Showing papers by "University of Bern published in 1989"

Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils.

Abstract: Introduction Neutrophil accumulation in a tissue is characteristic of inflammation and is observed in a variety of pathological conditions as disparate as infection, trauma, ischemia, and cancer. The process of tissue infiltration is best understood in bacterial infection, where neutrophils are selectively attracted in large numbers to phagocytose and kill the invaders. In other conditions neutrophils are presumably recruited as scavengers of damaged tissue or unwanted extracellular deposits like immune complexes or fibrin. Phagocytosis is accompanied by the release of granule enzymes, superoxide, H202, and a variety of bioactive lipids. Several of these products are required for the killing and digestion of microorganisms. They also induce inflammation and tissue damage, however, which is normally observed after neutrophil accumulation. Several neutrophil chemoattractants have been characterized in recent years; the best known are the anaphylatoxin C5a (1), formylmethionyl peptides of bacterial origin (2), plateletactivating factor (PAF; 3),1 and leukotriene B4 (LTB4; 4). These stimuli have different origins and modes of formation, and their occurrence in disease must thus be expected to vary in accord with the underlying pathophysiological process. C5a is formed upon complement activation via the classical pathway after interaction of microorganisms with antibodies or the formation of immune complexes, or via the alternative pathway after the nonimmune recognition of foreign materials. In bacterial infections, on the other hand, formylmethionyl peptides (which are released by the microorganisms) are likely to be the major attractants. PAFand LTB4 are of special interest because they can be generated by the neutrophils themselves and may thus function as autoor paracrine amplifiers of the responses elicited by other stimuli (5). It has been shown that CSa, formylmethionyl peptides, PAF, and LTB4 act via unrelated receptors, suggesting that neutrophil recruitment can result from the concerted action of multiple stimuli.

Risk of infectious complications in patients taking glucocorticosteroids.

Abstract: The association between corticosteroid therapy and subsequent infections was calculated by pooling data from 71 controlled clinical trials. The overall rate of infectious complications was 12.7% in the 2,111 patients randomly allocated to systemic corticosteroids and 8.0% in the 2,087 controls (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3-1.9; P less than .001). The risk of infection was particularly high in patients with neurologic diseases (RR, 2.8; 95% CI, 1.9-4.3; P less than .001) and less pronounced in patients with intestinal (RR, 1.4; 95% CI, 1.1-1.7; P = .02), hepatic (RR, 1.4; 95% CI, 0.9-2.3; P = .25), and renal (RR greater than 1; P = .03) diseases. The rate was not increased in patients given a daily dose of less than 10 mg or a cumulative dose of less than 700 mg of prednisone. With increasing doses the rate of occurrence of infectious complications increased in patients given corticosteroids as well as in patients given placebo, a finding suggesting that not only the corticosteroid but also the underlying disease state account for the steroid-associated infectious complications observed in clinical practice.

Inverse correlation between plasma vitamin E and mortality from ischemic heart disease in cross-cultural epidemiology.

Abstract: Essential antioxidants were determined in plasma of middle-aged men representing 16 European study populations, which differed sixfold in age-specific mortality from ischemic heart disease (IHD). In 12 populations with \"common\" plasma cholesterol (5.7-6.2 mmol/L) and blood pressure, both classical risk factors lacked significant correlations to IHD mortality, whereas absolute levels of vitamin E (alpha-tocopherol) showed a strong inverse correlation (r2 = 0.63, P = 0.002). Evaluating all populations, cholesterol and diastolic blood pressure were moderately associated, but their correlation was inferior to that of vitamin E. In stepwise regression and multiple regression analysis, mortality was predictable to 62% by lipid-standardized vitamin E, to 79% by vitamin E and cholesterol, to 83% after inclusion of lipid-standardized vitamin A (retinol), and to 87% by all the above parameters plus blood pressure. Thus, in the present study the cross-cultural differences of IDH mortality are primarily attributable to plasma status of vitamin E, which might have protective functions.

A combination of platelet-derived and insulin-like growth factors enhances periodontal regeneration.

