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Biomedical subjects

K A Kern

Publications and source records attributed to K A Kern.

At least 37 records · Page 2Linked to original sources

Changing role of splenectomy for hematologic disease.

In the past decade the development of accurate imaging and the evolution of the medical management of hematologic diseases has led to changes in the indications for splenectomy for these disorders. To assess the impact of these developments, a multi-institutional, retrospective review was undertaken. One hundred fifty-six splenectomies were performed for hematologic disorders between July 1, 1979 and June 30, 1991. Patients were divided into 2 groups: those undergoing splenectomy from 1979-1985 (Period I), and those undergoing splenectomy from 1986-1991 (Period II). Diseases were classified into 3 groups: cytopenic/anemic conditions, symptomatic splenomegaly, and Hodgkin's disease. Data was compared between the two periods using chi-square analysis. More splenectomies were performed for hematologic disorders during Period II than Period I (P < .005). This increase is secondary to a rise in the number of splenectomies performed for cytopenia/anemia during Period II. In contrast, splenectomies for splenomegaly and Hodgkin's disease decreased during Period II (P < .005 and < .05). More Hodgkin's patients were upstaged on the basis of positive laparotomy findings in Period II, compared to Period I (40% versus 10%, P = .01). Surgeons are now performing more splenectomies for cytopenic/anemic diseases, and fewer for splenomegaly and Hodgkin's disease. These results are consistent with recent trends: (1) earlier splenectomy in patients with cytopenia/anemia; (2) earlier medical intervention in infiltrative splenic disorders; and (3) more reliance on radiologic staging in Hodgkin's disease and widespread use of combination chemotherapy, leaving surgical staging for those cases in which treatment would be changed by laparotomy findings.

Adult↗

Medical malpractice involving colon and rectal disease: a 20-year review of United States civil court litigation.

To determine objectively the causes of malpractice litigation involving colon and rectal disease, a retrospective review was undertaken of all cases tried in the U.S. federal and state civil court system over a 21-year period from 1971 through 1991. Ninety-eight malpractice cases were identified from a computerized legal data base, involving 103 allegations of negligence. Allegations fell into five major categories: 1) failure to timely diagnose disease, principally colorectal cancer and appendicitis (n = 44/103; 43 percent); 2) iatrogenic colon injury (n = 25/103; 24 percent); 3) iatrogenic medical complications during diagnosis or treatment (n = 16/103; 15 percent); 4) sphincter injury with fecal incontinence, resulting from anorectal surgery or midline episiotomy (n = 10/103; 10 percent); and 5) lack of informed consent, especially regarding extent of procedures or risk of endoscopy (n = 8/103; 8 percent). These data may aid in design of risk prevention strategies related to the diagnosis and treatment of colorectal disease.

Anal Canal↗

Medicolegal analysis of errors in diagnosis and treatment of surgical endocrine disease.

BACKGROUND: The medicolegal impact of adverse events in surgical endocrine disease has not been described previously. This study was undertaken to determine the causes, costs, and outcomes of endocrine malpractice litigation. METHODS: Jury verdict reports from the U.S. civil court system from 1985 through 1991 were reviewed. Sixty-two malpractice cases were identified from 21 states. RESULTS: The 62 cases were classified into three categories, totaling 63 adverse events: (1) complications (n = 34, 54%) from thyroid (n = 32, 51%) or parathyroid (n = 2, 3%) surgery; (2) delayed diagnosis (n = 22, 35%) of thyroid cancer (n = 11, 18%), adrenal tumors (n = 9, 14%), and hyperparathyroidism (n = 2, 3%); and (3) medical morbidity (n = 7, 11%) from radioactive iodine (n = 5, 8%) or from propylthiouracil (n = 2, 3%). Surgical injuries, mostly recurrent nerve injuries by general surgeons, accounted for the greatest number of cases and the highest cost of litigation. CONCLUSIONS: Medical malpractice involving endocrine disease results in expensive litigation, a result of serious harm. Technical misadventures account for most cases, followed closely by delays in diagnosis. These data may aid design of risk prevention strategies in endocrine disease.

Costs and Cost Analysis↗

Causes of breast cancer malpractice litigation. A 20-year civil court review.

To determine objectively the patient and physician factors that lead to breast cancer malpractice litigation, a review was undertaken of all cases tried in the US federal and state civil court system over a 20-year period from 1971 through 1990. Forty-five cases were identified and all involved a delayed diagnosis of breast cancer (the mean delay was 15 months). The patients were young (mean age, 40 years). Of 45 cases studied, the majority of patients (37 [82%]) found a painless mass by self-examination of the breast. Only 22 patients (49%) had further workup, mostly by mammography (20 [44%]). The results of 16 mammograms (80%) were read as normal. Obstetricians and gynecologists were involved in the greatest number of cases (21 [50%]), followed by family practitioners and internists (17 [41%]), general surgeons (12 [28%]), and radiologists (4 [10%]).

