Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “THALIDOMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,153 records · Page 64Linked to original sources
PubMedDate not supplied

Liquid chromatographic determination of thalidomide in tablets, capsules, and raw materials.

A simple, isocratic liquid chromatographic method for assay of thalidomide in tablets, capsules, and raw materials was developed. The method uses a Nova-Pak octadecylsilane bonded-phase column (150 x 3.9 mm, 4 microns particle size), a mobile phase of acetonitrile-water (15 + 85), a flow rate of 1 mL/min, detection at 237 nm, and phenacetin as internal standard. Phosphoric acid was used in preparation of sample solutions to inhibit thalidomide hydrolysis. Assays ranged from 99.3 to 100.4% in raw materials from 4 manufacturers, from 79.7 to 104.8% in tablets from 7 manufacturers, and from 75.3 to 102.6% in capsules from 4 manufacturers. Assay method precisions for triplicate analyses on 5 days were 0.30% for tablets, 0.22% for capsules, and 0.22% for raw materials. Recovery from simulated tablet formulations was 100%. The method has been used to analyze individual tablets and capsules for determination of content uniformity.

Acetonitriles↗
PubMed1997

Thalidomide-induced toxic pustuloderma.

We report a case of toxic pustuloderma secondary to thalidomide in a patient with severe nodular prurigo. To our knowledge this is the first reported case. With the increasing use of thalidomide for a variety of dermatological conditions it is clearly important that this rare side-effect now be recognised.

Adult↗
PubMedDate not supplied

Suppression of serum tumour necrosis factor-alpha by thalidomide does not lead to reversal of tumour vascular collapse and anti-tumour activity of 5,6-dimethylxanthenone-4-acetic acid.

The antitumour agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA), developed in this laboratory as a potent analogue of flavone acetic acid (FAA), has a novel antitumour action involving both immune and vascular components. DMXAA induces the synthesis of tumour necrossi factor-alpha (TNF) and it has been hypothesised that this mediates its selective reduction of tumour blood flow and consequent induction of tumour necrosis. Unexpectedly, the drug thalidomide, while reducing the serum TNF response to DMXAA, potentiates its antitumour effect. We have investigated this in the MDAH-MCa-4 mammary carcinoma model, comparing it to previous data with the Colon 38 adenocarcinoma. We have related DMXAA-induced blood flow changes in the MCa-4 tumour to tumour growth delay, serum TNF and extractable TNF from tumour tissue. We have also compared the effect of thalidomide (387 mumol/kg) on DMXAA (80 mumol/kg) with that of a monoclonal anti-TNF antibody (50 micrograms/mouse). We find that tumour blood flow reduction is strongly correlated with tumour growth delay. Coadministration of anti-TNF antibody abolishes serum TNF levels and slightly reduces the antitumour effects of DMXAA. While tumour growth delay is not correlated with serum induced TNF levels, it is related to tumour TNF levels. We conclude that while the data are consistent with TNF being the principal mediator of the action of DMXAA, serum TNF levels do not reflect the antitumour response.

Adenocarcinoma↗
PubMed2000

8:45-9:00. Using PET 18F-FDG, 11CO, and 15O-water for Monitoring Prostate Cancer During a Phase II Anti-angiogenic Drug Trial with Thalidomide.

Assessing prostate metastases is difficult with conventional radiographic modalities as few patients have soft tissue involvement and most have only bone lesions. Even with FDG PET, problems due to decreased avidity compared to other tumor types can occur. We assessed PET's ability to monitor changes in such tumors during an anti-angiogenic therapy. We measured changes in tumor blood flow (15O), blood volume (11CO), 18F-FDG uptake and "metabolic volume" before and during thalidomide treatment, to see if these changes correlated with changes in PSA values.Six patients with androgen-independent prostate cancer were imaged with 18F-FDG, 11CO, and 15O water before and during (mean interval 63 days, range 55-76 days) thalidomide therapy (200-1200mg/day). Lesions were visually identified on FDG images (9 bone, 5 soft tissue lesions). VOI's were generated by 3D region growing, with a 50% maximum pixel threshold. These VOI's were registered with, and applied to, the 11CO and water studies. Correlations with PSA values were done using the Spearman rank test.The change in maximum (r = 0.77, p = 0.06) and mean FDG value (r = 0.83, p = 0.03), functional FDG volume (r = 0.66, p = 0.14), and 11-CO blood volume (r = 0.77, p = 0.06) all correlated with the change in PSA. Changes in blood flow values were smaller than the variance of the method for repeated measures, likely due to low flow values in bone.Changes in blood volume measured by 11CO, and the mean and peak activity and functional volume measured by 18F-FDG, correlate with changes in PSA and may be useful in monitoring anti-angiogenic therapy in prostate cancer.

