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Biomedical subjects

K L Hall

Publications and source records attributed to K L Hall.

29 records · Page 2Linked to original sources

Screening for gynecologic cancer. Vulvar, vaginal, endometrial, and ovarian neoplasms.

The success of the Pap smear in screening for cervical cancer illustrates many of the tenets of screening for disease. Unfortunately, no other gynecologic malignancy shares this success. Detection of most gynecologic malignancies occurs once they have become symptomatic and on clinical examination at the interval cancer-related checkup as recommended by the ACS. These examinations, done yearly in women older than 40 and every 3 years in younger women, can go a long way in the detection of genital tract disease. In detecting vulvar neoplasms, visual inspection of the entire perineum coupled with palpation to include Bartholin's glands and early biopsy of suspicious vulvar lesions promotes earlier diagnosis. Self-examination similar to breast self-examination and increased patient awareness are potential education goals for physicians as well as cancer and medical societies. Vaginal examination at the cancer checkup should continue. The finding that most vaginal cancers are picked up by abnormal cytology while they are still asymptomatic argues strongly for Pap testing after menopause. The knowledge that women who are status posthysterectomy for benign disease are not protected from developing vaginal cancers mandates continued Pap testing in this population as well. Because endometrial cancer is common, primary care physicians should maintain a high index of suspicion. Aspiration biopsy is a simple office-based procedure with low risk and good yield, and any woman in the perimenopausal and postmenopausal period who presents with atypical bleeding patterns should be evaluated. Although not recommended as a general screening test, the ACS does advocate endometrial sampling in the high risk woman at the time of menopause. The greatest challenge to primary care physicians may be the early detection of ovarian cancer. No single test is available, nor is any advocated in screening for this lethal disease. Currently, only periodic physical examination is recommended at the cancer checkup interval. Ultrasound, both transabdominal and transvaginal, may help in detecting adnexal masses, but is not sensitive enough to differentiate benign from malignant lesions. In this setting, and in the patient with suspected ovarian cancer, CA 125 and AFP may be helpful in determining which patients require surgical exploration. Women with positive family histories for ovarian cancer require greater vigilance and close follow-up with serial ultrasound and CA 125 determinations. As the population ages, cancer, which is primarily a disease of age, will continue to increase in incidence.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Metastasis of unknown origin.

Evaluation of the patient with metastasis of unknown origin should be structured to quickly identify treatable tumors or the need for palliation while avoiding prolonged hospital stays and testing that will result in neither improved treatment nor better prognosis. The evaluation should be symptom-directed and pathologically oriented. It is the responsibility of the family physician in caring for a patient with MUO to ensure that communication is facilitated between surgeon, oncologist, pathologist, and patient. The physical examination should include thyroid, breasts, pelvic, and rectal examinations. General lab analyses should include fecal occult blood testing, complete blood count, urinalysis, serum calcium, and liver function studies. Men should have assays for prostate-specific antigen and serum prostatic acid phosphatase. Women should undergo mammography and pelvic ultrasound. Undifferentiated carcinoma is likely to originate from either small cell bronchogenic, lymphoma, or germ cell, and thus, serum should be assayed for HCG and AFP. Further radiologic studies, in the absence of specific symptoms, should be limited to chest radiographs and abdominal CT. Contrast studies should be included only if there is organ dysfunction. Biopsy of the malignant tissue should be done early, and studies should include histochemistry, immunohistology, and electron microscopy. Tissues from female patients should be studied for estrogen and progesterone receptors. When a biopsy is planned, advance communication between the family physician or surgeon and the pathologist greatly increases the chance of identifying a primary site. It is important that the surgeon obtain sufficient material to enable study, not only by standard histologic techniques, but also by electron microscopy, special stains, estrogen receptor activity, hormonal markers, and tumor markers. Treatment of patients for whom a primary tumor remains undiscovered must include toxic therapies only for those with good functional status who are likely to respond. Therapy must be pursued for palliation of symptoms when they develop. As physicians, we must control the urge to do something at those times when doing nothing is more appropriate. We must provide continuous support for both the patient and family, protecting to the best of our ability their quality of life. A physician should never convey the impression that it is "not cost-effective" to look for the source of a patient's malignancy. It can be emphasized that further search for a primary tumor carries both medical risk and expense, yet is unlikely to locate the primary tumor or improve the response to therapy or the quality of life.(ABSTRACT TRUNCATED AT 400 WORDS)

Biomarkers, Tumor↗

Isolation and characterization of clonal vascular smooth muscle cell lines from spontaneously hypertensive and normotensive rat aortas.

