[Low dosage laser has no effect on pain].
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Biomedical subjects
Publications and source records attributed to H Nielsen.
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Short chain fatty acids (acetic, propionic and butyric) were instilled into the rectum of patients who had undergone Hartmann's procedure. The following parameters were examined before and after a 2-week treatment period with short chain fatty acids (100 ml twice daily at a total concentration of 150 mM): (1) microcirculatory effects in vivo using a laser Doppler flow technique, and (2) morphometrical changes in mucosal biopsies. The following parameters were significantly increased in all patients after treatment: (1) mucosal blood flow, (2) the fractional crypt cell epithelium plus surface epithelium volume in relation to total tissue volume down to the muscularis mucosa, (3) nuclear volume in the crypt and the surface epithelium, and (4) the fractional nuclear volume to total cell volume in the crypt and the surface epithelium. These data suggest that short chain fatty acids in the human colon have trophic and vasodilatory effects.
The pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(and -6)-carboxyfluorescein (BCECF) was used to measure intracellular pH (pHi) in rat mesenteric resistance arteries (internal diameter 152-289 microns) mounted in an isometric myograph for simultaneous measurements of force. Extracellular pH was measured using a pH-sensitive electrode. Experiments were designed to test contractile electrode. Experiments were designed to test contractile effects of changes in carbon dioxide tension (PCO2) on vessels precontracted with noradrenaline. An acute increase in PCO2 caused acute intracellular acidification and potentiation of contractility. The longer-term effect, however, was recovery of intracellular pH and vaso-relaxation. Opposite changes in tension and intracellular pH were observed by decreasing PCO2. Qualitatively similar changes in contractility were observed in response to changes in pHi induced by NH4Cl. Thus, effects on vessels precontracted with noradrenaline were biphasic. In another set of experiments, the amplitude of the transient responses to 50 microM noradrenaline in calcium-free media was significantly augmented by an increase in the PCO2, whereas the response to 5 microM noradrenaline 1 min after readdition of calcium to the medium was depressed by the rise in PCO2. These data suggest that acute intracellular acidification causes acute tension development and are consistent with the possibility that the biphasic response to changes in noradrenaline-induced contractility caused by changes in PCO2 may be ascribed to differential effects on calcium mobilisation processes.
Treatment with certain metal chelating agents causes a time-dependent bleaching of the Neo-Timm staining pattern of zinc visualized in synaptic vesicles. In the present study, the extent and time course of the reversible chelation of hippocampal vesicular zinc was investigated following intrahippocampal injection of the chelating agent diethyldithiocarbamate. The carbamate (1.0 microliters 45 mg ml-1, 200 mM) was injected unilaterally into the hippocampal region of adult rats, which were allowed to survive 15 min-6 h before sacrifice. Control animals either received injections of distilled water or were untreated. Computerized optical densitometry was performed on cryostat sections of brains stained with the Neo-Timm method. Injection of diethyldithiocarbamate into the hippocampal region resulted in a localized bleaching of the Neo-Timm staining pattern. The extent of the bleaching varied with time being most pronounced at 15 min survival and gradually decreasing with time. After 6 h survival, a faint bleaching of the injected hippocampal region was barely seen. Computerized optical densitometry confirmed and extended the observations providing a semi-quantitative measure of zinc in synaptic vesicles.
A retrospective survey of non-typhoid Salmonella bacteraemia in the period 1984 to 1988 was carried out by the five departments of clinical microbiology in Greater Copenhagen. A total of 168 patients were identified. A gradual increase was observed from 11 cases in 1984 to 58 cases in 1988. The corresponding incidence per 100,000 inhabitants in Copenhagen rose from 0.9 in 1984 to 5.0 in 1988. During the same period the total registered incidence of human Salmonella infections in Denmark increased from 17.6 to 67.4 per 100,000 inhabitants. The serotype most often isolated from bacteraemic patients was Salmonella dublin followed by Salmonella enteritidis and Salmonella typhimurium. Salmonella dublin demonstrated enhanced invasive and pathogenic properties. Predisposing factors were present in 56% of the patients; the most common was malignant disease. A fatal or complicated course of the bacteraemia was observed more frequently in patients with underlying diseases than in persons who had previously been healthy. A total of 17% of the patients died; one-fifth of these had a ruptured aortic aneurysm. It is concluded that the substantial increase in the number of cases and the often serious course taken by the infection demonstrate a need for increased efforts at prophylaxis.
