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H H Hansen

Publications and source records attributed to H H Hansen.

At least 19 recordsLinked to original sources
PubMed2006

A prospective study of PET/CT in initial staging of small-cell lung cancer: comparison with CT, bone scintigraphy and bone marrow analysis.

BACKGROUND: Small-cell lung cancer (SCLC) accounts for 15%-20% of all lung cancer cases. Accurate and fast staging is mandatory when choosing treatment, but current staging procedures are time consuming and lack sensitivity. PATIENTS AND METHODS: A prospective study was designed to examine the role of combined positron emission tomography/computed tomography (PET/CT) compared with standard staging (CT, bone scintigraphy and immunocytochemical assessment of bone marrow biopsy) of patients with SCLC. Thirty-four consecutive patients were included. Twenty-nine patients received initial PET/CT. RESULTS: PET/CT caused change of stage in 5/29 (17%). Excluding patients with unconfirmed findings or pleural effusion, the sensitivity for accurate staging of patients with extensive disease was the following: for standard staging 79%, PET 93% and PET/CT 93%. Specificity was 100%, 83% and 100%, respectively. CONCLUSION: The results from this first study on PET/CT in SCLC indicates that PET/CT can simplify and perhaps even improve the accuracy of the current staging procedure in SCLC. A larger clinical trial, preferably with consequent histological confirmation in case of discordance, however, is warranted.

Aged↗
PubMed2005

Regulation of activity-regulated cytoskeleton protein (Arc) mRNA after acute and chronic electroconvulsive stimulation in the rat.

The temporal profile of Arc gene expression after acute and chronic electroconvulsive stimulations (ECS) was studied using semi-quantitative in situ hybridisation in the rat cortex. A single ECS strongly and temporarily increased Arc mRNA levels in dentate granular cells with maximal induction seen up to 4 h after the stimulus, but returned to baseline at 24 h. A single ECS also increased expression of Arc mRNA in the CA1 and the parietal cortex, but the expression peaked within 1 h and returned to baseline levels within 2 h. Repeated or chronic ECS is a model of electroconvulsive therapy and it would be predicted that gene products involved in antidepressant effects accumulate after repeated ECS. However, repeated ECS reduced Arc gene expression in the CA1 24 h after the last stimulus. These results indicate that Arc is an immediate early gene product regulated by an acute excitatory stimulus, but not accumulated by long term repetitive ECS and therefore not a molecular biomarker for antidepressant properties. More likely, Arc is likely a molecular link to the decline in memory consolidation seen in depressive patients subjected to electroconvulsive therapy.

Animals↗
PubMed2005

Magnesium depletion enhances cisplatin-induced nephrotoxicity.

PURPOSE: Nephrotoxicity and magnesium (Mg)-depletion are well-known side effects to cisplatin (CP) treatment. The purpose of this present study was to investigate the role of Mg on CP induced changes in renal function. CP induced renal dysfunction was achieved by treatment with CP or vehicle (2.5 mg/kg) once weekly for 3 weeks. Since the CP-induced renal damage, including tubular reabsorption defects, is most prominent within the outer medulla (OM), changes in the expression pattern of OM aquaporins and sodium transporters including the Na,K-ATPase (alpha-subunit), type III Na,H-exchanger (NHE3), aquaporin 1 (AQP1) and 2 (AQP2) and the Na,K,2Cl-cotransporter (NKCC2) were investigated by semi-quantitative Western blotting. EXPERIMENTAL DESIGN: Rats had access to either a diet with standard Mg or to a Mg-depleted diet. Cisplatin was administered to female Wistar rats once a week for 3 weeks according to four regimens: (1) Cisplatin 2.5 mg/kg body weight i.p., to rats on a diet with standard Mg, (2) Cisplatin 2.5 mg/kg body weight i.p., to rats on a diet with low Mg, (3) Isotonic NaCl 2.5 ml/kg body weight i.p., to rats on a diet with standard Mg, (4) Isotonic NaCl 2.5 ml/kg body weight i.p., to rats on a diet with low Mg. RESULTS: CP had no effect on plasma creatinine or urea in rats with standard Mg intake, but the expression of all five transporters was significantly reduced when compared to vehicle treated rats on standard Mg-intake. Vehicle treated rats on low Mg-intake had a significant reduction in the expression of Na,K-ATPase, NHE3 and NKCC2, but unchanged expression levels of AQP1 or AQP2 when compared to standard treated controls. Forty percent of the CP-treated rats on low Mg-intake died during the experiment and the remaining animals had marked increased plasma creatinine and urea. Furthermore, the Western blot analysis revealed an almost complete disappearance of all four transporters, suggesting a dramatic synergistic effect of CP and Mg-depletion on renal function including the expression pattern of outer medullary sodium transporters and aquaporins. CONCLUSIONS: This study indicates a substantial additive effect of Mg-depletion on cisplatin induced renal toxicity as evidenced by significant changes in plasma creatinine and urea, renal failure induced mortality and loss of renal transporters. This should give cause for concern since the nephrotoxicity observed during cisplatin treatment might be substantiated by the known Mg-loss associated with cisplatin treatment especially in patients suffering from intense gastro-intestinal side effects.

