Adolescence alcohol exposure impairs fear extinction and alters medial prefrontal cortex plasticity.

After experiencing a traumatic event people often turn to alcohol to cope with symptoms. In those with post-traumatic stress disorder (PTSD) and a co-occurring alcohol use disorder (AUD), PTSD symptoms can worsen, suggesting that alcohol changes how traumatic memory is expressed. The objective of this series of experiments is to identify how alcohol drinking (EtOH), following cued fear conditioning and extinction, impacts fear expression in mice. Molecular (activity-regulated cytoskeleton-associated protein, Arc/arg3.1) and structural (dendrite and spine morphometry) markers of neuronal plasticity were measured following remote extinction retrieval. Mouse age (adolescent and adult) and sex were included as interacting variables in a full factorial design. Females drank more EtOH than males and adolescents drank more EtOH than adults. Adolescent females escalated EtOH intake across drinking days. Adolescent drinkers exhibited more conditioned freezing during extinction retrieval, an effect that persisted for at least 20 days. Heightened cued freezing in the adolescent group was associated with greater Arc/arg3.1 expression in layer (L) 2/3 prelimbic (PL) cortex, greater spine density, and reduced basal dendrite complexity. In adults, drinking was associated with reduced L2/3 infralimbic (IL) Arc expression but no behavioral differences. Few sex interactions were uncovered throughout. Overall, these data identify prolonged age-related differences in alcohol-induced fear extinction impairment and medial prefrontal cortex neuroadaptations.

Percutaneous Cholecystostomy for Severe Acute Cholecystitis: A Useful Procedure in High-Risk Patients for Surgery.

BACKGROUND: Acute cholecystitis has the potential to cause sepsis and death, particularly in patients with poor physiological reserve. The gold standard treatment of acute cholecystitis (cholecystectomy) is often not safe in high-risk patients and recourse is made to percutaneous cholecystostomy as either definite treatment or temporizing measure. The aim of this study is to evaluate early and late outcomes following percutaneous cholecystostomy in patients with acute cholecystitis treated at our institution. METHODS: All patients who underwent percutaneous cholecystostomy for acute cholecystitis (excluding patients with malignancy) between January 2005 and September 2014 were included in the study. RESULTS: A total of 53 patients (22 female, median age, 74 years; range, 27-95 years) underwent percutaneous cholecystostomy during the study period. In total, 12 patients (22.6%) had acalculous cholecystitis. The main indications for percutaneous cholecystostomy were significant co-morbidities (n = 28, 52.8%) and patients too unstable for surgery (n = 21, 39.6%). The median time to percutaneous cholecystostomy from diagnosis of acute cholecystitis was 3.6 days (range, 0-45 days). The median length of hospital stay was 27 (range, 4-87) days. The overall 90-day mortality was 9.3% with two further deaths at 12-month follow up. The mortality was significantly higher in patients with American Society of Anesthesiology grade 4-5 (18% vs 0% in American Society of Anesthesiology grade 2-3, p = 0.026) and in patients with acalculous cholecystitis (25% vs 4.5%, p = 0.035). The overall readmission rate was 18%. A total of 24 (45.2%) patients had surgery: laparoscopic cholecystectomy, n = 11; laparoscopic converted to open, n = 5; open total cholecystectomy, n = 5; open cholecystectomy, n = 1; laparotomy and washout, n = 1; laparotomy partial cholecystectomy and closure of perforated small intestine and gastrostomy, n = 1. CONCLUSION: Percutaneous cholecystostomy is a useful temporary or permanent procedure in patients with acute cholecystitis of both calculous and acalculous origin, who are unfit for surgery.

Ammonia recovery from anaerobically digested cattle manure by steam stripping.

