PubMed Health⌕ Search

Biomedical subjects

M Frydenberg

Publications and source records attributed to M Frydenberg.

At least 19 recordsLinked to original sources

Sex steroids modulate alpha 1-adrenoceptor-stimulated Ca2+ elevation in human cultured prostatic stromal cells.

BACKGROUND: Benign prostatic hyperplasia is an age- and androgen-dependent condition of urethral compression caused by prostatic contractility and glandular enlargement. In this study we investigate whether testosterone, dihydrotestosterone and estradiol modulate the ability of human cultured prostatic stromal cells (HCPSCs) to respond to the adrenoceptor agonists, noradrenaline (30 microM) and phenylephrine (100 microM), the protein kinase C activating phorbol ester, phorbol diacetate (PDA, 10 microM), and the L-type Ca(2+) channel activator, (-)-Bay K8644 (Bay K, 10 microM) with elevations of intracellular Ca(2+) ([Ca(2+)](i)). METHODS: Cells were loaded with the Ca(2+) sensitive fluorophore, FURA-2AM (10 microM) and changes in intracellular Ca(2+) determined before and 8-12 min after ligand addition. RESULTS: Compared to steroid-free (SF) controls, the incubation of HCPSC with testosterone (30 and 300 pM) significantly increased responses to both noradrenaline and phenylephrine. Responses to Bay K were significantly reduced between 30 nM to 300 pM but responses to PDA were not greatly affected. Compared to SF the addition of estradiol (E(2), 100 pM) did not affect responses to phenylephrine. The concomitant addition of dihydrotestosterone (DHT) and E(2) (to give ratios from 1:1 to 1,000:1) elevated the responses to noradrenaline and phenylephrine at the extreme ranges. Responses to PDA and Bay K generally increased as DHT:E(2) approached unity. CONCLUSIONS: These results indicate that sex steroids modulate the activities of HCPSCs through the regulation of both receptors and signal transduction processes.

Adrenergic alpha-1 Receptor Agonists↗

Having children with different men and subsequent cancer risk. A nationwide study in Denmark.

The more men by whom a woman has children, the more diverse will be the foetal antigens of paternal origin introduced into her bloodstream, and we investigated whether this has an impact on subsequent cancer risks. By using population registries we identified 64704 women who had children with at least two different partners from 1973 to 1996 in Denmark. We compared their cancer incidence with that of women who during the same time period had at least two births with no indication of partner change, adjusting for age, parity, socioeconomic factors and residence. The overall cancer incidence was more than 50% higher in women with two or more partners. Women having children with multiple partners had a higher incidence of cancer of the cervix and corpus uteri, a lower incidence of melanoma but a similar incidence of breast and ovarian cancer. Uncontrolled differences in lifestyle factors may explain the higher cancer risk associated with having multiple partners. The strong protective effect for melanoma was unexpected and deserves further study.

Adult↗

A1 and A2A adenosine receptor modulation of alpha 1-adrenoceptor-mediated contractility in human cultured prostatic stromal cells.

1. This study investigated the possibility that adenosine receptors modulate the alpha(1)-adrenoceptor-mediated contractility of human cultured prostatic stromal cells (HCPSC). 2. The nonselective adenosine receptor agonist, 5'-N-ethylcarboxamido-adenosine (NECA; 10 nm-10 microm), and the A(1) adenosine receptor selective agonist, cyclopentyladenosine (CPA; 10 nm-10 microm), elicited significant contractions in HCPSC, with maximum contractile responses of 18+/-3% and 17+/-2% reduction in initial cell length, respectively. 3. In the presence of a threshold concentration of phenylephrine (PE) (100 nm), CPA (1 nm-10 microm) caused contractions, with an EC(50) of 124+/-12 nm and maximum contractile response of 37+/-4%. The A(1) adenosine receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX 100 nm) blocked this effect. In the presence of DPCPX (100 nm), NECA (1 nm-10 microm) inhibited contractions elicited by a submaximal concentration of PE (10 microm), with an IC(50) of 48+/-2 nm. The A(2A) adenosine receptor-selective antagonist 4-(2-[7-amino-2-[furyl][1,2,4]triazolo[2,3-alpha][1,3,5,]triazin-5-yl amino]ethyl)phenol (Zm241385 100 nm) blocked this effect. 4. In BCECF-AM (10 microm)-loaded cells, both CPA (100 pM-1 microm) and NECA (100 pm-10 microm) elicited concentration-dependent decreases in intracellular pH (pH(i)), with EC(50) values of 3.1+/-0.3 and 6.0+/-0.3 nm, respectively. The response to NECA was blocked by Zm241385 (100 nm; apparent pK(B) of 9.4+/-0.4), but not by DPCPX (100 nm). The maximum response to CPA was blocked by DPCPX (100 nm), and unaffected by Zm241385 (100 nm). 5. NECA (10 nm-10 microm) alone did not increase [(3)H]-cAMP in HCPSC. In the presence of DPCPX (100 nm), NECA (10 nm-10 microm) caused a concentration dependent increase in [(3)H]-cAMP, with an EC(50) of 1.2+/-0.1 microm. This response was inhibited by Zm241385 (100 nm). CPA (10 nm-10 microm) had no effect on cAMP, in the presence or absence of forskolin (1 microm). 6. These findings are consistent with a role for adenosine receptors in the modulation of adrenoceptor-mediated contractility in human prostate-derived cells.

