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To study the cost-effectiveness of incorporating home semen analysis in screening for oligospermia and expediting time to evaluation.A decision analytic model was built using inputs from the medical literature. The index patient is the male partner in a couple seeking fertility, and entry into the model was assumed to be at the inception of the couple's attempts to conceive via natural means. Three main strategies are described and analyzed: (1) baseline strategy of no testing, (2) utilization of a home semen testing kit, (3) universal testing via a clinic visit and gold standard lab semen analysis. The primary outcome was detection of oligospermia (defined as sperm concentration15 million/mL). Strategies were ranked by months to evaluation by a male infertility specialist saved. Costs were considered from the patient perspective and were incorporated to determine the incremental cost per month saved to evaluation (ICMS) per 100,000 patients.Compared to a baseline strategy of no screening, utilizing a home test would save 89,000 months at the incremental cost of $7,418,000 for an ICMS of $45.51. Shifting to a strategy of universal gold standard clinic and lab testing saves an additional 3000 months but at an ICMS of $17,691 compared to the home testing strategy.Widespread adoption and the early usage of home semen analysis may be a cost-effective method of screening for oligospermia and facilitating further evaluation with an andrology specialist.

To examine the association between selective serotonin reuptake inhibitor (SSRI) use and semen quality.We performed a retrospective review of all men undergoing semen analysis (SA) for fertility evaluation from 2002-2020 at a single academic medical center. Men were excluded if they had prior exposure to spermatotoxic medications, clomiphene citrate, gonadotropins, selective estrogen receptor modulators, or medical conditions known to impact male fertility. SSRI exposure was defined by an outpatient prescription within 90 days prior to any semen test. Differences between men with and without SSRI exposure were assessed with Wilcoxon rank sum for continuous variables and chi-squared testing for proportions. Univariable and multivariable linear regression models were fit to evaluate the relationship between SSRI use and individual semen parameters, controlling for age at the time of the semen analysis and non-SSRI drug use.A total of 8861 men were identified, of whom 153 men (1.7%) were exposed to SSRIs prior to SA. Median age was 35 years (interquartile range: 32-39) and was similar between groups (P = .999). Non-SSRI medication use was significantly higher in men taking SSRIs (78.4% vs 23.3%,.001). On univariable and multivariable analyses, SSRI exposure was not associated with differences in semen volume, sperm concentration, motility, total motile sperm count, or normal morphology.In adult men undergoing fertility evaluation, SSRI exposure was not associated with impaired semen parameters. These data may help inform reproductive counseling and medical decision-making regarding SSRI use in men seeking paternity.

Objective To examine infertility-related fund-raising campaigns on a popular crowdfunding website and to compare campaign characteristics across states with and without legislative mandates for insurance coverage for infertility-related care. Design Retrospective cohort study. Setting Online crowdfunding platform (GoFundMe) between 2010 and 2020. Patient(s) GoFundMe campaigns in the United States containing the keywords “fertility” and “infertility.” Intervention(s) State insurance mandates for infertility treatment coverage. Main Outcome Measure(s) Primary outcomes included fund-raising goals, funds raised, campaign location, and campaigns per capita. Result(s) Of the 3,332 infertility-related campaigns analyzed, a total goal of $52.6 million was requested, with $22.5 million (42.8%) successfully raised. The average goal was $18,639 (standard deviation [SD] $32,904), and the average amount raised was $6,759 (SD $14,270). States with insurance mandates for infertility coverage had fewer crowdfunding campaigns per capita (0.75 vs. 1.15 campaigns per 100,000 population than states without insurance mandates. Conclusion(s) We found a large number of campaigns requesting financial assistance for costs associated with infertility care, indicating a substantial unmet financial burden. States with insurance mandates had fewer campaigns per capita, suggesting that mandates are effective in mitigating this financial burden. These data can inform future health policy legislation on the state and federal levels to assist with the financial burden of infertility.

