Cyproterone, norethindrone, medroxyprogesterone and levonorgestrel are less potent local human growth hormone and insulin-like growth factor I secretion stimulators than progesterone in human breast cancer explants expressing the estrogen receptor.

The aim of the present study was to compare the ability of natural progesterone and synthetic progestins to stimulate local growth hormone (GH) and insulin-like growth factor I (IGF-I) secretion by breast cancer explants. Explants obtained during surgery were divided according to their estrogen/progesterone receptor phenotype - ER(+)PR(-); ER(+)PR(+); ER(-)PR(+) - as determined by immunocytochemistry. Natural progesterone (10(-5) mol/l) and synthetic progestins (cyproterone acetate (5 x 10(-7) mol/l), norethindrone (10(-5) mol/l), medroxyprogesterone acetate (10(-7) mol/l), and levonorgestrel (10(-7) mol/l) were tested in vitro for their ability to induce secretion of proliferation-promoting agents such as human GH (hGH) and IGF-I. All hormone-dependent breast cancer cell types responded to progesterone stimulation with increased local hGH secretion, while in the non-malignant tissue this effect was observed only in PR(+) cells. Moreover, progesterone in only PR(+) cells in vitro stimulated local IGF-I secretion by both malignant and non-malignant tissue. Medroxyprogesterone and levonorgestrel increased GH secretion by both malignant and non-malignant ER(-)PR(+) breast cancer explants, while cyproterone stimulated it only in non-malignant tissue. None of the synthetic progestins tested in this experiment exerted an effect on GH secretion by both malignant and non-malignant tissue of ER(+) breast cancer explants. The present data additionally showed that, apart from cyproterone, which increased IGF-I secretion in the same manner as progesterone by both malignant and non-malignant ER(-)PR(+) breast explants, other progestins tested had either no effect on IGF-I local secretion or decreased it. Medroxyprogesterone and levonorgestrel induced a decrease in IGF-I secretion noted in ER(+) explants of non-malignant tissue and in malignant ER(-)PR(+) breast tissue. All progestins tested decreased IGF-I secretion by malignant ER(+)PR(+) explants. Taken together, the tested synthetic progestins widely used as oral contraceptives and in hormone replacement therapy were less potent than progesterone in inducing secretion of proliferation-promoting agents such as hGH and IGF-I in ER-containing breast tissue. Despite the lack of confirmation of the link between the use of progestins and breast cancer risk, patients should be informed that the use of certain estrogen/progestin preparations is of no influence on breast cancer risk while others may increase it.

Contribution of age and gender to outcome of blunt splenic injury in adults: multicenter study of the eastern association for the surgery of trauma.

BACKGROUND: The purpose of this study was to examine the contribution of age and gender to outcome after treatment of blunt splenic injury in adults. METHODS: Through the Multi-Institutional Trials Committee of the Eastern Association for the Surgery of Trauma (EAST), 1488 adult patients from 27 trauma centers who suffered blunt splenic injury in 1997 were examined retrospectively. RESULTS: Fifteen percent of patients were 55 years of age or older. A similar proportion of patients > or = 55 went directly to the operating room compared with patients < 55 (41% vs. 38%) but the mortality for patients > or = 55 was significantly greater than patients < 55 (43% vs. 23%). Patients > or = 55 failed nonoperative management (NOM) more frequently than patients < 55 (19% vs. 10%) and had increased mortality for both successful NOM (8% vs. 4%, p < 0.05) and failed NOM (29% vs. 12%, p = 0.054). There were no differences in immediate operative treatment, successful NOM, and failed NOM between men and women. However, women > or = 55 failed NOM more frequently than women < 55 (20% vs. 7%) and this was associated with increased mortality (36% vs. 5%) (both p < 0.05). CONCLUSION: Patients > or = 55 had a greater mortality for all forms of treatment of their blunt splenic injury and failed NOM more frequently than patients < 55. Women > or = 55 had significantly greater mortality and failure of NOM than women < 55.

Progesterone-induced secretion of growth hormone, insulin-like growth factor I and prolactin by human breast cancer explants.

