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Biomedical subjects

G Daugaard

Publications and source records attributed to G Daugaard.

At least 37 records · Page 2Linked to original sources
PubMed1999

Undetectable inhibin B serum levels in men after testicular irradiation.

A group of men treated with testicular irradiation for carcinoma in situ in the remaining testis after orchidectomy for unilateral testicular germ cell cancer was used as a model to study of the effect of selective eradication of germ cells on the levels of serum inhibin B in the human male. Thirteen men with verified spermatogenesis and detectable preirradiation levels of serum inhibin B (median, 55; range, 23-193 pg/mL) were investigated before and after testicular irradiation (14-20 Gy). All patients had undetectable levels of inhibin B 2-12 months (median, 5 months) after radiotherapy (<20 pg/mL). Correspondingly, serum FSH increased in all men after radiotherapy [from a median of 9.6 (range, 3.0-24) IU/L to a median of 28 (range, 15-70) IU/L); P < 0.001]. Histological investigation showed a Sertoli cell-only pattern in all patients after radiotherapy. Neither LH nor testosterone showed a significant decrease after radiotherapy. Our data indicate that inhibin B production sufficient to maintain detectable serum levels in adults requires spermatogenic activity.

Adult↗
PubMed1998

Effect of chemotherapy on carcinoma in situ of the testis.

BACKGROUND: Approximately 5% of patients with testicular cancer harbour carcinoma in situ (CIS) in the contralateral testis. CIS will progress into invasive tumour in about 50% of cases within five years. The present study evaluated the effect of platinum containing chemotherapy on CIS. PATIENTS AND METHODS: Thirty-three patients with disseminated germ-cell cancer and biopsy proven CIS of the testis were evaluated. RESULTS: CIS had disappeared in the first follow-up biopsy in 30 patients. Six patients had a relapse of CIS with or without invasive cancer after 30, 31, 47, 51, 76 and 95 months from start of chemotherapy. Two relapses were among six patients who initially received cisplatin, vinblastine and bleomycine and four among 27 patients who initially received cisplatin, etoposide and bleomycine. The estimated cumulative risk of CIS five and 10 years after chemotherapy was 21% and 42%, respectively. The estimated cumulative incidence of spermatogenesis was 64% and 81% at five and 10 years of follow-up, respectively. CONCLUSION: Platinum containing chemotherapy may eradicate CIS. However, patients with CIS may develop invasive cancer in spite of chemotherapy. In the light of the present data, we recommend radiotherapy to the affected testicle in patients with CIS in the contralateral testis and in patients with bilateral testicular CIS. In patients with extragonadal disease and CIS in one testicle, orchiectomy of the affected testicle is recommended. In patients for whom future fertility is an important issue, follow-up including repeated biopsies can be offered for a period of at least 10 years.

Adult↗
PubMed1998

Metabolic and hemodynamic evaluation of brain metastases from small cell lung cancer with positron emission tomography.

Brain metastases from small cell lung cancer respond to chemotherapy, but response duration is short and the intracerebral concentration of chemotherapy may be too low because of the characteristics of the blood-brain barrier. Positron emission tomography has been applied in a variety of tumors for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor rCMRglu, rCBF, and rCBV exerted a broad variability, but were higher than the corresponding values in white matter and higher than or similar to those of gray matter. Tumor rCMRglu and rCBF were highly correlated (P < 0.01, r = 0.79). No correlation between survival and metabolic or hemodynamic parameters could be demonstrated. After radiotherapy, mean tumor rCMRglu decreased from 0.40 to 0.31 micromol/g/min (not significant), and rCBF and rCBV remained unchanged. However, cortical rCBF demonstrated a trend of increased values after radiotherapy from 0.37 to 0.49 ml/g/min (P = 0.13). No change in rCMRglu was observed in gray or white matter after radiotherapy. Global CBF seems to be reversibly depressed by the metastases, but local hemodynamic changes in the tumor could not be detected with positron emission tomography in this study. An association between high tumor rCMRglu and rCBF as an indicator of hypoxia was not observed. Other methods for noninvasive in vivo analysis of tumor hemodynamics are needed, especially for discrimination between tumor necrosis and hypoxia.

Adolescent↗
PubMed1996

Combination chemotherapy with a five-drug regimen for invasive thymoma.

Nine patients with stage III and stage IV thymoma were treated with cisplatin, vincristine, lomustine, cyclophosphamide and prednisolone. Two patients (22%) obtained remission, and four patients (44%) showed no change for 11 to 31 months. It was found that this five-drug regimen did not improve the results obtained by other chemotherapy modalities for thymoma.

Adult↗
PubMed1996

Outcome for patients with leukemia, multiple myeloma and lymphoma who relapse after high dose therapy and autologous stem cell support.

