Aetiological bases of 46,XY disorders of sex development in the Hong Kong Chinese population.

OBJECTIVE: Disorders of sex development are due to congenital defects in chromosomal, gonadal, or anatomical sex development. The objective of this study was to determine the aetiology of this group of disorders in the Hong Kong Chinese population. SETTING: Five public hospitals in Hong Kong. PATIENTS: Patients with 46,XY disorders of sex development under the care of paediatric endocrinologists between July 2009 and June 2011. MAIN OUTCOME MEASURES: Measurement of serum gonadotropins, adrenal and testicular hormones, and urinary steroid profiling. Mutational analysis of genes involved in sexual differentiation by direct DNA sequencing and multiplex ligation-dependent probe amplification. RESULTS: Overall, 64 patients were recruited for the study. Their age at presentation ranged from birth to 17 years. The majority presented with ambiguous external genitalia including micropenis and severe hypospadias. A few presented with delayed puberty and primary amenorrhea. Baseline and post-human chorionic gonadotropin-stimulated testosterone and dihydrotestosterone levels were not discriminatory in patients with or without AR gene mutations. Of the patients, 22 had a confirmed genetic disease, with 11 having 5α-reductase 2 deficiency, seven with androgen insensitivity syndrome, one each with cholesterol side-chain cleavage enzyme deficiency, Frasier syndrome, NR5A1-related sex reversal, and persistent Müllerian duct syndrome. CONCLUSIONS: Our findings suggest that 5α-reductase 2 deficiency and androgen insensitivity syndrome are possibly the two most common causes of 46,XY disorders of sex development in the Hong Kong Chinese population. Since hormonal findings can be unreliable, mutational analysis of the SRD5A2 and AR genes should be considered the first-line tests for these patients.

Thermal response of a dental tissue induced by femtosecond laser pulses.

This paper reports a theoretical and experimental study for thermal transport in a thin slice of human tooth induced by a 120 fs, 800 nm pulse laser at a repetition rate of 1 kHz. The surface reflectivity of enamel and the convection heat transfer coefficient were determined using an inverse heat transfer analysis. Instead of a fully three-dimensional modeling, two simplified two-dimensional (2D) planar and axisymmetric heat conduction models were proposed to simulate the temperature fields. The temperature responses obtained from the 2D planar and axisymmetric model agree well with the experimental measurements. On the other hand, the one-dimensional (1D) result significantly differs from the 2D axisymmetric one, suggesting that care should be taken when a 1D thermal model is considered for estimating temperature response.

Chinese herbal medicine for functional constipation: a randomised controlled trial.

1. This was an 18-week prospective, randomised, double-blind, placebo-controlled clinical study on a Chinese herbal medicine--ma zi ren wan (MZRW)--for the treatment of functional constipation. 2. 120 subjects with functional constipation (Rome III criteria) were randomised (60 per arm) into the MZRW and placebo groups. Respective responder rates for the two groups were 43.3% and 8.3% during treatment, and 30.0% and 15.0% in the follow-up period (p<0.05). The MZRW group was superior to the placebo group in terms of increased complete spontaneous bowel movement as well as reduction in severity of constipation, straining at evacuation, and use of rescue therapy. No serious adverse effects were reported. 3. The dose of MZRW (7.5 g bid) was determined in a separate clinical trial. This study entailed a dose determination study and then a placebo-controlled clinical trial and can be a good reference for future studies.

Inhibition of angiogenic and non-angiogenic targets by sorafenib in renal cell carcinoma (RCC) in a RCC xenograft model.