Vascular smooth muscle cells were isolated from the aortas of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats by use of the explant method on collagen gels. Clonal cell lines derived from these enriched populations possessed ultrastructural characteristics of vascular smooth muscle cells in culture; they grew in hill and valley configuration, immunostained with the muscle actin antibody HHF35, and failed to react with von Willebrand Factor VIII antibody. Fourteen clonal cell lines were characterized for growth and ligand binding characteristics. Large variations in growth rate and cell density at saturation were exhibited by clones of both strains. Similar variability was noted for specific binding of endothelial 1 and Sar1,Ile8-angiotensin II to their receptors, indicating considerable phenotypic heterogeneity among the clonal cell lines. Six selected clones were further characterized for angiotensin II receptor linkage to G proteins. Cells of both strains exhibited comparable affinity shifts in the presence of GTP gamma S. These clonal cell lines should be useful for a variety of analyses of the comparative biology of aortic cells. It is possible that the diversity of phenotypic traits exhibited by these clones reflects the heterogeneity of vascular smooth muscle tissue found in vivo.

Actins↗

Relationships of body weight, forage composition, and corn supplementation to feed intake and digestion by Holstein steer calves consuming bermudagrass hay ad libitum.

Holstein steer calves (101 to 350 kg BW) consumed bermudagrass hay ad libitum without or with supplemental ground corn up to 1.0% of BW. As BW increased, total DMI increased quadratically (-2.459 + .05448 [BW]-.000073 [BW2] + .540 [corn DMI]; R2 = .83, sy.x = .655). Each kilogram of corn DM decreased bermudagrass DMI by .46 kg. Total digestible OM intake (kg) increased with BW and corn supplementation (.314 + .0127 [BW] + .441 [corn OM intake]; R2 = .79, sy.x = .444). Feed intake level accounted for approximately 2.5 times more variability in total digestible OM intake than digestion did. Corn supplementation decreased digestion of bermudagrass NDF (62.50 - 8.468 [corn DMI, % BW]; R2 = .13, sy.x = 8.121), with a similar decrease across BW. Increasing bermudagrass DMI (% of BW) decreased bermudagrass NDF digestion slightly, but variation accounted for was only 33% of that attributable to corn DMI (% of BW). Concentrations of common fiber fractions (NDF, ADF, cellulose, hemicellulose, and ADL) in bermudagrass explained very little variation in feed intake and digestion, indicating considerable influence of other factors. Bermudagrass intake and digestion were not related, and no substantial interactions were observed among steer BW, corn level, and bermudagrass composition.

Animal Feed↗

Actions of novel antidiabetic agent englitazone in hyperglycemic hyperinsulinemic ob/ob mice.

The effects of CP 68722 (racemic englitazone) were examined in ob/ob mice, in adipocytes and soleus muscles from ob/ob mice, and in 3T3-L1 adipocytes. Administration of englitazone at 5-50 mg.kg-1.day-1 lowered plasma glucose and insulin dose dependently without producing frank hypoglycemia in either the diabetic or nondiabetic lean animals. The glucose-lowering effect in ob/ob mice preceded the reduction in hyperinsulinemia. On cessation of drug, plasma insulin returned to untreated levels within 48 h, whereas plasma glucose rose slowly over 5 days. Englitazone (50 mg/kg) for 11 days lowered plasma glucose (22.2 +/- 1.4 to 14.0 +/- 1.9 mM), insulin (7.57 +/- 0.67 to 1.64 +/- 0.60 nM), nonesterified fatty acids (1813 +/- 86 to 914 +/- 88 microM), glycerol (9.20 +/- 0.98 to 4.94 +/- 0.03 mM), triglycerides (1.99 +/- 0.25 to 1.03 +/- 0.11 g/L), and cholesterol (6.27 +/- 0.96 to 3.87 +/- 0.57 mM), but no effects were observed 3 h after a single dose. Basal and insulin-stimulated lipogenesis were enhanced in adipocytes from ob/ob mice treated with 50 mg/kg englitazone for 11 days compared with lipogenesis in cells from vehicle-treated controls. Treatment of ob/ob mice with 50 mg/kg englitazone reversed the defects in insulin-stimulated glycolysis (from [3-3H]glucose) and glycogenesis and basal glucose oxidation (from [1-14C]glucose) in isolated soleus muscles. Englitazone (30 microM) stimulated 2-deoxy-D-glucose transport in 3T3-L1 adipocytes from 0.37 +/- 0.03 to 0.65 +/- 0.06 and 1.53 nmol.min-1.mg-1 protein at 24 and 48 h, respectively. Thus, englitazone has 1) insulinomimetic and insulin-enhancing actions in vitro and 2) glucose-, insulin-, triglyceride-, and cholesterol-lowering properties in an animal model of non-insulin-dependent diabetes mellitus (NIDDM) in which sulfonylureas have little or no effect. Thus, this new agent may have beneficial effects including a reduced risk of hypoglycemia in patients with NIDDM.

