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Biomedical subjects

M Palmer

Publications and source records attributed to M Palmer.

At least 163 records · Page 9Linked to original sources

Does gallium uptake in the pulmonary hila predict involvement by non-Hodgkin's lymphoma?

67Ga imaging of non-Hodgkin's lymphoma is useful for evaluating the presence of viable tumour in a residual mass after treatment. However, we have frequently seen gallium uptake in the pulmonary hila without other evidence of lymphoma. To study the significance of this finding, 79 patients with intermediate grade non-Hodgkin's lymphoma were reviewed. Thirty-seven (47%) had abnormal hilar gallium uptake. Twenty-three of these could be fully evaluated, and only five (22%) had hilar lymphoma. A pattern of bilateral, symmetric hilar uptake was seen in 19 patients, but only one had evidence of lymphoma. In 15 cases, this pattern was seen only on single photon emission computed tomography (SPECT). The aetiology of this uptake remains unknown. It is not treatment related, as 12 patients had hilar gallium uptake prior to chemotherapy. Unless confirmed by other methods, hilar gallium uptake should not be attributed to lymphoma, and should not influence patient management.

Alberta↗

T cell determinant structure: cores and determinant envelopes in three mouse major histocompatibility complex haplotypes.

T lymphocytes recognize discrete regions on an antigen. The specificity of the T cell responses in three mouse strains of differing major histocompatibility complex (MHC) haplotype to a protein antigen, lysozyme, was analyzed using a series of peptides that walk the antigen in single amino acid steps. These peptide series were synthesized using the pin synthesis system, which was modified to allow the peptides to be cleaved from the pins into a physiological buffer free of toxic compounds. This methodology overcomes many of the problems associated with the production of peptides for screening proteins for antigenic determinants. The T cell determinants for the three strains were markedly different. This result points out the limitations of algorithms predicting determinants without reference to the MHC, and the importance of the empirical methodology. This analysis of the T cell response to lysozyme constitutes the most complete study of reactivity to a foreign protein to date and illustrates many important features of antigen recognition by T cells, e.g., presence of major and minor determinant regions. The outer boundaries of each immunogenic region, the determinant envelope, are difficult to define from recently immunized lymph nodes because of the heterogeneity in T cell recognition. However, core sequences common to all the immunogenic peptides in a continuous sequence can be easily defined.

Amino Acid Sequence↗

Characterisation of virulent and benign strains of Bacteroides nodosus.

The extracellular proteases of 395 isolates of B. nodosus from ovine, bovine and caprine foot lesions were classified as either thermostable or thermolabile. Stable protease was associated with one and unstable protease with four distinctive isoenzyme patterns, each pattern differentiated by the relative mobility of paired isoenzymes. Pathogenicity tests on 64 isolates showed a correlation between the production of stable protease and the production of virulent ovine footrot lesions. The mean values for total protease activity, twitching motility and colony diameter were significantly higher for virulent compared to benign isolates, but the range of values overlapped. SDS-PAGE whole-cell electrophoretic profiles of virulent isolates were similar to the profiles of some benign isolates.

Analysis of Variance↗

Excessive weight gain after liver transplantation.

Twenty-eight patients (19 females, 9 males) were evaluated pre- and posttransplant to determine the frequency and find predictors of excessive weight gain after orthotopic liver transplant. Posttransplant, 21 patients gained and 7 patients lost weight as compared with their pretransplant dry weight. The majority of weight gain occurred between 2 and 16 months; 64.3% of patients (18/28 pts.) became overweight. All patients overweight prior to transplant (11 pts.) were more overweight posttransplant (P less than 0.005). Overweight and nonoverweight patients were similar in age, female predominance, etiology of liver disease, hypercholesterolemia, and hypertriglyceridemia pretransplant, as well as diabetes mellitus and medications including prednisone posttransplant. Overweight patients more commonly had a family history of diabetes mellitus, arteriosclerotic heart disease, and hypertension. They also had more hypertension, hypercholesterolemia, hypertriglyceridemia, abnormal physical findings related to the liver, and abnormal results of hepatic tests posttransplant. Mean rate of weight gain for overweight patients compared with nonoverweight ones during the first 16 months after transplant was 1.5 kg/month +/- 0.9 vs 0.4 kg/month +/- 0.4 for those not overweight. After 16 months mean rate of increase was slower for overweight patients (0.3 kg/month +/- 0.3), whereas weight appeared to stabilize in the nonoverweight ones. We conclude that excessive weight gain after liver transplant is common and occurs early. Since obesity may contribute to, as well as be a separate cause, of hepatic abnormalities, confusion may result when interpreting abnormal results of hepatic tests. Obesity prior to transplant predicts excessive weight gain posttransplant, although all patients may be at risk.