Animals↗
PubMed2004

Magnesium and potassium homeostasis during cisplatin treatment.

PURPOSE: Administration of cisplatin causes changes in magnesium and potassium metabolism. The purpose of this study was to investigate day-to-day changes in renal and intestinal homeostasis of magnesium (Mg) and potassium (K) during repeated cisplatin treatments in rats to provide guidelines for human supplementation studies. EXPERIMENTAL DESIGN: Rats were housed in metabolic cages with access to a diet containing excess Mg and K. Treatment was administered once a week for 3 weeks and comprised either cisplatin 2.5 mg/kg body weight i.p or, as sham treatment, isotonic NaCl 2.5 ml/kg body weight i.p. Urine and feces were collected every 24 h. Blood samples for measurement of plasma Mg and K were obtained from a permanent arterial catheter prior to each treatment cycle and at the termination of the study. RESULTS: Cisplatin exerted a significant negative effect on total Mg balance. This effect was cumulative with repeated doses of cisplatin. The observed difference was mainly due to the difference in Mg balance between the treatment day and the following 2-3 days. The cumulated urinary excretion of Mg did not differ significantly between the two groups at the end of follow-up. A significant decrease was observed in cumulated intestinal absorption in treated rats compared to control rats at the end of follow-up. Lowered intestinal absorption accounted for 90% of the difference in total Mg balance between the two groups as compared to the renal loss. Cisplatin treatment also exerted a negative effect on total K balance, although the difference between cisplatin-treated and control rats was not significant at the end of follow-up. CONCLUSIONS: The Mg loss associated with cisplatin treatment was mainly the result of lowered intestinal absorption and not, as presently thought, the result of increased renal elimination. Instead, an increased renal reabsorption capacity was observed in response to decreased intestinal absorption. The study further showed that Mg and K metabolism are subject to predictable changes in intestinal absorption and renal excretion with each cisplatin treatment, and that knowledge of these changes can be used in planning supplementation. Thus, the experimental observations support intravenous supplementation on the day of treatment and 2-3 days after treatment followed by oral supplementation until the next treatment.

Animals↗
PubMed2004

Do CA125 response criteria overestimate tumour response in second-line treatment of epithelial ovarian carcinoma?

Recent studies indicate that cancer antigen 125 (CA125) response criteria tend to overestimate a tumour reduction measured by standard WHO response criteria in recurrent epithelial ovarian carcinoma. The aim of the study was to validate the recently introduced GCIG (The Gynaecological Cancer Intergroup) CA125 response criteria in predicting a tumour response measured by WHO (World Health Organization) criteria. Changes in CA125 levels (GCIG criteria) were retrospectively compared with alterations in the tumour load (WHO criteria) during second-line chemotherapy with topotecan or paclitaxel-platinum in 124 consecutive patients with recurrent or refractory disease. In patients assessable by both response criteria (n=72), the overall response rate using GCIG CA125 criteria was 57% (95% confidence interval (CI): 45-69%) and significantly higher than the response rate of 39% (95% CI: 28-51%) using WHO response criteria (P=0.045). The GCIG CA125 criteria had a sensitivity of 96% (95% CI: 82-100%), a specificity of 68% (95% CI: 52-81%) and an accuracy of 79% (95% CI: 68-88%) in predicting a response measured by WHO criteria. In conclusion, the GCIG CA125 response criteria seem to overestimate a tumour response by WHO criteria when monitoring the efficacy of second-line chemotherapy with topotecan or paclitaxel-platinum in patients with epithelial ovarian carcinoma.

