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Biomedical subjects

D Larson

Publications and source records attributed to D Larson.

At least 73 records · Page 4Linked to original sources

Auger electron contribution to bromodeoxyuridine cellular radiosensitization.

Halogenated thymidine analogs become incorporated into the DNA of proliferating cells during S-phase and may be used clinically to radiosensitize tumors that are otherwise poorly responsive to radiation. Although radiosensitization has been studied for years, mechanisms of radiosensitization are poorly understood. One possible mechanism involves the release of short range, high-LET, Auger electrons following photoelectric absorption of an X ray by the K-shell of the incorporated halogen. Such absorption occurs only with X ray energies slightly greater than the K-shell binding energy. We report the results of an experiment designed to measure this effect, in which cultured monolayers of Chinese hamster V79 cells, with 32% replacement of thymidine by bromodeoxyuridine (BUdR), were exposed to monoenergetic X rays just below (13.450 KeV) or above (13.490 KeV) the K-edge (13.475 KeV) of bromine. Enhancement ratios calculated in five different ways were slightly increased (3-12%) above the K-edge compared to below. However, only a calculation using a linear-quadratic fit to the data and a surviving fraction of 0.01 demonstrated a statistically significant increased enhancement ratio (12%) above the K-edge. We conclude that Auger electrons produced following photoelectric absorption of X rays by the K-shell of bromine contribute minimally to observed BUdR cellular radiosensitization.

Animals↗

Mental health services among ambulatory patients with human immunodeficiency syndrome infections.

A retrospective study of 463 medical and social service records of patients with AIDS, ARC and minimally symptomatic individuals was conducted to examine mental health services delivered by primary medical care providers. A substantial minority of patients in all three groups had a psychiatric diagnosis and were prescribed psychotropic medications. Recognition of psychiatric complications varied by ethnicity and socioeconomic status.

AIDS-Related Complex↗

Short gracilis myocutaneous flaps for vulvovaginal reconstruction after radical pelvic surgery.

The short gracilis myocutaneous flap derives its blood supply from terminal branches of the obturator artery, and the vascular pedicle derived from the medial femoral circumflex artery is sacrificed. Twenty-one short gracilis myocutaneous flaps were used for vulvovaginal reconstructions in 11 patients undergoing radical pelvic surgery: bilateral flaps in nine patients for neovaginal construction after pelvic exenterations, bilateral flaps in one patient for vulvovaginal reconstruction after radical vulvovaginectomy, and a unilateral flap in one patient for vulvovaginal reconstruction after radical vulvectomy with partial vaginectomy. Major complications consisted of bilateral flap necrosis occurring in one patient who had received preoperative irradiation to the vulva and groin combined with chemotherapy. Minor degrees of necrosis (less than 5%) and/or separation of vaginal suture lines occurred in five patients without marked loss of the flaps. Vaginal caliber and depth are excellent in ten patients (91%) after follow-up of 1-22 months. The short gracilis flap is an excellent alternative to the more bulky gracilis flap, which derives its blood supply from perforating branches of the femoral artery. Based on our experience, the short gracilis flap provides adequately vascularized tissue for vulvovaginal reconstruction in patients after radical pelvic surgery, but should not be used in patients who have received extensive groin irradiation.

Adult↗

Replacement of the macronuclear ribosomal RNA genes of a mutant Tetrahymena using electroporation.

