Alterations in CRY2 and PER3 gene expression associated with thalamic-limbic community structural abnormalities in patients with bipolar depression or unipolar depression.

Objectives The current study aimed to identify shared and distinct brain structure abnormalities and their relationships with the expression of circadian genes in patients with bipolar or unipolar depression. Method A total of 93 subjects participated in this study, including 32 patients with bipolar depression (BDP), 26 patients with unipolar depression (UDP) and 35 age- and sex-matched healthy controls. Brain structural magnetic resonance imaging scans were obtained, and optimized voxel-based morphometry was used to explore group differences in regional gray matter volume (GMV). The mRNA expression levels of circadian genes in peripheral blood were measured using reverse transcription quantitative real-time polymerase chain reaction. Results Our results showed that the GMV in brain regions in the thalamus-limbic pathways had significantly increased in the BDP patients compared to controls, while the increased GMV in UDP patients compared to controls was limited to the thalamus. The mRNA expression levels of circadian-related genes decreased significantly in patients with BDP, but increased in patients with UDP, compared to controls. In addition, the GMV in the right thalamus in the patients with UDP was positively associated with mRNA levels of CRY2, while the GMV in the right hippocampus in the patients with BDP was negatively associated with mRNA levels of PER3. Conclusion Our study suggested that patients with BDP or MDD shared GMV abnormalities in the right thalamus. The PER3 and CRY2 genes might be critical to right hippocampal dysfunction in BDP and right thalamic dysfunction in UDP, respectively. The result provided potentially important molecular targets for the treatment of mood disorders.

Leaf open time sinogram (LOTS): a novel approach for patient specific quality assurance of total marrow irradiation.

There is no ideal detector-phantom combination to perform patient specific quality assurance (PSQA) for Total Marrow (TMI) and Lymphoid (TMLI) Irradiation plan. In this study, 3D dose reconstruction using mega voltage computed tomography detectors measured Leaf Open Time Sinogram (LOTS) was investigated for PSQA of TMI/TMLI patients in helical tomotherapy. The feasibility of this method was first validated for ten non-TMI/TMLI patients, by comparing reconstructed dose with (a) ion-chamber (IC) and helical detector array (ArcCheck) measurement and (b) planned dose distribution using 3Dγ analysis for 3%@3mm and dose to 98% (D98%) and 2% (D2%) of PTVs. Same comparison was extended for ten treatment plans from five TMI/TMLI patients. In all non-TMI/TMLI patients, reconstructed absolute dose was within ± 1.80% of planned and IC measurement. The planned dose distribution agreed with reconstructed and ArcCheck measured dose with mean (SD) 3Dγ of 98.70% (1.57%) and 2Dγ of 99.48% (0.81%). The deviation in D98% and D2% were within 1.71% and 4.10% respectively. In all 25 measurement locations from TMI/TMLI patients, planned and IC measured absolute dose agreed within ± 1.20%. Although sectorial fluence verification using ArcCHECK measurement for PTVs chest from the five upper body TMI/TMLI plans showed mean ± SD 2Dγ of 97.82% ± 1.27%, the reconstruction method resulted poor mean (SD) 3Dγ of 92.00% (± 5.83%), 64.80% (± 28.28%), 69.20% (± 30.46%), 60.80% (± 19.37%) and 73.2% (± 20.36%) for PTVs brain, chest, torso, limb and upper body respectively. The corresponding deviation in median D98% and D2% of all PTVs were < 3.80% and 9.50%. Re-optimization of all upper body TMI/TMLI plans with new pitch and modulation factor of 0.3 and 3 leads significant improvement with 3Dγ of 100% for all PTVs and median D98% and D2% < 1.6%. LOTS based PSQA for TMI/TMLI is accurate, robust and efficient. A field width, pitch and modulation factor of 5 cm, 0.3 and 3 for upper body TMI/TMLI plan is suggested for better dosimetric outcome and PSQA results.

Prevalence of human papillomavirus, Epstein-Barr virus, p21, and p53 expression in sinonasal inverted papilloma, nasal polyp, and hypertrophied turbinate in Hong Kong patients.

