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Biomedical subjects

J Hansen

Publications and source records attributed to J Hansen.

At least 199 records · Page 11Linked to original sources

Muscle metaboreflex triggers parallel sympathetic activation in exercising and resting human skeletal muscle.

Activation of a metabolically generated reflex in exercising skeletal muscle (muscle metaboreflex) in humans is known to trigger increases in sympathetic nerve activity (SNA) to resting skeletal muscles. In seven healthy human subjects, to determine whether this reflex mechanism also increases SNA to the exercising muscles, we recorded muscle SNA with microelectrodes in the right peroneal nerve and in fascicles of the left peroneal nerve selectively innervating the exercising muscles of the left foot. Subjects performed static toe extension at 20% maximal voluntary contraction alone or in combination with foot ischemia. Only static toe extension at 20% MVC during ischemia activated the muscle metaboreflex. This paradigm caused increases in SNA to exercising muscle that paralleled those to the resting muscles: during the first minute of exercise SNA was unchanged, but during the second minute SNA increased from 29 +/- 2 to 38 +/- 2 bursts/min (P < 0.05) to the exercising muscles and from 30 +/- 3 to 40 +/- 2 bursts/min (P < 0.05) to the resting muscles. These bilateral increases in SNA were maintained when metaboreflex activation was sustained by postexercise foot ischemia. In conclusion, these data provide neurophysiological evidence that the muscle metaboreflex evokes parallel sympathetic activation in exercising and resting human skeletal muscle.

Adult↗

Is nitric oxide involved in the tonic inhibition of central sympathetic outflow in humans?

Recent studies in experimental animals have advanced the concept that neuronal nitric oxide is an important component of the signal transduction pathways that tonically restrain sympathetic vasoconstrictor outflow from the brain stem. To determine whether or not this concept can be extended to the control of sympathetic outflow in humans, we recorded muscle sympathetic nerve activity (microelectrodes, peroneal nerve) in healthy human subjects during intravenous infusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) (3.6 to 6.7 mg/kg). The major new finding is that during intravenous L-NMMA mean arterial pressure increased (10 +/- 2 mm Hg, P < .05), whereas heart rate and sympathetic nerve activity decreased (P < .05) by 10 +/- 2 beats per minute and 61 +/- 5%, respectively. These reflex decreases were indistinguishable from those produced when blood pressure was increased comparably with phenylephrine, an internal vasoconstrictor control. When the L-NMMA-induced increase in blood pressure was attenuated experimentally to minimize baroreflex activation, sympathetic nerve activity and heart rate were unchanged. Furthermore, during infusion of L-arginine (323 to 513 mg/kg IV) to increase nitric oxide synthesis, mean arterial pressure decreased (12 +/- 2 mm Hg, P < .05), but heart rate and sympathetic nerve activity increased (P < .05) by 11 +/- 2 beats per minute and 98 +/- 27%, respectively. Thus, our experiments in humans provide no support for the emerging concept that nitric oxide is involved in the tonic restraint of central sympathetic outflow.

Adult↗

Cancer morbidity among Danish female pharmacy technicians.

OBJECTIVES: Pharmacy technicians maintain a substantial production and packing of pharmaceuticals and other chemicals, many of which are carcinogens. This study reports on cancer incidence among Danish female pharmacy assistants and dispensers. METHODS: Altogether, 8499 compulsory members were identified in the archives of the Association of Danish Pharmacy Technicians and followed through the files of the Danish Cancer Registry (1970-1990); observed figures were compared with those expected on the basis of national cancer incidence rates. RESULTS: The overall standardized incidence ratio [SIR] for cancer was 1.0 [N = 219, 95% confidence interval (95% CI) 0.8-1.1]. A 1.5-fold (N = 34; 95% CI 1.1-2.1) elevated risk of nonmelanoma skin cancer was found, especially for long-term pharmacy assistants (N = 15, SIR 2.8, 95% CI 1.6-4.6). An increased risk for non-Hodgkin's lymphoma appeared among long-term pharmacy dispensers (N = 5, SIR 3.7, 95% CI 1.2-8.9). In the entire group, the risk of tobacco-related tumors was significantly reduced (N = 8, SIRW 0.4, 95% CI 0.2-0.9), together with the probably socioeconomic-associated cervical cancer risk (N = 18, SIR 0.6, 95% CI 0.4-0.9). CONCLUSIONS: Sunlight is usually the dominant cause of nonmelanoma and melanoma skin cancer, but occupational factors may have contributed in this study in view of the uncommon localization observed for many of these cancers and the unelevated melanoma risk. In addition to the increased risk of non-Hodgkin's lymphomas, which may have been associated with exposure to organic solvents, the results do not indicate any other notable cancer risks during the follow-up.