Adult↗
PubMed2003

Severe intracellular magnesium and potassium depletion in patients after treatment with cisplatin.

The purpose of this study is (1) to evaluate skeletal muscle magnesium (Mg) and potassium (K) during treatment with cisplatin; (2) to evaluate the predictive value of plasma (P)-Mg for intracellular Mg during cisplatin treatment; and (3) to evaluate whether changes in intracellular K influence skeletal muscle Na,K-ATPase. In all, 65 patients had a needle muscle biopsy obtained before and 26 patients both before and after cisplatin treatment. Biopsies were analysed for Mg, K, and Na,K-ATPase concentrations, and P-Mg and P-K determined. Treatment with a total dose of approximately 500 mg (270 mg m(-2) surface area) cisplatin over 80 days was associated with reductions in muscle [Mg] (95% CI) (8.95 (8.23-9.63) to 7.76 (7.34-8.18) mumol g(-1) wet wt. (P<0.01), and muscle [K] (90.81 (83.29-98.34) to 82.87 (78.74-87.00) mumol g(-1) wet wt. (P<0.05), as well as in P-Mg 0.82 (0.80-0.85) to 0.68 (0.64-0.73) mmol l(-1) (P<0.01 but not in P-K (4.0 (3.8-4.1) vs 3.8 (3.7-4.0) mmol l(-1)). No simple correlations were observed between P-Mg and muscle [Mg], or between P-K and muscle [K], either before (n=65) or after (n=26) treatment with cisplatin. The changes in [Mg] and [K] were not associated with changes in the muscle Na,K-ATPase concentration. Following treatment with cisplatin, an approximately 15% decline in P-Mg was accompanied by an approximately 15% loss of muscle [Mg], as well as an approximately 10% reduction of muscle [K] and fatigue and muscle weakness previously ascribed to hypomagnesaemia may therefore also be well explained by muscle K depletion observed despite normal levels of P-K. There was no correlation between P-Mg and SM-Mg or between P-K and SM-K. Thus, P-Mg and P-K are not reliable indicators for Mg and K depletion during treatment with cisplatin. However, the majority of patients will present Mg and K depletion after cisplatin therapy and of these only very few patients will present a low P-Mg or P-K. Therefore, routine supplementation should be considered in all patients receiving cisplatin.

Adenosine Triphosphatases↗
PubMed2001

Results of reinduction therapy with paclitaxel and carboplatin in recurrent epithelial ovarian cancer.

OBJECTIVE: The purpose of the study was to evaluate the treatment results and toxicity of a retreatment regimen of paclitaxel and carboplatin in patients with ovarian cancer relapse. METHODS: A retrospective analysis of 241 consecutive patients with primary epithelial ovarian cancer receiving paclitaxel and a platinum analogue as first-line treatment was performed. Relapse treatment of platinum-sensitive patients consisted of paclitaxel (175 mg/m(2)) over 3 h followed by carboplatin at an area under the concentration-time curve of 5, repeated every 3 weeks. RESULTS: Forty-three patients with relapse were treated with paclitaxel and carboplatin after a median progression-free interval from the end of first-line chemotherapy of 15.8 months (range 6.0-41.7 months). In patients with evaluable disease the overall response rate was 84% (95% CI: 68.0-93.8%). The progression-free survival and overall survival from start of relapse treatment were a median of 9.7 months (range 1.4-26.9 months) and 13.1 months (range 4.5-35.5 months), respectively. In a multivariate Cox analysis independent prognostic factors for progression-free survival after first relapse were response to relapse treatment (P = 0.002, hazard ratio = 13.9) and time to first recurrence (P = 0.016, hazard ratio = 0.167). The planned treatment was accomplished by 67% of patients. Grade 4 neutrocytopenia over 1 week was observed in 9.3% of patients. Grade 1-2 peripheral neuropathy was reported in 30% of patients. Only 1 patient had her paclitaxel dose attenuated because of grade 4 neuropathy. CONCLUSION: Retreatment with paclitaxel and carboplatin in patients with platinum-sensitive epithelial ovarian cancer relapse yielded a high response rate and encouraging progression-free survival and overall survival. Paclitaxel-carboplatin reinduction therapy is generally well tolerated and the toxicity is manageable.

