Biomedical subjects
D Newman
Publications and source records attributed to D Newman.
Scintigraphic assessment of sympathetic innervation after transmural versus nontransmural myocardial infarction.
To evaluate the feasibility of detecting denervated myocardium in the infarcted canine heart, the distribution of sympathetic nerve endings using I-123 metaiodobenzylguanidine (MIBG) was compared with the distribution of perfusion using thallium-201, with the aid of color-coded computer functional map in 16 dogs. Twelve dogs underwent myocardial infarction by injection of vinyl latex into the left anterior descending coronary artery (transmural myocardial infarction, n = 6), or ligation of the left anterior descending coronary artery (nontransmural myocardial infarction, n = 6). Four dogs served as sham-operated controls. Image patterns were compared with tissue norepinephrine content and with histofluorescence microscopic findings in biopsy specimens. Hearts with transmural infarction showed zones of absent MIBG and thallium, indicating scar. Adjacent and distal regions showed reduced MIBG but normal thallium uptake, indicating viable but denervated myocardium. Denervation distal to infarction was confirmed by reduced norepinephrine content and absence of nerve fluorescence. Nontransmural myocardial infarction showed zones of wall thinning with decreased thallium uptake and a greater reduction or absence of MIBG localized to the region of the infarct, with minimal extension of denervation beyond the infarct. Norepinephrine content was significantly reduced in the infarct zone, and nerve fluorescence was absent. These findings suggest that 1) MIBG imaging can detect viable and perfused but denervated myocardium after infarction; and 2) as opposed to the distal denervation produced by transmural infarction, nontransmural infarction may lead to regional ischemic damage of sympathetic nerves, but may spare subepicardial nerve trunks that course through the region of infarction to provide a source of innervation to distal areas of myocardium.
Lack of bone accretion and amenorrhea: evidence for a relative osteopenia in weight-bearing bones.
Bone mineral density (BMD) was studied in young exercising amenorrheic girls to determine if density was compromised and the change related to injury. Ninety-eight volunteers (professional ballet dancers and controls) were studied in a cross-sectional study. Dancers and controls were further subdivided into normally cycling and amenorrheic subjects. Amenorrhea significantly lowered bone density of the spine (P less than 0.0001), wrist (P less than 0.03), and metatarsal (P less than 0.01); effects on the wrist were eliminated by controlling for age while controlling for weight eliminated all effects of amenorrhea at three sites. BMD of the metatarsal, a weight-bearing bone, showed an interaction between amenorrhea and dancing (exercising) P less than 0.035); surprisingly, dancing was associated with a further lowering of bone density. This interaction was eliminated when controlling for age, but not when controlling for weight. With multiple comparisons of the groups, spine, wrist, and metatarsal bone density was significantly lower in amenorrheic dancers when compared to normal dancers (P less than 0.05), even when controlling for age and weight in the metatarsal (P less than 0.05), and age in the spine (P less than 0.05). Estradiol levels correlated with bone density of both the wrist and the spine (r = 0.25, r = 0.23, P less than 0.02). Metatarsal density correlated with estradiol levels only in the dancers (r = 0.34, P less than 0.02). The only variable found to correlate with the occurrence of stress fractures was age of menarche. This was also the only variable of 9 (BMD of the wrist, spine or foot, calories ingested and expended, amount of calcium ingested, involvement in high energy activity, age of menarche or presence of amenorrhea) to predict stress fractures. Thus, BMD is significantly affected by the presence of amenorrhea but the effects are generally weight dependent. The compensatory increase in bone density generally seen in stressed bones, such as the metatarsal in ballet dancers, is deficient in amenorrheic premenopausal women even when controlling for weight but this effect may be age and estrogen dependent. Bone mass may not accumulate in the same manner in adolescents as in the mature women, thus putting them at risk for injury.
The painful shoulder: Part I. Extrinsic disorders.
Shoulder disorders are most commonly manifested by pain and limited function. Careful history and examination help the physician localize the problem to the shoulder joint, the surrounding tissues or adjacent sites that can cause referred pain to the shoulder. Common extrinsic causes of shoulder pain include postural problems and cervical spine disorders.