Journal Article↗
PubMed1997

New anti-angiogenesis agents: review of the clinical experience with carboxyamido-triazole (CAI), thalidomide, TNP-470 and interleukin-12.

Angiogenesis was postulated to be a critical prognostic factor and therapeutic focus for malignancy more than two decades ago. Recent studies indicate quantitative assessments of microvessel count to be an independent prognostic variable for disease-free and overall survival in a wide variety of tumors, and that angiogenesis may be a feasible target against which to intervene pharmacologically. Several new and old agents have been found to have anti-angiogenic activity and have reached clinical trial. This review will focus on four agents under investigation in the US: carboxyamido-triazole (CAI), thalidomide, TNP-470 and interleukin (IL)-12. CAI, originally identified for its anti-invasive capacity, has been shown to inhibit tumor and endothelial cell proliferation by inhibition of calcium uptake. It is administered orally, is generally well tolerated, and has been shown to induce disease stabilization and occasional reductions in tumor mass. Thalidomide was shown to inhibit growth factor-induced neovessel formation, a process that can also explain its earlier devastating clinical toxicity. It is administered orally, and is currently in phase II clinical trials for prostate cancer, glioblastoma multiforme and breast cancer. TNP-470 is a fumagillin analog that has been shown in in vivo models to be a potent inhibitor of angiogenesis at concentrations that are cytostatic to endothelial cells and tumor cells. Lastly, IL-12 may exert its anti-angiogenic effects through activation of interferon-gamma to up-regulate interferon-inducible protein-10, an anti-angiogenic cytokine. Phase I clinical trials of IL-12 have shown disease stabilization in several tumor types in response to s.c. administration or using genetically engineered IL-12-expressing patient fibroblasts. These promising new agents join the matrix metalloproteinase inhibitors as important new drugs in the anti-cancer armamentarium.

Journal Article↗
PubMed1983

Identification of adverse reactions to new drugs. I: What have been the important adverse reactions since thalidomide?

A consensus process was used to establish an agreed list of important adverse reactions to drugs identified since thalidomide. Ten physicians working in medicine in Britain and 10 physicians responsible for drug regulatory agencies in different countries were asked to list 10 important adverse reactions to drugs since thalidomide. From these 20 lists a measure of agreement was apparent. Eighteen important adverse reactions were identified for further study of the discovery processes now operating and of the delays occurring from marketing to alerting, from alerting to verification, and from verification to regulatory action. The results suggest that an empirical review of this type is necessary as a starting point for discussion of better systems to reduce delays in the discovery of adverse reactions to new drugs.

Drug Evaluation↗
PubMedDate not supplied

[Embryotoxic interactions between a hydrolysis product of thalidomide and the surfactant Tween 20 in mice].

N,N-phthaloyl-L-glutamic acid (NPLG), a hydrolysis product of thalidomide, and the surfactant Tween 20 were co-administered intraperitoneally to pregnant NMRI mice on days 9 and 8 2/3 p.c. at doses where the hydrolysis product as well as the surfactant alone induce minimal embryotoxicity. The combined substances (350 mg/kg NPLG + 1.0 ml/kg Tween 20) caused a potentiative teratogenic and an additive embryolethal response. Enhancement of the amount of Tween 20 in the combinations to 2.5 ml/kg led to the same potentiative teratogenic and, in addition, potentiative embryolethal response. Distribution studies using 14C-NPLG showed a strongly increased NPLG content in the maternal plasma under the influence of 2.5 ml/kg Tween 20 but not after co-administration with 1.0 ml/kg Tween 20. The malformations obtained were of the same type in all groups and mostly located in the vertebrae and ribs. These axial and paraxial defects were frequently more severe and included more affected elements after application of the combined than of the single substances. Extension of our experiments with the combined substances to treatment days 8 1/2 and 9 1/2 p.c. revealed that the first affected segment shifts in caudal direction depending on an increasing embryonal age at treatment. Limb malformations occurred at a low frequency; most of them were of the same type as described in cases of human thalidomide embryopathy.

