Critique of editorial philosophy.
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Humans↗
Biomedical subjects
E Eriksson
Publications and source records attributed to E Eriksson.
How reliable are measurements with arthrometers?
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Anterior Cruciate Ligament↗
Gelatinase A, membrane type 1 matrix metalloproteinase, and extracellular matrix metalloproteinase inducer mRNA expression: correlation with invasive growth of breast cancer.
Invasive breast cancer varies widely in biologic aggressiveness, from fairly indolent tumors to rapidly disseminating carcinomas. Matrix metalloproteinases have enzymatic activity and assist in tumor invasion by degrading basement membranes and extracellular matrix. The extracellular matrix metalloproteinase inducer EMMPRIN is thought to stimulate fibroblasts to produce the zymogen pro-gelatinase A. The membrane type 1-matrix metalloproteinase (MT1-MMP) is thought to assist in tumor invasion and metastasis by activating pro-gelatinase A, which shows enhanced expression in various tumors. Overexpression of gelatinase A has shown to correlate with a malignant phenotype in many tumor forms. The aim of the study was to investigate the mRNA expression pattern of MT1-MMP, gelatinase A, and EMMPRIN in breast tumors. Formalin-fixed paraffin-embedded breast tissue samples from 18 patients operated on with breast-conserving surgery for invasive breast carcinoma <20 mm between 1977 and 1985 were analyzed using the mRNA in situ hybridization technique. Most of the patients were node-negative (15/18) and underwent postoperative irradiation to the breast (16/18). The median age at diagnosis was 52 years (21-83 years). At the time of the study 11 patients were alive, 4 without recurrence; 7 patients had been operated for ipsilateral breast tumor recurrences, and 2 had distant metastases. The median follow-up was 112 months (102-193 months). Seven patients died of disseminated breast cancer; their median follow-up was 43 months (22-116 months). (35)S-labeled antisense and sense mRNA probes transcribed from linearized plasmids containing cDNA for the matrix metalloproteinases gelatinase A and MT1-MMP and the glycoprotein EMMPRIN were hybridized to 5 microm paraffin-embedded tissue sections. Several invasive carcinomas were surrounded by normal tissue and carcinoma in situ lesions. Gelatinase A, MT1-MMP, and EMMPRIN mRNA expression were detected in all of the carcinomas. The gelatinase A mRNA expression was mainly localized to stromal cells at moderate to high levels surrounding the invading carcinoma cells but was also seen in single cells at low levels in in situ lesions and in some normal glandular cells. MT1-MMP and EMMPRIN were expressed in all of the carcinomas and were mainly localized to tumor cells; but they were also seen to some extent in single cells at low levels in in situ lesions and in normal glandular cells. No differences in levels of expression for gelatinase A, MT1-MMP, or EMMPRIN were seen in patients who survived compared to patients who died from metastatic disease. The co-expression of gelatinase A, MT1-MMP, and EMMPRIN mRNA in invasive breast carcinoma supports the theory that these proteins interact and are important for the invasive phenotype in breast carcinoma. Hence EMMPRIN may be a central factor for stimulation of gelatinase A activation. Specific inhibition for individual MMP members could in the future be target-specific events in breast tumor progression. Inhibition of EMMPRIN could be such a target.
Adenocarcinoma↗
Antitumour activity of suramin analogues in human tumour cell lines and primary cultures of tumour cells from patients.
Suramin has shown promising antitumour activity against several tumour types, both in vitro and in vivo, but the clinical utility of this compound is hampered by its unfavourable toxicity profile. In the present study, the semi-automated fluorometric microculture cytotoxicity assay (FMCA) was employed for evaluation of the cytotoxicity of seven suramin analogues in vitro in a panel of human tumour cell lines and in primary cultures of tumour cells from patients. Like suramin, the analogues showed little sensitivity to resistance mechanisms involving P-glycoprotein, topoisomerase II, multidrug resistance associated protein and glutathione-mediated drug resistance. In the cell line panel, NF067 and FCE 26644 showed activity comparable with suramin. All analogues were less potent than suramin in patient cells except for FCE 26644. Correlation to suramin activity patterns in the cell line panel was highest for NF037 and low to moderate for the remaining analogues. In patient cells, high correlation coefficients were obtained for FCE 26644, NF110, NF031 and NF037. The results indicate that the cytotoxic activity of suramin on patient tumour cells is shared by the analogues with FCE 26644 being the most active. The pharmacophore for cytotoxicity in patient cells may be different from that observed in the cell lines.
