bluuebunny/crossref_metadata_2025 huggingface dataset:
Should LSIL with ASC-H (LSIL-H) in cervical smears be an independent category? A study on SurePath™ specimens with review of literature
Authors: Shidham Vinod B , Kumar Nidhi , Narayan Raj , Brotzman Gregory L
Published: May 2007

Background

Cervical smears exhibiting unequivocal features of ‘low grade squamous intraepithelial lesion’ (LSIL) are occasionally also admixed with some cells suspicious for, but not diagnostic of, ‘high grade squamous intraepithelial lesion’ (HSIL). Only a few studies, mostly reported as abstracts, have evaluated this concurrence. In this study, we evaluate the current evidence that favors a distinct category for “LSIL, cannot exclude HSIL” (LSIL-H), and suggest a management algorithm based on combinations of current ASCCP guidelines for related interpretations.

Methods

We studied SurePath™ preparations of cervical specimens from various institutions during one year period. Cytohisto correlation was performed in cases with cervical biopsies submitted to our institution. The status of HPV DNA testing was also noted in some LSIL-H cases with biopsy results.

Results

Out of 77,979 cases 1,970 interpreted as LSIL (1,523), LSIL-H (146), ‘atypical squamous cells, cannot exclude HSIL’ (ASC-H) (109), and HSIL (192) were selected. Concurrent biopsy results were available in 40% (Total 792 cases: 557 LSIL, 88 LSIL-H, 38 ASCH, and 109 HSIL). Biopsy results were grouped into A. negative for dysplasia (ND), B. low grade (HPV, CIN1, CIN1 with HPV), and C. high grade (CIN 2 and above).

The positive predictive values for various biopsy results in relation to initial cytopathologic interpretation were: a. LSIL: (557 cases): ND 32% (179), low grade- 58% (323), high grade- 10% (55); b. LSIL-H: (88 cases): ND 24% (21), low grade- 43% (38), high grade- 33% (29); c. ASCH: (38 cases): ND 32% (12), low grade- 37% (14), high grade- 31% (12); d. HSIL (109 cases): ND 5% (6), low grade 26% (28), high grade 69% (75). The patterns of cervical biopsy results in cases reported as LSIL-H were compared with that observed in cases with LSIL, ASC-H, and HSIL.

94% (32 of 34) of LSIL-H were positive for high risk (HR) HPV, 1 was negative for HR HPV but positive for low risk (LR), and 1 LSIL-H was negative for HR and LR both.

Conclusion

LSIL-H overlapped with LSIL and ASC-H, but was distinct from HSIL. A management algorithm comparable to ASC-H and HSIL appears to be appropriate in LSIL-H cases.
Human-robot cooperative movement training: Learning a novel sensory motor transformation during walking with robotic assistance-as-needed
Authors: Emken Jeremy L , Benitez Raul , Reinkensmeyer David J
Published: May 2007

Background

A prevailing paradigm of physical rehabilitation following neurologic injury is to "assist-as-needed" in completing desired movements. Several research groups are attempting to automate this principle with robotic movement training devices and patient cooperative algorithms that encourage voluntary participation. These attempts are currently not based on computational models of motor learning.

Methods

Here we assume that motor recovery from a neurologic injury can be modelled as a process of learning a novel sensory motor transformation, which allows us to study a simplified experimental protocol amenable to mathematical description. Specifically, we use a robotic force field paradigm to impose a virtual impairment on the left leg of unimpaired subjects walking on a treadmill. We then derive an "assist-as-needed" robotic training algorithm to help subjects overcome the virtual impairment and walk normally. The problem is posed as an optimization of performance error and robotic assistance. The optimal robotic movement trainer becomes an error-based controller with a forgetting factor that bounds kinematic errors while systematically reducing its assistance when those errors are small. As humans have a natural range of movement variability, we introduce an error weighting function that causes the robotic trainer to disregard this variability.

Results

We experimentally validated the controller with ten unimpaired subjects by demonstrating how it helped the subjects learn the novel sensory motor transformation necessary to counteract the virtual impairment, while also preventing them from experiencing large kinematic errors. The addition of the error weighting function allowed the robot assistance to fade to zero even though the subjects' movements were variable. We also show that in order to assist-as-needed, the robot must relax its assistance at a rate faster than that of the learning human.

Conclusion

The assist-as-needed algorithm proposed here can limit error during the learning of a dynamic motor task. The algorithm encourages learning by decreasing its assistance as a function of the ongoing progression of movement error. This type of algorithm is well suited for helping people learn dynamic tasks for which large kinematic errors are dangerous or discouraging, and thus may prove useful for robot-assisted movement training of walking or reaching following neurologic injury.
Laboratory study on "intracranial hypotension" created by pumping the chamber of a hydrocephalus shunt
Authors: Bromby Adam , Czosnyka Zofia , Allin David , Richards Hugh K , Pickard John D , Czosnyka Marek
Published: May 2007

Background

It has been reported that pumping a shunt in situ may precipitate a proximal occlusion, and/or lead to ventricular over-drainage, particularly in the context of small ventricles. In the laboratory we measured the effect of pumping the pre-chamber of hydrocephalus shunts on intracranial hypotension.

