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Biomedical subjects

J Andersen

Publications and source records attributed to J Andersen.

At least 271 records · Page 15Linked to original sources

High-dose combination alkylating agent preparative regimen with autologous bone marrow support: the Dana-Farber Cancer Institute/Beth Israel Hospital experience.

Fifty-nine patients received 61 courses of cyclophosphamide, cisplatin, and carmustine combined. The phase I study consisted of seven dose escalations. Dose levels 5 and 6 also included the attempted addition of melphalan at 40 and 80 mg/m2. The maximum tolerated dose for the three-drug combination was 5620 mg/m2 of cyclophosphamide, 165 mg/m2 of cisplatin, and 600 mg/m2 of carmustine. The dose-limiting toxic effect was fatal veno-occlusive disease of the liver in two of five patients treated at the highest dose level. Veno-occlusive disease of the liver was fatal in two of 40 patients treated at Dose level 4, the maximum tolerated dose. The median time to recovery of polymorphonuclear leukocyte counts to greater than 500/microliters and platelet counts to transfusion independence greater than 20,000/microliters was 19 and 22 days, respectively, after marrow reinfusion. Other toxic effects observed included postdischarge pulmonary toxicity, which appeared to respond to prednisone therapy. Thus, this combination of alkylating agents can be combined at close to the transplant dose of each individual agent. The response rate was high despite considerable prior treatment in most patients. Of 16 evaluable patients with breast cancer, 15 responded (six complete responses). Of six evaluable patients with sarcoma, six responded (one complete response). While patients with melanoma had had no prior treatment, 11 of 17 patients responded (65%). There are currently three patients who are disease-free. Two patients with melanoma were rendered disease-free by excisional biopsy of the only remaining nodule after good partial response, and a patient with metastatic breast cancer remains disease-free after a complete response at 36+ months.

Adult↗

Contralateral cancerous breast lesions in women with clinical invasive breast carcinoma.

Eighty-four consecutive autopsies of women with a clinical diagnosis of invasive breast carcinoma (BC) were examined by extensive histopathologic methods for malignant changes of the contralateral breast. Sixty-eight percent of the women were found to have primary contralateral BC, of which 33% were invasive and 35% in situ lesions. Another 16% had metastases to the breast. Only two women had had treatment for their contralateral BC. In eight cases a malignant lesion was diagnosed or suspected clinically, but in the remaining cases, the malignancies were identified only by histopathologic examination. No clinical data or histologic characteristics of the first BC had any predictive value for the risk of contralateral BC. In the contralateral breast, a significant coincidence was found between fibrocystic disease and the occurrence of primary malignant BC. The majority of the BC on both sides were of ductal type. Seventy-nine percent of the invasive contralateral BC were tumefacient, and 71% had axillary lymph node metastases. The mean survival time was comparable for women with and without contralateral primaries, but a significantly higher proportion of women with contralateral invasive BC died of disseminated BC. The frequency of contralateral malignancies is thus much higher than previously reported. The consequence of these findings may implicate a reevaluation of the treatment and control schedule regarding the contralateral breast in women with invasive BC.

Adult↗

Characterization of RNA-protein interactions in 7 S ribonucleoprotein particles from Xenopus laevis oocytes.

5 S RNA interactions with transcription factor protein A (TFIIIA) in 7 S particles from Xenopus laevis oocytes (Xlo) have been characterized by the use of an in vitro RNA exchange assay. 32P-labeled Xlo 5 S RNA can rapidly be incorporated into 7 S particles by simple incubation of the RNA with intact particles. Incorporation of the labeled RNA during exchange reaches an equilibrium within 20 min at 20 degrees C. Labeled Xlo 5 S RNA already incorporated in 7 S particles can be chased out by an excess of unlabeled 5 S RNA. Nondenaturing gel electrophoresis of 7 S particle samples segregates several ribonucleoprotein particles containing TFIIIA and 5 S RNA. Time course experiments reveal incorporation of 32P-labeled 5 S RNA first in a higher molecular weight ribonucleoprotein particle before incorporation into the 7 S particle. In the exchange process, the integrity of the higher order structure of the RNA is essential for a recognition of the 5 S RNA by TFIIIA. Denatured Xlo 5 S RNA exchanges poorly in the presence of EDTA, but can exchange into the particle at a high level if sufficient divalent cations are present to allow the higher order structure of the RNA to reform. Xlo 5 S RNA fragments that have the 5' or 3' ends deleted past helix I markedly lose their ability to exchange. Heterologous eukaryotic and eubacterial 5 S RNAs can exchange into 7 S particles, although the eubacterial 5 S RNAs exchange at a low level.

Animals↗

Venous muscle pump function in patients with primary lymphoedema: assessment by ambulatory strain gauge plethysmography.

