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Biomedical subjects

A M Davis

Publications and source records attributed to A M Davis.

At least 37 records · Page 2Linked to original sources
PubMed2001

Clinical, electrocardiographic, and histologic correlations in children with dilated cardiomyopathy.

OBJECTIVE: To determine whether presenting electrocardiography is related to histologic findings and clinical outcomes in children with dilated cardiomyopathy. BACKGROUND: Lymphocytic myocarditis is an important cause of childhood dilated cardiomyopathy, the outcome of which is unclear. The results of non-invasive investigations are often used to infer the presence or absence of lymphocytic myocarditis. METHODS: Thirty-four children, presenting acutely with dilated cardiomyopathy, underwent both early electrocardiography and endomyocardial biopsy. The parameters examined included heart rate, PR, QRS, and corrected QT intervals, R-wave voltages in Leads V(1) and V(6), S-wave voltages in Leads V(1) and V(6), and sum of SV(1) and RV(6). We expressed measurements as Z scores, based on published normal values for age and gender. RESULTS: A total of 15 patients had lymphocytic myocarditis on endomyocardial biopsy (Group I), and 19 had non-specific histologic findings (Group II). We did not distinguish the 2 groups by age, time to endomyocardial biopsy, or duration of follow-up. Group I patients had significantly smaller R-wave Z scores in Leads V(1) and V(6), and combined S in V(1) and R in V(6) Z scores (p < 0.02 for each). The positive and negative predictive values of an R-wave amplitude in V(6) < 5th percentile were 75% and 65%, respectively, for the diagnosis of lymphocytic myocarditis. An R-wave amplitude in V(6) > 95th percentile had a positive and negative predictive value of 80% and 63%, respectively, for the diagnosis of idiopathic dilated cardiomyopathy. Survival and freedom from late cardiac dysfunction were more common among Group I patients compared with Group II (p <or= 0.02 for both). CONCLUSION: Myocardial histology cannot reliably be inferred from the presenting electrocardiogram. Survival and outcome for children with lymphocytic myocarditis is better than for those with non-specific histology.

Biopsy↗
PubMed2001

T wave alternans threshold in normal children.

INTRODUCTION: Sustained microvolt-level T wave alternans (TWA) during exercise is a predictor of ventricular arrhythmia propensity in adult populations. TWA occurs in normal adults, but it is rare at < 70% of predicted maximum heart rate. An onset heart rate < or = 110 is believed to be significant. The aim of this study was to examine the feasibility of performing the test in children and to determine the normal heart rate threshold for sustained TWA in children. METHODS AND RESULTS: Alternans was evaluated during bicycle exercise in 100 normal volunteers aged 8 to 17 years. Adequate resting data were obtained in 76 of 100 children and was negative in all. Exercise data from 16 of 100 was excluded due to excessive noise. Median maximum heart rate was 192 (range 140 to 214). Sustained alternans was absent in 75 (89%) of 84. In the nine children with sustained alternans, median onset heart rate was 138 (range 120 to 158), and 7 of 9 had an onset heart rate > or = 135. Median heart rate threshold as a percentage of predicted maximum heart rate (220 - age) was 67% (range 58% to 76%). Only 1 subject (1.2%) had an onset heart rate < 60% of predicted maximum. There was no significant difference between age, gender, endurance, maximum heart rate, QRS duration, QT interval, or QTc in those with and those without sustained TWA. CONCLUSION: Noninvasive assessment of TWA is feasible at > or = 8 years of age. Sustained TWA was present in 11% of normal children, but was absent at heart rates below 120 and rare (1.2%) below 60% of predicted maximum heart rate.

Adolescent↗
PubMed2001

Mediastinal fibrosis.

Mediastinal fibrosis is the least common, but the most severe, late complication of histoplasmosis. It should be differentiated from the many other less-severe mediastinal complications of histoplasmosis, and from other causes of mediastinal fibrosis. Posthistoplasmosis mediastinal fibrosis is characterized by invasive, calcified fibrosis centered on lymph nodes, which, by definition, occludes major vessels or airways.

Adult↗
PubMed2001

Sciatic nerve resection in the thigh: a functional evaluation.

