Rectocele—does the size matter?

Objectives

Large rectoceles (>2?cm) are believed to be associated with difficulty in evacuation, constipation, rectal pain, and rectal bleeding. The aim of our study was to determine whether rectocele size is related to patient’s symptoms or defecatory parameters.

Methods

We conducted a retrospective study on data collected on patients referred to our clinic for the evaluation of evacuation disorders. All patients were questioned for constipation, fecal incontinence, and irritable bowel syndrome and were assessed with dynamic perineal ultrasonography and conventional anorectal manometry.

Results

Four hundred eighty-seven women were included in our study. Rectocele was diagnosed in 106 (22%) women, and rectocele diameter >2?cm in 93 (87%) women. Rectocele size was not significantly related to demographic data, parity, or patient’s symptoms. The severity of the symptoms was not correlated to the size or to the position of the rectocele. The diagnosis of irritable bowel syndrome was neither related to the size of the rectocele. Rectocele location, occurrence of enterocele, and intussusception were not related to the size of the rectocele. Full evacuation of rectoceles was more common in small rectoceles (79% vs. 24%, p?=?0.0001), and no evacuation was more common in large rectoceles (37% vs. 0, p?=?0.01). Rectal hyposensitivity and anismus were not related to the size of the rectocele.

Conclusion

In conclusion, only the evacuation of rectoceles was correlated to the size of the rectoceles, but had no clinical significance. Other clinical, anatomical factors were also not associated to the size of the rectoceles. Rectoceles’ size alone may not be an indication for surgery.     

Enhanced Bone Regeneration Using Porcine Small Intestinal Submucosa

Small instestinal submucosa (SIS) is an easily produced material that has been used experimentally for tissue engineering. To evaluate the ability of SIS to facilitate bone growth within a long-bone defect, a segment of the radius was surgically removed in adult, female Sprague-Dawley rats. The defect was either left unfilled or implanted with SIS, demineralized cortical bone (DMCB), or ovalbumin. The defect was evaluated radiographically and histologically after 3, 6, 12, and 24 weeks. Tissue remodeling within the defect was evident by week 3 in SIS- and DMCB-treated rats. Filling was characterized initially by infiltration of mononuclear cells and extracellular material in SIS-implanted rats and multifocal remodeling bone particles and cartilage formation in DMCB implanted rats. Cartilage was observed as early as 3 weeks and bone as early as 6 weeks in SIS-implanted rats. Filling of the defect arose from multiple foci in DMCB-implanted rats, but was contiguous with and parallel to the ulnar shaft in SIS-implanted rats, suggesting that defect repair by SIS may be conductive rather than inductive. Rats in which the defect was left unfilled demonstrated slow but progressive filling of the defect, characterized by mononuclear cell infiltrates and fibrous extracellular material. In summary, SIS facilitated rapid filling of a longbone defect. These results suggest that SIS may be useful as a bone repair material.     

Survival of Chlamydia muridarum within dendritic cells

Immune responses to Chlamydia trachomatis underlay both immunity and immunopathology. Immunopathology in turn has been attributed to chronic persistent infection with persistence being defined as the presence of organisms in the absence of replication. We hypothesized that dendritic cells (DCs) play a central role in Chlamydia immunity and immunopathology by favoring the long-term survival of C. muridarum. This hypothesis was examined based on (i) direct staining of Chlamydia in infected DCs to evaluate the development of inclusions, (ii) titration of infected DCs on HeLa cells to determine cultivability, and (iii) transfer of Chlamydia-infected DCs to naive mice to evaluate infectivity. The results show that Chlamydia survived within DCs and developed both typical and atypical inclusions that persisted in a subpopulation of DCs for more than 9 days after infection. Since the cultivability of Chlamydia from DCs onto HeLa was lower than that estimated by the number of inclusions in DCs, this suggests that the organisms may be in state of persistence. Intranasal transfer of long-term infected DCs or DCs purified from the lungs of infected mice caused mouse lung infection, suggesting that in addition to persistent forms, infective Chlamydia organisms also developed within chronically infected DCs. Interestingly, after in vitro infection with Chlamydia, most DCs died. However, Chlamydia appeared to survive in a subpopulation of DCs that resisted infection-induced cell death. Surviving DCs efficiently presented Chlamydia antigens to Chlamydia-specific CD4+ T cells, suggesting that the bacteria are able to both direct their own survival and still allow DC antigen-presenting function. Together, these results raise the possibility that Chlamydia-infected DCs may be central to the maintenance of T-cell memory that underlies both immunity and immunopathology.     