Ammonia recovery from anaerobically digested cattle manure effluents through steam stripping was studied at a stripping tower temperature of 98-99 degrees C and a steam-water ratio approximately 56-72 g/L. The digested manure effluents were first treated by microfiltration and then the permeate was used as feed in steam stripping. The stripping performance was evaluated under different feed pH values, ammonia concentrations and temperatures. The increase of the initial feed pH does not significantly improve ammonia stripping efficiency due to the fact that the stripped effluent pH is increased during steam stripping. This suggests that steam stripping of anaerobically digested manure effluents for ammonia recovery may not need pre-raised pH. In contrast, the pH value of the synthetic ammonia wastewater containing NH4Cl dramatically decreases after steam stripping. Increasing the feed temperature slightly improves ammonia stripping efficiency, but reduces the concentration of the recovered ammonia in the condensate due to an increased condensate volume at a higher feed temperature. Therefore, the feed temperature should be controlled at an optimum point that can compromise the condensate ammonia concentration and the ammonia stripping efficiency. Experimental results indicate that recovery of ammonia from anaerobically digested cattle manure effluents as NH4OH is technically feasible.

Preoperative chemo-radiation for carcinoma of the vulva with N2/N3 nodes: a gynecologic oncology group study.

PURPOSE: To determine if patients with carcinoma of the vulva, with N2/N3 lymph nodes, could undergo resection of the lymph nodes and primary tumor following preoperative chemo-radiation. METHODS AND MATERILAS: Fifty-two patients were entered in the study, but six patients did not meet the criteria of the protocol and were excluded. The remaining 46 patients are the subject of this report. Patients underwent a split course of radiation, 4760 cGy to the primary and lymph nodes, with concurrent chemotherapy, cisplatin/5-FU, followed by surgery. RESULTS: Four patients did not complete the chemo-radiation, because three expired and one refused to complete the treatment. Four patients who completed chemo-radiation did not undergo surgery, because two of them died of non-cancer-related causes, and in the other two patients, the nodes remained unresectable. Following chemo-radiation, the disease in the lymph nodes became resectable in 38/40 patients. Two patients who completed the course of chemo-radiation did not undergo surgery as per protocol because of pulmonary metastasis. One underwent radical vulvectomy and unilateral node dissection and the other radical vulvectomy only. The specimen of the lymph nodes was histologically negative in 15/37 patients. Nineteen patients developed recurrent and/or metastatic disease. The sites of failure were as follows: primary area only, 9; lymph node area only, 1; primary area and distant metastasis, 1; distant metastasis only, 8. Local control of the disease in the lymph nodes was achieved in 36/37 and in the primary area in 29/38 of the patients. Twenty patients are alive and disease-free, and five have expired without evidence of recurrence or metastasis. Two patients died of treatment-related complications. CONCLUSION: High resectability and local control rates of the lymph nodes were obtained in patients with carcinoma of the vulva with N2/N3 nodes treated preoperatively with chemo-radiation.

Evaluation of gemcitabine in patients with squamous cell carcinoma of the cervix: a Phase II study of the gynecologic oncology group.

PURPOSE: A multicenter Phase II trial was conducted to evaluate the activity and toxicity of gemcitabine in patients with previously treated squamous cell carcinoma of the uterine cervix. PATIENTS AND METHODS: Patients were required to have measurable disease with adequate performance status, bone marrow, hepatic, and renal function. Histologic confirmation of the primary diagnosis as squamous cell cancer of the uterine cervix was mandatory. Patients were allowed one prior chemotherapy regimen, usually cisplatin-based. The initial dose of gemcitabine was 800 mg/m(2) weekly times three with 1 week off until progressive disease or adverse effects prohibited further therapy. Doses were escalated or reduced based on previous cycle toxicity. RESULTS: Twenty-seven patients were entered into the trial. One patient never received the drug and 1 patient was inevaluable for response. A median of two cycles were administered to each patient (range: 1-7 cycles). The overall response rate (two partial responses) was 8% with 21% of patients having stable disease. The median progression-free interval was 1.9 months (range: 0.5-9.0) and overall survival was 4.9 months (range: 1.5-16.3). Two patients had grade 4 neutropenia; 1 patient had grade 4 anemia. The median WBC nadir in the 13 patients experiencing any leukopenia was 2300/microl (range: 400-3800). There was only one episode of grade 4 gastrointestinal toxicity. CONCLUSIONS: Gemcitabine as a single agent demonstrated minimal antitumor activity in previously treated patients with squamous cell cancer of the uterine cervix. Since gemcitabine in the dose and schedule employed is known to potentiate the cytotoxicity of cisplatin and radiotherapy (the current standard therapies for this disease), further development of gemcitabine would only be indicated in combination with these treatment modalities.