Adult↗

Massive screening for colorectal cancer. A single institution's public commitment.

Data from three massive screening programs for the detection of colorectal cancer and adenomatous polyps were reproducible through the collaboration of several departments at Roswell Park Memorial Institute, Buffalo, NY. The majority of carcinomas detected had demonstrated no lymph node metastases. The percentage of screenees with positive stool occult blood tests discovered to have colorectal cancer and adenomatous polyps was 19%, 24%, and 21% in 1982, 1984, and 1987, respectively. The cost-effectiveness of this large-scale screening effort by centers such as Roswell Park Memorial Institute has been demonstrated in accordance with high public acceptance and the high incidence of colorectal cancer.

Colitis, Ulcerative↗

Effect of weight reduction on hepatic abnormalities in overweight patients.

The effects of weight reduction on hepatic test results and physical findings related to the liver were retrospectively evaluated in 39 overweight patients screened to exclude other factors affecting the liver. An additional 11 overweight patients with primary liver disease were retrospectively evaluated to compare the effect of weight reduction in patients with liver disease with its effect in those without primary liver disease. This study showed that in overweight adults without primary liver disease, a weight reduction of greater than or equal to 10% corrected abnormal hepatic test results, decreased hepatosplenomegaly, and resolved some stigmata of liver disease. In similarly studied overweight patients with primary liver disease, some findings improved, but the changes did not correlate with a greater than or equal to 10% weight loss. Increased alanine aminotransferase activity was the most frequent hepatic enzyme abnormality in this population. For every 1% reduction in body weight, alanine aminotransferase activity improved by 8.1%. After other causes of liver disease are eliminated by clinical and biochemical parameters, weight reduction should be tried for overweight patients with abnormal hepatic test results in the absence of obvious primary liver disease as judged by clinical and biochemical parameters before extensive and expensive studies are undertaken.

Alanine Transaminase↗

99Tcm-nanocolloid imaging in inflammatory bowel disease.

We have used 99Tcm-labelled nanocolloid in an attempt to locate areas of inflamed bowel wall or abscesses in five patients with ulcerative colitis and nine with Crohn's disease. The scintigraphic findings were evaluated by comparison with those of recent barium studies and, in three patients, with surgical findings at laparotomy. It proved difficult to localize segments of inflamed bowel accurately with 99Tcm-nanocolloid because of the accumulation of radioactivity in the gut lumen, especially 2 or more hours after injection. However, there was little uptake of the labelled nanocolloid by areas of inflamed gut wall in the period before 2 h. When 99Tcm-nanocolloid scans were compared with 111In-WBC scans in eight patients who had both investigations, 99Tcm-nanocolloid scintigraphy was considerably less sensitive than 111In-WBC scintigraphy. One abscess was located correctly; the other was obscured by nearby bladder and bone marrow radioactivity. We conclude that 99Tcm-nanocolloid scanning is neither sensitive nor reliable enough for assessing the location of inflamed bowel wall or the presence of abscess in patients with inflammatory bowel disease.

Adult↗

Flexible pay arrangements. The need for a systematic approach.

Regrading large numbers of staff is a difficult and sometimes painful exercise. Mike Palmer and Graham Martin describe how job evaluation was used in a restructuring of pathology staff and argue that the technique will be increasingly valuable when pay is settled at the local level.

England↗

T cell dominance and the vaccine problem: modifying effects on immunogenicity by residues at a distance from the site of T cell recognition.

The design of the optimal T cell-inducing component of a vaccine requires consideration of events both at, and distant from, the T cell recognition site. This area is approached here by analysis of T cell immunodominance. After describing the unpredictability of defining dominant T cell-inducing determinants and the preference of empirical methods, the question of designing a solely T determinant vaccine is explored. In this regard, evidence is presented that T helper cell-inducing and T proliferation-inducing determinants are not necessarily identical. With regard to the influence of other determinants on the molecule, three issues are discussed with relevance to vaccine design: (1) 'preferential partnerships' between T and B cells of certain specificities (2) the existence of suppressor T cells, reactive against non-overlapping determinants (3) competitive antigenic determinants, restricted to the same or to a different MHC molecule.

Animals↗

The pseudoautosomal boundary in man is defined by an Alu repeat sequence inserted on the Y chromosome.