Adult↗
PubMed2001

Superiority of high-dose platinum (cisplatin and carboplatin) compared to carboplatin alone in combination chemotherapy for small-cell lung carcinoma: a prospective randomised trial of 280 consecutive patients.

PURPOSE: A prospective randomized trial in small-cell lung cancer (SCLC) was performed to determine if intensification of the platinum dose by giving cisplatin and carboplatin in combination to patients with SCLC yields higher response rates and survival, than carboplatin alone in a combination chemotherapy regimen. PATIENTS AND METHODS: Between September 1992 and October 1997, 280 patients were included in a two armed prospective randomized trial, stratified by stage of disease, LDH and performance status. The treatment was in arm A: three courses induction chemotherapy with carboplatin (AUC = 4, day 1), cisplatin (35 mg/m2, days 2 and 3), teniposide (50 mg/m2, day 1-5), vincristine (1.3 mg/m2, day 1) every four weeks, followed by cyclophosphamide (3 g/m2, day 84), 4-epirubicin (4-epidoxorubicin) (150 mg/m2, day 112), and finally one course cisplatin, carboplatin, teniposide and vincristine, (days 140-144). Arm B also comprised a total of six courses, identical to those in arm A except for omission of cisplatin. RESULTS: There were no significant differences in the overall treatment outcome for A vs. B, in terms of response rates (72% in both arms), complete response rates (40% and 34%, respectively), or median survival (314 days and 294 days, respectively). However, for patients with limited disease both the CR rate (54% vs. 37%, P < 0.05), overall survival (log-rank test, P < 0.05), and the two-year survival rate (11% vs. 6%, P < 0.05) were higher in the high-dose platinum arm compared to the carboplatin alone arm. CONCLUSIONS: The intensification of platinum dose (cisplatin plus carboplatin) in combination chemotherapy significantly increased the complete response rate, overall survival and number of two-year survivors among SCLC patients with limited disease compared to combination therapy with carboplatin alone, suggesting that a more aggressive treatment to this category of patients is worthwhile, while no difference in treatment outcome was observed for patients with extensive disease.

Adult↗
PubMed2001

Effects of cannabinoids on adrenaline release from adrenal medullary cells.

1. The objective of the present study was to analyse the peripheral effects of cannabinoids on adrenaline release from adrenal chromaffin cells. 2. In pithed rabbits with electrically stimulated sympathetic outflow, intravenous injection of the cannabinoid receptor agonists WIN55212-2 and CP55940 (5, 50 and 500 microg x kg(-1)) markedly lowered the plasma adrenaline concentration. The effect of WIN55212-2 was attenuated by the selective CB1 cannabinoid receptor antagonist SR141716A (500 microg x kg(-1)). WIN55212-3 (same doses as WIN55212-2), the enantiomer of WIN55212-2 lacking affinity for cannabinoid receptors, had no effect on the plasma adrenaline concentration. 3. In rabbit isolated adrenal glands, the release of adrenaline elicited by electrical stimulation was measured by fast cyclic voltammetry. Electrically-evoked adrenaline release was inhibited by WIN55212-2 (0.3, 1, 3 and 10 microM) and this effect was antagonized by SR141716A (1 microM). The non-cholinergic component of adrenaline release observed after blockade of nicotinic (by hexamethonium 100 microM) and muscarinic (by atropine 0.5 microM) acetylcholine receptors was not depressed by WIN55212-2. WIN55212-3 (10 microM) had no effect on adrenaline release. 4. No detectable specific CB1 receptor binding and mRNA expression were found in rabbit adrenal glands with autoradiography and in situ hybridization. 5. The results show that cannabinoids inhibit adrenaline secretion in rabbit isolated adrenal glands; the likely mechanism is a presynaptic CB1 receptor-mediated inhibition of acetylcholine release from preganglionic sympathetic neurons. The inhibition of adrenaline secretion in adrenal glands most probably accounts for the decrease in the plasma adrenaline concentration observed after cannabinoid administration in pithed rabbits.

