Primary ciliary dyskinesia: current state of the art

Primary ciliary dyskinesia (PCD) is usually inherited as an autosomal recessive disorder and presents with upper and lower respiratory tract infection, and mirror image arrangement in around 50% of cases. Cilia dysfunction is also implicated in a wider spectrum of disease, including polycystic liver and kidney disease, central nervous system problems including retinopathy and hydrocephalus, and biliary atresia. Cilia are complex structures, containing more than 250 proteins; recent studies have begun to locate PCD genes scattered throughout the genome. Screening tests for PCD include nasal nitric oxide and in vivo tests of ciliary motility such as the saccharin test. Specific diagnosis requires examination of cilia by light and electron microscopy, with epithelial culture in doubtful cases. This is only available in supra-regional centres, recently centrally funded by the National Commissioning Group. Treatment is not evidence based and recommendations are largely extrapolated from cystic fibrosis and other suppurative lung diseases.     

Influence of body mass index on clinicopathologic features, surgical morbidity and outcome in patients with endometrial cancer

Aim

To examine the influence of obesity on the patient characteristics and clinicopathologic features of endometrial cancer, and to find how treatment and prognosis were affected by obesity in women with endometrial cancer.

Methods

The data of 370 consecutive women operated for endometrial cancer were retrospectively reviewed. Patients were divided into three categories as <25, 25–29.9 and ≥30 according to BMI. All patients underwent primary surgical treatment including total abdominal hysterectomy, bilateral oophorectomy and peritoneal cytology. Pelvic lymphadenectomy was carried out for all patients except for those with no myometrial invasion regardless of the tumor grade or for whom it was technically impossible. Paraaortic lymphadenectomy was performed when pre- and intraoperative assessments suggested non-endometrioid or grade 3 endometrioid cancer, >50?% myometrial invasion and cervical involvement.

Results

Patients with a BMI (body mass index) of <25 were significantly younger. Patients with a BMI of ≥30 were statistically less likely to have >50?% myometrial invasion and more likely to have stage I disease. There were no significant differences in the incidences of positive pelvic and paraaortic lymph nodes and tumor grades between the three groups. Also, there were no differences in surgery type, the mean of removed pelvic and paraaortic lymph node number, hospital stay, blood loss and complications between the groups. The patients with a BMI of ≥30 had significantly longer operating time. There were no statistically significant differences in recurrences, the median number of months at recurrence or the site of recurrence between the three groups, as well as the 5-year overall and disease-free survival of patients. Multivariate proportional hazard models identified stage III and IV disease as significant covariates for mortality rates, while stage III and IV disease, hypertension and pelvic irradiation were identified as significant covariates for recurrence rates.

Conclusion

Positive peritoneal cytology, deep myometrial invasion and stage II–IV endometrial cancer were significantly more common in patients with a BMI of <25. There were no significant differences in tumor grade, surgical technique, surgical morbidity or adjuvant radiotherapy between the BMI groups. Recurrence and cancer-related mortality rates were not affected by the BMI.     

Urotensin II levels in patients with chronic kidney disease and kidney transplants

Objective.

Urotensin II is a potent vasoactive peptide that has been implicated in the pathophysiology of many diseases. There is no study reporting the role and level of this peptide in recipients of kidney transplant. So we aimed to study the plasma levels of urotensin II in this group of patients.

Methods.

Plasma urotensin II levels were analyzed in 110 subjects, who were divided into three groups: group 1 (35 kidney transplant recipients), group 2 (36 patients with chronic kidney disease), and group 3 (39 healthy controls).

Results.

Analysis of logarithmic transformation of urotensin II, i.e. log (urotensin II × 1000) levels, with a one-way analysis of variance yielded a P value of 0.001. Post-hoc analysis showed significantly higher log (urotensin II × 1000) levels in group 1 than groups 2 and 3 (P = 0.001 and 0.017, respectively). One of the important features of the subjects of this group was that they were taking immunosuppressive drugs because of renal transplantation.

