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Biomedical subjects

J Lamb

Publications and source records attributed to J Lamb.

At least 109 records · Page 6Linked to original sources

Immunological activity of a 38-kilodalton protein purified from Mycobacterium tuberculosis.

A 38-kilodalton (kDa) protein antigen from Mycobacterium tuberculosis was purified by monoclonal antibody TB71-based affinity chromatography. This molecule carries two nonoverlapping epitopes recognized by monoclonal antibodies TB71 and TB72, which are expressed substantially more strongly by M. tuberculosis than by Mycobacterium bovis. However, cross-reactive determinants between these two species were revealed on the 38-kDa protein by a rabbit anti-BCG serum. An immunoradiometric assay based on the TB71 and TB72 antibody pair specifically determined 38-kDa-antigen concentrations in mycobacterial extracts. Antibodies in sera from tuberculosis patients estimated by binding to 38-kDa-antigen-coated microtiter plates were positively correlated with TB72 competing titers. Unlike antibodies, T-cell proliferative responses to the 38-kDa protein were expressed equally by 60% of tuberculosis patients and healthy BCG-vaccinated subjects. Similarly, delayed-type hypersensitivity skin reactions were elicited in both M. tuberculosis- and M. bovis-sensitized guinea pigs. The results suggest the immunodominance of the species-specific B-cell and cross-reactive T-cell stimulatory epitopes.

Animals↗

A prospective comparison of iotrolan, iohexol and iopamidol for lumbar myelography.

The provisional results are presented of a comparative blind trial of iotrolan, iohexol and iopamidol for lumbar myelography. The aim of the trial was to assess the relative safety, tolerance and radiologic efficacy of the media. From the data available to date the incidence of side effects is similar for all three substances. Iotrolan does not provide specific imaging advantages.

Contrast Media↗

Reversal of cardiac transplant rejection without massive immunosuppression.

Although cyclosporine has decreased the severity of acute cardiac transplant rejection, most centers have continued to use high-dose intravenous steroids to treat acute rejection. To minimize the morbidity of antirejection therapy, acute rejection episodes in 37 cardiac transplant recipients were treated prospectively with only a boost of oral prednisone. Cyclosporine was continued at the same maintenance dose while oral prednisone was increased to 100 mg/day for 3 days, then rapidly tapered over 1 week to the maintenance dose. Seventy-six of 85 acute rejection episodes (90%) showed histologic resolution of mycocyte necrosis on repeat biopsy. Three acute rejection episodes (3.5%) resolved only after "rescue therapy" with intravenous steroid, and an additional three episodes (3.5%) required the combination of intravenous steroid and rabbit antithymocyte globulin to effect resolution. In addition, three acute rejection episodes (3.5%) resulted in graft loss. This was fatal in two patients and one patient underwent successful retransplantation. Oral steroid therapy alone is adequate therapy for most acute rejection episodes in cyclosporine-treated heart transplant recipients, and low infectious morbidity and mortality has been associated with this antirejection protocol.

Adolescent↗

Portasystemic shunt fraction quantification with colonic iodine-123 iodoamphetamine.

Portasystemic shunting was quantified in dogs with [123I]iodoamphetamine (IMP) administered transrectally into the colon and monitored externally with a gamma camera. IMP was absorbed rapidly and unchanged from the colon. After direct injection into the portal vein, IMP was almost completely extracted by the liver on the first pass, and the washout half-life was approximately 60 min. Based on these kinetic data, computer simulation of this biologic system was carried out. Errors associated with simplified models are calculated. The simplest model with insignificant error, which assumed that the tracer behaved like microspheres, was used to quantitate portasystemic shunt fraction in animals with surgically created shunts. Results were compared with the standard of 99mTc-labeled macroaggregated albumin infused into a branch of inferior mesenteric vein. For shunt fractions ranging from 0 to 100%, an excellent correlation was seen, indicating that this approach is potentially a simple, noninvasive method of portasystemic shunt fraction quantification.

Amphetamines↗

Right ventricular ejection fraction measured by first-pass intravenous krypton-81m: reproducibility and comparison with technetium-99m.

Study of the effects of various diseases and therapeutic manipulation of pulmonary vascular resistance on the right ventricle has been restricted by methodologic limitations. The radioactive gas in solution, krypton-81m was used to study the right ventricle and the technique was compared with a technetium-99m method. In 22 subjects, first-pass krypton-81m right ventricular ejection fraction, acquired both in list mode and electrocardiogram-gated frame mode, correlated well (r = 0.81 and 0.86, respectively, p less than 0.01) with that determined by technetium-99m first-pass studies over a broad range of ventricular function. The reproducibility of the technique was excellent (r = 0.84 and 0.95 for each acquisition mode, respectively). Krypton-81m first-pass studies provide accurate and reproducible estimates of right ventricular function. Use of krypton allows multiple measurements, with or without perturbations, over a short period of time.

