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Biomedical subjects

M Höckel

Publications and source records attributed to M Höckel.

At least 73 records · Page 4Linked to original sources

[Perforation in Crohn disease as a complication in pregnancy].

The manifestation of Crohn's disease with perforation in pregnancy has been described in one case only. In our case, a 25-year-old woman in the 28th week of pregnancy was admitted to our hospital with signs of an acute abdomen. Due to deterioration of the maternal and foetal situation, the child was delivered by a Caesarean section. Subsequently, exploration of the abdomen showed an ileum perforation with diffuse fibrinous peritonitis. In this case, the definitive diagnosis could not be made prior to laparotomy. The aim of surgical therapy in such cases should be the limited resection with end to end anastomosis. In diffuse peritonitis, discontinuous resection and secondary reconstruction after three to six months is preferred.

Abdomen, Acute↗

A novel combined operative and radiotherapeutic treatment approach for recurrent gynecologic malignant lesions infiltrating the pelvic wall.

Patients who have recurrent gynecologic malignant conditions infiltrating the pelvic wall still have a poor prognosis, although based on the biologic factor of the tumor, 50 per cent might be salvaged if local control is achieved. For patients with unilateral disease, we have designed a combined operative and radiotherapeutic treatment (CORT) that involves subtotal resection of the tumor, intraoperative placement of guiding tubes for postoperative high dose rate brachytherapy of the residual tumor and tumor bed at the pelvic wall and pelvic wall plasty with autologous tissue flaps. We use either flaps of the greater omentum and inferiorly based rectus abdominis muscle flaps from the abdominal route or (de-epithelialized) gluteal thigh flaps from the vaginal and perineal route to cover the tumor bed and overlying tubes. Thus, a protective distance between the radiation source and radiointolerant pelvic organs is created and the risk of local infection and hypoxia is reduced. With this combination of surgical and radiation treatment, the therapeutic ratio between tumor control and tissue damage in the pelvic area is thought to be improved. Higher local doses can be applied compared with conventional methods in instances in which surgical treatment has been performed and reirradiation with tumoricidal doses may be possible after primary or adjuvant radiation therapy. The encouraging first experience with the CORT concept in nine patients with a short follow-up period is reported.

Adult↗

Angiotropin treatment prevents flap necrosis and enhances dermal regeneration in rabbits.

Angiotropin is a potent angiogenesis factor isolated from the serum-free media of cultured, lectin-activated peripheral monocytes. In vitro, the purified substance stimulates migration, phenotypic differentiation, and tube formation, but not proliferation of capillary endothelial cells. When injected intradermally, angiotropin induces, in dose-dependent fashion, angiogenesis associated with skin hyperplasia. We have developed a flap model with insufficient blood supply and a model for contraction-free defect healing in rabbit skin. We show that (1) local pretreatment with angiotropin can prevent flap necrosis and (2) dermal regeneration after wounding can be augmented by angiotropin. From these results, we conclude that angiotropin might be of use as an adjuvant to healing in surgery.

Angiogenesis Inducing Agents↗

[A new experimental method for the treatment of pelvic wall recurrencies of gynecological malignancies].

Pelvic side wall recurrences of gynecological malignancies subsequent to primary or adjuvant radiation therapy have a bad prognosis, although in almost half of the cases, distant metastases are not present at the time of diagnosis of the local tumor progression. A radical operative resection of the pelvic wall recurrence is rarely possible and a second conventional percutaneous or intracavitary irradiation with a tumoricidal dose is no longer feasible, because of the limited radiation tolerance of the surrounding pelvic tissue. The different forms of chemotherapy applied at present are not curative. Based on considerations of tumor and radiation biology, we propose a new experimental treatment mode after subtotal tumor resection. Intraoperatively, guiding tubes for afterloading HDR brachytherapy are fixed equidistantly on the tumor bed resp. residual tumor at the pelvic side wall. Coverage of this area by a rectus abdominis muscle flap or de-epithelialized myocutaneous flap improves fixation and creates a protective distance between radiosensitive pelvic structures and the radioactive source inserted postoperatively. In addition, improved vascularization by the flap might reduce the potential of hypoxia induced radioresistance of the residual tumor. Under these circumstances it appears possible, to deliver a second tumoricidal radiation dose of a small volume to a precisely defined area of the pelvic side wall.