Relapses after autologous transplantation are a serious clinical problem in patients with haematological diseases. The decision making for handling of such patients is difficult and the aim of this retrospective analysis of posttransplant relapses was 1) to obtain information of practical importance for the management of future relapses and 2) to evaluate the basis for clinical phase I-II trials of salvage therapy combined with biological modifiers. Included in the study were 283 patients with acute leukemia, multiple myeloma and malignant lymphoma who relapsed after autologous transplantations during a five year period from 1989 to 1994. Chemo- and radiotherapy was given to 229 patients after relapse or due to progressive disease and the response evaluated after 90 days. Fifty four patients (24%) obtained a complete remission and 44 patients (19%) partial responses. The overall median survival from relapse was 5 months. In the group given salvage treatment the median survival was 7 months and in the 54 patients who obtained remission the median survival was 15 months. So far 6 of 14 patients in continuous complete remission have a remission time after relapse longer than the time in remission after transplantation. Survival after relapse depended upon the time from transplantation to relapse, primary disease and if salvage therapy was given. In conclusion posttransplant relapses can be treated but the strategy has to be evaluated in future clinical trials.

Adolescent↗
PubMed1996

Should the other testis be biopsied?

Testicular tumors are bilateral in approximately 5% of the cases, although the incidence of bilaterality is affected by the treatment of the primary tumor. A biopsy of the contralateral testis of testicular tumor patients will show carcinoma in situ (CIS) in 5% to 6% of cases. Virtually all untreated cases of CIS will progress into invasive testicular germ cell tumors. In some countries, most testicular tumor patients have a contralateral biopsy at the time of the primary orchiectomy; but in many countries, urologists are not always aware of the advantages of simultaneous contralateral biopsy. The policy in the United States does not encourage surgeons to perform a contralateral biopsy at the initial orchidectomy or to offer a biopsy to patients after referral to a specialist center. The diagnosis of CIS is not of mere academic interest, but makes it possible to offer the patient optimal treatment.

Adult↗
PubMed1993

Infections in patients treated with high-dose chemotherapy for germ cell tumours.

25 patients with disseminated germ cell tumours were treated with high-dose cisplatin and etoposide (40 mg/m2 and 200 mg/m2 daily x five, respectively) leading to severe myelosuppression. A comprehensive study was undertaken in order to identify and describe the bacterial, viral and fungal infections in this group of patients. Fever (> 38.5 degrees C) and leucopenia (white blood cell count < 1.0 x 10(9)/l) were observed in 61 of 90 treatment cycles (68%). A microbiological aetiology compatible with the clinical manifestations of infection could be identified in 33 of the 61 febrile episodes (54%). Bacteraemia occurred in 14 episodes in 12 patients. Eight episodes (57%) involved gram-positive aerobic bacteria.

Adult↗
PubMed1993

Tamoxifen and hypercalcaemia.

The present case demonstrates the importance of close observation, also of serum calcium, when initiating tamoxifen therapy, especially in patients with known osseous metastases. Hypercalcaemia should also be considered as a possible cause of CNS symptoms in patients newly started on endocrine treatment. Hydration with saline is the first step in the management of hypercalcaemia. In patients with a serum calcium level > 3.50 mmol/l (serum ionised calcium approximately 2.00 mmol/l) hydration should be combined with bisphosphonates.

Aged↗
PubMed1993

Therapy-related myelodysplasia and acute myeloid leukemia. Cytogenetic characteristics of 115 consecutive cases and risk in seven cohorts of patients treated intensively for malignant diseases in the Copenhagen series.

Therapy-related acute myeloid leukemia (t-AML), often presenting as myelodysplasia (t-MDS), has become the most serious long-term complication of cancer therapy and offers a unique opportunity to study chemical leukemogenesis. Seven cohorts of patients treated for six different types of primary tumor have been followed closely for leukemic complications, and 115 consecutive patients with t-MDS or t-AML, including 45 cases from the cohorts, have been investigated cytogenetically at our institutions during the past 16 years. In patients primarily treated with alkylating agents, the risk of t-MDS and t-AML increased by approximately 1% per year from 2 to at least 8 years after start of treatment. In most cases, the disease presented as t-MDS with loss of a whole chromosome 5 or 7, or various parts of their long arms, and the leukemias were of FAB-subtypes M1, M2, or M4. In patients treated with drugs targeting at DNA-topoisomerase II, such as etoposide, doxorubicin, 4-epidoxorubicin, or mitoxantrone combined with drugs reacting directly with DNA, such as cisplatin or alkylating agents, the risk of leukemia increased much more steeply from only one year after start of therapy. These early onset cases often presented as overt leukemia of FAB-subtypes M4 or M5 with balanced translocations to chromosome bands 11q23 and 21q22, whereas later onset cases often shared characteristics with cases observed after therapy with alkylating agents alone. Both alkylation of DNA and poisoning of DNA-topoisomerase II may result in development of t-AML with different clinical and cytogenetic characteristics. There may be a synergistic leukemogenic effect between the two types of drug, and in patients with germ cell tumors treated with etoposide, cisplatin and bleomycin, reassessment suggested the risk of leukemia to increase exponentially with increasing doses of cisplatin and etoposide.