BACKGROUND: It is widely recognised that sorafenib inhibits a range of molecular targets in renal cell carcinoma (RCC). In this study, we aim to use patient-derived RCC xenografts to delineate the angiogenic and non-angiogenic molecular targets of sorafenib therapy for advanced RCC (aRCC). METHODS: We successfully generated three patient RCC-derived xenografts in severe combined immunodeficient mice, consisting of three different RCC histological subtypes: conventional clear cell, poorly differentiated clear cell RCC with sarcomatoid changes, and papillary RCC. This study also used clear cell RCC cells (786-0/EV) harbouring mutant VHL to investigate the clonogenic survival of cells transfected with survivin sense and antisense oligonucleotides. RESULTS: All three xenografts retain their original histological characteristics. We reported that sorafenib inhibited all three RCC xenograft lines regardless of histological subtypes in a dose-dependant manner. Sorafenib-induced growth suppression was associated with not only inhibition of angiogenic targets p-PDGFR-ß, p-VEGFR-2, and their downstream signalling pathways p-Akt and p-ERK, cell cycle, and anti-apoptotic proteins that include cyclin D1, cyclin B1, and survivin but also upregulation of proapoptotic Bim. Survivin knockdown by survivin-specific antisense-oligonucleotides inhibited colony formation and induced cell death in clear cell RCC cells. CONCLUSION: This study has shed light on the molecular mechanisms of sorafenib in RCC. Inhibition of non-angiogenic molecules by sorafenib could contribute in part to its anti-tumour activities observed in vivo, in addition to its anti-angiogenic effects.

Hyperammonaemic encephalopathy in an adult patient with citrin deficiency associated with a novel mutation.

We report on an adult patient with citrin deficiency in Hong Kong, in whom a novel mutation was identified. The patient presented with recurrent hyperammonaemic encephalopathy due to impairment of the liver urea cycle enzyme argininosuccinate synthetase. This autosomal recessive condition is also characterised by interesting food preferences, notably aversion to carbohydrates and craving for protein-rich and/or lipid-rich foods, as well as neuropsychiatric symptoms. Plasma amino acid analysis is very useful in revealing urea cycle disorders, and mutational analysis of the SLC25A13 gene can confirm the diagnosis.

Impact of BD Kiestra InoqulA streaking patterns on colony isolation and turnaround time of methicillin-resistant Staphylococcus aureus and carbapenem-resistant Enterobacterale surveillance samples.

OBJECTIVES: To determine if using alternative streaking patterns on the BD Kiestra InoqulA can impact colony isolation and improve turnaround time (TAT) of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacterales (CRE) screening samples. METHODS: A total of 1571 positive MRSA screening samples were studied, of which 755 screening plates were streaked by the standard pattern (4-Quadrant uniform S200) and 816 plates were streaked by an alternative pattern (Zigzag 3.5-1 S200). A total of 424 CRE-positive screening samples were studied, of which 211 screening plates were streaked by the standard pattern (Zigzag 2.5-1 inoc S200) and 213 plates were streaked by an alternative customized pattern (Zigzag 3.5-1 vertstreak s200). RESULTS: There was a reduction in the number of MRSA screening plates with insufficient isolated colonies for confirmatory testing from 75 plates (9.9%) when using the standard pattern to 18 plates (2.2%) when using the alternative streaking pattern. MRSA cases with a TAT above 36 hours also reduced significantly from 144 (19.1%) to 20 (2.4%). The number of CRE screening plates with insufficient colonies for same-day confirmatory testing reduced from 16 (7.6%) when using the standard pattern to two plates (1.1%) when using the alternative customized pattern. CRE cases with a TAT above 36 hours also reduced from 16 (7.6%) to seven (3.3%). CONCLUSIONS: The change in streaking patterns resulted in more plates with sufficient isolated colonies as well as reduced man-hours and materials required to perform subculture of mixed colonies and overall improvements in TAT.

Validation of the Chinese Version of Obsessive-Compulsive Inventory-Revised.

BACKGROUND: The Obsessive-Compulsive Inventory-Revised (OCI-R) is a psychometrically sound and valid self-report measure for evaluating the severity of six dimensions of obsessive-compulsive symptoms: washing, obsessing, hoarding, ordering, checking, and neutralising. We aimed to validate the Chinese version of the OCI-R (C-OCI-R) in patients with obsessive-compulsive disorder (OCD) in Hong Kong. METHODS: The C-OCI-R was forward and backward translated and reviewed by an expert panel and a focus group. The internal consistency and test-retest reliability (2-week interval) were examined. Confirmatory factor analysis was used to examine the construct validity of the C-OCI-R. Concurrent validity was examined by the correlation between the C-OCI-R and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), whereas divergent validity was examined by the correlation of the C-OCI-R with the Beck Depression Inventory-Second Edition and the Hamilton Depression Rating Scale. RESULTS: 130 OCD patients were recruited. The C-OCI-R showed excellent internal consistency (Cronbach's alpha = 0.92) and test-retest reliability (Spearman's rho correlation coefficient = 0.96). The original six-factor model was supported by confirmatory factor analysis. Concurrent validity and divergent validity were established. However, the neutralising subscale may need further development, and the divergent validity of the obsessing subscale was unsatisfactory. The structure of OCD symptoms was similar in Chinese and western patients. CONCLUSION: The C-OCI-R is a valid and reliable measure for assessing the severity of obsessive-compulsive symptoms in local Chinese patients with OCD.