Abstract: The combination of platelet-derived growth factor (PDGF) and insulin-like growth factor one (IGF-1) has previously been shown to enhance repair of soft tissue wounds. Here we report initial observations following application of PDGF and IGF-1 to periodontitis-affected teeth in beagle dogs. 1 micrograms of PDGF and IGF-1 in an aqueous gel was applied to the root surfaces of test teeth following open flap debridement. Control sites received the gel alone. Block biopsies of the teeth and surrounding bone were taken 2 weeks after treatment. Histologic analyses of control specimens revealed a long junctional epithelial attachment, and no new bone or cementum formation. In contrast, growth factor treated sites exhibited significant amounts of new bone and cementum formation. A nearly continuous layer of osteoblasts lined the newly formed bone, and there was a dense cellular "front" at the coronal extent of the new bone. These preliminary results suggest that in vivo application of the combination of PDGF and IGF-1 may enhance regeneration of the periodontal structures.

Physiological mechanisms adopted by chondrocytes in regulating longitudinal bone growth in rats.

Abstract: 1. Chondrocyte activities within growth plate cartilage are the principal determinants of longitudinal bone growth, and it was the aim of this investigation to assess how these cell activities are modulated under various growth rate conditions. Using proximal tibial growth plates from rats of different ages, growth rate was determined by fluorochrome labelling and incident light fluorescence microscopy. Various cellular parameters contributing to longitudinal bone growth were quantified by light microscopic stereology. The size of the proliferating cell population ('growth fraction') was estimated by autoradiography (using [3H]thymidine labelling). 2. A comparison between data for suckling (21-day-old) and fast-growing (35-day-old) rats revealed that growth acceleration is achieved almost exclusively by cell-shape modelling, namely by an increase in final cell height and a decrease in lateral diameter, whereas final cell volume and surface area are slightly reduced. Cell proliferation rate in the longitudinal direction and net matrix production per cell remain unchanged. The physiological increase in linear growth rate thus appears to be based principally upon a controlled structural modulation of the chondrocyte phenotype. On the other hand, a physiological reduction in growth rate (i.e. growth deceleration) effected during the transition from pre-puberty (35-day-old rats) to maturity (80-day-old rats) is achieved by simultaneous decreases in several chondrocyte parameters, including cell height (i.e. phenotype modulation), cell volume and proliferation rate (in the longitudinal direction). However, chondrocytes continue to produce matrix at a level comparable to that attained during the period characterized by high growth rates (i.e. at 21 and 35 days). Cartilage matrix thus appears to play a subordinate role in regulating longitudinal bone growth rate. The duration of the hypertrophic cell activity (i.e. phenotype modulation) phase remains constant (at approximately 2 days) under the various growth rate conditions. 3. The findings presented in this study indicate that measurement of bulk parameters such as [35S]sulphate incorporation into matrix components, [3H]thymidine uptake by cells and growth plate height are of limited value as estimators of longitudinal bone growth, since changes in the parameters that these measurements quantify bear little relationship to changes in linear growth rate, and may be useful only as indicators of total growth plate activity.

Oxidative capacity of muscle and mitochondria: correlation of physiological, biochemical, and morphometric characteristics

Abstract: The oxidative capacity of cat skeletal muscles (soleus, gracilis, and gracilis chronically stimulated for 28 days) was derived from the total mitochondrial content in the muscle, the surface area of mitochondrial inner membranes, and respiratory activities of isolated mitochondria. Mitochondrial content was estimated by standard morphometry. The surface area of mitochondrial inner membranes per unit volume of mitochondria was estimated by a stereological method. The respiratory activities of isolated mitochondria were measured biochemically, using pyruvate/malate, glutamate/malate, succinate, or cytochrome c as substrate. Structurally and functionally, mitochondria from the three muscle types showed nearly identical characteristics. Oxidative activity was dependent on substrate; with succinate, 5.8 ml of O2 per min per ml of mitochondria was the rate most likely to represent physiological conditions. Oxidative activities of 3.1 ml.min-1.ml-1 with pyruvate/malate and 14.5 ml.min-1.ml-1 with cytochrome c as substrates were theoretical lower and upper bounds. The oxidative capacity of each of the three muscles was thus in direct proportion to the total volume of mitochondria in the muscle. The respiratory capacity of isolated mitochondria was very near to the maximal oxygen uptake rate of mitochondria that is commonly estimated in intact muscles of a wide variety of animals.

Subtrochanteric fractures of the femur. Results of treatment with the 95 degrees condylar blade-plate.