This study examined the relationship between stimulant medications used for the treatment of attention deficit hyperactivity disorder and semen parameters. We performed a retrospective cohort study at a large, academic institution between 2002 and 2020. We included men with a semen analysis without prior spermatotoxic medication use, empiric medical therapy exposure or confounding medical diagnoses (varicocele, Klinefelter’s syndrome, cryptorchidism, cystic fibrosis, diabetes, cancer or cancer-related treatment, and azoospermia). Men were stratified by stimulant exposure (methylphenidate or amphetamines). A multivariable linear regression was fit to assess the association between individual semen parameters, age, stimulant exposure and non-stimulant medication use. Of 8,861 men identified, 106 men had active prescriptions for stimulants within 90 days prior to semen testing. After controlling for age and exposure to non-stimulant medications, stimulant use was associated with decreased total motile sperm count (β: −18.00 mil/ejaculate and standard error: 8.44, p = 0.033) in the setting of decreased semen volume (β: −0.35 ml, and standard error: 0.16, p = 0.035), but not sperm concentration, motility and morphology. These findings suggest a role for reproductive physicians and mental health providers to consider counselling men on the potential negative impact of stimulants prescribed for attention deficit hyperactivity disorder on semen volume during fertility planning.

To determine whether health-conscious men are more likely to be concerned about infertility and self-initiate semen analysis at a laboratory/clinic or through a direct-to-consumer at-home product without a health care provider recommendation.Cross-sectional survey conducted online via ResearchMatch.org between November 2019 and January 2020. Men age 18 and older without children (n = 634) were included for analysis. Outcomes were likelihood of self-initiating a semen analysis, prevalence of infertility concern.Of the 634 participants, 186 expressed concern about infertility but only 29% were likely to discuss these concerns with a health care provider. More men would self-initiate a semen analysis using an at-home product than through a traditional laboratory/clinic (14.2% vs 10.4%, P = .04). Odds of self-initiating a traditional semen analysis were higher for men concerned about low testosterone (odds ratio [OR] 2.30, 95% confidence interval [CI] 1.12-4.74, P = .023) and infertility (OR 3.91, 95% CI 2.14-7.15, P.001). Self-initiating an at-home semen analysis was associated with concern for low testosterone and infertility as well as middle age (age 40-59: OR 3.02, 95% CI 1.16-7.88, P = .024) and fitness tracker use (OR: 1.95, 95% CI 1.12-3.39, P = .018).Many men were unlikely to discuss infertility concerns with a health care provider. Middle aged men and those who used fitness trackers were more likely to self-initiate fertility evaluation through at-home semen analysis. Concern about low serum testosterone was pervasive and strongly associated with concern for being infertile and self-initiating a semen analysis of any kind.

Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells. Glycosylation differences have been hypothesized to influence the immunogenicity of these synthetic concentrates. In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared to Chinese hamster ovary cell-derived factor VIII. Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor. Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites. Factor VIII desialylation did not influence binding to murine splenocytes or dendritic cells, nor surface co-stimulatory molecule expression. We did, however, observe increased levels of immunoglobulin M specific to baby hamster kidney-derived factor VIII in naïve hemophilia A mice. De-N-glycosylation enhanced immunoglobulin M binding, suggesting that N-glycan occupancy masks epitopes. Elevated levels of immunoglobulin M and immunoglobulin G specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased immunoglobulin G binding. Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of immunoglobulin M- and immunoglobulin G-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with diverse etiologies. Therefore, the identification of common disease mechanisms and therapeutics targeting these mechanisms could dramatically improve clinical outcomes. To this end, we developed induced motor neuron (iMN) models from C9ORF72 and sporadic ALS (sALS) patients to identify targets that are effective against these types of cases, which together comprise ~90% of patients. We find that iMNs from C9ORF72 and several sporadic ALS patients share two common defects - impaired autophagosome formation and the aberrant accumulation of glutamate receptors. Moreover, we show that an anticoagulation-deficient form of activated protein C, 3K3A-APC, rescues these defects in both C9ORF72 and sporadic ALS iMNs. As a result, 3K3A-APC treatment lowers C9ORF72 dipeptide repeat protein (DPR) levels, restores nuclear TDP-43 localization, and rescues the survival of both C9ORF72 and sporadic ALS iMNs. Importantly, 3K3A-APC also lowers glutamate receptor levels and rescues proteostasis in vivo in C9ORF72 gain- and loss-of-function mouse models. Thus, motor neurons from C9ORF72 and at least a subset of sporadic ALS patients share common, early defects in autophagosome formation and glutamate receptor homeostasis and a single therapeutic approach may be efficacious against these disease processes.

