The correlation between occupation type and fibromyalgia severity.

BACKGROUND: Fibromyalgia (FM) is a chronic pain disorder associated with financial burden, decreased work productivity and absenteeism. Occupational stressors and specific employment factors may contribute to the severity of FM. AIMS: To determine if occupation type or employment status correlates with FM diagnostic and severity parameters, as assessed via validated instruments including tender points (TP), Widespread Pain Index (WPI), Symptom Severity (SS) and pain regions. METHODS: We performed a cross-sectional study of 200 adult patients diagnosed with FM at a single-centre FM clinic. Demographic and clinical data were extracted from the electronic medical records. Occupations were manually grouped in an iterative modified-Delphi approach and participants were grouped by employment status (Working, Not Working/Disabled or Retired) for analysis. RESULTS: In our cohort, 61% were employed and 24% were not working/disabled, while the remainder were students, homemakers or retired. SS score was significantly higher (P < 0.001) in not working/disabled patients compared to those employed. Business owners had the lowest TP count (median = 14) and the lowest median SS score (median = 7). WPI was highest for Others (Arts/Entertainment, Driver/Delivery and Housekeeper/Custodian workers; median=16) and the lowest for Retail/Sales/Wait Staff (median = 11). CONCLUSIONS: Work-related factors, occupation type and employment status correlate with diagnostic and severity parameters of FM. Employed participants had significantly lower SS scores suggesting that work loss correlates with SS. Participants employed in entry-level jobs or jobs with higher physical or financial stressors may experience greater FM symptoms. Further studies are required to explore work-related factors and their impact on the diagnostic and severity parameters of FM.

Induction of specific immune unresponsiveness with purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. II. An analysis of the effects measured at the cellular and serological levels.

T lymphoblasts specific for foreign histocompatibility antigens and purified via mixed leukocyte culture (MLC) and 1 g velocity sedimentation procedures can be used as autoimmunogen to produce specific immunological unresponsiveness in adult animals. This unresponsiveness is positively correlated to the production of autoanti-idiotypic antibodies in the blast immunized animals and no evidence of coexisting alloimmunity was found. We consider this autoanti-idiotypic immunity to be the specific inducing agent of the immune tolerance. The blast immunization procedure will lead to selective reduction in T-cell reactivity against the relevant alloantigens as measured by MLC, cell-mediated lympholysis, or graft-versus-host assays. However, in individual animals, dichtomy in suppression between two T-cell assays could sometimes be observed indicating elimination of only a select group of idiotypic functionally distinct population of T cells in these blast-immunized animals. Attempts to abrogate already immune animals by the autoblast procedure were successful, in part suggesting the use of the present procedure when trying to induce in accelerated reversion of such immunity.

Induction of specific immune unresponsiveness using purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. I. Demonstration of general validity as to species and histocompatibility barriers.

Normal immunocompetent T lymphocytes can be induced into specific proliferation if confronted with the relevant alloantigen in vitro. Such mixed leuko-cyteculture-activated T lymphoblasts carring idiotypic receptors on their surface can be purified using velocity sedimentation and serve as immunogen if administered in adjuvant to the autologous host. Autoblast immunization can be shown to lead to specific, long-lasting unresponsiveness against the relevant alloantigens, while leaving reactivity against third-party antigens intact. When tested as to general validity, it could be shown to function in all species analyzed (mouse, rat, and guinea pig) as well as across both major and minor histocompatibility barriers. No negative side effects have been noted so far. It would thus seem clear that autoblast immunization using the above described scheme may serve as a general tool in inducing long-lasting, specific unresponsiveness in any species and across any histocompatibility barrier.

Target and reality of adjuvant endocrine therapy in postmenopausal patients with invasive breast cancer.

