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Biomedical subjects

W Waugh

Publications and source records attributed to W Waugh.

At least 19 recordsLinked to original sources
PubMed2000

Degradation pathways of a peptide boronic acid derivative, 2-Pyz-(CO)-Phe-Leu-B(OH)(2).

The peptide boronic acid derivative 2-Pyz-(CO)-Phe-Leu-B(OH)(2) is a potent inhibitor of 20S proteasome and a proposed anticancer agent. During preformulation studies, the compound presented erratic stability behavior. Efforts were made to isolate and identify the degradation products, thereby helping to identify possible mechanisms for the degradation. The reaction of 2-Pyz-(CO)-Phe-Leu-B(OH)(2) with hydrogen peroxide not only provided a convenient way to isolate the initial degradation products seen from hydrolysis in aqueous buffers but also showed that the major, initial degradation pathway was probably oxidative in nature. The isolated degradation products were characterized by nuclear magnetic resonance spectroscopy, mass spectrometry, and optical rotation dispersion. In the presence of hydrogen peroxide, the boronic acid group was cleaved from 2-Pyz-(CO)-Phe-Leu-B(OH)(2) to give an alcohol with an apparent retention of the original stereochemistry. Subsequent isomerization and further hydrolysis were then seen. Surprisingly, added ascorbate and EDTA accelerated rather than inhibited degradation. Degradation of 2-Pyz-(CO)-Phe-Leu-B(OH)(2) under acidic and basic conditions seemed to be mediated by an initial oxidative degradation pathway similar to that seen with the peroxide.

Ascorbic Acid↗
PubMed2000

The management of depression: the implications for managed care--roundtable discussion: Part 2.

One of the most commonly utilized drug classes today is antidepressant therapy, which accounts for billions of dollars in spending. Pharmacoeconomic tools may play an influential role in formulary decision making, particularly in this drug class. In part 2 of the roundtable discussion, a pharmacoeconomic model is presented that may clarify the health economic effects of placing serotonin-norepinephrine reuptake inhibitors on the drug formulary, particularly in the context of other antidepressant medications.

Antidepressive Agents↗
PubMed2000

The management of depression: the implications for managed care--roundtable discussion: Part 3.

From the standpoint of managed care, the rising cost of depression can be addressed in multiple ways. In the final portion of the roundtable discussion, the faculty discuss not only disease management programs for depression, but other initiatives health plans (including at the pharmacy level) are undertaking to address the rising costs associated with depression. They also discuss the effect of mental health coverage "parity" laws, which can be expected to drive costs even higher.

Antidepressive Agents↗
PubMed1990

Biological modification of protracted infusion of 5-fluorouracil with weekly leucovorin. A dose seeking clinical trial for patients with disseminated gastrointestinal cancers.

A clinical trial was designed to find the maximally tolerated dose of weekly leucovorin (LV) that could be combined with 4 weeks of protracted infusion (PI) of 5-fluorouracil (5FU) at a fixed dose of 200 mg/m2. A total of 36 patients with disseminated gastrointestinal malignancies were treated; 9 either progressed or died before receiving 4 weeks of treatment leaving 27 patients evaluable for toxicity and response. 5FU was given as a protracted infusion using an ambulatory infusion pump and indwelling venous access. LV doses included 20, 25, 50, and 75 mg/m2 given as an i.v. push at the time of weekly pump fill with 5FU. In all, 72% of the patients tolerated LV at 20 mg/m2 for 4 continuous weeks, whereas the higher doses required treatment rests prior to 4 weeks. The dose-limiting toxicity at all doses was stomatitis. No significant myelosuppression was seen; diarrhea was infrequent. Overall, 40% of the patients with measurable cancer had partial responses. In view of evidence of biologic and therapeutic effects of these weekly doses of 20 mg/m2 LV with 200 mg/m2 5FU per day given as a protracted infusion over 4 weeks, phase II trials and multimodality studies for patients with gastrointestinal malignancies are being initiated at our institution using this dose and schedule.

Aged↗
PubMed1986

Tibial osteotomy in the management of osteoarthritis of the knee.

The historical development of operations for osteoarthritis of the knee is reviewed with emphasis on an upper tibial osteotomy, which was first described by the author and his colleague, Jackson, in 1961. Although the operation was used indiscriminately to correct both valgus and varus deformities in the early years, medial compartment osteoarthritis is now the main indication. The significance of angular deformity in relation to load-bearing across the joint is discussed. In the operative procedure, it is important to achieve a few degrees of overcorrection. Tibial osteotomy is a satisfactory procedure for the young patient with medial compartment osteoarthritis, particularly before the stage of bony collapse or subluxation.

Humans↗
PubMed1985

Tibiofemoral alignment and the results of knee replacement.