Adult↗

Postpartum preeclampsia complicated by acute pulmonary edema.

Peripartum acute pulmonary edema can occur in patients with preeclampsia-eclampsia. Although the pulmonary edema frequently develops in the postpartum setting, the preeclampsia-eclampsia typically occurs antepartum. Postpartum preeclampsia also can occur with acute pulmonary edema following a relatively normal gestation and delivery.

Adult↗

The role of tumor necrosis factor-alpha in acute endotoxin-induced hepatotoxicity in ethanol-fed rats.

An in vivo model of ethanol ingestion in rats was used to examine tumor necrosis factor-alpha production after intravenous injection with lipopolysaccharide or saline solution. Four groups of 125-gm male Sprague-Dawley rats were given one of the following four diets: liquid ethanol diet (ethanol, 36% of calories), liquid control diet, chow ad libitum or control liquid diet pair-fed to match calories consumed by ethanol-fed rats. After 6 wk of diet, all rats were injected with 1 mg/kg lipopolysaccharide or 0.9% saline. AST concentrations in the ethanol-lipopolysaccharide group (388 +/- 54 U/ml) were significantly increased compared with those in control-saline, ethanol-saline and control-lipopolysaccharide groups (166 +/- 23, 166 +/- 18, 219 +/- 47; p < 0.01). Serum tumor necrosis factor-alpha concentrations for the ethanol-LPS group (3,990 +/- 624 pg/ml) were increased compared with those in control-saline (87 +/- 18), ethanol-saline (68 +/- 24) and control-LPS (695 +/- 165) groups (p < 0.001). A strong correlation was seen between serum tumor necrosis factor-alpha and AST concentrations (r = 0.91, p < 0.001). Treatment with lipopolysaccharide also increased transcriptional levels of tumor necrosis factor-alpha-specific mRNA from hepatic Kupffer cells isolated from rats fed the long-term ethanol diet by a factor of 3 compared with control rats. From these data, we conclude that long-term ethanol administration sensitized hepatic Kupffer cells to secrete high levels of tumor necrosis factor-alpha after lipopolysaccharide injection. Increased serum tumor necrosis factor-alpha concentrations correlated directly with increased levels of serum transaminase, which may have reflected hepatic injury.

Alanine Transaminase↗

Marrow transplant experience for children with severe aplastic anemia.

PURPOSE: The two major factors associated with lack of survival after allogeneic marrow transplant for severe aplastic anemia have been graft rejection and acute graft versus host disease (GVHD). As a result, survival for patients transplanted in the 1970s was approximately 68%. Improved survival during the 1980s was primarily related to the decrease in the incidence of acute GVHD with the use of combination methotrexate and cyclosporine for GVHD prophylaxis. Although the incidence of graft rejection has not changed, the time to graft rejection has been delayed. PATIENTS AND METHODS: One hundred forty children < 18 years of age received a marrow transplant for severe aplastic anemia at the Fred Hutchinson Cancer Research Center between May, 1971 and June, 1991. Four recipients of syngeneic marrow received a simple marrow infusion, 119 recipients of HLA-identical family member marrow received cyclophosphamide (CY), 200 mg/kg; most recipients of alternative donor marrow received CY plus 12.0 Gy fractionated total body irradiation. GVHD prophylaxis was MTX only for 91 recipients of HLA-identical family member marrow, and was MTX plus CSP for all other allogeneic marrow patients. Estimates of graft rejection, acute and chronic GVHD, survival and event-free survival (EFS) were determined by the Kaplan-Meier method. RESULTS: Two recipients of syngeneic marrow achieved engraftment with donor marrow infusion only and two required immunosuppression with CY. Among the 119 recipients of HLA-identical family member marrow the type of GVHD prophylaxis did not influence graft rejection but non-transfused patients had 10% incidence of rejection compared to 22% for transfused patients (p = 0.1). All patients with late graft rejection survive whereas those with early rejection usually do not. The incidence of acute GVHD was 27% and 11% for MTX recipients and MTX plus CSP recipients, respectively (p = 0.11), and the probability of chronic GVHD was 30% and 26%, respectively. Survival is 64% for recipients of MTX and 96% for recipients of MTX plus CSP (p = 0.007), but EFS was 60% and 71%, respectively (p = 0.48). Recipients of partially matched family member or unrelated marrow donor grafts have transplants complicated by infections and GVHD. Growth and development of CY only recipients is normal and several children have been born to these former patients. CONCLUSIONS: High dose CY is usually an effective preparative regimen for children with severe aplastic anemia and an HLA-identical family member marrow donor. Additional immunosuppression with anti-thymocyte globulin may result in a further decrease in graft rejection and improved EFS. Identification of a group of children who are unlikely to respond to immunosuppressive treatment could permit earlier transplantation for patients without HLA-identical family member donors available. Children who receive CY only have normal growth and development.

