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Biomedical subjects

E Newman

Publications and source records attributed to E Newman.

At least 37 records · Page 2Linked to original sources

Thematic resolution, PTSD, and complex PTSD: the relationship between meaning and trauma-related diagnoses.

The role of modifying schemas in trauma-focused psychotherapy has received theoretical and clinical attention. However, the relationship of schematic processing to posttraumatic stress disorder (PTSD) diagnosis has not been examined empirically. The current study-compared measures of thematic disruption among individuals with PTSD alone, PTSD with concurrent complex PTSD, and no PTSD. Eighty two participants were interviewed to assess PTSD status, complex PTSD status, traumatic life events, and trauma-related thematic processing. Results indicated that variables quantifying thematic disruption and thematic resolution significantly distinguished those individuals with concurrent PTSD plus complex PTSD from the other two groups. Exploratory analyses indicated that PTSD symptom severity and the interpersonal nature of the trauma were related to thematic disruption.

Adaptation, Psychological↗

Heart disease education and prevention program targeting immigrant Latinos: using focus group responses to develop effective interventions.

Although research has provided considerable knowledge concerning the positive effects of behavioral change on morbidity and mortality from heart disease and related risk factors, some segments of the population have not benefited equitably from this information. In April 1995, the National Heart, Lung, and Blood Institute (NHLBI) conducted seven focus groups to determine knowledge and attitudes about heart disease and associated risk factors, identify media usage and preferences, and assess publications usage and preferences among Spanish-speaking Latino immigrants residing in the Washington, D.C., metropolitan area. This information was gathered to assist in the development of key messages and strategies for the NHLBI Latino Community Cardiovascular Disease Prevention and Outreach Initiative, Salud para su Corazón--a heart disease prevention and education campaign. Findings from these focus groups indicate that Latinos may not benefit from heart disease prevention messages developed for the general population because of language and cultural differences. The researchers concluded that health education and disease prevention programs targeting the Latino community should develop educational materials and interventions that address language preferences and cultural values. Furthermore, to be effective, these programs should show people how to make positive behavioral changes based on their current circumstances, while remaining sensitive to the fact that Latino immigrants face major life adjustments and many are still greatly influenced by their country of origin.

Adolescent↗

A combined laparoscopic and endoscopic approach to acute primary gastric volvulus.

We describe the combined use of laparoscopic and endoscopic techniques in a case of acute primary gastric volvulus. Once the diagnosis is confirmed with a water-soluble upper gastrointestinal series, prompt intervention is required. With an atraumatic bowel grasper the stomach is re-oriented with the greater curvature in its normal anatomic position. Two transabdominal wall sutures are placed along the greater curvature to fix it to anterior abdominal wall. Upper endoscopy is then performed. Once confident that the gastric mucosa is viable, a 20F "pull-type" gastrostomy tube is placed endoscopically, guided by the external illumination and probing by the laparoscope. The gastrostomy tube now acts as an anterior anchor for the stomach allowing repositioning of the gastropexy sutures if necessary. Endoscopy confirms the placement of a broad, properly aligned gastropexy. Classically, gastric volvulus has been treated by laparotomy. Both endoscopic and laparoscopic techniques have been individually reported in the treatment of acute and chronic gastric volvulus, however, each has as its limitations. By combining the procedures we were able to better assess both the intra-abdominal and the intraluminal status of the stomach and its position before, during, and after fixation to the anterior abdominal wall. The postoperative stay seen with the combined technique was less than has been reported in patients treated by open surgery or by either the endoscopic or laparoscopic methods alone. The combined laparoscopic and endoscopic approach to acute gastric volvulus provides the benefit of a minimally invasive approach, to a better anterior gastropexy. This procedure should be considered when confronted with patients with acute primary, gastric volvulus.

Acute Disease↗

Prognostic factors associated with long-term survival for retroperitoneal sarcoma: implications for management.