Conclusions.

High urotensin II levels in recipients of kidney transplants could be drug-related (immunosuppressive drugs) and may be of practical importance that may be used to improve the long-term outcome of the patients.     

Evaluation of a surgical simulator for learning clinical anatomy

BACKGROUND: New techniques in imaging and surgery have made 3-dimensional anatomical knowledge an increasingly important goal of medical education. This study compared the efficacy of 2 supplemental, self-study methods for learning shoulder joint anatomy to determine which method provides for greater transfer of learning to the clinical setting. METHODS: Two groups of medical students studied shoulder joint anatomy using either a second-generation virtual reality surgical simulator or images from a textbook. They were then asked to identify anatomical structures of the shoulder joint as they appeared in a videotape of a live arthroscopic procedure. RESULTS: The mean identification scores, out of a possible score of 7, were 3.1 +/- 1.3 for the simulator group and 2.9 +/- 1.5 for the textbook group (P = 0.70). Student ratings of the 2 methods on a 5-point Likert scale were significantly different. The simulator group rated the simulator more highly as an effective learning tool than the textbook group rated the textbook (means of 3.2 +/- 0.7 and 2.6 +/- 0.5, respectively, P = 0.02). Furthermore, the simulator group indicated that they were more likely to use the simulator as a learning tool if it were available to them than the textbook group was willing to use the textbook (means of 4.0 +/- 1.2 and 3.0 +/- 0.9, respectively, P = 0.02). CONCLUSION: Our results show that this surgical simulator is at least as effective as textbook images for learning anatomy and could enhance student learning through increased motivation. These findings provide insight into simulator development and strategies for learning anatomy. Possible explanations and future research directions are discussed.     

Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality

Little is known about neural mechanisms underlying human personality and temperament, despite their considerable importance as highly heritable risk mediators for somatic and psychiatric disorders. To identify these circuits, we used a combined genetic and imaging approach focused on Monoamine Oxidase A (MAOA), encoding a key enzyme for monoamine metabolism previously associated with temperament and antisocial behavior. Male carriers of a low-expressing genetic variant exhibited dysregulated amygdala activation and increased functional coupling with ventromedial prefrontal cortex (vmPFC). Stronger coupling predicted increased harm avoidance and decreased reward dependence scores, suggesting that this circuitry mediates a part of the association of MAOA with these traits. We utilized path analysis to parse the effective connectivity within this system, and provide evidence that vmPFC regulates amygdala indirectly by influencing rostral cingulate cortex function. Our data implicate a neural circuit for variation in human personality under genetic control, provide an anatomically consistent mechanism for vmPFC-amygdala interactions underlying this variation, and suggest a role for vmPFC as a superordinate regulatory area for emotional arousal and social behavior.     

An Interaction of Oxytocin Receptors with Metabotropic Glutamate Receptors in Hypothalamic Astrocytes