Materials and methods

A simple physical model of the CSF space in a hydrocephalic patient was constructed with appropriate compliance, CSF production and circulation. This was used to test eleven different hydrocephalus shunts. The lowest pressure obtained, the number of pumps needed to reach this pressure, and the maximum pressure change with a single pump, were recorded.

Results

All models were able to produce negative pressures ranging from -11.5 mmHg (Orbis-Sigma valve) to -233.1 mmHg (Sinu-Shunt). The number of pumps required reaching these levels ranged from 21 (PS Medical LP Reservoir) to 315 (Codman Hakim-Programmable). The maximum pressure change per pump ranged from 0.39 mmHg (Orbis-Sigma valve) to 23.1 (PS Medical LP Reservoir).

Conclusion

Patients, carers and professionals should be warned that 'pumping' a shunt's pre-chamber may cause a large change in intracranial pressure and predispose the patient to ventricular catheter obstruction or other complications.
Is deck B a disadvantageous deck in the Iowa Gambling Task?
Authors: Lin Ching-Hung , Chiu Yao-Chu , Lee Po-Lei , Hsieh Jen-Chuen
Published: May 2007

Background

The Iowa gambling task is a popular test for examining monetary decision behavior under uncertainty. According to Dunn et al. review article, the difficult-to-explain phenomenon of "prominent deck B" was revealed, namely that normal decision makers prefer bad final-outcome deck B to good final-outcome decks C or D. This phenomenon was demonstrated especially clearly by Wilder et al. and Toplak et al. The "prominent deck B" phenomenon is inconsistent with the basic assumption in the IGT; however, most IGT-related studies utilized the "summation" of bad decks A and B when presenting their data, thereby avoiding the problems associated with deck B.

Methods

To verify the "prominent deck B" phenomenon, this study launched a two-stage simple version IGT, namely, an AACC and BBDD version, which possesses a balanced gain-loss structure between advantageous and disadvantageous decks and facilitates monitoring of participant preferences after the first 100 trials.

Results

The experimental results suggested that the "prominent deck B" phenomenon exists in the IGT. Moreover, participants cannot suppress their preference for deck B under the uncertain condition, even during the second stage of the game. Although this result is incongruent with the basic assumption in IGT, an increasing number of studies are finding similar results. The results of the AACC and BBDD versions can be congruent with the decision literatures in terms of gain-loss frequency.

Conclusion

Based on the experimental findings, participants can apply the "gain-stay, loss-shift" strategy to overcome situations involving uncertainty. This investigation found that the largest loss in the IGT did not inspire decision makers to avoid choosing bad deck B.
Selection for tameness modulates the expression of heme related genes in silver foxes
Authors: Lindberg Julia , Björnerfeldt Susanne , Bakken Morten , Vilà Carles , Jazin Elena , Saetre Peter
Published: May 2007

Background

The genetic and molecular mechanisms of tameness are largely unknown. A line of silver foxes (Vulpes vulpes) selected for non-aggressive behavior has been used in Russia since the 1960's to study the effect of domestication. We have previously compared descendants of theseselected(S) animals with a group ofnon-selected(NS) silver foxes kept under identical conditions, and showed that changes in the brain transcriptome between the two groups are small. Unexpectedly, many of the genes showing evidence of differential expression between groups were related to hemoproteins.

Results

In this study, we use quantitative RT-PCR to demonstrate that the activity of heme related genes differ betweenSandNSfoxes in three regions of the brain. Furthermore, our analyses also indicate that changes in mRNA levels of heme related genes can be well described by an additive polygenic effect. We also show that the difference in genetic background between the two lines of foxes is limited, as estimated by mitochondrial DNA divergence.

Conclusion

Our results indicate that selection for tameness can modify the expression of heme related genes in canid brain regions known to modulate emotions and behavior. The possible involvement of heme related genes in behavior is surprising. It is possible that hemoglobin modulates the behavior of canids by interaction with CO and NO signaling. Another possibility is that hemorphins, known to be produced after enzymatic cleavage of hemoglobin, are responsible for behavioral alterations. Thus, we hypothesize that hemoglobin metabolism can be a functionally relevant aspect of the domestic phenotype in foxes selected for tameness.
Implementing Baby Friendly Hospital Initiative policy: the case of New Zealand public hospitals
Authors: Moore Trinie , Gauld Robin , Williams Sheila
Published: May 2007

Background

Studies show that when the Baby Friendly Hospital Initiative (BFHI) is implemented breastfeeding rates increase. However, there are likely to be various barriers to BFHI implementation. This article reports on an empirical study of government-directed BFHI implementation in the New Zealand public hospital system. It focuses primarily on the barriers encountered through implementing the first Two Steps of the BFHI: developing BFHI policy and communicating it to staff; and providing necessary staff training.

Methods

Qualitative interview data were collected from six lactation consultants. These interviewees emerged via a purposive sample of public hospitals that represent the full range of New Zealand public hospitals. Using a content analysis technique, key themes were drawn from the transcribed interview data.

Results

Analysis revealed eight themes: the hospitals were in varying stages of BFHI policy development; hospital policy was not necessarily based on government policy; hospital policies were communicated in differing ways and dependent on resources; factors outside of hospital control impacted on capacity to improve breastfeeding rates; and complex organisational matters pose a barrier to educating personnel involved in the birthing process.

