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Surgical management of persistent müllerian duct syndrome.

OBJECTIVES: To describe the optimal surgical management of the testes and müllerian duct structures in patients with persistent müllerian duct syndrome. METHODS: We performed a comprehensive Medline literature search regarding the surgical management of persistent müllerian duct syndrome and extracted information regarding the etiology, pathogenesis, and treatment of this disorder. We specifically assessed the risks of retained müllerian structures versus surgical excision of the infantile uterus and fallopian tubes. Using this information, we formulated a comprehensive strategy for the management of patients with persistent müllerian duct syndrome. An illustrative case is described. RESULTS: No malignant degeneration of persistent müllerian structures has been reported. The risk of testicular neoplasia in persistent müllerian duct syndrome approximates the risk of neoplasia in other intra-abdominal gonads. Fertility has rarely been reported although virilization is unaffected. Surgical excision of the infantile uterus and fallopian tubes risks damage to vasa deferentia and the deferential blood supply to the testis. CONCLUSIONS: Surgical excision of persistent müllerian duct structure may result in ischemic and/or traumatic damage to the vasa deferentia and testes. Optimal surgical management is orchiopexy leaving the uterus and fallopian tubes in situ. Meticulous proximal salpingectomy and hysterectomy is indicated only in patients whose müllerian structures limit intrascrotal placement of the tests. Orchiectomy is indicated for testes that cannot be mobilized to a palpable location.

Congenital Abnormalities↗

Differential immune responses to acute lower respiratory illness in early life and subsequent development of persistent wheezing and asthma.

BACKGROUND: Recent epidemiologic evidence suggests that 2 wheezing syndromes coexist in early life: transient wheezing, limited to early childhood, and persistent wheezing, which starts in early childhood and persists beyond that age. OBJECTIVE: Whether the nature of the immune response occurring during acute lower respiratory illnesses (LRIs) in infancy differs between these 2 groups of wheezers has yet to be determined. METHODS: We compared total serum IgE levels and peripheral blood eosinophil counts obtained during the acute phase of the first LRI with those obtained during the convalescent phase or with well-baby samples in persistent (n = 49) and transient early wheezers (n = 88), as well as in children who had only nonwheezing LRIs (n = 43) during the first 3 years of life. RESULTS: Total serum IgE levels were significantly higher (P =.008) during the acute phase compared with the convalescent phase of the LRI in persistent wheezers, a response not observed in transient early wheezers (P =.7). Peripheral blood eosinophil counts were significantly reduced during the acute phase of the LRI (P =.009) in transient early wheezers, a response not observed among persistent wheezers (P =.7). Acute responses in children who had nonwheezing LRIs only were similar to those seen in transient early wheezers. CONCLUSION: Alterations in acute immune response to viral infection may be detected at the time of the first wheezing episode in subjects who will go on to have persistent wheezing symptoms.

Acute Disease↗

Double-blind randomised trial of co-amoxiclav versus placebo for persistent otitis media with effusion in general practice.

BACKGROUND: The treatment of persistent otitis media with effusion (OME) remains controversial, but this condition is the commonest reason for children to require ear, nose, and throat (ENT) surgery. Trials of antibiotics are inconclusive, are often weak methodologically, and have not been done in general practice. Our aim was a trial of an antibiotic for OME in such a population. METHODS: 433 children, aged 6 months to 6 years, with OME from 57 general practices entered a 3-month watchful waiting period. Of 223 (52%) with persistent bilateral OME, 162 were randomised double-blind to receive co-amoxiclav suspension (20 mg/kg amoxicillin, 5 mg/kg clavulanate potassium) or matching placebo, orally three times a day for 14 days. All cases also received xylometazoline 0.25% decongestant nosedrops thrice daily. Of the 61 not randomised, 13 children were referred to an ENT surgeon and parents refused consent in 48 cases. The main outcome measures were persistent OME in both ears and in one or both ears, as assessed clinically and by tympanometry. Analysis was by intention-to-treat. FINDINGS: 79 children in the treatment group and 70 in the placebo group were analysed for efficacy. 3 withdrew in the co-amoxiclav group (2 lost to follow-up, 1 due to side-effects); 6 withdrew in the placebo group (5 and 1, respectively). In addition, 4 tympanograms were uninterpretable in the controls. Compliance was over 90% in both groups. Persistent OME in both ears and in one or both ears were found at significantly lower rates in the co-amoxiclav group than in the controls at the 2-week follow-up: 53 vs 84% and 77 vs 93%, respectively. Odds ratios adjusted for sex, history of adenoidectomy, and upper respiratory tract infection at follow-up were 0.25 (95% CI 0.11, 0.58, p = 0.001) and 0.30 (0.10, 0.89, p = 0.03), respectively. Parents of children in the co-amoxiclav group reported significantly more side-effects than those of control children (44 vs 22%, p = 0.03). Side-effects were mostly gastrointestinal and mild. INTERPRETATION: Our study in a general-practice setting confirmed the positive short-term effect of antibiotic treatment for persistent middle-ear infection. Before referral to an ENT surgeon, children with persistent OME presenting to general practitioners could be considered for such treatment, depending on the individual child and possible adverse sequelae.