We examine the hypothesis that a knee replacement is most likely to survive successfully if it is stable with a coronal tibiofemoral angle close to 7 degrees of valgus, the accepted normal. The records of 428 knee replacements followed up for one to nine years were analysed. The highest success rate was indeed found in those so aligned at operation and such knees were most likely to remain stable. Nevertheless, half of the failures occurred in knees correctly aligned at operation and two-fifths in knees which had remained stable in this alignment; many failures must have been caused by factors other than malalignment. Some knees, well aligned at operation, deteriorated into severely varus or valgus positions; their failure rate was significantly higher than that for knees which remained normally aligned and higher also than for knees severely varus or valgus from operation onwards. Malalignment, in itself, may not be the most important cause of failure, though it probably does compound failure from other causes.

Aged↗
PubMed1985

Comparing the results of different types of knee replacement. A method proposed and applied.

Many knee replacement prostheses, embodying various principles of design, are now available and there is need for a method by which valid comparisons of results can be made. An important criterion of success is durability, so the length of time the prostheses have been in situ must be taken into account. Such a method is proposed here and is applied to the results of 673 knee replacements, of nine different types, implanted at the same hospital between 1970 and 1983. A prosthesis was considered to have failed if it had been removed or persistently caused severe pain. Two types of prosthesis were found to be significantly less successful than the other seven, between which none consistently showed significant superiority. Results for the seven types were similar despite the facts that they had been used for knees with different degrees of damage, some as secondary implants, and that they were of different design and at different stages of technical development. The more recently introduced types of prosthesis, designed to have theoretical advantages, were found in practice to be no more successful than the models they superseded.

Equipment Failure↗
PubMed1984

[Not Available].

Explore the source record for details and available documents.

History, Modern 1601-↗
PubMed1983

Knee replacement in rheumatoid arthritis.

This paper is based on experience gained from 583 primary knee replacements carried out at Harlow Wood Orthopaedic Hospital between 1968 and 1981. Various types of prostheses are discussed in relation to their application at various stages of destruction of the knee joint. Special problems concerning patients with rheumatoid arthritis and the problems of their damaged knee joints are emphasised. A plea is made for continued study which will recognise common factors essential for success.

Adult↗
PubMed1982

Continuous assessment of knee function and patient mobility.

A technique is described for measuring and analysing the load profile of the knees during daily routine. The method has been used on patients with chronic arthritis of the knee, both before and after joint replacement. Results are presented, and the logistics of carrying out such work are discussed. The method is applicable to joints other than the knee, diseases other than arthritis, and treatments other joint replacement.

Aged↗
PubMed1982

Articular changes associated with internal derangement of the knee.

A prospective study was made of 100 knees which had been operated on for various kinds of internal derangement. An observer, who did not know the clinical condition of the knee, recorded whether or not there were articular lesions of the femoral condyles. Lesions were found to be localised to a triangular area on the medial condyle and to a strip on the lateral condyle. Similar lesions have been described in association with flexion deformities in rheumatoid and osteoarthritic knees. Lesions were found in 49 out of 50 knees which had been locked for more than three days. They were also found in 29 knees in which there appeared to be full extension before operation, but where there was either a torn meniscus with a history of intermittent locking or serious anterolateral instability. In these cases it was considered that the final "screw-home" mechanism of full extension had been lost. Lesions were not present in 10 knees which appeared locked, but in nine of these the interval between injury and operation was less than three days. Lesions were not found in eight knees where there was full extension and no history of locking or instability. In four knees with a plica syndrome similar lesions were present.

Adolescent↗
PubMed1982

Estimating the survival time of knee replacement.

A method of analysing the results of knee replacement operations, which makes it possible to estimate the annual failure rate and the proportion of implants which will survive successfully for 10 years, is applied to the post-operative data for 365 operations, using Freeman, Sheehan and Manchester prostheses, carried out from 1972 to 1980 at Harlow Wood Orthopaedic Hospital. Two criteria of success are defined. On both, and for all prostheses, the annual failure rate is found to be much lower in the first two than in the later years. Thus, account must be taken of the period since operation if the success of different prostheses is to be validly compared. This is not possible using conventional statistical methods. But significant trends in annual failure rates and significant differences between prostheses can only be identified from samples larger than are usually available in individual series. Hence it will be necessary for many centres to co-operate in pooling results if reliable conclusions are to be reached and valid comparisons made.

Equipment Failure↗
PubMed1980

Antioxidants in purification, stabilization, and formulation of the antineoplastic agent 6-selenoguanosine.

6-Selenoguanosine (NSC 137679) was stablized and formulated as a lyophilized parenteral paroduct using ascorbic acid as an antioxidant. In addition to preventing the oxidation of 6-selenoguanosine to the corresponding diselenide in aqueous solution, ascorbic acid reduced the diselenide already in the bulk drug. Dithioerythritol and sodium bisulfite also were evaluated as antioxidants. Dithioerythritol had effects similar to ascorbic acid, while sodium bisulfite reacted rapidly with 6-selenoguanosine.

Antineoplastic Agents↗