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Biomedical subjects

P Bertram

Publications and source records attributed to P Bertram.

At least 37 records · Page 2Linked to original sources

The role of glucocorticoids and prostaglandin E2 in the recruitment of bone marrow mesenchymal cells to the osteoblastic lineage: positive and negative effects.

The role of glucocorticoids in bone formation presents a problem because although pharmacological doses in vivo give rise to osteoporosis, physiological concentrations are required for osteoblast (OB) differentiation in vitro. To try and rationalize this dichotomy, we investigated the effect of dexamethasone on the recruitment of OB precursors present in bone marrow. Using the CFU-f assay, we can measure (1) total colony formation; (2) the osteoblastic differentiation of the colonies defined as their ability to express alkaline phosphatase, synthesize collagen, and to calcify; and (3) colony expansion as either average colony surface area or average colony number. In control cultures and in the presence of 10(-10)-10(-9) M dexamethasone, colony formation and total cell number was maximal, but the addition of PGE2 had no effect on colony number and very few colonies expressed the OB phenotype. In the presence of 10(-8)-10(-7) M dexamethasone, colony numbers and total cell numbers were reduced but were increased by the addition of PGE2, the average colony cell number and surface area were relatively unchanged and a proportion of the colonies expressed APase, calcified and synthesized collagen. In cultures containing 10(-6)-10(-5) M dexamethasone, colony numbers were further reduced but were stimulated by the addition of PGE2 and some colonies differentiated; however, colony expansion was dramatically reduced by up to 80%. These results suggest that physiological levels of glucocorticoids are necessary for OB differentiation and allow the control of OB recruitment by PGE2. High levels of glucocorticoids drastically reduce proliferation of the OB precursors leading to glucocorticoid-induced osteoporosis.

Alkaline Phosphatase↗

Effect of age and ovariectomy on fibroblastic colony-forming unit numbers in rat bone marrow.

It is now thought that osteoblasts (OB) stem from mesenchymal precursor cells (fibroblastic colony forming units or CFU-f) in the bone marrow. As the availability of these cells may have a profound effect on bone formation, the effect of age and ovariectomy (OVX) on CFU-f numbers was studied. It was found that with increasing age the numbers of CFU-f in the marrow were drastically reduced. OVX had no effect on CFU-f levels in 4 week and 4 month old rats but raised CFU-f levels in 1 year old rats back to levels seen in younger rats. SHam operation alone had an effect on CFU-f levels in older rats and the OVX effects were indistinguishable from the sham effect until 20 d post operation when the sham levels returned to baseline. The results show that CFU-f levels follow a similar trend to the rates of bone formation seen in aged and OVX rats.

Age Factors↗

[Differentiated surgical therapy of diffuse peritonitis--a prospective study].

PATIENTS AND METHODS: In a prospective protocol 86 consecutive patients with a diffuse peritonitis were treated in the Surgical Clinic of the RWT-University in Aachen (FRG) from January 1992 to June, 1994. According to the "Mannheim Peritonitis-Score" three different stages were treated with different procedures. Stage-I-peritonitis (mild forms, MPS 0-20) was treated with the so-called standard procedure, Stage-II-cases (MPS: 21-29) with the closed postoperative lavage and severe stage-III-cases (MPS > 29) with the so-called "Etappenlavage" (multiple reexplorations and intraoperative lavage). RESULTS: 36 patients showed stage-I-, 29 stage-II-, and 21 stage-III-peritonitis. Mortality was 3% (1/36) in stage-I-, 24% (7/29) in stage-II-, and 33% (7/21) in stage-III-groups. The overall mortality of the whole group was 17% (15/86). The statistically expected mortality was 38% according to the MPS and 33% related to the APACHE-II-Score.

APACHE↗

Bone marrow cells are targets for the anabolic actions of prostaglandin E2 on bone: induction of a transition from nonadherent to adherent osteoblast precursors.

Although prostaglandin E2 (PGE2) is known to stimulate bone formation in vivo, its mechanism of action is not well understood. Circumstantial evidence suggests that bone marrow cells (BMC) may well be involved in this, and in order to investigate this further we have studied the effect of PGE2 on proliferation and matrix synthesis in high-density BMC cultures and on colony-forming unit (CFU-f) formation efficiency by BMC in vitro. High-density cultures of BMC formed a collagenous, calcified matrix, synthesized osteocalcin and expressed alkaline phosphatase activity. The addition of PGE2 caused a concentration-dependent increase in total (but not specific) APase activity, cell number, and collagen accumulation. It was found that PGE2 need only be present during the first 48 hours of the culture period and that longer exposure had no additional effect. PGE2 also caused a concentration-dependent increase in CFU-f formation, and it was found that this was due to the recruitment of new mesenchymal precursor cells from the nonadherent fraction of the BMC. Once again, the presence of PGE2 for only the first 48 hours of the culture period was enough to precipitate a maximal response. We conclude that one mechanism for the anabolic actions of PGE2 may be the recruitment of OB precursors from a population of nonadherent mesenchymal precursor cells present in the bone marrow.

