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Biomedical subjects

K M Peters

Publications and source records attributed to K M Peters.

At least 37 records · Page 2Linked to original sources

Alteration in the pattern of macrophage subtypes in chronic osteomyelitis compared with acute joint infection.

Macrophage subtypes were detected in cryostat sections of biopsies from patients with chronic osteomyelitis, acute joint infections and normal bone marrow, using monoclonal antibodies against different macrophage populations. The resident macrophage subtype 25F9, the gluco-corticoid-inducible macrophage RM 3/1 and the inflammatory type 27E10 were found in abundance in acute infections. They were also present in tissue sections of uninflamed bone marrow. By contrast, in about 50% of the biopsies from patients with chronic osteomyelitis a reduced number of macrophage subtypes, or even the lack of one or more macrophage subpopulations was found. The unusual absence of macrophage phenotypes seems to be restricted to the area of osteomyelitis because in the tissues of inflamed sinuses in these patients, the macrophage subtypes were present. These findings suggest a disturbance at the level of the macrophages which may contribute to the persistence of the inflammatory process in osteomyelitis.

Acute Disease↗

PMN elastase in bone and joint infections.

PMN (polymorphonuclear neutrophil) elastase is a proteolytic enzyme which is a biochemical marker for abnormal granulocyte stimulation. In inflammation and sepsis, excessive neutrophil stimulation results in significant amounts of PMN elastase being released into the plasma which indicates the severity of the disease and its prognosis. In 62 patients with osteomyelitis or suppurative arthritis, PMN elastase had a diagnostic sensitivity of 81%, which is comparable to the nonspecific erythrocyte sedimentation rate. Sensitivity of C-reactive protein (CRP) was 71%, fibrinogen 54% and leucocyte count 26%. PMN elastase was also useful in the follow up of patients with bone and joint infections; in the early post-operative period it became normal more quickly than the other findings unless the patients developed complications. Ten days after operation, PMN elastase was normal in 75% of the patients compared to the CRP which became normal in only 25%. Later both results were similar: on discharge from hospital, PMN elastase was normal in 77% and CRP in 71%.

Arthritis↗

Osteocalcin levels in chronic osteomyelitis.

Osteocalcin is a vitamin K-dependent bone protein synthesized by osteoblasts. In generalized bone disorders serum osteocalcin correlates with osteoblast activity. Bone resorption and new bone formation occur in chronic osteomyelitis, dependent on the level of inflammatory activity. In 17 patients with active chronic osteomyelitis undergoing surgery, the serum levels of osteocalcin, alkaline phosphatase and C-reactive protein were measured before and after treatment. The osteocalcin levels were within the normal range preoperatively (10.8 +/- 11.0 micrograms/l), in the early postoperative period, and at discharge. It is therefore not a helpful marker in the clinical management of this condition.

Alkaline Phosphatase↗

Pattern of macrophage subpopulations in post-traumatic bone infections after combined operative/antibiotic treatment.

Macrophage subpopulations were detected immunohistochemically with the aid of monoclonal antibodies in tissue sections of 15 patients with posttraumatic osteomyelitis at the beginning of therapy and after combined operative/antibiotic treatment. Macrophages represent the majority of the immunocompetent cells in osteomyelitis tissue. Before the start of therapy, the acute inflammatory macrophage subtype 27E10 was absent or rarely found in 8/13 evaluable biopsies from the osteomyelitis focus, and a further decrease in the expression of these macrophage antigens was observed after treatment. The RM3/1-positive macrophage associated with the down-regulation of inflammation was detectable to a low extent in 4/13 evaluable biopsies from the osteomyelitis focus before the start of therapy. After treatment of the infection, an increase in this subtype was found in the cellular inflammatory infiltrates in the tissue samples examined. In 8/15 biopsies a marked expression of the RM3/1 antigen was observed. At the start of treatment, the macrophage 25F9, which dominates in the late phase of inflammation, was missing in 3/13 tissue samples. After combined operative/antibiotic treatment the 25F9-positive macrophage was found in all patients, having increased in 7/14 biopsies studied. These data suggest that treatment of posttraumatic osteomyelitis leads to a local macrophage subtype distribution in the osteomyelitis focus resembling the pattern of a late inflammatory reaction.

