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Biomedical subjects

B Eriksson

Publications and source records attributed to B Eriksson.

At least 37 records · Page 2Linked to original sources

Differential increase in cerebrospinal fluid-acetylcholinesterase after treatment with acetylcholinesterase inhibitors in patients with Alzheimer's disease.

The clinical significance and the effects of pharmacological treatment of patients with Alzheimer's disease (AD) were evaluated by measurement of acetylcholinesterase (AChE) in the cerebrospinal fluid (CSF). CSF-AChE of AD patients was lower, not significantly, compared with controls. However, CSF-AChE was significantly increased after treatment of AD patients with AChE inhibitors (donepezil and galantamine). The increase was higher in patients treated with donezepil than in those treated with galantamine, which might be related to different mechanisms for the substances. The increase was also dose-dependent, and was especially marked in patients showing a clinical response. These data suggest that CSF biomarkers are capable not only of identifying a biochemical effect of drugs, but also of differentiating between different compounds in a dose-dependent manner.

Acetylcholinesterase↗

Viral safety of B-domain deleted recombinant factor VIII.

The possible transmission of blood-borne pathogens has been the impetus behind the development of recombinant products formulated in the absence of human-derived components. The viral safety of Chinese hamster ovary (CHO)-cell-based pharmaceuticals is well established. Over 100 million infusions have been administered without a single known incident of CHO-related viral transmission. The manufacturing process for B-domain deleted recombinant factor VIII (BDDrFVIII) builds on this safety record by using a state-of-the-art multitiered approach to viral safety. This approach includes: (1) extensive testing of the CHO cells used to produce BDDrFVIII; (2) routine viral monitoring of the cell culture production process; (3) a purification process in which a specific viral inactivation procedure has been included; (4) a final formulation that does not incorporate human albumin as the stabilizer; and (5) a thorough validation of the viral inactivation and removal capacity of the purification process. This multifaceted viral safety program offers the hemophilia community a factor VIII product with an exceptional degree of viral safety.

Animals↗

Real world pharmacy: assessing the quality of private pharmacy practice in the Lao People's Democratic Republic.

The private sector is a dominant actor in the provision of pharmaceuticals, particularly in developing countries. Private provision of drugs has been associated with risks regarding availability, affordability, rational use and drug quality. Ensuring an effective regulatory framework is therefore a major challenge for governments, yet the capacity of regulatory authorities is often outstripped by private sector growth. In the Lao People's Democratic Republic (Lao P.D.R.), a poor, landlocked country in South East Asia, the private provision of drugs has increased dramatically since the liberalisation of the economy in the late 1980s. This paper aims to describe the quality of the private pharmacy services in the Savannakhet province of Lao P.D.R. In order to do this, a monitoring instrument which serves to make the concept of Good Pharmacy Practice (GPP) operational was developed and applied to a sample of pharmacies. Service quality, as measured by three facility-specific indicators, showed a tendency to be lower in the most distant districts. Poor dispensing practices were manifest by a lack of information about drugs sold in 59% of cases, drugs not being labelled in 47% and different drugs being mixed in the same package in 26% of cases. The prices of four sample drugs were slightly higher in the remote districts. A 10-fold price difference for the same drug was recorded in one district. After reporting the findings, the paper discusses the possible influence of district and pharmacy variables on the quality of services, and goes on to discuss the price differences. It is concluded that further government interventions are needed in order to improve the quality of services and to focus regulatory action on a limited number of aspects, to ensure that drugs can be traced before trying to establish a comprehensive regulatory system.

Developing Countries↗

CSF-neurofilament and levodopa tests combined with discriminant analysis may contribute to the differential diagnosis of Parkinsonian syndromes.

The differentiation between Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is important for prognostic and therapeutic purposes. In order to evaluate the diagnostic capability of two tests reflecting these items, patients fulfilling strict clinical criteria for PD (n=35), MSA (n=36) and PSP (n=14), were consecutively included. An analysis of neurofilament protein (NFL), a marker of axonal degeneration in the cerebrospinal fluid (CSF) and a levodopa test, recorded with optoelectronic technique were performed. Using discriminant analyses, the test's abilities to predict the clinical PD or non-PD (MSA and PSP) diagnoses were compared. Whereas the CSF-NFL and levodopa tests predicted 79 and 85% correct diagnoses respectively, the combined test predicted 90% correct diagnoses. We conclude that the CSF-NFL and levodopa tests provide detailed information of clinical variables on which the clinical diagnostic criteria are based. As they are pathologically unrelated, the diagnostic precision increases compared to clinical diagnoses when they are combined.