Alkaline Phosphatase↗

Prevention of postoperative adhesions by single intraperitoneal medication.

Postoperative adhesions account for a significant morbidity after abdominal, gynecological, or cardiac surgery. A large number of compounds have been suggested to prevent such adhesions, but none is generally accepted. We have compared eight different substances that could be beneficial for the prevention of postoperative adhesions in a new standardized rabbit model with measurement of the areas of adhesion. In 10 groups of 20 rabbits an area of abrasion of the serosa of the ileum, the appendix, and the abdominal wall measuring 10,000 mm2 was created by an emery piston during celiotomy. The controls received no medication. The treatment groups received a single intraperitoneal administration of 1 ml per 100 g body wt of normal saline (NaCl), 5 mg taurolidine (T), 0.5 U plasmin/300 U DNase (PD), 2000 IU streptokinase/500 IU streptodornase (SS), 7 mg phosphatidylcholine (PC), 4 mg hyaluronic acid (HA), 7 mg sphingolipid (SL), 7 mg galactolipid (GL), or 0.5 ml tetrachlorodecaoxide (TCDO), respectively. Ten days later the extent of adhesions was quantified by morphometry. The total area of adhesions (+/- SEM) was found to be 1998 +/- 124 mm2 in controls. The application of NaCl reduced the adhesions to 1368 +/- 58 mm2, of T to 1012 +/- 48 mm2, of PD to 673 +/- 33 mm2, of SS to 360 +/- 44 mm2, of PC to 335 +/- 84 mm2, of HA to 328 +/- 76 mm2, of SL to 278 +/- 80 mm2, of GL to 261 +/- 67 mm2, and of TCDO to 240 +/- 45 mm2. The effects of PD, SS, PC, HA, SL, GL, and TCDO were significant in comparison to controls and NaCl. Our experimental data suggest that the two new lipid substances, SL and GL, are the most likely candidates for routine clinical use in the prevention of postsurgical adhesions.

Abdominal Muscles↗

Invasive squamous-cell carcinoma in giant anorectal condyloma (Buschke-Löwenstein tumor).

Giant condyloma acuminata, first described by Buschke and Löwenstein in 1925 as a penile lesion, is extremely rare in the anorectal region. The cauliflower-like tumor behaves clinically in a malignant fashion, although it shows no histomorphological criteria of malignancy. Up to the time of writing only 33 cases of anorectal origin, 42% with malignant transformation, have been published. The authors report 2 more cases of squamous-cell carcinoma in giant anorectal condylomata acuminata. Buschke-Löwenstein tumor is an intermediate entity between "ordinary" condyloma acuminata and squamous-cell carcinoma. Benign condyloma acuminata is caused by human papillomavirus 6 or 11. Carcinogenic cofactors promote the transition to giant, locally destructive condyloma acuminata and subsequent malignant transformation. Cure can only be achieved by early and radical excision. Formation of multiple fistulas and destruction of the sphincter may necessitate abdomino-perineal resection. Adjuvant radiation therapy should only be considered to render a tumor operable, as radiation may act as a cocarcinogenic effect and lead to a less differentiated and more aggressive cancer. The small number of cases reported and the variety of treatment regimens applied, however, do not allow the formulation of definitive therapeutic guidelines.

Anal Canal↗

PGE2 induces the transition from non-adherent to adherent bone marrow mesenchymal precursor cells via a cAMP/EP2-mediated mechanism.

When mesenchymal precursor cells from bone marrow are cultured in the presence of dexamethasone, the existence of distinct non-adherent and adherent populations can be demonstrated. The addition of PGE2, forskolin, or dibutyryl-cAMP can induce a transition from the former to the latter and this may be an important mechanism in the bone anabolic effects of PGE2. On the other hand, phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, and sulprostone, an agonist for the PGE2 receptor EP1/EP3 subtypes, had no effect. The phosphodiesterase inhibitor, isobutylmethylxanthine (IBMX), had a synergistic effect in combination with PGE2, whereas neomycin, an inhibitor of inositol phosphate activity, had no effect, and LiC1, an inhibitor of inositol triphosphate metabolism, had an inhibitory effect on the PGE2-induced transition. Consistent with this, the addition of PGE2 to non-adherent bone marrow cells caused a 100% increase in cAMP synthesis. These results suggest that the induction of the transition from non-adherent to adherent osteoblast precursor is mediated by the EP2-PGE2 receptor subtype via an increase in intracellular cAMP synthesis.

