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Biomedical subjects

H H Hansen

Publications and source records attributed to H H Hansen.

At least 163 records · Page 9Linked to original sources
PubMed1989

In vitro evaluation of the potential of aclarubicin in the treatment of small cell carcinoma of the lung (SCCL).

The sensitivity of eight cell lines established from treated and untreated patients with small cell carcinoma of the lung (SCCL) was tested in the clonogenic assay with 1 h and continuous exposure to aclarubicin (ACLA), adriamycin (ADR), daunorubicin (DAU) and mitoxantrone (MITO). The sensitivity to ADR, DAU and MITO covariated, and varied with a factor of five. The sensitivity to ACLA was independent of the sensitivity to ADR and varied only within a factor of two. Only ACLA showed pronounced increased potency with continuous incubation, and ACLA was the most potent drug in the three cell lines least sensitive to ADR. Two resistant cell lines were selected by treating NCI-H69 in vitro with DAU. One cell line (9-fold resistant to DAU) expressed large amounts of P-glycoprotein, the other cell line (4-fold resistant to DAU) had barely detectable glycoprotein. Both lines acquired resistance to ADR, ACLA and MITO. The cross-resistance to ACLA and MITO was only partial and ACLA was still the most potent drug on these lines. The sensitivity to ACLA of the cell lines least sensitive to ADR suggest that ACLA partially circumvents mechanisms of multidrug resistance. Together with the pronounced increase in potency with prolonged exposure, these results suggest that ACLA has a mechanism of action different from the 'classical' anthracyclines. In this context mitoxantrone is more similar to the classical anthracyclines although its structure is more dissimilar.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Differentiation between renovascular and essential hypertension by means of changes in single kidney 99mTc-DTPA clearance induced by angiotensin-converting enzyme inhibition.

Blood pressure (BP), plasma renin concentration (PRC), and 99mTc-labeled diethylenetriaminepenta acetate (DTPA) renography with determination of single kidney 99mTc-DTPA clearance and parenchymal mean transit time (MTT) were measured in exactly the same way on two consecutive days in 14 patients with renovascular hypertension (RVH), unilateral renal artery stenosis in nine and bilateral stenosis in five, and ten patients with essential hypertension (EH). The examination on day 1 served as a control for day 2 during which captopril (25 mg) was given orally one hour before measurements of PRC and DTPA clearance. Blood pressure was reduced by captopril in both groups, but the maximum decrease in systolic BP was slightly more pronounced (P less than .01) in RVH (22%, median) than EH (13%). Plasma renin concentration increased to a much greater extent (P less than .01) after captopril in RVH (366%) than in EH (46%), Single kidney 99mTc-DTPA clearance was significantly (P less than .01) reduced (-39.5%) and MTT considerably prolonged (170%) on the affected/most affected side in RVH, but both parameters were only slightly changed or unchanged on the unaffected/least affected side (-6.5%, -2% respectively) and were not significantly changed in any of the sides in EH. The degree of renal artery stenosis was significantly correlated to the increase in PRC (rho = -0.786, n = 14 patients, P less than .01), to the reduction in single kidney 99mTc-DTPA clearance (rho = 0.729, n = 19 kidneys, P less than .01) and to the prolongation in MTT (rho = -0.785, n = 16 kidneys, P less than .01). By analysis of the captopril-induced changes in 99mTc-DTPA clearance and MTT, it was possible to predict the existence of a moderate to several renal artery stenosis in arterial hypertension with a very high degree of probability, and the use of changes in 99mTc-DTPA clearance and MTT after angiotensin-converting enzyme (ACE) inhibition may become a valuable tool in differentiation between RVH and EH.

Adult↗
PubMed1989

Abnormal glomerular and tubular function during angiotensin converting enzyme inhibition in renovascular hypertension evaluated by the lithium clearance method.