Factors associated with healthcare utilization costs for statin therapy--a pilot study in Hong Kong.

BACKGROUND: Socio-economic status, comorbidities and adherence to statin therapy might affect the cost-effectiveness of statin therapy in hyperlipidemia. OBJECTIVE: To examine the effects size of demographic factors, clinical factors and adherence to statin therapy on the direct medical costs for Chinese patients at high risk of coronary heart disease (CHD). METHODS: This was a prospective, observational cohort study conducted in the outpatient departments of a public teaching hospital in Hong Kong. Patients at high risk of CHD who had been on statin monotherapy for < 12 months were recruited. Baseline demographic and clinical data were obtained. Statin adherence was monitored prospectively over 6 months using the Medication Event Monitoring System. Total direct medical costs per member per month (cPMPM), including cost for clinic visits, statin medication, laboratory tests on lipids and management of CHD events if any, were calculated from the perspective of a public healthcare organization. RESULTS: 83 patients completed the study. Median cPMPM in 80 patients (96% of 83 patients) without a new CHD event (USD 42) and for 3 (4%) patients who experienced CHD events (USD 444) were significantly different (p = 0.003). History of congestive heart failure (beta = 1,957, 95% CI = 1,006 - 2,909), male gender (beta = 584, 95% CI = 215 - 952), coronary atherosclerosis (beta = 1,436, 95% CI = 538 - 2,334) and diabetes mellitus (beta = 604, 95% CI = 136 - 1,07 1) were positive predictors for cPMPM. CONCLUSION: In this pilot study male gender, diabetes mellitus, congestive heart failure and coronary atherosclerosis appear to be significantly associated with higher costs for Chinese patients at high risk of CHD.

Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility.

Estrogen has been proposed to trigger breast cancer development via an initiating mechanism involving its metabolite, catechol estrogen (CE). To examine this hypothesis, we conducted a multigenic case-control study to determine whether polymorphisms of the genes responsible for CE formation via estrogen biosynthesis (CYP17) and hydroxylation (CYP1A1) and CE inactivation (COMT) are associated with an elevated risk for breast cancer in Taiwanese women, and whether the association between genotype and risk may be modified by estrogen exposure. One hundred and fifty breast cancer patients and 150 healthy controls were recruited. PCR-based RFLP assays were used to determine the genotypes of estrogen-metabolizing genes. The breast cancer risk associated with individual susceptibility genotypes varied among the three genes and was highest for COMT, followed by CYP1A1 and CYP17. After simultaneous consideration of all three genes and other well-established risk factors of breast cancer, the COMT genotype remained the most significant determinant for breast cancer development and was associated with a 4-fold increase in risk (95% confidence interval, 1.12-19.08). Furthermore, a trend of increasing risk for developing breast cancer was found in women harboring higher numbers of high-risk genotypes (P = 0.006), including the high activity CYP17 (CYP17 A2/A2), high inducibility CYP1A1 (CYP1A1 MspI vt/vt), and low activity COMT (COMT L/L) genotypes. The association of risk with the number of susceptibility genotypes was stronger in women with prolonged estrogen exposure (indicated by a higher number of estrogen exposure years or a higher number of estrogen exposure years between menarche and first full-term pregnancy), women with higher estrogen levels (implied by early menarche), and women with a higher body mass index (> or = 22.5). On the basis of comprehensive profiles of estrogen metabolism, this study supports the possibility that breast cancer can be initiated by estrogen exposure.