Adenosine A1 Receptor Agonists↗

Head injury as a risk factor for bipolar affective disorder.

BACKGROUND: Case reports have associated head injury with psychoses including affective disorders, but little is known regarding head injury as a risk factor for the onset of bipolar affective disorder. METHODS: The Danish Psychiatric Case Register and the Danish National Patients Register were linked together with the Danish Population Register, thus identifying 10,242 patients with bipolar affective disorder, and 102,420 matched controls. History regarding head injury was recorded from the National Patients Register data. Data were analysed using conditional logistic regression. RESULTS: Bipolar affective disorder was associated with an increased risk of a history of head injury (IRR=1.55; 95% CI 1.36-1.77). The increased risk was confined to head injury occurring less than 5 years before the first psychiatric admission. The finding could not be ascribed to increased accident proneness (as evaluated through the occurrence of other fractures not involving the skull). LIMITATIONS: In studies based on clinical diagnoses only and limited to patients who were hospitalised for psychiatric disorder, exposure was limited to injuries leading to admission to hospital. CONCLUSIONS: Head injury may be a contributing factor to the onset of bipolar affective illness. However, this factor is probably only relevant to a relatively small minority of cases.

Accidents↗

Gyrus bipolar electrovaporization vs transurethral resection of the prostate: a randomized prospective single-blind trial with 1 y follow-up.

The Gyrus system uses bipolar electrocautery with saline irrigation to vaporize prostatic tissue and is compared to transurethral resection of the prostate (TURP) in a randomized prospective study with 1 y follow-up. Outcomes measured were fluid absorption, blood loss, period of catheterization, hospital stay, symptom scores, quality of life, flow rates, and post-void residual volumes at 3, 6, and 12 months. All measured parameters were similar, although re-catheterization rates were higher (30% vs 5%) in the Gyrus group. Clot evacuation rates were higher in the TURP group (19% vs 0%). The Gyrus device is safe and produces results that are similar to TURP at 1 y.

Aged↗

Mental illness in new neurological patients.

OBJECTIVE: To determine the prevalence of psychiatric disorders in new neurological inpatients and outpatients, and examine whether they are recognised, treated, or referred to psychiatric consultation. METHODS: 198 consecutive patients referred for the first time to a neurologist were studied using a two phase design. ICD-10 psychiatric diagnoses were established by means of the SCAN (Schedules for Clinical Assessment in Neuropsychiatry). RESULTS: The overall prevalence of current mental disorders was 55.1% (95% CI: 46.2 to 63.8), and 65.0% (95% CI: 56.1 to 73.0) had at least once in their life had a psychiatric disorder. The most frequent current diagnoses were somatoform disorders (33.8%, (95% CI: 25.9 to 42.7%)), followed by phobias (21.8%; 95% CI: 15.3 to 30.0), substance use disorders (13.3%; 95% CI: 8.3 to 20.6) and depression/dysthymia (14.4; 95% CI: 9.1 to 21.8). The psychiatric morbidity markedly declined with increasing age. Compared with 63.5% of the women, 46.4% of the men had a psychiatric disorder. Substance use disorders were more frequent in men than women (p=0.002). Patients with a psychiatric disorder were more frequently seen in the outpatients' clinic than those without. The neurologists detected 14%-40% of the cases, 16.9% were in treatment, and only 4.6% were referred to mental health care. CONCLUSION: Psychiatric disorders, in particular somatoform disorders, are extremely common in neurological patients, especially in young and middle aged patients, outpatients, and women. The results call for more research on mental illness' impact on care and outcome in neurological patients.

