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Biomedical subjects

M R Mueller

Publications and source records attributed to M R Mueller.

13 recordsLinked to original sources

Influence of UW solution on in vitro platelet aggregability.

Bleeding problems in orthotopic liver transplantation (OLT), starting immediately after reperfusion of the graft, are complicating the outcome of transplantation. Platelets may be involved in this situation, but there is still a lack of information about the influence of UW solution on platelet function. We evaluated the effect of UW solution on in vitro platelet aggregability in healthy volunteers using whole blood electrical aggregometry and concluded, that UW solution causes impaired platelet aggregability and may contribute to bleeding problems during OLT. The mechanism of impairment remains unclear, since central pathways as well as membrane receptors seem to be involved. Furthermore, our data support the necessity of extended flushing of the liver graft after reperfusion.

Adenosine

Carcinogen-specific mutations in the p53 tumor suppressor gene in lung cancer.

Mutations of the p53 tumor suppressor gene, whose encoded protein is one of the chief regulators of the cell cycle, are proving to be the most common genetic alteration in human cancer. Point mutations have been detected in numerous human solid tumors. The types of point mutations in the p53 gene vary considerably in different kinds of human cancers, suggesting that specific etiologic agents are responsible for typical kinds and sites of mutations in the p53 gene. This study reports the detection of two unusual p53 mutations in a series of patients with lung cancer. The first case showed a one-base pair deletion at the end of exon 8, which is rarely affected by mutations, leading to a frameshift involving the following intron 8, exon 9, and intron 9. The second case exhibited two point mutations in codon 273, both either localized in the same codon on one allele or each mutation localized on a different allele in codon 273. Interestingly, the two mutations can be attributed to different mechanisms of base substitution. This is the first report of this kind. Because of evidence that the nature and site of p53 mutations reflect not only the mutagens involved in tumorigenesis but also the capacity for malignant transformation, the characterization of mutations of the p53 gene may provide a basis for assessing further risk factors, as well as for estimating prognosis in patients with lung cancer.

Adenocarcinoma

Clinical experience with minimally invasive thoracic surgery.

From October 1991 to June 1992 video-endoscopic lung surgery was applied in a total of 109 patients. In the first case a pulmonary cyst measuring 15 x 18 cm was resected. In 21 patients lung nodules were exstirpated by means of wedge resection. Moreover, metastasectomies, open lung biopsies, parietal pleurectomies, resections of bullae, and decortications, as well as 3 lower-lobe lobectomies were performed using video-endoscopic procedures. Closure of lung parenchyma was carried out using the 3 cm Endo-GIA stapler (Autosuture). In none of the patients were we forced to enlarge the intervention to a thoracotomy because of technical problems. Indications, operative technique and results are presented. This new technique offers all the known advantages of minimally invasive surgery to patients requiring thoracic surgery.

Anesthesia, General

In vitro hematological testing of rotary blood pumps: remarks on standardization and data interpretation.

Pump test procedures using blood will have to meet several standards not only to obtain reliable results in vitro but also to allow comparison of results of different investigators. This article reviews some of the issues that should be considered in pump testing, especially referring to the discussions held at the International Workshops on Rotary Blood Pumps in 1988 and 1991. The test loop itself should meet some requirements such as constant physiological temperature, standardized circulating volume, control of pressure and flow, and exact definition of the blood-contacting surface. Specifications have to be made concerning the test fluid blood, including sampling technique, anticoagulation, blood gases, pH, and glucose level. Only fresh blood should be used. Heparin is recommended for anticoagulation because it will be used also in vivo. Different procedures for cleaning and rinsing of plastic materials for reuse are mentioned. Bacterial overgrowth, which can lead to extreme oxygen consumption and acidosis, may be avoided through addition of antibiotics (e.g., gentamicin). To be able to compare data of the different working groups, a new modified index of hemolysis (MIH) has been defined.

Animals

Pulmonary surfactant in bronchoalveolar lavage after canine lung transplantation: effect of L-carnitine application.

