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1.
J Affect Disord ; 320: 527-533, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36209782

ABSTRACT

BACKGROUND: Electroconvulsive therapy (ECT) is used to treat severe psychiatric disorders and is associated with reduced risk of suicide and all-cause mortality in patients with severe depression. We investigated the causes of death occurring shortly after ECT and identified potential risk factors for medical causes of death. METHODS: Patients treated with ECT between 2012 and 2018 were included in this Swedish register-based study. Multivariate binary logistic regression was used to calculate odds ratios for covariates to determine potential predictors of 30-day mortality. RESULTS: Of the 20,225 included patients, 93 (0.46 %) died of suicide and 123 (0.61 %) died of medical causes after ECT. Cardiovascular disease was the most common medical cause of death (n = 49, 40 %). An older age, a Charlson Comorbidity Index of 1 or more, atrial fibrillation, kidney disease, reflux disease, dementia, and cancer were associated with increased risk of death by medical causes. LIMITATIONS: Real-life observational studies based on registry data may demonstrate associations, but cannot determine causality. If medical records had been available, we would be better able to determine if deaths were due to the ECT, anesthesia, pre-existing medical conditions, or the mental disorder. CONCLUSIONS: ECT appears to be a low-risk medical procedure. Older individuals with severe somatic diseases have the highest risk of death and extra measures should be considered to optimize their medical health during the pre-ECT workup, and during and after ECT.


Subject(s)
Electroconvulsive Therapy , Psychotic Disorders , Suicide , Humans , Electroconvulsive Therapy/adverse effects , Electroconvulsive Therapy/methods , Causality , Risk Factors
2.
Microbiol Spectr ; 9(3): e0093721, 2021 12 22.
Article in English | MEDLINE | ID: mdl-34878317

ABSTRACT

Rapid antigen tests may enhance the diagnostic yield of respiratory syncytial virus (RSV) infections, but studies have shown low sensitivity in adults. We evaluated the novel ImmuView RSV test in adult patients with influenza-like symptoms who were prospectively enrolled at three emergency departments in two Swedish hospitals during two influenza seasons, 2017 to 2018 and 2018 to 2019. The ImmuView RSV test was performed on nasopharyngeal swabs and results were compared to those of the BinaxNOW RSV test. In the first season, tests were performed on frozen samples, while unfrozen samples were used in the second season. For comparison, tests were also performed on selected samples from children. Of 333 included adult patients, the sensitivity of ImmuView and BinaxNOW was 27% for both tests and specificities were 98% and 100%, respectively. The interassay agreement was good (κ = 0.61). There was no significant difference in test performance between frozen and unfrozen samples. In samples from children, the sensitivities of ImmuView and BinaxNOW were 67% and 70%, respectively. In conclusion, the ImmuView RSV test showed low sensitivity and high specificity for identifying RSV in adult patients with influenza-like symptoms, comparable with the BinaxNOW RSV test. Rapid RSV testing is of limited value for diagnosing RSV infection in adults. IMPORTANCE By timely RSV diagnosis among patients with influenza-like symptoms, especially when influenza diagnostics turn negative, it is possible to prevent unnecessary antibiotic usage as well as reduce diagnostic testing, nosocomial transmission, and hospital stay. Previous rapid RSV tests have demonstrated poor sensitivity in adults, and we could demonstrate that the novel ImmuView RSV test similarly showed limited value for diagnosing RSV infection in adult patients. However, in contrast to many other studies, we investigated patient characteristics in cases with false-positive tests and we compared the performance between unfrozen and frozen samples. Thus, our results are important, as they generate new knowledge about rapid antigen tests.


Subject(s)
Antigens, Viral/analysis , Diagnostic Tests, Routine/methods , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Syncytial Virus, Human/isolation & purification , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , False Positive Reactions , Female , Humans , Influenza, Human/diagnosis , Male , Middle Aged , Point-of-Care Testing , Prospective Studies , Respiratory Syncytial Virus, Human/immunology , Sensitivity and Specificity , Young Adult
3.
Breast ; 59: 294-300, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34388695