Previous research evaluating the use of adjuvant endocrine therapy among postmenopausal breast cancer patients showed with 15-50% wide ranges of non-adherence rates. We evaluated this issue by analysing an unselected study group comprising of 325 postmenopausal women, diagnosed from 1997 to 2003 with hormonal receptor-positive invasive breast cancer. The different clinical situations that led to the discontinuation of adjuvant endocrine therapy were clearly defined and differentiated: non-adherence was not simply the act of stopping medication, but rather the manifestation of an intentional behaviour of the patient. Of the 287 patients who initiated endocrine therapy, 191 (66.6%) fully completed this treatment. Thirty-one patients (10.8%) showed non-adherence to therapy. Patients who had follow-up with a general practitioner, rather than in an oncologic unit, were more likely to be non-adherent (P=0.0088). Of 25 patients who changed medication due to therapy-related adverse effects, 20 (80%) patients fully completed the therapy after drug change. In adjuvant endocrine therapy, a lowering of the non-adherence rate to 10.8%, the lowest reported in the literature, is realistic when patients are cared for by a specialised oncologic unit focusing on the individual needs of the patients.

Levels of circulating cell-free serum DNA in benign and malignant breast lesions.

PURPOSES OF THE STUDY: We analyzed circulating cell-free DNA in the serum of patients with benign and malignant breast disease and in healthy individuals to determine its diagnostic value. BASIC PROCEDURES: Serum samples were obtained from 50 healthy individuals, 33 patients with malignant breast disease and 32 patients with benign breast disease. Circulatory DNA was extracted from serum samples. Cell-free DNA was quantified by real-time quantitative PCR for the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. Tissue samples from patients with malignant and benign breast lesions were histopathologically examined. MAIN FINDINGS: The mean levels of circulating cell-free DNA in serum samples were 41,149 genome equivalents (GE)/mL in patients with malignant disease, 30,826 GE/mL in patients with benign disease, and 13,267 GE/mL in healthy individuals. Healthy individuals had significantly lower levels of cell-free DNA than patients with malignant or benign breast disease (p=0.001, p=0.031). No significant difference was observed between malignant and benign disease. There was a correlation between cell-free DNA levels and tumor size but not with other tumor characteristics. PRINCIPAL CONCLUSION: Our results suggest that levels of circulating cell-free DNA in serum could have diagnostic value to discriminate between healthy individuals and patients with breast lesions but not between patients with malignant and benign breast lesions.

Breast cancer sagittal/horizontal plane location influences axillary lymph node involvement.

AIM: To assess the influence of tumour location on axillary lymph node involvement (ALNI) and prognosis in breast cancer by evaluating the significance of the sagittal/horizontal alignment. METHODS: We compared 57 patients with superficially located breast carcinomas up to 3.0 cm with patients having lesions in posterior planes of the breast. Both groups were matched according to age, time of diagnosis, tumour size, grade, hormonal receptor status and tumour site within the frontal plane. Histologic evidence of skin involvement, excluding tumours fulfilling the criteria for pT4b, was defined as inclusion criteria and reference plane for superficial tumour location. RESULTS: Tumours situated in the superficial region of the breast, compared to those located in deeper planes, have an increased risk of ALNI (p=0.023), whereas no difference was observed with reference to disease-specific survival (p=0.203). CONCLUSION: This study shows that ALNI is dependent on sagittal/horizontal as well as frontal tumour location. Clinicians should be aware that tumours lying posteriorly may be at increased risk of occult spread outside axillary lymph nodes.

[Chemotherapy for gynecological malignancies--a contraindication during pregnancy?]. / Chemotherapie bei gynäkologischen Tumoren--kontraindiziert in der Schwangerschaft?

Even though a malignant tumor during pregnancy is very rare it occurs in 0.02-0.1%. With the tendency in society to postpone childbirth to an older age, there will be more cancers diagnosed during pregnancy. The coincidence of malignant disease with pregnancy leads to an enormous emotional burden to the patient, the couple and the medical staff. Surgery for malignant tumors during pregnancy seems to be save. Radiotherapy on the other hand should be avoided. Chemotherapy is regarded to be save during the second and third trimester but it should not be applied during the first trimester because of its teratogenic effects. The most frequent malignant disorders during pregnancy are cervical cancer, breast cancer, melanoma and Hodgkin lymphoma. We discuss possible treatment options for breast cancer and gynecological tumors during pregnancy. Ovarian Cancer is a rare event during pregnancy. Because of frequent prenatal visits most of them are diagnosed at an early stage, with good prognosis. In case of advanced stage of ovarian cancer chemotherapy besides surgery is necessary. The former usually is preferred as monotherapy during pregnancy. To treat breast cancer during pregnancy a mastectomy with axillary lymphonodectomy is necessary to avoid radiotherapy. Indications for chemotherapy are the same as for not pregnant patients. Usually AC with and without 5-FU is used. For invasive cervical cancer surgery or radiotherapy +/- chemotherapy is indicated after induced abortion or cesarean section. Early termination of pregnancy is of no survival benefit to the mother in case of breast cancer and ovarian cancer. In these cases systemic therapy during pregnancy and delivery at 34 weeks is recommended.