Background Scavenger receptors play a significant role in clearing aged proteins from the plasma, including the large glycoprotein coagulation factors von Willebrand factor (VWF) and factor VIII (FVIII). A large genome-wide association study meta-analysis has identified genetic variants in the gene SCARA5, which encodes the class A scavenger receptor SCARA5, as being associated with plasma levels of VWF and FVIII. Objectives The ability of SCARA5 to regulate the clearance of VWF-FVIII was characterized. Methods VWF-FVIII interactions with SCARA5 were evaluated by solid phase binding assays and in vitro cell based assays. The influence of SCARA5 deficiency on VWF:Ag and half-life was assessed in a murine model. The expression pattern of SCARA5 and its colocalization with VWF was evaluated in human tissues. Results VWF and the VWF-FVIII complex bound to human recombinant SCARA5 in a dose- and calcium-dependent manner. SCARA5 expressing HEK 293T cells bound and internalized VWF and the VWF-FVIII complex into early endosomes. In vivo, SCARA5 deficiency had a modest influence on the half-life of human VWF. mRNA analysis and immunohistochemistry determined that human SCARA5 is expressed in kidney podocytes and the red pulp, white pulp, and marginal zone of the spleen. VWF was found to colocalize with SCARA5 expressed by littoral cells lining the red pulp of the human spleen. Conclusions SCARA5 is an adhesive and endocytic receptor for VWF. In human tissues, SCARA5 is expressed by kidney podocytes and splenic littoral endothelial cells. SCARA5 may have a modest influence on VWF clearance in humans.

Quantitative abnormalities of the von Willebrand factor-factor VIII (VWF-FVIII) complex associate with inherited bleeding or thrombotic disorders. Receptor-mediated interactions between plasma VWF-FVIII and phagocytic or immune cells can influence their hemostatic and immunogenic activities. Genetic association studies have demonstrated that variants in the STAB2 gene, which encodes the scavenger receptor stabilin-2, associate with plasma levels of VWF-FVIII. However, the mechanistic basis and pathophysiological consequences of this association are unknown. We have demonstrated that stabilin-2-expressing cells bind and internalize human VWF and FVIII in a VWF-dependent manner, and stabilin-2-deficient mice displayed prolonged human VWF-FVIII half-life compared with controls. The stabilin-2 variant p.E2377K significantly decreased stabilin-2 expression and impaired VWF endocytosis in a heterologous expression system, and common STAB2 variants associated with plasma VWF levels in type 1 von Willebrand disease patients. STAB2-deficient mice displayed a decreased immunogenic response to human VWF-FVIII complex, while coinfusion of human VWF-FVIII with the stabilin-2 ligand hyaluronic acid attenuated the immune response to exogenous FVIII. Collectively, these data suggest that stabilin-2 functions as both a clearance and an immunoregulatory receptor for VWF-FVIII, making stabilin-2 a novel molecular target for modification of the half-life of VWF-FVIII and the immune response to VWF-FVIII concentrates.

Essentials Initial immune cell interactions leading to factor (F) VIII immunity are not well characterized. We assessed cellular interactions and expression profiles in hemophilia A mice. MARCO+, followed by SIGLEC1+ and SIGNR1+ macrophages co-localize most with human FVIII. The splenic transcriptome highlights potential therapeutic targets to prevent inhibitors.SUMMARY: Background Developing factor VIII (FVIII) inhibitory antibodies is the most serious complication in hemophilia A treatment, representing a significant health and economic burden. A better understanding of the early events in an immune response leading to this outcome may provide insight into inhibitor development. Objective To identify early mediators of FVIII immunity and to detail immune expression profiles in the spleen and liver. Methods C57Bl/6 F8 E16 knockout mice were infused with 5-20 μg (2000-8000 IU kg-1 ) of recombinant FVIII. Spleens were frozen at various time-points post-infusion and stained for FVIII and cellular markers. Splenic and liver RNA expression analysis was performed 3 h post-infusion of 0.6 μg (240 IU kg-1 ) FVIII by nCounter technology using a 561-gene immunology panel. Results FVIII localization in the spleen did not change over 2.5 h. We observed significantly higher co-localization of FVIII with MARCO+ cells compared with SIGLEC1+ and SIGNR1+ in the splenic marginal zone. FVIII exhibited little co-localization with CD11c+ dendritic cells and the macrophage mannose receptor, CD206. Following FVIII infusion, the splenic mRNA profiling identified genes such as Tnfaip6 and Il23r, which are implicated in chemotaxis and a proinflammatory Th17 response, respectively. In contrast, an upregulation of Gfi1 in the liver suggests an anti-inflammatory environment. Conclusions FVIII co-localizes predominantly with marginal zone macrophages (MARCO+ ) in the murine spleen following intravenous infusion. Targeting pathways that are implicated in the early FVIII innate immune response in the spleen may lead to therapeutic interventions to prevent inhibitor formation.