3-Hydroxybutyric Acid↗

Effects of buffer or DL-methionine with different amounts of supplemental corn on feed intake and nutrient digestion by Holstein steers consuming bermudagrass hay.

Two latin squares were conducted to determine the effects on feed intake and nutrient digestion of adding a ruminal buffer or DL-methionine to supplemental ground corn for Holstein steers (avg BW of 286 and 222 kg in Exp. 1 and 2, respectively) with ad libitum access to bermudagrass hay. In Exp. 1, steers were not supplemented (control) or were given .5 (LC) or 1.0% BW/d (HC) of ground corn without or with .021% BW of sodium bicarbonate (B). Total DMI was 2.39, 2.71, 2.79, 2.81 and 2.98% BW (effects of supplementation [P less than .05], level of corn [P less than .05] and buffer [P less than .06]), and OM digested was 3.56, 4.65, 4.65, 4.96 and 5.34 kg/d for control, LC, LCB, HC and HCB, respectively (effects of supplementation and corn level, P less than .05). In Exp. 2, corn levels were .24 and .74% BW/d and .0022% BW of DL-methionine (M) replaced B. Total DMI was 2.85, 3.00, 2.99, 3.22 and 3.34% BW (effects of supplementation and corn level, P less than .05), and digestible OM intake was 3.78, 4.24, 4.30, 4.84 and 5.12 kg/d for control, LC, LCM, HC and HCM, respectively (effects of supplementation and corn level, P less than .05). Overall, changes in feed intake and digestion with additions of a ruminal buffer and DL-methionine to corn supplements were not marked; however, buffer addition increased DMI intake to the greatest degree with 1.0% BW/d of corn.

Animal Feed↗

A two-step timed sequential treatment for acute myelocytic leukemia.

Since 1980, adults with acute myelocytic leukemia (AML) have been treated on two clinical studies using intensive timed sequential therapy. All patients ages 16 to 80, including those with secondary AML (SAML) and those with AML preceded by a hematologic disorder (AHD), were treated, regardless of medical complications at the time of diagnosis. The first study combined high doses of cytarabine (ara-C, AC) and daunorubicin (DRN, D) in sequence (Ac2-D-Ac) and resulted in a complete remission rate of 55%. A group of these patients selected by functional status was able to receive a second course of therapy in remission, which resulted in a disease-free survival (DFS) of greater than 40% at 7 years. Because of toxicity in that study, 114 patients were entered on a second trial initiated 4 years ago, using a less aggressive first course, with amsacrine, to achieve a stable remission (Ac2-D-Amsa). This first treatment was followed by a more intensive second course (Ac6-D-Ac). With this two-step approach, a higher complete remission (CR) rate (76% for de novo AML and 54% for SAML-AHD) was achieved, and more patients were able to receive the second course of therapy. At the current median follow-up of 26 months, the median duration of DFS and overall survival are 11 and 14 months for patients with de novo AML. Age less than or equal to 55 is the most significant prognostic factor for both prolonged DFS and overall survival, with median durations of 17 and 18 months, respectively, for these younger patients. Patients with SAML-AHD remain relatively refractory to treatment despite aggressive chemotherapy, with median durations of DFS and overall survival of 9 months and 5 months, respectively.

Adolescent↗

Diagnosis of recurrent gynecologic malignancy with fine-needle aspiration cytology.

Between 1980-1985, 177 fine-needle aspirations were performed on 139 patients suspected of having recurrent gynecologic malignancy. Suspected sites of recurrence included a pelvic mass (122), peripheral lymph node (39), and a variety of other locations (16). There were 69 positives, 79 negatives, eight suspicious specimens, and 21 specimens inadequate for interpretation. Excluding suspicious or inadequate specimens, the results of the remaining 148 evaluable aspirations were confirmed by histopathologic correlation (35) or subsequent clinical course (113). Because there were no false positives, the specificity of the technique was 100%. The sensitivity was 68%, with an associated false-negative rate of 32%. The predictive value of a positive was 100%; that of a negative was 57%. An analysis of the false-negative results failed to show a correlation with cell type, lesion location, previous radiotherapy, or previous chemotherapy. The complication rate was less than 1%. These data support the conclusion that fine-needle aspiration cytology is a safe, highly specific method for diagnosing recurrent gynecologic malignancy. However, in patients with negative fine-needle aspiration cytology and suspected recurrent disease, it would appear that further evaluation is indicated.

Biopsy, Needle↗