Glomerular filtration rate (GFR) and tubular function were measured by means of the lithium clearance technique in 14 patients with renovascular hypertension (RVH) and eight patients with essential hypertension (EH) before and after oral administration of captopril 25 mg. In RVH captopril reduced 51-Cr-EDTA clearance (67.3 (median) to 47.5 ml min-1, P less than 0.01), proximal absolute reabsorption of fluid (53.9 to 41.5 ml min-1, P less than 0.01) and distal absolute reabsorption of sodium (2195 to 1402 mumol min-1, P less than 0.01), whereas proximal fractional reabsorption increased slightly (77.5 to 80.2%, P less than 0.02). In EH, however, these parameters were practically unaffected by captopril. In both RVH and EH plasma concentrations of angiotensin II and aldosterone were reduced after captopril, but atrial natriuretic peptide in plasma and urinary excretion rate of prostaglandin E2 were unchanged. Blood pressure decreased after captopril in both groups, but the maximum fall in systolic BP was more pronounced in RVH (22%) than EH (13%). It is concluded that angiotensin converting enzyme inhibition markedly reduced absolute reabsorption in both the proximal and distal tubules in RVH, in contrast to EH, predominantly due to fall in the GFR, and that the slight increase in proximal fractional reabsorption may be attributed to a reduction in the hydrostatic pressure in the peritubular vessels.

Adult↗
PubMed1989

High-dose platinum consisting of combined carboplatin and cisplatin in previously untreated ovarian cancer patients with residual disease.

A phase II trial of carboplatin, 300 mg/m2 day 1, and cisplatin, 50 mg/m2 days 2 and 3 every 4 weeks for six cycles, was performed in 42 previously untreated patients with residual disease after primary laparotomy. Overall, 79% of patients had primary residual tumor larger than 2 cm. The overall pathologic response rate (pathologic complete response [PCR] plus partial response [PPR]) in 37 evaluable patients was 62%, and in PCRs was 22%. Of the responding patients, 78% had primary residual tumor larger than 2 cm. The toxicity was cumulative but manageable, with thrombocytopenia being the main reason for dose reduction. Dose-limiting nephrotoxicity and neurotoxicity occurred in 22% and 7% of the patients, respectively. Combined high-dose platinum as a "single agent" appears to be as active as combination chemotherapy containing cisplatin, and the treatment is feasible. Further clinical trials of this combination alone or combined with other drugs are warranted.

Adult↗
PubMed1989

Intestinal obstruction in patients with advanced carcinoma of the ovaries treated with combination chemotherapy.

An analysis of incidence, risk factors and treatment results of intestinal obstruction caused by carcinoma of the ovaries was performed in 310 consecutive patients with carcinoma of the ovaries, The International Federation of Gynecology and Obstetrics stage IIB to IV, treated with combination chemotherapy. With a median observation time of 46 months, the incidence was 14 per cent and the cumulated risk was estimated to be 26 per cent at five years after treatment was begun. Risk factors were stages IIIB and IV, residual primary tumor size greater than 2 centimeters and presence of intestinal carcinomatosis at primary laparotomy. There was no difference in the survival time between 16 conservatively treated patients and 25 surgically treated patients (a median of 30 and 68 days, respectively, p greater than 0.30). The complication risk of surgical treatment was high (64 per cent), and surgical benefit--defined as survival greater than 60 days with total palliation of intestinal symptoms--was achieved in only 32 per cent.

Adult↗
PubMed1989

The clinical and screening age-at-onset distribution for the MEN-2 syndrome.

The decision to screen for multiple endocrine neoplasia type 2 (MEN-2) is generally based on family history, the rationale for this approach being the presumed 100% penetrance of the disease. To determine the validity of this presumption we have estimated--by applying modifications of the life-table method--the clinical and screening age-at-diagnosis distributions for MEN-2, using families from the Cancer Research Campaign Medullary Thyroid Cancer Register and one large American family. The clinical penetrance of MEN-2 is shown to be incomplete, an estimated 41% of gene carriers not presenting with symptoms by age 70 on the basis of clinical history. Screening by the standard tests for detecting the earliest manifestations of the syndrome increases the penetrance to an estimated 93% by age 31. There is no evidence of a difference in the age-at-diagnosis distributions between maternal and paternal transmission, or among different families, but there is some suggestion of an earlier onset of medullary thyroid cancer in female gene carriers, and of a tendency of pheochromocytoma to cluster in families. These results can be used to calculate risks to relatives of affected individuals, which in turn can be used to guide decisions on which individuals to screen.

Adrenal Gland Neoplasms↗
PubMed1989

[Pathophysiology of pelvic floor insufficiency].

