The Role of Ureaplasma and Mycoplasma Species in Recurrent Lower Urinary Tract Infection in Females: A Scoping Review.

It is unknown if recurrent urinary tract infection in the gynecologic population is associated with Mycoplasma and Ureaplasma genitourinary infections. The purpose of this scoping review is to highlight the literature surrounding Mycoplasma and Ureaplasma infections in the setting of recurrent urinary tract infections in the gynecologic population. MEDLINE ALL and Embase were searched to retrieve articles published in or after 1950 through 2024. Studies included were those with adults over age 18, non-pregnant, diagnosed with recurrent urinary tract infection and concurrent genitourinary infection with Ureaplasma or Mycoplasma published in English. Study designs eligible were quantitative, qualitative, and mixed methods studies. Publication types were also extended to conference abstracts and unpublished data. 2 independent investigators systematically performed title/abstract screening and full-text review using standardized inclusion criteria. For disagreements in either title and abstracts or full-text articles, consensus was reached through discussion by the 2 screeners and/or a 3rd final adjudicator. Screening and data extraction were performed on Covidence, a web-based platform for systematic review management. There were 1170 studies identified before title and abstract screening. 26 full-text articles were reviewed for eligibility. Of these, 23 full-text studies were excluded. 3 studies met full inclusion criteria and data extraction was performed on these 3 studies. There were 2 additional studies included after identification via other methods. There is a need for more recent and robust studies examining the role of Ureaplasma and Mycoplasma genitourinary infections amongst gynecologic patients with recurrent urinary tract infections.

Conceptos actuales en cirugía histeroscópica: superando barreras y ampliando límites / Current concepts in hysteroscopic surgery: Overcoming barriers by extending limits

Dentro de la patología intracavitaria estructural, los miomas submucosos plantean una mayor dificultad de manejo frente a los pólipos. Dentro de los miomas submucosos los miomas tipo0 y1 son más fáciles de tratar, dado que su separación del miometrio subyacente es técnicamente más fácil. Así, las cirugías histeroscópicas más complicadas son actualmente las miomectomías de miomas submucosos tipo2.Se ha empezado a describir también el manejo histeroscópico de miomas tipo3 por histeroscopia.Con este artículo planteamos hacer una revisión de los puntos más relevantes para llevar a cabo un tratamiento adecuado de este tipo de miomas, revisando su diagnóstico, las técnicas quirúrgicas, la preparación de la paciente y la forma de evitar complicaciones quirúrgicas.(AU)

Within structural intracavitary pathology, submucosal myomas are more difficult to manage than polyps. Of the submucosal myomas, type0 and type1 are easier to treat because their separation from the underlying myometrium is technically easier. Therefore, the most complicated hysteroscopic surgeries are currently type2 submucosal myomectomies.We have also begun to describe the hysteroscopic management of type3 myomas.With this article we propose to make a review of the most relevant points for the correct treatment of this type of myoma, reviewing its diagnosis, surgical techniques, patient preparation, and how to avoid surgical complications.(AU)

Role of cosyntropin in the management of postpartum post-dural puncture headache: a two-center retrospective cohort study.