Amoxicillin↗

Does a coexisting anxiety disorder predict persistence of depressive illness in primary care patients with major depression?

We assessed whether a coexisting anxiety disorder predicts risk for persistent depression in primary care patients with major depression at baseline. Patients with major depression were identified in a 12-month prospective cohort study at a University-based family practice clinic. Presence of an anxiety disorder and other potential prognostic factors were measured at baseline. Persistent depressive illness (major depression, minor depression, or dysthymia) was determined at 12 months. Of 85 patients with major depression at baseline, 43 had coexisting anxiety disorder (38 with social phobia). The risk for persistent depression at 12 months was 44% greater [Risk Ratio (RR) = 1.44, 95% confidence interval (CI) 1.02-2.04] in those with coexisting anxiety. This risk persisted in stratified analysis controlling for other prognostic factors. Patients with coexisting anxiety had greater mean depressive severity [repeated measures analysis of variance (ANOVA), p < 0.04] and total disability days (54.9 vs 19.8, p < 0.02) over the 12-month study. Patients with social phobia had similar increased risk for persistent depression (RR = 1.40, 95% CI 0.98-2.00). A coexisting anxiety disorder indicates risk for persistent depression in primary care patients with major depression. Social phobia may be important to recognize in these patients. Identifying anxiety disorders can help primary care clinicians target patients needing more aggressive treatment for depression.

Adolescent↗

Mechanisms and consequences of enterovirus persistence in cardiac myocytes and cells of the immune system.

In humans and experimental murine models enteroviruses, and in particular coxsackieviruses of group B (CVB), may induce chronic myocarditis associated with a persistent type of heart muscle infection. Persistent myocardial infection has been characterized by restricted viral replication and gene expression, which is capable of sustaining chronic inflammation. Altered replication and transcription of the virus, in addition to an immune response insufficient to recognize and clear infected cells entirely, are essential mechanisms for initiation and maintenance of persistent heart muscle infection. Viral cytotoxicity was found to be crucial for organ pathology both during acute and persistent infection, indicating that enterovirus myocarditis is a virus-induced rather than an immune-mediated disease. Notably, resistance to the development of persistent heart muscle infection is not linked to the H-2 haplotype of the host. In addition to persistently infected myocytes, detection of the replicative minus-strand RNA intermediate provided evidence for virus replication in lymphoid cells of the spleen, predominantly in splenic B lymphocytes, during the course of the disease. Whereas viral RNA was also detected in certain CD4+ helper T cells and Mac1+ macrophages, no enteroviral genomes were identified in CD8+ T cells. Detection of infected activated B lymphocytes both in heart tissue of CVB3-infected immunocompetent mice and syngenic SCID mice receiving splenocytes from CVB3-infected donors support the concept that B cell traffic may contribute to maintenance of chronic disease. Dissection of the diversity of viral and host-specific determinants in susceptible and resistant hosts will allow us to define the protective mechanisms that mediate resistance to the development of life-threatening acute and chronic enterovirus myocarditis.