Hyperfractionated radiation therapy plus chemotherapy in locally advanced cervical cancer: results of two phase I dose-escalation Gynecologic Oncology Group trials.

OBJECTIVE: The aims of this study were to assess the early and late toxicities of multiple-daily-fraction whole pelvic radiation plus concurrent chemotherapy with either hydroxyurea or 5-fluorouracil (5-FU)/cisplatin and to determine the maximum tolerated external radiation dose in conjunction with brachytherapy, when given with either of these drug regimens, as treatment for locally advanced carcinoma of the cervix. METHODS: The first study (GOG 8801) of 38 patients utilized hydroxyurea as a single oral dose of 80 mg/kg to a maximum of 6 g at least 2 h prior to a radiation treatment twice every week. In the second study (GOG 8901) of 30 patients, cisplatin and 5-FU were used concomitantly with radiotherapy. Fifty milligrams per square meter of cisplatin was administered on days 1 and 17 of external radiation. 5-FU was given by continuous intravenous infusion at a dose of 1000 mg/m(2)/day for 4 consecutive days on days 2, 3, 4, 5, and 18, 19, 20, and 21 of external radiation therapy. Both studies utilized external radiation given by an accelerated hyperfractionated regimen of 1.2 Gy per fraction, two fractions per day. All patients were treated 5 days per week with a minimum of 4 h between fractions. RESULTS: Acute toxicity was manageable on both protocols but nausea, vomiting, and myelosuppression were more severe with hydroxyurea. Chronic toxicity was primarily enteric and appeared to be dose-related. There was no obvious correlation seen between pelvic failure rates and the radiation dose or between the chemotherapy regimens used. CONCLUSIONS: The defined maximal tolerated dose of whole pelvic radiation was 57.6 Gy in 48 fractions which could be delivered in a hyperfractionated setting with concomitant chemotherapy, followed by brachytherapy. Follow-up is now sufficient that further adverse events should be rare.

Association between subjective sleep quality and depression on immunocompetence in low-income women at risk for cervical cancer.

OBJECTIVE: The purpose of this study was to investigate whether subjective sleep quality is more strongly associated with immunocompetence than depression among women at risk for cervical cancer. METHODS: Participants were 91 women referred for colposcopy because of abnormal results on a Pap smear. On the day of the procedure. participants completed the Center for Epidemiological Studies Depression Scale, two indices of subjective sleep quality (ie, satisfaction with sleep obtained and degree of sleep restfulness), and a health behaviors assessment questionnaire. Levels of peripheral blood lymphocyte subpopulations (helper T, cytotoxic/suppressor T, NK, and B cells) were also assessed at this time. Approximately 10 days later, the presence of depressive disorder was assessed using the Structured Clinical Interview for DSM-III-R. RESULTS: Hierarchical regression analyses revealed that satisfaction with the amount of sleep obtained was significantly associated with the circulating number and percentage of helper T cells (T(H)/CD4+) and the percentage of cytotoxic/suppressor T cells (T(C)/CD8+), after controlling for confounder variables (ie, age, smoking status, and drug use). Depression was significantly associated only with the percentage of T(C) cells. Sleep satisfaction remained significantly associated with the number and percentage of T(H) cells and percentage of T(C) cells after controlling for the variance explained by depression. CONCLUSIONS: Results of this study suggest that subjective sleep quality shares a significant and independent portion of the variance with immunity that is not accounted for by depression. Although the long-term impact of these immune alterations on disease progression needs to be directly explored, it may be important to systematically screen for and manage sleep disturbance in women at high risk for cervical cancer.