The macronucleus of the ciliate Tetrahymena contains approx. 10(4) ribosomal RNA gene molecules (rDNA) in the form of linear, autonomously replicating palindromes. Previous studies have shown that macronuclear rDNA molecules derived from wild-type (wt) inbred strain C3 out-replicate those derived from wt inbred strain B, in macronuclei initially heterozygous for both, leading to the complete loss of the B rDNA. However, rmm-1, a cis-acting laboratory-induced mutation obtained previously by mutagenesis of inbred strain C3, causes the mutant rmm-1 rDNA to be completely out-replicated by B rDNA. These findings suggest the following hierarchy of replication potential: wt C3 greater than wt B greater than C3-rmm-1. We used electroporation to test whether cells containing only rmm-1 macronuclear rDNA are favorable recipients for transformation with either wt B or C3 donor rDNA molecules. The donor rDNA molecules carried the selectable marker Pmr (paromomycin resistance) located in the coding region of the 17S rRNA. Transformants were obtained, at a frequency greater than 1 in 10(5), by electroporation under a wide range of electrical discharge parameters. The fraction of cells surviving electroporation varied between 2 and greater than 95% in successful experiments. Replacement ('transplacement') of the recipient rDNA was observed, consistent with the prediction that B and C3 rDNA should out-replicate rmm-1 rDNA. These findings are also consistent with the previous conclusion that the differential replication determinants reside in the 5'-nontranscribed spacer of the rDNA.

Animals↗

Current techniques for chest wall reconstruction: expanded possibilities for treatment.

Myocutaneous flaps and prosthetic materials have greatly facilitated reconstruction after massive chest wall resection. This series includes 112 such procedures. Latissimus dorsi, rectus abdominis, omental, pectoralis major, and contralateral breast flaps were used in 80 patients. Early in the series, 3 flaps were lost because of technical problems. Minor areas of incomplete healing that resolved completely with local wound care occurred in 16 of 80 flaps. Skeletal reconstruction was performed in 82 patients without complication. Marlex mesh was used for flat surfaces, and Marlex mesh with methyl methacrylate was used for the sternum and the curved surface of the lateral chest wall. These results have allowed an expansion of the indications for chest wall resection to include the curative treatment of primary chest wall tumors and palliative treatment for breast cancer patients with osteoradionecrosis, local recurrence (in select patients), chest wall infection, and tumors metastatic to the chest wall.

Adult↗

Gastrointestinal bleeding in competitive runners.

Competitive runners have been shown to develop previously undescribed clinical conditions, including "runner's anemia." This has been shown to be an iron-deficiency anemia of several etiologies including gastrointestinal bleeding. Although 8-23% of runners have been shown to have guaiac-positive stools after a marathon, the incidence of significant and prolonged bleeding is unknown. We report four cases of competitive runners with iron-deficiency anemia, gastrointestinal bleeding coinciding with running, and no definitive gastrointestinal pathology despite extensive evaluation.

Adult↗

Longitudinal dichotic listening patterns for aphasic patients. II. Relationship with lesion variables.

Dichotic listening scores and information on lesion size and location were obtained for aphasic patients. All patients had a reduction in dichotic scores at 1 month postonset of symptoms, but some patients returned to normal levels of performance by 6 months postonset. Lesion location was the main determinant of patterns of performance. Right ear scores from the dichotic digit test closely reflected the presence or absence of lesions involving Heschl's gyrus. What appeared to be an effect of lesion volume was confounded by the relationship between increasing lesion volume and a greater likelihood of damage to Heschl's gyrus.

Adult↗

Edema of the arm as a function of the extent of axillary surgery in patients with stage I-II carcinoma of the breast treated with primary radiotherapy.

Edema of the arm can be a significant complication following treatment of breast cancer. To determine the risk of arm edema and factors associated with this risk in patients treated with primary radiotherapy, we reviewed the records of 475 women with early breast cancer treated between 1968 and 1980. During this period, the use of axillary surgery prior to radiation gradually increased, and all patients received full axillary irradiation until late in the series. Based on the surgeon's report, the extent of axillary surgery was classified as either a sampling, a lower dissection, or a full dissection. Edema of the arm was scored on clinical grounds and ranged from mild hand swelling to an increased arm circumference of 8 cm. At 6 years, the actuarial risk of developing arm edema was 8% for the entire study population. This risk was 13% for 240 patients who had axillary surgery and 4% for 235 patients not undergoing axillary surgery (p = 0.006). For patients undergoing axillary surgery, the risk of arm edema was 37% with full dissection compared to 5% with sampling (p = 0.0003), and 8% with lower dissection (p = 0.03). The risk of arm edema at 6 years was 28% if more than ten nodes were removed, and 9% if one to ten nodes were removed (p = 0.03). However, the extent of axillary dissection was stronger predictor of subsequent edema than was the number of nodes obtained. The role of axillary irradiation could not be evaluated since 91% of patients received axillary irradiation. The use of chemotherapy, the site or size of the primary tumor, clinical nodal status, patient age and weight, type of suture, the use of a drain, and subsequent local or distant failure did not appear to be significant risk factors. We conclude that the combination of full dissection and full axillary irradiation results in an unacceptably high risk of arm edema.