ABSTRACT

BACKGROUND: Invasive lobular carcinoma (ILC) comprises 8-15 % of all invasive breast cancers and large population-based studies with >10 years of follow-up are rare. Whether ILC has a long-time prognosis different from that of invasive ductal carcinoma, (IDC) remains controversial. PURPOSE: To investigate the excess mortality rate ratio (EMRR) of patients with ILC and IDC and to correlate survival with clinical parameters in a large population-based cohort. MATERIAL AND METHODS: From 1989 through 2006, we identified 17,481 patients diagnosed with IDC (n = 14,583) or ILC (n = 2898), younger than 76 years from two Swedish Regional Cancer Registries. Relative survival (RS) during 20 years of follow up was analysed. RESULTS: ILC was significantly associated with older age, larger tumours, ER positivity and well differentiated tumours. We noticed an improved survival for patients with ILC during the first five years, excess mortality rate ratio (EMRR) 0.64 (CI 95 % 0.53-0.77). This was shifted to a significant decreased survival 10-15 years after diagnosis (EMRR 1.49, CI 95 % 1.16-1.93). After 20 years the relative survival rates were similar, 0.72 for ILC and 0.73 for IDC. CONCLUSIONS: During the first five years after surgery, the EMRR was lower for patients with ILC as compared to patients with IDC, but during the years 10-15 after surgery, we observed an increased EMRR for patients with ILC as compared to IDC. These EMRR between ILC and IDC were statistically significant but the absolute difference in excess mortality between the two groups was small.


Subject(s)
Breast Neoplasms , Carcinoma, Ductal, Breast , Carcinoma, Lobular , Aged , Female , Follow-Up Studies , Humans , Prognosis
5.
Acta Psychiatr Scand ; 140(3): 196-204, 2019 09.
Article in English | MEDLINE | ID: mdl-31334829

ABSTRACT

OBJECTIVE: Electroconvulsive therapy (ECT) is used in patients with severe forms of bipolar depression. ECT is effective but not all patients respond. The aim of this study was to determine prognostic factors for response to ECT in patients hospitalized for bipolar depression. METHODS: Data were obtained from several national Swedish registers. All patients with bipolar depression treated with ECT in any hospital in Sweden between 2011 and 2016 for whom information about ECT response was available were included (n = 1251). Response was defined as a score on the Clinical Global Impression - Improvement scale of one or two. Univariate and multivariate logistic regression were conducted to investigate associations between socio-demographic and clinical factors and response. RESULTS: Response was achieved in 80.2% patients. Older age was associated with higher response rate to ECT. Patients with comorbid obsessive-compulsive disorder or personality disorder, and patients previously treated with lamotrigine had lower response rate. CONCLUSION: Electroconvulsive therapy for bipolar depression was associated with very high response rates. The strongest prognostic factors were higher age, absence of comorbid obsessive-compulsive disorder or personality disorder, and less prior pharmacologic treatment.


Subject(s)
Bipolar Disorder/therapy , Electroconvulsive Therapy , Outcome Assessment, Health Care , Registries , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prognosis , Sweden , Young Adult
6.
J Intern Med ; 285(4): 419-428, 2019 04.
Article in English | MEDLINE | ID: mdl-30474313

ABSTRACT

BACKGROUND: Myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is receiving increasing interest as a prognostically adverse entity distinct from myocardial infarction with significant coronary artery disease (MI-CAD). However, data are still limited regarding long-term cardiovascular morbidity and cause-specific mortality in MINOCA. METHODS: This is a registry-based cohort study using data from patients admitted to Swedish coronary care units. We investigated various nonfatal outcomes (recurrent MI, hospitalization for heart failure or stroke) and fatal outcomes (cardiovascular, respiratory or cancer-related mortality) in 4069 patients without apparent acute cardiovascular disease, used as non-MI controls, 7266 patients with first-time MINOCA and 69 267 patients with first-time MI-CAD. RESULTS: Almost all event rates (median follow-up 3.8 years) increased in a stepwise fashion across the three cohorts [rates of major adverse events (MAE; composite of all-cause mortality, recurrent MI, hospitalization for heart failure or stroke): n = 268 (6.6%), n = 1563 (21.5%), n = 17 777 (25.7%), respectively]. Compared to non-MI controls, MINOCA patients had an adjusted hazard ratio (HR) of 2.12 (95% confidence interval 1.84-2.43) regarding MAE. MINOCA patients had a substantial risk of cardiovascular mortality and the highest numerical risks of respiratory and cancer-related mortality. Male sex, previous heart failure and chronic obstructive pulmonary disease had a stronger prognostic impact in MINOCA than in MI-CAD. Female MINOCA patients with atrial fibrillation were at particular risk. CONCLUSIONS: Patients with first-time MINOCA have a considerable risk of adverse events. This stresses the need for a comprehensive search of the cause of MINOCA, thorough treatment of underlying disease triggers and close follow-up.