Patients with a soft tissue malignancy involving the sciatic nerve who present with neurologic loss generally are advised to have an amputation. Twenty patients who underwent limb-sparing procedures with complete resection of the sciatic nerve as treatment for neurofibrosarcomas (12 patients), liposarcomas (four patients), malignant fibrous histiocytomas (two patients), recurrent desmoid tumor (one patient), and epithelioid hemangioendothelioma (one patient) were reviewed retrospectively. The mean age of these nine women and 11 men at the time of surgery was 51 years (range, 28-84 years). The right sciatic nerve was affected in 12 patients. These tumors were large and high grade. A mean of 22 cm of the nerve had to be resected (range, 8-42 cm). Ten patients received preoperative radiotherapy and 16 patients had intraoperative or postoperative radiotherapy. At a mean followup of 35 months (range, 7-97 months), 14 of the 20 patients were alive. Two patients had local recurrences develop (10%), whereas 12 patients had distant metastases. The function of the 10 patients as assessed by the Toronto Extremity Salvage Score averaged 74%. Most patients indicated that walking in the house is not difficult, but walking is compromised as soon as an effort is needed. Four patients walk without a cane, four needed one cane, and two needed two canes. The patients experienced stiffness, a sense of numbness, and premature fatigue. The use of analgesics was infrequent. Generally, patients rated themselves to be mildly to moderately disabled. From this small number of patients, it is shown that a tumor involving the sciatic nerve can be treated by limb-sparing surgery, including complete nerve resection, as an alternative to hip disarticulation or hindquarter amputation because the limb salvage option provides an acceptable functional outcome.

Activities of Daily Living↗
PubMed2001

Functional evaluation in distal femoral endoprosthetic replacement for bone sarcoma.

A multicenter study of successfully treated patients (mean age, 36.7 years) with a minimum 1-year followup (average, 35.4 months) after distal femoral endoprosthetic replacement for bone sarcoma was done using the 1987 and 1993 versions of the Musculoskeletal Tumor Society, the Short Form-36, and the Toronto Extremity Salvage Score functional evaluation criteria. Fifty-six patients (28 women and 28 men) fulfilled the criteria. Thirty-one Kotz prostheses (fixed hinge, uncemented) and 25 Modular Replacement System Prostheses (rotating hinge, cemented) were used. Thirty-five patients walked without aids, 19 used a cane, and two used crutches or a walker. The Musculoskeletal Tumor Society 1987 mean score was 28.1. The Musculoskeletal Tumor Society 1993 mean score was 80.4. The Toronto Extremity Salvage Score mean was 81.6. The Short Form-36 Physical Component Score had a mean of 43.2 and Mental Component Score mean of 54.2. The two groups of implants were comparable, except for the length of bone resection. Multivariate regression analysis revealed that patient age, existence of a pathologic fracture, and type of prosthesis all significantly accounted for differences in functional outcome as measured by the Musculoskeletal Tumor Society 1993, the Toronto Extremity Salvage Score, and the Short Form-36 Physical Component Score scales. Although both implants provided satisfactory function, the Musculoskeletal Tumor Society 1993 and the Toronto Extremity Salvage Score results were significantly better with the Modular Replacement System prosthesis. The effect of possible differences among surgeons or institutions was not addressed.

Adult↗
PubMed2001

Long-term followup of fresh femoral osteochondral allografts for posttraumatic knee defects.

Fresh osteochondral allografts were used to repair articular defects in the distal femur in 72 patients. Sixty patients were available for long-term followup (mean, 10 years) to determine graft survivorship and patient outcomes using a modified Hospital for Special Surgery score. Twelve of 60 grafts have failed with three having graft removal alone and nine being converted to total knee replacement. Kaplan-Meier survivorship analysis showed 85% graft survival at 10 years and 74% survival at 15 years. Patients with surviving grafts had good function, with a mean Hospital for Special Surgery score of 83 points at 10 years followup. Ten patients (17%) required meniscal transplantation whereas 41 (68%) required realignment osteotomy done simultaneously with the osteochondral allograft. Patients requiring meniscal transplantation, limb realignment, or both, had equally good outcomes at 10 years as those who underwent osteochondral transplantation alone. Likewise, transplantation to the medial or the lateral condyle had no bearing on long-term outcomes. Radiographs were available for 38 patients. These radiographs showed that 18 (48%) patients had no or mild arthritis, 10 (26%) had moderate, and 10 (26%) had severe arthritis. Late osteoarthritic degeneration as seen on radiographs was associated with outcomes, with patients with more severe arthritis having lower Hospital for Special Surgery scores. The authors think that osteochondral allograft transplantation is a valuable treatment option in patients with large osteochondral defects in the distal femoral articular surface.