BACKGROUND: The purpose of this study of human papillomavirus (HPV), Epstein-Barr virus (EBV), p21, and p53 in sinonasal inverted papilloma (IP) was to help elucidate its pathogenesis. METHODS: Seventy-three IPs, 48 nasal polyps, and 85 hypertrophied turbinates were subjected to HPV polymerase chain reaction (PCR) study. Seventy-three IPs, 30 nasal polyps, and 32 hypertrophied turbinates were subjected to EBV in situ hybridization (ISH), p21, and p53 immunohistochemical (IHC) studies. RESULTS: HPV was positive in 3 of 73 IPs (4.1%). All specimens were EBV negative. In all, 99% of IPs showed strong and diffuse p21 nuclear reactivity. Most nasal polyps and hypertrophied turbinates showed weak to moderate immunoreactivity of the basal and parabasal cells. Only focal p53 immunoreactivity of the basal and parabasal cells was found in 19% of IPs and 40% of nasal polyps. CONCLUSIONS: HPV prevalence of our IP is low. EBV is not present in IP. High p21 and low p53 expression in IP suggests a non-p53-dependent regulation pathway.

Treatment results of sinonasal inverted papilloma: an 18-year study.

BACKGROUND: This article reviews our treatment results of sinonasal inverted papilloma (SNIP) over the past 18 years. A retrospective observational study was performed. METHODS: Fifty-six patients with SNIP seen between 1990 and 2008 with follow-up of >2 years were retrospectively analyzed. RESULTS: Forty patients (71%) had primary endoscopic resection and 16 patients (29%) had endoscopic-assisted external approaches. Ten patients (18%) had small nasoethmoid residual disease resectable under local anesthesia in the outpatient department. Eight patients (14%) had recurrences requiring revision under general anesthesia, most of which were maxillary and frontal disease requiring additional external approaches. Comparing patients with and without a history of previous surgery (36% versus 64% of all patients), the former had a higher chance of requiring external approaches during the primary resection (45% versus 29%), a higher recurrence rate (45% versus 25%), and a higher chance of external approaches for revision (44% versus 22%). All the first recurrences were at the original tumor site. Eighty-nine percent of the first recurrences were diagnosed within the first 2 years postoperation. CONCLUSION: Thirty-two percent of our patients had recurrence after their primary resection. Recurrences in the nasoethmoid area are usually small and resectable endoscopically under local anesthesia in the outpatient department whereas those inside the maxillary and frontal sinuses are likely to require additional external approaches under general anesthesia. A minimum of 2 years of follow-up is recommended for the preliminary report on the treatment results of this condition. Lifelong follow-up is recommended for possible late recurrences and metachronous multifocal disease.

The roles and limitations of computed tomography in the preoperative assessment of sinonasal inverted papillomas.

BACKGROUND: Preoperative radiological assessment of sinonasal inverted papilloma (SNIP) is important in the planning of surgical treatment. This study investigates the roles and limitations of preoperative plain computed tomography (CT) scan in the preoperative assessment of SNIP. METHODS: Plain CT scans from 30 patients with SNIP were reviewed retrospectively by a radiologist who had no prior knowledge of the final surgical findings. Disease at each sinus was judged by the CT findings of opacity and additional signs. The overall disease was staged according to the staging system proposed by Krouse. All of the findings were compared with the final disease extent and staging confirmed by intraoperative and histological findings. RESULTS: Using opacity with additional signs for diagnosis, the range of accuracy of CT diagnosis for each sinus involvement was 83-97%. Staging by plain CT was concordant with postoperative staging in 80% of patients. Among the additional signs, focal hyperostosis or "bony strut" had the highest positive predictive value (100%) of tumor origin. CONCLUSION: Focal hyperostosis or bony strut is the most important CT sign predicting the origin of tumor. Although using multiple CT diagnostic signs provides a reasonable assessment of tumor origin and extent, accurate tumor mapping was still impossible because of inadequate differentiation of tumor from inflammatory pathologies. This drawback may be overcome by a complementary MRI scan. Since preoperative CT staging was inaccurate in 20% of cases, surgical planning should be flexible to provide for the need of the intraoperative findings.

Do-not-resuscitate decision: the attitudes of medical and non-medical students.

OBJECTIVES: To study the attitudes of both medical and non-medical students towards the do-not-resuscitate (DNR) decision in a university in Hong Kong, and the factors affecting their attitudes. METHODS: A questionnaire-based survey conducted in the campus of a university in Hong Kong. Preferences and priorities of participants on cardiopulmonary resuscitation in various situations and case scenarios, experience of death and dying, prior knowledge of DNR and basic demographic data were evaluated. RESULTS: A total of 766 students participated in the study. There were statistically significant differences in their DNR decisions in various situations between medical and non-medical students, clinical and preclinical students, and between students who had previously experienced death and dying and those who had not. A prior knowledge of DNR significantly affected DNR decision, although 66.4% of non-medical students and 18.7% of medical students had never heard of DNR. 74% of participants from both medical and non-medical fields considered the patient's own wish as the most important factor that the healthcare team should consider when making DNR decisions. Family wishes might not be decisive on the choice of DNR. CONCLUSIONS: Students in medical and non-medical fields held different views on DNR. A majority of participants considered the patient's own wish as most important in DNR decisions. Family wishes were considered less important than the patient's own wishes.

