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Biomedical subjects

L Gordon

Publications and source records attributed to L Gordon.

At least 19 recordsLinked to original sources

Endocardial localization and characterization of natriuretic peptide binding sites in human fetal and adult heart.

Specific, high affinity binding sites for 125I-human-alpha-atrial natriuretic peptide-(1-28)) (125I-hANP-(1-28)) were identified in human fetal and adult heart and the binding characterized using quantitative in vitro autoradiography. Binding sites were localized to atrial and ventricular endocardium, aorta, pulmonary arteries and epicardial mesothelium. Kinetic studies indicated a Kd value of 32 pM for ventricular endocardial 125I-hANP-(1-28) binding. The binding was completely inhibited by an excess (1 microM) of unlabelled hANP-(1-28), human brain natriuretic peptide-(1-32) (hBNP-(1-32)) and by the 'clearance receptor' specific ring-deleted analogue, C-ANP-(4-23). Competitive inhibition studies indicated a relative inhibitory potency for hBNP-(1-32) and C-ANP-(4-23) of 6% and 3% respectively. The data suggest that a distinct natriuretic peptide receptor subtype is expressed in the endocardium and in addition to a possible clearance function, may represent a site for feedback regulation and peptide interaction.

Analysis of Variance

Biomechanical analysis of a step-cut technique for flexor tendon repair.

We compared the strength of a new step-cut technique for flexor tendon repair with that of the widely used Kessler-Tajima technique, giving special attention to the relative contributions of the core and epitendinous sutures. 36 flexor digitorum profundus tendons from human cadavers were used. Corresponding digits from the same donor were paired, and the two tendons of each pair were placed in the Kessler-Tajima and step-cut groups, respectively. Each group had three subcategories of repair: (1) core repair alone; (2) epitendinous repair alone; and (3) full repair. In the Kessler-Tajima repair, the core stitch contributed more to ultimate tensile strength, while the epitendinous stitch contributed more to gap formation resistance. In the step-cut repair, however, the epitendinous stitch contributed more to both measures of strength. The full step-cut repair was 65% stronger in resisting gap formation and had 84% more ultimate tensile strength than the full Kessler-Tajima repair. We attribute the greater strength of the step-cut repair to the additional number of epitendinous loops, which lie perpendicular to the long axis of the tendon.

Cadaver

Induction of c-fos but not c-myc in S-91 cells by melanization signals.

Synthesis of the pigment melanin is a complex differentiated function performed by pigment cells in response to a variety of stimuli. The possible roles of the proto-oncogenes c-fos and c-myc in the control of pigmentation were studied using subconfluent, actively proliferating Cloudman S-91 murine melanoma cells stimulated to synthesize melanin by melanocyte stimulating hormone (MSH) or forskolin. Stimulation caused a significant increase in melanin synthesis when compared to control cells, but had no effect on cell growth. Northern analysis of total cellular RNA demonstrated rapid, transient induction of c-fos mRNA as early as 30 min after stimulation with MSH or forskolin. In contrast, there was no effect on the high constitutive expression of c-myc in these actively proliferating cells. These data strongly suggest that the induction of c-fos mRNA is an early genetic event in stimulation of melanin synthesis and thus this proto-oncogene may play a major role in the regulation of this differentiated function, as reported for other forms of cellular differentiation. In contrast, c-myc expression is unaffected and instead correlated with cellular proliferative capacity. These results are consistent with the hypothesis that the down-regulation of c-myc frequently observed during cell differentiation is not a necessary event, but rather reflects an associated decrease in cell growth rate. The S-91 melanoma system appears to provide a convenient model for study of the regulation for a single, well defined differentiated function that is independent of growth rate.

Animals

Cardiac denervation in the calf using cryoablation: functional evidence and regional tissue catecholamine content.

Twenty-six calves were subjected to a technique of cryoablation in order to establish an animal model of complete cardiac denervation. All 26 survived the procedure, and 20 were alive to be re-evaluated 2-4 weeks later. Mean heart rate in the denervated animals rose from 77 +/- 7.8 beats/min to 102 +/- 16.4 (P less than 0.01). Cryoablation abolished the heart rate responses to electrical stimulation of the vagus nerve and thoracic sympathetic trunk. The reduction in myocardial noradrenaline concentrations averaged 99% in the right atrium, 90% in the left atrium, 85% in the right ventricle and 90% in the left ventricle, when compared with tissue obtained from control animals. Cryoablation is a relatively simple means of accomplishing complete functional cardiac denervation in the calf. On the basis of the observed change in heart rate, the calf model appears to be more comparable with human heart transplant recipients than the dog.