Adolescent↗
PubMed2001

Pathologic fractures of the proximal femur secondary to benign bone tumors.

Pathologic fractures of the proximal femur secondary to benign bone tumors often are difficult to treat because of specific anatomic features of this region and the aggressiveness of the tumors. Between 1986 and 1996, 11 patients presented with a pathologic fracture of the proximal femur secondary to a benign bone tumor. All were treated with a uniform approach consisting of biopsy, intralesional curettage, high-speed burring, and reconstruction using morselized allograft, autograft, and a fixed-angle implant. The average followup was 4 years 3 months (range, 24-114 months). One patient was lost to followup. All fractures healed, and there were no local recurrences and no cases of avascular necrosis. Functional evaluation revealed generally good results. Patients scored a mean of 32.6 on the original Musculoskeletal Tumor Society scale and 95.8 on the revised version. The average Toronto Extremity Salvage Score was 91.3. With the numbers available, there were no significant differences between the study group and population norms in the Short Form-36. These results suggest that a uniform approach based on preservation of the femoral head can be applied successfully to the treatment of these lesions with good local tumor control, fracture healing, and acceptable functional outcomes.

Adolescent↗
PubMed2001

Is there a disassociation of maximal oxygen consumption and maximal cardiac output?

PURPOSE: The purpose of the present study was to determine whether maximal cardiac output (Q) is affected by the duration of the maximal exercise test. METHODS: Nine healthy men (N = 6) and women (N = 3) performed three separate maximal treadmill exercise tests, separated by at least 24 h, and underwent a body composition assessment by hydrostatic weighing, all within a 2-wk period. A baseline maximal exercise test was performed to establish VO(2max). The second and third tests, assigned randomly, were designed to elicit the subjects' predetermined VO(2max) in either 6 or 12 min. Heart rate (HR), blood pressure (BP), minutes of ventilation, and oxygen consumption (VO(2)) were measured during all tests. At the end of the 6- and 12-min tests, Q was measured using an acetylene rebreathing technique. Stroke volume (SV), mean arterial pressure (MAP), total peripheral resistance (TPR), and arteriovenous O(2) difference were calculated using standard equations. RESULTS: Repeated-measures ANOVA indicated that there were no significant differences in HR and VO(2max) between the baseline, 6-min, and 12-min tests. Paired t-tests revealed significantly greater Q (25.1 +/- 5.6 vs 23.7 +/- 5.2 L.min-1) and SV (138.3 +/- 31.5 vs 130.5 +/- 31.2 mL) in the 6- versus 12-min tests, respectively. There were no significant differences in systolic BP, diastolic BP, MAP, TPR, or arteriovenous O(2) difference. CONCLUSIONS: Despite there being no difference in VO(2max) between the two tests, the 6-min maximal exercise test resulted in a significantly greater Q than the 12-min test, because of a significantly greater SV. Thus, there was a disassociation between VO(2) and Q during maximal exercise.

Adult↗
PubMed2001

Estradiol enhances excitatory gamma-aminobutyric [corrected] acid-mediated calcium signaling in neonatal hypothalamic neurons.