Acute appendicitis (AA) is among the most common causes of acute lower abdominal pain leading patients to the emergency department. Significant debate remains on whether AA should be operated or not. A propensity score-matched analysis was performed in seven Italian Hospitals, with the aim to assess safety and feasibility both nonoperative management with antibiotics (AT) and surgical therapy with appendectomy (ST) for patients with AA. Data regarding all patients discharged from the participating centers with a diagnosis of appendicitis from January 1st, 2014 to December 31st, 2014 were collected retrospectively. Follow-up data were collected from January 1st, 2015 to December 31st, 2016. The complication-free treatment success of AT (53.7%) was significantly inferior to that of ST (86.4%) (P

To determine how robotic prostatectomy affects practice patterns of urologists, we examined the case volume characteristics among certifying urologists for the surgical treatment of prostate cancer. We hypothesized that the utilization of open and robotic prostatectomy as well as lymph node dissection changed dynamically over the last 10 years.A total of 6-month case log data of certifying urologists from 2003 to 2013 were obtained for the American Board of Urology. Cases were identified using Current Procedural Terminology codes for open radical prostatectomy (ORP) and laparoscopic or robotic-assisted laparoscopic prostatectomy (RALP) with a corresponding diagnosis of prostate cancer as defined by ICD-9 code 185.0.A total of 6,563 urologists submitted case logs, of which 68% (4,470/6,563) reported performing at least one radical prostatectomy (RP), totaling 46,030 RPs logged. There was a 376% increase in the performance of RALP over the study period with robotic volume increasing from 22% of all RP in 2003 to 85% in 2013. Among surgeons performing ORP, the median number performed was 2; of surgeons who performed RALP, the median number performed was 8 (P0.001). Overall, 39% of surgeons logging ORP performed 2 or fewer RP, whereas 19% of surgeons who performed RALP performed 2 or less RP (P0.001). The highest volume robotic surgeons (top 10% surgical volume) performed 41% of all RALP with the highest performing robotic surgeon recording 658 prostatectomies over 6 months. Oncologists represented 4.1% of all surgeons performing RP and performed 15.1% of all RP (P0.001); general urologists performed the majority of RP (57.8%). When performed open, there was no influence of surgeon specialty on the performance of lymph node dissection (LND); if performed robotically, oncologists were significantly more likely to perform LND compared with general surgeons (47% vs. 25.9%, respectively, P0.001).Robotic prostatectomies are performed 5 times more commonly than open prostatectomy and represent 85% of all RP performed by board-certified urologists in 2013. Compared to RALP, ORP are significantly more likely to be performed by lower volume surgeons. Oncologists perform a higher relative percentage of RPs and are significantly more likely to perform LND if performed robotically when compared with general urologists.

Objective: Vascular endothelial growth factor (VEGF) is an important angiogenic factor, and its receptors have been shown to be overexpressed in various human carcinomas. In this study, we investigated the role of scanning with iodine-123 (123I)-labelled VEGF165 in patients with highly malignant osteosarcoma. Methods: Two patients (a 15-year-old female and a 14-year-old male) with osteosarcoma were injected with 140 MBq [165 per patient] of 123I-VEGF165. Dynamic acquisition was initiated immediately after administration and carried out until 30 min after injection. Whole-body images were done in anterior and posterior views at various time points. All patients underwent single-photon emission tomography imaging. Results:123I-VEGF165 scans were positive in these patients. Sequential images clearly showed increased 123I-VEGF165 activity in osteosarcoma lesions. The tumour lesions were still visualized in whole-body images and single-photon emission tomography examinations 2 h after injection. Intravenous injection of 123I-VEGF165 did not cause any side effects. Conclusion: Our results suggest that 123I-VEGF165 receptor scintigraphy may be useful for the visualization of highly malignant osteosarcoma and/or metastasis and the angiogenic activity of the tumour.

