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Biomedical subjects

D Carr

Publications and source records attributed to D Carr.

At least 109 records · Page 6Linked to original sources

Tetracyclines of various hydrophobicities as a probe for permeability of Escherichia coli outer membranes.

The outer membrane of gram-negative cells excludes hydrophobic molecules and is responsible for the resistance of these cells to a number of dyes, detergents, and antibiotics. We describe a test for hydrophobic permeability in which a series of tetracyclines with various hydrophobicities are used. Normal Escherichia coli cells became more resistant as hydrophobicity was increased in this series, but mutants altered in outer membrane permeability remained susceptible. A mutant lacking all polysaccharide except 2-keto-3- deoxyoctonic acid in its lipopolysaccharide is virtually as susceptible to the hydrophobic drug 13- phenylmercapto -alpha-6- deoxytetracycline as to oxytetracycline (MIC 100 times lower than that of the wild type), and a mutant with another, as yet undefined outer membrane defect, acrA , also shows increased, although somewhat lesser, susceptibility (MIC 20 times lower than that of the wild type). Increased susceptibility to this tetracycline derivative is associated with greater fluorescence of the derivative when added to the cells, which we interpret as increased interaction of the derivative with hydrophobic domains, such as membranes, in the mutants. This series of tetracyclines may provide an assay for measuring the permeability of gram-negative organisms and their mutants to hydrophobic molecules.

Cell Membrane Permeability↗

Spontaneous and induced metastasis of naturally occurring tumors in mice: analysis of cell shedding into the blood.

The lung colonization capability (after iv inoculation) of each of 77 autochthonous virus-induced mammary tumors in C3H/Avy female mice was compared with its own spontaneous metastatic behavior. Twenty-four of these neoplasms had spontaneously metastasized to the lungs of the tumor bearer. The results were interpreted in the framework of dose-response studies on experimentally induced metastasis. These results indicate that tumors of high lung colonization potential (HCP) overgrow the lungs with iv doses as low as 10(4) cells, whereas tumors of low lung colonization potential (LCP) require at least 250 times this dose to achieve the same result. No general similarity was found between spontaneous and induced metastatic capability. Although some tumors showed good correspondence, others showed discrepancies and provided new information on mechanisms of cell shedding from primary tumors and on rate-limiting steps in metastasis. For example, from the dose-response studies, nonmetastatic tumors of HCP (iv) are deduced to be shedding very few cells. These findings suggest that escape from the primary tumor is an active process or else passive leakage of cells into vessels by hemorrhage, necrosis, or palpation should have resulted in spontaneous metastasis. Spontaneously metastatic tumors of LCP corroborate the view that metastasis is effected by a highly active subpopulation with special properties; otherwise, the required scale of passive cell release into the blood would be unrealistically large. Blood bioassay and time-course studies on pulmonary deposit formation indicate that shedding of metastatic cells occurs early in mammary tumor development.

Animals↗

Preoperative diagnosis and its effect on the treatment of carcinoma of the gallbladder.

In 19 patients with carcinoma of the gallbladder treated over a four year period, several features of percutaneous transhepatic cholangiography have been recognized which have increasingly provided an accurate diagnosis preoperatively. These features are due to intrahepatic invasion of the bile duct and by providing a diagnosis preoperatively can have a large bearing on the choice of therapy for a particular patient. The relative roles of surgical bypass and endoscopically or percutaneously placed prostheses are discussed.

Adult↗

Energy and nutrient intake of children with cancer.

Two hundred seventy-seven pediatric cancer patients received a nutritional assessment. Initial dietary intakes of patients with no prior treatment indicated a diet similar to that of the general population. The caloric intake was 75% of the RDA in a group of patients with non-malignant diseases and 80% of the RDA in the groups of patients with solid tumors and hematopoietic malignancies. Protein intake was greater than 100% of the RDA for all groups. Dietary iron was the nutrient lowest in intake, with a range of 70% to 78% of the RDA. At six-month evaluations, no significant changes occurred except for an increase in iron, niacin, riboflavin, and protein intakes in the group with solid tumors.

Adolescent↗

Nutritional parameters in children with cancer.

An analysis of commonly used nutritional parameters was made for 277 pediatric cancer patients. It is apparent that standard nutritional assessment parameters in the pediatric cancer patient may be difficult to interpret because of the disease state as well as of the treatment. On the basis of the findings of this study, dietary histories to determine caloric and protein adequacy and a measurement of weight/height percent may, in fact, be the most reliable indicators of nutritional status.

Adolescent↗

Experimental analysis of factors affecting metastatic spread using naturally occurring tumours.

This paper describes the applications and latest results of recently developed techniques in metastasis research using naturally occurring animal and human tumours. Intravenous inoculation of cells from murine mammary tumours into syngeneic recipients has shown that some are consistently capable of heavy pulmonary colonisation (HCP) while others have low colonisation potential (LCP). These distinct characteristics are stable over wide cell-dose ranges. Autopsies on a sample of 100 consecutive tumour-bearing C3H/Avy mice revealed that the incidence of spontaneous metastasis is 26%. When inoculated intravenously, cells from some of the spontaneously metastatic primary tumours had HCP and others LCP. We now report that, knowing the degree of pulmonary colonisation of a particular tumour after intravenous inoculation, the degree of its spontaneous metastasis in the original host, and the dose-response relationships mentioned above, it is possible to back-titrate the degree of cell shedding from the tumour into the blood stream. Other experiments reported here demonstrate that separate mammary tumours on the same animal have independent colonisation potentials and growth rates, that tumours appearing later on an animal are not necessarily more capable of metastatic spread than the earlier ones, and that tumour weight and length of presence on the host do not show any strong correlation with spontaneous metastatic spread. A moderately significant association between pulmonary colonisation potential and tumour growth rate is reported and evidence corroborating our earlier observations that ability to colonise the lungs is possessed only by neoplastic mammary cells is also presented. Similar investigation are, of course, much more difficult to organise on tumour spread in man because of ethical and logistic considerations but it is possible to circumvent some of these difficulties and we refer to some of our ongoing studies.

