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Biomedical subjects

M Evans

Publications and source records attributed to M Evans.

At least 289 records · Page 16Linked to original sources

Antiidiotypic antibodies against anti-DNA antibodies in sera of families of lupus patients.

We searched for antiidiotypes directed against anti-DNA in sera of healthy family members of lupus patients. Controls were healthy individuals without a personal or family history of lupus. No significant differences were noted between the family members' and the control group's sera with respect to binding to DNA or to non-anti-DNA F(ab')2 fragments. Family members' sera had higher binding to anti-DNA F(ab')2 and to normal IgG F(ab')2 fragments (P less than 0.01). Sera of the family members had significantly higher binding to anti-DNA F(ab')2 than to normal IgG F(ab')2 fragments (P less than 0.0036). Inhibition experiments have shown that the antiidiotype is directed against the framework determinants and not against the antigen binding sites of the idiotype. The antiidiotypic antibodies were directed against cross-reactive anti-DNA idiotypes and were not restricted to the idiotypes of the lupus proband. Age, sex, and blood relationship to the lupus patient did not influence the presence of antiidiotypes in the family members. The possible role of environmental factors in the induction of antiidiotypes and the role of the latter in regulating anti-DNA antibodies are discussed.

Adult↗

Early infective complications and late recurrent cancer in stapled colonic anastomoses.

Between 1978 and 1981, 73 patients with colonic or rectal cancer were randomized to have their anastomoses made by either a single interrupted layer of braided polyester sutures, or by a circular stapling instrument. Of these operations, 20 were considered to have been palliative, the remaining 53 being potentially curative. The incidence of local recurrence in the latter group was analyzed in relation to initial septic and anastomotic complications. The 53 patients were followed for a median of 36 months (range, 1 to 87); 24 were alive and well and 22 had died of disseminated cancer or unrelated causes. Seven patients died with local recurrent disease proved at laparotomy or autopsy after a median of 33 months (range, 3 to 72). Thirty anastomoses were stapled and 23 sutured; of the seven patients who died with local recurrent disease, six had stapled anastomoses (Fisher's exact probability F2 = 0.12; log rank chi-square = 3.53, 0.05 less than P less than 0.10). Two patients who died with locally recurrent disease had had clinically apparent anastomotic leaks and one other patient had had a radiologically demonstrated leak. This compares with a total of seven leaks (clinical or radiologic) in the remaining group of 46 patients with no recurrence (Fisher's exact probability F2 = 0.11). These results tend to support the hypothesis that anastomotic leaks may lead to locally recurrent disease, particularly after stapled anastomoses.

Colorectal Neoplasms↗

Cordocentesis in the diagnosis of intrauterine starvation.

Glycine and valine were measured in umbilical venous blood obtained by cordocentesis from 28 small-for-gestational-age fetuses. The values were compared with those from 62 appropriate-for-gestational-age fetuses. The ratio of glycine to valine was higher in the small-for-gestational-age fetuses and correlated significantly with the degree of fetal hypoxemia. These findings indicate that placental insufficiency is associated with a biochemical disturbance in the fetus that is similar to that observed in children with protein deprivation and kwashiorkor syndrome.

Blood Specimen Collection↗

Suppression of B cell responses by natural killer cells is mediated through direct effects on T cells.

We examined the ability of human natural killer (NK) cells to modulate T cell-dependent mitogen-induced B cell responses. Highly purified NK cells inhibited the polyclonal antibody responses of autologous pokeweed mitogen (PWM)-stimulated unfractionated mononuclear cells in a reverse hemolytic plaque-forming cell (PFC) assay. Investigation of the possible mechanism(s) of the suppressor activity of NK cells revealed that lysis of mitogen-stimulated cells was unlikely. Chromium-51 release cytotoxicity assays of PWM-stimulated mononuclear cells did not demonstrate lysis by NK cells. Additionally, the monoclonal antibody 13.3, which abrogates NK cell cytolysis, did not reverse NK cell-dependent suppression of PFC formation. The putative lytic molecule elaborated by NK cells, NK cytotoxic factor, did not suppress B cell responses, further supporting a nonlytic inhibitory mechanism. That NK cell-derived lymphokines such as IFN-alpha, IFN-gamma, or IL-2 were uninvolved in the down-regulation of B cells was corroborated by the failure of antibodies to these mediators to reverse the suppression. NK cells did not suppress PFC formation when T cells were replaced by supernatants from PWM-stimulated T cells; additionally, NK cells had no effect on the generation of these necessary T cell factors. However, the coculture of T cells with NK cells resulted in the induction of suppressor activity within the T cell population suggesting that this was the mechanism of NK cell-mediated suppression of B cell responses.