Adolescent↗

[Lymphocyte defects in chronic osteomyelitis. A prospective study].

In patients with chronic post-traumatic osteomyelitis, several deficits in immunological response were demonstrated. In a prospective trial of 20 patients with proven osteomyelitis, histological analysis of lymphocyte subsets in peripheral blood and in the infected bone tissue was performed. The effects of chronic osteomyelitis on lymphocyte subsets in the peripheral blood and in inflamed tissue were only slight. The T4/T8 ratio was diminished in only two patients and had no relationship to the clinical course. Interleukin 2 receptor determination was negative in 83% of biopsies of infected tissue. Osteomyelitis may possibly cause a defect in lymphocyte/macrophage cooperation.

Adolescent↗

[Osteomyelitis today--diagnostic imaging and therapy].

Plain radiography, bone scan and especially in infants sonography belong to the primary imaging methods for posttraumatic osteomyelitis. For further diagnostic check up of osteomyelitis CT, MRI and leukocyte scintigraphy are excellent methods. Treatment of posttraumatic osteomyelitis is today a combination of operation, local and systemic antibiotic therapy.

Adolescent↗

[Treatment of osteomyelitis and reconstructive measures in patients with war injuries].

54 wartime trauma patients injured by bombs, shell splinters or rockets were treated between 1985 and 1989 in the Orthopaedic Clinic of RWTH Aachen. Lesions of the lower limbs were dominating (78%). Treatment was often tedious, and up to 12 operations had to be performed. In 81% one extremity was injured, in 17% two extremities were involved. 78% of the patients were already primarily treated at home, mostly by amputations. 33% of the patients suffered from bone infections at admission. Infections were mostly caused by Staphylococcus aureus or Pseudomonas aeruginosa. In 41% of all patients operative treatment for osteomyelitis was necessary (37% sequesterectomies, 44% stabilisations with fixateur externe). In advanced bone infection amputations were indispensable in 28%. In 27% of our wartime trauma patients reconstructive surgery was performed (spongiosa transplantations in 91%, stabilisation with fixateur externe in 44%). In none of our patients treated with reconstructive surgery an amputation was necessary later on.

Adult↗

[The selection of spongiosa donors for a bone bank].

A prospective trial was carried out in 156 unselected patients (41 men, mean age 67.5 years, 115 women, mean age 71.4 years) who had undergone total hip joint replacement because of degenerative or inflammatory arthritis or fracture of the neck of the femur. The excised femoral heads were subjected to three-stage bone bank screening so as to ascertain how many of them would pass the clinical, biochemical and microbiological exclusion criteria. Only 26 out of 156 femoral heads (17%) proved to be acceptable for the bone bank. Ninety patients (58%) were excluded on clinical grounds such as old age (over 80 years), malignant neoplasms, rheumatoid arthritis, previous intraarticular injections or long-term steroid medication. Positive hepatitis serology excluded 19%, and raised preoperative neopterin concentration excluded 25%, though three months postoperatively this was confirmed in only 2%. Routine neopterin assay seems to be a useful step towards improved bone bank screening, since neopterin concentration is clearly increased in recent virus infections such as HIV. Bacterial contamination was of no practical importance. Because of the low proportion of femoral heads passed as suitable for the bone bank, the existing exclusion criteria will have to be critically scrutinized, and alternative procedures for harvesting bone safe for transplantation (freeze drying, autoclaving, irradiation) will have to be employed.

Aged↗

[PMN-elastase as a marker in diagnosis and follow-up of bone and joint infections].