Adult↗

Experience in treatment of metastatic pulmonary carcinoid tumors.

BACKGROUND: The only cure for patients with pulmonary carcinoids is surgery. In the present paper, we report the results of medical treatment of patients with metastatic tumors, their circulating hormone markers, and immunohistochemical profile of the tumors. PATIENTS AND METHODS/RESULTS: The response to systemic antitumoral treatment was studied in 31 patients with metastatic pulmonary carcinoids. Median survival from treatment start was 25 months. Alpha-interferon treatment has resulted in stable disease in 4 of 27 patients (median duration 15 months), while 23 patients showed progressive disease. Somatostatin analogues given as single drug treatment resulted in progressive disease. Streptozotocin and 5-fluorouracil resulted in progressive disease in seven of seven patients. Stable disease was obtained for 8 and 10 months respectively in two of two patients treated with streptozotocin + doxorubicin. Two of eight patients treated with cisplatinum + etoposide showed a significant decrease in tumor size lasting six and eight months respectively, and one displayed stable disease for seven months. Elevation of plasma chromogranin A was seen in 93%. CONCLUSIONS: The results of systemic antitumoral treatment of pulmonary carcinoids with distant metastases are generally discouraging. Chemotherapy with cisplatinum + etoposide, or doxorubicin combined with streptozotocin or paclitaxel may be of value. Alpha-interferon and octreotide offer efficient symptomatic relief, but stabilizes tumor growth in merely 15% of the cases. Plasma chromogranin A is the most frequently elevated tumor marker.

Adolescent↗

Allergic rhinoconjunctivitis, eczema, and sensitization in two areas with differing climates.

In this 5-year follow-up study we compared the prevalence of allergic rhinoconjunctivitis, eczema, and sensitization, in relation to several background factors, in two Swedish regions (Göteborg and Kiruna). In Göteborg, a city on the southwest coast, the climate is mild and humid. Kiruna is a town north of the Arctic Circle. Questionnaire replies and results of interviews were collected from all 412 7-8-year-old children of a population-based sample (203 in Göteborg and 209 in Kiruna); in addition, 192 children from Göteborg and 205 from Kiruna were skin-prick tested for sensitization to common aero-allergens. After 5 years, at 12-13 years of age, almost all of the initial study cohort were re-investigated. At follow-up the prevalence of allergic rhinoconjunctivitis was 17%, eczema 23%, and sensitization 32%. Allergic rhinoconjunctivitis and eczema were as common in Göteborg as in Kiruna, whereas sensitization was far more common in Kiruna. Children born during the pollen season had allergic rhinoconjunctivitis less often -- and were sensitized to pollen and animal protein less often -- than those born during the rest of the year. Sensitization to birch pollen, cat protein, and horse protein was less common in children living in Göteborg, the region with the highest frequency of cat ownership and horseback riding, and with the longest birch-pollen season. The girls were more commonly horseback riders but the boys were more often sensitized to horses. The results reinforce our previous findings: indoor climate may affect the development of sensitization and allergic diseases, to some extent independently; and if exposure to antigen is unavoidable, high doses might be better than low doses.

Adolescent↗

Marital status and cardiovascular risk in French and Swedish automotive industry workers--cross sectional results from the Renault-Volvo Coeur study.

OBJECTIVES: To compare the coronary risk profiles in a sample of the French and Swedish automotive industry employees who were married/cohabitant, divorced or single (never married). DESIGN: A cross-sectional study comparison from biological and questionnaire data between the French and Swedish samples. SETTING: Occupational health departments at Renault (employees from the north-west of France) and Volvo (employees from the south-west of Sweden). SUBJECTS: Two random samples of males aged between 45 and 50 years were examined in 1993, from Renault 1000, and from Volvo 1000. MAIN OUTCOME MEASURES: Biological data including cholesterol, blood pressure as well as the Framingham risk index. Self reported information regarding marital status, smoking, exercise, alcohol habits, and work stress assessed by the Karasek method, private social support indices, and type A behaviour according to the Bortner scale. RESULTS: More employees were married/cohabitant and fewer divorced or single at Renault. Apart from waist/hip ratio being marginally lower in Swedish single men, compared with married and divorced, no significant difference in biological cardiac risk factors (total cholesterol, blood pressure or Framingham risk index) was seen between the subgroups from any of the two countries. Compared with married/cohabitant men, it was shown that in men living alone smoking was more prevalent at Renault and Volvo. These men also showed less type A behaviour, a lower work control and a lower work support and fewer close friends. Alcohol consumption was reported in smaller amounts for Volvo employees living alone compared with married or divorced employees. Married/cohabitant and divorced staff showed similar values regarding all measured variables when compared within each country. CONCLUSIONS: Employees living alone in both France (Renault) and Sweden (Volvo) automotive companies seem to have increased nontraditional cardiac risk factors pertaining to life style and social network compared with married or divorced men. These results, in combination with the finding that more Volvo than Renault employees were living alone, suggest a higher risk for coronary heart disease amongst Volvo employees. This hypothesis will be evaluated in the 5 and 10 years follow up study.