A large series of rabbit hippocampal Neo-Timm stained sections were manually aligned, digitized, and by a modified median filtration noise reduced and reconstructed into a three-dimensional object. From the presented simulated grey tone cuts of this object, the reader may assemble a rabbit hippocampal model, that spatially illustrates its anatomy.
Mesenteric resistance arteries (internal diameter 174-337 microns) from rats, rabbits, pigs, and humans were isolated and mounted in a myograph. In all preparations, phenylephrine (alpha 1-adrenoceptor agonist) evoked concentration-dependent contractions that were antagonized by prazosin (alpha 1-adrenoceptor antagonist). B-HT 933 (alpha 2-adrenoceptor agonist), however, did not evoke contractions in any rat or rabbit vessels. In contrast, this agonist elicited contractions in some (five of 15) porcine and all (18) human vessels; in the vessels responsive to B-HT 933, the maximum responses amounted to 53 +/- 7 and 79 +/- 6%, respectively, of the responses to high potassium. The affinities of yohimbine (alpha 2-adrenoceptor antagonist) for the receptors mediating responses to B-HT 933 were 7.46 +/- 0.13 (pKB) and 7.57 +/- 0.10 (pA2), respectively. Prazosin (10(-8) M) antagonized the responses to norepinephrine in all preparations, whereas yohimbine (10(-7) M) caused significant inhibition of these responses in human vessels only; moreover, the inhibition in these vessels of the responses to norepinephrine caused by the combination of these two antagonists was greater than the antagonism caused by either antagonist alone. These results suggest the presence of postjunctional alpha 1-adrenoceptors that are involved in responses to norepinephrine in mesenteric resistance arteries from all species examined. Functional, postjunctional alpha 2-adrenoceptors appear to be present in porcine and human vessels, but this receptor seems to be involved in responses to norepinephrine in human vessels only.
Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to inhibit the chemotaxis and enhance the oxidative burst response of human neutrophils in vitro. The present study describes the effect of recombinant GM-CSF on the neutrophil and monocyte function in patients with lymphoma undergoing GM-CSF treatment. Patients with either Hodgkin's or non-Hodgkin's lymphoma were treated with various dosages (2-16 micrograms kg-1 body weight per day for 5 days) of rhGM-CSF by intravenous or subcutaneous route. Prior to and on day 5 of rhGM-CSF treatment, neutrophil and monocyte chemotaxis and chemiluminescence responses to f-Met-Leu-Phe, zymosan activated serum (ZAS) and opsonized zymosan (OZ) were determined. It was observed that chemotactic response of neutrophils to f-Met-Leu-Phe and ZAS was reduced, whereas the chemiluminescence response of both cell types to f-Met-Leu-Phe and zymosan was enhanced by up to 43-fold. rhGM-CSF treatment did not affect degranulation of the neutrophils as measured by release of vitamin B12 binding protein. Degree of modulation of neutrophil and monocyte function by rhGM-CSF was independent of rhGM-CSF dosages administered. These data suggest that phagocytic defence system may be enhanced by GM-CSF treatment and that this cytokine may be a useful therapeutic adjunct in compromised patients.
A total of 87 patients with mild or moderate degree of dementia of the Alzheimer type (AD) or vascular dementia (VD) was identified (DSM-III criteria), and their cognitive capacity was evaluated by means of rating scales and psychometric tests. Three years later 30 patients (34%) were dead. Significantly more VD than AD patients died. Eight of the survivors declined to participate in a follow-up study, and 1 patient was excluded by mistake. Of the survivors, 17 had indisputably suffered cognitive decline during the follow-up period (4 VD and 13 AD, 35%). In the case of 11 patients (2 VD and 9 AD) cognitive decline remained doubtful, and 20 patients (9 VD and 11 AD, 42%) underwent no intellectual deterioration during the follow-up period. The results underline the problems of early diagnosis of dementia according to DSM-III criteria. For both sexes a high ischemia score and a low body mass index predicted death. A low score on a verbal fluency test predicted death for men but not for women, and a high difference between systolic and diastolic blood pressure increased the risk of death for men but not for women.