Abstract: The results were retrospectively analyzed of 47 subtrochanteric fractures of the femur treated with a 95° condylar blade-plate to establish whether two different surgical techniques yielded different results. Before 1981, treatment consisted of extensive visualization of the fracture lines, permitti

Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer

Abstract: We compared a single perioperative cycle of adjuvant combination chemotherapy with no adjuvant treatment in a randomized trial (Ludwig Trial V) including 1275 patients with breast cancer who had no axillary-node metastases. The chemotherapy was administered on days 1 and 8, beginning within 36 hours after mastectomy, and consisted of cyclophosphamide, methotrexate, fluorouracil, and leucovorin. At a median follow-up of 42 months, the mean four-year disease-free survival (+/- SE) was 77 +/- 2 percent among the patients who received chemotherapy perioperatively, as compared with 73 +/- 2 percent among the patients who received no adjuvant treatment (hazard ratio, 0.77; 95 percent confidence interval, 0.61 to 0.98; P = 0.04). An advantage was observed for both premenopausal and postmenopausal women. The magnitude of the treatment effect was largest among patients with no or low estrogen-receptor content in the primary tumor. We conclude that chemotherapy modifies the post-operative course of node-negative breast cancer. Further trials to investigate an optimal selection of patients and treatments should be regarded as the best available therapeutic approach.

Effect of N-acetylcysteine on plasma cysteine and glutathione following paracetamol administration.

Abstract: The effect of oral N-acetyl-L-cysteine (NAC) on plasma sulphhydryls has been studied in healthy volunteers. Following NAC 30 mg.kg-1, total NAC in plasma (i.e. free NAC and NAC as disulphides) reached a median peak concentration of 67 nmol.ml-1 within 45 to 60 min, and disappeared with an apparent half-life of 1.3 h. Only a fraction of total NAC (AUC 163 nmol.ml-1.h) was in the form of free NAC (AUC 12 nmol.ml-1.h, peak concentration 9 nmol.ml-1). Free cysteine was markedly increased (peak increment 49 nmol.ml-1; AUC 80 nmol.ml-1.h). Total cysteine and free and total glutathione in plasma were unchanged. Following the administration of 2 g paracetamol plasma cysteine and glutathione decreased (median decrement in AUC over 3 h was 5.1 nmol.ml-1.h and 3.8 nmol.ml-1.h, respectively). In contrast, the administration of 2 g NAC together with paracetamol resulted in an increase in the AUC of cysteine (+29.2 nmol.ml-1.h) and glutathione (+4.6 nmol.ml-1.h). The data show that NAC leads to a marked increase in circulating cysteine, in part by reacting with cystine and thereby forming mixed disulphides with cysteine and releasing free cysteine as shown in vitro. NAC had no effect on plasma glutathione in the absence of increased stress on the glutathione pools. However, NAC supports glutathione synthesis when the demand for glutathione is increased, as during the metabolism of paracetamol.

Natural Heterogeneity of Thyroid Cells: The Basis for Understanding Thyroid Function and Nodular Goiter Growth

Abstract: IN THE recent past, some of the mechanisms have been unraveled which produce the characteristic heterogeneity of shape and function among the newly generated follicles arising in the process of transformation of a normal thyroid into a multinodular goiter (1–5) (Fig. 1). The two basic findings which paved the way toward an understanding of the processes that create diversity in the offspring of a growing cell population of a normal organ are: 1. The follicular cells of a normal thyroid are not identical among themselves, but rather they have a highly individual metabolic outfit which is transferred from the mother cell to its progeny. 2. Daughter follicles produced from mother follicles during goitrogenesis arise from a few predestined follicular cells endowed with an inherited propensity to replicate at higher than average rates. From these two premises a simple syllogism leads to the conclusion that whenever a thyroid gland is forced to grow, i.e. to generate new follicles, the daughter follicles may di...

Three Years' Experience with an Ileal Low Pressure Bladder Substitute

Abstract: At the beginning of this century it was realised that peristalsis would cause incontinence if bowel was used for augmentation or substitution of the bladder. Trans-section of the antimesenteric border and cross-folding of the intestinal segments (Goodwin's cup-patch technique) is an efficient means of solving this problem and has been successfully used in the Kock pouch. We anastomosed the ileal low pressure reservoir to the membranous urethra in 22 male patients following radical cystoprostatectomy for bladder cancer. The mean observation time was 16 months (range 3-36). The capacity of the bladder substitute increased with time, the average being 450 ml after 6 months. In the first 4 patients with a short (2-5 cm) intestinal segment between the pouch and the urethra, micturition was prolonged, residual urine varied from 50 to 300 ml and bacteriuria was found. Occasional expulsions of several ml of urine were caused by peristalsis within this short tubular segment. In the following 18 patients, the low pressure reservoir was anastomosed directly to the membranous urethra. Micturition was good, with no notable residual urine, no bacteriuria and no paroxysmal urinary incontinence. However, a safety pad is used by half of the patients because once or twice a week, mainly at night, a few ml of urine may be lost. No significant changes in serum electrolytes, bicarbonate or creatinine were noted. With the three different antireflux techniques used, no obstructive or inflammatory changes in the upper urinary tracts were found, although no long-term antibiotic prophylaxis was given.