Adipose Tissue↗

The role of bone scanning in Paget's disease.

In Paget's disease, the bone scan allows visualisation of the whole skeleton, permitting accurate assessment of disease extent. The scan appearances are usually characteristic, and as uptake of tracer depends upon skeletal metabolic activity, this study reflects the severity of Paget's disease, in addition to providing early appreciation of alterations in disease activity. While correlation of x-rays and bone scans in Paget's disease have shown that neither method alone detects all lesions, it is clear that the bone scan is the more sensitive technique. In addition, those sites that are occasionally missed by bone scan are metabolically inactive. The bone scan is the investigation of choice in Paget's disease, and radiology should be used to provide supplementary information, as and when required.

Bone and Bones↗

Does inhibition of prostaglandin synthesis increase the diagnostic accuracy of the intravenous urogram in renal artery stenosis?

Intravenous urography is the standard screening test for renovascular hypertension but there is a significant incidence of false negative and false positive results. In an attempt to improve the detection rate, indomethacin was administered orally to nine patients with renal artery stenosis (proven by arteriography and by divided ureteric function studies) before rapid-series intravenous urography. This urogram was compared independently by two observers with prior similar-series urograms. Indomethacin did not alter diagnostic accuracy.

Adolescent↗

A comparison of bone scanning and radiology in the assessment of patients with symptomatic Paget's disease.

Bone scans and X-rays from 23 subjects with symptomatic Paget's disease were evaluated. One-hundred and twenty-seven sites of Pagetoid involvement were found, of which 120 (94.5%) were recognised on the bone scan as compared to 94 (74%) on X-ray. The anatomical distribution and relationship of lesions on scan and X-ray to the patient's symptoms are also discussed. It is concluded that the bone scan is more sensitive than radiology in detecting Paget's disease and only rarely will a lesion that is seen on X-ray not be visualised by scanning.

Adult↗

Magnification lymphography.

Magnification lymphography was performed on 37 patients, 22 of whom were suffering from bladder carcinoma, and compared with non-magnification lymphograms by two observers independently. The magnification lymphograms were performed on a Siemens Microfocus Bi 125/3/50 RG tube with a 0.1 mm focal spot. In six of the 37 patients (16%) significant extra information was found on the magnification lymphograms compared to the non-magnification lymphograms. In 31 out of 37 patients (84%), the intranodal detail shown was better in the magnification radiographs. Against the additional information gained must be weighed the disadvantages of magnification lymphography which include increased radiation dose, lengthening of procedure time, increased cost and the critical nature of exposure factors. In conclusion, magnification lymphography has a place and the disadvantages seem to be outweighed by the advantages.

Adult↗

Renal osteodystrophy: an underdiagnosed condition.

With the availability of 1-alpha-hydroxycholecalciferol it is even more relevant to detect the earliest stages of renal osteodystrophy. Sixty-two patients, either on haemodialysis or recent recipients of a renal transplant and 10 controls underwent hand radiography by a standard technique and by a direct magnification technique employing a 0.1 mm focal spot. A comparison of intracortical striations, subperiosteal resorption and soft tissue calcification was made in the two groups and hand score calculated on the non-magnification radiographs. The results were assessed independently by two radiologists. In subperiosteal resorption, the non-magnification technique gave a 6% positive result compared to 47% with magnification (P less than 0.01). For intracortical striations, the non-magnification technique gave an 11% positive results, whereas magnification resulted in a 45% positive result (P less than 0.01). Soft tissue calcification was found in one patient only, and reduction in hand score was a rare occurrence. The use of a standard technique only, without magnification, for radiographing hands in patients with renal disease, will result in evidence of renal osteodystrophy being missed in a significant proportion of patients.

Adolescent↗

A comparison of bone scanning and radiology in the evaluation of patients with metabolic bone disease.

Bone scans and radiographs were evaluated in 80 patients with metabolic bone disease (27 with osteoporosis, 14 with primary hyperparathyroidism, 24 with renal osteodystrophy and 15 with osteomalacia). The bone scan did not suggest a metabolic bone disorder in any of 27 patients with histologically proven osteoporosis. In 22 (81%) patients radiographs were reported as showing osteoporosis. In 10 (70%) vertebral fractures were seen on X-ray while these were noted in 11 (41%) patients on the bone scan. Vertebral fractures were usually visualised on the bone scan when these had occurred less than one year previously. In primary hyperparathyroidism the bone scan was suggestive of a metabolic bone disorder in 7 of 14 (50%) patients, while radiographs were reported as showing evidence of hyperparathyroidism in three (21%) cases. The bone scan suggested the presence of a metabolic bone disorder in all 24 patients with renal osteodystrophy and 15 patients with osteomalacia while the correct diagnosis was obtained in 14 (58%) and nine (60%) of these patients on X-ray. It is concluded that the bone scan is the more sensitive investigation in patients with osteomalacia, primary hyperparathyroidism and renal osteodystrophy. For osteoporosis radiology is the investigation of choice but the bone scan may be of value in assessing the duration of vertebral collapse.

Animals↗