Adult↗
PubMed1992

Secondary surgery in patients with malignant germ cell tumors.

A total of 102 men treated for germ cell tumor with chemotherapy containing cisplatin was referred for a secondary operation with signs of tumor in the retroperitoneum or chest. Of the patients 85 underwent laparotomy, 14 underwent thoracotomy and 3 had both operations. Residual tumors were completely resected in 66 patients and incompletely resected in 30, while no tumor was found in 6. The resected specimen was malignant in 18 patients, of whom 11 had complete removal of all malignant tissue. All patients with malignancy in the resected specimen received further chemotherapy. Long-term disease-free status was obtained in 75% of those patients who had a complete resection, compared with 14% in the group with incomplete resection. There was no evidence of malignant disease at operation in 78 patients but 5 of them later died of the disease. Malignant tissue was present in the residual tumor in only 1 of 15 patients whose primary tumor was seminoma alone. Resection was attempted in 14 patients despite abnormal tumor markers preoperatively. Only 5 of these patients achieved a disease-free status and 2 of them died later of malignant disease. Over-all 79 of the 102 patients are without evidence of disease (medium postoperative observation 23 1/2 months). We conclude that a secondary operation constitutes an important part of the treatment of patients with germ cell cancer.

Adolescent↗
PubMed1992

High prevalence of Clostridium difficile diarrhoea during intensive chemotherapy for disseminated germ cell cancer.

A prospective, consecutive study of the aetiology of treatment-associated diarrhoea was conducted in 25 patients with disseminated germ cell cancer treated with intensive chemotherapy. Clostridium difficile was isolated in 45% of the diarrhoea episodes, which makes this species the most important bacterial pathogen in the development of clinically significant diarrhoea in this group of immunocompromised patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Treatment of poor-risk germ-cell tumors with high-dose cisplatin and etoposide combined with bleomycin.

Seventy-two patients with far advanced ('high-risk') germ-cell tumors were treated with cisplatin 40 mg/m2 i.v. and etoposide 200 mg/m2 i.v. daily for 5 days and bleomycin 15 mg/m2 i.v. once a week. At least 3 cycles of this treatment were given at three-week intervals to all patients. Seventy-five percent of the patients obtained CR and 67% are without evidence of disease after a median observation time of 47 months (range 5 to 80 months). Hematologic toxicity was severe and 10% of the patients died due to treatment-related toxicity. Neurotoxicity was a clinical problem in 58% of the patients. Glomerular filtration rate decreased significantly after 3 cycles (29% +/- 16%). No clinically significant pulmonary toxicity was observed. The specific role of high-dose cisplatin in such intensive treatment has until now been the subject of only one randomized study in which no superiority of high-dose cisplatin was found. Significant improvement of therapeutic outcome over that of today's standard treatment conceivably necessitates an even greater increase in dose intensity of the active drugs--or inclusion of new drugs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Management of extragonadal germ-cell tumors and the significance of bilateral testicular biopsies.

Forty-nine patients with assumed extragonadal germ-cell tumors (retroperitoneum: 39, mediastinum: 8, CNS: 2) were included in the present study. The patients were treated with 'high' (40 mg cisplatin/m2 and 200 mg etoposide/m2 daily x 5) or 'conventional' (20 mg cisplatin/m2 and 100 mg etoposide/m2 daily x 5) doses of cisplatin and etoposide together with bleomycin, depending on the presence or absence of poor prognosis factors. Forty-six patients were evaluable for response and 3 patients were classified as non-responders (1 early death, 2 toxic deaths). Eighty percent obtained complete remission and 76% are alive without evidence of disease after a median observation time of 41 months (88% of patients with primary tumor in the mediastinum, 72% with tumor in the retroperitoneal area, 87% of patients with seminoma and 71% with non-seminoma, respectively). In 48 patients testicular biopsies were performed. In 42% of patients with primary retroperitoneal tumors, carcinoma in situ testis (CIS) was diagnosed. None of the patients with tumors in mediastinum or CNS had CIS in the testicles. The therapeutic outcome for patients with extragonadal germ-cell tumors is now similar to that of patients with very advanced testicular cancer when considered in relation to the presence of prognostic factors. The coexistence of CIS and retroperitoneal tumor could indicate that these tumors are not truly extragonadal or that these lesions have a common malignant progenitor.