The effect of slice thickness on target and organs at risk volumes, dosimetric coverage and radiobiological impact in IMRT planning.

PURPOSE: Dose-volume histogram (DVH) has become an important tool for evaluation of radiation outcome as reflected from many clinical protocols. While dosimetric accuracy in treatment planning system (TPS) is well quantified, the variability in volume estimation is uncertain due to reconstruction algorithm that is investigated in this study. In addition, the impact of dose distribution and tumor control probability (TCP) were also investigated with CT slice thickness for IMRT planning. MATERIALS AND METHODS: A water phantom containing various objects with accurately known volume ranging from 1 to 100 cm(3) was scanned with 1, 2, 3, 5, and 10 mm slice thickness. The CT data sets were sent to Eclipse TPS for contour delineation and volume estimation. The data were compared with known volume for the estimation of error in the volume of each structure. IMRT Plans were generated on phantom containing four objects with different slice thickness (1-5 mm) to calculate TCP. ICRU-83-recommended dose points such as D 2%, D 50%, D 98%, as well as homogeneity and conformity index were also calculated. RESULTS: The variability of volumes with CT slice thickness was significant especially for small volume structures. A maximum error of 92% was noticed for 1 cm(3) volume of object with 10 mm slice thickness, whereas it was ~19% for 1 mm slice thickness. For 2 and 3 cm(3) objects, the maximum error of 99% was noticed with 10 mm slice thickness and ~60% with 5 mm. The differences are smaller for larger volumes with a cutoff at about 20 cm(3). The calculated volume of the objects is a function of reconstruction algorithm and slice thickness. The PTV mean dose and TCP decreased with increasing slice thickness. Maximum variation of ~5% was noticed in mean dose and ~2% in TCP with change in slice thickness from 1 to 5 mm. The relative decrease in target volume receiving 95% of the prescribed dose is ~5% with change in slice thickness from 1 to 5 mm. The homogeneity index increases up to 163% and conformity index decreases by 4% between 1 and 5 mm slice thickness, producing highly inhomogeneous and least conformal treatment plan. CONCLUSIONS: Estimation of a volume is dependent on CT slice thickness and the contouring algorithm in a TPS. During commissioning of TPS and for all clinical protocols, evaluation of volume should be included to provide the limit of accuracy in DVH from TPS, especially for small objects. A smaller slice thickness provides superior dosimetry with improved TCP. Thus, the smallest possible slice thickness should be used for IMRT planning, especially when smaller structures are present.

Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene.

Loss of heterozygosity (LOH) allows the expression of recessive mutation in tumor suppressor genes (TSG). Therefore, on the basis of Knudson's 'two-hit' hypothesis for TSG inactivation, the detection of a high LOH frequency in a chromosomal region is considered critical for TSG localization. One of these LOH regions in breast cancer is 16q22.1, which has been suggested to reflect the involvement of E-cadherin (E-cad), a cell-cell adhesion molecule. To confirm the tumorigenic role of E-cad, 81 sporadic invasive ductal carcinomas (IDCs) of the breast were tested for the 'two hits' required to inactivate this gene. A high frequency (37.3%) of LOH was detected in 67 informative tumors, but no mutation was found. To examine the possibility that transcriptional mechanisms serve as the second hit in tumors with LOH, specific pathways, including genetic variant and hypermethylation at the promoter region and abnormal expression of positive (WT1) and negative (Snail) transcription factors, were identified. Of these, promoter hypermethylation and increased expression of Snail were found to be common (>35%), and to be strongly associated with reduced/negative E-cad expression (P<0.05). However, unexpectedly, a significantly negative association was found between the existence of LOH and promoter hypermethylation (P<0.05), which contradicts the 'two-hit' model. Instead, since they coexisted in a high frequency of tumors, hypermethylation may work in concert with increased Snail to inactivate E-cad expression. Given that E-cad is involved in diverse mechanisms, loss of which is beneficial for tumors to invade but may also trigger apoptosis, this study suggests that maintaining a reversible mechanism, either by controlling the gene at the transcriptional level or by retaining an intact allele subsequent to LOH, might be important for E-cad in IDC and may also be common in TSGs possessing diverse functions. These findings provide clues to explain why certain TSGs identified by LOH cannot fulfil the two-hit hypothesis.