The Y chromosome, which in man determines the male sex, is composed of two functionally distinct regions. The pseudoautosomal region is shared between the X and Y chromosome and is probably required for the correct segregation of the sex chromosomes during male meiosis. The second region includes the sex-determining gene(s), the presence of which is necessary for the development of testes. The two regions have contrasting genetic properties: the pseudoautosomal region recombines between the X and Y chromosome; the Y-specific region must avoid recombination otherwise the chromosomal basis of sex-determination breaks down. The pseudoautosomal region is bounded at the distal end by the telomere and at the proximal end by X- and Y-specific DNA. We have found that the proximal boundary was formed by the insertion of an Alu sequence on the Y chromosome early in the primate lineage. Proximal to the Alu insertion there is a small region where similarity between the X and Y chromosomes is reduced and which is no longer subject to recombination.

Base Sequence↗

No treatment option for liver metastases from colorectal adenocarcinoma.

After an explanation of alternative treatment modalities, 30 patients with unresectable liver metastases from colorectal adenocarcinoma chose to have no treatment. Fourteen patients (47 percent) had synchronous liver metastases and 16 (53 percent) had metachronous lesions. Thirteen of the 30 patients (43 percent) had histologic documentation of liver metastases, with the remaining 17 patients diagnosed by liver scan, ultrasonography, or computerized axial tomography. Twenty-four of 30 patients (80%) had less than 25 percent liver involvement (Stage I), 23 of 24 patients had alkaline phosphatase levels less than twice normal, and 20 of 24 patients were asymptomatic from their liver metastases. The remaining six patients had liver stages II or III at the time of diagnosis. Overall mean survival of the 30 reported patients with untreated metastatic colorectal cancer to liver is 16 months (range, 2 to 58 months; median survival, 12 months).

Adenocarcinoma↗

Reassessment of the relationship between M-protein decrement and survival in multiple myeloma.

The relationship between percentage M-protein decrement and survival is assessed in 134 multiple myeloma patients. The correlation did not achieve statistical significance (P = 0.069). Multivariate analysis using the Cox proportional hazards model, including a number of previously recognised prognostic factors, showed only percentage M-protein decrement, creatinine and haemoglobin to be significantly correlated with survival. However, the R'-statistic for each of these variables was low, indicating that their prognostic power is weak. We conclude that neither the percentage M-protein decrement nor the response derived from it can be used as an accurate means of assessing the efficacy of treatment in myeloma. Mature survival data alone should be used for this purpose.

Actuarial Analysis↗

Evaluation of the therapeutic use of radioactive monoclonal antibodies C242 and C215 in transplanted murine tumours.

The therapeutic roles of monoclonal antibodies C242 and C215 labelled with 131I were investigated in transplanted mammary carcinomas. Fragments (10 mg) of mammary tumour from (A x Pc) F1 hybrid mice were implanted subcutaneously in 72 mice of the same strain. Twelve mice were injected with 131I-C242 starting from day 12 following tumour implantation, and eight out of 12 survived for 60 days. By contrast all but one of 36 control mice died within the same time period (P less than 0.0001). Twelve mice were injected with 131I-C215. Seven out of the 12 were alive at 60 days whilst all but 1 of 36 control animals had died (P less than 0.0001). In this study targeted immunotherapy using 131I-labelled antibodies C242 and C215 inhibited tumour growth and prolonged survival. Measurements of tumour area showed a 27-39 percent reduction in the mice receiving the radiolabelled conjugates C242 and C215 (P less than 0.004 and P = 0.028 respectively).

Animals↗

MIC2: a human pseudoautosomal gene.

MIC2 and XGR are the only known pseudoautosomal genes in man. MIC2 encodes the 12E7 antigen, a human cell-surface molecule of unknown function. XGR regulates, in cis, the expression of the XG and MIC2 genes. DNA probes derived from the MIC2 locus have been used in the construction of a meiotic map of the pseudoautosomal region and a long range restriction map into the X- and Y-specific chromosome domains. MIC2 is the most proximal marker in the pseudoautosomal region and recombination between the sex chromsomes only rarely includes the MIC2 locus. Our long-range restriction maps and chromosome walking experiments have localized the pseudoautosomal boundary within 40 kilobases adjacent to the 3' end of the MIC2 gene. The same maps have been used to predict the chromosomal location of TDF.

Amino Acid Sequence↗

Dose intensity analysis of melphalan and prednisone in multiple myeloma.

The average relative dose intensity (DI) of conventional oral melphalan and prednisone therapy received by 93 newly diagnosed multiple myeloma patients was correlated with survival and with percent reduction in M-protein. A survival advantage was shown with increasing average relative DI of melphalan and prednisone. Multivariate analysis showed survival to correlate with increasing DI of prednisone (P = .05) but not with the DI of melphalan (P = .93) nor with the percent decrement in M-protein (P = .10). These results suggest that the initial management of myeloma should be reassessed, with particular emphasis on more intensive therapy employing high-dose steroids.

Antineoplastic Combined Chemotherapy Protocols↗