Contrary to the situation in adulthood, gamma-aminobutyric [corrected] acid (GABA)(A) receptor activation during early brain development depolarizes neurons sufficiently to open L-type voltage-gated Ca(2+) channels. Because GABA is excitatory during the sensitive period of steroid-mediated brain sexual differentiation, we investigated whether estradiol modulates excitatory GABA during this period, by examining two parameters: 1) magnitude of GABA-induced calcium transients; and 2) developmental duration of excitatory GABA. Dissociated hypothalamic neurons from embryonic-day-15 rat embryos were loaded with the Ca(2+) indicator, fura-2, and transient rises in [Ca(2+)](i) (Ca(2+) transient) were measured after application of 10 microM muscimol, a GABA(A) receptor agonist. Cells were treated with 10(-10) M estradiol or vehicle from 0-3 days in vitro (DIV) and imaged on 4 DIV, whereas others were treated from 3-6 DIV and imaged on 7 DIV. The mean amplitude of Ca(2+) transients after muscimol administration were 68% and 61% higher in estradiol-treated neurons on 4 DIV and 7 DIV, respectively, relative to controls. Consistent with GABA becoming inhibitory in mature neurons, 50% fewer control neurons responded on DIV 7, relative to DIV 4. However, estradiol treatment maintained excitatory GABA on DIV 7 (72% in estradiol-treated vs. 35% in control). This is the first report of hormonal modulation of excitatory GABA, and it suggests that estradiol may mediate sexual differentiation by enhancing GABA-induced increases in intracellular Ca(2+).

Animals↗
PubMed2001

Arsenic alters the function of the glucocorticoid receptor as a transcription factor.

Chronic human exposure to nonovertly toxic doses of arsenic is associated with an increased risk of cancer. Although its carcinogenic mechanism is still unknown, arsenic does not directly cause DNA damage or mutations and is therefore thought to act principally as a co-mutagen, co-carcinogen, and/or tumor promoter. Previous studies in our laboratory demonstrated that effects of low-dose arsenic (III) (arsenite) on expression of the hormone-regulated phosphoenolpyruvate carboxykinase (PEPCK) gene were strongly associated with the glucocorticoid receptor (GR)-mediated regulatory pathway. We therefore examined specifically the effects of arsenite on the biochemical function of GR in hormone-responsive H4IIE rat hepatoma cells. Completely noncytotoxic arsenite treatments (0.3-3.3 microM) significantly decreased dexamethasone-induced expression of transiently transfected luciferase constructs containing either an intact hormone-responsive promoter from the mammalian PEPCK gene or two tandem glucocorticoid response elements (GRE). Western blotting and confocal microscopy of a green fluorescent protein-tagged-GR fusion protein demonstrated that arsenite pretreatment did not block the normal dexamethasone-induced nuclear translocation of GR. These data indicate that nontoxic doses of arsenite can interact directly with GR complexes and selectively inhibit GR-mediated transcription, which is associated with altered nuclear function rather than a decrease in hormone-induced GR activation or nuclear translocation.

Animals↗
PubMed2001

Classification of positive margins after resection of soft-tissue sarcoma of the limb predicts the risk of local recurrence.

We considered whether a positive margin occurring after resection of a soft-tissue sarcoma of a limb would affect the incidence of local recurrence. Patients with low-grade liposarcomas were expected to be a low-risk group as were those who had positive margins planned before surgery to preserve critical structures. Two groups, however, were expected to be at a higher risk, namely, patients who had undergone unplanned excision elsewhere with a positive margin on re-excision and those with unplanned positive margins occurring during primary resection. Of 566 patients in a prospective database, 87 with positive margins after limb-sparing surgery and adjuvant radiotherapy were grouped according to the clinical scenario by an observer blinded to the outcome. The rate of local recurrence differed significantly between the two low- (4.2% and 3.6%) and the two high-risk groups (31.6% and 37.5%). This classification therefore provides useful information about the incidence of local recurrence after positive-margin resection.

Female↗
PubMed2001

Proximal femoral allografts for reconstruction of bone stock in revision arthroplasty of the hip. A nine to fifteen-year follow-up.