Antibody Formation↗

Measurement of fracture movement in patients treated with unilateral external skeletal fixation.

Axial movement occurring at the fracture site has been determined in a group of healing tibial fractures treated by external skeletal fixation. Fracture movement was determined via a strain gauge transducer which was attached to the column of the external fixator and measured the deflection of the bone screw adjacent to the fracture site and the active loading or weight bearing given by the patient to the fractured limb was monitored using a force platform. The results for 27 subjects show that, with a rigid unilateral fixator, the axial movement occurring at the fracture site was initially small (mean = 0.28 mm at 5 weeks post fracture). This movement increases to reach a mean maximum value of 0.43 mm at 11 weeks post-fracture and then decreases, despite increased weight bearing, as fracture healing progresses. In the early stages of healing, the movement can be increased slightly if the fixator is fitted with a module which permits additional fracture site movement, although the resultant increase in movement is only a small proportion of the potential available with this module.

Bone Screws↗

Evaluation of lung dose correction methods for photon irradiations of thorax phantoms.

Radiation absorbed dose in lung is measured and calculated using several algorithms available on commercial treatment planning systems. Phantoms resembling the human thorax are used and irradiated with small and large photon beams of 60Co, 4, 6, and 10 MV X ray energies. The applicability and usefulness of the different calculation methods in clinical situations is discussed.

Lung↗

Identification of the origin of cells in human basal cell carcinoma xenografts in mice using in situ hybridization.

In an attempt to identify more clearly the origin of cells in human basal cell carcinoma xenografts in mice, paraffin and frozen sections were subjected to in situ DNA hybridization with biotin labelled human and murine DNA probes. Human skin and mouse skin sections were used as controls. As expected, the implanted epithelium reacted with the human DNA probe and the surface epithelium and most of the stromal cells reacted with the murine probe. However, the stroma immediately surrounding the implanted epithelium contained cells of human origin mixed with murine cells. Occasional murine cells (presumed inflammatory) were present in the human implanted epithelium. Assessment showed no correlation between the degree of differentiation of the implanted epithelium and the ratio of human/murine cells in the contiguous stroma. This technique provides a sensitive test for identifying human cells in xenografts and may be useful in assessing the role of stromal cells in the differentiation of a variety of carcinomas.

Animals↗

Interphase cytogenetics using biotin and digoxigenin labelled probes I: relative sensitivity of both reporter molecules for detection of HPV16 in CaSki cells.

This study was undertaken to develop technology for the detection of nucleic acid using two different DNA probe reporter molecules, the ultimate aim being to differentially label two nucleic acids within the same nucleus. Digoxigenin and biotin were used to label DNA probes. The absolute and relative sensitivity of digoxigenin and biotin labelled DNA probes for detecting integrated human papilloma virus 16 (HPV16) was investigated in CaSki cells by non-isotopic in situ hybridisation (NISH). Several methods for the detection of labelled probes were also investigated. The optimal sensitivity of digoxigenin labelled probe was equivalent to that of biotin when alkaline phosphatase was used as the final detector. The median number of discrete viral signals discernible in each cell with the most sensitive detection system was seven to eight with both labelled probes. The average number of HPV16 genomes in each CaSki cell, derived by dot blot hybridisation, was about 270. The calculated absolute sensitivity of NISH for viral detection in this system is complex because of variation of signal size and number. Nevertheless, one signal per nucleus equates to as little as 30 to 40 viral copies, and probably much less. The ability to distinguish up to 15 discrete signals with both digoxigenin and biotin labelled probes in the nuclei of CaSki cells indicates that these methods will be useful in interphase cytogenetics in material routinely fixed in aldehyde.

Alkaline Phosphatase↗

Organ donations should not be restricted to relatives.