Effects of the neutrophil-activating peptide nap-2, platelet basic protein, connective tissue-activating peptide iii,and platelet factor 4 on human neutrophils

Abstract: Platelet basic protein (PBP), connective tissue-activating peptide III (CTAP-III), and platelet factor 4 (PF-4) were purified from human platelet release supernatants by heparin-Sepharose ion-exchange and reversed-phase HPLC, and their neutrophil-activating effects were compared with those of NAP-2, a peptide of 70 amino acids corresponding to part of the sequence of PBP (1) and with sequence homology to NAF/NAP-1. NAP-2-induced elastase release and a rise in cytosolic free Ca2+ at concentrations between 0.3 and 100 nM, and neutrophil chemotaxis at concentrations between 0.03 and 10 nM. It was half as potent as NAF/NAP-1 in inducing exocytosis but showed the same activity in the other responses. By contrast, only minimal if any effects were obtained with PBP, CTAP-III, and PF-4 up to 100 nM. NAP-2 thus appears to behave like a typical chemotactic receptor agonist. It could be generated from PBP and/or CTAP-III released from activated platelets and lead to the accumulation of neutrophils in platelet aggregates.

Bisphosphonates: A New Class of Drugs in Diseases of Bone and Calcium Metabolism

Abstract: The bisphosphonates are a new class of drugs which have been developed in the past two decades for use in various diseases of bone, tooth, and calcium metabolism Three are on the market today, while others are under clinical or preclinical investigation This chapter will cover chemical and experimental aspects as well as clinical applications of these compounds Literature is essentially limited to one reference, usually the original report For two recent reviews, weighted somewhat differently and with more extensive references, see Fleisch (1983) and Francis and Martodam (1983)

Fractures of the odontoid process. Treatment with anterior screw fixation.

Abstract: Seventeen cases of Anderson and D'Alonzo Type II and "shallow" Type III fractures of the odontoid, treated by anterior screw fixation, were reviewed and compared with previously published series of fractures treated nonoperatively, treated with posterior C1-C2 arthrodeses, and with anterior screw fixation series. Although the nonunion rate (12%) and major complication rate (24%) in the present series were higher than those previously reported, the combined rates of all anterior screw fixation series were comparable to those of posterior C1-C2 arthrodesis studies. Three of the complications presented occurred in cases that in retrospect were inappropriate for the use of this technique. These included a verified nonunion and 2 individuals with markedly osteoporotic bone and unfavorable fracture type. Because of the difficulty involved in mastering anterior screw fixation of the dens, its use should be limited to experienced spine surgeons with the appropriate surgical facilities.

Lacustrine carbonates and pedogenesis: sedimentology and origin of palustrine deposits from the Early Cretaceous Rupelo Formation, W Cameros Basin, N Spain

Abstract: The Berriasian Rupelo Formation of the W Cameros Basin consists of a 2–200 m thickness of marginal and open lacustrine carbonate and associated deposits. Open lacustrine facies contain a non-marine biota with abundant charophytes (both stems and gyrogonites), ostracods, gastropods and rare vertebrates. Carbonate production was mainly biogenic. The associated marginal lacustrine (‘palustrine’) facies show strong indications of subaerial exposure and exhibit a wide variety of pedogenic fabrics. Silicified evaporites found near to the top of the sequence reflect a short hypersaline phase in the lake history. The succession was laid down in a low gradient, shallow lake complex characterized by wide fluctuations of the shoreline. Carbon and oxygen stable isotope analyses from the carbonates show non-marine values with ranges of δ13 from − 7 to − 11‰and δ18 from − 3 to − 7.5‰. Differences in the isotopic composition of open lacustrine carbonates are consistent with sedimentary evidence of variation in organic productivity within the lake. Analyses from the entire sample suite plot on a linear trend; isotopic compositions become lighter with increasing evidence of pedogenic modification. This suggests progressive vadose zone diagenesis and influence of meteoric waters rich in soil-derived CO2. The stable isotope data thus support evidence from petrography and facies relations that ‘palustrine’limestones form through pedogenic modification of lake carbonates.