Adrenal Glands↗
PubMed2001

Accumulation of the anandamide precursor and other N-acylethanolamine phospholipids in infant rat models of in vivo necrotic and apoptotic neuronal death.

It has been demonstrated that the endogenous cannabinoid receptor ligand, anandamide, and other N-acylethanolamines (NAEs), accumulate during neuronal injury in vitro, a process that may be linked to the neuroprotective effects of NAEs. The crucial step for generation of NAEs is the synthesis of the corresponding precursors, N-acylethanolamine phospholipids (NAPEs). However, it is unknown whether this key event for NAE formation is regulated differently in the context of insults causing necrotic or apoptotic neuronal death. To address this question, we monitored a range of cortical NAPE species in three infant rat models of in vivo neurodegeneration: (i) necrosis caused by intrastriatal injection of NMDA (25 nmol); (ii) apoptosis induced by systemic administration of the NMDA-receptor antagonist (+)MK-801 (3 x 0.5 mg/kg, i.p.); and (iii) apoptosis following focal necrosis triggered by concussive head trauma. A marked increase of all NAPE species was observed in both hemispheres 4 and 24 h after NMDA-induced injury, with a relatively larger increase in N-stearoyl-containing NAPE species. Thus, the percentage of the anandamide precursor fell from 1.1 to 0.5 mol %. In contrast, administration of (+)MK-801 did not alter cortical NAPE levels. Concussion head trauma resulted in a similar but less pronounced upregulation of NAPE levels at both 4 and 24 h as compared to NMDA injections. Increased levels of NAPE 24 h post-trauma possibly reflect that necrosis is still ongoing at this time point. Consequently, our data suggest that excitotoxic necrotic mechanisms of neurodegeneration, as opposed to apoptotic neurodegeneration, have a profound effect on in vivo NAE precursor homeostasis.

Animals↗
PubMed2001

Anandamide, but not 2-arachidonoylglycerol, accumulates during in vivo neurodegeneration.

Endogenous cannabinoid receptor ligands (endocannabinoids) may rescue neurons from glutamate excitotoxicity. As these substances also accumulate in cultured immature neurons following neuronal damage, elevated endocannabinoid concentrations may be interpreted as a putative neuroprotective response. However, it is not known how glutamatergic insults affect in vivo endocannabinoid homeostasis, i.e. N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), as well as other constituents of their lipid families, N-acylethanolamines (NAEs) and 2-monoacylglycerols (2-MAGs), respectively. Here we employed three in vivo neonatal rat models characterized by widespread neurodegeneration as a consequence of altered glutamatergic neurotransmission and assessed changes in endocannabinoid homeostasis. A 46-fold increase of cortical NAE concentrations (anandamide, 13-fold) was noted 24 h after intracerebral NMDA injection, while less severe insults triggered by mild concussive head trauma or NMDA receptor blockade produced a less pronounced NAE accumulation. By contrast, levels of 2-AG and other 2-MAGs were virtually unaffected by the insults employed, rendering it likely that key enzymes in biosynthetic pathways of the two different endocannabinoid structures are not equally associated to intracellular events that cause neuronal damage in vivo. Analysis of cannabinoid CB(1) receptor mRNA expression and binding capacity revealed that cortical subfields exhibited an up-regulation of these parameters following mild concussive head trauma and exposure to NMDA receptor blockade. This may suggest that mild to moderate brain injury may trigger elevated endocannabinoid activity via concomitant increase of anandamide levels, but not 2-AG, and CB(1) receptor density.

Animals↗