Alcohol Drinking↗

Health-related quality of life, anxiety and depression in patients with midgut carcinoid tumours.

In earlier studies it has been reported that patients with carcinoid tumours have a relatively good health-related quality of life (HRQoL) and low levels of anxiety and depression. The aims of this study were (a) to investigate the extent to which psychosocial function changes in patients with carcinoid tumours with time from diagnosis and its possible relation to tumour markers, and (b) to compare the HRQoL of patients with carcinoid tumours with that of healthy Swedish adults. Twenty-four patients reported on HRQoL (the EORTC QLQ-C30), anxiety and depression (the Hospital Anxiety and Depression Scale) five times during their first year of treatment. After one year, improvement in nausea/vomiting, flush and anxiety was reported, but there was deterioration of physical function, an increase in muscular pain and problems with dry skin. Levels of tumour markers were not associated with psychosocial function. Patients reported a lower HRQoL compared with healthy Swedish adults. Thus, deterioration of physical function was not accompanied by a deterioration of emotional function, and levels of tumour markers were not related to patients' HRQoL.

Activities of Daily Living↗

Private pharmacy practice and regulation. A randomized trial in Lao P.D.R.

OBJECTIVES: The objective of this study was to assess the effectiveness of government regulation of private pharmacy practice in a low-income country. METHODS: The intervention comprised inspections of the pharmacies, information, and distribution of documents to drug sellers and sanctions. It was implemented at two different intensity levels, active and regular intervention. The methods used to assess the effect of the interventions were interviews with the district drug inspectors, drug sellers and customers, inspection of drug purchases, and indicator surveys of pharmacies. Indicators for pharmacy-specific quality as well as for dispensing quality were developed. RESULTS: The main finding was one of strong overall improvements from initially low levels. The improvements were particularly marked by increases in the availability of essential materials for dispensing by 34% and in order in the pharmacy by 19%. Information given to customers increased from 35% to 51% and the mixing of different drugs in the same package went down from 17% to 9%. The pharmacies in the active intervention districts showed greater improvements for four of the six indicators, although statistically significant compared with the regular intervention districts only for the essential materials indicator. CONCLUSIONS: It was concluded that the regulatory activities have probably been an important factor behind the service quality improvements. It appeared feasible as well as effective to regulate private pharmacy practice in this particular low-income setting.

Developing Countries↗

Functional expression of Cre recombinase in sub-regions of mouse CNS and retina.

We describe a strategy for generating CNS and retina sub-region-specific mutations using the Cre/loxP system. Transgenic mice expressing Cre recombinase under the control of the c-kit promoter were established. Functional Cre expression was predominantly found to be restricted to the CA1, CA2 and CA3 regions of the hippocampus, the anterior region of the dentate gyrus, and to the ganglion cell layer of the retina.

Animals↗

Determination of estramustine phosphate and its metabolites estromustine, estramustine, estrone and estradiol in human plasma by liquid chromatography with fluorescence detection and gas chromatography with nitrogen-phosphorus and mass spectrometric detection.

Bioanalytical methods for the determination of estramustine phosphate by liquid chromatography and its four main metabolites estromustine, estramustine, estrone and estradiol by gas chromatography are described. For the estramustine phosphate assay the plasma was purified by protein precipitation followed by a C18 solid-phase extraction. For the metabolite assay the plasma samples were purified by a C18 solid-phase and liquid-liquid extraction procedure and derivatised by silanization. Thereafter, estramustine and estromustine were quantified by gas chromatography with nitrogen-phosphorus detection and estradiol and estrone were quantified by gas chromatography with selected ion monitoring. The methods were validated with respect to linearity, selectivity, precision, accuracy, limit of quantitation, limit of detection, recovery and stability. The limit of quantitation was 2.3 micromol/l for estramustine phosphate, 30 nmol/l for estromustine and estramustine, 12 nmol/l for estrone and 8 nmol/l for estradiol. The results showed good precision and accuracy for estramustine phosphate and the four metabolites. The intermediate precision was 6.2-13.5% (C.V.) and the accuracy was 91.8-103.9%.