Should we remove whole organs from living donors only in the case where they are genetically related to the intended recipients of such organs? The practice in a majority of European nations is to apply such a restriction. Yet this restriction obviously limits the availability of already scarce donor organs, and curtails the opportunities for altruistic action on the part of those who, in any given case, are not genetically related to the recipient. The author argues that we have a duty to maximise procurement of organs, and that we should respect the 'genetic relative' restriction only in response to compelling moral reasons. The author considers the principal objections to non-related donation and shows them to be misdirected. He concludes that non-related donation should be welcomed where clinically appropriate and truly voluntary.

Directed Tissue Donation↗

In situ hybridization studies of adenoviral infections of the lung and their relationship to follicular bronchiectasis.

We have used a probe against the adenovirus genome to study cultured epithelial cells specifically infected with various types of adenovirus and Graham 293 cells, which contain few copy numbers of a fraction of the adenovirus genome. We have also examined lung tissue obtained from three cases of acute adenovirus pneumonia, two cases of adenovirus pneumonia that had passed through the acute phase, and nine cases of follicular bronchiectasis. Our purpose was to determine whether the probe was effective in detecting a wide variety of adenovirus types, to determine whether it could detect adenovirus in lung tissue that had been fixed and stored in paraffin blocks for several years, and to test the hypothesis that adenovirus was an important cause of follicular bronchiectasis. The results show that the probe was able to detect adenovirus from Genera B1, B2, C, D, and E with a sensitivity of 5 to 10 copies/cell. The probe also detected adenovirus in 14 of 14 slides from three cases of acute disease, but failed to obtain a positive result in the cases examined after an acute infection or in any of the cases of follicular bronchiectasis. We conclude that the in situ hybridization technique is useful in the investigation of active adenovirus infection of the lung. The failure to show that the virus persisted in the chronic respiratory disease that follows adenovirus infection, or that it was present in cases of follicular bronchiectasis could be due to either a true absence, or to its presence in a latent form that is below the level of sensitivity of this technique.

Adenoviridae Infections↗

Preincisional intraparietal Augmentin in abdominal operations.

A total of 624 consecutive eligible patients undergoing abdominal operations received a single preoperative dose of amoxycillin/clavulanic acid (1.2 g Augmentin) for the prophylaxis of surgical wound infection. They were randomised to have the antibiotic injected intravenously at induction of anaesthesia (n = 328) or infiltrated subcutaneously along the line of the proposed incision (n = 296). The incidence of wound infections was considerably lower in the group given the antibiotic into the abdominal wall (8.4% compared with 15.9%--chi 2 = 7.90, P = 0.005). No significant differences were found in the incidence of other major or minor infective or non-infective postoperative complications between the groups. It is concluded that preincisional intraparietal injection is more effective than intravenous injection of Augmentin for the prophylaxis of surgical wound infection.

Abdomen↗

Bone mass is low in relatives of osteoporotic patients.

STUDY OBJECTIVE: To determine whether the failure to attain normal bone mass in young adulthood contributes to the later development of osteoporotic fractures. DESIGN: Case-control study. SETTING: Referral-based bone clinic at a large teaching hospital. PATIENTS: Sequential sample of 35 asymptomatic relatives, aged 19 to 59 years, of patients with osteoporotic fractures, and 24 patients with osteoporotic fractures. MEASUREMENTS AND MAIN RESULTS: Bone mineral density in the spine was measured by quantitative computed tomographic scanning. Bone mineral content in the os calcis was measured in 19 of the relatives of osteoporotic patients by single-photon absorptiometry. The values for bone mineral density in the spine were corrected to age 50 years with the regression equation derived from the normal values in the controls. The values were lower in relatives of osteoporotic patients than in controls. In men, the mean values (+/- standard deviation [SD]) for relatives were 91 +/- 16 mg/cm3, and for controls, 129 +/- 21 mg/cm3 (P less than 0.001). In women, the mean values for relatives were 96 +/- 17 mg/cm3 and for controls, 126 +/- 19 mg/cm3 (P less than 0.001). In the osteoporotic patients, the corrected mean value for men was 53 +/- 12 mg/cm3, and for women, 77 +/- 20 mg/cm3. The os calcis values did not correlate with the spine values and were mostly well within the normal range. CONCLUSIONS: Mean bone mass is lower in apparently healthy young and middle-aged adult relatives of osteoporotic patients than in normal persons with no family history of osteoporosis. Our findings suggest that the failure to attain an adequate peak bone mass may play an important role in the later development of osteoporotic fractures. Relatives of osteoporotic patients should be advised to have measurements of bone mass taken. This measurement should be taken at the spine, because peripheral sites do not appear to provide adequate information about early osteoporosis.