The painful shoulder: Part II. Intrinsic disorders and impingement syndrome.
Intrinsic disorders that can cause shoulder pain include arthritis, gout, pseudogout and osteonecrosis. In its mildest form, impingement syndrome may cause only minimal discomfort. At its worst, impingement syndrome may lead to rotator cuff tear. Bicipital tendinitis and rupture of the biceps tendon may also be associated with impingement. Early rehabilitative intervention is important. Physical therapy is directed toward restoring range of motion and muscle strength.
Effect of platelet release products on cytosolic calcium in cardiac myocytes.
The effect of platelet release products on cytosolic calcium [( Ca++]i) was examined by monitoring the fluorescence of chick embryonic heart cells loaded with the fluorescent calcium indicator indo-1 AM. Cell free filtrate of platelet release products was obtained from rabbit platelets activated with thrombin or collagen. This filtrate caused a rapid increase in both systolic and diastolic [Ca++]i in a dose-dependent manner. The effect was not blocked by pretreating the platelets with aspirin or a thromboxane synthetase inhibitor. It was not mimicked by a thromboxane analog, or by several substances known to be released from platelets including ADP, serotonin, or platelet activating factor. Apyrase or ATP-gamma S had no effect on the activity. The responsible product was heat-sensitive, trypsin-sensitive, and partitioned into the aqueous phase of a chloroform suspension. It has a low molecular weight (less than 3kD) and is sensitive to 2-mercaptoethanol. Protease inhibitor appears to prolong the activity. These results suggest that trypsin-sensitive peptide(s) released from activated platelets can increase [Ca++]i in cardiac cells.
Assessment of hearing loss in elderly people: the feasibility of a nurse administered screening test.
This paper examines the findings and implications of an exploratory study which was designed to determine the feasibility of a nurse administered hearing screen test for elderly patients. Theoretical and practical considerations which influenced the design of the hearing assessment test (HAT) and the method of the study are discussed. A sample of 27 elderly hospital inpatients, with a mean age of 81 years, participated in the study. The results of the new HAT were validated by comparison with audiometric assessment results. Analysis using the Generalized Linear Model showed a significant (P less than or equal to 0.01) relationship between the total HAT score and the audiometric measures, with the exception of the audiometric classification of hearing loss which was significant at P less than or equal to 0.05. The results demonstrate that the HAT is a potentially useful tool for nurses to use, but that refinement of the scale and further validity and reliability testing is required before it can be adopted as part of the nursing assessment of elderly people.
Tympanometry screening.
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Catheter ablation of cardiac arrhythmias.
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Genetic toxicity evaluation of McN-5195: a novel analgesic.
McN-5195, (+/-)-trans-3-(2-bromophenyl)octahydroindolizine, a novel analgesic, was tested for genotoxic potential in a battery of tests with endpoints of mutagenicity, chromosomal alterations and DNA damage/repair. McN-5195 was not mutagenic when tested in the Ames test using strains TA98, TA100, TA1535, TA1537 and TA1538, in the absence of metabolic activation and in the presence of Aroclor 1254-induced rat or hamster S-9. Negative results were also obtained in the mouse lymphoma assay in the absence of activation, but reproducible mutagenic responses were seen in this mammalian cell assay in the presence of rat S-9 at high levels of induced toxicity (reduced cell growth). Testing of the enantiomers of McN-5195 in this assay supported these findings. A predominance of small mutant colonies in the mouse lymphoma assay suggested a potential chromosomal effect of McN-5195. This was confirmed with positive findings in an in vitro cytogenetics assay using CHO cells, again at toxic exposure levels and only in the presence of S-9. McN-5195 did not induce DNA repair in the primary rat hepatocyte/DNA repair assay, nor did it induce alterations in vivo of chromosome structure or number when tested in a rat bone marrow cytogenetics assay. The findings from this battery of tests indicate that McN-5195 has modest genotoxic activity when tested in the presence of rat liver S-9 in in vitro systems sensitive to cytogenetic change. The absence of genotoxicity in vitro in Salmonella and intact liver cells and in vivo in rat bone marrow suggests that McN-5195 is unlikely to present a genotoxic risk to whole animals.