Hypothalamic astrocytes play a critical role in the regulation and support of many different neuroendocrine events, and are affected by oestradiol. Both nuclear and membrane oestrogen receptors (ERs) are expressed in astrocytes. Upon oestradiol activation, membrane‐associated ER signals through the type 1a metabotropic glutamate receptor (mGluR1a) to induce an increase of free cytoplasmic calcium concentration ([Ca²⁺]_i). Because the expression of oxytocin receptors (OTRs) is modulated by oestradiol, we tested whether oestradiol also influences oxytocin signalling. Oxytocin at 1, 10, and 100 nm induced a [Ca²⁺]_i flux measured as a change in relative fluorescence [ΔF Ca²⁺ = 330 ± 17 relative fluorescent units (RFU), ΔF Ca²⁺ = 331 ± 22 RFU, and ΔF Ca²⁺ = 347 ± 13 RFU, respectively] in primary cultures of female post‐pubertal hypothalamic astrocytes. Interestingly, OTRs interacted with mGluRs. The mGluR1a antagonist, LY 367385 (20 nm ), blocked the oxytocin (1 nm )‐induced [Ca²⁺]_i flux (ΔF Ca²⁺ = 344 ± 19 versus 127 ± 11 RFU, P < 0.001). Conversely, the mGluR1a receptor agonist, (RS)‐3,5‐dihydroxyphenyl‐glycine (100 nm ), increased the oxytocin (1 nm )‐induced [Ca²⁺]_i response (ΔF Ca²⁺ = 670 ± 31 RFU) compared to either compound alone (P < 0.001). Because both oxytocin and oestradiol rapidly signal through the mGluR1a, we treated hypothalamic astrocytes sequentially with oxytocin and oestradiol to determine whether stimulation with one hormone affected the subsequent [Ca²⁺]_i response to the second hormone. Oestradiol treatment did not change the subsequent [Ca²⁺]_i flux to oxytocin (P > 0.05) and previous oxytocin exposure did not affect the [Ca²⁺]_i response to oestradiol (P > 0.05). Furthermore, simultaneous oestradiol and oxytocin stimulation failed to yield a synergistic [Ca²⁺]_i response. These results suggest that the OTR signals through the mGluR1a to release Ca²⁺ from intracellular stores and rapid, nongenomic oestradiol stimulation does not influence OTR signalling in astrocytes.     

Imaging genetics: perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing.

Advances in molecular biology and neuroimaging have provided a unique opportunity to explore the relationships between genes, brain, and behavior. In this review, we will briefly outline the rationale for studying genetic effects on brain function with neuroimaging. We will then use studies of genetically driven variation in serotonin transporter function on corticolimbic structure and function to highlight the effectiveness of this strategy to delineate biological pathways and mechanisms by which individual differences in brain function emerge and potentially bias behavior and risk for psychiatric illness. In a series of studies, a relatively frequent regulatory variant of the human serotonin transporter gene (5-HTTLPR) has been demonstrated to bias the reactivity of the amygdala to salient environmental cues. Moreover, the 5-HTTLPR affects the development of a broader corticolimbic circuit and alters the functional integration of emotional information between the amygdala and medial prefrontal cortex. In turn, corticolimbic circuit function predicts individual differences in an experimental index of temperamental anxiety and, thus, might reflect a predictive biological marker of increased risk for mood disorders associated with the 5-HTTLPR.     

Three cases of oblique facial cleft: etiology, tomographic evaluation and reconstruction.

Three cases of oro-ocular clefts from different families are presented. Two of the cases had a normal chromosomal constitution. The defects in each case were evaluated by computerized tomography computerized tomography prior to surgery. The theories concerning etiology and classification of oblique facial clefts are discussed in the light of computerized tomography scan findings. One of the cases had a history of maternal bromocriptine mesylate usage for prolactinoma, suggesting a teratogenic effect, but no similar cases have been reported in the medial literature.     

Dual-ended, multifunction tools for microsurgery

A new concept in microsurgical instrumentation is herein described and the rationale for its design presented in the context of surgical efficiency. This new concept employs bipolarity or dual-endedness as a means to enable the microsurgeon to have access to various instruments without the need to exchange tools. The elimination of instrument exchange has increased the speed with which a microsurgeon can perform a variety of procedures as well as decrease fatigue associated with continuous visual reaccommodation between the microscope and surrounding operating room. Following considerable modification through several prototypical stages and long periods of laboratory testing, these instruments boast ideal balance in the hands of the surgeon, and the capacity for modification by the user, allowing a variety of instrument combinations. Hence, personal preference can dictate the ultimate tool configuration, thereby allowing customization of the instruments to the procedure as well as the surgeon, by virtue of an interlocking mechanism between instrument components. The resulting economy of movement and reduced instrument handling engendered by the use of these instruments reduces operating time and often eliminates the need for a highly trained surgical assistant. These instruments can be fitted with a removable extension allowing unipolar use or extended instrument length. Simplicity of design makes these instruments conducive to standard cleaning and sterilization procedures.