Abdominal Muscles↗

Purified monocyte-derived angiogenic substance (angiotropin) induces controlled angiogenesis associated with regulated tissue proliferation in rabbit skin.

Angiotropin is a differentiation factor for microvascular endothelial cells isolated from serum-free cultures of lectin-activated, porcine monocytes. We used an ear lobe model in rabbits, single intradermal injection of angiotropin to induce phenotypical changes of the endothelial cells in capillaries and postcapillary venules, vascular engorgement, and subsequent angiogenesis in dose-dependent manner. The vascular changes are associated with epidermal and stromal cell proliferation. Angiogenesis and tissue proliferation occur in the absence of tissue necrosis and do not lead to scar formation. Angiotropin-induced angiogenesis is not inhibited by local dexamethasone although it involves a defined turnover of inflammatory cells. Proliferation is transient and regressive events follow. The overall tissue reaction resembles changes found in the undamaged skin margin of a primary healing wound during the inflammatory/proliferative phase. From these observations we conclude that angiotropin is an important secretory product of activated peripheral macrophages that triggers inflammatory and proliferative reactions in wound healing by activating microvascular endothelial cells.

Angiogenesis Inducing Agents↗

Purified monocyte-derived angiogenic substance (angiotropin) stimulates migration, phenotypic changes, and "tube formation" but not proliferation of capillary endothelial cells in vitro.

Activated monocytes (macrophages, histiocytes) induce the formation of new blood vessels by secretion product(s). From conditioned serum-free media of porcine peripheral monocytes treated with concanavalin A, a substance with very strong angiogenic activity in vivo, designated as angiotropin, has been isolated and purified to homogeneity. We investigated the biological action of the monocyte-derived angiogenic substance on cultured capillary and large vessel (aorta) endothelial cells and on 3T3 fibroblasts, mimicking steps of the angiogenic pathway in vitro. We found that angiotropin does not stimulate the proliferation of capillary endothelial and 3T3 cells; however, in concentrations less than 1 ng/ml, it enhances random migration of capillary endothelial cells but not of 3T3 cells. On confluent monolayers of capillary and aortic endothelial cells angiotropin leads to defined changes of cell morphology that are dose dependent and reversible. In the presence of angiotropin, capillary endothelial cells rapidly form tubelike structures on gelatinized plates. This organizational state is not reached with aortic endothelial cells. The results indicate that the biological action of monocytic angiotropin is different from that of the angiogenic growth factors that stimulate the proliferation of endothelial cells and nonlymphoid mesenchymal cells and keep endothelial cells in the contact-inhibited epitheloid cell phenotype. We propose that angiotropin is directly involved in monocyte-induced angiogenesis.

Animals↗

Prevention of peritoneal adhesions in the rat with sustained intraperitoneal dexamethasone delivered by a novel therapeutic system.

The rat caecal crush model for the production of intraperitoneal adhesions was optimized with respect to an objective adhesion grading system based on the determination of the incidence of adhesions and the caecal adherent surface area. Intraperitoneal saline solution given before closure of the peritoneum significantly reduced the severity but not the incidence of adhesions. The addition of dexamethasone crystal suspension led to somewhat lower incidence of adhesions but the mean adherent surface area values were not different from the saline regimen. However, sustained release of dexamethasone by use of intraperitoneal biodegradable poly(lactide-co-glycolide) microparticles as a novel therapeutic system further reduced both the incidence and the severity of adhesions. Despite of the differences in therapeutic effects glucocorticoid-associated local and systemic adverse effects were similar in both regimens. As effective adhesion prophylaxis with glucocorticoids appears to be a balance between benefit and adverse reactions, optimal drug delivery is mandatory. The novel biodegradable therapeutic system is superior to the intraperitoneal crystal suspension regimen in the rat and should be tested further in clinical trials.