Titration of low K(d) binding sites: binding of arginine analogs to nitric oxide synthases.

Spectrophotometrically monitored ligand titration is an important method for the determination of equilibrium dissociation constants (K(d)) from nitric oxide synthases (NOS). Low K(d) sites such as the tetrahydrobiopterin and arginine binding sites present difficulties in that experiments often require enzyme concentrations of the same magnitude as the K(d). An analytical method based on computer simulation is described that allows the estimation of K(d) values without an independent means of monitoring free ligand or without an accurate prior determination of the number of binding sites. The K(d) for arginine is approximately 0.5 microM for the tetrahydrobiopterin replete neuronal and inducible isoforms (nNOS and iNOS), while the endothelial isoform has a slightly higher K(d) (1.5 microM). N-OH-arginine (an intermediate) binds to nNOS with a K(d) of around 0.2 microM, while the inhibitors N-methyl-arginine and N-nitro-arginine bind more tightly; our best K(d) estimates are 100 nM or lower.

Endoscopic terminal dacryocystorhinostomy.

OBJECTIVE: Traditional endoscopic dacryocystorhinostomy (DCR) involves creation of a lacrimal sac side hole that may close down in the presence of a partially patent lower lacrimal drainage system. Endoscopic terminal DCR is a modified DCR procedure designed to prevent this problem. METHODS: From September 1996 to June 1999, 16 patients (17 sides) had endoscopic terminal DCR that involved resection of the lacrimal sac-duct junction to achieve total separation of the lacrimal sac from the nasolarcrimal duct and creation of a terminal DCR opening. RESULTS: Ten of the 17 DCRs were primary and 7 were revisions. The follow-up ranged from 3 to 36 months. There were two failures. One failure was due to canalicular obstruction and the other was due to prolapse of orbital fat hindering proper fashioning of the mucosal flap. The overall success rate was 88%. CONCLUSIONS: Instead of creating a side hole in the lacrimal sac as proposed by most endoscopic DCR studies, we advocate total diversion of tear flow by performing a terminal DCR opening that would further improve the success rate of endoscopic DCR, particularly in cases of idiopathic and partial obstruction.

Endoscopic resection of inverted papilloma of the nose and paranasal sinuses.

The results of a retrospective study of 22 patients with inverted papillomas resected by the endoscopic approach are presented with a follow-up of 33 to 96 months. Twenty-one patients had unilateral disease and one patient had bilateral involvement. None of the patients had orbital or cranial extension. One patient had synchronous carcinoma in situ. Eight patients had undergone previous surgical procedures. Following endoscopic surgery, six patients had residual disease requiring further revisions. Three of these six patients eventually required excision via limited external approaches. No patient required lateral rhinotomy or mid-facial degloving procedures. No complication occurred in any of the patients. The advantages of endoscopic surgery include precise determination of tumour extent, preservation of normal mucosa and bony structures and avoidance of external scars. Close endoscopic follow-up is mandatory to ensure early recognition and treatment of recurrent disease. Although the endoscopic approach is gaining popularity for the treatment of inverted papilloma, indiscriminate application may result in a high recurrence rate. The endoscopic approach should be performed by experienced surgeons and restricted to carefully selected patients with nasal, ethmoidal and limited maxillary disease. More extensive disease should be managed by radical external approaches or by combining endoscopic with limited external approaches.

Spontaneous growth in Chinese patients with Turner's syndrome and influence of karyotype.

The pretreatment mixed cross-sectional and longitudinal height measurements of 203 patients with Turner's syndrome (TS) were analysed. Only one observation was included per year per child and a total of 858 observations formed the basis of the growth study. The mean and SD values were fitted separately by a second-degree polynomial function, giving smoothed growth curves. The spontaneous growth pattern of Chinese girls with TS runs parallel to published Caucasian TS growth curves. The mean final height of Chinese patients with TS was 142 cm compared to 147 cm and 139 cm observed in Northern European and Japanese patients, respectively. Patients with the 46, X, i(Xq) karyotype were found to be significantly shorter, whereas children with the 45, X/46, XY and 46, X, del(Xq) karyotypes were significantly taller among this group of patients. Patients with TS who were disomic for Xp are significantly taller than patients who were monosomic for Xp. Our results suggest that karyotype can have a significant effect on the growth of children with TS.

Ingested foreign bodies--a contemporary management approach.