BACKGROUND: Research suggests that postpartum post-dural puncture headache (PDPH) might be prevented or treated by administering intravenous cosyntropin. METHODS: In this retrospective cohort study, we questioned whether prophylactic (1 mg) and therapeutic (7 µg/kg) intravenous cosyntropin following unintentional dural puncture (UDP) was effective in decreasing the incidence of PDPH and therapeutic epidural blood patch (EBP) after birth. Two tertiary-care American university hospitals collected data from November 1999 to May 2017. Two hundred and fifty-three postpartum patients who experienced an UDP were analyzed. In one institution 32 patients were exposed to and 32 patients were not given prophylactic cosyntropin; in the other institution, once PDPH developed, 36 patients were given and 153 patients were not given therapeutic cosyntropin. The primary outcome for the prophylactic cosyntropin analysis was the incidence of PDPH and for the therapeutic cosyntropin analysis in exposed vs. unexposed patients, the receipt of an EBP. The secondary outcome for the prophylactic cosyntropin groups was the receipt of an EBP. RESULTS: In the prophylactic cosyntropin analysis no significant difference was found in the risk of PDPH between those exposed to cosyntropin (19/32, 59%) and unexposed patients (17/32, 53%; odds ratio (OR) 1.37, 95% CI 0.48 to 3.98, P = 0.56), or in the incidence of EBP between exposed (12/32, 38%) and unexposed patients (6/32, 19%; OR 2.6, 95% CI 0.83 to 8.13, P = 0.095). In the therapeutic cosyntropin analysis, in patients exposed to cosyntropin the incidence of EBP was significantly higher (20/36, 56% vs. 43/153, 28%; OR 3.20, 95% CI 1.52 to 6.74, P = 0.002). CONCLUSIONS: Our data show no benefits from the use of cosyntropin for preventing or treating postpartum PDPH.

Women in refuge: Syrian women voicing health sequelae due to war traumatic experiences and displacement challenges.

OBJECTIVE: The Syrian war created a mass exodus of people to neighboring countries. Jordan hosts approximately 1.4 million Syrians who sought refuge and protection. This research represents an effort to understand the subjective narratives of Syrian refugee women's war traumatic experiences and displacement challenges while living in Jordan and the consequences on their physical and mental health. METHODS: Data gathered between March and June 2014 included 24 in-depth interviews with Syrian refugee women who sought services from humanitarian organizations in Jordan. Interviews were conducted in Arabic and were audio recorded. A team of four researchers translated and transcribed the interviews. Group narrative methodology was utilized to analyze the interviews. RESULTS: The study suggests that Syrian refugee women experienced diverse war atrocities including shelling, loss of property, separation from family members, and threats to their lives and their beloved ones, among a few. In Jordan, they reported on multiple displacement challenges, which are perceived as a continuous traumatic experience, as well as somatization. Narratives of women also included sequelae to their physical and mental health due to such stressors. Barriers to obtaining physical and mental health services are discussed, including inadequate medical treatment, lack of mental health services, and stigma on mental health, which might be associated to somatization of mental illnesses. CONCLUSION: It is crucial that humanitarian organizations and host countries like Jordan bear the responsibility to enhancing accessibility to comprehensive trauma-focused physical and mental health services for Syrian refugees in a culturally and gender sensitive manner.

Environmental shedding of toxigenic Clostridioides difficile by asymptomatic carriers: A prospective observational study.

OBJECTIVES: The aim was to compare the burden of environmental shedding of toxigenic Clostridioides difficile among asymptomatic carriers, C. difficile-infected (CDI) patients and non-carriers in an inpatient non-epidemic setting. METHODS: C. difficile carriage was determined by positive toxin-B PCR from rectal swabs of asymptomatic patients. Active CDI was defined as a positive two-step enzyme immunoassay/polymerase chain reaction (EIA/PCR) test in patients with more than three unformed stools/24 hr. C. difficile environmental contamination was assessed by obtaining specimens from ten sites in the patients' rooms. Toxigenic strains were identified by PCR. We created a contamination scale to define the overall level of room contamination that ranged from clean to heavy contamination. RESULTS: One hundred and seventeen rooms were screened: 70 rooms inhabited by C. difficile carriers, 30 rooms by active CDI patients and 17 rooms by non C. difficile -carriers (control). In the carrier rooms 29 (41%) had more than residual contamination, from which 17 (24%) were heavily contaminated. In the CDI rooms 12 (40%) had more than residual contamination from which three (10%) were heavily contaminated, while in the control rooms, one room (6%) had more than residual contamination and none were heavily contaminated. In a multivariate analysis, the contamination score of rooms inhabited by carriers did not differ from rooms of CDI patients, yet both were significantly more contaminated than those of non-carriers odd ratio 12.23 and 11.16 (95% confidence interval 1.5-99.96 p 0.0195, and 1.19-104.49 p 0.035), respectively. DISCUSSION: Here we show that the rooms of C. difficile carriers are as contaminated as those of patients with active CDI and significantly more than those of non-carriers.