Antineoplastic Agents↗
Antidepressant drugs: does it matter if they inhibit the reuptake of noradrenaline or serotonin?
The current popularity of the selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression should not conceal the fact that noradrenergic neurones also seem to influence depressed mood. Selective noradrenaline reuptake inhibitors (NRIs) such as reboxetine thus seem to be at least as effective as the SSRIs. It has been suggested that NRIs influence depression by indirectly facilitating serotonergic transmission, or that SSRIs act by facilitating noradrenaline; however, the marked differences between SSRIs and NRIs with respect to effects and side-effect profile do not support any of these assumptions, but rather suggest that SSRIs and NRIs influence depression by parallel, independent pathways. In this review the possibility that certain symptoms within the depressive syndrome (and certain subtypes of depression) respond better to NRIs, whereas other symptoms (and subtypes) respond better to SSRIs, will be discussed. In addition, the putative usefulness of NRIs for indications other than depression will be commented upon.
Adrenergic Uptake Inhibitors↗
Informational and emotional support for cancer patients' relatives.
The purpose of this study was to find out what cancer patients' relatives think about the actions of health care professionals in terms of providing informational and emotional support. The sample consisted of 168 relatives of patients from oncological wards all over Finland. The data were collected with a questionnaire specifically developed for this study. Non-parametric tests were used for statistical analysis. The results clearly highlighted the importance of informing relatives about the patient's illness. However, less than one-third of the relatives said they received much information. Relatives' need for emotional support was clearly at a lower level than their need for information. Even so, only very little support was provided in relation to relatives' needs.
Adult↗
Participation of relatives in the care of cancer patients.
This study aims to find out how important it is for relatives to take part in the care of cancer patients and to see to what extent they actually do take part. Participation is defined as consisting of concrete care activities, emotional support and participation in decision-making concerning the patient's care. The sample comprised 168 relatives of cancer patients from oncology wards all over Finland. Data were collected with a questionnaire specifically developed for this study. Nonparametric tests were used for statistical analyses. The results showed that the most important aspect of relatives' participation was supporting the patient emotionally; providing concrete care and participation in decision-making were both considered less important. Over 80% of the relatives said they gave a considerable amount of support to the patient. Most relatives said that they visited the patient in hospital, talked to the patient about their concerns and were near them whenever they felt they needed that. On the other hand, relatives did not take part in discussions about care, nor were they informed about such a possibility.
Journal Article↗
Prevalence and characteristics of pressure ulcers. A one-day patient population in a Finnish city.
This article discusses the prevalence and characteristics of pressure ulcers in a one-day patient population in a Finnish city. The data was collected using two questionnaires. Data analysis was based on percentage distributions; statistical significances were tested with the Chi-square test. The measurement identified 186 patients with a total of 300 pressure ulcers. The majority (90%) of these patients were hospitalized and 10% were in outpatient care. The main causes for the development of pressure ulcers were inadequate turning and positioning and the patient's primary illness. Most of the ulcers were grade II. Only a few patients had ulcers that exposed bone. The preventive effort should extend from the nursing unit level, through the organizational level, to the level of society as a whole. It should consist of the identification of people at high risk for pressure ulcers and the provisions of quality care for these people.
Adolescent↗
Accelerated healing of full-thickness skin wounds in a wet environment.
Full-thickness skin wounds are preferably allowed to heal under controlled hydration dressings such as hydrocolloids. It was hypothesized that a wet (liquid) environment rather than a dry or moist one would accelerate the wound healing process. We compared skin repair by secondary intention in full-thickness skin wounds in wet (saline), moist (hydrocolloid), and dry (gauze) conditions in an established porcine wound healing model. The study included three animals with a total of 70 wounds layered in a standardized fashion on the back of young Yorkshire pigs. Twelve days after wounding, 0 percent of dry, 20 percent of moist, and 86 percent of saline-treated wounds were completely reepithelialized (p values = 0.0046 and 0.027 for saline wounds compared with dry and moist wounds, respectively). The accelerated healing was caused at least in part by faster contraction in wet wounds (p value < 0.005 compared with that of other groups 9 and 12 days after wounding). Development of granulation tissue was faster in moist conditions than it was for dry and wet wounds. The thickness and number of cell layers of the newly formed epidermis were greater in dry and wet wounds than in moist ones. It was concluded that these full-thickness porcine skin wounds healed faster in a wet environment than in a moist one. Dry wounds healed more slowly than moist wounds. The basic mechanisms of skin wound repair were influenced by the treatment modality as demonstrated by the observed differences in granulation tissue formation, reepithelialization, and rate of wound contraction.