Abnormalities, Drug-Induced↗
PubMed1987

[Generalized lichen planus with erosive lesions of the penis, treated with thalidomide. Report of a case and review of the literature].

A patient with generalized lichen planus with lesions in the infrequent localization like face, palms, soles and an extensive erosion of glans penis, is described in a 46 year old patient. He had received various treatment which include systemic steroids, without improvement. After treatment with thalidomide (initial doses 300 mg/day for 2 weeks and 200 mg/day for further 10 weeks) he presents resolution of his lesions and symptomatology. A review of lichen planus etiopathogenesis, making emphasis in the immunological hypothesis is made. As well as the different uses and action mechanism of thalidomide in various inflammatory dermatoses.

Humans↗
PubMed1963

Metabolic deficiencies in protozoa induced by thalidomide.

Thalidomide inhibits growth of some protozoa. This inhibition was counteracted by nicotinic acid, nicotinamide, nicotinamide adenine dinucleotide, and vitamin K(1). The mechanism of toxicity may be an interference of cellular oxidation. A protozoan test system is useful for studying the potential "side actions" of drugs in higher animals and man.

Animals↗
PubMed1963

Habilitation of patients with congenital malformations associated with thalidomide: psychiatric and psychological aspects.

Nearly 100 cases of congenital malformations associated with thalidomide ingestion by the mother have been reported in Canada to the Department of National Health and Welfare. Depression and selfcastigation have been the specific psychiatric reactions noted, particularly in the mother. In most cases it is preferable psychologically for the parents and the child if the child is kept at home rather than placed in an institution. Parents should be fully informed concerning the child's prognosis for future development. Most of the children followed up for about two years showed no intelligence defects. A prosthesis, if required, should be applied early (at three to six months) so that it may become a part of the child's body-image, but it should not interfere with play activities. Assessment by a psychiatrist and a psychologist is indicated at about six months.

Body Image↗
PubMed1963

Habilitation of patients with congenital malformations associated with thalidomide: prosthetic aspects.

The types of prostheses available for treatment of congenital amputations in children, and the assistance in habilitation which can be expected from their use, are described in this communication.The limb deformities in children commonly associated with the drug thalidomide are phocomelia and amelia. Prosthetic treatment of these is difficult, but in almost every case some assistance can be offered. The degree of this assistance will depend to a large extent on (1) the number of limbs involved, (2) the site of the deformity, (3) the intellectual capacity of the child. These factors are evaluated by a clinic team, consisting of a prosthetist, a therapist, a social worker, and a doctor, who acts as the clinical chief. They are also embodied into a prescription for a prosthesis and into a program of management. Subsequently, the clinic team also carry out an assessment of the result. The prosthetist makes available his knowledge of present-day appliances, and assures that the way is left open for use of new, and perhaps revolutionary prostheses, in the future.

Artificial Limbs↗
PubMed1963

Habilitation of patients with congenital malformations associated with thalidomide: surgery of limb defects.

The deformities commonly seen in "thalidomide babies" are described. These vary from relatively uncomplicated radial-ray defects to complete phocomelia of all four extremities. It is suggested that the care of these children is best carried out in a clinic accustomed to dealing with juvenile amputee problems. A plea is made for very early fitting of upper-extremity prostheses (at approximately three months of age) in cases of unilateral upper-limb deficiencies. A "bucket" for sitting should be supplied for children with quadrilateral phocomelia to sit in when they reach seven or eight months of age. Children with severe upper-limb malformations will be candidates for some form of externally powered prostheses.

Adolescent↗
PubMed1963

CANADIAN THALIDOMIDE EXPERIENCE.

Data are presented on 115 children, including three sets of twins, born in Canada in 1961 and 1962 with congenital malformations associated with the use of thalidomide by their mothers in early pregnancy. The epidemiological method is described. Of the 115 children, 74 were alive at the time of reporting, 41 of these being severely handicapped; 8 had been stillborn; 33 had died. Limb involvement was usually bilateral, affecting the upper limbs alone in 42 cases, and the upper and lower limbs in 41. Of 112 mothers, only 60 had had the drug prescribed by the physician providing maternity care; 87 were estimated to have first taken the drug before their last menstrual period or within 56 days thereafter. A plea is made for the development of better methods of collecting information on the occurrence of congenital malformations, with the aid of practising physicians.