Animals↗

Placental transfer of class G immunoglobulins treated with beta-propiolactone (beta-PL) for intravenous application--a case report.

Pregnant patients receive immunoglobulin preparations for the prevention of connatal viral infections of the newborn in the case of impending or manifest maternal infections. In the past, class G immunoglobulin preparations could only be given intramuscularly because of possible antigen independent complement activation by the Fc-part of the IgG molecule when administered intravenously. The I. M. application results in a delay in reaching maximum serum levels, and the levels are much lower compared to I. V. application. Today, I. V. tolerable IgG preparations exist because methods have been developed either to remove or to modify the IgG Fc-part. As the Fc-part is necessary for the placental transport of antibodies, the above mentioned manipulation can drastically impair the transport. In this study, an anti-HBs seronegative pregnant patient received an anti-HBs IgG preparation (greater than or equal to 500 IU anti-HBs) intravenously. These IgG molecules are rendered I. V. tolerable by modification of the Fc-part with beta-propiolactone (beta-PL). At delivery, the newborn's serum anti-HBs concentration was 13 mIU per ml, the mother's 35 mIU per ml. This result clearly demonstrates that IgG molecules which have been modified by treatment with beta-PL are transported from the circulation of the mother across the placenta to the fetus. The role of intravenously tolerable hyperimmunoglobulins with special respect to beta-PL treated preparations for the prevention of connatal infections is discussed.

Adult↗

Neomorphogenesis of blood vessels in rabbit skin induced by a highly purified monocyte-derived polypeptide (monocyto-angiotropin) and associated tissue reactions.

Chemotropic morphogenesis of new blood vessel patterns with active haemodynamics in the skin of rabbits was induced by intradermal injection of highly purified monocyto-angiotropin (MAT), one of the low-molecular-weight (4,500) polypeptide monokines exuded by activated mammalian (porcine) monocytes (macrophage type) on their culture in serum-free, fully synthetic media. Evidence is presented that neohypervascularization of the skin is associated with enhanced tissue function as represented by hair growth. Exclusively in the area of MAT injection, numerous capillary-like vessel formations arose from preexisting vessels, and the quiescent hair follicles (telogen) were activated to growing ones (anagen) within 1-2 weeks.

Animals↗

Metabolic changes in the rat liver during pregnancy. II. Tricarboxylic acid cycle.

During pregnancy the rat liver shows alterations in metabolism which apparently do not to occur in the non-pregnant animal. In our study, the following metabolite concentrations and enzyme activities in the liver of pregnant and non-pregnant rats were measured after fasting periods of 6 and 12 h: malate, fumarate, isocitrate, alpha-keto-glutarate, glutamate, malate-dehydrogenase, fumarate-hydratase, glutamate-dehydrogenase, isocitrate-dehydrogenase, aspartate-aminotransferase and after 12 h fast, the concentrations of acetyl coenzyme A and citrate. These results are discussed with regard to their possible importance for the maternal and fetal energy supply.

Animals↗

Determination of long-chain nonesterified fatty acids in sera of young women in different phases of the menstrual cycle. Application of a new gas chromatographic microliter method.

Nonesterified fatty acids (NEFA) from C12 to C24 have been determined in sera of 13 young women at menstruation, and in the follicular and luteal phase of the menstrual cycle applying a new gas chromatographic microliter method. Neither the total NEFA content nor the concentrations of individual fatty acids showed significant differences in the three phases of the menstrual cycle. With the exception of stearic acid we found almost constant relative concentration values for the individual fatty acids within the medium range of the long-chain NEFA spectrum. Intraindividual and interindividual dispersion was hardly greater than the variation caused by the method of determination itself, whereas the intra- and interindividual scattering of the rim fractions of the NEFA spectrum was much more distinct. The coefficients of variation for the as well as individual NEFA content related to all examined women at any phase of the menstrual cycle were lower than 40% with the exception of the rare erucic acid, behenic acid and lignoceric acid.