Antineoplastic Agents, Alkylating↗

The basic helix-loop-helix transcription factor E2-2 is involved in T lymphocyte development.

E2A, HEB and E2-2 genes encode a group of basic helix-loop-helix (bHLH) transcription factors that are structurally and functionally similar. Deletion of the genes encoding either of these proteins leads to early lethality and a block in B lymphocyte development. Evidence for a function in T lymphocyte development has, however, only been reported for E2A and HEB. To further elucidate the role of E2-2 at developmental stages that have proven difficult to study due to the early lethality phenotype of mice defective in E2-2, we generated and analyzed mice conditionally mutated in the E2-2 gene. These mice are mosaic with respect to E2-2 expression, consisting of cells with either one functional and one null mutated E2-2 allele or two null mutated alleles. Using this experimental model, we find that cells with a homozygous null mutated E2-2 gene are under-represented in B lymphocyte as well as T lymphocyte cell lineages as compared to other hematopoietic or non-hematopoietic cell lineages. Our data suggests that E2-2 deficiency leads to a partial block in both B and T lymphocyte development. The block in T cell development appears to occur at an early stage in differentiation, since skewing in the mosaicism is observed already in CD4+8+ double-positive thymocytes.

Alleles↗

Surgical strategy for large or malignant endocrine pancreatic tumors.

Endocrine pancreatic tumors (EPTs) are rare but have a remarkably better prognosis than adenocarcinoma of the pancreas. Patients with EPTs benefit from surgical and medical therapy, which may alleviate symptoms due to hormonal excess and increase survival. Patients with large or malignant EPTs with infiltrative disease may suffer from local complications, including gastrointestinal bleeding and obstruction and involvement of the superior mesenteric (SMV) and portal (PV) veins. Among 31 patients with operable and large or malignant EPTs, 7 had hormone-producing syndromes (insulin, glucagon), and 24 had clinically nonfunctioning EPTs. Surgery in these patients included vascular reconstruction of the SMV/PV (n = 4), resection of infiltrated adjacent organs (n = 5; stomach, transverse colon), or resection of concomitant liver metastases (n = 3). Four patients with conspicuously large insulinomas, and three with glucagonoma were successfully operated on with alleviation of hormonal symptoms. Among the 24 nonfunctioning EPTs, 5 patients had been explored earlier and their tumors judged inoperable due to locally invasive disease or misdiagnosis as pancreatic adenocarcinoma. The operations were performed with no mortality and low morbidity. We conclude that large and malignant EPTs with limited spread of disease may benefit from a combination of medical and surgical therapy.

Adult↗

Method for dissection of mesenteric metastases in mid-gut carcinoid tumors.

With adequate medical management the midgut carcinoid tumor generally is an indolent malignancy associated with substantial life expectancy and appreciable life quality, even in the presence of liver metastases and significant tumor burden. Abdominal complications may occur in this entity of carcinoids owing to entrapment of intestines and encasement of mesenteric vessels by mesenteric metastases and associated marked mesenteric fibrosis. This may be the cause of abdominal pain, disabling diarrhea, weight loss to the extent of malnutrition, and eventually the risk of death with acute or chronic intestinal obstruction or intestinal gangrene. Operative removal of the mesentericointestinal lesion is often indicated to prevent or treat these complications but may be technically difficult when mesenteric metastases extend in the vicinity of major vessels in the mesenteric root. At laparotomy 56 patients with advanced midgut carcinoids underwent removal of the mesenteric tumor with a method for preserving the mesenteric vessels. This was feasible by mobilizing and releasing the right colon and mesenteric root from posterior adhesions, identifying the mesenteric artery below the pancreas, and free-dissecting this artery on the tumor capsule in the mobilized mesentery. Dissection was successful even with tumors initially judged inoperable unless tumor growth completely surrounded the mesenteric vessels or extended retroperitoneally. One patient was subjected to distal intestinal artery bypass. Symptom relief was been substantial and often of long duration after mesenteric tumor removal in patients who prior to surgery often had threatening intestinal ischemia. Patients with advanced midgut carcinoids may benefit markedly from dissectional removal of mesenteric tumors, which (conceivably better than conventional wedge resection) preserves the length of the remaining intestine.

