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Biomedical subjects

P Davis

Publications and source records attributed to P Davis.

At least 289 records · Page 16Linked to original sources

Modern therapeutic approach for high grade astrocytoma: intracranial Ir-192 brachytherapy.

Prognosis of high-grade astrocytoma has been extremely disappointing and the median survival of patients with this tumor is less than 10 months at best. The most common cause of failure is local persistence of the tumor. Many neuro-oncologists have now turned to an alternative therapeutic approach involving brain brachytherapy (interstitial implantation) for the treatment of high-grade astrocytomas because in this manner a higher dose can be delivered to the tumor bed without excessively irradiating the surrounding normal brain tissue. Brachytherapy has shown some evidence of superior results in survival of malignant astrocytomas if properly performed by a qualified brachytherapy team. The objective of this report is to discuss the rationale and technique of brachytherapy in the management of high-grade astrocytoma as well as future prospects concerning this particular treatment modality.

Brachytherapy↗

A prospective analysis of patients with rheumatic diseases attending referral hospitals in Harare, Zimbabwe.

In a 10-month prospective study a research assistant identified 411 patients with rheumatic disease at the 2 referral hospitals in Harare. Rheumatic disease accounted for less than 1% of hospital admissions. Rheumatoid arthritis, the commonest condition, accounted for 18% of patients, many of whom had impaired functional capacity. Septic arthritis (16%) was common in younger patients, often affecting the hip or knee and often associated with other complications of disseminated staphylococcal infection. Osteoarthritis (9%), rheumatic fever (7%), gout (6%), human immunodeficiency virus associated musculoskeletal problems (6%) and systemic lupus erythematosus (5%) were relatively common while the spondyloarthropathies occurred less frequently. The spectrum of rheumatic disease seen in teaching hospitals in Harare, although significantly different from that seen in Europe and North America, approximates the pattern seen in developed countries more closely than previous studies from Africa would suggest.

Acquired Immunodeficiency Syndrome↗

Rheumatoid arthritis antirheumatic drug trials. I. Effects of standardization procedures on observer dependent outcome measures.

A study was designed to assess the effects of standardization procedures on reducing interobserver variability for outcome measures given in the current Food and Drug Administration and European League Against Rheumatism guidelines and others selected from the rheumatology literature. Over 2 days, 6 rheumatologists independently examined 6 patients with rheumatoid arthritis (RA) in predetermined order before and after standardizing their examination techniques. An important and beneficial effect of the standardization procedure was observed on the majority of outcome variables. Such reductions in observer variability have the potential to diminish sample size requirements for antirheumatic drug studies.

Adult↗

Rheumatoid arthritis antirheumatic drug trials. III. Setting the delta for clinical trials of antirheumatic drugs--results of a consensus development (Delphi) exercise.

Defining the minimum clinically important difference or delta to be detected in a clinical trial depends on a number of factors including the research hypothesis, patient characteristics, the nature of the intervention and the trial design. In 2 previous studies, we have developed standardized procedures for conducting outcome measurement based on current Food and Drug Administration and European League Against Rheumatism guidelines for RA clinical trials, and thereafter, determined the standard deviation for these outcome measures. In the final component of this series of studies, we employed a Delphi technique to establish estimates for delta and calculated the sample size requirements under different conditions of Type I and Type II error probabilities.

Arthritis, Rheumatoid↗

SLE in Zimbabwean patients: a review of clinical and serologic features and evaluation of criteria for classification.

The clinical and serologic features have been reviewed in a group of 18 black Zimbabwean patients with SLE, a rare condition in this racial group. The relative merits of the preliminary and revised criteria for the classification of the SLE have been assessed. The prevalence of individual clinical criteria was essentially similar in this group when compared to a larger North American cohort. Minor variations were attributable to racial and environmental differences. Serologic tests were identified. The revised criteria had greater sensitivity for SLE than the preliminary criteria although this was not the case if individual serologic items were omitted. Clinically, SLE is a uniform condition when our cases are compared with those in other areas. In areas where the technology does not exist to perform specific serologic testing, the preliminary criteria with their greater dependence on clinical features still have a useful role when compared to the revised criteria with their greater dependence on serologic testing.

Humans↗

Rheumatoid arthritis antirheumatic drug trials. II. Tables for calculating sample size for clinical trials of antirheumatic drugs.

The calculation of sample size requires knowledge of the standard deviation (SD) of index variables. Unfortunately, there are no published lists of SD and it is exceedingly difficult to locate variance estimates based on relevant populations. We used standardized procedures to determine in 60 patients with rheumatoid arthritis (RA) the SD of key outcome measures recommended in current Food and Drug Administration and European League Against Rheumatism guidelines for RA clinical trials. We anticipate that these tables will be useful to clinical researchers in selecting outcome measures as well as for calculating sample size requirements for future clinical studies in RA.

Anti-Inflammatory Agents↗

Specificity, sensitivity and diagnostic predictive value of selected laboratory generated autoantibody profiles in patients with connective tissue diseases.

We tested the hypothesis that the application of 5 laboratory generated serologic profiles facilitates the interpretation of individual autoantibodies in connective tissue diseases without loss of specificity, sensitivity or diagnostic predictive value. The predetermined laboratory generated autoantibody profiles were analyzed in 423 sera from patients with clinically diagnosed connective tissue diseases. All sera positive for one or more autoantibodies to a selected panel of nuclear antigens could be segregated into one of 5 profiles. The distribution of individual autoantibodies and profiles in the sera of patients with various connective tissue diseases were compared in terms of their respective diagnostic predictive value and sensitivity. The application of these profiles improved the sensitivity and diagnostic predictive value of these tests when compared to individual autoantibodies without loss of specificity, thus aiding clinical interpretation.