Confirmatory factory analysis of the Neck Disability Index in a general problematic neck population indicates a one-factor model

Background contextThe Neck Disability Index frequently is used to measure outcomes of the neck. The statistical rigor of the Neck Disability Index has been assessed with conflicting outcomes. To date, Confirmatory Factor Analysis of the Neck Disability Index has not been reported for a suitably large population study. Because the Neck Disability Index is not a condition-specific measure of neck function, initial Confirmatory Factor Analysis should consider problematic neck patients as a homogenous group.PurposeWe sought to analyze the factor structure of the Neck Disability Index through Confirmatory Factor Analysis in a symptomatic, homogeneous, neck population, with respect to pooled populations and gender subgroups.Study designThis was a secondary analysis of pooled data.Patient sampleA total of 1,278 symptomatic neck patients (67.5% female, median age 41 years), 803 nonspecific and 475 with whiplash-associated disorder.Outcome measuresThe Neck Disability Index was used to measure outcomes.MethodsWe analyzed pooled baseline data from six independent studies of patients with neck problems who completed Neck Disability Index questionnaires at baseline. The Confirmatory Factor Analysis was considered in three scenarios: the full sample and separate sexes. Models were compared empirically for best fit.ResultsTwo-factor models have good psychometric properties across both the pooled and sex subgroups. However, according to these analyses, the one-factor solution is preferable from both a statistical perspective and parsimony. The two-factor model was close to significant for the male subgroup (p<.07) where questions separated into constructs of mental function (pain, reading headaches and concentration) and physical function (personal care, lifting, work, driving, sleep, and recreation).ConclusionsThe Neck Disability Index demonstrated a one-factor structure when analyzed by Confirmatory Factor Analysis in a pooled, homogenous sample of neck problem patients. However, a two-factor model did approach significance for male subjects where questions separated into constructs of mental and physical function. Further investigations in different conditions, subgroup and sex-specific populations are warranted.     

Monoclonal antibodies recognizing epitopes on the extracellular face and intracellular N-terminus of the human erythrocyte anion transporter (band 3) and their application to the analysis of South East Asian ovalocytes

This report describes the production and characterization of 13 rodent monoclonal antibodies to the human erythrocyte anion transport protein AE1 (syn. band 3). Eleven antibodies (4 murine and 7 rat) recognize epitopes dependent on the integrity of the third extracellular loop of the protein. Two antibodies (1 murine and 1 rat) recognize epitopes on the N-terminal cytoplasmic domain. Quantitative binding studies using radioiodinated IgG and Fab fragments of antibodies to extracellular epitopes on AE1 ranged from 77,000 to 313,000 (IgG) and from 241,000 to 772,000 (Fab) molecules bound at saturation. The results indicate that the epitopes recognized by different antibodies vary in their accessibility and suggest that there is heterogeneity in the organization of individual AE1 molecules in the red blood cell membrane. Quantitative binding studies on South East Asian ovalocytes using several antibodies to AE1 and an anti-Wrb show a marked reduction in the number of antibody molecules bound at saturation. These results are consistent with the existence of highly cooperative interactions between transmembrane domains of AE1 in normal erythrocytes and the disruption of these interactions in the variant AE1 found in South East Asian ovalocytes.     

Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans

Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin-induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra.     

Utilization of monoclonal antibodies in the treatment of leukemia and lymphoma

The generation of murine monoclonal antibodies reactive with human leukemia and lymphoma cells has recently led to clinical trials that have begun to evaluate the use of these reagents in the treatment of various leukemias and lymphomas. Several of these studies have demonstrated that infusion of monoclonal antibody can cause the rapid and specific clearance of leukemic cells from the peripheral blood. Intravenously administered antibody also rapidly binds to bone marrow lymphoblasts, and in one instance, has resulted in the partial regression of tumor cell infiltrates in lymph nodes and skin. Unfortunately, clinically significant responses have not in general been achieved, but these clinical studies have identified specific factors that result in the development of resistance to antibody- mediated lysis in vivo. These factors include the presence of circulating antigen, antigenic modulation, reactivity of monoclonal antibody with normal cells, immune response to murine antibody, and the inefficiency of natural immune effector mechanisms. Current research is now being directed towards developing methods to circumvent each of these obstacles. Future clinical studies utilizing antibodies in vitro or with different specificity may demonstrate greater therapeutic efficacy. In addition, monoclonal antibodies can be used as carriers of other cytotoxic agents and in conjunction with other agents that will reduce the total load. Monoclonal antibodies represent new and powerful reagents that may in the near future become an additional therapeutic modality for patients with malignant disease.     

Trace-Forward Investigation of Mice in Response to Lymphocytic Choriomeningitis Virus Outbreak

During follow-up of a 2012 US outbreak of lymphocytic choriomeningitis virus (LCMV), we conducted a trace-forward investigation. LCMV-infected feeder mice originating from a US rodent breeding facility had been distributed to >500 locations in 21 states. All mice from the facility were euthanized, and no additional persons tested positive for LCMV infection.     

The management of epilepsy in pregnancy

While most women with epilepsy can expect a normal pregnancy outcome, epilepsy remains a significant contributor to both maternal and perinatal morbidity. Pre-pregnancy planning must address reliable contraception and optimisation of antiepileptic drug (AED) regimens to minimise teratogenic risk while maintaining seizure control. The most recent data from the AED registries regarding malformations is presented in this review, as is the limited data on the newer AEDs and studies linking neurocognitive outcomes to AED exposure. During pregnancy, important considerations include; therapeutic drug monitoring, surveillance for obstetric complications and vigilance for seizures during the intrapartum and postpartum period.