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Biomedical subjects

K Johansen

Publications and source records attributed to K Johansen.

At least 19 recordsLinked to original sources

Removal of noro- and enteroviruses, Giardia cysts, Cryptosporidium oocysts, and fecal indicators at four secondary wastewater treatment plants in Sweden.

The aim of this study was to investigate variation in the occurrence and removal of enteroviruses, noroviruses, Giardia cysts, Cryptosporidium oocysts, and the most commonly used fecal indicators in four Swedish secondary wastewater treatment plants (WWTPs). Paired samples were taken from the inlet and outlet of each WWTP. (Oo)cysts and indicators were enumerated with standard methods and viruses with a reverse transcriptase polymerase chain reaction. Giardia cysts and enteroviruses were constantly detected (mean numbers were 10(3.31) cysts and 10(4.44) polymerase chain reaction (PCR) units L(-1), respectively). Oocysts were found in 5 out of 19 samples (mean number was 20 L(-1)). Noroviruses were found between November and February, with an average titer of 10(3.29( L(-1). Mean cyst removal was 2.6 log, while noroviruses and enteroviruses were removed by 0.9 and 1.3 log, respectively. There was no correlation between the removals of pathogens and indicators (p > 0.05). Coliphage removal resembled human viral removal better than did F-specific phage.

Animals↗

Morphologic changes in tubular cells from in situ kidneys following experimental hypothermia and rewarming.

Although renal failure may occur following rewarming from deep accidental hypothermia, this subject has received little attention in experimental hypothermia and clinical case reports. In order to explore the integrity of hypothermic and posthypothermic renal morphology we used an experimental animal model of accidental hypothermia where the heart supports the circulation throughout cooling and rewarming without accompanying cardioplegia or ischemia. Ultrastructural changes in renal tubular cells from three groups of pentobarbital anesthetized Wistar rats: 1) controls (n=6) maintained at 37 degrees C for 4 h, 2) hypothermic rats (n=6) core-cooled and maintained at 15-13 degrees C for 4 h, and 3) rewarmed rats (n=10), were studied as a sensitive indicator of renal damage. Electron micrographs (EM) from hypothermic kidneys showed rounded up mitochondria with loss of contrast. These changes were observed in several though not all of the biopsies, but they were found in all kidneys. Areas exhibiting focal tubular necrosis were seen on most EM from three of these kidneys. EM from rewarmed kidneys showed alterations of mitochondrial ultrastructure with similarities to those observed after hypothermia, but in general the changes were more prominent. Extracellular edema, intracellular edema, swelling of mitochondria, margination of chromatin, necrosis of single tubular cells, and disrupting necrotic debris into tubular lumen could be found in micrographs from 7 of the 10 kidneys examined. Rewarming from experimental hypothermia, without episodes of ischemia or hypoxia, thus induces ultrastructural changes in renal tubular cells similar to changes observed in acute tubular necrosis, associated with renal failure.

Animals↗

Use of history science methods in exposure assessment for occupational health studies.

AIMS: To show the power of history science methods for exposure assessment in occupational health studies, using the dry cleaning industry in Denmark around 1970 as the example. METHODS: Exposure data and other information on exposure status were searched for in unconventional data sources such as the Danish National Archives, the Danish Royal Library, archives of Statistics Denmark, the National Institute of Occupational Health, Denmark, and the Danish Labor Inspection Agency. Individual census forms were retrieved from the Danish National Archives. RESULTS: It was estimated that in total 3267 persons worked in the dry cleaning industry in Denmark in 1970. They typically worked in small shops with an average size of 3.5 persons. Of these, 2645 persons were considered exposed to solvents as they were dry cleaners or worked very close to the dry cleaning process, while 622 persons were office workers, drivers, etc in shops with 10 or more persons. It was estimated that tetrachloroethylene constituted 85% of the dry cleaning solvent used, and that a shop would normally have two machines using 4.6 tons of tetrachloroethylene annually. CONCLUSION: The history science methods, including retrieval of material from the Danish National Archives and a thorough search in the Royal Library for publications on dry cleaning, turned out to be a very fruitful approach for collection of exposure data on dry cleaning work in Denmark. The history science methods proved to be a useful supplement to the exposure assessment methods normally applied in epidemiological studies.