The cytomegalovirus (CMV) promoter is considered to be one of the strongest promoters for driving the in vivo expression of genes encoded by DNA vaccines. However, the efficacy of DNA vaccines has so far been disappointing (particularly in humans), and this might be explained in part by histone deacetylase (HDAC)-mediated chromatin condensation. Hence, we sought to investigate whether increasing the expression of DNA vaccine antigens with the HDAC inhibitor OSU-HDAC42 would enhance the efficacy of DNA vaccines in vivo. A luciferase assay was used to determine the effects of OSU-HDAC42 on CMV promoter-driven DNA plasmids in vitro and in vivo. Three HDAC inhibitors were able to activate expression from the CMV promoter in NIH3T3 cells and MBT-2 bladder cancer cells. The expression of luciferase was significantly enhanced by co-administration of pCMV-luciferase and OSU-HDAC42 in mice. To explore whether OSU-HDAC42 could enhance the specific antitumor activity of a neu DNA vaccine driven by the CMV promoter, we evaluated therapeutic effects and immune responses in a mouse tumor natively overexpressing HER2/neu. Mice receiving OSU-HDAC42 in combination with the CMV-promoter neu DNA vaccine exhibited stronger antitumor effects than mice given the DNA vaccine only. In addition, a correlation between the antitumor effects and the specific cellular immune responses was observed in the mice receiving the DNA vaccine and OSU-HDAC42.

Inflammatory signals such as pathogen- and danger-associated molecular patterns have been hypothesized as risk factors for the initiation of the anti-factor VIII (FVIII) immune response seen in 25% to 30% of patients with severe hemophilia A (HA). In these young patients, vaccines may be coincidentally administered in close proximity with initial exposure to FVIII, thereby providing a source of such stimuli. Here, we investigated the effects of 3 vaccines commonly used in pediatric patients on FVIII immunogenicity in a humanized HA murine model with variable tolerance to recombinant human FVIII (rhFVIII). Mice vaccinated intramuscularly against the influenza vaccine prior to multiple infusions of rhFVIII exhibited a decreased incidence of rhFVIII-specific neutralizing and nonneutralizing antibodies. Similar findings were observed with the addition of an adjuvant. Upon exposure to media from influenza- or FVIII-stimulated lymph node or splenic lymphocytes, naive CD4(+) lymphocytes preferentially migrated toward media from influenza-stimulated cells, indicating that antigen competition, by means of lymphocyte recruitment to the immunization site, is a potential mechanism for the observed decrease in FVIII immunogenicity. We also observed no differences in incidence or titer of rhFVIII-specific antibodies and inhibitors in mice exposed to the live-attenuated measles-mumps-rubella vaccine regardless of route of administration. Together, our results suggest that concomitant FVIII exposure and vaccination against influenza does not increase the risk of inhibitor formation and may in fact decrease anti-FVIII immune responses.

There has been no study on antibiotic-resistant Propionibacterium acnes in Hong Kong.We investigated the prevalence and pattern of antibiotic-resistant P. acnes and to identify any associated factors for harbouring the resistant strains.Culture and sensitivity testing of P. acnes to commonly used antibiotics were performed. Resistance to tetracycline was defined at a minimal inhibitory concentration (MIC) of 2 μg/mL or more; erythromycin at an MIC of 0.5 μg/mL or more; clindamycin at an MIC of 0.25 μg/mL or more according to EUCAST. For breakpoints of doxycycline and minocycline, those with an MIC of 1 μg/mL or more were defined as resistant strains.Among the 111 specimens collected from 111 patients, 86 strains of P. acnes were recovered, one from each specimen. Twenty-five specimens had no growth. Forty-seven (54.8%) strains were found to be resistant to one or more antibiotics. Forty-six (53.5%), 18 (20.9%), 14 (16.3%), 14(16.3%) and 14 (16.3%) strains were resistant to clindamycin (CL), erythromycin (EM), tetracycline (TET), doxycycline (DOX) and minocycline (MR) respectively. Ten strains (11.6%) had cross resistance between the MLS antibiotics (erythromycin or clindamycin), one strain (1.2%) had cross resistance among the cyclines and 14 strains (16.4%) had cross resistance between the MLS and cycline antibiotics. Binary logistic regression showed an association between MLS antibiotic resistance with an increased age whereas cycline resistance was associated with the duration of treatment.Antibiotic-resistant P. acnes is prevalent in Hong Kong. Dermatologists should be more vigilant in prescribing antibiotics for acne patients.