BACKGROUND: Revision of a femoral component in a patient who has severe bone loss is a complex problem that is likely to increase with the increasing numbers of patients who have multiple revision hip arthroplasties. A valuable option in such a situation is use of a long-stem prosthesis that is cemented to a proximal femoral allograft but not to the host bone. METHODS: Between April 1984 and December 1989, sixty-three total hip arthroplasties in sixty consecutive patients were revised with a proximal femoral allograft-prosthesis construct. The average length of the allograft was 15 cm. The average age of the patients at the time of the revision was 62.5 years. All patients had undergone at least one previous total hip arthroplasty, and an average of 3.8 previous total hip arthroplasties had been performed in the series. Each patient was assigned a modified Harris hip score. Radiographs were examined for trochanteric union, allograft-host union, endosteal and periosteal resorption, component loosening, and fracture. RESULTS: At an average of eleven years (range, nine years and four months to fifteen years) after the revision, forty-five patients were alive, fourteen patients had died, and one patient had been lost to follow-up. The patients who had died or had been lost to follow-up had had a total of fifteen allografts (24%) and had been followed for an average of five years and seven months (range, two years and four months to eight years). The average preoperative Harris hip score for the sixty-three hips was 30 points (range, 6 to 65 points). At the latest follow-up evaluation, the average score for the hips with the original graft in situ was 71 points (range, 47 to 95 points). Five hips failed because of infection, and four of them were successfully revised. Three hips failed because of aseptic loosening, at an average of ten years and three months; two were successfully revised, and the third was awaiting revision at the time of writing. An additional operation was performed in three hips with allograft-host nonunion and in two with dislocation. Success was defined as a postoperative increase in the Harris hip score of greater than 20 points, a stable implant, and no need for additional surgery related to the allograft at the time of the review. The success rate for all hips was 78% (forty-nine of sixty-three) after an average of nine years of follow-up. The success rate for the patients who were alive at the time of follow-up was 77% (thirty-seven of forty-eight hips) after an average of eleven years of follow-up. CONCLUSIONS: The clinical and radiographic results at an average of eleven years after revision hip arthroplasty with a proximal femoral allograft are encouraging. This report represents our early experience; improvements in the technique have been made. We believe that this technique provides a viable option for treatment of the difficult problem of severe femoral bone loss.

Adult↗
PubMed2000

Developmental increase in (3)H-muscimol binding to the gamma-aminobutyric acid(A) receptor in hypothalamic and limbic areas of the rat: why is the ventromedial nucleus of the hypothalamus an exception?

Using in vitro autoradiography to measure binding of the gamma-aminobutyric acid(A) (GABA(A)) receptor agonist, muscimol, we examined male and female rats on postnatal days 1, 5, 10, and 20. There were no sex differences in muscimol binding in any hypothalamic or limbic regions examined. However, all regions exhibited a developmental increase in the density of binding, except the ventromedial nucleus (VMN) of the hypothalamus. We have previously shown that the adult VMN is the only hypothalamic nucleus containing an abundance of the alpha2 subunit of the GABA(A) receptor and lack of the alpha1 subunit. We hypothesize that the lack of alpha1 may be causally related to the lack of increase in muscimol binding.

Animals↗
PubMed2000

A comparison of staging systems for localized extremity soft tissue sarcoma.

BACKGROUND: Staging systems for soft tissue sarcoma (STS) are important to identify patients with similar systemic risk who might benefit from specific treatments. This study compared four commonly used staging systems for predicting systemic outcomes of patients with localized extremity STS, as proposed by the fourth and fifth editions of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system, the Memorial Sloan-Kettering Cancer Center (MSK) system, and the Surgical Staging System (SSS) of the Musculoskeletal Tumor Society. METHODS: Three hundred consecutive adult patients with newly diagnosed nonmetastatic STS of the lower extremity were treated at Memorial Sloan-Kettering Cancer Center between 1982 and 1989. Metastasis free survival was the end point of the study. The prognostic value of the four staging systems and their components were examined in univariate and multivariate analyses. The Akaike information criterion (AIC) was used to identify the system that best predicted the risk of systemic recurrence. RESULTS: Compartment status, depth, grade, and size were all independent predictors of outcome within their respective staging systems. However, when compared with one another, only depth, grade, and size retained their prognostic significance. Of the four models, the AIC predicted that the MSK was the best predictor of systemic relapse, followed by the fifth edition of the AJCC/UICC staging system. CONCLUSIONS: Staging systems such as the MSK system or the fifth edition of the AJCC/UICC system, which include tumor depth, grade, and size as prognostic factors, are the most predictive of systemic relapse in patients presenting with localized extremity STS. Both of these systems identify the same group of patients at the highest risk who would be the most suitable for adjuvant chemotherapy trials.

Adolescent↗
PubMed2000

An ovarian steroid hormone regimen that increases hypothalamic oxytocin expression alters [3H] muscimol binding in the hypothalamic supraoptic nucleus of the female rat.