Abnormalities, Drug-Induced↗
PubMed1976

Thalidomide anomalies of the ear.

Eighteen 12- to 16-year-old patients with thalidomide embryopathy were examined otologically and neurotologically to clarify both morphological and functional ear anomalies. Ear anomalies were found in the external, middle, and inner ears. However, the inner ear, especially the vestibular portion of the labyrinth, was more extensively undeveloped both morphologically and functionally. Dysfunctions were concomitant in the oculomotor and the vestibular systems.

Abducens Nerve↗
PubMed1999

Enantioseparation of thalidomide and its hydroxylated metabolites using capillary electrophoresis with various cyclodextrins and their combinations as chiral buffer additives.

The separation of thalidomide (TD) and its hydroxylated metabolites including their simultaneous enantioseparation was studied in capillary electrophoresis (CE) using four different randomly substituted charged cyclodextrin (CD) derivatives, the combinations of some of them with each other, and beta-CD. TD, as well as two metabolites recently found in incubations of human liver microsomes and human blood, 5-hydroxythalidomide (5-OH-TD) and one of the diastereomeric 5'-hydroxythalidomides (5'-OH-TD), are neutral compounds. Therefore, they were resolved using charged chiral selectors in CE. Two different separation modes (normal polarity and carrier mode) and two different capillaries (fused-silica and polyacrylamide-coated) were tested. Based on the behavior of the individual CDs, their designed combinations were selected in order to improve the separation selectivity and enantioselectivity. Under optimized conditions all three chiral compounds and their enantiomers were resolved simultaneously.

Acrylic Resins↗
PubMed2000

Investigation of the stereoselective in vitro biotransformation of thalidomide using a dual cyclodextrin system in capillary electrophoresis.

A previously developed capillary electrophoresis method for the simultaneous separation and enantioseparation of thalidomide (TD) and its hydroxylated metabolites was extended to one additional biotransformation product. The dual chiral selector system using native beta-cyclodextrin (beta-CD) and the negatively charged sulfobutyl ether-beta-CD (SBE-beta-CD) was slightly modified up to a concentration of 12 mg/mL running buffer of each CD. The carrier mode in which these buffer additives transport the neutral compounds to the detector as well as the use of a polyacrylamide-coated capillary were necessary to achieve reproducible enantioseparations of all eight analytes. The optimized method was applied to the analysis of the in vitro biotransformation of TD by rat liver microsomes. The S-enantiomer undergoes metabolism preferentially by hydroxylation in the phthalimide ring, whereas R-(+)-TD is mainly transformed to diastereomeric 5'-hydroxythalidomide (5'-OH-TD) pairs. The chiral capillary electrophoresis of incubation samples of TD enantiomers in combination with X-ray diffraction data allowed us to determine the absolute configuration of all metabolites and furthermore to follow the enantio- and stereoselective effects of metabolism in detail.

Animals↗
PubMed2004

Thalidomide in POEMS syndrome: case report.

We report a patient with incapacitating POEMS syndrome characterized by serum monoclonal protein, polyneuropathy, organomegaly, endocrinopathy, mesangiocapillary glomerulonephritis, massive ascites formation, and pulmonary hypertension. A dramatic improvement in the clinical condition occurred after administration of thalidomide, a drug with known anti-angiogenetic, anti-proliferative, and anti-cytokine properties.

Angiogenesis Inhibitors↗
PubMed1984

Thalidomide. A promising new treatment for rheumatoid arthritis.

In an open study, oral administration of thalidomide to 7 female patients with classic or definite rheumatoid arthritis, in doses ranging from 6.9 to 15 mg/kg/day, led to clinical improvement within several weeks. In 4 women, remission lasted long after discontinuation of the drug. All patients showed normalization or marked reduction of the erythrocyte sedimentation rate, and several showed a significant decrease in rheumatoid factor titer. Adverse side effects included drowsiness, constipation, and edema of the lower limbs, which disappeared after discontinuation of the drug.

Adult↗