Animals

Improved preservation of skeletal muscle in amputated limbs using pulsatile hypothermic perfusion with University of Wisconsin solution. A preliminary study.

To determine whether pulsatile hypothermic perfusion with University of Wisconsin preservation solution is superior to topical cooling as a method for the preservation of amputated limbs, six pairs of amputated canine limbs were preserved for twelve to fifteen hours. One limb of each pair was subjected to topical cooling and the other, to pulsatile hypothermic perfusion with University of Wisconsin solution. The bioenergetic status of the limbs was monitored by 31phosphorus magnetic-resonance spectroscopy, and histological evaluation was performed to assess ischemic changes in the preserved tissue. The pH and tissue levels of adenosine triphosphate declined three times more slowly in the limbs that were preserved by pulsatile hypothermic perfusion than in the topically cooled limbs. Consistent with these findings, the perfused limbs also had less histological evidence of ischemic injury. The data from this in vitro study show that pulsatile hypothermic perfusion with University of Wisconsin solution, in combination with an optimum degree of topical cooling, is superior to topical cooling alone as a method of preserving the bioenergetic status of amputated limbs.

Adenosine

Endometrial adenocarcinoma without prior hormone replacement in a diabetic patient with gonadal dysgenesis.

Patients with dysgenetic gonads and Turner syndrome are unlikely to develop endometrial carcinoma unless they have received unopposed estrogen replacement therapy. This case describes a 54-year-old woman with Turner syndrome and primary amenorrhea who developed adenocarcinoma of the endometrium without having received hormone replacement. Vaginal bleeding, a pelvic mass, and sepsis were the presenting symptoms. The patient also had diabetes mellitus and hypothyroidism. Polyglandular endocrine patterns are known to occur with a high frequency in these patients. The woman's chromosome studies revealed a modified 46,X,i(Xq) (isochromosome X). This is the first report of an isochromosome X patient to develop endometrial cancer without receiving estrogen replacement. The etiology of this rare case may be an increased propensity for patients with X-chromosome deletions to develop neoplasms in general, or extragonadal estrogen production.

Adenocarcinoma

Fetal fracture healing in a lamb model.

A large animal model to assess fetal fracture repair and the ability to close excisional bony defects is presented. Incisional and excisional ulnar fractures were made in 14 midgestation fetal lambs, harvested at serial time points, and subjected to high-resolution low-kilovolt magnification radiographs, magnetic resonance imaging scans, and histologic analysis. Fetal fracture healing was characterized by early closure of excisional defects and rapid fracture healing with minimal or no soft-tissue inflammation or callus formation. Magnetic resonance imaging scans of the fractures revealed a characteristic pattern compatible with the histologic findings, namely, minimal inflammation in soft tissue adjacent to the fracture site. Histologic and magnification radiographic findings indicated that complete bony repair occurred within 21 days in incisional defects and within 40 days in excisional defects. In both cases, healed fetal bone resembled normal bone matrix. Excisional defects, including periosteum, of greater than three times the width of the bony cortex closed rapidly with virtually normal-appearing bony matrix and with minimal or no callus formation.

Animals

Demonstration that bone mass is greater in black than in white children.