Adult↗

[14C]deoxyglucose uptake and imaging in malignant melanoma.

Since malignant tumors utilize more glucose than normal tissues, tumor uptake and autoradiographic imaging studies using the 14C-labeled glucose analog 2-deoxyglucose (DG) provide a useful preclinical system to determine if similar human tumors will image in vivo with positron emission tomography (PET) using 18F-labeled DG (FDG-PET). We studied B16 murine melanomas of increasing metastatic potential (F1, low; BL-6, intermediate; F10, high) as a feasibility study to determine the potential for human melanoma imaging using FDG-PET. Male C57BL-6 mice (50 g) were implanted sc with 1-mm3 fragments of B16 melanomas. Fourteen days later mice were injected ip with 1.25 muCi of [14C]DG. Sixty minutes later tumor (T) and gastrocnemius muscle (M) were harvested, solubilized, and counted for [14C]DG dpm/mg to estimate glucose utilization. Autoradiographic imaging was carried out similarly, using 2.0 muCi or [14C]DG with 30-day exposure of T and M tissue sections (20 microns thick) to X-ray film. The uptake of [14C]DG (expressed as dpm/mg; % injected dose/g; and tumor-to-muscle uptake ratios) was 6 to 10 times higher in tumors than in muscle tissue (P less than 0.001). All three melanoma cell lines imaged successfully with [14C]DG autoradiography. Tumor uptake of [14C]DG did not correlate with increasing metastatic potential. The experimental B16 murine melanomas F1, BL-6, and F10 extract glucose at higher rates than muscle tissue, a property necessary for successful PET imaging of cutaneous melanoma. The lack of correlation between glucose extraction and metastatic potential suggests that the demands for glucose during tumor growth and metastasis are not related. This is the first laboratory study to predict that human malignant melanoma will image with FDG-PET.

Animals↗

Technique for high volume drainage beneath large tissue flaps.

We have found that a chest tube placed beneath large tissue flaps and connected to a standard closed pleural drainage system gives superior results in terms of approximation of tissues and evacuation of the fluid to any available self-contained suction drain. This system makes continuous high volume drainage possible without sacrificing the mobility of the patient or the sterility of the drainage system. Quantifying daily drainage into the closed pleural drainage system is easy for nurses and surgical staff alike. We suggest that this type of drainage system is applicable to a wide variety of reconstructions of the abdominal and chest walls involving extensive soft tissue flaps.

Abdominal Muscles↗

Gastric cancer: a neoplastic enigma.

Effective therapy for gastric cancer remains elusive, and thus surgeons, oncologists, and radiotherapists are continually confounded. Multiple attempts to improve survival in gastric cancer patients have failed, including extended lymphadenectomy (by American surgeons), single- or multiple-agent chemotherapy, and combined-modality therapy (multiple-agent chemotherapy combined with radiation therapy). Such studies have been plagued by the high volume of inadequate antitumor responses or by lethal toxicity. At present, chemotherapy remains the best hope for effective adjuvant therapy, but new routes of drug delivery that will decrease systemic toxicity must be developed. Since gastric cancer recurs locoregionally and infrequently metastasizes to distant sites until very late in its course, theory suggests intraperitoneal (IP) chemotherapy applied to locoregional sites should decrease recurrence without significant systemic toxicity. Such treatments have been effective in other malignancies that commonly occur IP, such as ovarian cancer. Intracavitary chemotherapy protocols for gastric cancer are under development and will soon produce data on treatment efficacy. Such studies offer a theoretic basis for improved survival from gastric cancer; however, only well-controlled treatment trials will confirm if theory can be translated into clinical reality.

Adenocarcinoma↗

Metabolic imaging of human extremity musculoskeletal tumors by PET.

The measurement of glucose utilization rate (GUR) by positron emission tomography (PET) using 18F-2-fluoro-2-deoxy-D-glucose (FDG) is a valuable method to assess the grade of malignancy of brain tumors. We have designed a feasibility trial to determine whether PET could be used to image and predict the grade of malignancy of human extremity musculoskeletal tumors. Five patients with extremity tumors (four soft-tissue tumors and one osteogenic tumor) were studied. Peak and mean apparent GURs were determined in the tumor region. All tumors were subsequently resected and graded in a standard fashion using the NCI grading system. Peak apparent GURs ranged from 3.3 mg/100 g/min to 15.2 mg/100 g/min, with the highest values found in the high grade tumors. Although the number of patients studied was small, a good correspondence was shown between GURs and histopathologic grading. Our results indicate that PET can be used to image and evaluate the metabolic activity of human musculoskeletal tumors.

Adolescent↗

Autoradiographic imaging of rat sarcoma in different anatomical sites using 2-[14C]deoxyglucose.