Air Pollutants, Occupational↗

Pharmacodynamic effects of low molecular weight heparin in obese subjects following subcutaneous administration of 75 IU/kg on plasma tissue factor pathway inhibitor and nitric oxide.

AIM: Pharmacodynamic effects of the low molecular weight heparin tinzaparin on plasma levels of tissue factor pathway inhibitor (TFPI) and nitric oxide (NO) were compared in obese subjects, as well as in normal healthy controls. METHODS: Obese (n = 13) patients received a single 75 IU/kg SC injection (the deep vein thrombosis prophylaxis dose) of tinzaparin. Blood samples were obtained pre- and postadministration of drug and at different intervals over 24 h and assayed for total TFPI and NO stable metabolites (nitrates and nitrites) plasma levels, using a specific immunoassay and calorimetric methods. RESULTS: Mean maximum plasma TFPI levels approached 150-230 ng/ml at the 0.8 h and up to 5 h posttinzaparin dose compared to basal TFPI levels of 35-90 ng/mL. Plasma TFPI levels were still about 2-fold above basal levels at 12 h and fell to basal levels at 16 h after tinzaparin dose. Basal plasma levels of NO, but not TFPI, were significantly lower (P < 0.01) in obese patients compared to controls. Similar TFPI (3-fold above basal at peak) and NO pharmacodynamic profiles for tinzaparin at 75 anti-Xa IU/kg were demonstrated in obese and in normal healthy subjects. Plasma NO (nitrate + nitrite) showed a lag time of about 5-6 h posttinzaparin followed by a steady increase with a peak at 12-15 h and slow decline with a significant residual level at 24 h in obese and healthy subjects. CONCLUSIONS: Data suggest a normal responsiveness of vascular endothelial cells and other cellular compartments to tinzaparin with regard to the pharmacodynamic profiles of plasma TFPI and NO in obese subjects.

Adolescent↗

An outbreak of mumps in Sweden, February-April 2004.

Between 24 February and 26 April 2004, Västra Götaland county in Sweden reported 42 cases of suspected mumps. A descriptive study of the cases was undertaken. A questionnaire was administered by telephone and vaccine effectiveness was calculated using the screening method. Seventy four per cent (31/42) of the suspected cases were interviewed by telephone. Eight out of the 42 serum samples were positive or equivocal for mumps IgM by ELISA. Mumps virus genome was identified in 21/42 (50%) saliva samples. Eleven were selected for sequencing and all were confirmed to be mumps virus. Cases were predominantly from 2 small towns. Eighteen out of 19 cases that developed bilateral swelling could be linked to one small town. The median age of interviewed cases was 43 years (range 5 to 88). Six cases were admitted to hospital, 5 of which were older than 30 years. The highest incidence occurred in the 35 to 44 years age group. Vaccine effectiveness was estimated to be 65% for 1 dose and 91% for 2 doses. This descriptive study shows the increasing age of mumps cases with increasing vaccine coverage. Vaccine effectiveness was particularly high for 2 doses. Second-dose uptake must be ensured, as primary vaccine failure is well documented in mumps. Stronger precautions must be taken to avoid pools of susceptible older individuals accumulating due to the increased risk of complications.

Adolescent↗

[Vaccination offers good protection against measles, mumps and rubella. To refuse vaccination would seriously threaten our good immunity status].

Since vaccination against measles, rubella and mumps (MMR) was introduced in Sweden in 1982 for children at 1.5 and 12 years of age these diseases have almost completely disappeared. Severe side effects have been rare. Threats against the continued protection from these diseases include a lessening inclination on the part of parents to vaccinate their children, a weakening of the vaccine-induced immunological response with time, and possibly also genetic changes in strains of circulating wild type virus. By law physicians are bound to report diagnosed cases as well as new or severe side effects. Continuous laboratory analysis of antibodies and circulating viruses is also necessary.