Arm↗

A large region controls tRNA gene transcription.

We find that tRNA gene transcription is controlled by a region much larger than the previously described internal segments known as A and B boxes. In a Bombyx mori silkworm tRNA2Ala gene, transcriptionally important sequences extend at least from -13 to +146, and thus include sequences both upstream and downstream from the 98 base-pair primary transcription unit. We show that the apparent size of this control region can be manipulated by the conditions used to measure transcription in vitro. Specifically, the use of high concentrations of templates to overcome the effect of an inhibitory substance in crude extracts can make the control region appear smaller. We propose that this finding explains much of the observed variability in the sequence requirements for transcription of different tRNA genes. If so, large size is likely to be a general feature of tRNA gene control regions.

Animals↗

Rh immune globulin after genetic amniocentesis: impact on pregnancy outcome.

Although Rh immune globulin is commonly given to Rh-negative women undergoing genetic amniocentesis, there is little documentation of the necessity, efficacy, or safety of this policy. In this study, reproductive outcomes in 147 women each receiving 150 micrograms of Rh immune globulin after genetic amniocentesis were compared with those of an equal number of Rh-positive amniocentesis control women. No significant differences were found in the incidence of midtrimester pregnancy loss, mean gestational age at delivery, mean birth weight, or frequency of preterm deliveries (P greater than 0.05 for all parameters). While two antepartum stillbirths occurred in the study group and none in the control population, causes unrelated to Rh immune globulin administration were apparent for both fetal deaths (one multiple congenital anomaly syndrome, one abruptio placentae at 38 weeks). Of the 103 Rh-negative women giving birth to Rh-positive infants, none were overtly sensitized at the time of delivery. It is concluded that second trimester Rh immune globulin administration does not increase the risk of pregnancy loss.

Abortion, Spontaneous↗

A pulsed Doppler echocardiographic method for calculating pulmonary and systemic blood flow in atrial level shunts: validation studies in animals and initial human experience.

The purpose of this study was to assess the accuracy of a quantitative two-dimensional range-gated Doppler echocardiographic method for estimating systemic and pulmonary flows in an open-chest canine preparation with a variable-sized atrial level shunt mimicking an atrial septal defect. In addition, we also report our initial experience with 10 children who had isolated atrial septal defects and who had pulmonary and systemic flow rations (QP:QS) determined by Doppler echocardiography simultaneously with green dye-shunt calculations in the cardiac catheterization laboratory. Ten mongrel dogs weighing 20 to 30 kg were anesthetized, intubated, and mechanically ventilated. Previously calibrated electromagnetic flow probes were placed around the ascending aorta and main pulmonary artery, and an atrial level shunt was created by inserting one-half inch diameter cannulae into the left and right atrial appendages and connecting both cannulae to 3/4 inch tubing that passed through a previously calibrated extracorporeal mechanical roller pump. This permitted quantitation as well as regulation of shunt size and direction. With each step-by-step variation in shunt magnitude, systemic and pulmonary flows were estimated by Doppler echocardiography and were matched to the simultaneous electromagnetic flowmeter recordings. Doppler-estimated systemic blood flow was obtained by imaging and recording Doppler flow velocities in the ascending aorta with the transducer positioned directly over the vessel. Doppler pulmonary flow was obtained by imaging the main pulmonary artery on the short-axis view and by determining flow velocity with the sample volume placed distal to the pulmonic valve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Validation of a Doppler echocardiographic method for calculating severity of discrete stenotic obstructions in a canine preparation with a pulmonary arterial band.