As sarcomas are known to have accelerated glycolysis, we used the radiolabeled glucose analogue 2-deoxy-d-[U-14C]glucose in autoradiographic imaging studies of a methylcholanthrene-induced rat fibrosarcoma placed in an i.m. site, and in models of pulmonary and hepatic metastases. Fifty muCi of 2-deoxy-d-[U-14C]glucose were injected i.p. into groups of rats bearing tumors in these three sites; sacrifice of animals for imaging was carried out 45 min later. Excellent imaging of sarcoma tissue in all three anatomical sites was obtained, with high visual contrast compared to the normal tissue background. Using densitometry of autoradiographs, tumor/tissue ratios were 7.1 for i.m. tumors, 3.8 for pulmonary metastases, and 2.8 for hepatic metastases. Autoradiographic imaging of sarcomas may be obtained based upon avidity of neoplastic tissue for the glucose analogue 2-deoxy-d-[U-14C] glucose. Such imaging is not dependent upon anatomical site and reproducibly images rat sarcomas in muscle, lung, and liver.

Animals↗

Inhibition of established rat fibrosarcoma growth by the glucose antagonist 2-deoxy-D-glucose.

Sarcoma cells exhibit higher rates of glycolysis than normal tissues and may be dependent on glucose utilization for growth. Accordingly, we tested the ability of the glucose antimetabolite 2-deoxy-D-glucose (2-DG) to inhibit the growth of an established methylcholanthrene-induced rat fibrosarcoma in three groups of F344 rats with increasing subcutaneous inoculations of tumor (2 X 10(6) cells, 1 X 10(7) cells, and 1 mm tumor fragments). Rats were randomized to receive 2-DG or saline solution at doses of 0.75 gm/kg, 1.5 gm/kg, or 1.75 gm/kg, beginning 3 days after tumor implantation and continuing for 10 days. Tumors were removed and weighed on day 14. We measured tissue [14C]-2-DG levels in tumor, brain, liver, and muscle after intraperitoneal injection of radiolabeled 2-DG. In these same tissues we determined the activity of glucose-6-phosphatase (G-6-Pase), an enzyme which dephosphorylates the intracellular glycolytic inhibitor 2-DG-6-phosphate, thus reversing the antitumor effect of 2-DG. All groups treated with 2-DG had a significant reduction in tumor weight of 50% to 70% when compared with saline solution-treated controls. Toxicity was substantial at the highest dose of 2-DG, but minimal toxicity was noted at intermediate and low doses. Tumor had the greatest uptake of [14C]-2-DG, with low levels of G-6-Pase leading to prolonged retention and highest tissue levels of radiolabeled 2-DG. Use of 2-DG inhibits established sarcoma growth because it is rapidly transported into tumors, cannot be metabolized after phosphorylation, and is dephosphorylated and released slowly from tumor cells. Rat sarcoma growth is dependent on glucose utilization and can be effectively inhibited by glucose antagonism.

Animals↗

Branched chain amino acid-enriched solutions in the septic patient. A randomized, prospective trial.

A prospective, randomized trial was undertaken to compare the nutritional efficacy in surgical stress of a standard amino acid solution and two branched chain-enriched amino acid solutions: one enriched primarily with valine, the other with leucine. The study comprised 37 patients in the surgical intensive care unit who received isocaloric, isonitrogenous parenteral nutrition started within 24 hours of the onset of major operation, injury, or sepsis. Nitrogen retention was marginally but statistically significantly better on days 5, 7, and 10 in both groups of patients receiving the branched chain-enriched solutions, but differences in cumulative nitrogen balance were not statistically significant. Amino acid composition appeared to be important in that the group receiving the leucine-enriched solution appeared to maintain hepatic protein synthesis better (as manifest by higher short-turnover plasma protein concentrations) and required less exogenous insulin to maintain euglycemia. Improved outcome was not seen in the groups receiving the branched chain-enriched solutions.

Adolescent↗

Use of a branched chain amino acid enriched solution in patients under metabolic stress.

The metabolic response to stress results in proteolysis, increased gluconeogenesis, and negative nitrogen balance. Infusion of BCAA has been shown experimentally to decrease protein degradation and stimulate protein synthesis. Such infusion may modify the response of patients to metabolic stress. An amino acid solution containing 45 percent BCAA as a component of central vein parenteral nutrition was infused into 20 moderately to severely stressed postoperative patients in a prospective, nonrandomized fashion. Infusion was begun within 24 hours postoperatively and continued for 7 to 14 days. Patients received 1.6 g protein equivalents per kg body weight daily and 30 kcal/kg body weight daily. Nutritional indexes as measured by albumin and transferrin values were maintained during the study period. Nitrogen balance became increasingly positive over the period of infusion without an increase in the urinary excretion of 3-methylhistidine. There were no serious clinical or biochemical side effects of the BCAA infusion, although a statistically significant increase in alkaline phosphatase was observed. These results suggest that central vein parenteral nutrition utilizing a 45 percent BCAA enriched solution can promote nitrogen retention without serious side effects in moderately to severely stressed patients.

Adolescent↗