The aim of the study was to evaluate the potential of human breast cancer tissue to secrete growth hormone (GH), insulin-like growth factor I (IGF-I) and prolactin in response to 10(-7) M progesterone stimulation. Explants were divided according to estrogen receptor (ER)/progesterone receptor (PR) phenotype (ER(-)PR(-); ER(+)PR(-); ER(+)PR(+); ER(-)PR(+)). Our results show distinct differences in cultured breast cancer tissue responses to progesterone stimulation with regard to secretion of proliferative agents such as GH, IGF-I and prolactin. All but ER(-)PR(-) breast cancer cell types responded in vitro to progesterone stimulation with an increase in local GH secretion, while in non-malignant tissue progesterone induced local GH secretion only in PR(+) cells. Moreover, only in PR(+) cells did progesterone stimulate local IGF-I and prolactin secretion, in both malignant and non-malignant tissue. This study provides evidence for the first time that in PR(+) breast cancer tissue, progesterone may increase GH, prolactin and IGF-I secretion in both malignant and surrounding non-malignant tissue. These hormones may act as local growth factors that stimulate the proliferation of mammary tumors.

Organ donation: a statewide survey of trauma surgeons.

PURPOSE: Organ procurement organizations (OPOs) operate under the premise that Americans would donate organs and/or tissue if placed in appropriate circumstances. This study evaluated opinions of Pennsylvania trauma surgeons regarding OPOs and organ donation. METHODS: Ninety-six Pennsylvania trauma surgeons were surveyed and descriptive results calculated. RESULTS: Ninety percent were familiar with criteria for organ donation, and about 76% would invoke their institution's brain death policy even if families did not desire to donate organs. A small portion did not routinely pronounce patients brain dead that met criteria. One fourth indicated trauma surgeons should have no role in requesting organs. A majority believed trauma surgeons should have a role in organ donation requests, either alone or with an OPO representative, and most indicated that they could influence a family's decision. CONCLUSION: Requestor attitude is important, and our results show an overall positive attitude toward donation and a solid level of knowledge regarding donor eligibility. Hospital development programs to improve donation consent should emphasize decoupling of brain death discussion and donation request, work to improve staff attitudes about approaching patients, and address donor eligibility criteria.

Colonoscopy in octogenarians and older patients.

INTRODUCTION: Colonoscopy in the elderly has been considered by many to be risky because of mechanical bowel preparation and dehydration, electrolyte disturbances, conscious sedation, and hypoxic complications. We hypothesized that colonoscopy in octogenarians and older patients is a safe procedure. MATERIALS AND METHODS: A retrospective review of 803 patients who underwent colonoscopy from January 1997 to October 1997 was performed. The patients were grouped by age: group A (17-49 years) had 166 patients (20%); group B (50-79 years) had 534 patients (67%); and group C (80 years and older) had 103 patients (13%). Results were considered significant at p value less than 0.05 unless otherwise noted. RESULTS: Blood in the stool (84%) and history of colonic vascular disease (5.8%) were the most common indication in group C (84%). Colonoscopy was used in group A (18%) more often than in the other groups to rule out inflammatory bowel disease. History of colon polyps was a more common indication in group B (20%) than in the other groups. Group A had a significantly higher incidence of normal examinations (84%) and diagnosis of inflammatory bowel disease (14%). Group B had a higher incidence of polyps than the other groups. Group C had the highest incidence of vascular disease (15%). Diverticular disease and carcinoma were more common in groups B (37%) and C (52%). The amount of sedation in the groups did not significantly differ. Completion of the colonoscopy to the cecum or anastomotic sites did not differ among the groups (p > 0.05), nor did complication rates among groups (p > 0.05). CONCLUSIONS: Colonoscopy is safe in octogenarians and older patients. Age does not, by itself, confer an increased risk to the procedure.

Traumatic carotid artery dissection: a significant incidental finding.