Subject(s)
Coronary Artery Disease/mortality , Myocardial Infarction/mortality , Aged , Cause of Death , Coronary Angiography , Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Coronary Artery Disease/pathology , Female , Humans , Male , Middle Aged , Myocardial Infarction/epidemiology , Myocardial Infarction/pathology , Prognosis , Proportional Hazards Models , Recurrence , Registries , Sweden/epidemiology , Treatment Outcome
7.
Int J Cardiol ; 261: 18-23, 2018 06 15.
Article in English | MEDLINE | ID: mdl-29563017

ABSTRACT

BACKGROUND: Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCAs) is an increasingly recognized entity. No previous study has evaluated predictors for new major adverse cardiacvascular events (MACEs) and death in patients with MINOCA. METHODS: We conducted an observational study of MINOCA patients recorded between July 2003 and June 2013 and followed until December 2013 for outcome events. Out of 199,163 MI admissions, 9092 consecutive unique patients with MINOCA were identified. The mean age was 65.5 years and 62% were women. MACE was defined as all-cause mortality, rehospitalization for acute MI, ischemic stroke and heart failure. Hazard ratio and 95% confidence interval (HR; 95% CI) was calculated using Cox-regression. RESULTS: A total of 2147 patients (24%) experienced a new MACE and 1254 patients (14%) died during the mean follow-up of 4.5 years. Independent predictors for MACE after adjustment, were older age (1.05; 1.04-1.06), diabetes (1.44; 1.21-1.70), hypertension (1.25; 1.09-1.43), current smoking (1.38; 1.15-1.66), previous myocardial infarction (1.38; 1.04-2.82), previous stroke (1.69; 1.35-2.11), peripheral vascular disease (1.55; 1.97-2.23), chronic obstructive pulmonary disease (1.63; 1.32-2.00), reduced left ventricular ejection fraction (2.00; 1.54-2.60), lower level of total cholesterol (0.88; 0.83-0.94) and higher level of creatinine (1.01; 1.00-1.03). Independent predictors for all cause death were age, current smoking, diabetes, cancer, chronic obstructive pulmonary disease, previous stroke, reduced left ventricular fraction, lower level of total cholesterol and higher levels of creatinine and CRP. CONCLUSIONS: The clinical factors predicting new MACE and death of MINOCA patients seem to be strikingly similar to factors previously shown to predict new cardiovascular events in patients with MI and obstructive coronary artery disease.


Subject(s)
Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/mortality , Aged , Aged, 80 and over , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Predictive Value of Tests , Registries , Risk Factors , Sweden/epidemiology , Treatment Outcome
8.
Eur Psychiatry ; 45: 154-160, 2017 09.
Article in English | MEDLINE | ID: mdl-28865389

ABSTRACT

BACKGROUND: Electroconvulsive therapy (ECT) effectively treats severe depression, but not all patients remit. The aim of the study was to identify clinical factors that associate with ECT-induced remission in a community setting. METHODS: Depressed patients who underwent ECT in 2011-2014 were identified from the Swedish National Quality Register for ECT. Remission was defined as self-rated Montgomery-Åsberg Depression Rating Scale scores of 0-10 after ECT. Other registers provided data on previous antidepressant use, comorbidities, and demographics. RESULTS: Of 1671 patients fulfilling the inclusion criteria, 42.8% achieved remission. Older age, education length over 9 years, psychotic symptoms, shorter duration of preceding antidepressant use, pulse width stimulus≥0.50ms, absence of substance use disorders, anxiety diagnosis, lamotrigine, and benzodiazepines, were associated with remission. CONCLUSIONS: This study shows that psychotic subtype of depression and older age are clinically relevant predictors of a beneficial ECT effect. Additionally, ECT outcomes can be further improved by optimizing the treatment technique and concomitant medication.


Subject(s)
Depressive Disorder, Major/therapy , Electroconvulsive Therapy/statistics & numerical data , Patient Satisfaction/statistics & numerical data , Self-Assessment , Adult , Aged , Anticonvulsants/therapeutic use , Antidepressive Agents/therapeutic use , Depressive Disorder, Major/drug therapy , Female , Humans , Male , Middle Aged , Treatment Outcome
9.
J Pediatr Urol ; 13(1): 79.e1-79.e7, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28087231