Consumer-run services research and implications for mental health care.

Mental health consumers/survivors developed consumer-run services (CRSs) as alternatives to disempowering professionally run services that limited participant self-determination. The objective of the CRS is to promote recovery outcomes, not to cure or prevent mental illness. Recovery outcomes pave the way to a satisfying life as defined by the individual consumer despite repetitive episodes of disorder. Recovery is a way of life, which through empowerment, hope, self-efficacy, minimisation of self-stigma, and improved social integration, may offer a path to functional improvement that may lead to a better way to manage distress and minimise the impact of illness episodes. 'Nothing about us without us' is the defining objective of the process activity that defines self-help. It is the giving of agency to participants. Without such process there is a real question as to whether an organisation is a legitimate CRS or simply a non-governmental organisation run by a person who claims lived experience. In considering the effectiveness of CRSs, fidelity should be defined by the extent to which the organisation's process conveys agency. Unidirectional helping often does for people what they can do for themselves, stealing agency. The consequence of the lack of fidelity in CRSs to the origins of the self-help movement has been a general finding in multisite studies of no or little difference in outcomes attributable to the consumer service. This, from the perspective of the research summarised herein, results in the mixing of programmatic efforts, some of which enhance outcomes as they are true mutual assistance programmes and some of which degrade outcomes as they are unidirectional, hierarchical, staff-directed helping efforts making false claims to providing agency. The later CRS interventions may provoke disappointment and additional failure. The indiscriminate combining of studies produces the average: no effect.

Effects of developmental hyperserotonemia on the morphology of rat dentate nuclear neurons.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social cognition, disordered communication, restricted interests and repetitive behaviors. Furthermore, abnormalities in basic motor control, skilled motor gestures, and motor learning, are common in ASD. These characteristics have been attributed to a possible defect in the pre- and postnatal development of specific neural networks including the dentate-thalamo-cortical pathway, which is involved in motor learning, automaticity of movements, and higher cognitive functions. The current study utilized custom diolistic labeling and unbiased stereology to characterize morphological alterations in neurons of the dentate nucleus of the cerebellum in developing rat pups exposed to abnormally high levels of the serotonergic agonist 5-methyloxytryptamine (5-MT) pre-and postnatally. Occurring in as many as 30% of autistic subjects, developmental hyperserotonemia (DHS) is the most consistent neurochemical finding reported in autism and has been implicated in the pathophysiology of ASD. This exposure produced dramatic changes in dendritic architecture and synaptic features. We observed changes in the dendritic branching morphology which did not lead to significant differences (p>0.5) in total dendritic length. Instead, DHS groups presented with dendritic trees that display changes in arborescence, that appear to be short reaching with elaborately branched segments, presenting with significantly fewer (p>0.001) dendritic spines and a decrease in numeric density when compared to age-matched controls. These negative changes may be implicated in the neuropathological and functional/behavioral changes observed in ASD, such as delays in motor learning, difficulties in automaticity of movements, and deficits in higher cognitive functions.

Glucocorticoids interact with noradrenergic activation at encoding to enhance long-term memory for emotional material in women.

