Association of ADAMTS7 gene polymorphism with cardiovascular survival in coronary artery disease.

Recent genetic studies have revealed an association between polymorphisms at the ADAMTS7 gene locus and coronary artery disease (CAD) risk. Functional studies have shown that a CAD-associated polymorphism (rs3825807) affects ADAMTS7 maturation and vascular smooth muscular cell (VSMC) migration. Here, we tested whether ADAMTS7 (A/G) SNP is associated with cardiovascular (CV) survival in patients with established CAD. A cohort of 1,128 patients with angiographic proven CAD, who were followed up prospectively for a mean follow-up period of 63 (range 6-182) mo, were genotyped for rs3825807 A/G. Survival statistics (Cox regression) compared heterozygous (AG) and wild-type (AA) with the reference homozygous GG. Kaplan-Meier (K-M) survival curves were performed according to ADAMTS7 genotypes for CV mortality. Results showed that 47.3% of patients were heterozygous (AG), 36.5% were homozygous for the wild-type allele (AA) and only 16.2% were homozygous for the GG genotype. During the follow-up period, 109 (9.7%) patients died, 77 (6.8%) of CV causes. Survival analysis showed that AA genotype was an independent risk factor for CV mortality compared with reference genotype GG (HR = 2.7, P = 0.025). At the end of follow-up, the estimated survival probability (K-M) was 89.8% for GG genotype, 82.2% for AG and 72.3% for AA genotype (P = 0.039). Carriage of the mutant G allele of the ADAMTS7 gene was associated with improved CV survival in patients with documented CAD. The native overfunctional ADAMTS7 allele (A) may accelerate VSMC migration and lead to neointimal thickening, atherosclerosis progression and acute plaque events. ADAMTS7 gene should be further explored in CAD for risk prediction, mechanistic and therapeutic goals.

Biaxial nematic phase in the Maier-Saupe model for a mixture of discs and cylinders.

We analyze the global phase diagram of a Maier-Saupe lattice model with the inclusion of shape-disordered degrees of freedom to mimic a mixture of oblate and prolate molecules (discs and cylinders). In the neighborhood of a Landau multicritical point, solutions of the statistical problem can be written as a Landau-de Gennes expansion for the free energy. If the shape-disordered degrees of freedom are quenched, we confirm the existence of a biaxial nematic structure. If orientational and disorder degrees of freedom are allowed to thermalize, this biaxial solution becomes thermodynamically unstable. Also, we use a two-temperature formalism to mimic the presence of two distinct relaxation times, and show that a slight departure from complete thermalization is enough to stabilize a biaxial nematic phase.

Caixa de lembranças: relato de experiência com um grupo de mulheres com queixa de depressão em uma clínica escola / Ingles - caixa de lembranças: relato de experiência com um grupo de mulheres com queixa de depressão em uma clínica escola / Espanhol - caixa de lembranças: relato de experiência com um grupo de mulheres com queixa de depressão em uma clínica escola

Este artigo apresenta um relato de experiência de duas estudantes do último ano da graduação em Psicologia, com a prática psicanalítica de grupos durante estágio obrigatório com ênfase em Saúde Mental, dentro de uma clínica escola, sob supervisão e orientação da professora supervisora. Os atendimentos foram baseados na perspectiva psicanalítica winnicottiana, com aplicação teórico-prática em um grupo terapêutico composto por mulheres com queixas de depressão, através da oficina terapêutica "Caixa de Lembranças". A proposta do grupo foi pautada no uso de um recurso mediador dialógico, que se caracterizou como materialidade mediadora, que tinha como objetivo favorecer a expressão emocional das integrantes do grupo, de forma livre e menos defendida, favorecendo condutas genuínas e espontâneas. A vivência da grupoterapia apontou a particularidade e subjetividade de cada caso e a necessidade em se adaptar o tratamento para cada indivíduo, uma vez que o atendimento em grupo não teve o mesmo efeito em todas as integrantes, o que não significa que não tenha sido eficaz, acredita-se que movimentos de mudanças foram observados nos envolvidos.