ABSTRACT

INTRODUCTION: Hypospadias, which is a surgically treated congenital malformation of the male urethra, may have a negative impact on quality of life. This aspect has previously been subject to limited research. This study examined the long-term psychosocial outcome of a large cohort of adult males born with hypospadias. OBJECTIVE: The purpose of this case-control study was to assess a possible negative influence on the psychosocial outcome in adult males with hypospadias. STUDY DESIGN: Males with hypospadias treated in Sweden and aged ≥18 years old participated in this follow-up study. Age-matched men and university students were recruited as controls. The participants answered a questionnaire designed to reflect the subjective quality of life, social factors, need of support and follow-up, and the perceived impact of the disease upon upbringing. It also looked at the validated Psychological General Well-Being (PGWB) questionnaire and Relationship Questionnaire (RQ). RESULTS AND DISCUSSION: A total of 167 patients (median age 34 years, 63% distal, 24% mid, and 13% proximal hypospadias) and 169 controls (median age 33 years) participated in the study. Patients had their first operation at 4 years of age (median) and the median follow-up time was 29 years following the first surgery. Men with hypospadias had a comparable total quality of life level with a mean total PGWB score of 82 (normal range 78-83) compared with 85.6 in controls. Scores on wellbeing and vitality were lower, even if the differences were small. Hypospadias did not affect marital status, presence of children in the family, frequency of employment or experience of bullying. These men more often lived at home with their parents (P=0.001) and had a lower level of education (P=0.004), even if the educational level in both patients and controls was high compared with the general Swedish population. Patients with proximal hypospadias were shorter compared with controls (P=0.003), which was consistent with the prenatal growth restriction associated with hypospadias. The group with proximal hypospadias expressed a greater need for medical (45.5%) follow-up compared with mid (28.2%) and distal (18.1%) cases (P=0.001). Patients with proximal hypospadias tended to avoid close relationships because of fear of being hurt. CONCLUSIONS: The findings suggested that patients treated for hypospadias have a good HRQoL, can be expected to have a normal psychosocial life, and marry and have children. Repeated follow-up and psychological support during childhood/adolescence is however of great importance for patients with more proximal hypospadias.


Subject(s)
Hypospadias/psychology , Hypospadias/surgery , Sickness Impact Profile , Surveys and Questionnaires , Urologic Surgical Procedures, Male/methods , Adaptation, Psychological , Adolescent , Adult , Age Factors , Case-Control Studies , Child , Follow-Up Studies , Humans , Hypospadias/pathology , Male , Psychology , Quality of Life , Risk Assessment , Statistics, Nonparametric , Sweden , Treatment Outcome , Urologic Surgical Procedures, Male/psychology
10.
Andrology ; 5(2): 286-293, 2017 03.
Article in English | MEDLINE | ID: mdl-27992969

ABSTRACT

The aim of this study was to investigate sexual function and fertility in adult men born with hypospadias. Patients born with hypospadias, age-matched controls, and a group of circumcised men completed a questionnaire constructed to reflect their psychosexual situation and fertility. Core gender identity, sexual orientation, and gender role behavior was also assessed. 167 patients [63% distal, 24% mid shaft and 13% proximal, mean age 34 (19-54) years], 169 controls from the general population [mean age 33 (19-48) years] and 47 controls circumcised because of phimosis (mean age 26 [19-44]) participated and completed the questionnaire. There were no differences in having a partner, reported fertility, age at sexarche (mean age 17.8), number of sex partners or sexual interest between the patients and controls. More patients than controls reported anejaculation. Reported glanular sensitivity was lower in hypospadias patients and circumcised controls compared with non-circumcised controls. The odds of being satisfied with their sexual life increased with a higher penile perception score in patients (OR = 1.54, p = 0.01). There was no association with penile length. Sexual orientation, core gender identity and gender role behavior were sex-typical in both patients and controls. Patients with proximal hypospadias had a lower reported fertility, experienced anejaculation more often, and were less satisfied with their sexual life. Men born with hypospadias have a good long-term outcome concerning sexual function and fertility. Men born with proximal hypospadias have a more impaired outcome concerning both sexual function and fertility. As satisfaction with genital appearance is important for sexual life satisfaction, clinical, and psychological follow-up into adulthood is especially important in boys born with proximal hypospadias.


Subject(s)
Fertility/physiology , Gender Identity , Hypospadias/psychology , Personal Satisfaction , Sexual Behavior/psychology , Sexuality/psychology , Adult , Humans , Hypospadias/physiopathology , Male , Middle Aged , Sexual Behavior/physiology , Sexuality/physiology , Surveys and Questionnaires , Young Adult
11.
J Pediatr Urol ; 12(5): 304.e1-304.e7, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27499280