Adolescent↗

Antimicrobial bowel preparation. Oral, parenteral, or both?

It has been suggested that wound infection rates after colorectal operations are influenced more by the presence of adequate tissue levels of antimicrobials at the time of contamination than by the extent of bacterial colonization of the intestinal lumen. There are, however, theoretical grounds for the belief that both levels are important. The authors therefore conducted a random control trial in 119 consecutive patients undergoing elective colorectal operations, comparing the results in a group receiving purely parenteral antimicrobial prophylaxis with those in one having a combined oral and parenteral regimen. The results in 83 contemporary nonrandomized patients, all of whom had the combined prophylactic regimen, are also reported. Oral bowel preparation resulted in a significantly smaller number of operation cultures showing growth of fecal gram-negative aerobes and anaerobes than did the purely parenteral regimen. There were more isolations of enterococci in the combined group but the excess did not achieve statistical significance. The rates of infective complications were higher in the parenteral than in the combined group, the difference in wound infection rates being statistically significant; the figures were 27.6 percent and 13.9 percent, respectively (P = .04). It is concluded that, in colorectal operations, it is advisable not only to ensure adequate tissue levels of antimicrobials but also to reduce the risk of endogenous bacterial infection by partially decontaminating the bowel.

Administration, Oral↗

The effectiveness of a soluble calcium preparation as a gut phosphate binder.

We determined the phosphate binding capacity of a soluble commercial calcium preparation by carrying out metabolic balances on four normal subjects and by administering it for 4 weeks to six patients treated by maintenance hemodialysis. Each tablet of Sandocal 1000 (Sandoz, Australia) contained 1 g of elemental calcium as calcium lactate-gluconate 5.23 g and calcium carbonate 0.8 g. The metabolic balance study was performed over two consecutive nine-day periods. A constant, normal diet was consumed throughout, but in the second period one Sandocal 1000 tablet was added to each of the three major daily meals. Each period consisted of four days of equilibrium, then five days of collection of urine and feces. Polyethylene glycol 4,000 was used as a continuous fecal marker and carmine red was used to indicate gut transit time. Calcium supplementation increased fecal phosphate excretion by 11.2 +/- 2.3 mmol/d (SD), and decreased urinary phosphate by 8.4 +/- 2.6 mmol/d. Plasma calcium levels were unchanged, while plasma phosphate levels rose slightly. The increase in fecal phosphate was similar to that previously reported when calcium carbonate 8 g/d or aluminum hydroxide 6.4 g/d were administered. In the patients treated by maintenance hemodialysis, the reduction in plasma phosphate induced by Sandocal 1000, three tablets daily, was similar to that obtained with aluminum hydroxide 1.8 +/- 1.2 g/d. Hence, this calcium preparation appears to have a phosphate binding capacity similar to that of standard doses of aluminum hydroxide.

Adult↗

Design and performance of a fracture monitoring transducer.

The answer to the question, 'when is a fracture healed?' is not simple, since the healing process is progressive and it is not possible to specify a time when the fracture can be said to have healed. In the past the assessment of fracture healing has, in the main, been subjective, relying upon the skill of the interpreter. A more objective method would be an advantage for many reasons, and since the bone is intended to be load bearing it is reasonable to assess healing by measuring the mechanical integrity of the bone. To do this a 'clamp on' transducer has been developed which, when fitted to the support column of an external fixator, enables the stiffness of a fracture to be determined during the healing process. Over the past 6 years this system has been used for both clinical and research work. It has enabled various forms of treatment to be evaluated in terms of 'rate of healing' and it also indicates the safe point at which the fixator can be removed.

Biomechanical Phenomena↗