Osteoporosis and hip fractures are less common and bone mass is greater in black than in white women. To determine if bone mass is greater in black than in white children, bone mineral density (BMD) of the midradius by single-photon absorptiometry and BMD of the lumbar spine (L1-L4), trochanter, and femoral neck by dual-photon absorptiometry were measured in 20 black boys, 18 black girls, 33 white boys, and 35 white girls between the ages of 7 and 12 years. Mean age (10.4 +/- 0.3 versus 10.2 +/- 0.2 years) and body weight (39 +/- 2 versus 38 +/- 2 kg) in the blacks and whites, respectively, were not different in the two groups, and the ages and weights of the boys and girls were not different from each other. BMD were significantly greater in black than in white children at each site, in the black than in white boys at the trochanter and femoral neck, and in the black than in white girls at each site. In both races, BMD varied directly with age and body weight. Multivariate analysis showed that BMD were greater at the midradius, lumbar spine, trochanter, and femoral neck in the black than in the white children, that BMD of the lumbar spine was greater in the girls than in the boys, and that BMD of the trochanter and femoral neck were greater in the boys than in the girls. There were significant partial correlations between race and BMD and between BMD and body weight at each site, between sex and BMD at the lumbar spine, trochanter, and femoral neck, and between age and BMD at the midradius, trochanter, and femoral neck. Race, sex, age, and body weight together accounted for 49-66% of the variation in bone mass. Thus, BMD of the midradius, spine, and hip are greater in black than in white children, body weight and age are important determinants of bone mass, and some sex differences in bone mass are present at this age.

Absorptiometry, Photon

Re-use of the recipient vessels of a microvascular transplant.

Three cases are described in which a second microvascular free flap, transplanted after a delay of several months, was provided perfusion by re-using the recipient vessels of the first flap in end-to-end fashion. In each patient healing of the second flap was uneventful, and both transplants continue to survive. Prior to harvesting the second transplant, a careful intraoperative examination was performed in which the vascularity of the original transplant was assessed. In each case, recipient vessel re-use represented the least risky of several options. The results of the present series suggest that vascularization from the transplant bed or surrounding tissues proceeds despite the fact that, initially, the only source of blood for the free flap flows through a single axial vessel. This single vessel can therefore be divided without loss of the transplant as long as the transplant bed has already provided vascularization to the flap. In our opinion, the timing of the second procedure and the quality of the transplant bed are the key factors in the survival of the transplants.

Adolescent

Acute plastic deformation of the ulna in a skeletally mature individual.

Acute plastic deformation of a bone refers to traumatic bending or bowing without a detectable cortical defect. We present a case that is unusual in that bowing of the ulna occurred in a skeletally mature individual and was associated with injury to the distal radioulnar joint. In this patient, the symptoms were severe enough to warrant an ulnar osteotomy. The patient regained satisfactory function. Acute plastic deformity should be suspected whenever abnormal curvature of a long bone is noted, even in adults. If the distal radioulnar joint is dislocated, the deformation should be corrected as soon as possible to avoid permanent loss of forearm rotation.

Adolescent

A new system for high-resolution DNA sequence mapping interphase pronuclei.

Cosmid clones containing human or hamster inserts have been hybridized in situ and localized with fluorescent reporter molecules in interphase nuclei (pronuclei) obtained after fusion of hamster eggs with either human or hamster sperm. Hamster egg cytoplasm processes the tightly packaged sperm DNA into large diffuse networks of chromatin fiber bundles, providing hybridization targets more extended than those available in somatic interphase cell nuclei. Pronuclear physical distances between hybridization signals were measured in micrometers and correlated to genomic distances determined by restriction fragment analyses, using cosmids from the Chinese hamster DHFR region and from the human Factor VIII/color vision pigment gene region (Xq28). The mean pronuclear distances between hybridization sites were about three times as large as those measured in somatic interphase cells for equivalent genomic distances. The relationship between physical and genomic distances was linear from less than 50 kb to at least 800 kb. The results show that physical distance in the sperm-egg system promises to extend the mapping range obtainable in somatic interphase nuclei below 50 kb and up to at least 800 kb.

Animals

Comparison of four objective methods of monitoring digital venous congestion.

This study sought to determine which of the four most commonly used objective monitoring modalities--pulse oximetry, laser Doppler flowmetry, skin surface temperature measurement, and skin surface fluorescence--is best able to detect early digital venous congestion. Digital venous congestion was induced in 12 hands by inflating a digital cuff to 5 mm Hg above the resting diastolic pressure. The cuff remained inflated for 1 hour while monitoring was done at 10-minute intervals. The baseline and experimental laser Doppler indices differed by at least 30% in each subject, and the laser Doppler index was always less than 40% during venous congestion. Skin surface fluorescence gave falsely normal results in three of eight hands, while pulse oximetry failed to detect venous congestion in any hand. The difference in temperature between the control and experimental fingers almost always exceeded the threshold of 2.5 degrees C. The results indicate that both laser Doppler flowmetry and skin surface temperature measurement are highly accurate methods of monitoring early digital venous congestion that are noninvasive and easy to use. Skin surface temperature measurement has further advantages in that thermometers are less expensive and easier to transport than laser Doppler devices. In contrast, skin surface fluorescence is invasive and cumbersome in addition to being less sensitive to experimentally induced early digital venous congestion than either laser Doppler flowmetry or skin surface temperature measurement. Pulse oximetry is unreliable in detecting early digital venous congestion.