PURPOSE: Retroperitoneal soft tissue sarcomas are rare tumors. Studies characterizing long-term follow-up and patterns of recurrence are limited. The purpose of this analysis is to identify patterns of recurrence and prognostic factors associated with long-term survival after resection of retroperitoneal soft tissue sarcomas. METHODS: Between July 1, 1982, and June 30, 1990, 198 adult patients were identified from our prospective soft tissue sarcoma database carrying the diagnosis of retroperitoneal soft tissue sarcoma who were eligible for > or = 5 years of follow-up. Of these, 48 patients (25%) were documented to be alive > or = 5 years from the time of operation. Statistical analysis was by log-rank or Wilcoxon test for univariate analysis. Multivariate analysis was by the Cox model. RESULTS: The recurrence rate during the follow-up period was approximately 5% per year from the time of initial operation. Of the patients who were disease-free for > or = 5 years from initial surgery, 40% recurred by 10 years. Radiation therapy was the only factor significant (P = .02) for a reduction in the risk of local recurrence. Age < or = 50 years and high-grade tumors were significant factors (P = .003 and .009, respectively) for an increased risk of distant metastasis. Incomplete gross resection was the only factor significant for an increased risk of tumor mortality (P = .003). CONCLUSION: Complete surgical resection at the time of primary presentation is likely to afford the best chance for long-term survival. With long-term follow-up, it is clear that recurrence will continue to occur, and a 5-year disease-free interval is not a cure. Patients with an incomplete initial resection, age less than 50 years, and high-grade tumors are candidates for investigational adjuvant therapy.

Disease-Free Survival↗

The effect of blood transfusion on tumor growth in sarcoma-bearing rats.

BACKGROUND: The effect of blood transfusion on tumor growth is controversial. Under experimental conditions, even similar animal models can give varied results. This study was undertaken to characterize the nature of the effect of blood transfusion on tumor growth. METHODS: Sixty-five Fischer 344 rats subcutaneously implanted with a methylcholanthrene-induced sarcoma were studied with additive blood transfusion at 1% tumor burden in two separate experiments. In experiment 1, the effects of syngeneic fresh whole blood transfusion (5, 10, and 15 ml/kg) and allogeneic (5 ml/kg) were tested. To determine if stored blood influenced the results, experiment 2 was performed with syngeneic blood transfusion (15 ml/kg) and allogeneic blood transfusion at 5 ml/kg. Tumor dimensions were determined daily by external measurement, and tumor weight and growth rate were calculated. RESULTS: No significant differences in final tumor weights or tumor growth rates were found in transfused rats compared with controls. This held true for syngeneic blood transfusion regardless of dose, allogeneic blood transfusion, and regardless of whether the blood was fresh or stored. CONCLUSIONS: Additive blood transfusion does not affect tumor growth in this animal model. This finding, together with the general inconclusiveness in the reported literature on this topic, speaks against a dominant role for the effect of blood transfusion on tumor behavior.

Animals↗

The Müller cell: a functional element of the retina.

Müller cells are the principal glial cells of the retina, assuming many of the functions carried out by astrocytes, oligodendrocytes and ependymal cells in other CNS regions. Müller cells express numerous voltage-gated channels and neurotransmitter receptors, which recognize a variety of neuronal signals and trigger cell depolarization and intracellular Ca2+ waves. In turn, Müller cells modulate neuronal activity by regulating the extracellular concentration of neuroactive substances, including: (1) K+, which is transported via Müller-cell spatial-buffering currents; (2) glutamate and GABA, which are taken up by Müller-cell high-affinity carriers; and (3) H+, which is controlled by the action of Müller-cell Na(+)-HCO3- co-transport and carbonic anhydrase. The two-way communication between Müller cells and retinal neurons indicates that Müller cells play an active role in retinal function.

Animals↗

Substernal goiter.

The management of a substernal goiter is a problem which has challenged surgeons since its first description in 1749. While the overall incidence in the United States has decreased with the routine use of iodized salt, the development of large multinodular substernal goiters in the rest of the world is still common. In addition, even in those regions where they are less common, knowledge of their treatment is important as they can represent up to 7% of mediastinal tumors. Certainly, the majority are large, benign masses found in the superior and anterior mediastinum, although from 3 to 15% can be malignant in nature. The presenting symptoms generally relate to the compressive nature of the mass on nearby structures. Up to 90% of patients report some form of respiratory symptoms in association with these masses. Diagnostic evaluation should include chest x-ray and computed tomographic (CT) scan. Needle aspiration biopsy should be avoided due to its dangerous substernal location. The treatment is surgical, as medical therapy is generally unsuccessful. Perioperative management should include careful evaluation of the airway as the extent of compression and deviation caused by the mass can lead to a difficult intubation. The vast majority of substernal goiters can be removed via a cervical incision; occasionally sternotomy or thoracotomy is necessary. Although rare, tracheomalacia secondary to prolonged compression of the trachea by the mass needs to be watched for postoperatively. Overall, the results of surgical treatment are excellent, as morbidity and mortality are minimal and patients can expect full relief of symptoms secondary to these mediastinal masses.

Female↗

The potential of sheep for the study of osteopenia: current status and comparison with other animal models.

