Assessment of hot flushes and vaginal dryness among obese women undergoing bariatric surgery.

OBJECTIVE: Menopausal symptoms are associated with a negative impact on the quality of life, leading women to seek medical treatment. Obesity has been linked to higher levels of menopausal symptoms such as hot flushes. This assessment will explore whether the prevalence and bother of hot flushes and vaginal dryness change from pre- to post-bariatric surgery among obese midlife women. METHODS: This study is a longitudinal analysis of data from 69 women (ages 35-72 years) undergoing bariatric surgery with reported reproductive histories and menopausal symptoms at preoperative and 6-month postoperative visits. Prevalence of and degree of bother of hot flushes and vaginal dryness at pre- and post-surgery were compared using McNemar's test and Wilcoxon signed-rank test. RESULTS: The reported degree of bother of symptoms associated with hot flushes decreased from pre- to post-surgery (p < 0.01). There was no significant change in the prevalence of hot flushes or vaginal dryness in the overall study sample. CONCLUSIONS: The degree of bother of symptoms associated with hot flushes among midlife women may decrease after bariatric surgery. These results highlight important secondary gains, including less bothersome menopausal symptoms, for women who choose bariatric surgery for weight loss.

Medical strategies for weight loss in the overweight and obese patient.

In recent years, obesity has become a major public health problem in Western countries. The World Health Organization has defined obesity as a global epidemic of the third millennium. Treatment options for weight management include dietary intervention, physical activity, behavior modification, pharmacotherapy and surgery. However, the complexity of this chronic condition necessitates a coordinated multidisciplinary team-approach to the care of obese patients who fail weight control. The long-term duration of the treatment and the necessity of monitoring compliance and effectiveness should be considered. The objective of this article was to review the major controlled randomized clinical trials dealing with the different medical strategies for weight loss and its maintenance in overweight and obese patients.

Sealing effect of fibrin glue on the healing of gastrointestinal anastomoses: implications for the endoscopic treatment of leaks.

BACKGROUND: The adoption of advanced laparoscopic techniques for complex surgical procedures has raised the concern that the leak rate might be higher than for open surgery, particularly in the surgeon's early experience or in difficult cases. In this study, the sealing effect of fibrin glue on leaking gastrointestinal anastomoses was evaluated in an experimental swine model. METHODS: A standardized gastrojejunostomy was performed on 20 female pigs (mean weight, 47.7 +/- 5.7 kg). A leak was created on the anterior surface of the anastomosis. The animals were randomized to either fibrin glue or no treatment of the leak. Clinical conditions and vital signs, including body temperature, heart rate and, respiratory rate, were collected three times a day. Preoperative and postoperative complete and differential blood count and lactate dehydrogenase levels were determined. Postmortem analysis was performed when the animals were killed. RESULTS: Clinical signs of peritonitis developed in the control animals by the second or third postoperative day. Findings that confirmed the presence of an anastomotic leak at the postmortem examination were the presence of food or gastrojejunal juices in the abdominal cavity, a localized abscess, or a positive air leak test. Fibrin glue treatment prevented the development of peritonitis in all the animals. Complete sealing of the leak was observed on postoperative day 7 in all treated animals, except one in which an asymptomatic contained leak developed. The postoperative total white blood count was significantly increased in the untreated group (24.69 +/- 5.5 vs 12.74 +/- 3.7 10(3)/ul p < 0.001, paired t-test), as compared with the treated group (15. 55 +/- 2.4 vs 14.89 +/- 2.7 10(3)/ul; p = 0.24). CONCLUSION: In this study, fibrin glue showed reproducible sealing effects on leaking gastrojejunal anastomoses. Fibrin glue application may be a valuable approach for the treatment of gastrointestinal anastomotic leaks.

Bryostatin/ionomycin-activated T cells mediate regression of established tumors.