Blunt traumatic carotid artery dissection remains controversial in terms of diagnostic screening, reported incidence, and management. Treatment options include observation, anticoagulation and endovascular stenting, and aggressive surgical repair of the carotid artery injury. Blunt traumatic carotid artery dissections were reviewed through a retrospective study of trauma registry records. Seven patients were identified from 3342 patients over 3 years. Six patients were identified incidentally during magnetic resonance imaging (MRI) cervical spine/brain screening and one patient during angiographic evaluation for possible penetrating neck injury without MRI/magnetic resonance angiography (MRA). A total of 189 patients underwent MRI screening over this 3-year period, demonstrating a relative incidence of 3.7 per cent, contrasting with the reported incidence of 0.08 to 0.4 per cent for all trauma patients. All seven patients suffered severe head injuries (mean Glasgow Coma Score = 4.7) requiring mean intensive care unit and hospital stays of 15.6 and 23.7 days, respectively. None of the patients showed evidence of stroke with CT scanning on presentation. None of the patients demonstrated clinical focal neurologic signs or symptoms indicating carotid injury or stroke. Six patients survived their acute trauma and were discharged to rehabilitation after initiation of observation (one patient) or anticoagulation (five patients). All six patients showed neurological improvement without deterioration clinically or radiographically. In conclusion we propose early aggressive screening through MRI/MRA of severely injured patients to detect occult carotid artery dissections. Conservative medical treatment for this occult injury has been effective in this series of patients.

Axillary lymph node dissection in breast cancer: an evolving question?

Axillary lymph node dissection (ALND) is performed for staging purposes. Sentinel lymph node biopsy may decrease the cost and morbidity of ALND. Are there patients that the procedure is not indicated avoiding cost and morbidity? We retrospectively studied the incidence of lymph node metastasis in 423 patients with T1 breast cancer. Thirty-one T1a, 146 T1b, and 246 T1c tumors were seen. The mean age was 61 years. Ten per cent were premenopausal, and 84 per cent were postmenopausal. Tumor size averaged 1.29 cm. Eighty-one per cent of the tumors were node negative and 19 per cent were node positive. One T1a patient (3 per cent) had an axillary metastasis, 19 T1b patients (13%), and 61 T1c patients (25%) were node positive, respectively. Seventy-three per cent were ER positive. Thirty-three patients (8%) died from cancer. Eighty-seven per cent received surgery with axillary lymph node dissection (ALND), and three per cent had surgery without ALND. Younger age, increased tumor size, premenopausal status, and ER negativity affected node positivity rates (P < 0.05). Death from breast cancer was more common among node-positive patients (P < 0.05). No difference was found regarding the performance of ALND and survival (P > 0.05). We feel that ALND can be safely omitted in T1a to reduce the morbidity and the expense of breast cancer treatment. In T1b and T1c tumors, the use of ALND is necessary, but morbidity and cost can be reduced by the use of sentinel lymph node biopsy.

[Single sigmoidoscopy for screening of colorectal cancer]. / Jednorazowa sigmoideoskopia w badaniach przesiewowych raka jelita grubego.

Once-only sigmoideoscopy of person aged 57 is successful and safe method of screening of colorectal cancer. However acceptance of invitation to screening was about 25%. Because of that we postulated once-only sigmoideoscopy screening for patients aged 57 hospitalized from other than digestive tract neoplasms causes.

Inhibition of adenovirus DNA polymerase by modified nucleoside triphosphate analogs correlate with their antiviral effects on cellular level.

Adenovirus (Ad) infection results in significant morbidity and mortality in both immunocompetent and immunosuppressed hosts. There is currently no licensed chemotherapy effective in dealing with this virus infection. In this study the anti-adenoviral activity of a group of modified nucleoside analogs was investigated. The most efficient 3-fluorosubstituted nucleoside triphosphate inhibitors of Ad DNA polymerase were 3'-fluorothymidine triphosphate (IC50 0.63 microM), 2',3'-dideoxy-3'-fluoroguanosine triphosphate (IC50 0.71 microM) and 2',3'-dideoxy-3'-fluorouridine triphosphate (IC50 2.96 microM). The most efficient 2',3'-dideoxynucleoside triphosphates were 2',3'-dideoxycytidine triphosphate (ddCTP; IC50 1.0 microM), 2',3'-dideoxyadenosine triphosphate (IC50 1.6 microM) and 2',3'-dideoxythymidine triphosphate (IC50 1.82 microM). Kinetic studies indicate competitive inhibition of adenovirus DNA polymerase by ddCTP. These data confirm results previously obtained at the cellular level using a focus reduction assay involving Ad2-infected FL cells. Whereas the D-enantiomers 3'-fluorothymidine and 2',3'-dideoxycytidine are potent inhibitors of adenoviral replication, the corresponding L-enantiomers exhibited no inhibitory activity.

