Inhibition of medullary raphé/parapyramidal neurons prevents cutaneous vasoconstriction elicited by alerting stimuli and by cold exposure in conscious rabbits

In conscious rabbits, microinjection of muscimol into the medullary raphé/parapyramidal region decreased fluctuation (coefficient variation) of resting ear blood flow (from 62 +/- 8 to 25 +/- 4%, P < 0.01, n = 8). The muscimol injection also prevented falls in ear blood flow that normally occur in response to alerting stimuli and to cold exposure. Thus, raphé/parapyramidal neurons constitute an important brainstem center for mediating cutaneous vasoconstriction initiated by alerting stimuli and by cold exposure.     

Heparin-mediated extracorporeal LDL precipitation treating a peripheral arterial disease patient suffering from repeated postoperative bypass occlusion

Acute occlusion of a peripheral artery is a serious complication in peripheral arterial disease (PAD). Traditionally open surgical intervention in combination with antithrombotic therapy is the choice for treatment but the beneficial effects of both strategies are limited often by the patient's situation and therapeutic side effects. Heparin-mediated extracorporeal low-density lipoprotein precipitation (H.E.L.P.) apheresis efficiently removes circulating atherogenic lipoproteins, fibrinogen and C-reactive proteins as well as various proinflammatory and procoagulatory factors. We first report H.E.L.P. apheresis treating a PAD patient suffering from repeated postoperative femoropopliteal bypass graft occlusion, first, intensively, followed by weekly intervals. Limb amputation was avoided and the patient is doing well now. Angiography revealed bypass graft remained patent half a year after operation. This case report might help to design the regime for preventing postoperative bypass occlusion in patients with hyperlipidemia or hyperfibrinogenemia.     

Phase II trial of gemcitabine as second-line chemotherapy of uterine leiomyosarcoma: a Gynecologic Oncology Group (GOG) Study

OBJECTIVE: To determine the antitumor activity and toxicity profile of gemcitabine as second-line chemotherapy in patients with recurrent or persistent uterine leiomyosarcoma (LMS). METHODS: Intravenous gemcitabine was administered over 30 min at a dose of 1000 mg/m(2) on days 1, 8, 15, with cycles repeated every 28 days. Eligibility criteria included measurable disease, performance status 0-2, adequate bone marrow function, creatinine <1.5 mg%, bilirubin <1.5x institutional normal, SGOT/alkaline phosphatase <3x institutional normal, and signed informed consent. Standard Gynecologic Oncology Group (GOG) toxicity and response criteria were utilized. RESULTS: Forty-eight patients were enrolled on the study. Three were deemed ineligible upon central pathology review, another received an inadequate course of protocol treatment, and two others were not reassessed for response; thus 44 patients were evaluable for toxicity and 42 for toxicity and response. The median age was 52.5 (range: 31-82) years. Thirty-five patients had received prior chemotherapy and 11 had undergone prior radiotherapy. Sites of measurable disease were pelvic (n = 9) and extrapelvic (n = 35). A median of two (range: 1-13) cycles was received. The schedule was well tolerated; there were no treatment-related deaths. The only grade 4 toxicities included neutropenia (n = 7), nausea and vomiting (n = 2), and dermatologic (n = 1). One (2.3%) patient achieved a complete response and eight (18.2%) experienced a partial response, for an overall response rate of 20.5%. CONCLUSION: Gemcitabine demonstrates activity in patients with persistent or recurrent uterine LMS and should be considered in multiagent regimens treating this patient population.     

Cisplatin as initial chemotherapy in ovarian carcinosarcomas: a Gynecologic Oncology Group study

OBJECTIVES: Carcinosarcomas of the ovary are rare; hence, although most patients recur after surgical resection or have metastatic disease at the time of diagnosis, only anecdotal information is available concerning the activity of cytotoxic drugs against these lesions. The Gynecologic Oncology Group (GOG) initiated a concerted effort to study cytotoxic therapy for these cancers in 1976. This report presents data on cisplatin, the first of the agents to be studied in this disease. METHODS: One hundred thirty-six eligible patients with ovarian carcinosarcoma received cisplatin (50 mg/m(2)) every 3 weeks until disease progression or unacceptable toxicity. RESULTS: Among 44 patients evaluable for response, one complete (2%) and eight partial (18%) responses resulted. An additional 10 (23%) patients exhibited stable disease, while 25 (57%) had increasing disease. Median progression-free survival in 130 patients evaluable for this endpoint was 5.2 months. Median survival in the same 130 patients was 11.7 months. Adverse effects >/=grade 2 among the 132 patients evaluable for toxicity included leukopenia (14%), neutropenia (17%), thrombocytopenia (2%), anemia (10%), nausea and vomiting (40%), azotemia (3%), neurotoxicity (4%), fever (2%), and tinnitus (1%). CONCLUSIONS: These data provide the first objective evidence that cisplatin is active as an initial therapy for patients who have carcinosarcoma of the ovary. The overall response rate (20%) is similar to that seen in carcinosarcomas of the uterus.     

The course of maternal depressive symptoms and maternal sensitivity as predictors of attachment security at 36 months

We examined the course of maternal depressive symptoms and children's attachment security at 36 months in a large sample of mother-child pairs from 10 sites across the country participating in the NICHD Study of Early Child Care (N = 1077). Maternal depressive symptoms predicted higher rates of insecure attachment. Women who reported intermittent symptoms across the first 36 months had preschoolers who were more likely to be classified as insecure C or D; women with chronic symptoms were more likely to have preschoolers who were classified as insecure D. Symptoms reported only during the first 15 months were not associated with elevated rates of later insecurity. After controlling for potentially confounding demographic variables, maternal sensitivity (observed at 6, 15, 24, and 36 months) did not meaningfully account for links between attachment security and patterns of depressive symptoms. However, the course and timing of maternal depressive symptoms interacted with maternal sensitivity to predict insecurity. Women with late, intermittent, or chronic symptoms who were also low in sensitivity were more likely to have preschoolers who were insecure, in contrast to symptomatic women who were high in sensitivity. These data have implications for understanding the combined impact of maternal depressive symptoms and maternal sensitivity on children's socioemotional development.     