Conclusion

The findings of this study provide empirical support for prior articles about the process of BFHI policy development and implementation. The study also shows that implementation is multi-faceted and complex.
A high-throughput method for detection of DNA in chloroplasts using flow cytometry
Authors: Rowan Beth A , Oldenburg Delene J , Bendich Arnold J
Published: May 2007

Background

The amount of DNA in the chloroplasts of some plant species has been shown recently to decline dramatically during leaf development. A high-throughput method of DNA detection in chloroplasts is now needed in order to facilitate the further investigation of this process using large numbers of tissue samples.

Results

The DNA-binding fluorophores 4',6-diamidino-2-phenylindole (DAPI), SYBR Green I (SG), SYTO 42, and SYTO 45 were assessed for their utility in flow cytometric analysis of DNA in Arabidopsis chloroplasts. Fluorescence microscopy and real-time quantitative PCR (qPCR) were used to validate flow cytometry data. We found neither DAPI nor SYTO 45 suitable for flow cytometric analysis of chloroplast DNA (cpDNA) content, but did find changes in cpDNA content during development by flow cytometry using SG and SYTO 42. The latter dye provided more sensitive detection, and the results were similar to those from the fluorescence microscopic analysis. Differences in SYTO 42 fluorescence were found to correlate with differences in cpDNA content as determined by qPCR using three primer sets widely spaced across the chloroplast genome, suggesting that the whole genome undergoes copy number reduction during development, rather than selective reduction/degradation of subgenomic regions.

Conclusion

Flow cytometric analysis of chloroplasts stained with SYTO 42 is a high-throughput method suitable for determining changes in cpDNA content during development and for sorting chloroplasts on the basis of DNA content.
Drama-based education to motivate participation in substance abuse prevention
Authors: Stephens-Hernandez Aileen B , Livingston Jonathan N , Dacons-Brock Karen , Craft Howard L , Cameron Amura , Franklin Steven O , Howlett Allyn C
Published: May 2007

Background

The substance abuse prevention goal of the theatre production "TUNNELS" was to provide community education on substance abuse to an audience in Durham, NC and surrounding communities. The education effort intended to increase awareness and understanding of the risk and protective factors associated with alcohol and other drug use, and to promote pro-active behaviors in substance abuse prevention within the adult community. It was hypothesized that community-based education via drama would change attitudes toward alcohol and substance abuse, and increase participation in family and community activities aimed at substance abuse prevention.

Methods

A focus group comprised of educators, substance abuse researchers and local substance abuse counselors developed "life stories" of users of alcohol and other drugs and a local playwright incorporated these and other experiences into a series of six vignettes. The production was publicized throughout the Durham area, and 700 adults attending the play signed a consent form and completed the pre-play survey. The participant pool was restricted to those adults who completed both the time-1 and time-2 surveys and resided within Durham and surrounding communities. Paired comparisons of mean responses were analyzed using a paired sample two-tailed t-test. A telephone survey three months after the play assessed attitudes toward substance abuse as a disease, and whether the respondents had increased their participation in prevention activities including discussions of the play with others.

Results

Viewing the play increased the knowledge base of participants regarding substance abuse as a disease, even though the audience demonstrated an appreciation of risk and protective factors prior to attending the performance. In the pre-play survey, participants indicated a strong opinion that parental involvement in teen life was important, and therefore this was not increased as a result of viewing the play. It was found that the drama increased intent to participate in substance abuse prevention activities at home and in the community. Follow-up surveys performed three months after the performance indicated that participants had discussed the play with others and had increased their participation in substance abuse prevention activities, particularly regarding donations of money.

Conclusion

Drama incorporates a component of emotional response to the informational content, and the combination of emotion and information works together to promote individual intentions to become more involved in family and community prevention activities. This study demonstrates the efficacy of drama as a mechanism to educate and motivate. Support for this mechanism is warranted at the level of state, local community, school district, and faith-based and community organizations.
Moving research into practice: lessons from the US Agency for Healthcare Research and Quality's IDSRN program
Authors: Gold Marsha , Taylor Erin Fries
Published: May 2007

Background

The U.S. Agency for Healthcare Research and Quality's (AHRQ) Integrated Delivery Systems Research Network (IDSRN) program was established to foster public-private collaboration between health services researchers and health care delivery systems. Its broad goal was to link researchers and delivery systems to encourage implementation of research into practice. We evaluated the program to address two primary questions: 1) How successful was IDSRN in generating research findings that could be applied in practice? and 2) What factors facilitate or impede such success?

Methods

We conducted in-person and telephone interviews with AHRQ staff and nine IDSRN partner organizations and their collaborators, reviewed program documents, analyzed projects funded through the program, and developed case studies of four IDSRN projects judged promising in supporting research implementation.

Results

Participants reported that the IDSRN structure was valuable in creating closer ties between researchers and participating health systems. Of the 50 completed projects studied, 30 had an operational effect or use. Some kinds of projects were more successful than others in influencing operations. If certain conditions were met, a variety of partnership models successfully supported implementation. An internal champion was necessary for partnerships involving researchers based outside the delivery system. Case studies identified several factors important to success: responsiveness of project work to delivery system needs, ongoing funding to support multiple project phases, and development of applied products or tools that helped users see their operational relevance. Factors limiting success included limited project funding, competing demands on potential research users, and failure to reach the appropriate audience.