Heart Ventricles↗

Reduced infection in cardiac transplant recipients.

Despite the introduction of cyclosporine immunosuppression, infectious morbidity and mortality in cardiac transplant recipients has remained high. To decrease infectious complications, lower doses of cyclosporine and oral prednisone than previously reported were used for maintenance immunosuppression in 22 operative survivors of orthotopic cardiac transplantation. Twelve infections occurred in 10 patients followed 8 +/- 5 months. Fifty-five percent of patients had no infectious complications. There were no deaths. Seven infections required hospitalization for a mean of 12 days. Infection rate per patient for the first 3 months after transplantation was 0.23 compared with a range of 0.82 to 1.06 in series previously reported in which higher doses of steroids were used. Lowered doses of steroid can be used for maintenance immunosuppression and treatment of rejection with acceptable short-term results. With such a protocol, a low incidence of controllable infectious complications with no deaths has been observed.

Adolescent↗

Fine needle aspiration cytology, in relationships to clinical examination and mammography in the diagnosis of a solid breast mass.

The accuracy of clinical examination, mammography and fine needle aspiration cytology in identifying malignancy has been assessed in 1655 breast masses from two time periods. Clinical examination and mammography remained consistent at identifying malignancy but 9 per cent of all breast carcinomas were considered benign by both techniques (sensitivity 91 per cent). Fine needle aspiration cytology, when performed by multiple aspirators in the first study period, had a sensitivity of only 66 per cent for malignancy. During the second period of study, when all aspirates were performed by a single aspirator, sensitivity rose to 99 per cent. The two patients with false negative cytology in this latter period had both clinical and mammographic evidence of malignancy. No patient with malignant cytology was subsequently shown to have benign disease. It is concluded that a combination of clinical examination and mammography, with fine needle aspiration cytology performed by committed individuals with aptitude for the technique and interpreted by experienced pathologists, can identify all patients with breast cancer before surgery.

Adult↗

Determination of N-7-[2H3]methyl guanine in rat urine by gas chromatography-mass spectrometry following administration of trideuteromethylating agents or precursors.

A gas chromatographic-mass spectrometric method has been developed for the determination of N-7-[2H3]methyl guanine in urine in the presence of large natural levels of N-7-methyl guanine. Urine is fractionated on heptanesulfonic acid-treated C-18 Sep-pak cartridges, followed by derivatization to give a volatile N-heptafluorobutyryl-O6-2,3,4,5, 6-pentafluorobenzyl derivative which is separated on an SE52 fused silica capillary column. Using N-7-ethyl guanine as an internal standard, the total amount of N-7-methyl guanine is determined by gas chromatography-flame ionization detection. The percentage of N-7-[2H3]methyl guanine is then measured by gas chromatography-mass spectrometry, enabling the amount of deuterated base to be determined. Preliminary experiments with [2H3]methyl methanesulfonate in rats showed measurable excretion of N-7-[2H3]methyl guanine. 4-(Di[2H3]methylamino)antipyrine alone gave no detectable amount of alkylated base, but coadministration of nitrite resulted in excretion of deuterated N-7-methyl guanine.

Alkylating Agents↗

The Edinburgh randomised trial of screening for breast cancer: description of method.

Edinburgh was selected as one of the centres in the UK Seven-year Trial of Breast Screening of women aged 45-65 which began in 1979. Subsequently, our study was extended to a randomised trial with its own control population within the city. Half the practices were randomly allocated for screening, giving a cluster sampling of women. The total number in the trial is 65,000. Women with previously diagnosed breast cancer are excluded. Women allocated for screening are invited to the clinic and screened according to the procedures specified in the U.K. protocol, having clinical examination every year and mammography on alternate years. The two modalities of screening are assessed independently and the role of nurses is being evaluated. Breast cancer incidence is monitored by pathology register and the local cancer registry office and deaths from the General Register office. Long-term follow-up will be obtained through flagging at NHS Central Register. To determine the value of screening, standard statistical methods will be used to compare breast cancer mortality rates in the whole of the screening population with that of the controls. This trial has a power of 83% of detecting a reduction in mortality of 35% after 7 years of follow-up and a power of 95% of detecting a similar reduction at 10 years (alpha = 0.05, one-sided test).

Breast Neoplasms↗

Haemoglobin GPhiladelphia and its interaction with haemoglobin S and alpha-thalassaemia in Nigerians.