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Multiple myeloma (MM) is characterized by an increased susceptibility to infections and to other malignancies. Selected related immune functions were studied. Spontaneous and interleukin-2-stimulated natural killer (NK) cell activities were normal in 19 patients with MM compared with 62 controls. In contrast, interferon-stimulated NK cells had a significantly lower increase in activity in MM than in controls. The normal improvement in lytic NK cell activity after addition of indomethacin to the mononuclear cell cultures (to inhibit prostaglandin-mediated suppression) was not observed in cultures from MM patients. As reported for other lymphoproliferative disorders, the levels of soluble interleukin-2 receptors in serum were significantly higher in MM (600 U/ml median value) compared with controls (317 U/ml median value), P less than 0.0001, and the concentration of interleukin-2 receptors was significantly correlated with the concentration of monoclonal immunoglobulin in serum. Blood monocyte chemotactic responsiveness was significantly lower in MM patients with both zymosan-activated serum and f-Met-Leu-Phe as cytotaxins, suggesting reduced ability to accumulate at inflammatory foci. In contrast, release of reactive oxygen radicals, believed to be associated with the killing ability of monocytes, was normal after in vitro stimulation.
Human resistance arteries (144-332 microns diam) from colon, pericardial fat, and skeletal muscle were mounted in a myograph for measurements of isometric contractions under conditions of partial depolarization by potassium chloride. In all preparations, both phenylephrine (alpha 1-selective agonist) and B-HT 933 (alpha 2-selective agonist) evoked concentration-dependent contractions that were antagonized by the alpha 1-selective antagonist prazosin (10(-8) M) and the alpha 2-selective antagonist yohimbine (10(-7) M), respectively. The affinities (expressed as pKB values) of prazosin for the receptor mediating the responses to phenylephrine were 8.88-9.41, whereas the affinities of yohimbine for the receptor mediating the responses to B-HT 933 were 7.71-7.97. Norepinephrine (mixed alpha 1-agonist/alpha 2-agonist) also elicited concentration-dependent responses that were modestly, but significantly, antagonized by prazosin alone and yohimbine alone at the above-mentioned concentrations. The two antagonists in combination, however, effectively antagonized the responses to this agonist. These findings strongly suggest the presence of functional, postjunctional alpha 1- and alpha 2-adrenoceptors in isolated human resistance arteries from colon, pericardial fat, and skeletal muscle and that responses to norepinephrine in these vessels are mediated by both alpha-adrenoceptor subtypes.
118 episodes of fungemia occurring at Rigshospitalet, Copenhagen, between 1984 and 1988 were reviewed retrospectively. Underlying diseases in the patients were dominated by malignancies, primarily hematological disorders, and intraabdominal diseases requiring major abdominal surgery. Predisposing factors identified in the patients were ongoing antibacterial chemotherapy (83%), central venous catheters (72%), major abdominal surgery (39%), and neutropenia (32%). 120 fungal strains were isolated, of which 88 (73%) were Candida albicans, 23 strains representing 8 other Candida species were also isolated, as were 9 strains belonging to 7 other fungal genera. There were only 5 strains resistant to 5-fluorocytosine (MICs greater than or equal to 25 mg/l), and no strain was resistant to amphotericin B. Treatment with antifungal agents was given in 78 patients, generally a combination of amphotericin B and 5-fluorocytosine. In 14 patients (all non-hematological) the only treatment was removal of a permanent central venous catheter. The outcome was poor in patients with hematological disorders (mortality 76%), whereas patients with malignant and non-malignant intraabdominal diseases had a mortality of 35%. All patients with a permanent central venous catheter as the only risk factor recovered rapidly after removal of the catheter.