ABSTRACT

INTRODUCTION: Bladder exstrophy is a rare, congenital, complex malformation where the underlying cause is largely unknown. Both environmental and genetic mechanisms are thought to be involved. There are divergent results concerning the prevalence, birth descriptive data, and potential maternal risk factors for bladder exstrophy. Few previous studies have reflected nationwide populations, population registers, or spanned a longer period of time. OBJECTIVE: To describe and assess bladder exstrophy and the potential maternal risk factors, for a time period of four decades, by conducting a nationwide register study of bladder exstrophy in Sweden. METHODS: A matched-design, case-control, linkage-analysis study nested within the entire pool of live births in Sweden between 1973 and 2011 was performed. Cases with bladder exstrophy were identified using nationwide population-based birth and health registers. Inclusion criteria were people born in Sweden with the classification of bladder exstrophy according to the ICD coding system. Cases were matched with five controls per patient, based on birth year and sex. Prevalence was assessed and birth descriptive data were compiled. Potential maternal risk factors were obtained from medical birth registers of cases and assessed using conditional and multivariate logistic regression models to obtain odds ratios as a measure of the relative risk. Classification of the diagnosis in the registers constituted a possible limitation for determining the correct study population, which demanded strict validation and inclusion criteria. All data were collected prospectively, thereby avoiding potential recall bias. RESULTS: The prevalence was calculated to be approximately 3 per 100,000 live births, with a male-to-female ratio of 1.14:1. In 92.5% of the cases, bladder exstrophy was an isolated malformation without associated major malformations. However, 41% had had surgery for congenital inguinal hernia and 11% of the male subjects had been operated on for cryptorchidism. A significantly higher proportion of cases had a birth weight <1500 g compared with controls, but other characteristics were comparable with controls. High maternal age was the only significant potential associated maternal risk factor. CONCLUSIONS: One hundred and twenty children born with bladder exstrophy in Sweden during the last four decades were identified; this resulted in prevalence in Sweden of 3 per 100,000. The prevalence was stable over time and the sex ratio was equal. Birth characteristics were comparable to controls, and bladder exstrophy generally occurred as an isolated malformation without major associated malformations. Advanced maternal age was the only significant potential maternal risk factor.


Subject(s)
Bladder Exstrophy/epidemiology , Adult , Case-Control Studies , Female , Fetus , Humans , Infant, Newborn , Male , Maternal Age , Pregnancy , Pregnancy Complications/epidemiology , Prevalence , Risk Factors , Sweden , Young Adult
12.
Clin Radiol ; 70(8): 830-4, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25976498

ABSTRACT

AIM: To investigate the association between exposure to ionising radiation from pelvimetric examinations in utero and school performance. MATERIAL AND METHODS: This was a population-based cohort study comprising 46,066 children born in the county of Östergötland, Sweden, from 1980 through 1990. Through record linkage between Swedish registers, children exposed in utero to X-ray pelvimetry examination were compared to other children born in the same county during the study period, as well as to their unexposed siblings. Outcome variable was primary school grades, expressed in centiles and calculated through linear regression. RESULTS: In the univariate analysis, children exposed to X-ray pelvimetry in utero had higher school grades compared to unexposed children (point estimate 3 centiles, 95% confidence interval [CI]: 1.5 to 4.6). When sex, mother's education and income, birth order, and birth position were included in the analysis; however, the difference was reduced and the association was no longer statistically significant (PE 1.4, 95% CI: -0.1 to 2.8). Comparing exposed children with their siblings showed no statistical difference in univariate analysis or in multivariate analysis. CONCLUSION: No suggestion was found of a negative effect on school performance from in utero exposure of diagnostic X-ray pelvimetry.


Subject(s)
Prenatal Exposure Delayed Effects/epidemiology , Child , Educational Status , Female , Humans , Male , Pelvimetry/adverse effects , Pelvimetry/methods , Pregnancy , Sweden/epidemiology , X-Rays/adverse effects
13.
Ann Oncol ; 26(6): 1149-1154, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25839671

ABSTRACT

BACKGROUND: In published radiotherapy trials, the failure rate in the control arm among patients with one to three positive nodes is high compared with that seen with modern adjuvant treatments. Therefore, the generalizability of the results has been questioned. The aim of the present study was to compare relative survival in breast cancer patients between two Swedish regions with screening mammography programs and adjuvant treatment guidelines similar with the exception of the indication of radiotherapy for patients with one to three positive nodes. PATIENTS AND METHODS: Between 1989 and 2006, breast cancer patients were managed very similarly in the west and southeast regions, except for indication for postoperative radiotherapy. In patients with one to three positive nodes, postmastectomy radiotherapy was generally given in the southeast region (89% of all cases) and generally not given in the west region (15% of all cases). For patients with one to three positive nodes who underwent breast-conserving surgery, patients in the west region had breast radiotherapy only, while patients in the southeast region had both breast and lymph nodes irradiated. RESULTS: The 10-year relative survival for patients with one to three positive lymph nodes was 78% in the west region and 77% in the southeast region (P = 0.12). Separate analyses depending on type of surgery, as well as number of examined nodes, also revealed similar relative survival. CONCLUSION: Locoregional postoperative radiotherapy has well-known side-effects, but in this population-based study, there was little or no influence of this type of radiotherapy on survival when one to three lymph nodes were involved.