Physiologic profile of recreational male and female novice and experienced Tae Kwon Do practitioners

AIM: Subjects, 28 recreational male and female novice and experienced Tae Kwon Do practitioners (age 19-42 years), were examined on 6 physiological parameters: body composition (BF%, skinfold measures), flexibility (sit-and-reach and leg-splits tests), lower and upper-body dynamic muscular strength (leg press and bench press), abdominal strength and endurance (1-minute timed, bent-knee sit-ups test), lower extremity explosive power (vertical jump-and-reach test), and cardiovascular endurance (graded exercise treadmill test). METHODS: Subjects were assigned to 1 of the 4 following groups: Tae Kwon Do experienced and trained men (MT), Tae Kwon Do experienced and trained women (FT), novice Tae Kwon Do men (MN), and novice Tae Kwon Do women (FN). RESULTS: Results of multiple testing procedures and comparison across groups indicated that Tae Kwon Do black belts were more athletically fit as compared with that of novice Tae Kwon Do practitioners of the same sex in spite of the fact that male and female black belts were older than their novice counterparts. Experienced Tae Kwon Do subjects were stronger as measured by lower body strength and showed better aerobic performance capacity as well as lower percent body fat. Additionally, MT subjects demonstrated higher flexibility. CONCLUSION: The highly diverse training, repeated and continuous use of the legs and arms alone or combined with maximal stretching, and high intensity exercise may account for observed differences among groups.     

Evaluation of irofulven (MGI-114) in the treatment of recurrent or persistent endometrial carcinoma: A phase II study of the Gynecologic Oncology Group

OBJECTIVE: This multi-center phase II trial was conducted by the Gynecologic Oncology Group to evaluate the activity and toxicity of irofulven in patients with previously treated adenocarcinoma of the endometrium. METHODS: Eligible patients had documented recurrent or persistent endometrial carcinoma after receiving definitive locoregional therapy, and were required to have measurable disease, performance status of 0-2, and adequate bone marrow, hepatic and renal functions prior to study entry. Patients were allowed one prior chemotherapy regimen. The initial dose of irofulven was 11 mg/m(2)/day for four days administered intravenously. Cycles were repeated every 28 days. Doses were escalated or reduced based on previous cycle toxicity. RESULTS: Twenty-five patients were enrolled onto the trial. There was one (4%) confirmed complete response. Seven (28%) patients had stable disease, with a median duration of 10.4 (range: 4.4-21.6) months. Patients received a median of one (range: 1-5) cycle of protocol treatment. There were three early treatment-related deaths due to renal failure and severe electrolyte disturbances. Two patients experienced grade 4 hematologic adverse effects. CONCLUSION: Irofulven administered at the dose and schedule used in this trial was minimally active and resulted in significant toxicity.     

Modulation of DNA repair processes by arsenic and selenium compounds

Nickel, cadmium, cobalt and arsenic compounds are well known carcinogens to humans and experimental animals. In addition to the induction of mainly oxidative DNA damage, they interfere with nucleotide and base excision repair (BER) at low, non-cytotoxic concentrations. In case of arsenic, an inactivation of DNA repair has also been observed for the trivalent and pentavalent methylated metabolites, with the strongest effects exerted by MMA(III) and DMA(III). As potential molecular targets, interactions with so-called zinc finger proteins involved in DNA repair and/or DNA damage signaling have been identified. For example, arsenite suppresses poly(ADP-ribosyl)ation at extremely low, environmentally relevant concentrations. Also, Fpg and XPA involved in BER and NER, respectively, are inactivated by arsenite, MMA(III) and DMA(III). Nevertheless, an interaction with the zinc finger structures of DNA repair proteins may also occur by essential trace elements such as certain selenium compounds, which appear to exert anticarcinogenic properties at low concentrations but may compromise genetic stability at higher concentrations.     

A phase II trial of CI-958 in recurrent platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study

OBJECTIVES: To estimate the antitumor efficacy of CI-958 in patients with measurable recurrences of platinum-sensitive ovarian carcinoma and to determine the nature and degree of toxicity of CI-958 in these patients. METHODS: Patients received CI-958 560 mg/m2 intravenously every 3 weeks and tumor measurements were performed every one to two cycles. RESULTS: Of 23 patients entered in the study, there was one complete response and 10 patients had stable disease with short response durations. CONCLUSIONS: CI-958 has minimal activity in recurrent platinum-sensitive ovarian carcinoma at the dose and schedule tested.     

Digital beam attenuator technique for compensated chest radiography

The feasibility of producing patient-specific beam attenuators for chest radiography has been investigated using an anthropomorphic phantom and a human volunteer. A low-dose test exposure is digitized, processed, and used to print a small cerium filter, which is placed in the x-ray beam near the collimator. The final radiograph is recorded on film. The technique results in relatively uniform film exposure, so that structures in all regions of the chest are simultaneously displayed with optimal film contrast. The equalized exposure improves image quality in the normally underpenetrated regions and reduces the role of cross-scatter from the lungs. The image is analogous to optical or computer-processed unsharp masking techniques, but the processing is accomplished in the x-ray beam and results in an improved exposure distribution, giving advantages that cannot be achieved with image processing techniques alone.