The muscles of the pelvic floor form a complexly built sustaining structure, which bears the whole weight of the visceral column. The pelvic floor is reinforced by a supporting framework of fasciae. Some of the pelvic muscles are important sphincteric elements for occlusion of the anal canal, the vagina and the urethra. Any weakening of the ingenious construction of the pelvic diaphragm consequently reduces its functions of support or continence. Possible effects are visceral prolapse and incontinence.

Fascia↗
PubMed1989

Reproducibility of iodine-123-hippuran renoscintigraphy in the normal pig at various flow rates.

Twenty-two pigs with normal kidney function and upper urinary tracts were examined with renoscintigraphies once a week for 4 weeks. In order to study the influence of urine flow on the reproducibility, renoscintigraphies were undertaken during various urinary flow rates. Renal split function was reproducible at any level of and independent of the urinary flow rates. For parenchymal and pelvic mean transit times a normogram was constructed for selected urinary flow intervals. An inverse relationship to urine production was seen. Parenchymal and pelvic transit times were fully reproducible when data were compared in two or three consecutive examinations of the same kidney at the same urinary flow rate. Both parenchymal and pelvic mean transit times were however significantly different (p less than 0.001) in kidneys studied from one urinary flow rate to another. Single kidney hippuran clearance was fully reproducible when compared in the same urinary flow interval. However a significant difference was found (p less than 0.05) when single kidney hippuran clearance was compared in renographies undertaken at different urinary flow intervals. Furthermore the study suggests that the size of hippuran clearance is dependent on the urine production, since an increase in hippuran clearance was seen in relation to increase in urinary flow. In conclusion this pig study showed, that monitoring of the urinary flow rate is extremely important in this very commonly used clinical investigation, and that the investigation should be performed in the same state of hydration at any renography to obtain reproducible results.

Animals↗
PubMed1989

Chemotherapy in adenocarcinoma of the lung.

Adenocarcinoma of the lung (ACL) attracts increasing attention because of the fast rising incidence. Systemic chemotherapy with cytostatic agents has been widely used for patients with inoperable ACL, but a standard treatment has not yet been defined. A review of the literature revealed that the highest response rates observed for single agents and combination chemotherapy in ACL in randomized studies were 22% and 38%, respectively, while the longest median survivals were 35 weeks and 34 weeks. Independent prognostic factors for survival in ACL patients were performance status, prior non-radical resection, liver metastases, white blood cell count and serum values of lactate dehydrogenase and aspartic aminotransaminase. Using logistic regression analysis, the only significant predictor of response was measurable disease parameter, while 26 other variables were not significant. Response to chemotherapy was not a major prognostic factor for survival, probably because of the low rate of complete responses (4%). Chemotherapy in ACL remains experimental and the prognosis for these patients is poor. High priority should therefore be given to the identification of new agents or combination regimens with appreciable activity. The knowledge of prognostic factors should be used for optimal design of trials and interpretation of the results.

Adenocarcinoma↗
PubMed1989

Chemotherapy in ovarian carcinoma.

Chemotherapy in ovarian carcinoma has changed from single agents through combinations without cisplatin to combinations including cisplatin. First-line treatment should be as potent as possible and thereby prolong the progression-free interval and the overall survival and increase the cure rate. This has been obtained with cisplatin, but new active agents are needed to improve the results. The present non-invasive response evaluation methods such as tumour markers, abdominal computed tomography or ultrasound scans are unsatisfactory with a false-negative rate of about 50-60%. In view of this and the experimental nature of chemotherapy in ovarian cancer, a second-look laparotomy cannot be avoided to assess the efficacy of a treatment. Salvage therapy with well known drugs has only a restricted indication, as the overall results are generally poor. In addition, a common international prognostic index would be of great value for the comparison of the results of the different trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Single-agent chemotherapy for advanced adenocarcinoma of the lung. A review.