Subject(s)
Breast Neoplasms/radiotherapy , Mastectomy , Aged , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Catchment Area, Health , Chemotherapy, Adjuvant , Female , Humans , Lymphatic Metastasis , Mammography , Mastectomy/adverse effects , Mastectomy/mortality , Middle Aged , Radiotherapy, Adjuvant , Registries , Residence Characteristics , Risk Factors , Survival Analysis , Sweden/epidemiology , Time Factors , Treatment Outcome
14.
J R Soc Interface ; 11(96): 20140233, 2014 Jul 06.
Article in English | MEDLINE | ID: mdl-24789561

ABSTRACT

Urological reconstructive surgery is sometimes hampered by a lack of tissue. In some cases, autologous urothelial cells (UCs) are not available for cell expansion and ordinary tissue engineering. In these cases, we wanted to explore whether autologous mesenchymal stem cells (MSCs) from bone marrow could be used to create urological transplants. MSCs from human bone marrow were cultured in vitro with medium conditioned by normal human UCs or by indirect co-culturing in culture well inserts. Changes in gene expression, protein expression and cell morphology were studied after two weeks using western blot, RT-PCR and immune staining. Cells cultured in standard epithelial growth medium served as controls. Bone marrow MSCs changed their phenotype with respect to growth characteristics and cell morphology, as well as gene and protein expression, to a UC lineage in both culture methods, but not in controls. Urothelial differentiation was also accomplished in human bone marrow MSCs seeded on a three-dimensional poly(ε-caprolactone) (PCL)-collagen construct. Human MSCs could easily be harvested by bone marrow aspiration and expanded and differentiated into urothelium. Differentiation could take place on a three-dimensional hybrid PCL-reinforced collagen-based scaffold for creation of a tissue-engineered autologous transplant for urological reconstructive surgery.


Subject(s)
Bone Marrow Cells/cytology , Mesenchymal Stem Cells/cytology , Tissue Engineering/methods , Urothelium/cytology , Cell Culture Techniques , Cell Differentiation , Collagen , Humans , Plastic Surgery Procedures , Tissue Scaffolds , Transplantation, Autologous
15.
J Clin Endocrinol Metab ; 99(4): 1425-32, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24476073

ABSTRACT

CONTEXT: Congenital adrenal hyperplasia (CAH), CYP21A2 deficiency, results in cortisol and aldosterone deficiency and increased production of androgens, with a good genotype phenotype correlation. OBJECTIVE: The objective of the investigation was to study psychosocial outcomes in relation to clinical severity, CYP21A2 genotype, in men and women. DESIGN: This was an epidemiological study with a matched case control design. SETTING: The setting of the study was all known CAH patients in Sweden. PARTICIPANTS: Five hundred eighty-eight patients, more than 80% with known severity of CAH, and 100 controls per patient matched for sex, year, and place of birth participated in the study. MAIN OUTCOME AND MEASURES: Proxies for quality of life were selected: level of education, employment, income, sick leave, disability pension, marriage, and children. RESULTS: Women with salt-wasting (SW) CAH had completed primary education less often [odds ratio (OR) 0.3], not explained by neonatal salt crisis or hypoglycemia because the men did not differ from controls. Men and women in the less severe I172N genotype group were more likely to have an academic education (OR 1.8). SW women were more likely to have an income in the top 20th percentile (OR 2.0). Both men and women had more disability pension (OR 1.5) and sick leave (OR 1.7). The men more often had long-lasting employment (OR 3.1). Men were more often (OR 1.6) and women were less often married (OR 0.7). Patients had children less often (OR 0.3). CONCLUSIONS: This study shows important outcome differences regarding education; employment; marriage and fertility, depending on sex; and severity of CAH. The mechanisms behind this and the increased risk for sick leave or disability pension in both men and women should be identified to improve medical and psychological care.