The treatment of recurrent brain metastases with stereotactic radiosurgery.

Between May 1986 and August 1989, we treated 18 patients with 21 recurrent or persistent brain metastases with stereotactic radiosurgery using a modified linear accelerator. To be eligible for radiosurgery, patients had to have a performance status of greater than or equal to 70% and have no evidence of (or stable) systemic disease. All but one patient had received prior radiotherapy, and were treated with stereotactic radiosurgery at the time of recurrence. Polar lesions were treated only if the patient had undergone and failed previous complete surgical resection (10 patients). Single doses of radiation (900 to 2,500 cGy) were delivered to limited volumes (less than 27 cm3) using a modified 6MV linear accelerator. The most common histology of the metastatic lesion was carcinoma of the lung (seven patients), followed by carcinoma of the breast (four patients), and melanoma (four patients). With median follow-up of 9 months (range, 1 to 39), all tumors have been controlled in the radiosurgery field. Two patients failed in the immediate margin of the treated volume and were subsequently treated with surgery and implantation of 125I to control the disease. Radiographic response was dramatic and rapid in the patients with adenocarcinoma, while slight reduction and stabilization occurred in those patients with melanoma, renal cell carcinoma, and sarcoma. The majority of patients improved neurologically following treatment, and were able to be withdrawn from corticosteroid therapy. Complications were limited and transient in nature and no cases of symptomatic radiation necrosis occurred in any patient despite previous exposure to radiotherapy. Stereotactic radiosurgery is an effective and relatively safe treatment for recurrent solitary metastases and is an appealing technique for the initial management of deep-seated lesions as a boost to whole brain radiotherapy.

Expression of two novel mouse Iroquois homeobox genes during neurogenesis.

Members of the Drosophila Iroquois homeobox gene family are implicated in the development of peripheral nervous system and the regionalization of wing and eye imaginal discs. Recent studies suggest that Xenopus Iroquois homeobox (Irx) genes are also involved in neurogenesis. Three mouse Irx genes, Irx1, Irx2 and Irx3, have been previously identified and are expressed with distinct spatio-temporal patterns during neurogenesis. We report here the cloning and expression analysis of two novel mouse Irx genes, Irx5 and Irx6. Although Irx5 and Irx6 proteins are structurally more related to one another, we find that Irx5 displays a developmental expression pattern strikingly similar to that of Irx3, whereas Irx6 expression resembles that of Irx1. Consistent with the notion that Mash1 is a putative target gene of the Irx proteins, all four Irx genes display an overlapping expression pattern with Mash1 in the developing CNS. In contrast, the Irx genes and Mash1 are expressed in complementary domains in the developing eye and olfactory epithelium.

Dose perturbations due to contrast medium and air in mammosite treatment: an experimental and Monte Carlo study.

In the management of early breast cancer, a partial breast irradiation technique called MammoSite (Proxima Therapeutic Inc., Alpharetta, GA) has been advocated in recent years. In MammoSite, a balloon implanted at the surgical cavity during tumor excision is filled with a radio-opaque solution, and radiation is delivered via a high dose rate brachytherapy source situated at the center of the balloon. Frequently air may be introduced during placement of the balloon and/or injection of the contrast solution into the balloon. The purpose of this work is to quantify as well as to understand dose perturbations due to the presence of a high-Z contrast medium and/or an air bubble with measurements and Monte Carlo calculations. In addition, the measured dose distribution is compared with that obtained from a commercial treatment planning system (Nucletron PLATO system). For a balloon diameter of 42 mm, the dose variation as a function of distance from the balloon surface is measured for various concentrations of a radio-opaque solution (in the range 5%-25% by volume) with a small volume parallel plate ion chamber and a micro-diode detector placed perpendicular to the balloon axis. Monte Carlo simulations are performed to provide a basic understanding of the interaction mechanism and the magnitude of dose perturbation at the interface near balloon surface. Our results show that the radio-opaque concentration produces dose perturbation up to 6%. The dose perturbation occurs mostly within the distances <1 mm from the balloon surface. The Plato system that does not include heterogeneity correction may be sufficient for dose planning at distances > or = 10 mm from the balloon surface for the iodine concentrations used in the MammoSite procedures. The dose enhancement effect near the balloon surface (<1 mm) due to the higher iodine concentration is not correctly predicted by the Plato system. The dose near the balloon surface may be increased by 0.5% per cm3 of air. Monte Carlo simulation suggests that the interface effect (enhanced dose near surface) is primarily due to Compton electrons of short range (<0.5 mm). For more accurate dosimetry in MammoSite delivery, the dose perturbation due to the presence of a radio-opaque contrast medium and air bubbles should be considered in a brachytherapy planning system.