PMN elastase, a proteolytic enzyme, is a biochemical marker for pathologic granulocyte stimulation. In the presence of sepsis, excessive neutrophil stimulation occurs and significant amounts of PMN elastase are released into the plasma and serve as an indicator for the severity of the disease and the prognosis. PMN elastase is also a useful parameter for preoperative diagnostic management and postoperative follow-up of bone and joint infections. In patients with osteomyelitis and joint empyema (n = 48) PMN elastase had a sensitivity of 77%, which was only exceeded by that of the unspecific erythrocyte sedimentation rate (sensitivity 89%). Sensitivities of other inflammation parameters were lower: C-reactive protein (CRP) 67%, fibrinogen 50%, neopterin 32% and leukocyte count 21%. Determination of PMN elastase levels was also helpful in postoperative follow-up of patients with bone and joint infections. In the early postoperative period PMN elastase levels normalized more quickly than the other parameters unless patients actually developed complications. At the first postoperative determination (day 2-4 after surgery) 38% of the patients (n = 24) already had PMN elastase levels within the normal range (less than or equal to 40 micrograms/l) (CRP 13%). After 10 days PMN elastase was normal in 57% and CRP in 30% of the patients. Later on both parameters reacted similarly: by the time of discharge from hospital levels of PMN elastase were normal in 70% and CRP levels in 74%.

Acute-Phase Proteins↗

[Immune competence of human tissue lymphocytes in contact with loosened hip joint prostheses. On the topic of cellular or humoral rejection reaction as the mechanism of loosening].

In several investigations rejections were accused of being a possible cause for the loosening of hip endoprostheses. Using immunocytochemical techniques we studied the number and type of lymphocytes in the tissue adjacent to loosened hip endoprostheses. Tissue samples were taken from 18 patients being reoperated for a loosened endoprostheses. Impressive lymphocyte infiltrates were found in 4 of 18 patients (22%). These infiltrates only consisted of T-cells. In the other samples only few lymphocytes were detected belonging to T- and B-lymphocyte population, respectively. In our patients T-cell mediated rejections were of minor importance for the loosening of total hip replacement. B-cell accumulations were detected in none of the samples.

Aged↗

[Neopterin as a marker of aspecific immunostimulation with Propionibacterium avidum KP-40 in patients with gastrointestinal tumors. A prospective randomized study].

This prospective randomized study demonstrated that a preoperative intravenous infusion of 10 mg of the bacterial preparation Propionibacterium avidum KP-40 to patients with gastrointestinal tumors significantly (P less than 0.001) enhanced the secretion of neopterin, measurable as long-lasting (greater than 16 days) elevated urine excretion. Postoperative re-infusion of P. avidum KP-40 caused (statistically significant (p less than 0.001] re-enhancement of neopterin urine levels.

Adult↗

Differential regulation of liver P-450III cytochromes in choline-deficient rats: implications for the erythromycin breath test as a parameter of liver function.

Progressive liver fibrosis in rats develops when they are fed a diet deficient in choline. This diet also results in a pronounced and selective decrease in the liver microsomal content of a phase I drug-metabolizing enzyme belonging to the cytochrome P-450III gene family. Because P-450III cytochromes characteristically catalyze the N-demethylation of erythromycin, we believed that the production of breath CO2 from erythromycin would be dramatically reduced in choline-deficient rats. However, when 12 choline-deficient rats were compared with 9 control rats, the reduction in CO2 production from erythromycin (mean decrease 71%) was essentially identical to that from aminopyrine (mean decrease 69%), a substrate believed to be metabolized normally by the hepatocyte in fibrotic liver disease. Furthermore, we found that the relative erythromycin and aminopyrine demethylase activities were comparable when measured in vitro in liver microsomes prepared from the choline-deficient rats. To determine the molecular basis for the erythromycin demethylase activity in the choline-deficient rats, the liver microsomes were subjected to immunoblot analysis using a variety of polyclonal and monoclonal antibodies capable of distinguishing individual P-450III-related proteins. Our studies confirm that a major erythromycin demethylase belonging to the P-450III family, termed P-450p, was greatly reduced in the choline-deficient rat liver. However, the specific concentration of a second P-450p-related protein was essentially normal and that of a third P-450p-related protein was actually increased in the choline-deficient rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyrine↗

Behaviour of lymphocyte subsets in response to immunotherapy with Propionibacterium avidum KP-40 in cancer patients.