Animals↗

Characteristics of a macrophage culture persistently infected with herpes simplex virus type 1.

BACKGROUND: Persistence of herpes simplex type 1 (HSV-1) has been reported in sensory neurons, corneal epithelium, and lymphocytes, although other cell types such as macrophages should also be considered as hosts for HSV-1 persistence. Here we report the establishment and characterization of HSV-1 persistence in an immortalized murine macrophage-like cell line (P388D1). METHODS: The persistently HSV-1 infected culture (P388D1per) was obtained from surviving P388D1 macrophages infected with HSV-1 MP strain at multiplicity of 0.001. P388D1per was characterized by [corrected] extracellular production of viruses, cells expressing viral antigens, and cells releasing infectious viruses. Viral plaque size and cytophatic effect were determined in viruses (HSVA and HSVB) obtained from two different P388D1per passages. Host and viral proteins were detected in P388D1per and in P388D1 cells infected with HSV-1 by metabolic [35S]-methionine labeling assays. RESULTS: P388D1per culture was characterized [corrected] by cyclic production of infectious viruses from non-detectable to 10(6) TCID50/mL, [corrected] from 1.0 to 15.0% cells expressing viral antigens and macrophages released infectious viruses from 0.008 to 12.5%. Differences in viral plaque size and cytopathic effect morphology between HSVA, HSVB and HSV-1 were observed. Similar patterns of viral proteins were observed in P388D1per and in P388D1 infected with HSV-1. Nonetheless, the characteristic interference effect of HSV-1 on host protein synthesis was not observed in P388D1per culture. CONCLUSIONS: An HSV-1 persistently infected immortalized macrophage culture was established and characterized. Virus produced during persistence showed phenotypic alterations with respect to the original virus. P388D1per cell protein synthesis was not affected by the presence of HSV-1.

Animals↗

Non-specific musculoskeletal pain in preadolescents. Prevalence and 1-year persistence.

A 1-year follow-up study of 1756 third- and fifth-grade schoolchildren was conducted with a structured pain questionnaire to assess the prevalence and persistence of self-reported musculoskeletal pain symptoms and disability caused by pain. At follow-up, 1626 (92.7%) children participated in the study. Pain at least once a week persisted in 270 (52.4%) of the 564 children who reported musculoskeletal pain at least once a week in at least one part of the body at baseline. Of the regional pain symptoms, neck pain had highest persistence and, in girls, significantly more than in boys. Persistence of pain was not related to school grade. Widespread pain, determined as in the criteria for fibromyalgia, was found in 132 children (7.5%) and persisted in 35 children (29.7%, 95% CI 21.9-38.4) at follow-up. Disability was more severe in children with pain symptoms in more than one area. This study showed that about half of the preadolescents complaining of musculoskeletal pain at least once a week at baseline had persistent pain symptoms at follow-up. The prognosis of widespread pain in preadolescents was almost the same as the previous findings in adults.

Child↗

Persistent sodium channel activity mediates subthreshold membrane potential oscillations and low-threshold spikes in rat entorhinal cortex layer V neurons.

Entorhinal cortex layer V occupies a critical position in temporal lobe circuitry since, on the one hand, it serves as the main conduit for the flow of information out of the hippocampal formation back to the neocortex and, on the other, it closes a hippocampal-entorhinal loop by projecting upon the superficial cell layers that give rise to the perforant path. Recent in vitro electrophysiological studies have shown that rat entorhinal cortex layer V cells are endowed with the ability to generate subthreshold oscillations and all-or-none, low-threshold depolarizing potentials. In the present study, by applying current-clamp, voltage-clamp and single-channel recording techniques in rat slices and dissociated neurons, we investigated whether entorhinal cortex layer V cells express a persistent sodium current and sustained sodium channel activity to evaluate the contribution of this activity to the subthreshold behavior of the cells. Sharp-electrode recording in slices demonstrated that layer V cells display tetrodotoxin-sensitive inward rectification in the depolarizing direction, suggesting that a persistent sodium current is present in the cells. Subthreshold oscillations and low-threshold regenerative events were also abolished by tetrodotoxin, suggesting that their generation also requires the activation of such a low-threshold sodium current. The presence of a persistent sodium current was confirmed in whole-cell voltage-clamp experiments, which revealed that its activation "threshold" was negative by about 10mV to that of the transient sodium current. Furthermore, stationary noise analysis and cell-attached, patch-clamp recordings indicated that whole-cell persistent sodium currents were mediated by persistent sodium channel activity, consisting of relatively high-conductance ( approximately 18pS) sustained openings. The presence of a persistent sodium current in entorhinal cortex layer V cells can cause the generation of oscillatory behavior, bursting activity and sustained discharge; this might be implicated in the encoding of memories in which the entorhinal cortex participates but, under pathological situations, may also contribute to epileptogenesis and neurodegeneration.