Animals↗
Prevention of pressure ulcers in acute and long-term care facilities in Finland: results of a survey.
The purpose of this study was to identify those healthcare organizations that have a high incidence of pressure ulcers, and to determine what their staffs do to prevent pressure ulcer formation. The sample was formed from 11 hospitals in one large city on a certain day in Finland in 1998. The researchers sent questionnaires to 154 hospital units and achieved a 94% response rate. Psychiatric; gynecologic; obstetric; and eye, ear, nose, and throat units were not included. The data were collected using two questionnaires: The first gathered data about the organization and the second about the patients. Fifty-seven percent of the units surveyed reported having patients with pressure ulcers. Of these units, 45% were acute and 55% were long-term care. Thirty-nine percent of all units had a pressure ulcer team. Units with pressure ulcer patients had a staffing level of 0.6 registered nurses and practical nurses per bed, compared with 0.7 registered nurses and practical nurses per bed for those units without pressure ulcer patients. The average length of stay on the unit was less for those without pressure ulcers compared to those with ulcers (P < 0.001) and only 18% of the units without pressure ulcers had a pressure ulcer team. According to the results, those units with pressure ulcer patients identified the need for more preventive measures more frequently than the units without ulcer patients. In conclusion, pressure ulcers seem to predominate in long-term care settings, and the educational level of healthcare staffing seems to impact the occurrence of pressure ulcers. Common preventive measures are used by the staff in both acute and long-term care settings.
Finland↗
Laminin-5 as a marker of invasiveness in cervical lesions.
BACKGROUND: Treatment decisions for cervical cancer, a common disease worldwide, depend on demonstrating whether or not tumor invasion of the surrounding tissue has occurred. Invasion can be difficult to assess by standard histopathologic methods, especially when limited amounts of tissue are available. Several studies of a variety of cancers have reported increased expression of laminin-5-an important attachment protein for epithelial cells-in invasive carcinomas. This study was designed to investigate whether the presence of laminin-5 is related to the invasive capacity of cervical lesions. METHODS: We used immunohistochemical methods to stain archival, paraffin-embedded sections of cervical lesions with a polyclonal antibody specifically targeting the gamma2 chain of human laminin-5 protein. The study sample included 23 lesions of mild and moderate dysplasia (cervical intraepithelial neoplasia [CIN] 1 and 2, respectively), 32 lesions of severe dysplasia or carcinoma in situ (CIN 3), 15 lesions of microinvasive cancer, and 20 lesions of frankly invasive cancer. Cellular proliferative activity was also investigated by the use of monoclonal MIB-1 (directed against the antigen Ki-67) and anticyclin A antibodies. RESULTS: Invasiveness of cervical lesions was positively associated with immunohistochemical staining of the gamma2 chain of laminin-5 (two-sided P =.001). All CIN 1 and CIN 2 lesions-except one CIN 2 lesion later shown to be invasive cancer-and 21 CIN 3 lesions tested negative for the gamma2 chain of laminin-5. Eleven CIN 3 lesions and all invasive cancers tested positive for this protein. One lymph node metastasis and a pleural metastasis from one of the patients with invasive cancer showed strong immunohistochemical positivity. Proliferative activity increased with advancement of the lesion but was not confined to cells positive for the gamma2 chain of laminin-5. CONCLUSIONS: These data suggest that antibodies directed against the gamma2 chain of laminin-5 can identify cervical lesions with invasive capacity and thus may be useful as a sensitive marker of early invasion.
Biomarkers, Tumor↗
A novel anti-herpes simplex virus type 1-specific herpes simplex virus type 1 recombinant.
