The effect of age on complications in women undergoing minimally invasive sacral colpopexy.

INTRODUCTION AND HYPOTHESIS: Previous research has demonstrated similar complication rates in older and younger women undergoing abdominal sacral colpopexy via laparotomy. The objective of this study was to compare perioperative complications in older and younger women undergoing minimally invasive sacral colpopexy. METHODS: This was a retrospective study of laparoscopic and robotic sacral colpopexies performed from January 2009 to May 2012 at a large academic center. Patient demographics, surgical data, and perioperative complications were compared in women < 65 and ≥65 years of age. Primary outcome was the difference in major complications. RESULTS: A total of 302 women underwent minimally invasive sacral colpopexy during the study period. Mean age was 58.5 ± 8.8 years and 84 subjects (27.8 %) were ≥65 years. Older women were more likely to have had a prior hysterectomy (60.7 vs 39.0 %, p = 0.001) and had more severe preoperative prolapse (86.9 % vs 71.9 % ≥ POPQ stage III, p = 0.01). There was no significant difference in duration of hospitalization (1.4 vs 1.4 days, p = 0.54). Overall, there were significantly more major complications in women ≥ 65 years (unadjusted OR 1.84, 95 % CI 1.02-3.35, p = 0.04). After controlling for BMI, route of surgery, estimated blood loss (EBL), and operating room time, age ≥ 65 remained a significant predictor of complications (adjusted OR 2.28, 95 % CI 1.21-4.29, p = 0.01). CONCLUSIONS: Our findings suggest that older women have a higher rate of major complications following minimally invasive sacral colpopexy, even after controlling for BMI, route of surgery, EBL, and operating room time. This increased risk should be addressed during preoperative counseling and may influence surgical planning.

Idiotype variant cell populations in patients with B cell lymphoma.

Using isolated idiotype (Id) protein we generated panels of antibodies in two patients with follicular lymphoma, one of whom had never received prior chemo-or radiotherapy. Flow cytometry and frozen section tissue staining of tumor with these monoclonal antibodies (mAb) revealed multiple subpopulations within each tumor. Individual mAb stained between 7% and 83% of surface Ig+ cells in the tumor samples. These subpopulations were overlapping and no single antibody recognized all the tumor cells. However, combinations of antibodies seemed to capture total tumor in both cases. In some instances, the percentage of tumor stained by a single mAb varied over time, and differed between lymph nodes sampled at the same time. Because a single species of Id protein was used to generate mAb in each case, it appears that the antibodies were directed against idiotopes variably shared by different populations within each tumor, and this was confirmed by crossblocking studies. Tumor cells from one patient were fused to a nonsecreting heteromyeloma line K6H6/B5, and most of the resulting hybrids secreted Id protein. Four mAb were used to screen the Id proteins secreted by these hybrids, and 11 different variants (16 maximal) were found. Southern blot analysis of rearranged Ig genes was done in two hybrids and biopsy material. Identically rearranged light-chain genes were seen but it appeared as though extensive somatic variation had occurred in heavy chain genes. These studies indicate that: striking Id variation can exist at diagnosis in untreated patients, the percentage of tumor represented by an individual variant may change with time and may differ between tumor sampled from different anatomical locations, and somatic variation appears to be responsible for the observed heterogeneity. Although this degree of variation makes anti-Id antibody therapy more difficult, appropriate combinations of mAb should be more efficacious than single antibodies in such cases.

High-dose thiotepa with autologous bone marrow transplantation for metastatic malignant melanoma: results of phase I and II studies of the North American Bone Marrow Transplantation Group.

We evaluated thiotepa in escalating dose in a broad phase I and II study using cryopreserved autologous bone marrow transplantation to assure hematopoietic recovery. Thiotepa was administered intravenously (IV) over two hours daily for three consecutive days followed in three to four days by marrow transplantation. The daily dose ranged from 60 to 525 mg/m2 (total dose, 180 to 1,575 mg/m2). A total of 71 patients with malignant melanoma were treated. Forty-three patients (61%) had received prior cytotoxic therapy and 28 were untreated. Sixty-two patients (87%) had melanoma disseminated to at least one visceral site, nine patients had skin and/or lymphatic metastases only. As of January 1, 1988 one patient was too early to be evaluated, 15 patients were inevaluable for tumor response, four patients had a complete response (CR), and 25 patients had a partial response (PR) to treatment. The response rates (95% confidence interval) for the 55 evaluable patients and for all 71 treated patients were 53% (40% to 65%) and 41% (30% to 53%), respectively. The median duration of response was 3 months, with a range of 1 to 31 + months. Three patients were alive and well without evidence of tumor more than 1 year after treatment. Analysis of patient subsets indicated that neither total dose, previous cytotoxic therapy, or sites of metastases influenced response rate. In this study, high-dose thiotepa has demonstrated a high response rate in patients with metastatic malignant melanoma with both PRs and CRs noted. Although most of the responses were not durable, 10% of the responses lasted more than 1 year. Future studies will evaluate additional methods for increasing the response rate and improving the duration of response.