Esophageal atresia--a rabbit model to study anastomotic healing and the use of tissue adhesive fibrin sealant.
The problem of bringing together two relatively widely separated, small, and fragile ends of a sick newborn baby's atretic esophagus remains a formidable surgical task, wherein the incidence of anastomotic leakage ranges from 10% to 27%. Recently, a multicomponent tissue adhesive fibrin sealant (Tisseel) has been licensed in Canada and declared useful for sealing gastrointestinal (GI) tract anastomoses. To study whether Tisseel might decrease the leakage rate of esophageal anastomoses in neonatal esophageal atresia and perhaps limit stricture formation, a rabbit model of esophageal atresia was developed. Twenty New Zealand white rabbits weighing 2.8 to 3.7 kg underwent thoracotomy and resection of a segment of esophagus with end-to-end, interrupted silk-sutured anastomosis under tension, to mimic the conditions found in newborn esophageal atresia. Four died immediately following operation. Ten rabbits had their anastomosis sealed with Tisseel, six control animals did not. All animals consumed variable amounts of water and food, starting 24 hours after surgery. Survival averaged 10.5 days (range, 5 to 20 days). Eight animals (five experimental, three control) were evaluated by means of barium esophagograms 1 week postoperatively, and all except one control animal demonstrated radiologic evidence of anastomotic leakage. Autopsy specimens revealed gross leakage in nine animals (seven experimental, two control). However, histology revealed leakage and periesophageal abscess formation in all experimental animals and in four control animals. The remaining two controls revealed only some degree of esophageal stenosis. This experiment showed no demonstrable benefit from the use of a fibrin sealant in preventing esophageal anastomotic leakage, such as that which occurs in repaired esophageal atresia.
Electromagnetic beam modes driven by anisotropic electron streams.
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Report of the United States cooperative study of extracorporeal shock wave lithotripsy.
Extracorporeal shock wave lithotripsy effectively fragments urinary calculi in the upper urinary tract and upper ureter. These fragments pass completely by 3 months in 77.4 per cent of the patients with single stones. Risk of obstruction, increased postoperative pain, need for additional urological operations and retained fragments are low for stones less than 1 cm. in size. As the number of stones treated or single stone size increases above 1 cm. the risk for these factors increases. Adjunctive urological surgical management is required in 9 per cent of the patients preoperatively and 8 per cent postoperatively. Only 0.6 per cent of the patients require some type of open operation to resolve the stone problems after extracorporeal shock wave lithotripsy. Hemorrhage, obstruction by fragments, severe pain and urinary infection all constitute known complications and require careful urological management of all patients. Hospitalization averages 2 days after treatment and patients usually return to work within a few days after they are discharged from the hospital.
Extracorporeal shock wave lithotripsy: the Methodist Hospital of Indiana experience.
A total of 982 patients underwent 1,416 treatments with extracorporeal shock wave lithotripsy for upper urinary tract calculi between February 23 and December 17, 1984. A single treatment was performed in 90 per cent of the patients. Morbidity was extremely low and hospital stay was short (3.0 days). Adjunctive procedures were required in 13 per cent of the patients. Of the kidneys 72 per cent were free of stones at the 3-month followup, while 23 per cent contained small (less than 5 mm.), asymptomatic fragments believed to be passable spontaneously. Only 1 per cent of the patients required surgical removal of the calculi. Morbidity was related directly to stone burden, while results were inversely related to stone burden. Extracorporeal shock wave lithotripsy is the preferred form of management for symptomatic upper ureteral and renal calculi less than 2 cm. in diameter.
The relation between myocardial ischemia and the ejection fraction response to exercise in patients with normal or abnormal resting left ventricular function.