Electrical cutting device for laparoscopic removal of tissue from the abdominal cavity.

The extraction of large tissue masses from the abdominal cavity during laparoscopic surgery is a time-consuming, complicated process. A new prototype instrument is introduced that allows quick laparoscopic removal of fibromas, ovaries, or other tissues from the abdomen. A cylinder with a coning knife at its intra-abdominal end is placed inside the trocar sleeve and is rotated by an electrical micro-engine attached to the trocar. Cylindrical tissue blocks are cut step by step out of the main specimen and removed from the peritoneal cavity through the sleeve with a grasping forceps. Tissue removed is suitable for histologic examination. The principal application is morcellation of fibromas, whereas use in ovarian disease is limited. This new device provides a safe and effective approach inside the abdominal cavity.

Aging, serum estradiol levels, and pregnancy differentially affect vascular reactivity of the rat uterine artery.

OBJECTIVES: To investigate the effects of aging, ovarian ablation, and pregnancy on vascular reactivity of the rat uterine artery. METHODS: Segments of uterine artery from 3-month-old pregnant and nonpregnant Wistar rats and from aged and ovariectomized animals, both 9 months of age, were exposed in vitro to vasoactive mediators. Absolute contractile force as well as endothelium-dependent and -independent vascular reactivity were determined. Isometric tension was recorded using a modified Mulvany myograph system. Results were compared with analysis of variance and Bonferroni-Dunn post hoc analysis and correlated with serum estradiol levels. RESULTS: Aging up to 9 months decreased absolute tension of uterine arteries in vitro elicited by KCl (P < .0001), while not affecting receptor-operated responses to norepinephrine, endothelin-1, and angiotensin II. After ovarian ablation maximal contraction to norepinephrine was selectively reduced in the aged animal (P = .0053). Pregnancy increased absolute tension to KCl (P < .0001), norepinephrine (P < .008), and endothelin-1 (P = .0003), whereas relative contractile force (percentage of KCl) induced by norepinephrine and endothelin-1 remained unchanged and that induced by angiotension II decreased (P = .0001) in pregnant animals. In addition, pregnancy increased sensitivity to the endothelium-dependent vasodilator acetylcholine (P = .0022) but decreased that to the endothelium-independent vasodilator sodium nitroprusside (P = .0062). Endothelium-dependent relaxation correlated with serum estrogen levels remained unchanged in 9-month-old Wistar rats, which physiologically exhibited high serum estrogen concentrations but was impaired with regard to both maximum relaxation (P < .0001) and sensitivity in aged rats (P = .0007) after ovariectomy. CONCLUSIONS: Vascular contractility is impaired in the uterine artery of the aged rat as evidenced by reduced responses to KCl, whereas responses to receptor-operated agonists remain unchanged. Functional ovaries are essential to preserve endothelium-dependent relaxation in aging animals. During pregnancy, contractile machinery and endothelium-dependent relaxation are enhanced. In contrast, contractions to angiotensin II and endothelium-independent relaxation to sodium nitroprusside are reduced in late pregnancy. These changes in reactivity of the uterine artery may be important for the regulation of blood flow in the uterus according to physiologic needs.

Chronic blockade of nitric oxide synthase and endothelin receptors during pregnancy in the rat: effect on reactivity of the uterine artery in vitro.