This paper presents the experience report of two undergraduate students in Psychology, with group psychoanalytic practice during compulsory internship with emphasis on Mental Health, within a school clinic, under the supervision and guidance of a qualified supervising teacher. The consultations were based on the Winnicottian psychoanalytic perspective, with theoretical and practical application in a therapeutic group composed of women with complaints of depression, through the therapeutic workshop "Memory Box". The group's proposal was based on the use of a dialogical mediating resource, which was characterized as mediating materiality, which aimed to favor the emotional expression of the group members, freely and less defended, favoring genuine and spontaneous conduct. The experience of group therapy pointed to the particularity and subjectivity of each case and the need to adjust the treatment to each individual, since group care did not have the same effect on all members, which does not mean that it was not effective, it is believed that changes and personal growth were observed in all involved.

Este artículo presenta la experiencia de dos estudiantes de pregrado en Psicología, con práctica psicoanalítica grupal durante una pasantía obligatoria con énfasis en Salud Mental, dentro de una clínica escolar, bajo la supervisión y orientación de un maestro supervisor calificado. Las consultas se basaron en la perspectiva psicoanalítica winnicotiana, con aplicación teórica y práctica en un grupo terapéutico compuesto por mujeres con quejas de depresión, a través del taller terapéutico "Caja de Memoria". La propuesta del grupo se basó en el uso de un recurso de mediación dialógica, que se caracterizó como materialidad mediadora, cuyo objetivo era favorecer la expresión emocional de los miembros del grupo, libremente y menos defendidos, favoreciendo una conducta genuina y espontánea. La experiencia de la terapia grupal señaló la particularidad y subjetividad de cada caso y la necesidad de ajustar el tratamiento a cada individuo, ya que la atención grupal no tuvo el mismo efecto en todos los miembros, lo que no significa que no fue efectiva, es creía que se observaron cambios y crecimiento personal en todos los involucrados.

Maier-Saupe model for a mixture of uniaxial and biaxial molecules.

We introduce shape variations in a liquid-crystalline system by considering an elementary Maier-Saupe lattice model for a mixture of uniaxial and biaxial molecules. Shape variables are treated in the annealed (thermalized) limit. We analyze the thermodynamic properties of this system in terms of temperature T, concentration c of intrinsically biaxial molecules, and a parameter Δ associated with the degree of biaxiality of the molecules. At the mean-field level, we use standard techniques of statistical mechanics to draw global phase diagrams, which are shown to display a rich structure, including uniaxial and biaxial nematic phases, a reentrant ordered region, and many distinct multicritical points. Also, we use the formalism to write an expansion of the free energy in order to make contact with the Landau-de Gennes theory of nematic phase transitions.

Luteal phase concentrations of a progestagen-associated endometrial protein (PEP) in the serum of cycling women with adequate or inadequate endometrium.

We previously demonstrated that the human endometrium synthesizes and secretes a specific protein designated "Progestagen-associated Endometrial Protein" or PEP. This work was undertaken to determine luteal phase levels of PEP in serum of cycling women with histologic evidence of adequate endometrium (endometrium in phase) or inadequate endometrium (endometrium out of phase by 3-4 days). The results provide a normative curve with 95% confidence limits for serum PEP concentrations vs normalized cycle day in women with adequate endometrium (judged by histologic endometrial dating), and indicate that the PEP concentration increases exponentially after day 22, with a mean doubling time of 2.95 +/- 1.60 (mean +/- SD) days (based on serial data from 13 women). More importantly, the proportion of serum PEP values falling outside of the 95% confidence limits was significantly greater (p less than 0.001) in women with inadequate endometrium (83%) than in women with adequate endometrium (16%). Therefore, determination of PEP in serum, rather than the more invasive endometrial biopsy examination, may serve as a method of choice for evaluating endometrial adequacy in infertile women.