There is a great need to develop an animal model for postmenopausal osteoporosis; a model that will be useful for the understanding of the pathogenesis of the disease as well as the investigation of new therapies. The requirements for such an animal model are discussed and ones that have been used in the past include nonhuman primates, dogs, cats, rodents, rabbits, guinea pigs, and minipigs. Advantages and disadvantages of these models are briefly reviewed. Sheep are a promising model for various reasons; they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and have hormone profiles similar to women. Ovariectomy results in a slight loss of bone from the ovine iliac crest, and biochemical markers such as osteocalcin are well characterized. Physiological disadvantages are lack of natural menopause, that normal estrus cycles are restricted to fall and winter and that they have a different gastrointestinal system. Sheep have cortical bone that is plexiform in structure although haversian remodeling is seen in older animals. When and if biomechanical incompetence of bone follows ovariectomy is presently unknown. There is no ideal model for the study of postmenopausal osteoporosis; all have advantages and disadvantages. Researchers in this field must recognize the limitations of the model they choose, and select one that will fulfill their needs.

Absorptiometry, Photon↗

Comparison of serum CA 72-4 and CA 19-9 levels in gastric cancer patients and correlation with recurrence.

BACKGROUND: This longitudinal prospective study evaluates the serum levels of the tumor markers CA 72-4 and CA 19-9, alone or in combination, in gastric cancer patients. PATIENTS AND METHODS: Serum tumor markers CA 72-4 and CA 19-9 were measured in 52 patients who had gastric adenocarcinomas and 32 with benign gastric disorders. Serial measurements of these markers were carried out in 30 cancer patients at a median follow-up time of 38 months. RESULTS: CA 72-4 and CA 19-9 had sensitivities of 42% and 46% for the preoperative detection of gastric cancer. Sensitivity for the two combined was 63%. CA 72-4 provided 100% specificity, compared to 72% for CA 19-9. Postoperatively, 17 cancer patients remained disease-free. Sixteen of these maintained normal levels of CA 72-4, and 10 of CA 19-9. Thirteen patients developed recurrent disease. In 9, serum CA 72-4 levels rose from near-normal after surgery and reached diagnostic values approximately 6 months before clinical diagnosis of recurrence. Only 3 patients exhibited such a pattern with CA 19-9. CONCLUSIONS: CA 72-4 is a reliable marker in gastric cancer. Postoperative serial sampling of CA 72-4 may facilitate early identification of recurrences.

Adenocarcinoma↗

Clinical presentation of disorders of extreme stress in combat veterans.

Disorders of extreme stress (DES), previously referred to as disorders of extreme stress not otherwise specified and/or complex posttraumatic stress disorder, is a proposed diagnosis designed to describe the symptom presentation of those repeatedly exposed to traumatic stressors. Little is known, however, about the applicability of DES to combat veterans. We clinically assessed combat veterans for the presence or absence of DES in order to provide descriptive clinical information about the severity and patterns of endorsement of DES symptoms among combat veterans. Results indicate that DES is relevant to veterans and the implications of these results for both diagnoses and treatment are discussed.

Combat Disorders↗

Transforming growth factor beta 1 (TGF beta 1) is an autocrine positive regulator of colon carcinoma U9 cells in vivo as shown by transfection of a TGF beta 1 antisense expression plasmid.

A transforming growth factor beta1 (TGF beta1) antisense expression plasmid under constitutive control of the Rous sarcoma virus promoter was introduced into the highly tumorigenic and invasive colon carcinoma U9A cell line, which uses its autocrine TGF beta1 as a growth-stimulating factor. Stable transfectants were infrequent, and only the K6 transfectant exhibited 39 and 33%, respectively, of the levels of TGF beta1 mRNA and active, secreted TGF beta1 protein of the parental line. K6 exhibited no change in TGF beta2 expression, and TGF beta3 expression was not detected in either parental or transfectant cells. Compared to the parental line, the K6 antisense transfectant exhibited a 3-fold increase in lag time in anchorage-dependent colony formation. The parental line was 44 times as invasive through a collagen l-coated polycarbonate membrane in vitro as K6 cells and, after s.c. injection at low-cell inocula, U9A cells induced tumors 75 times as large in vivo as did the K6 antisense transfectant. The decreases in in vitro invasion and anchorage-dependent colony formation seen in K6 cells were largely reversed by the addition of TGF beta1. Tumors that did arise from the K6 antisense transfectant cells had lost antisense TGF beta1 expression and expressed the same TGF beta1 mRNA levels as controls. U9A cells were more metastatic to the liver after intrasplenic injection than K6 cells. These findings demonstrate a role for autocrine TGE beta1 in colon cancer tumorigenicity and invasion. They also show that a relatively small decrease in TGF beta1 levels was enough to markedly decrease colon carcinoma cell aggressiveness. This is not unprecedented, as we had found in an earlier study that a small, 2-4-fold increase in TGF beta1 protein levels in human colon cancers correlated with disease progression to metastases (E. Friedman et al., Cancer Epidemiol, Biomarkers & Prev., 4:549-554, 1995).