Adverse Drug Reaction Reporting Systems↗

[Prescription of central nervous system stimulants].

BACKGROUND: The Child and Adolescent Unit at Nordland Psychiatric Hospital has conducted a review of the prescription practice in its region with regard to central nervous system stimulants. MATERIAL AND METHODS: Data were collected from the region's pharmacies on the type of drug, the type of medical practitioners prescribing them, and patients's sex, age and community of residence. RESULTS: The total numbers of users of Ritalin/Dexamin (methylphenidate/dextroamphetamine) were 199 children (under 18) and 21 adults (above 18). The male/female ratio was 4:1, boys between 8 and 13 being the largest group. Users in the below-18 group constituted 0.35% of their age group in our region. Prescriptions to children were in 188 out of 199 cases written by child psychiatrists or paediatricians. Prescription patterns in the seven local hospital areas in the region were almost identical, with one area forming an exception. INTERPRETATION: This survey suggest that because of insufficient knowledge of the diagnostic criteria for attention deficit/hyperactivity disorders, many children with this type of problems do not get the treatment they may need. Adequate treatment based on competent diagnostic assessment is assumed to relieve distress and counteract the development of further problems. Similar surveys in other Norwegian regions would enable us to compare prescription practice nation-wide.

Adolescent↗

Anticoagulant pharmacodynamics of tinzaparin following 175 iu/kg subcutaneous administration to healthy volunteers.

Tinzaparin, a sodium salt of a low-molecular-weight heparin (LMWH) produced via heparinase digestion, is used for the treatment of deep vein thrombosis (DVT) and pulmonary embolism in conjunction with warfarin for the prevention of DVT in patients undergoing hip or knee replacement surgery, and as an anticoagulant in hemodialysis circuits. Its average molecular weight ranges between 5500 and 7500 daltons (Da); the percentage of chains with molecular weight lower than 2000 Da is not more than 10% in the marketed tinzaparin formulation. While this fraction is generally considered pharmacologically inactive, this has never been evaluated in vivo. The importance of the < 2000 Da fraction on the anticoagulant pharmacodynamics of tinzaparin assessed by anti-Xa and anti-IIa activity was studied in a two-way crossover trial. In this trial, 30 healthy volunteers received a single 175 IU/kg subcutaneous administration of tinzaparin containing approximately 3.5% of the < 2000 Da fraction and a tinzaparin-like LMWH containing 18.3% of the < 2000 Da fraction. The anti-Xa/anti-IIa ratios of the drug substances were comparable at 1.5 and 1.7 for tinzaparin and the tinzaparin-like LMWH, respectively. Both formulations were safe and well tolerated. Mean maximum plasma anti-Xa activity (A(max)) was approximately 0.818 IU/ml at 4 h following tinzaparin injection. Mean maximum plasma anti-IIa activity was 0.308 IU/ml at 5 h postdose. Intersubject variation was lower (< 18% for both anti-Xa and anti-IIa metrics) than in previous fixed-dose administration studies. There was no correlation between anti-Xa or anti-IIa AUC or A(max) and bodyweight in the present study supporting the weight-adjusted dosing regimen. Individual anti-Xa and anti-IIa profiles following the single 175 IU/kg subcutaneous administration of the tinzaparin-like LMWH were similar to that obtained with tinzaparin. Based on average equivalence criteria, the two LMWH preparations were determined to be bioequivalent using either anti-Xa or anti-IIa activity as biomarkers. The calculated intrasubject variabilities were low (< 14% for anti-Xa activity and < 18% for anti-IIa activity) yielding little evidence for a significant Subject x Formulation interaction. In summary, anti-Xa and anti-IIa activity following a single subcutaneous administration of tinzaparin 175 IU/kg to healthy volunteers yielded activity consistent with targeted therapeutic levels derived from previous trials in adult DVT patients. Weight-based dosing for the treatment of DVT appears rational based on the reduction in anti-Xa and anti-IIa variability consistent with the recommendation derived from earlier fixed-dose pharmacokinetic studies. Furthermore, differences in the percentage of molecules in the < 2000 Da molecular weight fraction of tinzaparin do not translate into differences in anti-Xa and anti-IIa activity in vivo.