Mitoxantrone, folinic acid, 5-fluorouracil and prednisone as first-line chemotherapy for advanced breast carcinoma. A phase II study.

The purpose of this prospective clinical trial was an attempt to find an effective and relatively non-toxic schedule for patients with metastatic breast cancer who decline to receive aggressive cytotoxic chemotherapy. A total of 36 patients with disseminated breast cancer were treated with mitoxantrone 8 mg/m2 intravenously (i.v.) day 1, folinic acid 400 mg/m2 in a 2-h i.v. infusion with 5-fluorouracil 500 mg/m2 as an i.v. bolus 1 h later, days 1 and 8 at 3-week intervals plus prednisone 20 mg/m2 orally daily with diminishing doses over several weeks. Objective regressions were observed in 24/36 (67%) patients, 9 being complete (25%). Responses were seen at all disease sites, mainly pleural/lung, bone and liver. The median duration of response was 8 months (range 4-25+) and the median survival 12 months (range 3-26+). Myelosuppression, mainly leucopenia and thrombocytopenia, was the major toxicity but without complications. Other toxicities included mild or moderate nausea and/or vomiting (50%), stomatitis (33%) and diarrhoea (11%). Alopecia was minimal. No cases of cardiotoxicity were detected. The substantial response rate obtained with this relatively well tolerated regimen against advanced breast cancer warrants its assessment in a larger number of patients.

Menstrual induction: its place in clinical practice.

From June 1973 to October 1974, 221 patients underwent menstrual induction in the private offices at a University Medical Faculty Group located in its major teaching hospital with ready access to operating room facilities. The rationale for subclassifying early abortion as "menstrual induction" is discussed. In this series menstrual induction was performed on patients who were 7 to 21 days beyond the date of an expected menses. Histologic examination of the tissue removed was consistent with a diagnosis of pregnancy in 98.2% of the patients. Complication rates following the use of the practices outlined in this report were acceptably low.

cis-Platinum, adriamycin, and hexamethylmelamine versus cyclophosphamide in advanced ovarian carcinoma.

Fifty-three evaluable patients with disseminated ovarian carcinoma (FIGO III or IV) not treated with prior chemotherapy were randomized to receive either combination chemotherapy consisting of cis-platinum 40 mg/m2 IV on day 1, adriamycin 40 mg/m2 IV on day 1, and hexamethylmelamine 150 mg/m2 PO on days 2-10 up to a maximum of 200 mg on a 4-weekly cycle, or moderate-dose cyclophosphamide alone 40 mg/kg given IV intermittently every 3 weeks. Entry was from 1. 11. 1978 until 30. 4. 1981 (last follow-up 31. 10. 1981). Pretreatment characteristics in both groups of patients, regarding median age at diagnosis, median time from diagnosis to chemotherapy, FIGO stage, histology, differentiation grade, type of surgery, residual disease, previous radiotherapy, and median performance status, were comparable. Objective responses were seen in 18 of 27 (66%) of patients receiving cyclophosphamide alone (range 5--32+ months) and in 10 of 26 (38%) of patients treated with the combination (range 3--30+ months), this difference being statistically significant (chi 2 = 4.228; P less than 0.05). The median duration of objective response (11 vs 10 months) and the median survival (12 vs 11 months) were greater in the cyclophosphamide group, but these differences were not statistically significant. The toxicity of the combination was more severe. It is concluded that there is no therapeutic advantage for this combination schedule over the alkylating agent used alone.

A randomized trial of two regimens of cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone in advanced breast cancer.