Pulmonary epithelium is known to undergo a preneoplastic process prior to the development of lung carcinoma. Squamous dysplasia and atypical adenomatous hyperplasia have been identified and classified as preinvasive lesions of squamous cell carcinoma and peripheral pulmonary adenocarcinoma, respectively. However, these commonly recognized preinvasive lesions do not completely explain the development of all histological types of lung carcinoma. By examining 114 resection lung specimens, we concluded that there are four histological patterns of bronchial epithelial dysplasia based on morphological features (basal cell dysplasia, columnar cell dysplasia, bronchial epithelial dysplasia with transitional differentiation, and squamous dysplasia). The histological patterns were further characterized by immunohistochemistry. Basal cell dysplasia was focally positive for cytokeratin (CK) 17 and 10/13; columnar cell dysplasia was generally positive for CK7, 8, and 18; bronchial epithelial dysplasia with transitional differentiation had a heterogeneous immunoprofile, while squamous dysplasia was positive for CK10/13 and focally positive for CK17. Various degrees of abnormal expression of p53 and Ki-67 were found in the different types of bronchial epithelial dysplasia. The cases were divided into three groups based on degree and extent of bronchial epithelial dysplasia. By Crosstabs McNemar test, the Mann-Whitney U-test (for two independent groups), the Kruskal-Wallis one-way nonparametric ANOVA (for >2 independent groups) and Spearman correlation analysis, the degree and extent of bronchial epithelial dysplasia was shown to be positively correlated with the incidence of bronchogenic carcinoma and multifocal primary lung carcinoma (P

To investigate the timing and mode of surgical management in patients with severe acute pancreatitis (SAP).The timing, mode of operation and mortality were reviewed retrospectively in 50 SAP cases undergoing laparotomy in our hospital from 1985 to 1994.The overall mortality was 14% and 85.7% of the mortality falls on the age between 40 to 60 years, with no difference in etiology and sex. The operative mortality reduced gradually in patients with longer duration of illness (P0.05). The operative mortality of 31.8% in patients undergoing laparotomy within 12 h after hospitalization was significantly higher (P0.05) than in these operated on later. When the number of injured extra-pancreatic organs increased, the mortality also increased significantly (chi(2) = 5.99, P0.05). The related mortality with shock, pancreatic necrosis and multiorgan failure (MOF) was 31.8%, 31.6% and 28%, respectively (P0.05). The main procedures of surgical management were pancreatic debridement and/or drainage, and combined surgical measures.The laparotomy timing is an important factor influencing mortality as well as the severity of pancreatic necrosis, sepsis, and MOF. Delayed laparotomy and 24 h preoperative management is recommended. Surgery adopted should be simple, efficient in drainage and debridement.

To study the efficacy of 40-O-(2-hydroxyethyl)-rapamycin (SDZ RAD) in preventing chronic renal allograft rejention in rats.The rat model of chronic renal allograft rejection was made with micro-surgery. The recipients were divided into two groups. The recipients in the study group were treated with SDZ RAD at a dose of 0.5 mg x kg(-1) x d(-1) by means of gavage and the controls with vehicle.After 24 weeks of treatment, proteinuria, glomerular sclerosis, vascular intimal thickening and the infiltration of monocytesmacrophages and lymphocytes in the study group were decreased, in consistence with the reduced expression of ICAM-1, VCAM-1, TGF-beta(1) and PDGF-AA mRNA.It is suggested that SDZ RAD can prevent chronic renal allograft rejection and the reduced expression of above adhesion molecules and growth factors may be involved in the mechanism.