The musculovenous pump function was assessed by ambulatory strain gauge plethysmography in 11 patients with primary lymphoedema. The venous function was within the normal range regarding both venous reflux and expelled volume. The values were compared with ten patients with chronic venous insufficiency and oedema. The values for venous function were clearly abnormal for the patients with venous insufficiency and different from those with primary lymphoedema. Ambulatory strain gauge plethysmography may be a useful non-invasive method in distinguishing between oedema of lymphatic or venous origin.

Adult↗

Corneal transplantation using long-term cultured donor material.

Twenty-seven corneal transplantations with a mean duration of donor incubation of 14.3 days (group 1) and 36 transplantations with a mean duration of incubation of 29.8 days (group 2) were followed for 18 months. No significant difference was found in graft survival between the two groups (81 versus 80%). Almost all graft failures were found among pre-operatively defined high-risk cases, i.e. previously transplanted and/or vascularized recipient cornea. The profile of the corneal thickness curve was almost identical in the two groups, and normal values were reached in both. Visual acuity was 0.5 or better in 23% of the cases in group 1, and 35% in group 2. These figures were highly influenced by co-existing and complicating eye disease i.e. amblyopia, cataract, macular degeneration and glaucoma. The results show that 2 weeks and 4 weeks cultured cornea do not differ with respect to graft survival and thickness. The over all results indicate that long-term cultured donor material is suitable for corneal transplantation and fully comparable to material stored by other methods.

Adolescent↗

High-dose combination alkylating agent chemotherapy with autologous bone marrow support for metastatic breast cancer.

Seventeen patients with metastatic breast cancer were treated with a high-dose combination chemotherapy regimen and autologous bone marrow support. Thirteen patients had prior combination chemotherapy. Fifteen patients were treated with a phase II regimen of cyclophosphamide (5.625 g/m2), cisplatin (165 mg/m2), and BCNU (600 mg/m2). Bone marrow harvest and reconstitution were uncomplicated. All patients became profoundly myelosuppressed. Fourteen of 16 evaluable patients (88%) responded, including six complete responses (CRs) (38%). The median time to tumor progression was 5 months. The median survival was 8 months. CRs occurred more frequently in patients with no prior chemotherapy for metastatic disease, inflammatory breast cancer; and patients treated within 3 months of first recurrence. The rate of tumor regression was rapid, with a median of 11 days to partial response (PR) and 12 days to CR. Those patients achieving a PR by day 7 had a greater likelihood (P = .03) of attaining a CR than those patients whose PR occurred later. Three deaths (18%) occurred, all in women with inflammatory breast cancer treated with prior chemotherapy. High-dose combined alkylating agent therapy produced high PR and CR rates in metastatic breast cancer patients, most of whom had failed prior chemotherapy. The rate of tumor regression was rapid. Current efforts are directed at developing a regimen using drugs specifically active in breast cancer, with an intent of combining an effective high-dose regimen with additional modalities of therapy in the treatment of breast cancer.

Adenocarcinoma↗

Pharmacokinetics of dibromodulcitol in humans: a phase I study.

A combined clinical and pharmacokinetic phase I study of the substituted hexitol dibromodulcitol (DBD), administered as a single oral monthly dose, has been performed. Twenty-three patients with advanced neoplasms received DBD doses ranging from 600 to 1,800 mg/m2 body surface area (BSA). The dose-limiting toxicity was myelosuppression, with both significant granulocytopenia and thrombocytopenia occurring at dose levels of 1,500 to 1,800 mg/m2. The average pharmacokinetic parameters for DBD, calculated on the basis of a one-compartment model with first-order absorption and elimination, include the elimination constant, .005 +/- .002/min; absorption constant, .012 +/- .009/min; and an apparent volume of distribution, 1.03 +/- .4 L/kg. The area under the drug concentration curve (AUC) and the peak drug level (Cmax) were linearly related to the dose administered (P less than .001). The mean AUC was 18.7 +/- 6.1 mmol/L min, and the mean Cmax was 47.1 +/- 16.8 mumol/L when normalized to a DBD dose of 1 gm/m2. The elimination constant was significantly reduced in patients with abnormal hepatic function (P less than .01). The elimination constant was not correlated with renal function. The half-life of DBD in plasma (158 minutes) was considerably shorter than the four-to eight-hour half-life of total radioactivity in plasma measured by previous investigators following the administration of radiolabeled DBD.

Absorption↗

Radiation dose in investigations of the large bowel. Comparison of radiation doses in examinations of the colon with double-contrast barium enema with the Welin modification and colonoscopy.

Because of the increasing and repeated application of colonoscopy and double-contrast barium enema with the Welin modification in connection with the checking of patients who have been treated for neoplastic polyps, we have found it valuable to examine the amount of radiation that the patients are exposed to in the two kinds of examinations. The radiation dose in the examination of the colon with the Welin modification (35 examinations) and at colonoscopy (114 examinations) was, on an average, 387 and 10 mSv, respectively. Since colonoscopy gives a possibility not only of diagnosis but also of treatment and also exposes the patients to 40 times less radiation than X-ray examination with the Welin modification, we recommend colonoscopy for diagnosis and treatment of neoplastic colonic polyps.

Adolescent↗