Evidence from the animal literature suggests that post-training glucocorticoids (GCs) interact with noradrenergic activation at acquisition to enhance memory consolidation for emotional stimuli. While there is evidence that GCs enhance memory for emotional material in humans, the extent to which this depends on noradrenergic activation at encoding has not been explored. In this study, 20-mg hydrocortisone was administered to healthy young women (18-35 yrs old) in a double-blind fashion 10 min prior to viewing a series of emotional and neutral images. Saliva samples were taken at baseline, 10 min after drug or placebo administration, immediately after viewing the images, 10, 20, and 30 min after viewing the images. Participants returned 1 week later for a surprise recall test. Results suggest that, hydrocortisone administration resulted in emotional memory enhancement only in participants who displayed an increase in endogenous noradrenergic activation, measured via salivary alpha-amylase at encoding. These results support findings in the animal literature, and suggest that GC-induced memory enhancement relies on noradrenergic activation at encoding in women.

Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.

Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles have a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided.

Mucopolysaccharidosis type II: identification of 30 novel mutations among Latin American patients.

In this study, 103 unrelated South-American patients with mucopolysaccharidosis type II (MPS II) were investigated aiming at the identification of iduronate-2-sulfatase (IDS) disease causing mutations and the possibility of some insights on the genotype-phenotype correlation The strategy used for genotyping involved the identification of the previously reported inversion/disruption of the IDS gene by PCR and screening for other mutations by PCR/SSCP. The exons with altered mobility on SSCP were sequenced, as well as all the exons of patients with no SSCP alteration. By using this strategy, we were able to find the pathogenic mutation in all patients. Alterations such as inversion/disruption and partial/total deletions of the IDS gene were found in 20/103 (19%) patients. Small insertions/deletions/indels (<22 bp) and point mutations were identified in 83/103 (88%) patients, including 30 novel mutations; except for a higher frequency of small duplications in relation to small deletions, the frequencies of major and minor alterations found in our sample are in accordance with those described in the literature.

Associations between parenting behavior and anxiety in a rodent model and a clinical sample: relationship to peripheral BDNF levels.

Adverse early-life environment is associated with anxiety-like behaviors and disorders. Brain-derived neurotrophic factor (BDNF) is sensitive to this environment and could be a marker of underlying brain changes. We aimed at evaluating the development of anxiety-like behaviors in a rat model of early adversity, as well as the possible association with BDNF levels. Similar associations were investigated in a sample of adolescent humans. For the rat study, Wistar rat litters were divided into: early-life stress (ELS, limited access to nesting material) and control groups. Maternal behavior was observed from days 1 to 9 of life and, as adults, rats were subjected to behavioral testing and BDNF measurements in plasma, hippocampus, amygdala and periaqueductal gray. For the human study, 129 adolescents were evaluated for anxiety symptoms and perceived parental care. Serum BDNF levels and the Val66Met polymorphism of the BDNF gene were investigated. We found that ELS dams showed more pure contact, that is, contact with low care and high control, toward pups, and their adult offspring demonstrated higher anxiety-like behaviors and plasma BDNF. Also the pure contact correlated positively with adult peripheral BDNF. Similarly in humans, there was a positive correlation between maternal overprotection and serum BDNF only in Met carriers. We also found negative correlations between maternal warmth and separation anxiety, social phobia and school phobia. Finally, our translational approach revealed that ELS, mediated through variations in maternal care, is associated with anxiety in both rats and humans and increased peripheral BDNF may be marking these phenomena.

Report of a Large Brazilian Family With a Very Attenuated Form of Hunter Syndrome (MPS II).

Hunter syndrome, or Mucopolysaccharidosis type II (MPS II), is a rare X-linked recessive disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). The phenotypic spectrum varies from severe to attenuated clinical forms. We report a large Brazilian family with 16 affected individuals exhibiting a very attenuated form of MPS II. Fourteen female carriers were also identified. Twelve affected male patients, whose ages ranged from 1 to 35 years, were examined. Molecular analysis showed a novel missense mutation (p.A77D) in the IDS gene, confirming the diagnosis. Nine of the family members presented some degree of heart damage, though only the proband became symptomatic and required heart transplantation. One 19-year-old adult and 1-year-old twin boys each had a normal echocardiogram. Short stature was found in two adults while macrocephaly was found in one; the remaining adults had anthropometric measures within normal range. All affected adults had normal cognitive development and were able to perform normal daily activities, except one who had mild learning disability. Two patients died due to natural causes beyond 70 years of age. The female carriers did not present any signs of disease. In this large family with a mild form of MPS II and variable degree of clinical manifestations, it is noteworthy that several affected individuals have remained asymptomatic even at advanced age and even without enzyme replacement therapy.