Subject(s)
Adrenal Hyperplasia, Congenital/epidemiology , Adrenal Hyperplasia, Congenital/psychology , Adolescent , Adrenal Hyperplasia, Congenital/genetics , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Cohort Studies , Female , Genetic Association Studies , Humans , Male , Middle Aged , Psychology , Quality of Life/psychology , Severity of Illness Index , Steroid 21-Hydroxylase/genetics , Sweden/epidemiology , Young Adult
16.
Sex Dev ; 7(4): 173-9, 2013.
Article in English | MEDLINE | ID: mdl-23571770

ABSTRACT

Hypospadias is a congenital malformation and a milder form of 46,XY disorder of sexual development (DSD). In the present study, we investigated 13 haplotype tagging single nucleotide polymorphisms (SNPs) covering the steroid-5-alpha reductase (SRD5A2) and androgen receptor(AR) gene region, respectively, in a cohort consisting of 260 individuals with mild hypospadias and 77 with severe disease, in addition to 471 healthy male controls. The investigated genes are known to have an important role in the hormone-dependent stage of sexual development. Our study revealed one novel marker located in the AR gene region (rs5919436; g.67024320C>G) to be significantly associated with an increased risk of severe hypospadias (adjusted p value: 0.02; odds ratio: 2.98). In concordance with this finding, we detected an association of a haplotype tagged by the minor allele of rs5919436 (adjusted p value: 0.04). We further detected no association between the investigated disease and the haplotype tagging polymorphisms covering the SRD5A2 gene, which is of importance considering the conflicting results reported previously. In conclusion, our data implicate that the AR rs5919436 (g.67024320C>G) polymorphism may act as a novel genetic marker for increased susceptibility to severe hypospadias in Caucasians.


Subject(s)
Genetic Association Studies , Genetic Predisposition to Disease , Hypospadias/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Androgen/genetics , White People/genetics , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics , Alleles , Case-Control Studies , Haplotypes/genetics , Humans , Male , Membrane Proteins/genetics
17.
Sex Dev ; 6(6): 292-7, 2012.
Article in English | MEDLINE | ID: mdl-23154282

ABSTRACT

Hypospadias is a frequent congenital malformation in boys and is characterized by incomplete fusion of the urethral folds. The steroidogenic factor-1 (SF-1, NR5A1) gene plays a key role in hypothalamic-pituitary-steroidogenic organ development, and has previously been reported to be mutated in individuals with 46,XY disorder of sex development. Here, we investigated the role of SF-1 in hypospadias, a milder form of 46,XY disorder of sex development. We performed direct sequencing analysis of the SF-1 gene in 2 male Caucasian twins exhibiting very severe hypospadias, and in 95 Caucasian boys with mild and severe hypospadias. We further extended the analysis by investigating 332 mild and severe hypospadias cases and 422 male controls using TaqMan assays. Our sequencing revealed a novel heterozygous p.R313H (c.938G>A) missense mutation in each twin, and no mutations in the 95 Caucasian cases. Instead, a missense p.G146A (c.437G>C), and a silent known p.P125P (c.375C>T) polymorphism, respectively, was found in several of the latter cases. Further investigation of the 2 polymorphisms in the larger material of cases and controls showed no significant genotypic or allelic association. In conclusion, the SF-1 gene may not play a significant role in the development of hypospadias in Caucasians.


Subject(s)
Genetic Predisposition to Disease , Hypospadias/genetics , Polymorphism, Genetic , Steroidogenic Factor 1/genetics , Diseases in Twins , Heterozygote , Humans , Male , Mutation, Missense , Sequence Analysis, DNA , White People
18.
J Clin Endocrinol Metab ; 97(12): 4588-95, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23015652

ABSTRACT

CONTEXT: A randomized controlled study was conducted comparing the outcome of surgery for congenital cryptorchidism at 9 months or 3 yr of age. OBJECTIVE: The aim of the study was to investigate whether surgery at 9 months is more beneficial than at 3 yr and to identify early endocrine markers of importance for testicular development. PATIENTS AND METHODS: A total of 213 biopsies were taken at orchidopexy, and the number of germ and Sertoli cells per 100 seminiferous cord cross-sections and the surface area of seminiferous tubules and interstitial tissue were analyzed. Inhibin B, FSH, LH, and testosterone were determined. Testicular volume was assessed by ultrasonography and by a ruler. RESULTS: The number of germ and Sertoli cells and testicular volume at 9 months were significantly larger than at 3 yr. The intraabdominal testes showed the largest germ cell depletion at 3 yr. At both ages, testicular volume correlated to the number of germ and Sertoli cells. None of the hormones measured during the first 6 months of life (LH, FSH, testosterone, and inhibin B) could predict the number of germ or Sertoli cells at either 9 or 36 months of age, nor could hormone levels predict whether spontaneous descent would occur or not. CONCLUSION: Morphometric and volumetric data show that orchidopexy at 9 months is more beneficial for testicular development than an operation at 3 yr of age. Testicular volume was furthermore shown to reflect germ cell numbers in early childhood, whereas endocrine parameters could not predict cellular structure of the testis or its spontaneous descent.