The Chinese population is the biggest ethnic group in the world. However, there are few reports on the treatment outcome of childhood acute lymphoblastic leukaemia (ALL) among the Chinese population.Sixty-five children with ALL were treated with a modified protocol of the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia protocol X(MRC UKALL X) at the Prince of Wales Hospital, Hong Kong. Most patients were ethnic Chinese. They were divided into groups A and B, depending on whether their presenting leucocyte count being was less or greater than 50 x 10(9)/l, respectively. Group A patients of received induction, early intensification (week 5), cranial irradiation, and maintenance for 3 years. Group B patients received an additional late intensification (week 20).The median follow-up duration was 6.8 years(range: 3.4-10.1 years). The event-free and overall survival rates of all patients at 7 years were 66% (confidence interval [CI] 53-76) and 75% (CI 63-84), respectively. The event-free survival rates of groups A and B at 7 years were 67% (CI 52-79) and 60% (CI 32-80), respectively (P= 0.39). The overall survival rates of groups A and B at 7 years were 80% (CI 66-89) and 60% (CI 32-80), respectively (P = 0.07). With this treatment protocol, the factors which adversely affected the outcome were age (2 years and10 years) and T-cell subtype. Sex, white blood count at diagnosis, and FAB subtypes were not statistically significant prognostic factors.The treatment outcomes were comparable with those reported from the MRC UKALL X trials.

Monoamine oxidase B (MAO-B) may play a role in the progression and cause of Parkinson's disease (PD), given consideration of the biochemistry and pathophysiology of the disease, and experiments on primates and humans. Assuming that the structural gene determines enzyme activity, an association study was undertaken to examine MAO-B genetic polymorphisms and look for the unique MAO-B gene alleles which occurred at a higher frequency in PD patients.Sixty-five PD patients, diagnosed according to the criteria set by a Core Assessment Program for Intracerebral Transplantations Committee, and 108 healthy controls were enrolled in this study. Genomic DNA was extracted from peripheral leukocytes by using a puregene kit. Polymerase chain reaction (PCR) was used to amplify the MAO-B genome. The PCR products were screened by restriction enzyme Hae III digestion and analyzed by single-stranded conformational polymorphism (SSCP).Two bands with different mobility shifts, defined as MAO-B allele 1 and allele 2, were observed in SSCP analysis. Neither genotypes nor allelic frequencies of MAO-B showed a significant difference between PD patients and controls in our study.Polymorphism of MAO-B genome was demonstrated in this study. It failed to show an association of a genetic marker with PD. However, this did not necessarily exclude the MAO-B locus from playing a role in causing PD because a polymorphism different from the one evaluated here may show some disease association.

We analyzed the AluI restriction fragment length polymorphism (RFLP) of the apolipoprotein B (apoB) gene to determine the association between AluI allelic distribution and the occurrence of ischemic stroke in Taiwan. A total of 44 healthy volunteers and 159 ischemic stroke patients were included in the study. The allele frequency of AluI was very similar in the two groups, 0.87 in the patient group and 0.89 in the control group, for the major allele A-. The distribution of A-/A-, A-/A+, and A+/A+ genotypes of the patients was not significantly different from that of the controls. Among ischemic stroke patients, the A+ allele of the AluI restriction site was significantly associated with elevated apoB levels. The results of this study suggest that the presence of the rare AluI RFLP may contribute to an elevated plasma apoB level, which is a known risk factor for ischemic stroke.

Participating in this study were 305 Chinese college students in Hong Kong. Objectives included (i) examination of the psychometric properties of the Chinese version of the Derogatis Sexual Functioning Inventory (DSFI), (ii) exploration of the associations among various domains of sexual functioning, and (iii) description of Chinese students' sexual behavior. The Chinese DSFI shows satisfactory internal consistency, except the Information, Drive, and Satisfaction subscales. In general, sex-related domains such as sexual information, experience, drive, attitudes, fantasy, and satisfaction were related to each other and to body image. Compared to their counterparts in the U.S., Chinese college students were relatively sexually inexperienced and conservative. Mean ages of students having their first sexual intercourse experience were 17.14 for males and 18.13 for females; 11% of the students had premarital sexual intercourse experience, and the mean frequencies were once weekly for males and once or twice per month for females. Compared to female students, twice as many males acknowledged masturbation (21.4 vs. 43.8%), 4.2-8.2% students had experienced oral-genital sexual stimulation and 0-1.2% anal sexual activities.