Regulation of blood flow in the microcirculation: role of conducted vasodilation.

This review is concerned with understanding how vasodilation initiated from local sites in the tissue can spread to encompass multiple branches of the resistance vasculature. Within tissues, arteriolar networks control the distribution and magnitude of capillary perfusion. Vasodilation arising from the microcirculation can 'ascend' into feed arteries that control blood flow into arteriolar networks. Thus distal segments of the resistance network signal proximal segments to dilate and thereby increase total oxygen supply to parenchymal cells. August Krogh proposed that innervation of capillaries provided the mechanism for a spreading vasodilatory response. With greater understanding of the ultrastructural organization of resistance networks, an alternative explanation has emerged: Electrical signalling from cell to cell along the vessel wall through gap junctions. Hyperpolarization originates from ion channel activation at the site of stimulation with the endothelium serving as the predominant cellular pathway for signal conduction along the vessel wall. As hyperpolarization travels, it is transmitted into surrounding smooth muscle cells through myoendothelial coupling to promote relaxation. Conducted vasodilation (CVD) encompasses greater distances than can be explained by passive decay and understanding such behaviour is the focus of current research efforts. In the context of athletic performance, the ability of vasodilation to ascend into feed arteries is essential to achieving peak levels of muscle blood flow. CVD is tempered by sympathetic neuroeffector signalling when governing muscle blood flow at rest and during exercise. Impairment of conduction during ageing and in diseased states can limit physical work capacity by restricting muscle blood flow.

Ectopic pregnancy early diagnosis markers.

Ectopic pregnancy (EP) is a high-risk medical condition with an incidence of 1.9% in reported pregnancies, and has proven to be the most common cause of pregnancy-related deaths in the first trimester. The clinical symptoms can mimic non-EP conditions, thus creating a challenge for developing diagnostic criteria and new diagnostic tools. Early diagnosis of ectopic pregnancy is essential in order to minimize the morbidity and to assess the need for urgent surgical intervention. Currently, ultrasound and serum biomarkers are used by clinicians for early detection and diagnosis. This review summarizes and comments on the available literature on the various markers including their utility and their statistical parameters.

NFKBIZ polymorphisms and susceptibility to pneumococcal disease in European and African populations.

The proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) has a central role in host defence against pneumococcal disease. Both rare mutations and common polymorphisms in the NFKBIA gene encoding the NF-kappaB inhibitor, IkappaB-alpha, associate with susceptibility to bacterial disease, but the possible role of polymorphisms within the related IkappaB-zeta gene NFKBIZ in the development of invasive pneumococcal disease (IPD) has not been reported previously. To investigate this further, we examined the frequencies of 22 single-nucleotide polymorphisms spanning NFKBIZ in two case-control studies, comprising UK Caucasian (n=1008) and Kenyan (n=723) individuals. Nine polymorphisms within a single UK linkage disequilibrium (LD) block and all four polymorphisms within the equivalent, shorter Kenyan LD block displayed either a significant association with IPD or a trend towards association. For each polymorphism, heterozygosity was associated with protection from IPD when compared with the combined homozygous states (for example, for rs600718, Mantel-Haenszel 2 x 2 chi(2)=7.576, P=0.006, odds ratio (OR)=0.67, 95% confidence interval (95% CI) for OR: 0.51-0.88; for rs616597, Mantel-Haenszel 2 x 2 chi(2)=8.715, P=0.003, OR=0.65, 95% CI: 0.49-0.86). We conclude that multiple NFKBIZ polymorphisms associate with susceptibility to IPD in humans. The study of multiple populations may aid in fine mapping of associations within extensive regions of strong LD ('transethnic mapping').