Systemic therapy with cytostatic agents has been widely used in the management of inoperable adenocarcinoma of the lung (ACL). However, chemotherapy for this tumor type remains experimental, and the prognosis is still poor. Thus, the literature on single-agent chemotherapy was reviewed in order to establish critical background material for the planning and evaluation of future studies. Only vindesine, dibromodulcitol, doxorubicin and hexamethylmelamine have displayed overall response rates exceeding 10% in randomized studies. Several of the most promising agents with response rates above 20% in non-randomized studies, i.e., 5-fluorouracil, mitomycin C, vinblastine and ifosfamide, have not been adequately evaluated in randomized trials in ACL. There is no published evidence to suggest the superiority of single-agent chemotherapy over the best supportive treatment, with respect either to survival or to quality of life. There are considerable methodological problems in designing, executing, analyzing and reporting these studies. Some of the problems could be solved by use of the internationally accepted guidelines for reporting results of cancer treatment, which might make more rapid progress possible.

Adenocarcinoma↗
PubMed1988

Combination chemotherapy for advanced adenocarcinoma of the lung. A review.

Combination chemotherapy has been used widely in the treatment of inoperable adenocarcinoma of the lung (ACL), but without uniform success. This review summarizes current knowledge of combination chemotherapy in ACL, with the aim of establishing critical background material for future studies. Not all the numerous combinations applied in non-randomized studies have produced response rates above 20% when evaluated in randomized trials. This holds true for the following regimens: cyclophosphamide + lomustine + methotrexate (response rates 14%-38%), hexamethylmelamine + doxorubicin + methotrexate (13%-32%), methotrexate + doxorubicin + cyclophosphamide + lomustine (13%-24%), cyclophosphamide + doxorubicin + cisplatin (0-36%), cyclophosphamide + bleomycin + cisplatin (20%), mitomycin C + vinblastine + cisplatin (26%-33%), cyclophosphamide + doxorubicin + etoposide + cisplatin (29%) and vindesine + cisplatin (33%). None of these combinations has been shown to be clearly superior to single-agent treatment. Nor has any specific regimen been shown to have clear advantages over other active combination chemotherapy regimens or over the sequential administration of either single agents or combined treatments. The prognosis for patients with inoperable ACL remains dismal. None of the studies considered in this review revealed median survival times exceeding 47 weeks. High priority should therefore be given to the identification of new compounds with significant activity against ACL.

Adenocarcinoma↗
PubMed1988

A phase I evaluation of N10-propargyl-5,8-dideazafolic acid.

The quianazoline antifolate N10-propargyl-5,8-dideazafolic acid (ICI 155,387), an inhibitor of thymidylate synthetase (TS), was evaluated for clinical toxicity in a phase I trial. The compound was given once every week as a bolus injection. Fourteen patients with advanced cancer were treated at doses of 10-30 mg/m3. Four patients from the lowest to the highest dose developed severe renal toxicity, detected by a reversible decrease in the Cr-EDTA clearance. Hepatotoxicity was observed with transient elevations of alanine aminotransferase (ALT) in 10 patients and alkaline phosphatase in nine patients. Neither the incidence nor the severity of these toxicities was dose related. Two patients developed feelings of fatigue, which in one patient coincided with a decrease in Cr-EDTA clearance. No myelotoxicity, dermatological, gastrointestinal toxicity or mucositis was seen. No tumour responses due to ICI 155,387 occurred. The severity and the erratic nature of the renal side-effects suggest that this schedule cannot be recommended for further development of this compound in Phase II trials.

Adult↗
PubMed1988

The cytotoxic activity of cisplatin, carboplatin and teniposide alone and combined determined on four human small cell lung cancer cell lines by the clonogenic assay.

Using the clonogenic assay to compare the cytotoxic activity of cisplatin and carboplatin on four human small cell lung cancer cell lines, cisplatin was shown to be equally or more potent than carboplatin at equitoxic doses with 1 h incubation. Increased potency of carboplatin was revealed when the drugs were tested with continuous incubation, although cisplatin still was the most potent drug when compared on a microgram to microgram basis. This relative increase in potency of carboplatin can at least partly be explained by the development of a more reactive form of the drug when stored in tissue culture medium. By combining either cisplatin or carboplatin with teniposide additive cell kill was obtained. Additivity was also obtained when cisplatin was combined with carboplatin. Since the two drugs have a different toxicity pattern a clinical synergy may be obtained by combined use of these two analogues.

Antineoplastic Combined Chemotherapy Protocols↗