Ambulatory Care↗

The effect of choosing different units of analysis when estimating risk of presence of dental caries in the primary dentition.

BACKGROUND: Data on caries are usually collected with the tooth surface or the tooth as the unit, but subsequently analysed by aggregating the data at the level of the individual. AIMS: To evaluate how different units of analysis may affect the result of the statistical analyses in a study of the association between deciduous dental caries and a set of risk factors. METHOD: 293 children (mean age: 7.5 yrs) from two primary schools in Dar es Salaam, Tanzania were examined. Thus the study design was cross-sectional. Logistic regression analysis was used to determine the association between caries experience and nutritional status, socioeconomic background, and microbiological and salivary characteristics using the subject, the tooth, and the tooth surface as unit of analysis, allowing for the fact that teeth and surfaces within the same individual must be considered non-independent. RESULTS: When aggregated data were used, point estimates were larger in some instances. The precision of the estimates increased considerably when the tooth as compared to the individual was used as the unit of analysis. No or limited gain in precision was obtained when the tooth surface as compared to the tooth was used as unit of analysis. CONCLUSIONS: The choice of unit of analysis may strongly influence the result of the statistical analyses and thus the conclusion of an investigation.

Buffers↗

Protein kinase G activation of K(ATP) channels in human-cultured prostatic stromal cells.

In this study, we identify and investigate the role of protein kinase G (PKG) in cells cultured from human prostatic stroma. Cells were used for immunocytochemistry, contractility or K(+) fluorescent imaging studies. All cultured prostatic stromal cells showed PKG immunostaining. Phorbol 12,13 diacetate (PDA, 1 microM) elicited contractions from human-cultured prostatic stromal cells that could be blocked by both the L-type Ca(2+) channel blocker, nifedipine (3 microM), and the protein kinase C inhibitor, bisindolylmaleimide (1 microM). The nitric oxide donor, sodium nitroprusside (SNP, molar pIC(50) 5.16+/-0.17) and the cGMP-phosphodiesterase inhibitor, zaprinast (50 microM), inhibited PDA (1 microM)-induced contractions. The PKG activator beta-phenyl-1, N(2)-ethenoguanosine-3',5'-cyclic monophosphate (PET-cGMP, molar pIC(50) 6.96 +/- 0.25) also inhibited PDA (1 microM)-induced contractions. Glibenclamide (10 microM) and Rp-8-Br-cGMPS (5 microM), but not iberiotoxin (100 nM) or Rp-cAMP (5 microM), reversed this inhibition. In human-cultured prostatic stromal cells loaded with the K(+) fluorescent indicator, 1,3-Benzenedicarboxylic acid, 4,4'-[1,4,10,13-tetraoxa-7,16-diazacyclooctadecane-7,16-diylbis(5-methoxy-6,2-benzofurandiyl)]bis-, tetrakis [(acetyloxy) methyl] ester (PBFI), PET-cGMP (300 nM) caused a reduction in intracellular K(+) that was blocked by glibenclamide (10 microM) and Rp-8-Br-cGMPS (5 microM), but not by iberiotoxin (100 nM). These data are consistent with the hypothesis that, in human-cultured prostatic stromal cells, PKG inhibits contractility through the activation of K(ATP) channels.

Adenosine Triphosphate↗

Accuracy of caries detection with four storage phosphor systems and E-speed radiographs.