Conclusion

Forging stronger partnerships between researchers and delivery systems has the potential to make research more relevant to users, but these benefits require clear goals and appropriate targeting of resources. Trade-offs are inevitable. The health services research community can best consider such trade-offs and set priorities if there is more dialogue to identify areas and approaches where such partnerships may have the most promise. Though it has unique features, the IDSRN experience is relevant to research implementation in diverse settings.
Factors associated with excessive bleeding in cardiopulmonary bypass patients: a nested case-control study
Authors: Jimenez Rivera Juan J , Iribarren Jose L , Raya Jose M , Nassar Ibrahim , Lorente Leonardo , Perez Rosalia , Brouard Maitane , Lorenzo Jose M , Garrido Pilar , Barrios Ysamar , Diaz Maribel , Alarco Blas , Martinez Rafael , Mora Maria L
Published: May 2007

Introduction

Excessive bleeding (EB) after cardiopulmonary bypass (CPB) may lead to increased mortality, morbidity, transfusion requirements and re-intervention. Less than 50% of patients undergoing re-intervention exhibit surgical sources of bleeding. We studied clinical and genetic factors associated with EB.

Methods

We performed a nested case-control study of 26 patients who did not receive antifibrinolytic prophylaxis. Variables were collected preoperatively, at intensive care unit (ICU) admission, at 4 and 24 hours post-CPB. EB was defined as 24-hour blood loss of >1 l post-CPB. Associations of EB with genetic, demographic, and clinical factors were analyzed, using SPSS-12.2 for statistical purposes.

Results

EB incidence was 50%, associated with body mass index (BMI)< 26.4 (25–28) Kg/m2, (P= 0.03), lower preoperative levels of plasminogen activator inhibitor-1 (PAI-1) (P= 0.01), lower body temperature during CPB (P= 0.037) and at ICU admission (P= 0.029), and internal mammary artery graft (P= 0.03) in bypass surgery. We found a significant association between EB and 5G homozygotes for PAI-1, after adjusting for BMI (F = 6.07;P= 0.02) and temperature during CPB (F = 8.84;P= 0.007). EB patients showed higher consumption of complement, coagulation, fibrinolysis and hemoderivatives, with significantly lower leptin levels at all postoperative time points (P= 0.01,P< 0.01 andP< 0.01).

Conclusion

Excessive postoperative bleeding in CPB patients was associated with demographics, particularly less pronounced BMI, and surgical factors together with serine protease activation.
Electroporation-based methods for in vivo, whole mount and primary culture analysis of zebrafish brain development
Authors: Hendricks Michael , Jesuthasan Suresh
Published: May 2007

Background

Electroporation is a technique for the introduction of nucleic acids and other macromolecules into cells. In chick embryos it has been a particularly powerful technique for the spatial and temporal control of gene expression in developmental studies. Electroporation methods have also been reported for Xenopus, zebrafish, and mouse.

Results

We present a new protocol for zebrafish brain electroporation. Using a simple set-up with fixed spaced electrodes and microinjection equipment, it is possible to electroporate 50 to 100 embryos in 1 hour with no lethality and consistently high levels of transgene expression in numerous cells. Transfected cells in the zebrafish brain are amenable to in vivo time lapse imaging. Explants containing transfected neurons can be cultured for in vitro analysis. We also present a simple enzymatic method to isolate whole brains from fixed zebrafish for immunocytochemistry.

Conclusion

Building on previously described methods, we have optimized several parameters to allow for highly efficient unilateral or bilateral transgenesis of a large number of cells in the zebrafish brain. This method is simple and provides consistently high levels of transgenesis for large numbers of embryos.
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome
Authors: Morcel Karine , Camborieux Laure ,   Programme de Recherches sur les Aplasies Müllériennes (PRAM), Guerrier Daniel
Published: May 2007

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part (2/3) of the vagina in women showing normal development of secondary sexual characteristics and a normal 46, XX karyotype. It affects at least 1 out of 4500 women. MRKH may be isolated (type I) but it is more frequently associated with renal, vertebral, and, to a lesser extent, auditory and cardiac defects (MRKH type II or MURCS association). The first sign of MRKH syndrome is a primary amenorrhea in young women presenting otherwise with normal development of secondary sexual characteristics and normal external genitalia, with normal and functional ovaries, and karyotype 46, XX without visible chromosomal anomaly. The phenotypic manifestations of MRKH syndrome overlap with various other syndromes or associations and thus require accurate delineation. For a long time the syndrome has been considered as a sporadic anomaly, but increasing number of familial cases now support the hypothesis of a genetic cause. In familial cases, the syndrome appears to be transmitted as an autosomal dominant trait with incomplete penetrance and variable expressivity. This suggests the involvement of either mutations in a major developmental gene or a limited chromosomal imbalance. However, the etiology of MRKH syndrome still remains unclear. Treatment of vaginal aplasia, which consists in creation of a neovagina, can be offered to allow sexual intercourse. As psychological distress is very important in young women with MRKH, it is essential for the patients and their families to attend counseling before and throughout treatment.
Successful whole lung lavage in pulmonary alveolar proteinosis secondary to lysinuric protein intolerance: a case report
Authors: Ceruti Michele , Rodi Giuseppe , Stella Giulia M , Adami Andrea , Bolongaro Antonia , Baritussio Aldo , Pozzi Ernesto , Luisetti Maurizio
Published: May 2007

Background

Pulmonary alveolar proteinosis (PAP) is a rare disease characterised by accumulation of lipoproteinaceous material within alveoli, occurring in three clinically distinct forms: congenital, acquired and secondary. Among the latter, lysinuric protein intolerance (LPI) is a rare genetic disorder caused by defective transport of cationic amino acids. Whole Lung Lavage (WLL) is currently the gold standard therapy for severe cases of PAP.