Anemia, Aplastic↗

[Pharmacological treatment of benign prostatic hyperplasia].

Over the last five to ten years, new treatment modalities have appeared at an increasing pace. The emerging pharmacological treatment modalities have all been used on a large scale. The exact indications and limitations of these methods have not yet been definitely established. Careful analysis of the symptomatology is crucial in counseling the patient. The Danish Prostatic Symptom Score model (DAN-PSS) is proposed. However, treatment benefits should exceed harm and there must be a reasonable cost-effectiveness. Pharmacological agents that reduce prostatic size and/or the tone in the prostate are effective in treatment of benign prostatic hyperplasia. Selective alpha-1 blockers seem to be useful in patients with uncomplicated benign prostatic hyperplasia and mild to moderate symptoms. The side effects of hormone therapy are prohibitive for use in patients with a benign disease. Data currently available indicate a yet to be defined role for 5-alpha-reductase inhibitors.

Adrenergic alpha-Antagonists↗

Malignant mesothelioma after environmental exposure to blue asbestos.

To determine the magnitude of the population at risk from non-occupational exposure to crocidolite at Wittenoom, Western Australia (WA), a cohort of 4,890 residents who never worked for the mining company Australian Blue Asbestos (ABA) has been assembled from all 18,553 available records: the local school register, hospital attendances, the WA electoral roll, birth certificates, workers who answered a mailed questionnaire in 1979, participants in a cancer-prevention programme using vitamin-A dietary supplements, and other sources. The majority of subjects were relatives and friends of ABA employees, and nearly half the cohort were either born at Wittenoom or first went there as children under 10 years of age. As most residents were at Wittenoom when the mine and mill were in operation during the period 1943 to 1966, 82% were first exposed to crocidolite 20 or more years ago. The proportion of other workers (i.e., not employed by ABA) and their families increased once the mining operations ceased. To date, 24 cases of mesothelioma have been reported in this cohort: 9 males and 15 females. Time from first exposure to diagnosis ranged from 23 to 44 years and residence in Wittenoom ranged from 6 weeks to 11 years.

Adolescent↗

Autologous transplantation with peripheral blood mononuclear cells collected after administration of recombinant granulocyte stimulating factor.

Peripheral blood mononuclear cells (PBMC) were collected after the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and used as the sole source of hematopoietic stem cells after myeloablative therapy with busulfan (Bu) and cyclophosphamide (Cy). These studies were performed in 12 patients with malignancies (4 non-Hodgkin's lymphoma, 5 breast cancer, 1 testicular carcinoma, 1 Wilm's tumor, and 1 undifferentiated carcinoma) who had bone or bone marrow disease or had low marrow cellularity. rhG-CSF (16 micrograms/kg/d) was administered for 5 to 7 days by subcutaneous injection and PBMC were collected for 2 to 5 days beginning on day 4 after initiation of rhG-CSF, using continuous-flow blood-cell separators that processed 10 to 12 L of whole blood. From a median of three collections, a mean of 24.0 x 10(8) (+/- 10.5 SD) total nucleated cells/kg containing 12.6 x 10(8) (+/- 4.5 SD) mononuclear cells/kg, 7.3 x 10(6) (+/- 4.3 SD) CD34+ cells/kg and 20.5 x 10(4) (+/- 28.1 SD) granulocyte-macrophage colony-forming units (CFU-GM)/kg were harvested and cryopreserved. After the administration of Bu 14 to 17 mg/kg and Cy 120 to 150 mg/kg, PBMC were thawed and infused. One patient received rhG-CSF after the infusion of PBMC and the remaining 11 patients did not receive postinfusion growth factors. Mean days to recovery of neutrophil levels of 0.1, 0.5, and 1.0 x 10(9)/L were 11.4 (range, 9 to 13), 12.7 (range, 10 to 15), and 13.6 (range, 11 to 16) and the mean day to platelet transfusion independence was 13.3 (range, 7 to 49). Time to recovery of neutrophils to 0.5 and 1.0 x 10(9)/L and platelets to 20 x 10(9)/L was more rapid than in historical patients treated with Bu and Cy who received marrow alone or marrow followed by the posttransplant administration of rh-G or GM-CSF. No graft failures have been observed with a follow-up of 4 to 12 months. These results indicate that PBMC collected after rhG-CSF lead to rapid hematopoietic recovery after myeloablative chemotherapy.

Antigens, CD↗

Dose-response testing with nickel sulphate using the TRUE test in nickel-sensitive individuals. Multiple nickel sulphate patch-test reactions do not cause an 'angry back'.