A prospective study of all foreign body complaints presenting through our Accident and Emergency Department was conducted in a population where the condition is endemic. All patients were managed by otolaryngologists. Six hundred and eight patients were attended to yielding 179 foreign bodies. Making use of modern equipment and a practical approach, the requirement for examination under general anesthesia was 6.3 per cent. In this series there was a complication rate of 0.5 per cent.

Cytogenetic and DNA analysis of two neuroectodermal tumors without a simple t(11;22).

Cytogenetic analysis was conducted on tumor biopsy material from two pediatric, small, round, blue-cell tumors whose histology failed to give a clearcut diagnosis. The first case showed a complex composite karyotype within which there were two normal chromosomes 11 and one abnormal chromosome 22 present. The composite karyotype in the second case was similarly complex but this time included an abnormal chromosome 11 but no corresponding abnormal chromosome 22. Analysis of tumor mRNA from both cases using a Reverse Transcriptase PCR test with primers derived from a Ewing's sarcoma t(11;22)(q24;q12) breakpoint sequence showed both to have abnormal, chimeric transcribed messengers, each of different lengths. Further analysis of case 2 using chromosome painting and centromeric probing confirmed the abnormal chromosome 11 to be a der(11)t(11;22)(q24;q12) and also revealed two additional minor clones containing a der(22), which may be the karyotypic locations of the t(11;22) fusion sequences. Taken into consideration with clinical and histologic information, the results of these investigations indicated that both were neuroectodermal tumors (Ewing sarcomas of the chest wall/Askin tumors). The comparative values of both cytogenetic and molecular analysis in the diagnosis of neuroectodermal tumors and the detection of covert chromosome rearrangements are discussed.

Epithelial damage by Helicobacter pylori in gastric ulcers.

On review of 136 consecutive biopsies of benign gastric ulcer, Helicobacter pylori was detected in 78 cases (57.3%). The gastric epithelium colonized by Helicobacter pylori showed a characteristic constellation of changes, including loss of apical mucous portion of individual cells, drop-out of epithelial cells, epithelial pits, erosions and cellular tufts, indicative of cellular injury and regeneration. Among the 58 Helicobacter-negative cases, similar changes were not observed in the ulcer edges, except for two cases which exhibited some cellular tufts. Thus, the topographic association of Helicobacter pylori with epithelial damage in the gastric ulcer edges in more than half of the cases suggests that this organism probably plays an aetiological role in ulcerogenesis, at least in these cases. Furthermore, the epithelial changes are so distinctive that they can serve as a helpful histological indicator for the presence of Helicobacter pylori in gastric biopsies.

A clinical comparison of budesonide nasal aerosol, terfenadine and a combined therapy of budesonide and oxymetazoline in adult patients with perennial rhinitis.

The efficacy of budesonide, terfenadine and a combination of budesonide and oxymetazoline in the treatment of perennial rhinitis was evaluated by a double blind, parallel group study. Adult patients with perennial rhinitis were randomized into three groups. Group 1 patients received budesonide nasal aerosol 400 micrograms/day for 21 days and oxymetazoline nasal drops for the first three days. Group 2 and 3 patients received budesonide 400 micrograms/day and terfenadne tablet 60 mg twice/day respectively. Nasal symptoms were assessed by the patients before and daily during the treatment period using a simple scoring system. One hundred and forty-two patients were recruited and 130 completed the study. Budesonide, but not terfenadine, significantly reduced all nasal symptoms from baseline (p less than 0.05). Terfenadine could significantly relieve the nasal blockage (p less than 0.05) more than other nasal symptoms. Budesonide with or without oxymetazoline nasal drops provided a better control of nasal symptoms than terfenadine (p less than 0.05). Budesonide with oxymetazoline for the first three days showed a faster relief of nasal blockage than budesonide alone (p less than 0.05). Mild and transient adverse effects were encountered in all three groups. It is concluded that nasal symptoms of perennial rhinitis are more adequately controlled by budesonide than by terfenadine.

Diagnosis of nasopharyngeal carcinoma.

The diagnosis of nasopharyngeal carcinoma rests on perceptive symptom analysis, a careful clinical examination, and the selection of appropriate clinical investigations. A high index of suspicion is required. When mirror examination fails to provide a satisfactory view of the nasopharynx, flexible or rigid nasopharyngeal endoscopy is mandatory. Serologic examination of IgA antibodies to Epstein-Barr virus early antigen and viral capsid antigen is helpful in identifying high-risk patients. Biopsy material should be sent fresh to the laboratory for analysis so that special staining can be carried out in cases of doubtful diagnosis.