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Biomedical subjects

L Winkelman

Publications and source records attributed to L Winkelman.

18 recordsLinked to original sources
PubMed1996

A bleomycin/ifosfamide/cisplatin regimen exhibits poor activity against persistent or recurrent squamous gynecologic cancers.

Persistent or recurrent squamous malignancies of the female genital tract are usually incurable by conventional therapy, and results of single agent chemotherapy have been disappointing. We undertook this study to confirm a previously reported response rate of 69%, using a regimen of bleomycin 30U, ifosfamide 5g/m2 with mesna 6g/m2, and cisplatin 50 mg/m2 (BIP) for recurrent cervical cancer. This regimen was used to treat persistent or recurrent squamous cancers in women with cervical cancer (n = 11), vaginal cancer (n = 1) and vulvar cancer (n = 1). Results were reviewed retrospectively and toxicities graded according to the criteria of the Gynecologic Oncology Group. No complete responses were seen. One patient had a partial response (10%, 95% confidence interval 0-28%). Five patients (50%), exhibiting stable disease during therapy with BIP, progressed after cessation of therapy. Of 9 women with symptoms after one cycle. Significant toxicities included neutropenic fever (3 grade 3, 3 grade 4), emesis (1 grade 3), confusion (2 grade 4), vaginal bleeding (2 grade 3), and renal failure (1 grade 3). Eight patients were transfused with a total of 28 units of red cells. After 23 months of follow-up, all patients were dead of disease. Mean survival was 10 months. Toxicity associated with this regimen can be significant, and results appear no better than those reported with single agent therapy.

Adult↗
PubMed1994

Salvage mitomycin/5-fluorouracil after platinum-based therapy for women with advanced ovarian cancer and related gynecologic malignancies.

PURPOSE: to determine response rates, survival, and toxicity of a regimen of mitomycin-C and 5-fluorouracil in patients previously treated with platinum-based combinations for ovarian cancer and related gynecologic malignancies. PATIENTS AND METHODS: retrospective chart review of all cases of persistent or recurrent ovarian, fallopian tube, and peritoneal carcinoma treated with mitomycin-C 7 mg/m2 followed by continuous infusion of 5-fluorouracil 600 mg/m2/day over 4 days. RESULTS: 26 patients were treated after a median of 2 prior platinum-based regimens, 22 with ovarian cancer, 3 with peritoneal cancer, and one with fallopian tube cancer. Only 2 patients completed 6 or more cycles. 2 patients had partial responses (8%); no complete responses were seen. 24 patients died a median of 3 months after the initiation of therapy, while 2 patients were alive 4 and 8 months after beginning therapy. All deaths were attributable to disease, not complications of treatment. 8 patients required dose modification or treatment delay for toxicity. Nine patients required a total of 11 unscheduled admissions. CONCLUSIONS: toxicity attributable to mitomycin-C/5-fluorouracil therapy of ovarian cancer is acceptable, but responses are few. More effective alternative should be sought.

Adult↗
PubMed1992

Production and therapeutic use of a factor XI concentrate from plasma.

Factor XI deficiency is an uncommon bleeding disorder usually manifested by excessive bleeding after surgery or trauma. Until recently the only effective therapy has been fresh-frozen plasma (FFP) infusion. We describe the efficacy and safety of a new factor XI concentrate produced from human donor plasma by a modification of the method used for antithrombin III concentrate. The mean recovery of factor XI in the circulation measured on 62 occasions was approximately 91% of the injected dose, and the mean half-disappearance-time was 52 h. The concentrate was used for 31 invasive procedures in 30 patients, including 16 patients who had a definite bleeding tendency on previous occasions, with normal haemostasis being achieved in all but 1. Only 1 patient (previously experiencing allergy to FFP) experienced adverse effects during infusion. Monitoring of liver function tests and viral antibody status in suitable patients has shown no evidence of transmission of hepatitis viruses, HIV-1 or parvovirus B19. We conclude that this concentrate provides effective treatment for patients with factor XI deficiency. Preliminary results suggest safety from virus transmission, but this needs to be established in further studies of previously untreated patients.

Adolescent↗
PubMed1990

A simple plasma anticoagulant-exchange method to increase the recovery of factor VIII in therapeutic concentrates.

Donor blood, primarily anticoagulated by acid citrate dextrose formula A (ACD-A), was separated by means of the HemaScience Autopheresis C plasmapheresis device. The citrated plasma was collected directly into a solution of heparin and calcium chloride to achieve a final plasma-ionised calcium concentration of approximately 2 mM, and a heparin concentration of 1.0 IU/ml. Heparin at this concentration provided adequate anticoagulation, and did not result in insoluble cryoprecipitates. Three pairs of donor-matched 4-kg plasma pools (anticoagulant-exchanged variant and ACD-A-anticoagulated control) were constructed and subsequently fractionated to an intermediate stage. The mean recovery of factor VIII from 3 anticoagulant-exchanged pools (394 IU/kg) was 23% greater than the mean recovery from the matched control pools (319 IU/kg). This increased recovery was not achieved at the expense of specific activity.

Anticoagulants↗
PubMed1989

Severely heated therapeutic factor VIII concentrate of high specific activity.