Adolescent↗
PubMed1992

Renal function in patients with untreated acute myocardial infarction.

This study provides data on plasma volume (PV), extracellular volume (ECV) and renal function in 8 untreated patients with acute myocardial infarction (AMI). At day 2 and day 10 after AMI, glomerular filtration rate (GFR), urinary excretion rate of water (Vu), sodium clearance (CNa) and lithium clearance (CLi) were used for assessing reabsorption rates of sodium and water in proximal and distal nephron segments. PV and blood pressure at day 2 were not significantly different from values at day 10. Heart rate (HR), weight and ECV at day 2 were significantly increased when compared with values at day 10 (78 vs. 62 pr. min and 17.0 vs. 16.2 1, respectively). Plasma norepinephrine values were slightly elevated at day 2 and day 10. GFR was initially high and decreased from day 2 to day 10 (118 vs. 104 ml min-1) together with CLi and Ck. However, Vu, CNa and fractional excretion rate of sodium increased markedly from day 2 to day 10. The results suggest that sodium and water retention in the initial phase of AMI without left ventricular failure is due to an increase in tubular reabsorption in distal nephron segments mediated by mechanisms other than the sympathetic nervous system.

Absorption↗
PubMed1991

Increased risk of myelodysplasia and leukaemia after etoposide, cisplatin, and bleomycin for germ-cell tumours.

Among the cytostatic drugs only the alkylating agents have been firmly established as being leukaemogenic. This report describes 4 cases of acute myeloid leukaemia and 1 of myelodysplasia occurring in a cohort of 212 patients with germ-cell tumours treated with etoposide, cisplatin, and bleomycin. The mean cumulative risk of leukaemic complications was 4.7% (SE 2.3) 5.7 years after start of etoposide-containing chemotherapy, and, compared with the risk in the general population, the relative risk of overt leukaemia was 336 (95% CI 92-861). No leukaemias were detected in a previous cohort of 127 patients with germ-cell tumours treated with cisplatin, bleomycin, and vinblastine. The increased risk of leukaemia was most probably due to etoposide alone or in combination with cisplatin or bleomycin, since other published work has also not revealed an excess of leukaemias among patients with germ-cell tumours treated with only cisplatin, bleomycin, and vinblastine. The risk of leukaemia was dose related since all 5 patients with leukaemic complications were among the 82 who had received a cumulative dose of more than 2000 mg/m2 etoposide, whereas no leukaemias were observed among 130 patients who had received up to 2000 mg/m2 (p = 0.004). 3 of the leukaemic patients had balanced chromosome translocations affecting bands 11q23 and 21q22. These translocations, and perhaps also other balanced aberrations, seem to be characteristic of myelodysplasia and acute leukaemia occurring after therapy with cytostatic agents acting on DNA-topoisomerase II.

Acute Disease↗
PubMed1991

Effects of Felodipine on the dog kidney: a lithium clearance study.

This study was performed in order to investigate the possible influence of sympathetic nerve activity on the effects of the dihydropyridine calcium antagonist felodipine on absolute and fractional reabsorption rates of sodium and water in proximal and distal tubular segments in the dog kidney. Clearance of 51Cr-EDTA was used as a measure of glomerular filtration rate (GFR). GFR, urinary excretion rates of sodium and water, and lithium clearance (C-Li) were used for assessing the absolute and fractional tubular reabsorption rates. Felodipine infusion into the right renal artery increased renal vascular conductance (renal blood flow divided by renal arteriovenous pressure gradient) significantly (by 9%) while GFR remained unchanged. Calculated absolute proximal reabsorption rates remained unchanged while distal sodium reabsorption rate increased significantly from 2.1 +/- 0.3 to 2.7 +/- 0.4 mmol min-1. Sodium clearance (C-Na) increased from 0.22 +/- 0.08 to 0.40 +/- 0.07 ml min-1. The alpha-adrenergic blockade with phentolamine did not affect renal haemodynamic or excretory variables, nor did it influence the haemodynamic response to felodipine. After alpha-adrenergic blockade felodipine caused an increase in C-Na from 0.28 +/- 0.06 ml min-1 to 0.63 +/- 0.04 ml min-1, which was significantly greater than that measured after felodipine alone. The distal load (C-Li) was not significantly different from that obtained after felodipine alone, but distal sodium reabsorption rate increased less significantly after alpha-adrenergic blockade. The results suggest that felodipine, by its effect on tubular flow and/or composition, activates local alpha-adrenergic reflex mechanism(s), which stimulates distal sodium reabsorption, thereby attenuating the natriuretic effect.

Absorption↗