Administration of sequential estradiol (E(2)) and progesterone (P) for 2 weeks followed by withdrawal of P 48 h prior to sacrifice will increase oxytocin (OT) messenger ribonucleic acid (mRNA) levels in the paraventricular and supraoptic nuclei (PVN and SON) of the ovariectomized rat. Progesterone is known to mediate certain of its effects via binding to the gamma aminobutyric acid A (GABA(A)) receptor. E(2) and P are known to modulate the specific binding of the GABA(A) receptor agonist, muscimol, in certain brain regions. In the present study ovariectomized rats received empty or steroid-filled Silastic capsules for 2 weeks according to one of the following schedules: E(2) only (E(2) group) vs. sequential E(2) and P in which P was either removed 48 h prior to killing (E(2)/P- group) or sustained until sacrifice (E(2)/P+ group). [3H]muscimol binding was measured in several brain regions of the animals. The steroid sequence that is known to increase SON OT mRNA (E(2)/P-) selectively decreased [3H]muscimol binding in the SON of ovariectomized rats. The results suggest that changes in GABA(A) receptor binding may, in part, play a role in the regulation of steroid-induced increases in hypothalamic OT expression.

Animals↗
PubMed2000

Developmental switch in the expression of GABA(A) receptor subunits alpha(1) and alpha(2) in the hypothalamus and limbic system of the rat.

The GABA(A) receptor is a pentameric ligand gated ion channel complex assembled from a family of at least 17 different subunits encoded by distinct genes. Two subunits, alpha(1) and alpha(2), exhibit age dependent expression throughout several areas of the brain. In general, the density of immunoreactive product for alpha(1) is greatest in the adult brain, while alpha(2) is highest in younger tissue. Since the developmental switch in alpha(1) and alpha(2) coincides with the end of the sensitive period for steroid-mediated sexual differentiation of the brain, we hypothesized that GABA(A) receptor subunit expression may be involved in this process. We have examined the age-dependent expression of alpha(1) and alpha(2) in discrete regions of the hypothalamus and limbic system of males and females. While we did not detect any dramatic sex differences in alpha(1) or alpha(2) immunoreactive density, each region exhibited a unique developmental profile. In the ventromedial nucleus of neonatal animals immunoreactivity is highest for alpha(1), while in the adult the signal for alpha(2) is greater; the opposite of that observed in the ventrolateral thalamus. There is no age dependent change for alpha(1) in the preoptic area, while alpha(2) shows a small, but significant increase. Immunoreactive densities for both subunits increase in the arcuate nucleus and the hippocampus, but decrease in the lateral amygdala. We conclude that these regional differences in subunit expression across development determine individual characteristics of brain areas and may play a role in establishing unique physiological responses to GABA.

Aging↗
PubMed2000

Predictors of functional outcomes following limb salvage surgery for lower-extremity soft tissue sarcoma.

BACKGROUND AND OBJECTIVES: Patient function has been conceptualized by clinical measures such as joint motion, muscle strength, disability, and general health status. The purpose of the current study was to evaluate tumor and treatment variables predictive of these conceptually different posttreatment functional outcomes in patients treated with limb preservation surgery for lower-extremity soft tissue sarcoma. METHODS: One hundred seventy-two patients with minimum 1-year follow-up were evaluated using the following outcomes: impairment, measured by the 1987 and 1993 versions of the Musculoskeletal Tumor Society Rating Scale (MSTS); disability, measured by the Toronto Extremity Salvage Score (TESS); and general health status, using the Short Form-36 (SF-36). Tumor and treatment-related variables (age, gender, presenting disease status, anatomic site, tumor size, grade, depth, prior excision, irradiation, bone resection, motor nerve sacrifice, and complications) were extracted from the STS database. RESULTS: Large tumor size, bone resection, motor nerve resection, and complications were predictive of lower MSTS 1987 and 1993 scores. Patients with large, high-grade tumors who required motor nerve resection were more disabled, as reflected by lower TESS scores. Only age and prior surgery were adverse predictors of SF-36 score. CONCLUSIONS: These results demonstrate that different factors are predictive of different patient outcomes, specifically, impairment, disability, and general health status. It is important to define function when counseling patients regarding their potential recovery based on tumor and treatment-related variables. J. Surg. Oncol. 2000;73:206-211.

Activities of Daily Living↗