Pulmonary surfactant during lung transplantation was investigated in the control group of a canine single lung transplantation model by measuring dipalmitoyl-phosphatidylcholine, the main phosphocholine fraction of surfactant in bronchoalveolar lavage. In a second group of dogs, L-carnitine, an essential cofactor for transfer of long-chain fatty acids into the mitochondria, was applied. Organ function after pulmonary artery flushing with modified Euro-Collins solution and hypothermic storage for 4 hours was adequate in both groups, with significantly higher arterial oxygen pressure levels in the L-carnitine group after 12 (p less than 0.05) and 24 (p less than 0.025) hours, respectively. In the control group, a reduction of the dipalmitoyl-phosphotidylcholine portion on total phosphotidylcholines was observed 4 and 12 hours after transplantation of the left lung (p less than 0.005 and p less than 0.01, respectively, both specified by Student's t test for dependent data, not significant by Bonferroni correction). In the simultaneously stored right lungs, a constant fall of the dipalmitoyl-phosphotidylcholine portion was demonstrated. In the L-carnitine group, significantly higher dipalmitoyl-phosphotidylcholine levels were observed in the transplanted left lungs after 4 hours (p less than 0.01) and in the continuously stored right lungs after 24 hours (p less than 0.005), when compared with the control group. These results suggest that dipalmitoyl-phosphotidylcholine portion on total phosphotidylcholine decreases parallel to the extent of the ischemic damage. Furthermore, the application of L-carnitine improved pulmonary function after transplantation, possibly by reducing the impairing effect of ischemia on alveolar type II cell metabolism and thereby on pulmonary surfactant system.

1,2-Dipalmitoylphosphatidylcholine

Connective-tissue disease following breast augmentation: a preliminary test of the human adjuvant disease hypothesis.

It has been proposed that scleroderma in particular or connective-tissue diseases in general may be caused by exposure to silicone-containing materials used for breast augmentation. We performed a historical cohort study to estimate the point prevalence of this potential complication sometimes referred to as "human adjuvant disease." Three-hundred and seventy-eight patients who underwent augmentation mammaplasty with silicone-containing envelope-type prostheses from 1970 through 1981 were surveyed. Regional musculoskeletal syndromes, fibrositis, or osteoarthritis occurred in a third (38 of 125) of our responders. No patient developed an inflammatory systemic rheumatic disease during the period of observation (mean 6.8 years for the 125 subjects). Using calculations based on risk for development of rheumatic disease, it does not appear likely that augmentation mammaplasty is a significant or major inducer of inflammatory connective-tissue diseases in general. However, the number of patients surveyed was small, and our results must be considered preliminary. We could not exclude a specific risk for the development of scleroderma.

Adult

Assessing physician/patient perceptions in rheumatoid arthritis. A vital component in patient education.

Patient education surveys were completed by 101 patients with rheumatoid arthritis and by 28 rheumatologists to assess and compare patients' reports with physicians' perceptions of patients' needs regarding content, provider, and education program delivery methods. Both groups agreed on the importance of patients' education about arthritis, especially on the topics of medication, physician/patient communication, quackery, and maintaining ambulation. A higher proportion of physicians reported that patient education was needed in psychosocial areas, activities of daily living, sexual concerns, and community resources. Patients sought more education in disease process, diagnostic procedures, and nutrition. Patients rated pharmacists and nutritionists significantly more important as educational sources than did physicians. Both groups reported individual patient/practitioner meetings as the preferred delivery method. Physicians reported group education to be valuable for some psychosocial topics; patients disagreed significantly. Despite considerable consensus, disagreements were evident in the psychosocial area and in the role of allied health professionals. Clarification, understanding, and resolution of these differences should be sought before implementing patient education programs.

Adult

Gold therapy in patients with systemic lupus erythematosus.

Despite a progressively more favorable prognosis in systemic lupus erythematosus (SLE) a need remains for therapeutic agents with greater benefit and less toxicity than corticosteroids and immunosuppressive drugs. Therefore, we treated 16 patients with SLE but without renal diseases with auranofin, a drug with proved efficacy and safety in rheumatoid arthritis. A modest diminution in overall disease activity, as judged by the investigators, and a reduction in maintenance corticosteroid dosage was achieved. However, neither laboratory assessments nor more objective clinical measurements of SLE disease activity disclosed any improvement over baseline. One case each of proteinuria and thrombocytopenia was observed, most likely related to underlying disease and not the drug, suggesting that auranofin may be safe in patients with SLE. A controlled trial, utilizing a broader spectrum of patients with SLE, may be warranted.

Adrenal Cortex Hormones

NaHCO3 therapy corrects the increased urinary Na, K, Cl and H2O excretion induced by NH4Cl.