Serum lipid profiles in patients receiving endocrine treatment for breast cancer--the results from the Celecoxib Anti-Aromatase Neoadjuvant (CAAN) Trial.

BACKGROUND: Anti-aromatase therapy is important in the treatment of breast cancer. Cyclooxygenase-2 (COX-2) inhibitors may be effective in chemoprevention. A proof of principle study was performed to investigate the efficacy and side effects including changes in lipid profiles of combining anti-aromatase therapy and COX-2 inhibitor preoperatively in hormone sensitive postmenopausal breast cancers. METHODS: From February 2002 to April 2003, 41 postmenopausal women with histologically proven LABC were recruited. The patients were randomly assigned to receive exemestane 25 mg daily and celecoxib 400 mg twice-daily (group A), exemestane 25 mg daily (group B) and letrozole 2.5 mg daily (group C. RESULTS: Observed clinical response rates were 61.5%, 60% and 54.5% for Groups A-C, respectively, with no pathologic complete response. Cholesterol levels for Group A dropped progressively and a statistical difference was observed between fifth week after operation and preoperative level (P = 0.026). In addition, Group A has significantly lowered cholesterol and LDL levels than Groups B and C after 18 weeks of treatment. CONCLUSION: The initial results show that different neoadjuvant anti-aromatase therapies has similar efficacy but the combination with celecoxib may have an advantageous effects on the serum lipid profiles.

Mitochondrial Lon regulates apoptosis through the association with Hsp60-mtHsp70 complex.

Human Lon protease is a mitochondrial matrix protein with several functions, including protein degradation, mitochondrial DNA (mtDNA) binding, and chaperone activity. Lon is currently emerging as an important regulator of mitochondria-contributed tumorigenesis due to its overexpression in cancer cells. To understand the mechanism of increased Lon in tumor cells, we studied the interactome to identify the chaperone Lon-associated proteins by proteomics approaches using the cells overexpressing Lon. In the present study, we designed a method connecting co-immunoprecipitation (Co-IP) to in-solution digestion for the shotgun mass spectrometry. We identified 76 proteins that were putative Lon-associated proteins that participated in mitochondrial chaperone system, cellular metabolism and energy, cell death and survival, and mtDNA stability. The association between Lon and NDUFS8 or Hsp60-mtHsp70 complex was confirmed by Co-IP and immunofluorescence co-localization assay. We then found that the protein stability/level of Hsp60-mtHsp70 complex depends on the level of Lon under oxidative stress. Most importantly, the ability of increased Lon-inhibited apoptosis is dependent on Hsp60 that binds p53 to inhibit apoptosis. These results suggest that the mechanism underlying cell survival regulated by Lon is mediated by the maintenance of the protein stability of Hsp60-mtHsp70 complex. This new knowledge of chaperone Lon interactome will allow us to better understand the cellular mechanism of Lon in mitochondrial function and of its overexpression in enhancing cell survival and tumorigenesis.

The COMT L allele modifies the association between MAOB polymorphism and PD in Taiwanese.