Adult↗

Transjugular intrahepatic portasystemic shunt vs surgical shunt in good-risk cirrhotic patients: a case-control comparison.

HYPOTHESIS: In good-risk patients with variceal bleeding undergoing portal decompression, surgical shunt is more effective, more durable, and less costly than angiographic shunt (transjugular intrahepatic portasystemic shunt [TIPS]). DESIGN: Retrospective case-control study. SETTING: Academic referral center for liver disease. PATIENTS: Patients with Child-Pugh class A or B cirrhosis with at least 1 prior episode of bleeding from portal hypertension (gastroesophageal varices, portal hypertensive gastropathy). INTERVENTION: Portal decompression by angiographic (TIPS) or surgical (portacaval, distal splenorenal) shunt. MAIN OUTCOME MEASURES: Thirty-day and long-term mortality, postintervention diagnostic procedures (endoscopic, ultrasonographic, and angiographic studies), hospital readmissions, variceal rebleeding episodes, blood transfusions, shunt revisions, and hospital and professional charges. RESULTS: Patients with Child-Pugh class A or B cirrhosis undergoing TIPS (n = 20) or surgical shunt (n = 20) were followed up for 385 and 456 patient-months, respectively. Thirty-day mortality was greater following TIPS compared with surgical shunt (20% vs 0%; P =.20); long-term mortality did not differ. Significantly more rebleeding episodes (P<.001); rehospitalizations (P<.05); diagnostic studies of all types (P<.001); shunt revisions (P<.001); and hospital (P<.005), professional (P<.05), and total (P<. 005) charges occurred following TIPS compared with surgical shunt. CONCLUSIONS: Operative portal decompression is more effective, more durable, and less costly than TIPS in Child-Pugh class A and B cirrhotic patients with variceal bleeding. Good-risk patients with portal hypertensive bleeding should be referred for surgical shunt.

Case-Control Studies↗

Mucosal and plasma IgA from HIV-1-exposed uninfected individuals inhibit HIV-1 transcytosis across human epithelial cells.

HIV-1-specific IgA has been described in the genital tract and plasma of HIV-1 highly exposed, persistently seronegative (HEPS) individuals, and IgA from these sites has been shown to neutralize HIV-1. This study examines the ability of IgA isolated from HEPS individuals to inhibit transcytosis across a tight epithelial cell layer. A Transwell system was established to model HIV-1 infection across the human mucosal epithelium. The apical-basolateral transcytosis of primary HIV-1 isolates across this mucosal model was examined in the presence and the absence of IgA isolated from the genital tract, saliva, and plasma of HEPS individuals enrolled in both a sex worker cohort in Nairobi, Kenya, and a discordant couple cohort in Italy. In the absence of IgA, HIV-1 primary isolates were actively transported across the epithelial membrane and were released on the opposite side of the barrier. These transcytosed HIV-1 particles retained their ability to infect human mononuclear cells. However, IgA purified from the mucosa and plasma of HEPS individuals was able to inhibit HIV-1 transcytosis. Inhibition was seen in three of six cervicovaginal fluid samples, five of 10 saliva samples, and three of six plasma samples against at least one of the two primary HIV-1 isolates tested. IgA from low risk, healthy control subjects had no inhibitory effect on HIV-1 transcytosis. The ability of mucosal and plasma IgA to inhibit HIV-1 transcytosis across the mucosal epithelium may represent an important mechanism for protection against the sexual acquisition of HIV-1 infection in HEPS individuals.

Anti-HIV Agents↗

Sensitivity deviation: instrumental linearity errors that influence concentration analyses and kinetic evaluation of biomolecular interactions.