Monitoring styles in women at risk for cervical cancer: implications for the framing of health-relevant messages.

We explored the interaction effects of individual attentional style (high versus low monitoring) and the framing of informational messages on the responses of women undergoing diagnostic follow-up (colposcopy) for precancerous cervical lesions. Prior to the colposcopic procedure, patients (N=76) were randomly assigned to one of three preparatory conditions: (a) Loss-framed message, which emphasized the cost of nonadherence to screening recommendations; (b) Gain-framed message, which emphasized the benefit of adherence; and (c) Neutrally-framed message. It was hypothesized that low monitors (who are more positively biased about their health) would show a more adaptive pattern of response to loss-framed information than high monitors (who are more negatively biased about their health). The results of a series of hierarchical multiple regression analyses were consistent with this prediction. Low monitoring was associated with greater knowledge retention (beta=.61, p<.05) and less canceling/rescheduling of follow-up appointments in the loss condition than in the neutral condition (beta=.82, p<.002). High monitoring, however, was associated with greater intrusive ideation when information was presented in the loss-oriented frame as compared to the neutral frame (beta=.99, p<.01). Knowledge retention and screening adherence were not affected by the framing manipulation. The differences between high versus low monitors as a function of loss or neutral frame suggest an interaction effect, wherein both the type of framing message and the individual's attentional style lead to distinctive cognitive-affective and behavioral patterns. The findings may have clinical implications for the tailoring of health messages to the individual's signature style.

High-dose chemotherapy, autologous bone marrow or stem cell transplantation and post-transplant consolidation chemotherapy in patients with advanced breast cancer.

This study was designed to determine the complete response (CR) rate, event-free survival (EFS) and overall survival (OS) in patients with metastatic breast cancer treated with an adriamycin-based induction regimen, high-dose chemotherapy consisting of cyclophosphamide and thiotepa with autologous bone marrow or stem cell reinfusion, followed by post-transplant 5-fluorouracil and cisplatin. Forty-eight consecutive patients were enrolled and 35 received two to four cycles of a cytoreductive chemotherapy regimen followed by high-dose chemotherapy which included cyclophosphamide and thiotepa. Thirty-three patients with non-progressive disease received at least one cycle of post-transplant 5-fluorouracil and cisplatin. Fifty percent of patients with evaluable disease responded to induction chemotherapy. Three of the 34 patients (9%) evaluable for response to high-dose chemotherapy achieved CR, eight (24%) achieved partial response (PR), 12 (35%) had stable disease (SD) and 11 (32%) had progressive disease (PD). The median time to neutrophil recovery was 11.5 days (range, 8 to 40 days) post- reinfusion. The median time to platelet independence was 14.5 days (range, 8 to 44 days). The median follow-up is 24.5 months (range, 1 to 96 months). The actuarial probability of EFS for all patients is 17% at 4 years. The EFS for patients receiving all four cycles of post-transplant chemotherapy is 27% at 4 years, compared to 36% at 1 year for patients not receiving any post-transplant chemotherapy. Ten of the 48 patients (21%) are alive, and seven of these (15%) have no evidence of disease. High-dose chemotherapy with autologous bone marrow or peripheral blood-derived stem cell transplantation followed by post-transplant consolidation chemotherapy in patients with metastatic breast cancer results in a proportion of patients without evidence of disease at 4 years.

Applications of the monitoring process model to coping with severe long-term medical threats.

Guided by the monitoring process model (MPM), the authors explored the illness responses of 2 samples: high monitors (who are cognitively vigilant to and amplify threat-related cues) and low monitors (who avoid them and blunt their impact). Both samples-101 women with human papillomavirus-related precancerous cervical dysplasia and 75 HIV-infected gay men-were undergoing long-term medical follow-up and management. Structural equation analysis showed an adequate fit of the MPM to the data within each sample, supporting the model's heuristic value: High monitors experienced greater disease-related intrusive ideation, which triggered greater avoidant ideation to forestall panic, particularly in the more threatened HIV-positive sample. However, efforts to avoid disturbing intrusive thoughts were ineffective, requiring increasingly extreme defensive strategies (i.e., denial and mental and behavioral disengagement).