The in vitro effect of Pseudomonas aeruginosa elastase on human monocyte function was examined. Mononuclear cells isolated from the peripheral blood of healthy individuals were incubated with various concentrations of elastase, and the chemotactic activity and chemiluminescence response of these cells were measured after washing the cells free of the enzyme. Elastase at concentrations of 0.1 micrograms/ml and higher inhibited the chemotactic activity of monocytes towards F-Met-Leu-Phe and zymosan-activated serum. The inhibition of chemiluminescence response was observed at as low as 0.125 micrograms/ml elastase. Monocytes/macrophages are known to be involved in the inflammation observed in the lungs of patients infected by P. aeruginosa. The inhibition of monocyte function by elastase may serve as an escape mechanism for this bacterium from these cells.
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The recent development of rDNA vectors for transformation of Tetrahymena combined with improved microinjection technology should lead to a renewed interest in this organism. In particular, the rDNA itself constitutes an attractive system for biochemical studies. The rDNA is amplified to a level of 2% of the total DNA and exists as extrachromosomal molecules. Furthermore, the rDNA is homogeneous in sequence because it is derived from a single gene during sexual reorganization. In order to facilitate studies of this molecule, we report here a compilation of previously published sequence information together with new sequence data that completes the entire sequence of the 21 kb rDNA molecule.
One hundred and twenty Danish homosexual men were enrolled to characterize risk factors for anal type-specific human papillomavirus (HPV) expression and to examine its association with anal epithelial atypia. Detection of HPV strongly correlated with immunosuppression measured by T-lymphocyte subset markers and rose nearly linearly from 7.3% among subjects with CD4/CD8 ratios above 1.0 to 35.3% among those with a ratio below 0.4 (p trend = 0.003). No association was found between presence of HPV and a wide range of lifestyle factors including number of sex partners/year, smoking, alcohol consumption and illegal drug intake. However, self-reported history of anal condyloma in the past year was correlated with HPV (p less than 0.001). Simultaneous testing for presence of HPV in the oral cavity showed evidence of HPV 16,18 and 31,33,35. Anal smears were abnormal in 19.5% of the men and correlated strongly with presence of HPV (OR = 6.1, p less than 0.001). Type-specific associations were found with HPV 31/33/35 (OR = 8.5) and HPV 16/18 (OR = 3.1) only. The association remained significant after adjusting for immune status. Overall, HPV was detected in 50% of the cases with abnormal smears. However, HPV was found in all subjects with abnormal smears and a CD4/CD8 ratio below 0.4, compared to only 3 of 14 subjects with abnormal smears and a ratio greater than or equal to 1.3. In conclusion, (1) HPV may be missed in a substantial number of infected subjects with a normal immune system. This may have an impact on studies trying to describe risk factors for HPV transmission and its correlation with cancer development. (2) The finding of HPV 16,18 and 31,33,35 in the oral cavity makes oral-genital sexual activity at least a hypothetical route of transmission for these HPV types. (3) HPV appears to play a central role in the development of anal epithelial abnormality.
The quartz content of ordinary building materials such as concrete, mortar and bricks is 10-50%. The extension of concrete building which has occurred since 1960 and the subsequent repairs and preparation by means of mechanical tools result in increased concentrations of dust containing quartz. Measurements at various types of work in Danish building sites reveal that the quantity of respirable quartz constitutes 0.16-1.8 mg/m3 (limit 0.1 mg/m3). Corresponding figures are found in investigations from abroad. Cases of silicosis have been reported among builders abroad and, in Denmark, only few cases of occupational dust lung conditions have been notified to the Workers' Supervision Authorities. Whether or not quartz in dust at building sites also causes an increase in the occurrence of cancer of the lung, as is the case in sandstone workers exposed to pure quartz, has not yet been proved. The latent period of several decades for the development of silicosis is such that it may well be feared that the cases now reported are only the beginning of increased occurrence of the disease in coming years among particularly exposed concrete workers, bricklayers, unskilled workers, electricians, joiners and carpenters. Relevant technical methods have already been developed to limit exposure to quartz-containing dust at building sites. Prophylactic measures should be accelerated.