Many scientific instruments utilise multiple element detectors, e.g. CCD's or photodiode arrays, to monitor the change in a position of an optical pattern. For example. instruments for affinity biosensing based on surface plasmon resonance (SPR) or resonant mirror are equipped with such detectors. An important and desired property of these bioanalytical instruments is that the calculation of the movement or change in shape follows the true change. This is often not the case and it may lead to linearity errors, and to sensitivity errors. The sensitivity is normally defined as the slope of the calibration curve. A new parameter is introduced to account for the linearity errors, the sensitivity deviation, defined as the deviation from the undistorted slope of the calibration curve. The linearity error and the sensitivity deviation are intimately related and the sensitivity deviation may lead to misinterpretation of kinetic data, mass transport limitations and concentration analyses. Because the linearity errors are small (e.g. 10 pg/mm2 of biomolecules on the sensor surface) with regard to the dynamic range (e.g. 30,000 pg/mm2), they can be difficult to discover. However, the linearity errors are often not negligible with regard to a typical response (e.g. 0-100 pg/mm2). and may therefore cause serious problems. A method for detecting linearity errors is outlined. Further on, this paper demonstrates how integral linearity errors of less than 1% can result in a sensitivity deviation of 10%, a value that in our opinion cannot be ignored in biospecific interaction analysis (BIA). It should also be stressed out that this phenomenon also occurs in other instruments using array detectors.

Kinetics↗

Blood plasma coagulation studied by surface plasmon resonance.

A surface plasmon resonance (SPR) apparatus was used to investigate blood plasma coagulation in real time as a function of thromboplastin and heparin concentrations. The response curves were analyzed by curve fitting to a sigmoid curve equation, followed by extraction of the time constant. Clotting activation by thromboplastin resulted in increased time constant, as compared to spontaneously clotted plasma, in a dose dependent way. Addition of heparin to the thromboplastin-activated plasma counteracted this effect. Atomic force microscopy (AFM) pictures of sensor surfaces dried after completed clotting, revealed differences in fibrin network structures as a function of thromboplastin concentration, and the fiber thickness increased with decreased thromboplastin concentration. The physical reason for the SPR signal observed is ambiguous and is therefore discussed. However, the results summarized in the plots and the fibrin network properties observed by AFM correlate well with present common methods used to analyze blood coagulation.

Anticoagulants↗

Nasal immunization of mice with virus-like particles protects offspring against rotavirus diarrhea.

Rotavirus is the major cause of diarrhea among young infants in both humans and animals. Immune protection of newborns by vaccination is difficult to achieve since there is not enough time to mount an immune response before exposure to the virus. We have designed a vaccination strategy mediating transfer of neutralizing antibodies from the mother to the offspring during pregnancy and/or lactation. Adult female mice were nasally immunized with virus-like particles (VLPs) made of viral proteins VP2 and 6 (VLP2/6) or VP 2, 6, and 7 (VLP2/6/7) derived from the RF rotavirus strain in the presence or absence of cholera toxin. Both vaccines elicited serum and milk antibodies against the respective VPs. Four days after parturition, suckling pups were challenged orally with RF rotavirus. Pups from mothers immunized with VLP2/6/7 but not VLP2/6 were protected against rotavirus diarrhea, indicating that VP7 plays a key role in protection. Protection was mediated by milk rather than serum antibodies, and mucosal adjuvants were not required. In conclusion, VLPs containing VP7 administered nasally to mothers represent a promising vaccine candidate for the protection of suckling newborns against rotavirus-induced diarrhea, even in the absence of a mucosal adjuvant.

Administration, Intranasal↗

[The first rotavirus vaccine approved in the USA and Europe].

A new live oral rotavirus vaccine (Rotashield) has now been approved both in the USA and Europe. In large multicentre trials involving over 10,000 children, the vaccine has been shown to have a manifest protective effect, first and foremost against severe rotavirus-induced diarrhoea, but to be associated with certain side effects. The Advisory Committee on Immunisation Practices and the American Academy of Paediatrics are now recommending that Rotashield be included in the child vaccination programme. Use of the vaccine in Europe is likely to vary from one country to another. The issue of general recommendations for its use in Sweden should await the results of cost-benefit analysis and review of experience of the vaccine's use in the USA. In addition, a more comprehensive identification of rotavirus serotypes occurring in Sweden is a prerequisite for adequate assessment of the vaccine's necessity in this country.