Clinical and biochemical studies in mucopolysaccharidosis type II carriers.

The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16-57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for non-carriers; there was, however, an overlap between carriers' and non-carriers' values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations.

Vascular anatomy of the hamster retractor muscle with regard to its microvascular transfer.

BACKGROUND: The hamster retractor muscle (RET) is used as an in vivo model in studies of skeletal muscle ischemia-reperfusion injury. The RET is unique in that the muscle can be isolated while preserving the primary vascular supply so that its contractile function can be measured simultaneously with local microvascular responses to experimental interventions. The goal of this study was to understand the anatomical origin of the vascular supply to the RET and determine whether the RET can be used as a free flap after surgical isolation of the thoracodorsal vessels. METHODS: Microdissection was performed to determine the anatomy of the vasculature that supplies and drains the RET. RESULTS: Distinct numbers and patterns of feed arteries (2-4) and collecting veins (1-3) were identified (n = 26 animals). Dye injection (n = 8) of the thoracodorsal artery demonstrated that the RET remains perfused following its isolation on the thoracodorsal pedicle. Heterotopic allograft transplantation of the RET (n = 2) was performed by anastomosing the thoracodorsal vessels to the femoral vessels using the end-to-side technique. CONCLUSIONS: The anatomical relationships indicate that the RET can be used as a free flap model for evaluating the effect of preservation strategies and transplantation on skeletal muscle microcirculation and contractile function.

FDG-PET findings in patients with galactosaemia.

Despite treatment with a galactose-restricted diet, many galactosaemia patients develop lifelong cognitive impairment, speech abnormalities and a gamut of neurological problems including cognitive impairment and tremors. No study has explored changes in cerebral glucose metabolism in patients with galactosaemia. Five patients with galactosaemia had ages ranging from 20 to 40 years (mean age 28 years) and eight similarly aged controls received brain [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. PET scans were analysed using a previously validated template methodology of regions of interest (ROIs). Count ratios for each anatomical ROI were compared between the galactosaemic patients and the healthy controls. Statistical parametric mapping (SPM) software was also used to further analyse the data. ROI analysis showed that galactosaemic patients had significant bilateral decreases in cerebral glucose metabolism in the superior temporal gyrus, medial occipital lobe, parietal lobe, cerebellum, calcarine cortex, superior frontal cortex, and superior parietal cortex when compared with controls. Significant increases were seen in the cingulate gyrus and temporal poles, bilaterally. SPM analysis revealed foci of decreased glucose metabolism in the caudate, cerebellum, precentral gyrus and cerebellar tonsils of galactosaemic patients. SPM also showed increased glucose metabolism in the subcallosal gyrus and claustrum. The results show significant abnormalities in cerebral function in patients with galactosaemia, particularly with widespread decreases in cortical metabolism. These abnormalities appear to be in brain regions that may be associated with the neuropsychological deficits in these patients. PET brain scans may be of value in galactosaemia patients to evaluate for dysfunction.

Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer disease.