Action Potentials↗

Doxorubicin-induced persistent oxidative stress to cardiac myocytes.

We recently reported a cardioselective and cumulative oxidation of cardiac mitochondrial DNA (mtDNA) following subchronic administration of doxorubicin to rats. The mtDNA adducts persist for up to 5 weeks after cessation of doxorubicin treatment. Since the evidence suggests that this persistence of mtDNA adducts cannot be attributed to a lack of repair and replication, we investigated whether it might reflect a long-lasting stimulation of free radical-mediated adduct formation. Male Sprague-Dawley rats received weekly s.c. injections of either doxorubicin (2 mg/kg) or an equivalent volume of saline. Cardiac myocytes isolated from rats following 6 weekly injections of doxorubicin expressed a much higher rate of reactive oxygen species (ROS) formation compared to saline controls. This higher rate of ROS formation persisted for 5 weeks following the last injection. Associated with this was a persistent depression of GSH in heart tissue, while protein-thiol content was not markedly altered. These data suggest that the accumulation and persistence of oxidized mtDNA may be due, not to the stability of the adducts, but to some as yet undefined toxic lesion that causes long-lasting stimulation of ROS generation by doxorubicin. This persistent generation of ROS may contribute to the cumulative and irreversible cardiotoxicity observed clinically with the drug.

8-Hydroxy-2'-Deoxyguanosine↗

Embolotherapy of persistent endoleaks after endovascular repair of abdominal aortic aneurysm with the ancure-endovascular technologies endograft system.

PURPOSE: Endoleak is a potential complication after endovascular repair of abdominal aortic aneurysm (AAA). It may result in continued growth of the aneurysm and potentially result in aneurysm rupture. The authors present their experience with embolotherapy in patients with persistent perigraft flow treated with the Ancure-Endovascular Technologies endograft system. MATERIALS AND METHODS: Between February 1996 and August 1998, 54 patients underwent successful repair of AAA with use of the Ancure system. All underwent operative angiography and discharge computed tomography (CT). Follow-up included CT at 6, 12, and 24 months, and CT was also performed at 3 months if an endoleak was present on the discharge CT. Persistent endoleak was defined as perigraft flow still present on the 6-month CT. Seven of 21 initial endoleaks persisted at 6 months. Six patients returned for embolization of the perigraft space and outflow vessels including lumbar arteries and the inferior mesenteric artery (IMA). RESULTS: Five of the six patients had leaks from the proximal (n = 1) or distal attachment sites (n = 4) of the Ancure system with outflow into lumbar arteries and/or the IMA; one leak was caused by retrograde IMA flow. The six patients underwent nine embolization procedures with only one minor complication. Follow-up CT showed complete resolution of endoleak and decrease in size of the aneurysm sac in all patients. CONCLUSIONS: Although endoleak is commonly seen initially with the Ancure system, persistent leak occurred in 13% of the patients in the study. Persistent flow in most patients arises from a graft attachment site combined with patent outflow vessels such as the IMA or lumbar arteries. Persistent endoleaks can be effectively and safely embolized with use of a combination of coil embolization of the perigraft space and embolization of outflow vessels. Such intervention resulted in a decrease in size of the aneurysm sac.

Aged↗

Multiple-dose vials: persistence of bacterial contaminants and infection control implications.