Case presentation

We describe the case of an Italian boy affected by LPI who, by the age of 10, developed digital clubbing and, by the age of 16, a mild restrictive functional impairment associated with a high-resolution computed tomography (HRCT) pattern consistent with pulmonary alveolar proteinosis. After careful assessment, he underwent WLL.

Conclusion

Two years after WLL, the patient has no clinical, radiological or functional evidence of pulmonary disease recurrence, thus suggesting that WLL may be helpful in the treatment of PAP secondary to LPI.
Craniopharyngioma
Authors: Garnett Matthew R , Puget Stéphanie , Grill Jacques , Sainte-Rose Christian
Published: May 2007

Craniopharyngiomas are benign slow growing tumours that are located within the sellar and para sellar region of the central nervous system. The point prevalence of this tumour is approximately 2/100,000. The onset of symptoms is normally insidious with most patients at diagnosis having neurological (headaches, visual disturbances) and endocrine (growth retardation, delayed puberty) dysfunctions. Craniopharyngiomas are thought to arise from epithelial remnants of the craniopharyngeal duct or Rathke's pouch (adamantinomatous type) or from metaplasia of squamous epithelial cell rests that are remnants of the part of the stomadeum that contributed to the buccal mucosa (squamous papillary type). The neuroradiological diagnosis is mainly based on the three components of the tumour (cystic, solid and calcified) in the characteristic sellar/para sellar location. Definitive diagnosis is made following histological examination of a surgical specimen. The differential diagnosis includes other tumours in this region (pituitary adenoma), infectious or inflammatory processes (eosinophilic granuloma), vascular malformations (aneurysm) and congenital anomalies (Rathke's cleft cyst). The current treatment is gross total excision of the tumour, if there is no hypothalamic invasion or, in the presence of hypothalamic invasion, a sub-total resection with post-operative radiotherapy. Endocrine disturbances are normally permanent and need careful replacement. Overall, there is an 80% 5 year survival, though this can be associated with marked morbidity (hypothalamic dysfunction, altered neuropsychological profile).
Absolute quantitative real-time polymerase chain reaction for the measurement of human papillomavirus E7 mRNA in cervical cytobrush specimens
Authors: Scheurer Michael E , Dillon Laura M , Chen Zhuo , Follen Michele , Adler-Storthz Karen
Published: May 2007

Background

Few reports of the utilization of an accurate, cost-effective means for measuring HPV oncogene transcripts have been published. Several papers have reported the use of relative quantitation or more expensive Taqman methods. Here, we report a method of absolute quantitative real-time PCR utilizing SYBR-green fluorescence for the measurement of HPV E7 expression in cervical cytobrush specimens.

Results

The construction of a standard curve based on the serial dilution of an E7-containing plasmid was the key for being able to accurately compare measurements between cervical samples. The assay was highly reproducible with an overall coefficient of variation of 10.4%.

Conclusion

The use of highly reproducible and accurate SYBR-based real-time polymerase chain reaction (PCR) assays instead of performing Taqman-type assays allows low-cost, high-throughput analysis of viral mRNA expression. The development of such assays will help in refining the current screening programs for HPV-related carcinomas.
Acute small bowel obstruction as a result of a Meckel's diverticulum encircling the terminal ileum: A case report
Authors: Thakor Avnesh S , Liau Siong S , o'Riordan Dermot C
Published: May 2007

Background

In the developed world, small bowel obstruction accounts for 20% of all acute surgical admissions. The aetiology for majority of these cases includes postoperative adhesions and herniae. However, a relatively uncommon cause is a Meckel's diverticulum. Although this diagnosis is primarily reported in the adolescent population, it should also be considered in adults.

Case Presentation

In the present report, we present a rare case where a fit and healthy 74-year-old gentleman, with no previous history of abdominal surgery, presented with the cardinal symptoms and signs of small bowel obstruction as the result of a Meckel's diverticulum encircling his terminal ileum. Initial investigations included a supine abdominal x-ray showing dilated loops of small bowel and computerised tomographic imaging of the abdomen, which revealed a stricture in the terminal ileum of unknown aetiology. At laparotomy, multiple loops of distended small bowel were seen from the duodeno-jeujenal junction to the terminal ileum, which was encircled by a Meckel's diverticulum. The Meckel's diverticulum was then divided to release the obstruction, mobilised and subsequently removed. Finally, the small bowel contents were decompressed into the stomach and the nasogastric tube aspirated, before returning the loops of bowel into the abdomen in sequence. The patient made a good postoperative recovery and was discharged home 5 days later.