Mutations in the K-ras gene were found to be of predictive value in the clinical outcome of non-small cell lung cancers, but its role in predicting the survival of colorectal cancer patients is still inconclusive. Point mutations in codon 12 or 13 of K-ras gene were analyzed in 64 colorectal cancers composing 4 Dukes' stage. A, 34 stage B, 21 stage C and 5 stage D. DNA extracted from the paraffin-embedded tissues of the 64 patients was amplified with the polymerase chain reaction and subsequently analyzed by direct cycle sequencing. Thirteen of sixty-four (20%) resected colorectal cancer specimens were found to have K-ras gene mutation at either codon 12 or 13. Log rank tests found that K-ras gene mutation and Dukes' stage were associated with patients' survival. When stratified by Dukes' stage, the patients with mutated K-ras genes in the stratum of stage A or B were found to have shorter survival times than those without mutated K-ras genes (P = 0.003), but this was not the case in the stratum of stages C and D. The relative risk of mortality in the stratum of stage A or B was 7.74 (95% confidence interval: 1.72-34.89) by Cox regression analysis. We thereby conclude that K-ras gene mutation is a usefull predictor of the survival of early stage colorectal cancers.

Point mutations of the K-ras gene were analyzed in 25 periampullary cancers (21 ampulla vater cancers, two common bile duct cancers and two duodenal cancers), two gallbladder cancers and six cholangiocarcinomas. DNA extracted from the paraffin-embedded tissues was amplified with the polymerase chain reaction and subsequently analyzed by direct cycle sequencing at codons 12, 13 and 18 of the K-ras gene. Codon 61 was first screened with single strand conformation polymorphism and then sequenced by direct cycle sequencing. No point mutation was found in any of the 25 periampullary cancers or the two gallbladder cancers. These results are similar to previous reports. Mutation of the K-ras gene seems not to play an important role in tumorigenesis of periampullary cancer. In two of six (33%) cholangiocarcinoma patients, point mutations were found. Both mutations were transitions, GGT to GAT at codon 12. The incidence of mutation was greater than that in Thailand (about 8%) but less than that in Japan (about 60%). Mutation of the K-ras gene may play varied roles in the tumorigenesis of cholangiocarcinoma, depending on geographic area.

Microsatellite polymorphisms of 75 unrelated Taiwanese males were analyzed for (GATA) repeats in DYS19 on chromosome Y and tetranucleotide simple repeats in D12S67 on chromosome 12. A simple nonisotopic technique based on polymerase chain reaction electrophoresis on native polyacrylamide gels followed by silver staining was used. In the 75 unrelated males, four alleles on DYS19 and five alleles on D12S67 were detected. Different allele frequencies, heterozygosity rates and information on the nature of the repeat loci were determined in these unrelated individuals. The resulting polymorphisms are of great assistance in ethnologic studies, forensic investigation and deficiency cases in paternity testing.

In 21 cases of prostate adenocarcinoma and 4 cases of prostate hyperplasia, neuroendocrine (NE) cells were studied immunohistochemically with anti-chromogranin antibody. NE cells were detected in 8 cases (38.8%), in which 4 were found positive for serotonin and 2 for glucagon. 25 cases of prostatic specimens and 7 cases of nonprostatic adenocarcinomas were labelled with prostate-specific antigen (PSA). It was shown that expression of PSA was closely correlated with differentiation of prostatic adenocarcinomas. Reaction of PSA was stronger in well-moderately differentiated adenocarcinoma than in poorly differentiated one. For staining pattern, positive reaction of PSA was located in the apical border in well-moderately differentiated adenocarcinoma, but in the cytoplasm and cell membrane in poorly differentiated one.

Nineteen lymph nodes of a HIV-positive boy were studied histologically and immunohistologically. According to Stutte's classification of HIV-related lymphadenopathy, 84% of the lymph nodes were at the third or fourth stages in relation to clinical status ARC/AIDS. Lymph follicle atrophy, angiogenesis, histiocytic proliferation and destruction of the normal reticulum frame were observed. Immunohistochemical studies showed most of the remaining lymphocytes to be T cells and changes in the distribution of S-100 positive cells. Ki 1 positive cells existed mainly at the second stage. The significance of these changes is discussed.