Neuropathology of the acquired immune deficiency syndrome (AIDS): a report of 135 consecutive autopsy cases from Switzerland.

Abstract: Neuropathological changes were studied in a consecutive autopsy series of 135 cases, comprising 73% of all patients who died of AIDS in Switzerland between April 1981 and December 1987. Central nervous system involvement was found in 119 patients (88%), 19 of which had multiple concomitant intracerebral lesions. Among the non-viral opportunistic infections, encephalitis due toToxoplasma gondii was most frequent and occurred in 35 patients (26%), followed by central nervous system infection withCryptococcus neoformans, which was found in five patients (4%). Cytomegalovirus (CMV) encephalitis was present in 14 patients (10%). Disseminated microglial nodules without morphological or immunocytochemical evidence of CMV was encountered in 18 patients (13%). However, in all but two of these patients there was evidence of extracerebral CMV infection, suggesting that CMV was responsible for these nodular encephalitides. Nine patients (7%) had progressive multifocal leukoencephalopathy (PML); in five of these, demyelination was associated with extensive tissue destruction and cyst formation. HIV-associated encephalopathy was observed in 21 patients (16%) and showed two characteristic morphological patterns: progressive diffuse leukoencephalopathy (PDL) and multifocal giant cell encephalitis (MGCE). PDL was observed in 13 cases and characterized by diffuse pallor and gliosis of the cerebral and cerebellar white matter with scattered multinucleated giant cells, but without significant inflammatory response. MGCE was found in eight patients and characterized by clusters of numerous multinucleated giant cells, rod cells, macrophages, lymphocytic infiltrates and occasional necroses. In our view, PDL and MGCE represent the two opposite variants of HIV-induced encephalopathies, with overlapping intermediate manifestations.

The neutrophil-activating peptide NAF/NAP-1 induces histamine and leukotriene release by interleukin 3-primed basophils.

Abstract: IgE-independent mediator release from basophils is considered an important event in inflammation, particularly in nonallergic immediate hypersensitivity and in allergic late-phase reactions. This study demonstrates that after exposure to IL-3, basophils release histamine and leukotrienes in response to the neutrophil-activating peptide NAF/NAP-1. Thus, the sequential action of two pure cytokines can promote basophils mediator release. In the presence of IL-3, NAF/NAP-1 functions like a "histamine-releasing factor" and may therefore not only induce cellular infiltration but also provoke symptoms of hypersensitivity reactions.

Microsurgical reoperation following lumbar disc surgery Timing, surgical findings, and outcome in 92 patients

Abstract: ✓ Ninety-two patients who underwent microsurgical reoperation for persistent or new complaints following initial lumbar intervertebral disc surgery were evaluated retrospectively. Sixty percent of all pain relapses occurred within 1 year following the first operation; thereafter, the probability of a relapse declined steadily and was as low as 0.1% per year between 5 and 20 years. The results of microsurgical reoperation in terms of pain relief and working capability were considered “excellent” in 22% of patients, “good” in 30%, and “satisfactory” in 29%. Thus, 81% of the patients could be considered as treated successfully and in 19% the result was not successful. The most common intraoperative findings were: a true recurrence at the same level in 43% of cases, a new herniation at another level in 15%, and a small recurrent fragment embedded in epidural fibrosis in 23%. Five percent of patients had severe epidural fibrosis as the only pathology. In 15%, reoperation was performed within 1 month to treat p...

Submillimeter optical reflectometry

Abstract: The development of optical reflectometers with a spatial resolution in the submillimeter range is reviewed. Optical time-domain reflectometers (OTDRs) and optical low-coherence reflectometers (OLCRs) for nondestructive diagnostics of waveguide devices are discussed. Techniques, system performances, and experimental results are discussed for OTDRs and for OLCRs. Fields of applications for these techniques are indicated, and some preliminary conclusions are presented. A dynamic range of approximately 100 dB and a spatial resolution in the range of 10-60 mu m were achieved with both types of reflectometers. Nondestructive diagnostics on waveguide components and integrated optics circuits are feasible at these performance levels. >

The calcium pump of the surface membrane and of the sarcoplasmic reticulum.

Abstract: The molecular architectures of SMP and SRP differ, yet the functional analogies between CAM-associated SMP and SRP are numerous. Most of the divergences observed may have their root in different behavior during dephosphorylation (see Table 1).