One-hundred evaluable patients with progressive advanced breast carcinoma untreated by cytotoxic chemotherapy but resistant to hormone therapy and irradiation were randomly allocated to receive either a combination of cyclophosphamide (600 mg/m2), methotrexate (40 mg/m2), 5-fluorouracil (600 mg/m2) IV every 3 weeks and prednisone 20 mg/m2 PO daily, with diminishing doses (intermittent group), or a combination of cyclophosphamide (100 mg/m2 PO on days 1-15, alternating with a 15-day rest period), methotrexate 20 mg/m2 IV, 5-fluorouracil 500 mg/m2 IV weekly for 20 weeks and prednisone 20 mg/m2 PO daily, with diminishing doses in the remission induction period, followed by a maintenance regimen of cyclophosphamide 100 mg/m2 PO on days 1-15, methotrexate 20 mg/m2 IV on days 1, 8 and 15, 5-fluorouracil 500 mg/m2 IV on days 1, 8, and 15, and prednisone 20 mg/m2 PO on days 1-15, with a 3-week rest period between the courses (intensive group). Entry was from 1 December 1982 to 30 November 1983. Objective responses were seen in 20/49 (41%) patients in the intermittent group and 34/51 (67%) in the intensive group (chi 2 = 6.72; P less than 0.01). The estimated median duration of response was 11 months in the intermittent group and 14 months in the intensive group. The estimated median survival was greater in the intensive group, but the difference was not statistically significant, although this parameter can be influenced with alternative additional chemotherapy. Toxicity was similar in both groups. These data suggest there are no therapeutic and survival advantages to the 3-weekly IV protocol compared with our previous regimen CMFP.

High-dose epirubicin as primary chemotherapy in advanced breast carcinoma: a phase II study.

A total of 40 patients with metastatic breast cancer were treated with 120 mg/m2 i.v. epirubicin every 3 weeks for a maximum of 10 cycles. Nine achieved a complete response and 17 showed a partial response, for an objective response rate of 65% (95% confidence interval, 47%-83%); the median duration of response was 7 months (range, 1-15 months) and median survival amounted to 13 months (range, 2-20 months). Leucopenia (grade 2 or 3) was seen in 14 patients on day 21 of the cycle. A subset of nine patients underwent blood counts on day 10, when all had marked neutropenia (less than 1 x 10(9)/l). Other toxicity was frequent and included nausea/vomiting (80%), alopecia (95%) and stomatitis (35%). Five patients showed a significant fall in cardiac output, but this reverted to normal after treatment. Epirubicin should have a role in the development of high-dose regimens for the treatment of advanced breast cancer.

Serum and peritoneal fluid proteins in women with and without endometriosis.

We examined the proteins in serum and peritoneal fluid of women with endometriosis (and of healthy controls) for evidence of an autoimmune response that might account for their impaired fertility. No antibodies against endometrial glycoproteins or against "progestin dependent endometrial protein" (PEP) were found in any serum or peritoneal fluid sample. Levels of PEP were not different in serum from women with moderate to severe endometriosis (n = 6), with mild endometriosis (n = 21), or from disease-free cycling controls (n = 19). PEP levels in peritoneal fluid from mild endometriosis and from controls did not differ but were elevated ten times in fluid obtained in the secretory phase from women with moderate to severe disease. This suggests that PEP levels in peritoneal fluid reflect the extent of ectopic endometrial growth. The salient finding was a heretofore undescribed protein (mol wt 70,000) in secretory phase peritoneal fluid samples (18/20) and its absence during the proliferative phase (0/35).

Persistence of ureaplasma urealyticum in the genital tract after antibiotic therapy.

Urine samples from 65 couples attending an infertility clinic were tested for the presence of Ureaplasma urealyticum. Of 36 couples found to harbor the organism, 35 were given antibiotic treatment in an attempt to eradicate these organisms from the genital tract. After the initial antibiotic therapy, tests of 12 of 27 couples (44%) still were Ureaplasma positive; after a second course of treatment, tests for 4 of 9 were positive. Two couples had Ureaplasma organisms that were resistant to all antibiotics tested. One couple remained positive after five courses of treatment, in spite of the demonstrated in vitro sensitivity of the isolate to antibiotics used. Pregnancies in treated patients occurred among those who were Ureaplasma negative after doxycycline therapy.