Managing intractable pain with an intrathecal catheter and injection port: technique and guidelines.

The objective of our study was to describe an effective technique for the management of chronic intractable pain in patients with intermediate life expectancy or as a long-term screening device prior to implantable pump therapy. In the study, an InDura intraspinal catheter is connected to a BardPort, which is accessed transdermally. We describe our surgical technique, recommended dosage calculations, cost comparison to an implantable infusion pump, and our experience with 13 cases. In our series of 13 patients, there was one seroma and one dural leak. There were no infections, and all were functioning well in the 12 cancer patients until their deaths. One case was converted to an implantable pump. There were no malfunctions or infections of the intrathecal infusion system in the 12 cancer patients. This intrathecal drug infusion system should be considered in the treatment armamentarium for chronic intractable pain and cancer pain.

Cofactors of alcohol-related trauma at a rural trauma center.

To analyze the cofactors of alcohol-related trauma at a rural, Level II trauma center, 127 admitted trauma patients were interviewed about psychological problems, social factors, and medical histories. Patients were divided into two groups, blood alcohol content (BAC) positive and BAC negative, for analysis. Seventy-one patients (56%) were BAC negative; 56 (44%) were BAC positive. Forty-three of the 82 males (52%) had positive BAC tests, compared with 13 of the 45 females (29%) (P = .01). Fifty-one of the 56 BAC-positive patients (91%) were aged 21 to 50 years, compared with 29 of the 71 BAC-negative patients (41%) (P = .0001). Ten of the 12 patients (83%) who were recently unemployed were BAC positive, compared with 46 of the 115 patients (40%) who were not recently unemployed (P = .004). Eleven of the 12 patients (92%) with positive drug screens were BAC positive, compared with 45 of the 115 patients (39%) with negative drug screens (P = .0005). These results show that there are important cofactors of alcohol-related trauma in rural areas.

HIV infection among rural trauma patients: a blind serosurvey and literature review.

Human immunodeficiency virus (HIV) seroprevalence rates among rural trauma patients range between 0.15 and 1.32 per cent. A random sample of trauma patients treated at our rural trauma center between September 1994 and November 1995 was enrolled into a blind HIV serosurvey. Five hundred sixty-six of 1315 trauma patients (43%) were tested. Two of the 566 patients (0.35%) were HIV positive. A review of aggregate data for HIV infection among rural trauma patients in the United States show that 28 of the 4639 patients (0.60%) are HIV positive. We conclude that there was a low HIV incidence among our trauma patients from September 1994 to November 1995, and the cost-effectiveness of HIV testing for rural trauma patients is questionable with incidences between 0.5 and 1.0 per cent.

Complications of epidural infusions for analgesia in postoperative and trauma patients.

Few studies compare complications of continuous and bolus epidural analgesia. Ninety-eight postoperative and trauma patients receiving epidural infusions over 15 months were retrospectively studied. Continuous epidural analgesia was used for pain management in 60 patients (61%). Bolus epidural analgesia was administered to 38 patients (39%). Sixty patients reported 98 complications. Sixty-eight per cent of complications occurred in patients receiving continuous infusions. For the continuous infusions, motor blockade (18%), nausea/vomiting, (18%), and catheter leaks (12%) were the most common complications. For bolus infusions, nausea/vomiting (25%), mental status changes (21%), and erythema at placement site (13%) were encountered. Continuous infusions were associated with an increased incidence of complications compared with bolus infusions (P < 0.05). Patients undergoing abdominal surgery had an increased incidence of complications compared with other patients (P < 0.05). Epidural catheters are safe and effective for pain management, but they are not without risk. Hemodynamic stability and pulmonary status should be considered when evaluating patients.

[Surgical treatment of lung cancer in patients over 80 years of age]. / Khirurgicheskoe lechenie raka legkogo u lits starshe 80 let.

Growth of the specific fraction of individuals over 80 years of age among patients with lung carcinoma is illustrated by its incidence in Moscow. These patients account today for up to 8% of the total number of cases. Some of them may be successfully treated by operation. This was demonstrated in 11 cases. Recommendations on pre- and postoperative management of such patients are given. The authors emphasize that the patient's fate and the method of treatment should be prescribed only in an oncological medical institution.