Adult

The Allen's test: analysis of four methods.

Forty nonrandomly selected hands were studied with use of four types of Allen's test: (1) the digital systolic blood pressure method, (2) the subjective method, (3) the pulse oximeter method, and (4) the laser Doppler flowmetry method. The digital systolic blood pressure method, regarded as the standard, indicated abnormal pressure in three hands. Laser Doppler flowmetry gave the same results as those obtained by the digital systolic pressure method and, in addition, was easier to perform. Pulse oximetry falsely indicated adequacy of the collateral circulation in two of the three hands with abnormal digital systolic pressure. Eleven hands, including the three with abnormal digital systolic pressure, were abnormal according to the subjective method. The results of the present study indicate the following: (1) the laser Doppler Allen's test is accurate, quick, and easy to perform; (2) the pulse oximeter Allen's test should not be used because of potentially dangerous consequences to the patient in the event of a falsely normal result; and (3) the subjective Allen's test can be used as a quick screening test.

Adult

Occurrence of schizotypal and borderline symptoms in parasuicide patients: comparison between subjective and objective indices.

Seventy-six patients were interviewed within a week of admission following a parasuicide episode. Axis II diagnosis on DSM-III was made for schizotypal, borderline, histrionic, and antisocial personality disorder. In addition patients completed a self-rating questionnaire, the Schizotypy Questionnaire of Claridge & Broks (1984), which assesses schizotypal and borderline personality traits. The objective and subjective indices of schizotypal and borderline symptoms correlated significantly but allocation of patients to a diagnosis missed several patients who nevertheless rated themselves as having a high frequency of these symptoms. There was an asymmetry of symptom pattern reminiscent of Foulds & Bedford's (1975) hierarchy model. The presence of schizotypal symptoms appeared to be higher in the hierarchy: they predicted borderline symptoms, but a high frequency of borderline symptoms did not necessarily predict schizotypy. We suggest that the occurrence of schizotypal symptoms should become a more explicit focus of clinical assessment and treatment of these patients, especially those who repeatedly harm themselves and we suggest ways in which cognitive therapies may be adapted to do this.

Adolescent

Male-sex-ratio trait in Drosophila pseudoobscura: frequency of autosomal aneuploid sperm.

Males with the SR X chromosome show the "sex-ratio" (sr) phenotype in which they produce almost entirely daughters. The few sons (about 1%) are invariably sterile X/O males and result entirely from nullo-XY sperm. The "male-sex-ratio" (msr) phenotype is a modified form of sr in which SR/Y males produce a higher frequency of sterile X/O sons. The msr trait is due to the presence of the SR X-chromosome in males which are also homozygous for one or more autosomes from the L116 strain. Here the frequency of nullo-3 and diplo-3 sperm from msr males was measured by crossing to a compound-3 strain and found to be 13.8% and 3.2%, respectively, of the total viable sperm. The sr males produced very low levels of nullo-3 sperm at a frequency not different from control X/Y males and a slightly elevated frequency of diplo-3 sperm over X/Y males. The msr males were found to have only 12% the fecundity of sr males and in matings to cause a high frequency of brown inviable eggs. These results indicate that high rates of autosomal aneuploidy are not restricted to chromosome 3 but also occur for chromosomes 2, 4 and 5. The overall frequency of autosomal aneuploid sperm is estimated to be approximately 50%. Microscopic studies of meiosis in testes from msr males indicates meiotic nondisjunction and meiotic chromosome loss are responsible for the msr phenotype. Last, microscopic studies of sperm cysts from msr males reveal high levels of spermiogenic failure.

Anaphase