Conclusion

This report highlights the importance of considering a Meckel's diverticulum as a cause of small bowel obstruction in individuals from all age groups and especially in a person with no previous abdominal pathology or surgery.
Association of cerebrospinal fluid anti-ribosomal P protein antibodies with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus
Authors: Hirohata Shunsei , Arinuma Yoshiyuki , Takayama Maki , Yoshio Taku
Published: May 2007

We explored the relationship of antibodies to the whole ribosomal P proteins (P0, P1, and P2) in cerebrospinal fluid (CSF) with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus (SLE). CSF samples were obtained from 71 SLE patients (52 patients with diffuse psychiatric/neuropsychological syndromes [diffuse NP-SLE] and 19 patients with neurological syndromes or peripheral neuropathy [focal NP-SLE]) as well as from 24 patients with non-inflammatory neurological disease. Immunoglobulin G (IgG) antibodies to the C-terminal 22-amino acid ribosomal P synthetic peptide (anti-PC22) and those to purified bovine ribosomal P proteins (P0, P1, and P2) (anti-whole P) were determined by enzyme-linked immunosorbent assay; affinity-purified IgG anti-PC22 were used as the standard. The concentrations of antibodies to epitopes other than the C-terminal 22 amino acids of ribosomal P proteins were calculated by subtracting anti-PC22 from anti-whole P (anti-PEX.C22). CSF anti-whole P levels were significantly elevated in diffuse NP-SLE compared with focal NP-SLE or control patients. By contrast, there were no significant differences in CSF anti-PC22 levels among the three groups. Of note, CSF anti-PEX.C22 levels were significantly elevated in diffuse NP-SLE compared with the other two groups. CSF anti-PEX.C22 levels were not significantly correlated with CSF anti-PC22 levels, but with CSF antibodies against the recombinant ribosomal P0 protein lacking the C-terminal 22 amino acids (C22-depleted rP0). Moreover, levels of CSF anti-PEX.C22 or CSF anti-C22-depleted rP0, but not CSF anti-PC22, were significantly correlated with CSF anti-neuronal cell antibodies (anti-N). These results indicate that CSF IgG antibodies to the epitopes other than the C-terminal 22 amino acids of ribosomal P proteins, which might contain one of the major targets of CSF anti-N, are associated with the development of diffuse NP-SLE.
Early Pituitary-Gonadal Activation before Clinical Signs of Puberty in 5- to 8-Year-Old Adopted Girls: A Study of 99 Foreign Adopted Girls and 93 Controls
Authors: Teilmann Grete , Boas Malene , Petersen Jørgen H. , Main Katharina M. , Gormsen Magdalena , Damgaard Karen , Brocks Vibeke , Skakkebæk Niels E. , Jensen Tina Kold
Published: May 2007

Context: Recent studies have indicated that internationally adopted girls are at high risk of developing precocious puberty. Clinical studies including a contemporary control group are lacking.

Objective: The objective was to study clinical, biochemical, and ultrasonographic markers of pituitary-gonadal activation in prepubertal adopted girls and a control group in the same age categories.

Setting: The study took place at University Hospital, Copenhagen, Denmark.

Design and Participants: The study included randomly selected internationally adopted girls [(n = 99; mean age, 6.9 (5.1–8.5) yr] and controls of Danish origin [n = 93; mean age, 6.8 (5.2–8.5) yr] who were studied cross-sectionally.

Methods: Height, weight, and pubertal stage were assessed with serum levels of reproductive hormones. Size and morphology of internal genitals were evaluated by ultrasonography. Bone age was evaluated by x-ray of the left hand.

Results: Serum values of FSH were significantly higher in prepubertal adopted girls compared with controls [median, 1.4 (95% confidence interval, 0.4–3.6) vs. 1.0 (0.4–2.4) IU/liter; P <0.001]. Serum estradiol was above detection limit (>18 pmol/liter) in 46.5% of prepubertal adopted girls and 20.7% of controls (P = 0.001). In prepubertal adopted girls, the proportion of measurable samples increased significantly with age [odds ratio, 2.5 (95% confidence interval, 1.3–5.0; P = 0.009]. In controls, the odds ratio was 1.0 (0.6–1.7) (P = 0.9). Serum SHBG levels were significantly lower in prepubertal adopted girls compared with controls [99.0 (50.4–153.0) vs. 115.0 (53.1–202.1); P < 0.001].

Conclusion: Five- to 8-yr-old adopted girls showed signs of increased pituitary as well as gonadal activity despite prepubertal phenotype in the majority of girls. Our findings suggest that early onset of puberty in adopted girls is centrally driven.
Thyrotropin Activates Guanosine 5′-Diphosphate/Guanosine 5′-Triphosphate Exchange on the Rate-Limiting Endocytic Catalyst, Rab5a, in Human Thyrocytes in Vivo and in Vitro
Authors: van den Hove Marie-France , Croizet-Berger Karine , Tyteca Donatienne , Selvais Charlotte , de Diesbach Philippe , Courtoy Pierre J.
Published: May 2007

Context: We have previously reported that the TSH receptor/cAMP cascade enhances the coordinate expression of the rate-limiting endocytic catalysts, Rab5a and Rab7, which respectively promote thyroglobulin (Tg) internalization and transfer to lysosomes, thereby accelerating thyroid hormone secretion.

Objective: We address whether TSH further controls Rab5a activity by promoting its GTP-bound state.

Design: We compared Rab5a activation in seven pairs of hyperactive and corresponding quiescent thyroid tissues; TSH effect was reproduced on polarized cultures of normal human thyrocytes.

Patients: We studied seven euthyroid patients bearing hyperactive autonomous adenomas; normal thyroid tissue for culture.