Subject(s)
Cryptorchidism/metabolism , Cryptorchidism/pathology , Cryptorchidism/surgery , Hormones/metabolism , Orchiopexy , Testis/physiopathology , Age Factors , Child, Preschool , Cryptorchidism/physiopathology , Follicle Stimulating Hormone/blood , Follicle Stimulating Hormone/metabolism , Hormones/blood , Humans , Infant , Infant, Newborn , Inhibins/blood , Inhibins/metabolism , Luteinizing Hormone/blood , Luteinizing Hormone/metabolism , Male , Orchiopexy/methods , Orchiopexy/rehabilitation , Organ Size , Spermatogenesis/physiology , Testis/metabolism , Testis/surgery , Testosterone/blood , Testosterone/metabolism
19.
Int J Androl ; 32(5): 473-8, 2009 Oct.
Article in English | MEDLINE | ID: mdl-18336536

ABSTRACT

Cryptorchidism is a known risk factor for testicular cancer and the secular increase in testicular cancer incidence might have been paralleled by a similar increase in cryptorchidism. Data on trends in prevalence of cryptorchidism are however conflicting and decreases have recently been reported. To analyse Swedish trends in rates of orchiopexy, we used the Swedish Hospital Discharge Register to identify all cases of orchiopexy carried out for cryptorchidism between 1977 and 1991, that is, before the era of outpatient orchiopexies in Sweden. Observed trends were analysed in 5-year age groups. The estimated average annual per cent changes (EAPCs) and the years in which the EAPC significantly changed were estimated using Joinpoint Regression. Finally, we estimated the cumulative incidence of orchiopexy by birth cohort. Among boys aged less than 10, the orchiopexy rate started to decrease in the early 1980s. EAPCs were -2.88 (95% confidence interval (CI): -5.48, -0.21) among boys aged 5-9 and -6.63 among those aged 0-4 (95% CI: -8.84, -4.37). Among subjects aged at least 10, the rate decreased over the whole study period. Although the use of orchiopexy rates to measure prevalence of cryptorchidism has limitations, our findings may suggest that cryptorchidism prevalence decreased in Sweden starting from the early 1980s.


Subject(s)
Cryptorchidism/surgery , Testis/surgery , Adolescent , Child , Child, Preschool , Cohort Studies , Cryptorchidism/epidemiology , Humans , Incidence , Infant , Infant, Newborn , Male , Sweden/epidemiology
20.
Hum Reprod ; 23(7): 1607-13, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18420648

ABSTRACT

BACKGROUND: Low pregnancy rate has been reported in women with congenital adrenal hyperplasia (CAH) and little information on pregnancy and children is known. METHODS: In a Swedish study, 62 adult women with CAH, aged 18-63 years, and 62 age-matched controls were followed-up. Medical records, including those concerning pregnancies and deliveries, were examined and the 21-hydroxylase genotype of patients was noted. All women answered a questionnaire concerning sexual and reproductive health including health of the children. RESULTS: Pregnancy and delivery rates were significantly lower in women with CAH (P < 0.001, P < 0.0056, respectively), and the severity of the 21-hydroxylase-mutation correlated with the reduced number of children born. More women with salt-wasting CAH were single and had not attempted pregnancy. Pregnancies were normal except for a significantly increased incidence of gestational diabetes in CAH patients (P < 0.0024). The children had normal birthweight and no malformations were observed. A later follow-up of the children showed a normal intellectual and social development. The sex ratio of the offspring differed significantly, with 25% boys in the CAH group compared with 56% among controls (P < 0.016). CAH women had more gynaecological morbidity during menopause. CONCLUSIONS: Pregnancy and delivery rates are reduced in women with CAH mainly due to psychosocial reasons. The outcome of children did not differ from controls. The unexpected sex ratio in children born to mothers with CAH warrants further research.


Subject(s)
Adrenal Hyperplasia, Congenital , Fertility , Pregnancy Outcome , Steroid 21-Hydroxylase/genetics , Adolescent , Adrenal Hyperplasia, Congenital/complications , Adrenal Hyperplasia, Congenital/genetics , Adult , Diabetes, Gestational/etiology , Female , Follow-Up Studies , Humans , Male , Menarche , Middle Aged , Pregnancy , Sex Ratio , Sweden
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