In 15 patients the influence of unspecific immunostimulation/immunomodulation was studied. Patients constituting the therapeutical group suffered from colorectal- and gastric carcinoma, respectively, and were preoperatively treated with 10 mg whole cell preparation of immunomodulating Propionibacterium avidum KP-40. This adjuvant immunotherapy resulted in a significant increase (p less than 0.01) of the natural killer (NK)-cell population, however, total leukocyte and lymphocyte count as well as helper- and suppressor T-lymphocyte subsets did not significantly differ form control values.

Adjuvants, Immunologic↗

Preoperative immunostimulation with propionibacterium avidum KP-40 in patients with gastric carcinoma: a prospective randomized study.

Sixty-eight patients admitted for resection of gastric carcinoma entered a prospectively randomized trial. Patients in the therapy group (n = 34) received a preoperative controlled infusion of 10 mg Propionibacterium avidum KP-40. The therapy and control group did not differ with regard to postoperative complications, tumor recurrence rates (therapy group: 41%, control group: 38%), and patient survival rates (survival rate in the therapy group after 25 months: 53%, in the control group after 25 months: 50%).

Adenocarcinoma↗

Comparative study on lymphocyte subpopulations in cancer patients after immunostimulation with propionibacteria and in renal transplant patients after combined immunosuppression.

In two groups of patients the influence of unspecific immunostimulation (group 1) and combined immunosuppression (group 2) on lymphocyte subpopulations was studied. Patients constituting group 1 suffered from gastric and colorectal carcinoma, respectively, and were preoperatively treated with 10 mg whole cell preparation of immunostimulating Propionibacterium avidum KP-40 (Köln-Propioni, strain 40). Patients of group 2 were submitted to combined immunosuppressive therapy and treated with antilymphocyte globulin, prednisone, and azathioprine subsequent to renal transplantation. Immunostimulation with P. avidum KP-40 resulted in a significant increase (p less than or equal to 0.01) of the natural killer (NK) cell population, whereas total leukocyte and lymphocyte counts as well as helper and suppressor T lymphocyte subsets did not evidently differ from control values. On the contrary after immunosuppression all subsets of lymphocytes as well as NK cells significantly decreased.

Azathioprine↗

Phase II study of recombinant human tumor necrosis factor in colorectal carcinoma.

Fifteen patients with colorectal carcinoma received a 30-min intravenous infusion of recombinant human tumor necrosis factor (rHuTNF) to investigate the value of rHuTNF in the treatment of colorectal carcinoma. Patients received 5 x 10(5) U/m2 (217 micrograms/m2) on day 1, and in the absence of serious side effects 10 x 10(5) U/m2 (435 micrograms/m2) on day 3 and 15 x 10(5) U/m2 (652 micrograms/m2) on day 5. The cycle was repeated on day 28. Full dose escalation was possible in all patients. There was a minor response in one patient (disappearance of retroperitoneal lymph nodes). All other patients showed progressive disease. At the dose and schedule used, rHuTNF had minimal therapeutic activity in colorectal carcinoma.

Adolescent↗

Monitoring of tumor necrosis factor therapy with neopterin.

As neopterin is only secreted by stimulated macrophages, serum neopterin levels are an important marker for cellular immunity. Daily determinations of serum neopterin were performed in five patients with advanced colorectal carcinoma receiving a therapy with tumor necrosis factor (TNF). 24 h after every TNF infusion a significant, but only short-lasting increase of neopterin was observed. This effect was dependent on the applicated TNF dose. These results prove that determinations of serum neopterin levels are a helpful parameter for monitoring an immunomodulating therapy with TNF.

Biopterins↗