A recombinant herpes simplex virus (HSV) capable of inhibiting its own replication as well as the replication of wild-type virus would have greatly increased safety as a general purpose vector for in vivo gene transfer, antitumor therapy, and viral vaccine against HSV infection. By using a tetracycline repressor (tetR)-mediated HSV-1 viral replication switch [Yao and Eriksson (1999). Hum. Gene Ther. 10, 419-427], we have generated a novel anti-HSV-1-specific HSV-1 recombinant (CJ83193) that expresses a trans-dominant negative HSV-1 UL9 origin-binding protein, UL9-C535C. The de novo synthesis of CJ83193 can be suppressed by UL9-C535C by at least 1 x 10(6)-fold in non-tetR-expressing cells, and is subject to tetracycline regulation over a range of four to five orders of magnitude in a tetR-expressing osteosarcoma line. In particular, the UL9-C535C peptides expressed from the CJ83193 genome can inhibit the replication of wild-type HSV-1 by 100- to 200-fold in single-step growth assays. The construction of CJ83193 creates a new general strategy for developing recombinant viral vectors able to function as an intracellular therapy against wild-type viral infections.
Animals↗
A novel tetracycline-inducible viral replication switch.
With the cloning of DNA encoding the trans-dominant negative mutant form of the HSV-1 origin-binding protein UL9, UL9-C535C, under the control of the tet operator-bearing hCMV major immediate-early promoter (pcmvtetO), this article demonstrates that the tetR-mediated mammalian transcription repression switch (Yao et al., Hum. Gene Ther. 9:1939-1950, 1998) can be converted to a novel HSV-1-specific viral replication switch. Using this viral replication switch, the plaque-forming efficiency of infectious HSV-1 DNA can be reversibly regulated by tetR over 100-fold in transient viral infection assays. Moreover, while less than 0 PFU/ml of HSV-1 was detected from tetR-expressing cells transfected with infectious HSV-1 DNA and plasmid pcmvtetOUL9-C535C in the presence of tetracycline, close to 1000 PFU/ml of HSV-1 was produced when similar experiments were carried out in the absence of tetracycline. The tetracycline treatment led no reduction in HSV-1 synthesis in cells transfected with infectious HSV-1 DNA alone. Taken together, given that the UL9-C535C-associated antiviral activity can be silenced in the context of this HSV-1 replication switch, the establishment of this reversible switch would allow construction of a new generation of HSV-1 recombinants able to inhibit its own replication as well as replication of wild-type virus.
Animals↗
Personality disorders in relation to anthropometric, endocrine and metabolic factors.
Subjects with abdominal obesity show several signs of a perturbed regulation of the hypothalamic-pituitary-adrenal (HPA) axis. This is known to occur after chronic, submissive stress. Perceived environmental stress is depending on personality characteristics. Therefore, personality disorders (PD:s) were examined in relation to HPA axis status, other endocrine and metabolic variables as well as anthropometry. Men (no.=284) aged 51 years, recruited in similar subgroups of low, median and high waist/hip circumference ratio (WHR) from a sample of 1302 men. Measurements of personality disorders by Structured Clinical Interview for DSM-III-R, Axis II (SCID II), body mass index (BMI, weight, kg/height2, m2), WHR and abdominal sagittal diameter (D), dexamethasone suppression test (0.5 mg, salivary measurements of cortisol), insulin-like growth factor I (IGF-I), testosterone and metabolic variables. Men with cluster A (paranoid, schizotypal, schizoid) PD showed an increased BMI, WHR and D, independent of dexamethasone suppression. Testosterone was decreased in these men in relation to a blunted dexamethasone suppression. BMI, WHR and D were increased in men with cluster B (borderline, histrionic, narcissistic) and cluster C (avoidant, dependent, obsessive compulsive, passive aggressive) PD, only in relation to a blunted dexamethasone suppression. Furthermore, IGF-I was low in cluster B. Metabolic variables were differently associated to clusters of PD but generally followed obesity. Path-analytic models suggested that cluster B and C PD were followed by blunted dexamethasone suppression and obesity. Men with cluster A PD showed centralized body fat distribution, independently of dexamethasone suppression. In contrast, men with impulsive (cluster B) and anxious (cluster C) personality disorders seem often to have abdominal obesity only in combination with a blunted dexamethasone suppression test, suggesting a HPA axis disturbance. These results suggest that PD:s are involved in the development of abdominal obesity in men, with different endocrine and metabolic profiles depending on the type of PD. This might hypothetically be due to frequent exposure and/or an increased sensitivity to environmental stress factors, caused by aberrant personalities.
Anthropometry↗
Treatment of ankle sprains.
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Ankle Injuries↗
How do we treat first time traumatic shoulder dislocations in young athletes?
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Adolescent↗
Objective measurement of sagittal laxity of the knee.
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Anterior Cruciate Ligament Injuries↗