Diarrhea, Infantile↗

Encapsulation of rotavirus into poly(lactide-co-glycolide) microspheres.

Two small-scale double emulsion techniques for incorporation of formaldehyde-inactivated rotavirus particles (FRRV) into poly(lactide-co-glycolide) (PLG) microspheres were developed and optimised. The effects of high-speed homogenisation versus vortex mixing on the double emulsion stability, microsphere size, entrapment efficiency and in vitro release of FRRV in the second emulsification step were studied. A stable double emulsion was verified only when using vortex mixing in this step. Slow removal of the organic phase allowed measurement of the size of the emulsion droplets and subsequent prediction of the size of the resulting microspheres. Microspheres in the size range of 1-10 microm were prepared using both techniques. The homogenisation technique was sensitive to changes in the operating time, the emulsification energy and the volume of the outer aqueous phase, while the vortex technique was more robust. Rotavirus was released in vitro in a triphasic manner with both techniques. The more robust vortex technique was selected for preparation of PLG microspheres containing rotavirus for in vivo studies. After immunisation of mice with a single intramuscular injection, the PLG-FRRV microspheres elicited an IgG antibody response in serum detected by ELISA equally high as that elicited with FRRV alone. These results indicate that the antigenicity of FFRV was retained after incorporation into PLG microspheres using the vortex technique.

Animals↗

Emergency carotid thromboendarterectomy: safe and effective.

Whether to perform emergency carotid thromboendarterectomy (CTEA) in the presence of crescendo transient ischemic attacks or stroke-in-evolution is controversial, with the operative mortality in some reports exceeding 20% and improvement in neurologic deficit of less than 40% in others. Our anecdotal experience with emergency CTEA for acute, persistent, or crescendo neurologic deficit had been strikingly better than published reports. Accordingly, we carried out a restrospective comparison of 43 such patients undergoing emergency CTEA with 237 patients concurrently undergoing elective CTEA for conventional indications. A standard protocol followed in emergency CTEA patients included carotid Doppler ultrasonography, computed cerebral tomography (CT), four-vessel cerebral arteriography, and intravenous heparin. Exclusions from emergency CTEA included coma or cerebral CT scan evidence for either hemorrhagic or ischemic infarction with edema. Operative techniques included standard carotid endarterectomy with Dacron patch or direct suture, eversion endarterectomy, or shortening resection. No mortality or central neurologic complications resulted among the 43 emergency CTEA patients, in comparison to no deaths and one temporary hemiparesis (0.4% central neurologic morbidity) in the 237 elective CTEA patients. Our results suggest that in the absence of coma or cerebral CT scan evidence for an unstable blood-brain barrier, emergency carotid reconstruction can be performed safely and with excellent outcome notwithstanding the magnitude and severity of the acute preoperative neurologic deficit.

Aged↗

Surface plasmon resonance (SPR) analysis of coagulation in whole blood with application in prothrombin time assay.

It is previously shown that surface plasmon resonance (SPR) can be used to study blood plasma coagulation. This work explores the use of this technique for the analysis of tissue factor induced coagulation, i.e. prothrombin time (PT) analysis, of whole blood and plasma. The reference method was nephelometry. The prothrombin time analysis by SPR was performed by mixing two volumes of blood/plasma, one volume of thromboplastin, and one volume of CaCl2 solution directly on a sensor surface. The measurements show good agreement between nephelometry and SPR plasma analysis and also between SPR plasma and whole blood analysis. The effect of anticoagulant treatment on the clotting times was significant both quantitatively and qualitatively. The impact on the SPR signal of different physiological events in the coagulation process is discussed, and tentative interpretations of the sensorgram features are given. The major advantage of the SPR method compared to nephelometry is the possibility to perform analysis on whole blood instead of plasma. In conclusion, SPR is a promising method for whole blood coagulation analysis.

Anticoagulants↗