Animals↗

Phase I study of 5-day continuous infusion fluorodeoxyuridine and high-dose folinic acid with oral hydroxyurea.

Fluorodeoxyuridine (FUdR), the deoxynucleoside metabolite of 5-fluorouracil (5-FU), can be converted in a single step to fluorodeoxyuridine monophosphate (FdUMP), which binds covalently to thymidylate synthase (TS). Ribonucleotide reductase, an obligatory enzyme in the synthesis of deoxynucleotides, can be inhibited by hydroxyurea. Recognizing the well-established synergism between 5-FU and folinic acid (leucovorin), we hypothesized that the simultaneous administration of FUdR, leucovorin, and hydroxyurea might afford more effective inhibition of TS. Thirty-six patients with neoplastic disease considered refractory to standard therapy were entered into this phase I protocol. Treatment was administered on days 1 through 5 of a 28-day cycle and consisted of folinic acid (500 mg m-2 day-1) and FUdR at escalating doses of 0.1, 0.15, or 0.2 mg kg-1 day-1 both administered by continuous i.v. infusion, and hydroxyurea given p.o. once per day at doses ranging from 0 to 250o mg in 500-mg increments. The hydroxyurea and FUdR levels were escalated in a sequential fashion. The majority of patients had refractory breast or lung cancer. Dose-limiting toxicities were mucositis and diarrhea at the maximally tolerated dose of 0.15 mg/kg FUdR and 2000 mg hydroxyurea per day in conjunction with high-dose folinic acid. Hematological toxicity was minor. Of the 18 patients in whom response could be evaluated, none had evidence of objective disease regression. Mucositis and diarrhea are the dose-limiting toxicities when continuous infusions of FUdR and high-dose folinic acid are combined with oral hydroxyurea, effects that are consistent with the observed toxicities for FUdR when administered alone or in combination with leucovorin.

Administration, Oral↗

Effect of perioperative blood transfusion on recurrence and survival in 232 primary high-grade extremity sarcoma patients.

BACKGROUND: Allogeneic blood transfusion (BT) has been implicated as an unfavorable factor influencing cancer recurrence and overall survival. METHODS: To investigate this, 232 consecutive localized, high-grade extremity soft tissue sarcoma (STS) patients admitted between January 1, 1983, and December 31, 1989, were analyzed from our prospective database by univariable and Cox multivariable statistical methods. RESULTS: Twenty-eight patients developed a local recurrence (LR). Factors found significantly unfavorable for the rate of developing an LR by uni- and multivariable tests were age > 60 years and positive microscopic margin. Eighty-nine patients developed a distant metastasis (DM) and 72 patients died of their tumor. Median follow-up of survivors was 48 months. Unfavorable factors for DM and tumor mortality (TM) by univariable analysis included large size, deep tumor (that involved or was below the superficial fascia), positive microscopic margin, invasion of a vital structure, operative blood loss, duration of operation, and perioperative BT (whole blood or packed cells -24 to +48 h of curative operation). Multivariable analysis found large size, deep tumor, and positive margin significant independent unfavorable factors for DM and TM. The effect of BT was not a significant independent prognosticator for LR, DM, or TM by multivariable analysis (p = 0.26, 0.56, 0.08, respectively). The only factor that was found to be significant in a multivariable analysis of factors contributing to postmetastasis survival was time < 6 months until metastasis (p = 0.008). BT had no significant impact on postmetastasis survival (p = 0.42). There was a significant association between BT and deep, large tumors. As the size of deep tumors increased from < 5, > or = 5 < 10, > or = 10 < 15, or > or = 15 cm, the amount transfused was 15, 16, 49, and 68% (p < 0.00001). Also, BT was significantly (p < 0.005) associated with low hematocrit at initial diagnosis, blood loss during surgery, and the length of the surgical procedure. CONCLUSIONS: These data emphasize the importance of size, depth, and margin on distant recurrence and death for localized high-grade extremity STS. In the absence of a randomized trial, the impact of allogeneic blood transfusion would appear to be due to its strong association with large size and deep tumor invasion. This study also highlights the importance of a multivariable analysis and long-term follow-up to better define this controversial question.