OBJECTIVE: To evaluate the accuracy of caries detection using four intra-oral storage phosphor plate systems exposed with two different exposure times and one film system. METHODS: Under in vitro and standardised conditions 365 approximal and 159 occlusal surfaces were radiographed using four storage phosphor plate systems: DenOptix, Cd-dent, Digora (blue and white plates) and one film system: Ektaspeed Plus. The plates were exposed twice with 10% and 25% of the time needed for the film. Four observers recorded approximal enamel/dentine and occlusal dentine caries using a five-point confidence scale. Caries presence was validated histologically and diagnostic accuracy of the systems by using ROC curve areas (Az). RESULTS: The shorter exposure time for approximal caries, Digora(white)(Az=0.68) and Ekta Plus (Az=0.69) were significantly more accurate than the other systems (Az=0.64-0.65). For occlusal caries using the same exposure time, no significant difference was found between the digital systems (Az=0.76-0.77), which all showed to be significantly less accurate than Ekta Plus (Az=0.81). Using the longer exposure time for approximal caries, no significant difference was found between DenOptix (Az=0.68), Digora(blue) (Az=0.69), Digora(white) (Az=0.69) and Ekta Plus (Az=0.69) which were all significantly more accurate than Cd-dent (Az=0.65). For occlusal caries using the same exposure time, Digora(blue) (Az=0.81) was the most significantly accurate of the digital systems. When approximal caries was the diagnostic task, the longer exposure time resulted in significantly higher accuracy with the DenOptix and Digora(blue) systems but not with the Cd-dent and Digora(white) systems. For occlusal caries, the longer exposure time resulted in a significant improvement only with the Digora(blue) system. CONCLUSION: For approximal caries using the longer exposure time, no significant difference in diagnostic accuracy was found between DenOptix, Digora(blue), Digora(white) and Ekta Plus which were all significantly more accurate than the Cd-dent. For occlusal caries using the longer exposure time, Digora(blue) was found to be the most accurate of the digital systems. The exposure time had an influence on the diagnostic accuracy with the DenOptix and Digora(blue) systems for approximal and with the Digora(blue) system for occlusal caries detection.

Area Under Curve↗

Occupational accidents aboard merchant ships.

OBJECTIVES: To investigate the frequency, circumstances, and causes of occupational accidents aboard merchant ships in international trade, and to identify risk factors for the occurrence of occupational accidents as well as dangerous working situations where possible preventive measures may be initiated. METHODS: The study is a historical follow up on occupational accidents among crew aboard Danish merchant ships in the period 1993-7. Data were extracted from the Danish Maritime Authority and insurance data. Exact data on time at risk were available. RESULTS: A total of 1993 accidents were identified during a total of 31 140 years at sea. Among these, 209 accidents resulted in permanent disability of 5% or more, and 27 were fatal. The mean risk of having an occupational accident was 6.4/100 years at sea and the risk of an accident causing a permanent disability of 5% or more was 0.67/100 years aboard. Relative risks for notified accidents and accidents causing permanent disability of 5% or more were calculated in a multivariate analysis including ship type, occupation, age, time on board, change of ship since last employment period, and nationality. Foreigners had a considerably lower recorded rate of accidents than Danish citizens. Age was a major risk factor for accidents causing permanent disability. Change of ship and the first period aboard a particular ship were identified as risk factors. Walking from one place to another aboard the ship caused serious accidents. The most serious accidents happened on deck. CONCLUSIONS: It was possible to clearly identify work situations and specific risk factors for accidents aboard merchant ships. Most accidents happened while performing daily routine duties. Preventive measures should focus on workplace instructions for all important functions aboard and also on the prevention of accidents caused by walking around aboard the ship.

Accidents, Occupational↗

A case-control study of the androgen receptor gene CAG repeat polymorphism in Australian prostate carcinoma subjects.

BACKGROUND: The development of prostate carcinoma is androgen-dependent. The coding sequence of the androgen receptor (AR) gene contains a CAG repeat polymorphism that has been shown to influence AR activity in vitro. Studies of this polymorphism as a prostate carcinoma risk factor have been conflicting. METHODS: A matched case-control design was used in a clinic-based multicenter study of Australian prostate carcinoma subjects. Cancer subjects were matched by age and locality with controls, all of whom had a serum prostate specific antigen (PSA) level of less than 4 mg/L. Conditional logistic regression was used to determine the relative risk of prostate carcinoma dependent on AR gene CAG number. The association of disease characteristics at diagnosis with the polymorphism also was assessed. RESULTS: Five hundred forty-five cases of prostate carcinoma and 456 matched case-control pairs were recruited. Association studies of disease characteristics at diagnosis showed age at diagnosis to be associated with AR CAG number by univariate (P = 0.004) and multivariate (adjusting for PSA, stage, and grade) linear regression (P = 0.018). No association was observed between the polymorphism and disease stage (TNM-based categories; P = 0.277), histologic grade (P = 0.41), or PSA level at diagnosis (P = 0.48). In the pairwise case-control analysis, the odds ratio of prostate carcinoma for a change of 5 CAG repeats gave an odds ratio of 0.9821 (95% confidence interval, 0.84-1.15). CONCLUSIONS: In this Australian study population, the AR CAG repeat polymorphism was not a risk factor for prostate carcinoma, but a shorter repeat sequence was associated with earlier age at diagnosis.