A new method for the manufacture of a heated factor VIII concentrate of high specific activity (2-6 IU factor VIII:C/mg protein) has been developed. Addition of heparin to cryoprecipitate extract at acid pH precipitated fibrinogen and fibronectin. Factor VIII was then recovered from the supernatant by precipitation with glycine and sodium chloride. After re-solution and desalting on Sephadex G-25, the concentrate was sterile-filtered and lyophilised. The dried product was stable to heating in the final container at 80 degrees C for 72 h. Data from 25 consecutive batches of concentrate prepared from 1,200-1,500 kg plasma pools are presented. The mean final yield of heated product was 190 IU factor VIII:C/kg plasma. The concentrate has been found to be safe and effective in clinical use.

Chemical Precipitation↗
PubMed1987

Interim results of surveillance for NANBH in patients receiving heated concentrates produced in England.

Coagulation factor concentrates prepared in England are all subjected to heating in solution or in the lyophilised state. Concentrates of factor VIII, factor IX (II and X), factor VII and factor XI are terminally heated in the lyophilised state at 80 degrees C for 72 h but the current fibrinogen concentrate withstands only 70 degrees C for 24 h. 33 patients receiving factor VIII concentrate (code 8Y) and factor IX concentrate (code 9A) for the first time have had regular liver function tests (LFTs) and we have at least some data on 26 of them exposed for greater than 3 months. Of these 26 patients, four had received no blood products before 8Y, 15 had received only cryoprecipitate before 8Y, and seven had received no blood products before 9A. Nine have missed only one or none of their two-weekly tests, four have missed two or three tests and on the remaining 13, the LFT follow-up has been unsatisfactory, although in some cases clinical examination has been helpful. 12 batches of 8Y from greater than 70,000 donations and seven batches of 9A from greater than 40,000 donations have been used. In 13 patients who have had regular prospective LFTs, none has had an ALT or AST level above twice normal. One patient followed only irregularly has shown an isolated ALT rise at eight weeks, unconfirmed at nine or at 17 weeks.

Blood Coagulation Factors↗
PubMed1986

Pasteurisation induced changes in an antithrombin III concentrate.

The changes that take place when a therapeutic antithrombin III (AT III) concentrate is heated in the presence of citrate ion have been assessed. There is some loss of heparin cofactor antithrombin activity and of heparin binding ability. Protein aggregates are also formed during heating. These aggregates are not AT III but impurities in the concentrate.

Antithrombin III↗
PubMed1986

A pasteurised concentrate of human plasma factor XIII for therapeutic use.

A therapeutic concentrate of factor XIII containing both A and B sub-units has been prepared from 300 kg pools of human plasma. The process starts from a cold-ethanol fraction from cryoprecipitate supernatant and therefore does not interfere with the recovery of other clinically valuable plasma proteins. Factor XIII is purified approximately 600-fold from plasma by precipitation with sodium citrate and by the removal of fibrinogen by brief heating. The product has been pasteurised in sorbitol solution to inactivate blood-borne viruses, ultrafiltered to remove sorbitol, adsorbed with bentonite and freeze-dried in a formulation meeting requirements for intravenous injection.

Drug Contamination↗
PubMed1986

Heat-treated NHS factor VIII concentrate in the United Kingdom--a preliminary study.

Three patients who have been given intermediate purity NHS heat-treated factor VIII concentrate have been followed prospectively for 7-10 months. None had previously received more than six donor units of blood products containing factor VIII. There were no clinical side effects from concentrate administration, haemostasis was satisfactory and no patient developed clinical or laboratory evidence of hepatitis or HTLV III/LAV infection. Heat treatment resulted in the loss of slightly more than 20% of factor VIII activity but in vivo recovery of factor VIII and half disappearance times were within the expected range.

Acquired Immunodeficiency Syndrome↗
PubMed1985

A pasteurized antithrombin III concentrate for clinical use.

A method for large-scale production of a pasteurized antithrombin III (AT III) concentrate for therapeutic use has been adapted from published methods. It includes the following steps: (1) batchwise adsorption onto heparin-Sepharose from plasma depleted of cryoprecipitate and prothrombin complex; (2) chromatographic elution at high salt concentration; (3) pasteurization for 10 h at 60 degrees C in the presence of added citrate ion; (4) desalting on Sephadex G-25, and (5) sterile filtration and freeze-drying. Seven batches prepared in this manner gave a mean yield of 269 U AT III/kg plasma. The product passed all the usual animal safety and pyrogenicity tests and has been used successfully in several courses of treatment of congenital deficiencies.

Adsorption↗
PubMed1973

The contractile and regulatory proteins of insect flight muscle.

1. Myosin, actin and the regulatory proteins were prepared from insect flight muscle. 2. The light subunit composition of the myosin differed from that of vertebrate muscle myosin. The ionic strength and pH dependence of the myosin adenosine triphosphatase (ATPase) were measured. 3. Actin was associated with a protein of subunit molecular weight 55000 and was purified by gel filtration. Impure actin had protein bound at a periodicity of about 40nm. 4. Regulatory protein extracts had tropomyosin and troponin components of subunit molecular weight 18000, 27000 and 30000. Crude extracts of regulatory proteins inhibited the ATPase activity of desensitized or synthetic actomyosin; this inhibition was relatively insensitive to high Ca(2+) concentrations. Purified insect regulatory protein produced as much sensitivity to Ca(2+) as did the rabbit troponin-tropomyosin complex. 5. Synthetic actomyosins were made from rabbit and insect proteins. Actomyosins containing insect myosin had a low ATPase activity that was activated by tropomyosin. The Ca(2+) sensitivity of actomyosins containing insect myosin or actin, with added troponin-tropomyosin complex from rabbit, was comparable with that of rabbit actomyosin.

Actins↗