Adenoid cystic carcinoma of Bartholin's gland: a review of the literature and report of a patient.

We report the case of a 77-year-old white female with adenoid cystic carcinoma of Bartholin's gland. To date only 45 cases of adenoid cystic carcinoma of Bartholin's gland have been reported in the world literature. The longest reported survival is 27 years. This patient was originally diagnosed 33 years ago and presented with her fourth recurrence. She was treated with radical surgery and did well for 6 months, but later died secondary to renal failure. Adenoid cystic carcinoma of the Bartholin's gland is a rare tumor of the vulva. When diagnosed the treatment should be tailored to the patient. When margins are found to be positive, adjuvant radiotherapy may prove to be beneficial.

Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells.

PURPOSE: To study the toxicity and efficacy of combined granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration for mobilization of hematopoietic progenitor cells (HPCs). MATERIALS AND METHODS: Cohorts of a minimum of five patients each were treated subcutaneously as follows: G-CSF 5 micrograms/kg on days 1 to 12 and GM-CSF at .5, 1, or 5 micrograms/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 micrograms/kg on days 1 to 12 and G-CSF 5 micrograms/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 micrograms/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) were performed on each harvest. RESULTS: The principal toxicities were myalgias, bone pain, fever, nausea, and mild thrombocytopenia, but none was dose-limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of CFU-GM per kilogram collected per harvest that represented 35.6 +/- 8.9- and 33.7 +/- 13.0-fold increases over baseline, respectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased concentrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maximal mobilization achieved (r = .74, P = .001). CONCLUSION: Combined G-CSF and GM-CSF administration effectively and predictably mobilizes HPCs and facilitates apheresis.

Sequential changes in serum iron and ferritin in patients undergoing high-dose chemotherapy and radiation with autologous bone marrow transplantation: possible implications for treatment related toxicity.

In an effort to define the pattern of iron flux during high-dose chemotherapy or chemo/radiotherapy, we prospectively measured serum iron, iron binding capacity, and ferritin in patients undergoing autologous bone marrow transplantation for various malignancies. Sequential measurement of serum iron from days -7 to +12 was carried out in 88 evaluable patients, and simultaneous measurement of iron, ferritin, and total iron binding capacity was carried out in 32 patients. We found that there was a predictable rise in serum iron on day -2 or -3, and that this was accompanied by an increase in the saturation of transferrin. In addition, there was a similar increase in serum ferritin levels, which peaked by day +2. We suggest that the timing of this change in serum iron and saturation of transferrin may be important in mediating endothelial cell damage and, hence, organ toxicity in the setting of AuBMT. Based on these findings, we suggest that large clinical studies could be a source of patient samples to measure surrogate endpoints such as lipid peroxidation products (malondialdehyde or isoprostanes), or protein oxidation products following high-dose chemo/radiotherapy to determine the role of iron in cellular injury. It is possible that pharmacological manipulations to reduce free radical production or to chelate iron during the days prior to bone marrow reinfusion might help to reduce tissue injury in the setting of bone marrow transplantation.

Malignant pericardial effusions: pathophysiology and clinical correlates.

Cardiac tamponade resulting from malignant pericardial effusions is a life-threatening oncologic emergency. As many as 21% of all patients with cancer may be at risk for this complication. A malignant effusion often signifies progressing disease, creating stress and anxiety for patients and their families. By understanding the pathophysiology and pertinent risk factors, the nurse may identify an effusion before it progresses to cardiac tamponade. The goal of management is removal of fluid, restoration of hemodynamic functioning, and prevention of fluid reaccumulation. Emotional support and reassurance, as well as accurate information regarding the disease and treatment, also are critical in assisting patients to adapt to these changes in disease status.

Vaginal and vulvar adenosis. An unsuspected side effect of CO2 laser vaporization.