1-Methyl-3-isobutylxanthine↗

[Prevention and therapy of intra-abdominal adhesions. A survey of 1,200 clinics in Germany].

A survey of 1200 hospitals in Germany was undertaken to estimate the current standards of prevention and treatment of postoperative peritoneal adhesions. The 751 (62.2%) evaluated questionnaires showed a representative distribution according to postal zones and annual laparotomies. The rate of coeliotomies for adhesional bowel obstruction is 2.6%. Starch-powdered gloves are used in 54.2% and washed before operating in 69.3%. Dry swabs and towels are used in 60.7 and 22.5%, respectively. Most of the surgeons suture the peritoneum. Adhesions are divided in patients with respective symptoms but without intestinal obstruction by 32.6% and during laparotomies for non-adhesion-related diseases by 20.4%. Long intestinal tubes and plication procedures are applied by 43.9 and 33.7%, respectively. Medication is administered for routine prophylaxis of adhesion by 6%, for prevention of recurrencies by 17.2%. Although it has been revealed that adjuvant measures for prevention of adhesions are needed, as of today, no regimen has proofed its efficacy and gotten accepted for clinical usage.

Abdomen↗

[A new suture device for continuous sutures in the intestinal tract].

A new surgical sewing device for continuous sutures of gastrointestinal anastomoses with needle and suture material was used for the first time to construct a latero-lateral enterostomy (functional end-to-end anastomosis) in the small intestine of pigs. In ten animals the course was mainly uneventful during the observation period of 10 days. One animal developed a postoperative anastomotic leakage. In five cases adhesions between the anastomotic region and the small intestine were found on postmortem examination, but there was no evidence of any slight leakage. On the whole, the sewing device operated faultlessly. At present, clinical use seems possible for long sutures, which are time-consuming when sewn manually, but it is still premature. One major disadvantage of the device is its size, which restricts its application to extra-abdominal tasks. Nonetheless, the principle of a mechanical device for running sutures should be investigated further.

Anastomosis, Surgical↗

[Pneumatosis cystoides intestinii].

Pneumatosis cystoides intestinalis (PCI), a condition involving submucosal or subserosal gas-containing cysts of the wall of the gastrointestinal tract, is a rare entity. It is mostly diagnosed between the third and fifth decades of life without a clear sexual predominance. Different aetiopathogenetic factors are under discussion, the most probable being a bacteriologic cause (Clostridium perfringens) in combination with minimal leaks in the mucosal barrier. There are no pathognomonic symptoms; the clinical picture ranges from incidental findings to haematochezia. Diagnosis is based on plain abdominal film and X-ray following barium enema. Methods of treatment in symptomatic cases are oxygen and antibiotic (metronidazole) therapies and, in severe cases, resection of the diseased part of the intestine.

Colectomy↗

Reduced secretion of interleukin-1 and tumor necrosis factor-alpha by neonatal monocytes.

Monocytes were isolated from peripheral blood of preterm and term newborn infants and adult controls, and their capacity to secrete the inflammatory mediators interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) was investigated. Lipopolysaccharide (LPS)-stimulated neonatal monocytes secreted significantly less IL-1 (median: 1.1 U/ml) than monocytes from adult controls (median: 7.3 U/ml). In addition TNF-alpha production by LPS-stimulated neonatal monocytes (median: 610 pg/ml) was significantly lower when compared with controls (median: 2230 pg/ml). Our data provide evidence that neonatal monocytes have a profoundly impaired cytokine secretion.

Adult↗

[Surgical therapy of myasthenia gravis and thymoma].

Between 1986 and 1992 eighteen patients underwent transsternal radical thymectomy at the Department of Surgery of the RWTH Aachen. Operation was indicated for myasthenia gravis (n = 14) or suspect of thymoma (n = 4). Patients with myasthenia were preoperatively classified according to Osserman and postoperatively with respect to their clinical status and drug dosages. Patients with thymoma were classified according to Masaoka. After a mean follow-up period of 43.6 months 76.9% of the patients with myasthenia demonstrated a significant improvement. All patients with thymoma were free of recurrence.

Adolescent↗

[Intraluminal splinting of problematic intestinal anastomoses with biomaterial tubes].

We performed small intestinal dissection in 80 laboratory rats. A critical anastomosis was achieved by two point adaptation of small intestine with single sutures. 10 control animals receiving no intestinal splinting died within two days of operation. The remaining 70 animals underwent intestinal internal splinting with tubes of different absorbable (Polyglactine, Collagen, and B111) and non-absorbable (Polyurethane) biomaterials. Significantly smaller leakage rates in the therapy groups proved the principle of internal splinting of complicated anastomoses in this animal model to be effective.

Anastomosis, Surgical↗