Due to sporadic infections attributed to contaminated multiple-dose medication vials (MDV), some authorities have suggested discarding all MDV within 24 hours. We inoculated 11 commonly used medications with suspensions of 10 bacterial species previously associated with contaminated parenteral solutions and determined microbial persistence at both room and refrigerator temperature. At 22 degrees C, atropine, curare, folic acid, NPH insulin and triamcinolone did not allow microbial persistence beyond 4 hours. Lidocaine and heparin were sterile by 24 hours. Regular insulin, immune serum globulin, and myochrysine allowed persistence for up to 7 days. At 4 degrees C, bacterial persistence was significantly prolonged for all medications including those MDV requiring refrigeration. No organisms proliferated; however, F. meningosepticum and P. maltophilia were particularly persistent at both temperatures. The risk of persistent MDV contamination appears to be dependent upon specific pharmaceutical, microbe and storage temperature interactions. Recommendations for the refrigeration of MDV medications may require reevaluation on a product-by-product basis.

Bacteria↗

Persistence of the left superior caval vein: can it potentiate obstructive lesions of the left ventricle?

Recent evidence has suggested that persistence of the left superior caval vein is associated with a high incidence of obstructive lesions of the left heart. To shed more light on this issue 1085 patients with congenital heart disease were studied retrospectively, with the aim of estimating the prevalence of a persistent left superior caval vein and its associated anomalies, focusing attention on obstructive lesions in the left and right ventricles. Patients with isomerism of the atrial appendages, or hypoplastic left heart syndrome, were excluded. A persisting left superior caval vein was present in 57 patients (5.2%). The overall incidence of obstructive lesions of the left heart was higher in patients with than in those without a persistent left superior caval vein (31.6 versus 7.8%,p < 0.001). Relative hypoplasia of the left ventricle was also higher in patients with persistent left superior caval vein (14 versus 0.8%, p < 0.001). The obstructive lesions found in the left heart, compared with the number in those without a left caval vein, were: mitral stenosis, 5.2 versus 0.7%; subaortic stenosis, 5.3 versus 0.9%; aortic coarctation, 17.5 versus 5.8% (p < 0.01); all of these in association, 3.5 versus 0.4%. In contrast, the incidence of obstructive lesions of the right heart was similar in the two groups of patients. It is concluded that persistence of the left superior caval vein can perturb the normal development of the left ventricle, being strongly associated with obstructions to left ventricular inflow and outflow.

Aortic Coarctation↗

Persistence of volatile compounds in the breath after their consumption in aqueous solutions.

The persistence of volatile compounds in the breath was monitored after their consumption in aqueous solutions. Factors studied were variation in volatile release patterns between panelists, effect of adding hydroxy propyl methyl cellulose (HPMC), and differences among compounds. For any given compound, the extent of volatile persistence was broadly similar for all panelists. Adding HPMC at concentrations in excess of c did not substantially affect persistence. The largest differences in persistence were observed when compounds were compared (>20-fold). The differences were modeled using a quantitative structure property relationship approach, based on the persistence data from 41 compounds. Major components of the model were terms that described the hydrophobicity and vapor pressure of a molecule. The model was validated with a test set, which showed that there was a significant correlation between persistence predicted by the model and the actual values observed.

Adult↗

Relative persistence of behavior: a fundamental measure of relative reinforcing effects.

Relative persistence of behavior is measured in terms of rates of behavior at a higher schedule value divided by rates of behavior at a lower schedule value and then multiplied by 100 to express the result as a percentage. Relative persistence of behavior is a direct function of reinforcer size over a broad range of values. In 1 study, food was the reinforcer; however, in most studies of persistence, drug reinforcers were used, and the drugs were taken orally or intravenously. A variety of reinforcing drugs were studied: barbiturates, opioids, psychomotor stimulants, a dissociative anesthetic, and alcohol. Both ratio and interval schedules were used to study relative persistence of behavior in human participants, male and female rhesus monkeys (Macaca mulatta), and rats. Thus, studies of persistence are based on results of an extensive set of conditions. The results support the proposition that relative persistence of behavior is a fundamental measure of relative reinforcing effects.

