration, and the cellularity approached normal values. No hemopoietic regeneration was observed in those skeletal parts that do not show hemopoiesis, even under normal circumstances.

Animals↗
PubMed1976

The repopulation of lymph nodes of dogs after 1200 R whole-body x-irradiation and intravenous administration of mononuclear blood leukocytes.

Fresh and cryopreserved autologous or allogeneic mononuclear blood cells (MBCs) intravenously injected in 1200 R total-body x-irradiated dogs repopulated lymph nodes within 10 days after tranfusion. Several parameters of the lymphopoietic regeneration were correlated with the number of cells transfused and with the number of colony-forming units contained in the cell suspension when they were cultured in agar (CFUc). Values within the normal or close to normal range were reached in the mesenteric nodes of most of the animals transfused with 10 X 10(9) MBC or more. These values were obtained when 5 X 10(5) CFUc or more were transfused. Axillary nodes showed lower values than mesenteric nodes. They were mostly under the normal range but well over those of the irradiated controls. Frozen and thawed MBCs seem to be as effective as fresh cells for lymphopoietic restoration. The mesenteric nodes of dogs transfused with allogeneic MBCs showed higher cellularity and larger cortical-paracortical areas than those of dogs tranfused with approximately the same number of autologous cells. The repopulation of lymph nodes parallels that of the marrow.

Animals↗
PubMedDate not supplied

Surgical and electrical methods in the treatment of congenital and posttraumatic pseudarthrosis of the tibia.

This is a report of two adult patients with posttraumatic and seven children with congenital pseudarthroses treated by surgical and electrical methods. Interest was focused primarily on congenital pseudarthroses because of the unquestionable severity of these cases and consequently a very high benefit/risk ratio. Three procedures were used: external (Hoffmann) fixation combined with monophasic or biphasic pulsed current stimulation; internal (transtarsal) fixation combined with pulsed electromagnetic field stimulation; and surgical treatment only, as above, without electrostimulation. Healing was achieved in both treated cases of posttraumatic pseudarthrosis and in nine of 14 instances in cases of congenital pseudarthrosis stimulated electrically, as well as in two instances with no electrostimulation. In seven instances, the bone remained healed for nine months or more, the longest period being almost 5.5 years. Both pulsed current and electromagnetic field stimulation seem to enhance the process of bone healing. However, comparison between the different stimulation methods cannot be made on the basis of the limited material presented here, and the need for more basic studies still exists. Concerning the surgical treatment, it seems that transtarsal fixation is a better choice for congenital pseudarthrosis than fixation with an AO-plate, Rush pin or Hoffmann apparatus.

Adolescent↗