Antibody Specificity↗

Are we competent?

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Education, Medical↗

Human immunodeficiency virus-related connective tissue diseases: a Zimbabwean perspective.

Our clinical experience with patients in Zimbabwe suggests that an arthropathy may be a feature of HIV disease. This takes two forms: the first is a reactive arthropathy usually affecting the large, lower limb joints with no other clinical features of a connective tissue disease. The second form is seen in association with features of complete or incomplete Reiter's syndrome with involvement of large and small peripheral joints (having an asymmetric distribution). Although this arthropathy may been seen in association with HIV positive asymptomatic disease and often is the reason for first presentation at hospital, the majority of our patients have clinical features of persistent generalized lymphadenopathy, plus or minus features of constitutional illness (such as fever, weight loss, and diarrhea). A small percentage of our patients have arthropathy in association with secondary systemic infection. Other locomotor conditions have been observed, although their numbers are too small to determine whether or not they truly are related to HIV disease. In Zimbabwe there is no association between the development of HIV-associated arthropathy and the presence of HLA-B27.

Arthritis↗

Proenkephalin A-derived peptide E and its fragments alter opioid contractility in the small intestine.

The human and canine small intestine exhibit increased contractility when exposed to exogenous or endogenous opioid peptides. The response of the canine small intestine to the proenkephalin A-derived peptide, peptide E and related processing fragments [Met5]enkephalin, BAM-12P, BAM-18P and BAM-22P was investigated by administering each peptide to isolated, small intestine segments which causes a significant increase in intraluminal pressure. Concentration-response curves from intraarterial bolus administration of peptide E, [Met5]enkephalin, BAM-12P, BAM-18P and BAM-22P showed decreasing efficacy with decreasing amino acid chain length while naloxone (305 nM) significantly antagonized the response. Results using the classical guinea pig ileum/myenteric plexus longitudinal muscle and mouse vas deferens bioassays with specific opioid receptor antagonists provide evidence that peptide E and BAM-18P are relatively specific to the mu opioid receptor, [Met5]enkephalin is more delta specific, BAM-22P is both mu and kappa specific and BAM-12P is kappa opioid receptor specific. These studies demonstrate that locally released (and possibly circulating) peptide E and related processing fragments increase contractility in the small intestine and may be active through more than a single receptor mechanism, particularly the mu receptor.

Animals↗

Differentiation between rat brain and mouse vas deferens delta opioid receptors.

Certain enkephalin analogues, including those which contain the conformationally restricted amino acid E-(2R,3S)-cyclopropylphenylalanine [2R,3S)-delta E Phe), have been shown to have high affinity for brain delta opioid receptors but are much less active in mouse vas deferens bioassays. To investigate whether there are differences between delta opioid receptors in brain and mouse was deferens, the ability of a selective delta opioid compound, [D-Pen2,pCl-Phe4,D-Pen5]enkephalin (pCl-DPDPE), and [D-Ala2,(2R,3S)-delta E Phe4,Leu5]enkephalin methyl ester (CP-OMe), to inhibit [3H]pCl-DPDPE binding in both rat brain and mouse vas deferens were measured. pCl-DPDPE recognized brain and mouse vas deferens binding sites with equal affinity, however, CP-OMe showed 33 fold lower affinity in mouse vas deferens compared to brain. This suggests that mouse vas deferens delta opioid receptors may be distinct from brain delta opioid receptors.

Animals↗

Molecular basis of the variation exhibited by avian infectious bronchitis coronavirus (IBV).

IBV serotype-specific, virus neutralising (VN) antibody is induced by the S1 subunit of the spike (S) glycoprotein. A Portuguese isolate (Port/322/85) is considered to be an in vivo recombinant. VN tests showed that it belongs to the Massachussetts (Mass) serotype. Correspondingly, the sequence of S1 and S2 was extremely similar to that of older Mass isolates. However, the matrix (M) glycoprotein and upstream gene sequences were atypical of these Mass strains and more closely resembled other serotypes isolated in Europe. The recombination event had occurred within the sequence between the M and S genes (corresponding to mRNA 3) or near the 3' terminus of the S2 gene.

Amino Acid Sequence↗

[D-Pen2,D-Pen5]enkephalin analogues with increased affinity and selectivity for delta opioid receptors.

The conformationally restricted, cyclic disulfide-containing enkephalin analogue [D-Pen2,D-Pen5]enkephalin (DPDPE) was modified by halogenation (F, Cl, Br, I) of the phenylalanine-4 residue in the para position. The potency and selectivity of these analogues for the delta opioid receptor was greater than that of the parent peptide. The analogues possessed greater potency and affinity for the delta receptors than DPDPE in the mouse vas deferens assay and in radioreceptor assays (against [3H]DPDPE), respectively. [p-ClPhe4]DPDPE was the most selective in the radioligand binding assays (IC50(mu)/IC50(delta) = 574), being about 5-fold more delta opioid receptor selective than DPDPE in this assay, whereas [p-IPhe4]DPDPE was the most selective in the classical bioassay systems using the mouse vas deferens and guinea pig ileum assays (IC50(GPI)/IC50(MVD) = 17,374), making it nearly 9-fold more selective than DPDPE in direct comparisons using the same assay conditions.

Amino Acid Sequence↗

The association between HLA and rheumatoid arthritis in Zimbabwean blacks.

HLA-A, B, C, DR and DQ typing was done on 26 black Zimbabweans with rheumatoid arthritis and the respective antigen frequencies were compared with those in a group of 119 normal individuals from the same ethnic background. Only the DR4 antigen was significantly increased in frequency in the patients, confirming the association with this disease seen in other Black African populations.

Arthritis, Rheumatoid↗