During a 15-month period, September 1984 through January 1986, 10 women who were treated in the Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, Pennsylvania Hospital, Philadelphia, Pennsylvania, developed vaginal or vulvar adenosis after CO2 laser vaporization. The indications for therapy were condylomata of the cervix, vagina and vulva refractory to conservative management in 3 patients, vulvar intraepithelial neoplasia in 3, lichen sclerosus in 1 and cervical intraepithelial neoplasia with condylomata on the cervix and vagina in 3. All the patients underwent treatment of the vagina. Most underwent treatment of the cervix, and some underwent treatment of the vulva at various degrees of intensity and depth. During the posttreatment colposcopic follow-up examination, all the patients demonstrated lesions colposcopically consistent with adenosis of the vagina or vulva within the area treated with the CO2 laser. Biopsies of the lesions were performed, adenosis was confirmed histologically, and endometriosis was ruled out histologically. This entity has not been previously associated with CO2 laser vaporization, and its clinical significance is undetermined. Further follow-up is indicated.

Kinetic determination of alkaline phosphatase activity based on hydrolytic cleavage of the P-F bond in monofluorophosphate and fluoride ion-selective electrode.

Alkaline phosphatase catalyzes the hydrolytic cleavage of the P-F bond in monofluorophosphate with the subsequent release of fluoride ions. A kinetic potentiometric method is described in which a fluoride ion-selective electrode is used for the sensitive and selective measurement of the released F- for the determination of alkaline phosphatase activity. It is shown that monofluorophosphate can be used as an alternative substrate for alkaline phosphatase. The reaction demonstrates a well-defined correlation with the hydrolysis of the P-O bond in 4-nitrophenyl phosphate. The serum alkaline phosphatase was determined in human serum samples by the potentiometric technique, and the results obtained compared well with a standard spectrophotometric method.

Sulconazole nitrate 1% cream in the treatment of chronic moccasin-type tinea pedis caused by Trichophyton rubrum.

Sulconazole nitrate 1% cream applied twice daily was compared with its vehicle in the treatment of 229 patients with chronic moccasin-type tinea pedis confirmed by positive results of a potassium hydroxide preparation. At admission in this randomized, double-blind, parallel multicenter trial, 131 patients had positive dermatophyte cultures; Trichophyton rubrum was identified in 121 (92%). After 4 weeks of treatment, patients were examined and, if necessary, were treated for an additional 2 weeks. Sulconazole cream was significantly more effective than the vehicle in the treatment of chronic T. rubrum tinea pedis; 57% of patients were cured by sulconazole, compared with 13% cured with the vehicle. Relapse rates, assessed 2 weeks after the end of treatment, were significantly lower in patients treated with sulconazole than in those receiving vehicle (27% vs 71%). The 103 patients with moccasin-type tinea pedis whose cultures were not positive for T. rubrum achieved similar results.

Extended carbon dioxide laser vaporization in the treatment of subclinical papillomavirus infection of the lower genital tract.

This study examined the use of extended carbon dioxide laser vaporization in 25 women with histologically confirmed, multicentric subclinical papillomavirus infection of the lower genital tract to determine whether carbon dioxide laser can eradicate subclinical papillomavirus infection. An extended carbon dioxide laser procedure involved vaporization of the epithelium of the entire lower genital tract. We performed the procedure under colposcopic guidance. Vaporization was carried out in continuity, to an appropriate tissue depth, while using recommended power densities for the respective target tissue. For sexually active study patients, male consorts were evaluated and treated concurrently to reduce the risk of recurrent infection. Postoperative morbidity was considerable, with moderate to severe vulvar pain and febrile reactions occurring in 100 and 76% of patients, respectively. Histologic persistence of subclinical papillomavirus infection was documented in 88% of study patients at follow-up examination. Neither treatment of the male consort nor sexual abstinence significantly improved treatment outcome. These data suggest that extended carbon dioxide laser procedures cause significant short-term morbidity without effectively eradicating subclinical papillomavirus infection of the female lower genital tract.