We have shown that adoptive transfer of tumor-sensitized lymphocytes activated in vitro with bryostatin-1 and ionomycin (B/I), and expanded in culture, can induce regression of small established tumors. We set out to determine whether similar treatment would be effective against larger tumors and what cells mediate this effect. We also attempted to shorten the ex vivo culture period with the ultimate aim of developing a more clinically useful protocol. BALB/c mice were injected in one footpad with IL-2-transfected 4T07 mammary tumor cells. Ten days later, popliteal draining lymph nodes (DLN) were harvested and activated with B/I for 18 h. Mice with either 3-day or 10-day 4T07 flank tumors were treated with cyclophosphamide (100 mg/ kg ip, CYP) alone or CYP followed the next day by infusion of either B/I-activated lymphocytes transferred immediately or activated cells that had been expanded in vitro for 3 or 10 days. In some experiments, mice were also treated with rat anti-mouse CD4 monoclonal antibody (GK1.5) or anti-CD8 antibody (2.43). All mice receiving CYP alone or CYP + sensitized, nonactivated DLN cells demonstrated progressive tumor growth. One hundred percent (6/6) of mice treated with CYP + AIT with B/I-activated,10-day expanded cells had complete regression of 3-day flank tumors. Treatment with activated, nonexpanded cells, induced tumor regression in a majority of mice, but was not as reliable as AIT with expanded cells. We developed a protocol with a shortened expansion period (3-day) that was efficacious for treatment of 4T07 when adoptively transferred to either 3 or 10 day tumor-bearing mice. In vivo depletion of CD4(+) cells had no effect on regression of 3-day tumors, but treatment with anti-CD8 antibody abrogated the effect of immunotherapy. Adoptive transfer of B/I-activated cells, with or without long-term expansion, induced regression of early and late stage 4T07 tumors and is dependent on CD8(+) but not CD4(+) T cells.

Laparoscopic pancreatic necrosectomy.

We describe a patient with infected pancreatic necrosis who was treated successfully with minimally invasive surgery. Five weeks after an episode of acute uncomplicated pancreatitis, he was found to have infected pancreatic necrosis and splenic vein thrombosis. The patient underwent a laparoscopic pancreatic necrosectomy, splenectomy, and cholecystectomy. Seven days after surgery, the patient was discharged and continued to be asymptomatic for the 6 months of follow-up.

Biochemical, hematologic, and immunologic alterations following hepatic cryotherapy.

Hepatic cryosurgery causes hepatocellular damage primarily by inducing the formation of ice crystals. Cell necrosis is enhanced using two or more freeze-thaw cycles. The resultant damage to hepatocytes induces alterations in a number of biochemical and hematologic parameters, including hepatic function tests, serum bilirubin, serum and urine myoglobin, platelet count, and coagulation measures. Further, in experimental models, cryogenic surgery appears to stimulate the immune system of the host leading to an anti-tumor immune response. These perturbations in biochemical and hematologic parameters are usually transient, and long-term adverse sequelae are uncommon and preventable.

Sensitizing T-lymphocytes for adoptive immunotherapy by vaccination with wild-type or cytokine gene-transduced melanoma.

BACKGROUND: For the relatively nonimmunogenic B16-F10 murine melanoma, it has been found that genetically engineered expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) but not interleukin (IL)-2, IL-4, or interferon-gamma (IFN-gamma) resulted in a vaccine that could induce resistance to rechallenge. Because T cells from lymph nodes draining the sites of some progressive tumors can mediate tumor regression after in vitro activation, it seemed possible that even apparently nonimmunogenic melanoma cells might induce similar preeffector cells in the vaccine-draining lymph nodes (DLNs). METHODS: C57BL/6 mice were vaccinated with B16-F10 cells that were either unmodified or genetically modified to produce IL-2, IL-4, GM-CSF, or IFN-gamma. DLNs were harvested 10 days after vaccination for adoptive immunotherapy (AIT). The DLN cells were activated with bryostatin 1 and ionomycin (B/I), expanded for 10 days in culture, and transferred to mice with 3-day pulmonary metastases. Pulmonary nodules were counted 14 days after AIT. RESULTS: Adoptive transfer of expanded DLN lymphocytes sensitized by inoculation of WT B16-F10, or IL-4, GM-CSF, or IFN-gamma expressing cells significantly reduced pulmonary metastases. Despite the spontaneous regression of IL-2-transduced B16-F10 tumors, DLN from mice inoculated with IL-2 producing B16 cells had little or no antitumor activity. CONCLUSIONS: B16-F10 vaccination strategies that apparently do not induce systemic immunity can effectively sensitize DLN preeffector cells.

Biologic therapy of melanoma with cytokines and lymphocytes.