OBJECTIVE: Reports suggest that catechol-O-methyltransferase (COMT(L/L)) (Val(158)/Met) and monoamine oxidase B (MAOB) intron 13 genotype polymorphism is associated with PD. To understand the ethnicity-specific effects of genetic polymorphism, we performed a case-control study of the association between PD susceptibility and polymorphism of MAOB and COMT, both separately and in combination, in Taiwanese. METHODS: Two hundred twenty-four patients with PD and 197 controls, matched for age, sex, and birthplace, were recruited. MAOB and COMT polymorphism genotyping was performed by using PCR-based restriction fragment length polymorphism (RFLP) analyses. chi(2), OR, and Fisher's exact tests were used to compare differences in allelic frequencies and genotypes. RESULTS: The MAOB G genotype (G in men and G:/G in women) was associated with a 2.07-fold increased relative risk of PD. COMT polymorphism, considered alone, showed no correlation with PD risk; however, a significant synergistic enhancement was found in PD patients harboring both the COMT(L) and MAOB G genotypes. CONCLUSIONS: These results suggest that, in Taiwanese, PD risk is associated with MAOB G intron 13 polymorphism, and this association is augmented in the presence of the COMT(L) genotype, indicating an interaction of these two dopamine-metabolizing enzymes in the pathogenesis of sporadic PD. However, the relatively low frequencies of these combined genotypes in our study necessitates confirmation with a larger sample size.

A computer-aided treatment planning technique for universal wedges.

Some modern accelerators provide only one wedge built into the head of the treatment machine. A continuous range of wedge angles can be generated using wedged and unwedged beams in different proportions. However, this may pose difficulty in treatment planning since the planners will have to work with twice as many beams to achieve a desirable dose distribution. We have developed a simple algorithm to solve the treatment planning problem involving wedged and open beam combinations. The algorithm is based on the assumption that the user has some knowledge of the dose distribution to be optimized. Some properties of the distributions are then used to set up the system of equations for optimization. Unlike other optimization techniques, it does not require specification of dose value to every interest point selected, and it allows each specified dose value to vary within a clinically acceptable range. Examples are given to illustrate the application of the algorithm for some standard treatment plans.

Treatment plan evaluation using dose-volume histogram (DVH) and spatial dose-volume histogram (zDVH).

OBJECTIVE: The dose-volume histogram (DVH) has been accepted as a tool for treatment-plan evaluation. However, DVH lacks spatial information. A new concept, the z-dependent dose-volume histogram (zDVH), is presented as a supplement to the DVH in three-dimensional (3D) treatment planning to provide the spatial variation, as well as the size and magnitude of the different dose regions within a region of interest. MATERIALS AND METHODS: Three-dimensional dose calculations were carried out with various plans for three disease sites: lung, breast, and prostate. DVHs were calculated for the entire volume. A zDVH is defined as a differential dose-volume histogram with respect to a computed tomographic (CT) slice position. In this study, zDVHs were calculated for each CT slice in the treatment field. DVHs and zDVHs were compared. RESULTS: In the irradiation of lung, DVH calculation indicated that the treatment plan satisfied the dose-volume constraint placed on the lung and zDVH of the lung revealed that a sizable fraction of the lung centered about the central axis (CAX) received a significant dose, a situation that warranted a modification of the treatment plan due to the removal of one lung. In the irradiation of breast with tangential fields, the DVH showed that about 7% of the breast volume received at least 110% of the prescribed dose (PD) and about 11% of the breast received less than 98% PD. However, the zDVHs of the breast volume in each of seven planes showed the existence of high-dose regions of 34% and 15%, respectively, of the volume in the two caudal-most planes and cold spots of about 40% in the two cephalic planes. In the treatment planning of prostate, DVHs showed that about 15% of the bladder and 40% of the rectum received 102% PD, whereas about 30% of the bladder and 50% of the rectum received the full dose. Taking into account the hollow structure of both the bladder and the rectum, the dose-surface histograms (DSH) showed larger hot-spot volume, about 37% of the bladder wall and 43% of the rectal wall. The zDVHs of the bladder revealed that the hot-spot region was superior to the central axis. The zDVHs of the rectum showed that the high-dose region was an 8-cm segment mostly superior to the central axis. The serial array-like of the rectum warrants a closer attention with regard to the complication probability of the organ. CONCLUSIONS: Although DVH provides an averaged dose-volume information, zDVH provides differential dose-volume information with respect to the CT slice position. zDVH is a 2D analog of a 3D DVH and, in some situations, more superior. It provides additional information on plan evaluation that otherwise could not be appreciated. The zDVH may be used along with DVH for plan evaluation and for the correlation of radiation outcome.