This study examines the relation between myocardial ischemia and the left ventricular (LV) ejection fraction (EF) response to exercise in patients with normal or abnormal resting EF. We studied 69 patients aged 25 to 78 years (mean 52 years) by radionuclide ventriculography (at rest and during peak upright exercise) and by exercise thallium-201 imaging. In 27 patients with resting EF less than 50%, the EF response to exercise was normal (greater than or equal to 5% increase) in 13 patients and abnormal in 14. The thallium scans showed reversible defects in 11 of the 14 patients (79%) with abnormal response but none in any of the patients with normal responses (p = 0.0001). In the 42 patients with resting EF greater than or equal to 50%, the EF response to exercise was normal in 23 and abnormal in 19. Reversible defects were present in 13 of the 19 patients (68%) with abnormal response and in only 3 of 23 patients (13%) with normal response (p = 0.0001). Therefore, an abnormal EF response to exercise was seen in 11 of 11 patients with resting EF less than 50% and in 13 of 16 patients (81%) with resting EF greater than or equal to 50% who had reversible thallium defects; normal EF responses were seen in 13 of the 16 patients (81%) with resting EF less than 50% and in 20 of 26 patients (77%) with resting EF greater than or equal to 50% who had no reversible thallium defects. Thus, in patients with abnormal resting LV function an abnormal EF response to exercise suggests the presence of myocardial ischemia rather than a nonspecific response to stress.
Lack of genotoxicity of the cancer chemopreventive agent N-(4-hydroxyphenyl)retinamide.
As part of the preclinical drug safety evaluation of the cancer chemopreventive agent N-(4-hydroxyphenyl)retinamide (HPR) in vitro and in vivo tests were conducted to assess its genotoxic activity. Negative findings from HPR testing were demonstrated in the Ames Salmonella/microsomal activation test, the L5178Y mouse lymphoma assay, and a rat bone marrow cytogenetics study. These data imply that HPR lacks the ability to induce point mutations or chromosomal aberrations, and is therefore not genotoxic. Limited testing of retinyl acetate in the Ames test, the L5178Y mouse lymphoma assay, and the primary rat hepatocyte/DNA repair assay yielded consistently negative results. These findings and previously published results concerning retinoid genotoxicity are discussed.
Integration and ethnic spatial concentration: the changing distribution of the Anglo-Jewish community.
"This paper identifies the changing locational patterns of the Jewish community in Britain during the past century. Two major trends are identified. At the national level there has been movement out of many small provincial communities to the large urban centres, particularly Greater London and Manchester. Within the city, there has been movement out of the traditional inner city ghettos to the suburbs, thus reflecting the upward socio-economic mobility and integration of what was an immigrant group. Both these trends closely mirror the general patterns of population movement in Britain during the twentieth century." The lack of reliable data for the Jewish population is noted, and a methodology is suggested for identifying the changing locational patterns and intensity of Jewish community life. The method is applied to the case of Greater London.
Use of protein-based standards in automated colorimetric determinations of fructosamine in serum.
We have developed an automated colorimetric assay for glycated serum proteins (or fructosamines), measuring the reducing activity of serum in alkaline solution (pH 10.35) at 37 degrees C. The calibrants were prepared from a synthetic fructosamine (1-deoxy-1-morpholinofructose), although secondary standards of glycated bovine albumin were more robust in routine application. Interference was appreciable only with icteric specimens (bilirubin greater than 60 mumol/L), and between-batch imprecision (CV) was less than 2%. The range of fructosamine concentrations measured in 502 healthy (nondiabetic) blood donors was 1.87-2.87 mmol/L. There were no significant (p greater than 0.05) age- or sex-related differences in this population sample. Fructosamine accurately reflected blood glucose control as evidenced by the significant correlation with glucose concentrations in fasting plasma (r = 0.82, p less than 0.001) and with glycated hemoglobin (HbA1c) (r = 0.87, p less than 0.01) in 115 patients with type 2 (non-insulin-dependent) diabetes mellitus. The test is simple and rapid to perform (75 samples per hour) and provides an alternative to HbA1c determinations for monitoring blood glucose control and assessing the effects of changes in diabetes management.