Blood Transfusion↗

The effect of systemic hyperinsulinemia with concomitant amino acid infusion on skeletal muscle protein turnover in the human forearm.

In vitro, insulin has been shown to increase skeletal muscle (SM) protein synthesis and decrease SM protein breakdown. Whether these same effects are found in vivo in man is less clear. The study of the effect of hyperinsulinemia (INS) on SM protein turnover (SMPT) is complicated by hypoaminoacidemia, which can obviate the true effect of insulin on SMPT. To prevent this, we studied the effect of INS on SMPT in the human forearm with amino acid (AA) infusion to ensure adequate substrate for full evaluation of insulin's effect. Twelve healthy volunteers (aged 53 +/- 3 years) were studied. Steady-state AA kinetics were measured across the forearm after a systemic 2-hour primed continuous infusion of 3H-phenylalanine (3H-Phe) and 14C-leucine (14C-Leu) in the postabsorptive (PA) state and in response to systemic INS (71 +/- 5 microU/mL). AAs were infused during INS as 10% Travasol (Travenol Laboratories, Deerfield, IL) at .011 mL/kg/min to maintain PA branched-chain AA (BCAA) levels, known regulators of SMPT, and to mildly elevate total AA levels. The negative PA net balance of both Phe and total Leu carbons (LeuC) became positive with INS + AA infusion (Phe from -16 +/- 2 to 12 +/- 3 nmol/min/100 g [P < .01]; LeuC from -26 +/- 6 to 24 +/- 7 nmol/min/100 g [P < .01]).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of flushing of the liver graft upon plasma calcium and magnesium concentrations.

Previous studies of total and ionized calcium in the plasma of liver transplant recipients have been conducted in patients with preexisting liver disease or who received blood transfusion. The intraoperative decline in plasma total and ionized calcium has been attributed to the effects of liver disease and/or the citrate in transfused blood. The present study was conducted in normal porcine recipients of liver stored either with EuroCollins or University of Wisconsin (UW) solution for 6 hr, compared with livers flushed with Ringer's lactate without storage. No blood transfusion was given. Mean total plasma calcium levels declined significantly after storage with UW solution to a nadir approximately 65-70% of preoperative levels. This decline persisted for two to five days. Mean levels of plasma ionized calcium declined lowest after flushing with UW solution but only to 82% of preoperative (NS). There was an increase in plasma total magnesium in the recipients of livers flushed with EuroCollins or UW solutions, which resolved within 30 min and which was probably related to magnesium content of the flushing solution. It is concluded that while the changes in plasma total and ionized calcium are moderate and of little clinical significance, they could be aggravated under clinical conditions by massive blood transfusion. Changes in plasma magnesium seemed to be directly attributable to the magnesium content of flushing solutions but the same relationship did not exist for changes in plasma calcium.

Animals↗

Effect of systemic hyperinsulinemia in cancer patients.

Data defining the isolated effect of insulin on whole body protein and glucose metabolism in cancer patients are limited. Ten normal volunteers (controls), age 55 +/- 3 years (mean +/- SEM); 8 cancer patients, age 61 +/- 3 years, weight loss 2 +/- 1% (CANWL); and 8 cancer patients, age 55 +/- 2 years, weight loss 18 +/- 2% (CAWL), were studied in the post-absorptive state. Whole body leucine kinetics were determined during a baseline and then a study period during which insulin was infused at 1.0 milliunits/kg/min to achieve a high physiological level of 71 +/- 6, 83 +/- 5, and 64 +/- 5 microunits/ml in controls, CANWL, and CAWL, respectively. Whole body net balance equals protein synthesis minus protein breakdown. Glucose disposal (mg/kg/min) is the rate of D30 infusion at steady state. Glucose disposal of CANWL and CAWL during the study period was significantly (P less than 0.05, analysis of variance) less than controls (3.91 +/- 0.6 in CANWL, 3.66 +/- 1.0 in CAWL, and 5.87 +/- 0.6 mg/kg/min in controls), suggesting resistance to insulin with respect to carbohydrate metabolism. Hyperinsulinemia, under euglycemic and near basal amino acid conditions, significantly reversed the negative postabsorptive leucine net balance (P less than 0.05, analysis of variance) by decreasing protein breakdown in controls as well as weight-stable and weight-losing cancer patients, suggesting that cancer patients are not resistant to the anti-catabolic effect of insulin with respect to whole body protein metabolism.

Body Weight↗