[Luteinized cystic hyperplasia of the ovaries during pregnancy. A case report]. / Hyperplasie kystique lutéinisée des ovaires au cours de la grossesse. A propos d'un cas.

Multiple lutein cyst (MLC) and luteoma are two aspects of ovarian hyperplasia induced by high levels of human chorionic gonadotrophin (HCG). Using a case report of MLC, the authors compare it with luteoma (the anatomoclinical and pathogenic data). Luteoma are more frequent with multipara, whereas MLC are more often seen with paucipara. Maternal virilization can occur in both cases but MLC does not seem to be responsible for fetal virilization. The fetus could be protected by the placenta, thanks to increased aromatase activity and sex binding globulin production. MLC and luteoma are usually found by chance. The pathology must be known, because of their spontaneous regression after delivery. So, the attitude will be conservative under the control of biopsies.

Cytotoxic chemotherapy of disseminated cutaneous malignant melanoma--a prospective and randomized clinical trial of procarbazine, vindesine and lomustine versus procarbazine, DTIC and lomustine.

Forty-three patients with measurable disseminated cutaneous malignant melanoma, stages III-IV, and without previous cytotoxic chemotherapy or immunotherapy, were randomly allocated from 30 June 1980 to 30 November 1984, to receive either a schedule of procarbazine (100 mg/m2 p.o., max 150 mg) days 1-10, vindesine (3 mg/m2 i.v., max 5 mg) days 1 and 8, and CCNU (150 mg/m2 p.o., max 200 mg) day 1, (regimen A), with 4-6 weeks interval between the courses, or a combination of procarbazine (100 mg/m2 p.o., max 150 mg) days 1-10, DTIC (250 mg/m2 i.v. max 400 mg) days 1-5, and CCNU (150 mg/m2 p.o. max 200 mg) day 1 (regimen B), also repeated every 4-6 weeks. Twenty-one patients were treated according to regimen A and 22, by regimen B. Objective responses (three PR, two CR) were seen in 5 out of 21 patients (23.8%) in group A and 8 out of 22 (four PR, four CR), (36%) in the group B, this difference not being statistically significant. The median duration of response was 8 and 10 months, respectively, and the estimated median survival 10 months for regimen A and 14 months for regimen B. Regimens A and B must be regarded as of no value in view of poor response rate and the unacceptable toxicity, respectively. Therefore, we are now conducting a further phase II study, to determine, prospectively, whether the previously noted high response rate obtained with our previous POC protocol can be reaffirmed.

Moderate-dose cyclophosphamide for disseminated ovarian carcinoma: a phase II study.

Fifty-six evaluable patients with advanced ovarian carcinoma (FIGO III or IV), without prior cytotoxic chemotherapy, were studied to assess the activity of single-agent moderate-dose cyclophosphamide, 40 mg/kg to a maximum dose of 3000 mg, given intravenously as a bolus injection every 3 weeks. All patients were treated as outpatients. Moderate-dose cyclophosphamide resulted in 36 (64%) objective responses (19 CR, 17 PR). Nausea and severe vomiting occurred in all patients, but no patient needed hospitalization for this complication. Other side-effects observed were alopecia (100%), leukocytes less than or equal to 2500/microliters (18%), chemical cystitis (11%) and sepsis (4%). The median duration of response was 11 months, and the estimated median survival by the life-table method for responders was 16 months and for non-responders 4 months (P less than 0.001). Clinical trials previously performed by our group comparing cyclophosphamide alone, either vs cis-platinum, adriamycin and hexamethylmelamine or vs Hexa-CAF, showed a better remission rate with the use of moderate-dose cyclophosphamide alone. Therefore we suggest further investigation of this agent in a moderate dose in disseminated ovarian carcinoma.

Increase in diaphragm use in a university population.