OBJECTIVE: To investigate the effects of chronic blockade of nitric oxide (NO) production and endothelin (ET-1) receptor antagonism on endothelial and vascular smooth muscle function of the uterine artery in vitro obtained from nonpregnant and pregnant rats. METHODS: Pregnant or nonpregnant Wistar rats were either treated orally for up to 18 days with the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the ETA-/ET beta-receptor antagonist bosentan, or both, or they received no treatment (controls). Absolute contractile force as well as endothelium-dependent and -independent vascular reactivity of uterine arteries were determined in vitro. Isometric tension was recorded. ANOVA and the Mann-Whitney U test were used for statistical analysis. RESULTS: Pregnancy increased absolute tension (mN/mm) elicited in uterine arteries by ET-1 (P < .01), serotonin (P < .05), norepinephrine (P < .02), and KCl (P < .0001). Chronic treatment with L-NAME or L-NAME plus bosentan, but not with bosentan alone, reduced contractions to KCl in pregnant and nonpregnant rats (P < .005-.0001), while pregnancy-induced enhancement in tension development remained unchanged in all groups (P < .005). After exposure of uterine arteries to L-NAME in vitro, vascular sensitivity to ET-1 was augmented in uterine arteries of pregnant but not of nonpregnant animals (P < .05). L-NAME-pretreatment did not influence the pregnancy-induced increase of vascular sensitivity to acetylcholine but reduced maximal relaxation in nonpregnant animals (P < .05). In addition, pregnancy diminished sensitivity of uterine arteries to sodium nitroprusside (P < .002), which was abolished by chronically administered L-NAME. Bosentan had no influence on vasodilation in vitro. CONCLUSION: Neither endothelin-1 nor nitric oxide seem to contribute to the augmented tension to depolarization and receptor-operated stimulation of vascular smooth muscle cells in rat uterine arteries during pregnancy. In addition, pregnancy is associated with increased NO production in uterine arteries, as evidenced by augmented endothelium-dependent relaxations, increased NO release by endothelin-1, and decreased sensitivity to sodium nitroprusside.

Chronic blockade of nitric oxide-synthase and endothelin receptors during pregnancy in the rat: effect on pregnancy outcome.

OBJECTIVES: To investigate the effects of endothelin-1 (ET-1) receptor antagonism and/or chronic blockade of nitric oxide (NO) production on pregnancy outcome in the rat. METHODS: Pregnant or nonpregnant Wistar rats were either treated orally for up to 18 days with the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the ETA-/ETB-receptor antagonist bosentan (Roche Basel, Switzerland) or both, or received no treatment (controls). Blood pressure, body weight, and drug intake were measured at regular intervals. Pregnancy outcome and proteinurea were also determined. Analysis of variance and paired Student t test were used for statistical analysis. RESULTS: Chronic L-NAME treatment increased systolic blood pressure by 69 and 64 mmHg in pregnant and virgin rats respectively (P < .05). Bosentan-blunted, L-NAME-induced hypertension at the beginning (P < .05), but not at the end of the treatment period in all rats examined. N omega-nitro-L-arginine methyl ester-treatment in pregnancy reduced the number of living fetuses at term (P < .05) and caused proteinurea (P < .05). Bosentan tended to reverse the effects of L-NAME on fetus number and proteinurea, but both effects failed to reach statistical significance. CONCLUSIONS: The effects of chronic, NO-synthase-blockade on blood pressure in gravid rats can be reversed only temporarily by ETA-/ETB-antagonism, suggesting an involvement of endothelin-1 in the early phase of the L-NAME-induced, preeclampsia-like syndrome during pregnancy, although at later stages other mechanisms may come into play.

Primary carcinoma of the fallopian tube. A report of 19 cases with literature review.

Primary carcinoma of the fallopian tube is the rarest cancer of the female genital tract with an incidence of 0.5% of all gynecologic tumors. Since the first report in 1847 about 1,500 cases have been published. Due to similarity of the clinical presentation the staging and therapeutic management have been adapted to that of ovarian cancer. We retrospectively evaluated all the 19 patients who had been diagnosed with primary carcinoma of the fallopian tube at the Department of Obstetrics and Gynecology of the University of Zurich between 1977 and 1998. All lesions were staged according to the rules of FIGO adopted in 1991. At the time of diagnosis the median age was 62 (46-87) years. Twelve (63%) women revealed FIGO stage III-IV, whereas four (21%) and three (16%) patients were diagnosed in stage I and stage II, respectively. Eight (42%) women were nullipara. Histology showed serous-papillary carcinoma, in ten (53%) cases. The 5-year survival rate was 22% for all FIGO stages and 80% for stage I. None of the patients with stage III and IV survived 5 years. Ovarian cancer and primary carcinoma of the fallopian tube are similar in many aspects. Both carcinomas have a similar age distribution, show an increase among nulliparous women, are often of serous papillary histology, have a poor prognosis with stage and residual tumor size as important prognostic factors, and respond initially well to platinum-based chemotherapy. Nevertheless, there appears to be a difference between the two diseases: primary carcinoma of the fallopian tube is more often diagnosed in an earlier stage. This many be due to lower abdominal pain resulting from tubal dilatation and to abnormal bloody-watery discharge.