The diagnosis of Hb SS/GPhiladelphia disease was made in four young Nigerians from separate families. Their Hb electrophoretic patterns on cellulose acetate membrane at alkaline pH were similar to those obtained in sickle-cell haemoglobin C (HbSC) disease, but their clinical features and haematological data were consistent with the diagnosis of homozygous sickle-cell disease. Family studies also revealed that they had inherited an additional alpha-chain mutant haemoglobin. In one of the families, fingerprints of the globin peptides and amino acid analysis confirmed that the mutant haemoglobin was Hb GPhiladelphia (alpha 2 68 Asn----Lys beta 2 A). The results of the whole blood solubility test for sickle-haemoglobin provided firm support for the diagnosis of homozygous sickle-cell disease and distinguished clearly Hb SS/GPhiladelphia disease from Hb SC disease and Hb AS from Hb AGPhiladelphia heterozygotes. Restriction endonuclease mapping of the globin genes of the propositus and some relatives of one of the families revealed also that they were carriers of the alpha-thalassaemia-2 gene (deletion-type). The globin gene-analysis data indicate also that the alpha GPhiladelphia and alpha-thalassaemia genes are linked closely in Nigerians.

Adolescent↗

Specific craniofacial defects induced by jervine in the cultured rat embryo.

The Veratrum-derived steroidal alkaloid, jervine, induces cyclopia and limb malformations in sheep, and various other craniofacial malformations in several other mammalian and avian species. In the present study, the question whether jervine acts directly or indirectly on mammalian embryos to produce malformations and the nature of the target tissue or cells were examined using whole-embryo cultures of the CD rat. Embryos were explanted into culture at the presomite, early neurula stage and cultured in the presence or absence of jervine for 48 hours. Jervine (at 1-5 micrograms/ml) induced an oblong-head appearance and ventrally displaced optic vesicles, with little or no other effects observed on overall growth and development. The specific target tissue in the embryo was found to be the cranial neuroepithelium. This specificity of action is quite unusual since most teratogens examined in whole-embryo culture to date have various nonspecific effects on embryonic growth and differentiation.

Animals↗

Localization and excision of occult breast lesions.

Between 1976 and 1982, 190 non-palpable mammographic abnormalities considered to be suspicious of malignancy were excised using a needle localization technique. The indications for biopsy, technique for localization, method for confirmation of excision and histopathological preparation are presented. The histopathological diagnosis of these lesions were 150 benign and 40 malignant. There was no clear correlation between the mammographic appearances and the occurrence of cancer. Compared with 100 consecutive women with palpable breast cancer the impalpable and mammographically detected tumours were smaller, more often non-invasive and associated with negative axillary nodes.

Adult↗

Microcalcification and its relationship to cancer of the breast: experience in a screening clinic.

The mammograms and specimen radiographs of 45 women in whom the presence of microcalcification played a major part in the decision to biopsy, were studied to determine possible distinguishing features. A mammographic lesion of 150 mm2 or less with an irregular density and five or more calcific particles, especially if palpable, was very likely to be an invasive carcinoma. With improved resolution, it should become possible to distinguish those calcifications covering 150 mm2 or less in the mammograms which are associated with parenchymal structures and those that are associated with stromal elements. Features that may potentially distinguish some benign parenchymal calcifications and those parenchymal calcifications associated with non-invasive malignancy are described. There will probably remain a few benign parenchymal associated calcifications which are identical to the calcifications associated with non-invasive cancer. Implications for improvement in technique are considered.

Aged↗

Feature-positive effect in adults and attention to portion of stimulus array.

In three experiments, adult humans were tested in a feature-positive or feature-negative simultaneous symbol task. In Experiment 1, some persons focused on the correct side of the stimulus cards, whereas other persons focused on the not-correct side of the stimulus cards. The feature-positive group learned faster than the feature-negative group did in the correct side condition; the feature-negative group learned faster than the feature-positive group did in the not-correct side condition. In Experiments 2 and 3, all persons focused on both the correct and not-correct sides of the stimulus cards. Under these circumstances, feature-positive and feature-negative performances were comparable. These results indicated that the usual superiority of feature-positive over feature-negative learning results from a tendency to attend to only a portion of the stimulus array.

Attention↗

Multiple arrangements of the human embryonic zeta globin genes.

Rearrangements which are most readily explained by homologous crossover between misaligned segments of DNA in the region of the human embryonic zeta (zeta) globin genes have been identified in individuals of three different racial origins. These recombination events have resulted in a surprisingly high prevalence of chromosomes with single (0.4%) and triplicated (1.3%) zeta genes with apparently no significant effect on the phenotype.

Chromosomes, Human, 16-18↗