Animals↗

Effects of display luminance, stimulus meaningfulness, and probe duration on visible and schematic persistence.

Partial report performance is conceived of as consisting of two independent sources of information: visible persistence and schematic persistence. Following the work of Di Lollo and Dixon (1988), these two sources of information were separated experimentally by varying interstimulus interval and stimulus onset asynchrony independently. In the present experiment we asked whether visible persistence and schematic persistence would be affected by display luminance, stimulus meaningfulness, or probe duration. The results were fit accurately by an extension of the Di Lollo and Dixon independent-decay model in which display luminance affected visible persistence but stimulus meaningfulness and probe duration affected neither form of persistence directly.

Adult↗

Microbiome features associated with persistent intestinal carriages of Escherichia coli ST131 in a Southeast Asian cohort study.

Escherichia coli sequence-type 131 (ST131) is the dominant global extraintestinal pathogen capable of asymptomatic intestinal carriage and sustained household transmission, challenging infection control. Despite its clinical significance, the ecological determinants of gut persistence remain poorly understood. We performed shotgun metagenomics on fecal samples to investigate gut microbiome features associated with ST131-positive samples, distinct host carrier statuses (persistent, intermittent and non-carriers) and household risks in a study of a Southeast Asian cohort. Here, we show that ST131 carriage was associated with compositional shifts without reducing species alpha-diversity. Regression analyses identified depletion of commensal taxa and the 1,5-anhydrofructose degradation pathway in ST131-positive samples. Persistent carriers exhibited highly perturbed microbiome enriched with pathobionts, aerobactin- and lipopolysaccharide (LPS)-biosynthesis pathways. Comparing household risk groups to control, revealed that biotin biosynthesis and 1,5-anhydrofructose degradation may influence ST131 co-colonization through both direct and indirect mechanisms. Machine learning analyses identified metabolic pathways as stronger discriminators of persistent carriage than taxonomic features. Genomic-resolved analysis of clinical ST131 isolates revealed conserved genes for iron-acquisition, LPS and antibiotic resistance determinants. Overall, while commensals and metabolism may influence initial ST131 colonization, persistent carriage is associated with specific microbial and metabolic adaptations, providing potential targets to limit intestinal ST131 persistence.

Humans↗

Recovery and persistence of stuttering among relatives of stutterers.

Recovery and persistence of stuttering were examined in the first-degree relatives of a large group of adult persistent stutters. The percentage of recovered individuals reported in these families supports the hypothesis that recovered and persistent stuttering are not independent disorders. Sex and type of relative were significant variables in the distributions of recovery and persistence of stuttering. Handedness in male subjects and birth order did not distinguish between recovered and persistent stutterers. Female recovered stutterers had significantly earlier ages of stuttering onset than the other groups (male recovered stutterers and male and female persistent stutterers). Female recovered stutterers also tended to recover earlier than male recovered stutterers, and the durations of stuttering symptoms were similar in both sexes.

Adolescent↗

Links between maternal care and persistent infant crying in the early months.

A community sample was screened to select three groups of infants and their mothers according to how much the babies cried at 6 weeks of age, the peak age for infant crying. The three groups--of moderate (n = 55), evening (n = 38) and persistent criers (n = 67) and their mothers--were assessed by diary, observation and questionnaire measures of mother and infant characteristics and interactions at 6 weeks and 5 months of infant age. At 6 weeks, mothers of persistent criers spent more time interacting with and physically stimulating their babies. Below-optimum maternal sensitivity/affection was linked to moderately increased crying in the infants overall. However, most mothers of persistent criers showed optimum sensitivity and affection, while no significant links between maternal sensitivity/affection and infant crying were found in the persistent crying group. By 5 months, when infant crying declined, the range and size of differences between mothers of persistent criers and other mothers declined. Home observations and a standard play measure failed to show group differences in maternal sensitivity, affection and intrusiveness at this age. The findings show that persistent infant crying in the early months often occurs in spite of high quality maternal care, so that in most cases the crying is probably not due to inadequate parenting. The need to distinguish general community cases from those at social or medical risk is emphasized and the findings' implications for professionals are discussed.

Adult↗