Adult↗

Obstetric complications in women with schizophrenia.

It is not known whether schizophrenic women have increased incidence of complications during pregnancy and delivery. Data from the Danish Medical Birth Register were used to compare 2212 births to 1537 schizophrenic women in Denmark with a random sample of all deliveries in Denmark during 1973-1993 (122931 births to 72742 women). The schizophrenic women had fewer antenatal care visits. They were at lower risk of pre-eclampsia, but tended to have lower Apgar scores. There were no other differences in the incidence of specific complications such as placenta previa, placental abruption, and abnormal fetal presentation. Schizophrenic women were at increased risk of interventions such as Cesarean section, vaginal assisted delivery, amniotomy, and pharmacological stimulation of labor. There were no important differences between the deliveries to schizophrenic women who gave birth before and after their first admission to a psychiatric department. These results show no evidence that schizophrenic women have a greater frequency of specific obstetric complications than non-schizophrenic women. Nevertheless, they are at increased risk for interventions during delivery.

Adult↗

Mental disorders among internal medical inpatients: prevalence, detection, and treatment status.

OBJECTIVE: To determine the prevalence of ICD-10 mental disorders among internal medical inpatients, the relation between mental disorder, age, and gender, and the recognition and referral of the disordered patients. METHOD: 294 consecutive medical inpatients were examined with a two-phase design using the SCAN (Schedules for Clinical Assessment in Neuropsychiatry) for ICD-10 psychiatric diagnoses. Information from questionnaires and interviews with patients, doctors, nurses, and from medical records. RESULTS: The prevalence of current mental disorders was 38.7%, being heavily increased in young patients. Main diagnoses were somatoform disorders (17.6%), phobias (12.9%), substance use disorders (10.9%), and depression (8.3%). Psychiatric consultations were very few. About 38-56% of the cases were recognized by medical doctors and nurses, and only about 20% were in mental health treatment. CONCLUSION: The prevalence of mental disorders among internal medical inpatients is high and increased in young patients and women. Detection and referral are low, and few are treated.

Adult↗

Testosterone- and phorbol ester-stimulated proliferation in human cultured prostatic stromal cells.

Prostatic stromal proliferation may be commonly associated with the development of benign prostatic hyperplasia. In this study, we investigate the role of testosterone and protein kinase C in stimulating cultured stromal cell proliferation. Testosterone increased the uptake of [(3)H]-thymidine into the human cultured prostatic stromal cells, this was reduced by the protein kinase C inhibitors, bisindolylymaleimide (10 nM) and myristoylated protein kinase C inhibitor (mPKCi, 20 microM), but not by Gö 6983 (1 microM) or Gö 6976 (1 microM). Cells responded to the addition of the PKC activators phorbol 12,13 dibutyrate (PDB), phorbol 12,13 diacetate (PDA), 12-deoxyphorbol 13-acetate (DPA) and 12-deoxyphorbol 13-tetradecanoate (DPT) with proliferation (order of potency DPT> or =PDB>>PDA=DPA). The DPT-stimulated proliferative response was inhibited after cells were electroporated with PKCalpha antisense, but not mismatch oligonucleotides (8 microM). These results indicate that PKCalpha is involved in the proliferative response of human cultured prostatic stromal cells.

Cell Division↗

How many patients are needed? Variation and design considerations in bone histomorphometry.