Melanoma has a somewhat unpredictable behavior, and spontaneous regressions do occasionally occur. Many have surmised that these are the result of immunologic attack by the host. Immunologic treatment has been more successful for melanoma than for most other neoplasms, even with relatively crude therapies, such as bacterial products. With the availability of recombinant cytokines, immunotherapy for melanoma has entered a new era. Interleukin-2 (IL-2), which acts entirely through immunologic mechanisms, has been tested extensively, either alone, in combination with other cytokines, or with adoptive cellular therapy. Alone, it has only modest antitumor activity, even at high doses. Its utility may be greater when combined with immunocompetent cells, especially tumor-sensitized T lymphocytes, in adoptive immunotherapy. On the other hand, nonspecific lymphokine-activated killer (LAK) cells do not appear to add significantly to the efficacy of IL-2 alone. Interferon-alpha (IFN-alpha) [corrected] also has had fairly limited activity in the advanced disease setting, but, on the basis of a recently completed randomized trial, has arguably become the "standard of care" in the adjuvant setting for patients with high-risk melanoma, particularly node-positive patients. A number of regimens combining IL-2, IFN-alpha, and chemotherapeutic agents have yielded striking response rates in small trials and await confirmation in larger studies. With better delineation of the host immune response and definition of relevant tumor antigens, we can look forward to exciting results with combinations of vaccines, cytokines, and adoptive cellular approaches, particularly in patients with micrometastatic disease.

Bryostatin 1 activates splenic lymphocytes and induces sustained depletion of splenocyte protein kinase C activity in vivo after a single intravenous administration.

Bryostatin 1 activates and subsequently down-regulates protein kinase C (PKC) in vitro and has potential use as an immunomodulator and as an anti-cancer agent. Despite extensive examination of its activities in vitro and anti-tumor effects in vivo, previous studies have failed to document that bryostatin 1 modulates total cellular PKC activity in tumor or normal tissues when administered in vivo. After a single bolus injection of bryostatin 1 (1.0 microgram) in normal C57BI/6 mice, blood was drawn at various intervals and assayed for bryostatin 1 levels. In addition, spleens from bryostatin-treated mice were harvested 10 min to 10 days after treatment, weighed and analyzed for cell numbers, PKC activity and cell surface phenotypes. Bryostatin 1 levels in plasma rose rapidly, reaching peak levels of 56.5 nM less than 1 min after injection, and then declined to undetectable levels by 1 h. A similar pattern was observed when bryostatin 1 was incubated with leukemia cells in vitro, raising the possibility that the rapid fall in plasma levels results from intracellular uptake and binding. Bryostatin 1 induced marked depletion of total splenocyte PKC activity (as much as 69% relative to control values) at 24-96 h after drug administration, but not at earlier times (i.e. 1 h). A single injection of bryostatin 1 also induced expression of the T cell activation marker CD69, leading to positivity in 53% of cells at 3-24 h versus 11% in control mice, and resulted in marked splenomegaly, associated with increased numbers of nucleated cells at 48-96 h. Together, these studies demonstrate that despite rapid disappearance of the drug from plasma, a single i.v. dose of bryostatin 1 exhibits significant and sustained effects on normal murine spleen cells, including early lymphocyte activation, prolonged depletion of PKC activity, splenocyte proliferation and splenomegaly. These findings may have implications for attempts to understand the in vivo effects of bryostatin 1 in normal host tissues.

A comparison of the success rates of resident and attending strabismus surgery.

Residency training involves surgery by resident surgeons at various levels of experience and proficiency, supervised by an experienced attending physician. We reviewed the results of strabismus surgery performed at four institutions with two residency training programs. Five hundred twenty-two cases with follow up greater than 6 weeks were evaluated. These cases included 315 attending procedures and 207 resident procedures under direct attending supervision. Success was defined as a strabismic deviation of 8 prism diopters or less. Average postoperative follow-up was 57 weeks and did not differ between groups. There was no statistical difference between the resident success rate of 58% (121/207) and the attending success rate of 69% (217/315) after adjusting for population differences. The average final deviation of the patients postoperatively was 7 delta for the attending group and 10 delta for the resident group. Amblyopia was significantly more frequent in the resident cases (P < .001). Adjustable sutures were used significantly more often in attending cases (P < .0001). This study supports the premise that resident strabismus surgery is as successful as attending surgery.