[Chemotherapy of endometrial cancer revisited]. / Stellenwert der Chemotherapie in der Behandlung des Endometriumkarzinoms.

The current status and future directions of chemotherapy in the management of endometrial cancer are reviewed. For patients with advanced or recurrent endometrial carcinoma the most active single drugs are doxorubicin, epirubicin, cisplatin, carboplatin, paclitaxel, ifosfamide, 5-fluorouracil and vincristine with response rates ranging from 18 to 36%. Data at the present time support the conclusion that if chemotherapy is indicated a combination of doxorubicin + cisplatin is the standard chemotherapy for patients with advanced or recurrent endometrial carcinoma and yields a response rate of 47-60%. A first trial using a combination of these drugs with paclitaxel promises an increase in response rate to 73%, but data regarding prolongation of survival are not yet available. Up to now the benefit of neither chemotherapy nor endocrine therapy could be established in the adjuvant setting.

[Neurofibromatosis of the breast in a patient with Morbus von Recklinghausen]. / Neurofibromatose der Brust bei Morbus von Recklinghausen.

Neurofibromatosis is a rare autosomal dominant disorder with several subtypes. Common is the appearance of specific skin alterations. Neurofibromas occurring in the breast are very rare, and in such cases they are most common in the areolar area. A case of a 46-year-old woman with von Recklinghausen's disease of the breast is reported, and the literature will be discussed.

[Minimally invasive surgery in the treatment of extrauterine pregnancy]. / Minimal invasive Chirurgie zur Behandlung der Extrauteringravidität.

Of 147 patients operated by endoscopy, 86 (59%) were treated conservatively by linear salpingotomy or tubal aspiration and 61 (41%) were treated by salpingectomy. One patient with a history of bilateral salpingectomy had a cornual implantation and was also successfully treated by laparoscopic technique. There were no intraoperative complications. In eight patients (4.5%) with postoperative complications, a second operation was performed because of persistent trophoblast and/or hemorrhage. Six patients were treated by laparoscopic salpingectomy. All complications were associated with conservative treatment and typically occurred with a delay of up to 23 days. In six of these instances, the surgeon was rather inexperienced in laparoscopic operation. After an average follow-up time of 22 months, the pregnancy rate was 68%, of which 73% were intrauterine pregnancies. Laparoscopic treatment of ectopic pregnancies has proven to be an effective and safe procedure even at a teaching hospital. Since all complications occurred after conservative treatment this data suggests that salpingectomy should be the treatment of choice in ectopic pregnancy, whereas linear salpingotomy should only be performed when specially indicated.

[Preservation of fertility in tumour patients]. / Erhaltung der Fertilität bei Tumorerkrankungen.

The success rates of present-day chemotherapy have provoked a rising awareness with regard to the preservation of quality of life among successfully treated patients. Among other factors, quality of life also implies the capacity to procreate. Unfortunately, both in men and women chemotherapy often irreversibly destroys the production of gametes, thereby causing permanent infertility. By its long-standing experience with the cryopreservation of oocytes, zygotes and embryos, reproductive medicine may offer assistance to those patients. Whereas the storage of cryopreserved semen has now become standard in most institutions, the options for the preservation of fertility in women suffering of malignant disease are still limited. Although cryopreservation of non-fertilized oocytes or of pronuclear cells has been established, both the number of oocytes that can be collected within the short time interval between the first detection of the tumour and the initiation of chemotherapy and the modest developmental capacity per frozen/thawed oocyte markedly limit the option of ovarian hyperstimulation and assisted reproduction. Several successful deliveries of healthy infants have now proven the feasibility of ovarian tissue cryopreservation and later orthotopic transplantation after successful tumour therapy. Further refinement of the techniques involved, but also the formation of multidisciplinary networks are expected to offer a solution for young women struck by cancer but striving to survive and to lead a fulfilled life.