In osteoporosis research, bone histomorphometry plays an important role in documenting the biological effects and possible side-effects of new drug treatments. To ensure that the study is properly scaled, it is important to be concerned with the risk of type II error; that is, the risk of failing to detect a real difference. We therefore calculated the necessary sample size in bone histomorphometric studies according to a specified difference of 15% between two groups. The calculations were based on variance components estimated from three different studies: women with a distal fracture of the forearm (n = 22); patients with pituitary insufficiency (n = 21); and patients with primary hyperparathyroidism (n = 21). Using a significance level of 0.05 and a risk of type II error of 0.20, the statistical power of two different designs was compared: a single biopsy design comparing the responses in two groups after the treatment; and a paired biopsy design in which individual differences (posttreatment minus baseline) were calculated before the comparison of the two groups. We found that the mineral apposition rate, wall thickness, and erosion depth are statistically powerful indices that, in the single biopsy design, require no more than n = 25 in each group to detect differences of 15% between the groups. Bone volume, erosion surface, osteoid surface, mineralizing surface, and activation frequency need group sizes of 100-600 individuals to find a 15% difference to be statistically significant. However, the effect of bisphosphonate treatment, for instance, is large enough to reduce the group size to 20 individuals concerning activation frequency. The remodeling balance reaches extreme group sizes of several thousand for a 15% difference to be statistically significant, but for a 5 microm (approximately 150%) improvement, about 100 individuals are required in the single biopsy design. An analysis of the components of variance showed that the variation between individuals is small and often negligible compared with the variation within individuals, and sample sizes needed for the paired biopsy design are therefore larger than those for the single biopsy design. In conclusion, the most cost-effective histomorphometric study design within a randomized clinical trial appears to be a single biopsy design comparing posttreatment biopsies with scaling performed according to the statistical power of the indices of interest.

Biopsy↗

Obstetric complications and risk for severe psychopathology in childhood.

The purpose of the study was to assess the association of obstetric complications with risk for mental disorders resulting in hospitalization before the age of 15. Records from all births in Denmark from 1973 through 1993 were linked to records of all psychiatric hospitalizations. Diagnoses were grouped into seven broad categories. A reference population of 10% of births in Denmark from 1973 to 1990 was used for comparison. Obstetric complications were associated with the range of mental disorders occurring in childhood. The strongest predictors were a variable indicating the interaction of birth weight with speed of growth and the 5-minute Apgar score. There was no diagnostic group that stood out as different with respect to obstetric complications. These results are consistent with the hypothesis of the continuum of reproductive casualty.

Adult↗

The in vivo effect of red clover diet on ventral prostate growth in adult male mice.

The incidence of clinically significant prostate disease in Asian men is lower than in Western men and appears to be influenced by dietary and environmental factors. The aim of this study was to examine the effect of dietary isoflavones on prostate growth in intact male mice using an extract of red clover. The results demonstrated that prostate, but not testis, size was significantly reduced over 28 days of a red clover isoflavone supplemented diet. Histological examination revealed an increase in apoptotic cells, rather than a reduction in proliferative activity in the epithelium. These findings support the hypothesis that dietary red clover isoflavones can induce apoptosis and lead to a reduction in prostate size.

Animal Feed↗

The metaplastic effects of estrogen on mouse prostate epithelium: proliferation of cells with basal cell phenotype.

The exogenous administration of estrogens to male mice alters the hypothalamic-pituitary-gonadal axis and reduces androgen levels, leading to a regression of the prostatic epithelium. As well, a specific direct response to estrogens is the induction of epithelial squamous metaplasia. The aims of this study were to identify the process by which the prostatic epithelium is transformed in intact adult male mice using the synthetic estrogen, diethylstilbestrol. A comparison of the effects of diethylstilbestrol in the three lobes revealed a hierarchy of response, with the anterior lobe being the most responsive, the dorsolateral lobe less responsive, and the ventral lobe the least responsive. The effect of castration was used to distinguish between the epithelial responses to estrogen administration and androgen deprivation. The results demonstrate that transformation of the epithelium involved proliferation of cells with a basal cell phenotype, the onset of cytokeratin 10 expression, up-regulation of progesterone receptor expression, and loss of the cell cycle inhibitor, p27(Kip1) expression; none of these changes was observed after castration. Mice lacking functional estrogen receptor alpha failed to respond, demonstrating a requirement for estrogen receptor alpha in the epithelium and/or stroma to mediate the proliferative response to estrogen in the prostate gland.

Animals↗