Main Outcome Measurements: Rab5a GDP/GTP exchange factor activity [Rab5a-guanine nucleotide exchange factor (GEF)], expression of Rabex-5 (a Rab5a-GEF), and function of thyrocytes in vitro were the main outcome measures.

Results: In autonomous adenomas, constitutive activation increased both total activity and sedimentability (membrane recruitment) of Rab5a-GEF, compared with perinodular tissues. Increased Rab5a-GEF activity correlated with increased expression of Rabex-5 and Rab5a, as well as with Tg store depletion. In polarized human thyrocyte monolayers, TSH did not affect total Rab5a-GEF activity after 2 h but promoted its membrane recruitment; after 4 d, TSH increased both Rab5a-GEF activity and Rabex-5 expression and recruitment onto membranes where Rabex-5 coimmunoprecipitated with Rabaptin-5 and Rab5a. Sedimentable Rab5a-GEF perfectly correlated with apical endocytosis and lysosomal transfer of 125I-Tg, and with basolateral secretion of 125I-derived hormones.

Conclusion: This study provides the first clinical and experimental evidence that regulation of the activity of a rate-limiting endocytic catalyst finely tunes a tightly controlled cellular function that ultimately governs whole body metabolism.
Health Status, Mood, and Cognition in Experimentally Induced Subclinical Hypothyroidism
Authors: Samuels M. H. , Schuff K. G. , Carlson N. E. , Carello P. , Janowsky J. S.
Published: May 2007

Objective: The objective of the study was to determine whether subclinical hypothyroidism causes decrements in health status, mood, and/or cognitive function.

Design: This was a double-blinded, randomized, crossover study of usual dose l-thyroxine (L-T4) (euthyroid arm) vs. lower dose L-T4 (subclinical hypothyroid arm) in hypothyroid subjects.

Patients: Nineteen subjects on L-T4 therapy for primary hypothyroidism participated in the study.

Measurements: Subjects underwent measurements of health status, mood, and cognition using validated instruments: Short Form 36, Profile of Mood States, and tests of declarative memory (paragraph recall, complex figure), working memory (N-back, subject ordered pointing, digit span backward), and motor learning (pursuit rotor). The same measures were repeated after 12 wk on each of the study arms.

Results: Mean TSH levels increased to 17 mU/liter on the subclinical hypothyroid arm (P < 0.0001). Mean free T4 and free T3 levels remained within the normal range. The Profile of Mood States fatigue subscale and Short Form 36 general health subscale were slightly worse during the subclinical hypothyroid arm. Measures of working memory (N-back, subject ordered pointing) were worse during the subclinical hypothyroid arm. These differences did not depend on mood or health status but were related to changes in free T4 or free T3 levels. There were no decrements in declarative memory or motor learning.

Conclusions: We found mild decrements in health status and mood in L-T4-treated hypothyroid subjects when subclinical hypothyroidism was induced in a blinded, randomized fashion. More importantly, there were independent decrements in working memory, which suggests that subclinical hypothyroidism specifically impacts brain areas responsible for working memory.
Identification and Functional Characterization of a Novel Mutation in the Calcium-Sensing Receptor Gene in Familial Hypocalciuric Hypercalcemia: Modulation of Clinical Severity by Vitamin D Status
Authors: Zajickova Katerina , Vrbikova Jana , Canaff Lucie , Pawelek Peter D. , Goltzman David , Hendy Geoffrey N.
Published: May 2007

Context: Familial hypocalciuric hypercalcemia (FHH) is a benign condition associated with heterogeneous inactivating mutations in the calcium-sensing receptor (CASR) gene.

Objective: The objective of the study was to identify and characterize a CASR mutation in a moderately hypercalcemic, hyperparathyroid individual and his family and assess the influence of vitamin D status on the clinical expression of the defect.

Subjects: We studied a kindred with FHH, in which the proband (a 34-yr-old male) was initially diagnosed with primary hyperparathyroidism due to frankly elevated serum PTH levels.

Methods: CASR gene mutation analysis was performed on genomic DNA of the proband and family members. The mutant CASR was functionally characterized by transient transfection studies in kidney cells in vitro.

Results: A novel heterozygous mutation (F180C, TTC>TGC) in exon 4 of the CASR gene was identified. Although the mutant receptor was expressed normally at the cell surface, it was unresponsive with respect to intracellular signaling (MAPK activation) to increases in extracellular calcium concentrations. The baby daughter of the proband presented with neonatal hyperparathyroidism with markedly elevated PTH. Vitamin D supplementation of both the proband and the baby resulted in reduction of serum PTH levels to the normal range. The serum calcium level remained at a constant and moderately elevated level.

Conclusion: The identification of a novel CASR gene mutation established the basis of the hypercalcemia in the kindred. Concomitant vitamin D deficiency modulates the severity of the presentation of FHH.
Total Inhibin Is a Potential Serum Marker for Epithelial Ovarian Cancer
Authors: Tsigkou Anastasia , Marrelli Daniele , Reis Fernando M. , Luisi Stefano , Silva-Filho Agnaldo L. , Roviello Franco , Triginelli Sérgio A. , Petraglia Felice
Published: May 2007

Context: Total inhibin is the sum of precursors, subunits, and mature molecules of inhibin, which the normal ovary nearly stops to produce after menopause, whereas ovarian tumors still release.