The purpose of this study was to develop an open-chest animal preparation to validate the accuracy of a two-dimensional Doppler echocardiographic method for estimating pressure drops across discrete stenotic obstructions. Six mongrel dogs underwent median sternotomy and catheters were placed in the right ventricle, distal main pulmonary artery, and aorta of each. A 1/8 inch umbilical tape was sewn to the posterior rim of the pulmonary artery just above the anulus and was progressively tightened to vary the degree of stenosis. Ultrasound and Doppler studies were performed with a 2.5 MHz phased-array unit with capabilities for pulsed or continuous-mode Doppler and real-time imaging. Peak systolic main pulmonary arterial flow velocities were recorded by Doppler echocardiography within the jet distal to the band from an oblique parasternal short-axis echocardiographic view and corrected for angle of incidence between the direction of Doppler sampling and the presumed direction of flow. Doppler velocities were converted to gradients with a simplification of the Bernoulli equation (gradient = 4 X maximal Doppler flow velocity2 ). Maximal Doppler-determined systolic pulmonary arterial velocities showed a good linear correlation with the 63 measured pressure drops (r = .95, SEE +/- 36.3 cm/sec). An excellent correlation was also found between Doppler-calculated and actual pressure gradients (r = .96, SEE +/- 7.26 mm Hg). Our results suggest that this Doppler method for measuring gradients across discrete stenotic obstructions may be quite accurate in clinical applications.

Animals↗

B-mode real-time ultrasonic carotid imaging: impact on decision-making and prediction of surgical findings.

The roles of B-mode real-time ultrasonic imaging (USI) and carotid angiography (CAG) in deciding on endarterectomy were analyzed. When greater than 50% stenosis and/or complicated ulceration were predicted by both techniques, endarterectomy was undertaken in 21/25; by only CAG in 5/8; and by only USI in 10/21. In vessels with adequate surgical data, stenosis was accurately predicted by CAG in 27/32, USI in 20/32, and ulceration by both CAG and USI in 21/29. USI results were sometimes used to justify endarterectomy despite unimpressive CAG. CAG is a better predictor of stenosis, whereas both are limited in predicting ulceration.

Arterial Occlusive Diseases↗

B-mode, real-time carotid ultrasonic imaging. Correlation with angiography.

B-mode, real-time ultrasonic imaging was prospectively evaluated as a screening test for atherosclerotic occlusive vascular disease in the carotid bifurcation region, as defined by carotid angiography in 100 carotid systems in 50 patients. Preliminary reliability studies for each technique assessed agreement between examiners. Sensitivities of ultrasonography for stenosis greater than 50% of luminal diameter, complicated plaque ulceration, complete occlusion, and "surgical disease" by any of these parameters were 79%, 26%, 25%, and 73%, respectively. Thirty-seven percent of the 100 carotid systems were found to contain surgically relevant disease by angiography, compared with 19% and 56%, respectively, of the carotid systems with negative and positive ultrasonographic results. Judicious use of ultrasonography as a screen for angiography requires awareness of these limitations.

Aged↗

Computed tomographic scan correlates of auditory comprehension deficits in aphasia: a prospective recovery study.

Lesion localization and volume as assessed on computed tomography were analyzed to determine their relationships to auditory comprehension deficits following left hemisphere ischemic stroke in 39 patients. Auditory comprehension was initially tested approximately four weeks after onset, and then monthly for five months, using the Token Test, a series of commands of increasing complexity. Computed tomographic scans obtained five months after onset were used for lesion localization and volume determination. Lesions in the posterior superior temporal and infrasylvian supramarginal regions were strongly associated with poor outcome. Patients with initially preserved auditory comprehension tended to have lesions that spared these regions, whereas patients with persistent deficits had lesions that included these regions. Six of 8 patients who initially had severe deficits in auditory comprehension but recovered completely lacked lesions in these regions. Lesion volume except when very large or very small was not closely associated with outcome.

Adult↗