Bacteremias and fungemias in oncologic patients with central venous catheters: changing spectrum of infection.

Ninety central venous catheters were inserted into 80 patients undergoing therapy for malignant neoplasms. Bacteremia and fungemia occurred in 18 of 41 treatment courses in patients with acute leukemia and in nine of 55 treatment courses in patients with solid tumors and lymphomas. Although gram-negative organisms accounted for nine (33%) cases of infection, the majority of disseminated infections were caused by gram-positive organisms (12 [45%] cases) or fungi (six [22%] cases). Central venous catheters may be helpful in the treatment of patients undergoing intensive therapy with cytotoxic agents, but the shift in-spectrum of infection to gram-positive bacteremias in patients with these catheters compared with patients treated using peripheral vein access must be appreciated.

Influence of dietary iron deficiency on hemoglobin, myoglobin, their respective reductases, and skeletal muscle mitochondrial respiration.

Male weanling rats were fed a control diet (46 ppm iron) or an iron-deficient diet (11 ppm iron) for 7 wk to determine the influence of iron deficiency on heme proteins and skeletal muscle mitochondrial respiration. At the end of 7 wk, the hemoglobin in the blood of the iron deficient rats was 35% less and skeletal muscle myoglobin was 20 to 37% less than in the control animals. The concentration of myoglobin in the heart was not appreciably diminished by iron deficiency. Cytochrome c concentration was 20% less in the heart and 35% less in the mixed-fiber gastrocnemius in the iron-deficient animals. Iron deficiency did not influence the activity of metmyoglobin reductase in either heart or skeletal muscle. There was about 30% more methemoglobin reductase activity in the red blood cells of the iron-deficient animals, which resulted in methemoglobin levels that were so low as to be virtually unmeasurable. In the iron-deficient rats, skeletal muscle mitochondrial respiration with either pyruvate-malate or palmitylcarnitine as substrate was 17 to 20% less than in the control animals. This study demonstrates that dietary iron deficiency of sufficient severity to reduce blood Hb and skeletal muscle myoglobin or cytochrome c also results in an impaired skeletal muscle oxidative capacity. The study also illustrates the preferential utilization of iron, not only between tissues, but within tissues, and tissue specific adaptive responses to iron deficiency.

Quantitation and estimation of lymphocyte subsets in tissue sections. Comparison with flow cytometry.

A quantitation method for lymphocyte subsets in immunoperoxidase-stained frozen tissue sections was compared with flow cytometry in 23 cases of non-Hodgkin's lymphoma. Close correlations were obtained, demonstrating the accuracy of the technic. Weak intensity of fluorescence and fragility of the tumor cells during the fluorescence-activated cell sorter (FACS) analyses were the most likely explanations for a number of the discrepancies observed. The tissue quantitation method was precise, particularly at low values, where it was better than the FACS. A simpler and faster estimation method employing categories within 10 percentage units was also tested in this study; this method correlated as well with the FACS as the quantitation method and gave the best interobserver correlations.

A prospective randomized trial of central venous catheter removal versus intravenous amphotericin B in febrile neutropenic patients.

Empiric amphotericin B therapy was compared to central venous catheter Githdrawal in a prospective randomized trial. Of 32 febrile, neutropenic patients with indwelling Broviac catheters and without documented infection, 14 had persistent fever while receiving broad spectrum antibacterial drugs. Six patients were randomized to catheter removal and eight patients received amphotericin B empirically. None of six patients responded to catheter removal and six of eight defervesced after receiving antifungal therapy (p less than 0.01). Of the six patients in whom catheters were removed, two later became afebrile while on subsequent therapy with amphotericin B. Culture and histologic evaluation of the removed catheters failed to implicate the prosthesis as an infectious source. Central venous catheters in a persistently febrile neutropenic host need not be removed, unless local difficulties or bacteremia with skin commensal organisms occur. Amphotericin B can be infused through a central venous catheter in febrile, neutropenic patients unresponsive to empiric antibacterial drugs, with many patients becoming afebrile as a result of this therapy.

Monocytic leukemoid reaction, glucocorticoid therapy, and myelodysplastic syndrome.

A leukemoid reaction is a complex and poorly understood response by the bone marrow to a variety of stresses; although any peripheral blood cell line may be involved, it is rarely a purely monocytic event. A case is reported of a true monocytic leukemoid reaction in a patient with myelodysplastic syndrome related to the effect of corticosteroids on the underlying marrow disorder.

Macular and paramacular detachment of the neurosensory retina associated with systemic diseases.