Objective: The aim of the present study was to evaluate whether the serum concentration of total inhibin has the sensitivity/specificity characteristics to become a diagnostic test for epithelial ovarian cancer in postmenopausal women.

Design: This was a controlled, cross-sectional study.

Setting: The study was conducted at the University of Siena.

Patients: Blood specimens were collected from postmenopausal women with: 1) epithelial ovarian cancer, stage II-III (n = 89); 2) benign ovarian tumors (n = 25); 3) breast (n = 10), colon (n = 10), and stomach (n = 10) cancers; and 4) controls (n = 95). In the group of women with epithelial ovarian cancer, blood specimens were also collected after surgical removal of the tumor. In four cases of women with stage IIC mucinous tumor, blood specimens were collected during the follow-up time.

Intervention: Total inhibin was measured by a new double-antibody ELISA.

Results: Women with epithelial ovarian cancers showed serum total inhibin levels significantly higher than those with benign tumor or with nonovarian tumors or controls (P < 0.001). Patients with serous (n = 40) or mucinous tumors (n = 17) showed the highest total inhibin levels (P < 0.001). At 95% specificity, the total inhibin assay detected 37 of 40 (93%) serous tumors and 16 of 17 (94%) mucinous tumors. When total inhibin was combined with CA-125, all cases of serous and mucinous tumors were detected, and the overall sensitivity for epithelial ovarian cancers was 99% at 95% specificity. A significant decrease of total inhibin levels was shown in women with serous and mucinous carcinoma as result of surgery (P < 0.001). In the four women who were followed up, recurrence was associated to an increase of total inhibin levels.

Conclusions: The present data show that total inhibin is a sensitive and specific marker of epithelial ovarian cancers in postmenopausal women. Total inhibin may therefore be combined with CA-125 for noninvasive diagnosis of epithelial ovarian cancer and may also be a useful serum marker to monitor disease-free intervals.
Cerebral Ischemia Probably Related to Isotretinoin
Authors: Laroche Marie-Laure , Macian-Montoro Francisco , Merle Louis , Vallat Jean-Michel
Published: May 2007

OBJECTIVE:

To report a case of cerebral ischemia in a patient receiving oral isotretinoin for severe acne.

CASE SUMMARY:

A 30-year-old right-handed man was admitted for left facial paralysis and dysarthria. He had received oral isotretinoin 45 mg/day for 3 months for treatment of severe acne. A cerebral computed tomography scan showed hypodensity in the right middle cerebral territory corresponding to cerebral ischemia. The patient reported having experienced a similar episode 7 years before, after 3 months' treatment with oral isotretinoin. No risk factors were identified. Isotretinoin was discontinued on admission and the disorders resolved.

DISCUSSION:

Our patient did not present thrombotic risk factors and was not being treated with any drug other than isotretinoin; however, he developed 2 episodes of cerebral ischemia following 2 episodes of oral isotretinoin treatment. According to the Naranjo probability scale, the relationship of cerebral ischemia to administration of isotretinoin was probable. Other reports of thrombotic accidents, as well as some cases of hemorrhage in patients receiving isotretinoin, have been published. This drug seems to act on the coagulation process by a still unexplained mechanism.

CONCLUSIONS:

Given that isotretinoin is a treatment prescribed most frequently for adolescents and young adults and that cerebral ischemia can produce serious handicaps, an evaluation of vascular risk should be made prior to treatment with this drug.
Treatment of Serratia marcescens Meningitis with Prolonged Infusion of Meropenem
Authors: Nicasio Anthony M , Quintiliani Richard , DeRyke C Andrew , Kuti Joseph L , Nicolau David P
Published: May 2007

OBJECTIVE:

To describe the use of and cerebral spinal fluid (CSF) penetration o a prolonged infusion meropenem regimen in a patient with Serratia marcescen meningitis.

CASE SUMMARY:

A 54-year-old female was diagnosed with S. marcescen meningitis associated with an epidural abscess 57 days after surgery for a herniated spinal disk. Meropenem 2000 mg every 8 hours was administered as a prolonged (3 h) infusion for the purpose of optimizing pharmacodynamic exposure Meropenem concentrations were measured from the patient's blood and CSF (via a lumbar drain). The prolonged infusion regimen resulted in concentrations in both serum and CSF above the meropenem minimum inhibitory concentration (MIC) o 0.047 μg/mL for 100% of the dosing interval. After 6 days of therapy, the patien showed no further signs of infection and was subsequently discharged to a rehabilitation facility. At follow-up, she had completed a 4 week course of the prolonged infused therapy without relapse or adverse events.

DISCUSSION:

Gram-negative infections of the central nervous system result in high morbidity and mortality. These infections are often difficult to treat because o poor antibiotic penetration coupled with increasing antibiotic resistance. Although there are 2 other case reports that describe the use of prolonged infusion o meropenem, our patient had a lumbar drain in place, thereby allowing us to collect multiple CSF samples and more accurately assess meropenem exposure at the site of infection. CSF penetration was 6.4% in this patient, resulting in 100% time above the MIC throughout the dosing interval.

CONCLUSIONS:

In this patient with meropenem-susceptible S. marcescensmenin gitis, the use of a high-dose prolonged infusion of meropenem resulted in adequate exposure at the site of infection and a successful clinical response.