The aim of this study was to employ the TRUE test assay to confirm the presence or absence of the 'angry back' phenomenon, i.e. that a strong positive patch-test reaction heightens adjacent patch-test response. In addition, we wished to establish the dose-response relationship for nickel sulphate patch tests among nickel-sensitive patients. Seventy-two nickel-sensitive patients, 36 in Odense and 36 in Stockholm, were tested with a 10-step nickel sulphate dilution series (TRUE test) and two placebo patches. The position of the patches was rotated, to provide a balanced spatial distribution of the different concentrations. Readings were performed blind. The results were analysed by means of polynomial multiple-regression methods and a logistic dose-response model. Half the patients (38/72) had a threshold patch-test concentration for nickel sulphate in the range of 3-0.3 microgram/cm2. The 'angry back' phenomenon was not apparent in this study, as the spill-over effect was not statistically significant. Strong reactions to high concentrations of nickel sulphate did not enhance the response to adjacent lower concentrations of nickel sulphate.

Dermatitis, Allergic Contact↗

Availability of data on humans potentially exposed to suspected carcinogens in the Danish working environment.

For the majority of suspected carcinogens only little or no human evidence exists, and in general on-going epidemiologic studies fail to address this fast growing group of chemicals. A survey based on a Danish occupational surveillance system concerning data on present and historical import, production and use of the 167 chemicals evaluated by the International Agency for Research on Cancer as possible or probable carcinogens, shows that about 110 of these chemicals are on the market in Denmark at present. Only 32 are used in industry in relatively large quantities. For some of these chemicals it is possible to identify clusters of companies, including historical cohorts of potentially exposed workers. Measurements of airborne pollutants are available for some few of the suspected carcinogens, indicating decreasing time trends and various levels in different industries. In spite of some limitations, this information on potential exposure has on ad hoc basis been linked to an existing cancer registry based occupational surveillance system, and various studies based on the total body of data are on-going, as a preliminary approach to give at least some human evidence to some widespread animal carcinogens.

Carcinogens, Environmental↗

The exercise pressor response to sustained handgrip does not augment blood flow in the contracting forearm skeletal muscle.

Previous studies have advanced the concept that during sustained handgrip (SHG) reflex increases in blood pressure are able to partially offset increases in tissue pressure and thus effectively maintain increases in muscle blood flow during mild to moderate levels of sustained handgrip. However, this concept is based upon measurements of blood flow to the entire forearm. The aim of this study was to evaluate this concept by simultaneously measuring time-dependent changes in systemic arterial pressure and blood flow in an active muscle during the actual period of exercise. To accomplish this aim, we measured 133Xenon washout from the extensor carpi radialis longus muscle over 3 min of SHG at 15, 30 and 45% of maximal voluntary contraction (MVC). During sustained handgrip at 15% MVC, muscle blood flow increased more than 20 fold from rest to exercise (P < 0.05), even though mean arterial pressure increased by only 12 +/- 4 mmHg. This large exercise-induced hyperaemia was abolished during SHG at both 30 and 45% MVC, despite large and progressive increases in mean arterial pressure of 29 +/- 3 and 54 +/- 5 mmHg, respectively. We conclude that at levels of handgrip above 15% MVC blood pressure ceases to be an important determinant of blood flow in the active skeletal muscle. Importantly, the increases in forearm blood flow that have been reported previously with such levels of static handgrip do not appear to be directed to the most active muscle.

Adult↗

Survival of Danish cancer patients 1943-1987. Respiratory system.

Cancers of the respiratory system are among the most common types of malignant neoplasms in the industrialized world. Thus, this group constitute about 20% of all male and about 8% of all female cancers diagnosed in Denmark during the recent years. Altogether respiratory cancers contribute with around 3,700 (14%) new cases of the about 26,000 cancers diagnosed a year, including skin cancers. Since lung cancer, which in general have a very bad prognosis with a relative 5-year survival of 6%, is the far major cancer subtype in the respiratory system (about 90% of all respiratory cancers), the survival of all respiratory cancers combined is poor. However, the survival of the relative rarely sinonasal and laryngeal cancers are fairly good with 5-year relative survival rates in men of 47% and 61% and in women of 51% and 62%, respectively, during the 1980s. In general, only very small improvements in survival during the period of registration have been observed, the largest being in sinonasal neoplasms, where the 5-year relative survival for the men have increased from 18% around 1945 to 47% around 1985, and for the women from 30% around 1945 to 51% around 1985. Since the aetiology of the major part of respiratory cancers is fairly known, i.e. especially tobacco smoking and to some extent several factors in the working environment, it seem most likely that the major progress will come from primary prevention.

Age Factors↗