We have reviewed 168 cases of angiographically proved SRD of the macular region of unknown etiology that were seen at The Cleveland Clinic Foundation. Thirty-seven percent of these patients had documented coincident systemic diseases. Of that group, patients with autoimmune disease appeared to have ocular symptoms during the active phase of the systemic illness. Nine cases are reported characterizing the coincidence of exacerbation of systemic disease with recurrent serous detachment of the neurosensory retina. It is our hypothesis that in patients with autoimmune disease, the choroiditis is secondary to the damage caused by immune complexes. Thus, in these patients, SRD was a manifestation of the systemic illness.

Monoclonal antibodies--therapeutic and diagnostic uses in malignancy.

Murine monoclonal antibodies represent an attractive type of antitumor therapy because of their potential for exquisite specificity, production in large, pure quantities and mediation of in vivo cytotoxic effects. With maturing monoclonal antibody technology has come the use of these antibodies in clinical studies in patients with malignancy. These trials have established that monoclonal antibodies can be safely administered in large doses, that their pharmacokinetics and tissue penetration can be predicted and that in some instances a therapeutic effect can be produced by their infusion. A number of problems have also been identified by these studies, including antigenic heterogeneity of the tumor, the presence of free serum antigen, the immunogenicity of the xenogeneic antibody, modulation of the surface antigen by the antibody and a finite capacity of human effector mechanisms to mediate cytotoxicity directed by murine antibodies. Other workers are concurrently investigating the use of monoclonal antibodies in the ex vivo elimination of cells from bone marrow, as probes for serum tumor marker antigens and as carriers for radioimaging agents or toxins. Although most of these endeavors are at the earliest stages, promising preliminary results presage an important role for native and altered monoclonal antibodies in the diagnosis and treatment of malignant conditions.

Microbial contamination of cellular products for hematolymphoid transplantation therapy: assessment of the problem and strategies to minimize the clinical impact.

BACKGROUND: Hematopoietic progenitor stem cells (HPSC) are a specialized transfusion product used for transplantation. Microbial contamination may occur during harvest or subsequent manipulation of these cells. The same difficulties in ensuring a safe, sterile, final product are faced in the preparation of other cell-therapy products directly obtained from donors. Detection of contamination is problematic, and the clinical significance of infusing contaminated HPSC is controversial. METHODS: Chimeric Therapies' manufacturing and clinical experience with BM HPSC products and validation of a culture method for detection are described. In addition, this paper reviews the literature concerning contaminated blood products, including rates and circumstances of contamination, organisms, methods of detection, and the clinical significance of infusion of contaminated products. RESULTS: Seven of 33 BM harvest products received at Chimeric Therapies were culture positive for skin commensal organisms. Three of seven were culture positive in the infused product. This compares with literature reports of 0-42%. No patients had significant infusion reactions or evidence of infection related to the contamination. DISCUSSION: The risks associated with microbial contamination with skin commensals are insignificant compared with other components of transplantation. Contamination with pathogens can be eliminated with careful good manufacturing practices (GMP). A series of practical recommendations are presented for the reduction of contamination in HPSC and cell-therapy products.

The generation of the rifamycin binding site in the beta subunit of E. coli RNA polymerase through subunit interactions.

Spectral studies were performed using rifampicin quinone to investigate the generation of the rifamycin binding site in the beta subunit of E. coli RNA polymerase due to subunit interactions. The spectrum of rifampicin quinone is not significantly altered in the presence of the beta subunit. In the case of the alpha 2 beta subassembly, a negative difference spectral band at 330 nm is observed for rifampicin quinone, whereas in the presence of either the holoenzyme or core polymerase a positive band at 348 and a negative one at 318 are observed. In affinity labeling studies using 3-(2-bromo[1-14C]acetamidoethyl)-thiorifamycin, it was demonstrated that the isolated beta subunit is nonspecifically modified by this reagent. However, in the case of both the alpha 2 beta subassembly and core polymerase, the beta subunit is specifically modified.

Innovations in quality.

To strengthen their operations many hospitals have embraced total quality management (TQM) strategies used by companies throughout the world. California Hospitals examines how some of these hospitals have used TQM to improve clinical outcomes, cut costs, boost staff morale and increase patient satisfaction.

Monoclonal antibody therapy of lymphoid malignancy.

Monoclonal antibodies which bind to tumour cell surface antigens have produced regressions of malignancies in an increasing number of clinical trials. The largest experience to date is in the treatment of refractory B and T lymphoid tumours using a variety of intravenously administered mouse monoclonal antibodies. Treatment with antibodies against common differentiation antigens or very specific anti-idiotype antibodies has been effective in both cases. Toxicity has been acceptably low. A number of problems which limit the application and efficacy of monoclonal antibody therapy of lymphoid malignancy have been identified. Most prominent among these are tumour heterogeneity, which allows non-antibody binding subpopulations of the tumour to escape therapy, and the patient's immunological response to the monoclonal antibody-tumour cell complex. As more experience is accumulated, solutions to these problems will be found.