Chromatography, Gas↗

The influence of oral contraceptives on the composition of bile.

The increased risk of cholelithiasis during intake of oral contraceptives may be due to estrogen-induced saturation of the bile with cholesterol. In a randomized, prospective, crossed-over double-blind study 20 healthy women after roentgenological exclusion of gall-stones received either 1.0 mg of norethindrone acetate and 50 microgram ethinyl estradiol daily - as usual in oral contraception - for 21 days with 7 days of placebo treatment in each cycle or one fifth of this hormone dose in form of a continuous daily medication. After a 4 month's treatment the medication form was crossed-over. At the beginning of the study, before the cross-over and after the study bile was collected by duodenal intubation after a 12-h fast and the lithogenic index as a measure for cholesterol saturation of the bile was determined. No correlation between the dose and the lithogenic index was demonstrated, neither in 15 women, who had used oral contraceptives before the study nor in five women without any previous hormonal contraceptives.

Adult↗

A microliter method for the gas chromatographic determination of long-chain non-esterified fatty acids in human serum or plasma.

Non-esterified fatty acids (NEFA) from C12 to C24 are assayed in human serum or plasma in a four-step procedure: extraction, volume reduction, methylation and gas chromatography. NEFA are extracted with chloroform--heptane--methanol from 50--100 microliter of serum or plasma buffered with phosphate. After adding ethyl acetate the volume of the extract is reduced under partial reflux to 5--7 microliter. Potassium carbonate, methyl iodide and a crown ether are added to the dry concentrate and the NEFA are selectively methylated with a yield of 100% by heating in a microrefluxer for 10 min. Gas chromatography is carried out with 1 microliter of the reaction mixture on a packed column by temperature-programmed operation. Thirteen individual fatty acids are determined in sera of normal adults. The coefficients of variation for 24 determinations of a pooled serum were 2.7% for the total NEFA content and 3--10% for most of the individual NEFA.

Butylated Hydroxytoluene↗

Kinetic studies on bacterial plasma membrane ATPase (F1). Nucleotide-induced long term inactivation of ATP hydrolyzing activity is linked to the formation of multiple "tight" enzyme nucleotide complexes.

ADP and the ATP analogs Nb-S6ITP (6-[(3-carboxy-4-nitrophenyl)thio]-9-beta-D-ribofuranosylpurine 5'-triphosphate) and AMP-P(NH)P (adenyl-5'-yl imidodiphosphate) interact with soluble plasma membrane ATPase (F1) from Micrococcus species in two ways: (i) at short incubation times, these inhibitors exhibit the kinetics of competitive inhibition, (ii) at long incubation times, these inhibitors induce an inactivation of the ATPase which can be reversed only in the case of AMP-P(NH)P. Kinetic treatment of the long term inactivation by ADP or Nb-S6ITP reveals a pseudo-first order process via the formation of an enzyme-inhibitor complex for which a Km analogous constant is obtained that is identical with the corresponding Ki value of the competitive inhibition. The long term inactivation by ADP and Nb-S6ITP involves the successive "tight" binding of 6 +/- 1 nucleotides/F1 molecule. One additional ADP molecule/F1 complex which is also "tightly" bound has no effect on the ATPase activity. The long term inactivation by ADP and Nb-S6ITP is inhibited at higher inhibitor concentrations according to a kinetics analogous to a substrate excess inhibition. Evidence is presented indicating that the mechanism of ATP hydrolysis by F1 and the long term inactivation by ADP or Nb-S6ITP are related processes. The mechanism of long term inactivation by AMP-P(NH)P appears to be different from that of ADP or Nb-S6ITP.

Adenosine Diphosphate↗