Angiography↗

Distribution of (76)Br-labeled antisense oligonucleotides of different length determined ex vivo in rats.

Oligonucleotides may hybridize with high selectivity to an RNA sequence and can be used for the monitoring of gene expression or for its inhibition in experimental or therapeutic purposes. As part of the development of positron emission tomography (PET) methods, different lengths (30, 20, 12 and 6 mer) of antisense phosphorothioate oligonucleotides complementary to rat chromogranin A were labeled with [(76)Br] using a prosthetic group. The (76)Br-oligonucleotides were injected into rat's tail vein (1-2 MBq/rat), and the radioactivity distribution was analyzed after 20 h using whole body autoradiography or by measurement of organ radioactivity concentration. The whole body autoradiography showed different distribution depending on the oligonucleotide length. The organs with highest uptake changed from kidney cortex (with 6 or 12 mer), kidney cortex and liver (with 20 mer), to liver and spleen (with 30 mer). With 20 or 30 mer sequences, uptake could be observed in the adrenals. Kidneys and livers from rats receiving 20 mer or 30 mer (76)Br-oligonucleotides were analyzed with respect to subcellular distribution and DNA/RNA/protein fraction. 30%-45% of the radioactivity was found in the nuclear fraction. More than 80% of the radioactivity was recovered in the high molecular weight fraction (as proteins or oligonucleotides longer than 10 mer) using size exclusion (NAP 5) gelfiltration or cetylpyridinium bromide (CPB) precipitation. This work indicates the potential to perform kinetic whole body studies of (76)Br-oligonucleotides using PET.

Animals↗

Demonstration of [11C] 5-hydroxy-L-tryptophan uptake and decarboxylation in carcinoid tumors by specific positioning labeling in positron emission tomography.

In three patients with carcinoid liver and/or lymph node metastases, we studied the process of tumor tracer uptake and decarboxylation by means of positron emission tomography (PET) using 5-hydroxy-L-tryptophan (5-HTP) 11C-labeled in the beta-position (HTP) and later the same day with 5-HTP 11C-labeled in the carboxyl group (HTC). With HTP, in which the 11C-label follows the molecule through decarboxylation to form 11C-serotonin, a high tumor accumulation of the tracer was found. With HTC, in which the label is rapidly eliminated from the tissues as 11CO2 if decarboxylation takes place, there was virtually no uptake by the tumors. By utilizing data from PET scanning with both tracers, we could quantify the decarboxylation rate and tissue accumulation of [11C]-serotonin and hence the enzymatic action of aromatic amino acid decarboxylase.

5-Hydroxytryptophan↗

Expression of CD44 variant isoforms and association to the benign form of endocrine pancreatic tumours.

BACKGROUND: The expression of CD44 and its isoforms have been shown in many neoplastic tissues to serve as prognostic indicators, therefore, the feasibility of using these as prognostic markers in endocrine pancreatic tumour patients was examined. PATIENTS AND METHODS: Immunohistochemistry (IHC) was performed on 26 tumour samples (5 gastrinomas, 3 glucagonomas, 10 non-functioning tumours, 6 insulinomas, 2 mixed insulinoma and glucagonomas) with monoclonal antibodies against CD44s (standard form) and variant isoforms (v4, v5, v6, v7, v7-8, v9, v10). Staining was correlated to the tumour proliferation, malignancy, metastasis and patients survival. RESULTS: There was variable expression of CD44s. All tumours showed complex expression of many isoforms. CD44v6 and CD44v9 were down regulated in malignant tumours. There was statistical significance of CD44v6 expression in benign tumours (P < 0.05) compared to malignant tumours and near significance in CD44v9 expression (P = 0.0574). Survival of the patients with CD44v6 positive staining was higher than those who were negative (P = 0.0822). Moreover, the expression was well correlated to the patients without any distant metastases (CD44v6, p < 0.001; CD44v9, P < 0.01). Tumour proliferation (Ki67 index) correlated directly to the malignancy (P < 0.05) and there was inverse correlation between Ki67 index and CD44v6 (P < 0.05) as well as v9 (P < 0.05). CONCLUSIONS: Endocrine pancreatic tumours express CD44s and isoforms differentially. Expression of the two isoforms of CD44, namely v6 and v9 seem to be related more to benign form of the tumour and could serve as a predictor of good prognosis.

Adenoma, Islet Cell↗