Flow cytometric analysis of peripheral blood lymphocytes in ulcerative colitis and Crohn's disease.

Using two colour immunofluorescence with fluorescein isothiocyanate and phycoerythrin labelled monoclonal antibodies, multi-parameter flow cytometry was used to examine the antigenic characteristics of peripheral blood lymphocytes in whole blood of patients with ulcerative colitis and Crohn's disease who were not taking immunosuppressive drugs. The numbers of CD4+ and CD8+ lymphocytes in patients with ulcerative colitis and Crohn's disease remained unchanged so that the CD4/CD8 ratio was the same as that of normal control subjects. In Crohn's disease there were many activated T cells (CD3+, CD25+). Although natural killer cells in active Crohn's disease were lower than in normal control subjects, cytotoxic T lymphocytes, as defined by CD3+, CD16+, did not differ in patients with inflammatory bowel disease compared with normal control subjects. For B cell subsets, there were differences in Leu-1+ B cells, Leu-8+ B cells, Fc epsilon R+B cells (Leu-16+, Leu-20+), and activated B cells (Leu-12+, Leu-21+) between patients with inflammatory bowel disease and normal control subjects. These differences are compatible with local activation of B cells in the inflamed colon.

Selective activation of T cells in newly diagnosed insulin-dependent diabetic patients: evidence for heterogeneity of T cell receptor usage.

Cell surface phenotyping of 58 newly diagnosed diabetic children and 25 controls confirmed the presence of activated T cells, expressing HLA class II antigens or receptors for interleukin-2 (IL-2R, CD25) in the majority of the patients. Some of these cells putatively include those involved in islet cell destruction, as reported previously. Monoclonal antibodies recognizing three families of the variable regions of the beta chain (V beta) of the T cell receptor were used to determine the percentage of peripheral blood cells expressing those specific gene segment products. The number of the activated T cells from each V beta family was compared with that of the resting T cells of the same family in the patients and the controls. In 18 out of 58 (31%) of these patients there was evidence of oligoclonal proliferation of activated T cells as judged by marked increases in cells expressing a V beta family in the IL-2R+ T cell pool, compared with the total T cell pool. However, different V beta families were augmented in individual patients, indicating considerable heterogeneity of T cell activation in different patients. These results are in contrast to murine models of autoimmunity, where virtually monoclonal T cell activation, restricted to a single V beta family has been reported.

[Changes in the physiological role of the neurotransmitters during individual development]. / Izmenenie fiziologicheskoi roli neirotransmitterov v techenie individual'nogo razvitiia.

Classical neurotransmitters acetylcholine and biogenic monoamines act as multifunctional substances throughout the metazoan ontogenesis. A suggested cyclic scheme describes developmental changes of neurotransmitter functions from the oocyte maturation to neuron formation.

Does acute volume overloading in the setting of left ventricular dysfunction and pulmonary hypertension affect the defibrillation threshold?

The impact of acute volume overload hemodynamics on the DFT with concurrent moderate left ventricular systolic dysfunction is unknown. Ten mongrel dogs (17.2 kg), using a crossover study design, each had baseline (study 1) hemodynamic, echocardiographic, and DFT measurements. These measurements were repeated after left ventricular dysfunction was induced using a norepinephrine (5 micrograms/kg per min) infusion (study 2). Hemodynamic and DFT parameters were obtained simulating acute heart failure by volume overload with an 0.9% normal saline infusion to an associated mean pulmonary capillary wedge pressure of > 19 mmHg (study 3). Numerous significant echocardiographic and hemodynamic parameters were noted when the animals from studies 1 and 2, 2 and 3, and 1 and 3 were compared. A significant difference in the DFT was observed only when study animals 1 and 3 were compared (P < 0.02). None of the dogs were hypoxemic at the time of the acute heart failure DFT. The mechanism of this finding remains unknown. This data would suggest that acute volume overload with associated left ventricular dysfunction does adversely affect the DFT in a canine model.

Occlusion and infection in Broviac catheters during intensive cancer therapy.

Before administration of intensive cytotoxic therapy, 90 central venous catheters were inserted into 80 patients with malignancies. Twenty-seven episodes of bacteremia and fungemia occurred during 96 treatment courses. The majority of these infections were due to gram-positive bacteria (45%) or fungi (22%), although gram-negative organisms accounted for 33%. Catheter occlusion occurred in patients receiving intravenous phenytoin, but blood products could be infused without difficulty. An increase in gram-positive bacteremias in patients with these catheters and drug-induced catheter occlusion must now be appreciated.