Micropuncture studies conflict as to whether the proximal volume reabsorptive defect of acute hyperchloremic metabolic acidosis corrects when the acidosis is repaired with NaHCO3. Whether NaHCO3 improves the elevation in urinary solute and water excretion rates induced by acidosis in euvolemic animals, reflecting normalization of proximal reabsorption, has not been previously examined. In these studies in awake rats, NH4Cl caused the plasma bicarbonate concentration to fall from 22 to 11 mEq/l concomitantly with a 1 1/2- to 3-fold increase in sodium, potassium, chloride and volume urinary excretion rates. Isotonic NaHCO3 (5% body weight) infusion restored the plasma bicarbonate concentration to 21 mEq/l and urinary electrolyte and volume excretion rates returned to control values. Comparable volume expansion with NaCl did not correct the acidosis or improve urinary excretion rates. We conclude that correction of acute metabolic acidosis by NaHCO3 therapy repairs the natriuresis, kaluresis, chloruresis and diuresis, presumably by improving proximal reabsorption.

Acidosis

The effect of a copper intrauterine device during the early stages of pregnancy in the rabbit.

Copper wire intrauterine devices (CuIUD) were surgically inserted into mature female rabbits 15 days prior to artificial insemination. Gold wire intrauterine devices and sham surgery served as controls. Animals were autopsied 48, 72, 96, 120, 144, and 192 hours after artificial insemination. At autopsies performed 48 to 144 hours after insemination, the reproductive tract was flushed and the embryos were examined. At 192 hours, implantation sites were counted and measured. A significant (P less than 0.05) loss of copper from the devices was observed when the devices were weighed after autopsy. The CuIUD had no effect on ovulation, fertilization, or embryo transport up to 120 hours after artificial insemination. The presence of a CuIUD resulted in a slight, but not statistically significant, increase in embryonic degeneration by 120 hours, almost total absence of blastocysts from the uterus by 144 hours, and complete absence of implantation sites 192 hours after insemination. The antifertility effect of a copper intrauterine device appears to occur in the late preimplantation stage of pregnancy in the rabbit.

Animals

The effect of a copper intrauterine device on the uterine histology and progestational response in pregnant and immature rabbits.

A copper wire intrauterine device (GuIUD) was inserted into mature female rabbits 14 days prior to artificial insemination (AI), and its effect on the histology of the pregnant uterus was studied 48 to 192 hours after AI. In a related study, estrogen-primed immature femal rabbits were fitted with a device consisting of 321 mm of copper wire wound around a 17-mm plastic carrier and treated subcutaneously for 5 days with 0.1 mg of progesterone daily. Uterine tissue samples were obtained on the following day, examined histologically, and tested for carbonic anhydrase activity. In both studies, gold wire devices, similar to the respective copper devices, and sham surgery served as controls. In the pregnant rabbit, the McPhail score (McPhail MK: J Physiol (Lond) 83:145, 1934) measuring arborization of the luminal epithelium was significantly lower in tissue surrounding the CuIUD than in tissue anterior to the CuIUD or in tissue from the contralateral control horn bearing an AuIUD or subjected to sham surgery, 96 to 192 hours after AI. The morphologic development of the epithelial cell structure was retarded only in areas surrounding the CuIUD 96 to 192 hours after AI. There were no observable differences in the stroma or in the leukocytic infiltration of the tissue. In the estrogen-primed immature rabbits, the ability of the tissue to react to exogenous progesterone was depressed in tissue surrounding the copper device, as determined by the lower McPhail score, compared with tissue anterior to the copper device or from contralateral controls. Similary, progestational stimulation of carbonic anhydrase was blocked significantly in tissue surrounding the CuIUD and, to a lesser extent, in tissue anterior to the CuIUD. The data suggest that copper ions eluted from the CuIUD produce a contraceptive effect by locally blocking the action of progesterone on the epithelial tissue.

Animals

Platelet function after total artificial heart replacement: clinical application and experiment.

Clinical application of artificial blood pumps for mechanical circulatory support has been hampered by thromboembolic events. The underlying mechanisms are complicated and may differ from patient to patient. Because the calf is commonly used for artificial heart studies, the object was to determine the value of data gained in an animal model. To this end, the average of 10 calf experiments was compared with three clinical applications of an orthotopically implanted total artificial heart in patients with terminal heart failure. Platelet reactivity was investigated in vitro by collagen-induced whole blood aggregometry, radioimmunoassay methods, and scanning electron microscopy over a 10-day period. An analogous periodicity of platelet function was found in human and animal recipients. Improvement of platelet function preceded that of platelet counts in the early postoperative phase. Exaggerated responses to aggregative agents were observed at days 3 and 7. On the basis of our data, we believe that we can comment about the prospective course of the function and number of human platelets, which may contribute to the identification of critical phases of such treatment, during total artificial heart replacement.

Adult