A striking increase observed in the demand for the diaphragm method at a contraception clinic for university women was documented by means of a record review and questionnaire. Record reviews completed at the conclusion of each semester from December 1973 to December 1976 showed a statistically significant increase in diaphragm acceptors. In the fall semester of 1976, diaphragm acceptors (49% of 151 patients) surpassed pill acceptors (46%). Data from 123 questionnaires revealed that concern for pill and IUD side effects was the primary reason for diaphragm choice. The study numbers are small, but a definite trend is evident. These educated young women may be forerunners, and an increase in diagphragm use in the general population may be seen in the near future.

PIP: The Albany Medical College instituted weekly contraception clinics at the Health Service of a local university. The clinic offered inexpensive contraceptive service for students and patient counseling. The clinic has been self-supporting through low, fee-for-service charges. Record reviews completed at the end of each semester from December 1973 to December 1976 showed a marked increase in diaphragm acceptors. In the fall of 1976, diaphragm acceptors (49% of 151 patients) surpassed pill acceptors (46%). Concern for pill and IUD side effects was the primary reason for diaphragm choice based on data from 123 interviews. During the first year of operation a total of 196 patients were served: 146 (74%) chose pills, 17 (9%) selected the IUD, and only 13% (26) opted for the diaphragm. In fall 1976, 49% chose the diaphragm. 46% chose the pill. The biggest disadvantages of the diaphragm are that it is messy and interferes with spontaneity. The advantages of the diaphragm, other than lack of side effects, are safety and reliability of the method, and a lack of need for constant protection because of infrequent relations. The condom was the backup method used most frequently; 11 used no backup of any kind. 74% reported that they used the diaphragm with every contact; 40% did not.

Inclusion of conserved buried water molecules in the model structure of rat submaxillary kallikrein.

A new approach to the molecular modelling of homologous serine proteases is adopted, by including a set of 21 buried waters known to be preserved in enzymes sharing the primary specificity of trypsin, in the homology modelling of rat submaxillary gland kallikrein. Buried waters--water molecules sequestered from bulk solvent within a protein matrix--appear to be integral conserved components of all serine proteases of known structure and should be incorporated into serine protease models built on the basis of sequence/structural homology to this family. The absence of such waters might induce errors in a force field simulation, favouring the formation of nonexistent hydrogen bonds and locally inaccurate structure. The kallikrein model refinement has led to the conclusion that an additional buried water should be added to the original rigid matrix of 21 conserved water molecules. The structurally preserved protein cavities of such waters validate the modelled structure.

Combination cytotoxic chemotherapy with procarbazine, vincristine, and lomustine (POC) in disseminated malignant melanoma: 8 years' follow-up.

Forty-four consecutive ambulatory patients (24 male, 20 female; median age, 56 years [range, 21-76]) with evaluable disseminated malignant melanoma (stages III/IV) were entered in this study from October 1, 1975, to July 21, 1980 (last follow-up, October 31, 1983); they were treated with procarbazine (100 mg/,m2 orally; maximum dose, 150 mg) on Days 1-10, vincristine (1.4 mg/m2 iv; maximum dose, 2 mg) on Days 1 and 8, and lomustine (150 mg/m2 orally; maximum dose, 200 mg) on Day 1, repeated every 4-6 weeks. Twenty-one patients (48%) showed objective responses; 11 of these (25%) were complete responses. Nine patients had received previous chemotherapy, but none were treated with the drugs used in this protocol. Responses were seen mainly in cutaneous and/or nodal sites and pulmonary metastases. The median duration of remission was 10 months and the median survival of responders was 21 months compared to 5 months for nonresponders. Four responding patients are still alive and in complete response for 70+, 83+, 94+, and 95+ months, while one is alive, but in progression (83+ months). The toxicity of this regimen was clinically tolerable and hospitalization was not required. In our initial study the response rate was 60% (18 responses among 30 patients) and this regimen continues to have significant antitumor activity against disseminated malignant melanoma.