OBJECTIVE: To evaluate the utility of MRI hippocampal and entorhinal cortex atrophy in predicting conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD). METHODS: Baseline brain MRI was performed in 139 patients with MCI, broadly defined, and 63 healthy controls followed for an average of 5 years (range 1 to 9 years). RESULTS: Hippocampal and entorhinal cortex volumes were each largest in controls, intermediate in MCI nonconverters, and smallest in MCI converters to AD (37 of 139 patients converted to AD). In separate Cox proportional hazards models, covarying for intracranial volume, smaller hippocampal volume (risk ratio [RR] 3.62, 95% CI 1.93 to 6.80, p < 0.0001), and entorhinal cortex volume (RR 2.43, 95% CI 1.56 to 3.79, p < 0.0001) each predicted time to conversion to AD. Similar results were obtained for hippocampal and entorhinal cortex volume in patients with MCI with Mini-Mental State Examination (MMSE) scores > or = 27 out of 30 (21% converted to AD) and in the subset of patients with amnestic MCI (35% converted to AD). In the total patient sample, when both hippocampal and entorhinal volume were entered into an age-stratified Cox model with sex, MMSE, education, and intracranial volume, smaller hippocampal volume (RR 2.21, 95% CI 1.14 to 4.29, p < 0.02) and entorhinal cortex volume (RR 2.48, 95% CI 1.54 to 3.97, p < 0.0002) predicted time to conversion to AD. Similar results were obtained in a Cox model that also included Selective Reminding Test (SRT) delayed recall and Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol as predictors. Based on logistic regression models in the 3-year follow-up sample, for a fixed specificity of 80%, the sensitivities for MCI conversion to AD were as follows: age 43.3%, MMSE 43.3%, age + MMSE 63.7%, age + MMSE + SRT delayed recall + WAIS-R Digit Symbol 80.6% (79.6% correctly classified), hippocampus + entorhinal cortex 66.7%, age + MMSE + hippocampus + entorhinal cortex 76.7% (85% correctly classified), age + MMSE + SRT delayed recall + WAIS-R Digit Symbol + hippocampus + entorhinal cortex 83.3% (86.8% correctly classified). CONCLUSIONS: Smaller hippocampal and entorhinal cortex volumes each contribute to the prediction of conversion to Alzheimer disease. Age and cognitive variables also contribute to prediction, and the added value of hippocampal and entorhinal cortex volumes is small. Nonetheless, combining these MRI volumes with age and cognitive measures leads to high levels of predictive accuracy that may have potential clinical application.

Impaired access of lymphocytes to neoplastic prostate tissue is associated with neoangiogenesis in the tumour site.

Recent reports demonstrated that neovasculature of certain murine tumours inhibits migration of lymphocytes to malignant tissues. We examined the possible existence of this phenomenon in human prostate adenocarcinoma by relating extent, patterns and composition of leucocyte infiltrates in adenocarcinoma specimens (N=28) to microvessel density and percentages of these vessels expressing adhesion molecules CD54, CD106 and CD62E. Specimens of nodular hyperplasia (N=30) were used as a control for nonmalignant prostate. Increased microvessel density was detected in foci of adenocarcinoma, as compared with adjacent benign areas (P=0.004) or hyperplastic specimens (P=0.001). Only CD54 was detected on prostate vasculature; percentages of CD54-expressing vessels in adenocarcinoma lesions and adjacent areas were higher than in hyperplasia (P=0.041 and P=0.014, respectively). Infiltrating leucocytes were either scattered diffusely in tissue or organised into clusters mainly composed of CD4-positive lymphocytes; smaller percentage of tissue was occupied by clustered infiltrates in adenocarcinoma foci (mean=0.7; median=0; range=0-5) than in adjacent tissue (mean=2.5; median=1; range=0-15; P=.021) and hyperplasia (mean=1.9; median=2; range=0-5; P=.006). In adenocarcinoma foci, microvessel density tended to negatively correlate with percentage of tissue occupied by an overall leucocyte infiltrate (mean=8.6; median=7.5; range=30) and negatively correlated with percentage of tissue occupied by clustered infiltrate (P=0.045). Percentage of CD54-expressing vessels positively correlated with percentage of tissue occupied by an overall (mean=12; median=10; range=30; P=0.01) and clustered (P=0.023) infiltrate in hyperplasia, whereas in carcinoma-adjacent benign areas, correlation was detected only for clustered infiltrates (P=0.02). The results indicate that impaired access of lymphocytes to malignant lesions is associated with increased numbers of newly formed blood vessels, whereas vascular CD54 likely contributes to extravasation of lymphocytes only in benign prostate tissue.