Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study

The objective of this study was to describe the prevalence of Klinefelter syndrome (KS) prenatally and postnatally in Denmark and determine the influence of maternal age. All chromosomal examinations in Denmark are registered in the Danish Cytogenetic Central Registry. Individuals with KS diagnosed prenatally or postnatally were extracted from the registry with information about age at the time of diagnosis and mother's age. In the period 1970-2000, 76,526 prenatal examinations on male fetuses resulted in the diagnosis of 163 fetuses with KS karyotype, corresponding to a prevalence of 213 per 100,000 male fetuses. Standardization according to maternal age resulted in a prevalence of 153 per 100,000 males. Postnatally, 696 males of 2,480,858 live born were diagnosed with KS, corresponding to a prevalence among adult men of approximately 40 per 100,000. Less than 10% of the expected number was diagnosed before puberty. Advanced maternal age had a significant impact on the prevalence. KS is severely underdiagnosed in Denmark. Only approximately one fourth of adult males with KS are diagnosed. There is a marked delay in diagnosis of the syndrome. A delay in treatment with testosterone may lead to decreased muscle and bone mass with subsequent risk of osteoporosis.     

Childhood disintegrative disorder

In 1908 a Viennese remedial educator Theodor Heller described six children under the name of dementia infantilis who had insidiously developed a severe mental regression between the 3rd and 4th years of life after normal mental development. Neuropathological and other medical conditions are sometimes associated with this disorder, but contrary to earlier belief this is not typical. Interest in childhood disintegrative disorder has increased markedly in recent years and in this review attention is given to more recently published cases based on ICD-9, ICD-10 and DSM-IV diagnostic systems. Information is provided related to nosology, epidemiological data, differential diagnosis, aetiology, treatment and outcome.     

Colon cancer controls versus population controls in case-control studies of occupational risk factors

Background  

Since updated population registers do not exist in many countries it is often difficult to sample valid population controls from the study base to a case-control study. Use of patient controls is an alternative option if the exposure experience under study for these patients are interchangeable with the experience for population controls. Patient controls may even be preferable from population controls under certain conditions. In this study we examine if colon cancer patients can serve as surrogates for proper population controls in case-control studies of occupational risk factors.     

Low CYP1A2 activity associated with testicular cancer

The incidence rate of testicular cancer has increased during the last 50 years. An interplay between changing environmental factors and individual susceptibility, e.g. in foreign compound metabolizing enzymes, may have important influences on the risk of testicular cancer. The cytochrome P4501A2 (CYP1A2) enzyme and the bimodally expressed enzyme N-acetyltransferase2 (NAT2) metabolize many procarcinogens/carcinogens. The aim of this population-based case-control study was to investigate if CYP1A2 or NAT2 activity measured as a ratio of urinary metabolites of dietary caffeine is a risk factor in testicular cancer. 378 men participated (80 seminomas, 104 non-seminomas and 194 controls). The CYP1A2 activity was lower in the cases than in the controls [median and 30-70% percentiles: 4.7 (3.9-5.7) and 5.2 (4.4-6.4), respectively]. The subjects were classified in tertiles with low, medium or high CYP1A2 activity. A low CYP1A2 activity was associated with the highest risk of testicular cancer. Including all participants except men using drugs suspected to influence CYP1A2 activity (n = 15), medium and low activity conferred odds ratios (ORs) of 1.54 [confidence intervals of 95% (CI(95%)) 0.93-2.55] and 2.11; CI(95%) (1.23-3.62), respectively, of having testicular cancer. Excluding smokers (n = 157) the ORs of medium and low activity were 3.63; CI(95%) (1.53-8.60) and 4.70; CI(95%) (2.03-10.89), respectively. After further exclusion of cases that had received chemotherapy or radiation (n = 47), similar significant results were achieved. In the groups with the lowest CYP1A2 activity the ORs for seminoma and non-seminoma were 2.12; CI(95%) (0.93-4.81) and 2.10; CI(95%) (1.02-4.32). The phenotype of NAT2 was not associated with testicular cancer. In conclusion, we found no association of NAT2 phenotype to testicular cancer, whereas significant associations between CYP1A2 activity and testicular cancer were shown.     

Stem cells for obstetricians and gynecologists

Stem cells are a subject of immense research interest, and may in the not too far future provide the basis for a number of new therapies aimed at substituting damaged or lacking cells, tissues, and even organs. A number of stem cell types have been identified, including embryonal stem cells, umbilical cord blood stem cells, and bone marrow stem cells. Two of the most promising stem cell types, embryonal stem cells and umbilical cord blood stem cells, are obtained from sources within the field of gynecology and obstetrics, namely fertility clinics performing in-vitro fertilization, and labor wards, respectively. This review focuses on the biological potentials of stem cells with a primarily gynaecological-obstetrical perspective. It is not the aim of this review to discuss the many important ethical aspects of stem cell technologies.     

No rules without exception: long-term complete remission observed in a study using a LH-RH agonist in platinum-refractory ovarian cancer

OBJECTIVE: Second-line chemotherapy in platinum/paclitaxel-resistant ovarian cancer induces an objective response in <15% and third-line chemotherapy results in responses less than 10%. Chemotherapy always results in side effects with the risk of a low quality of life. Endocrine therapy is used world-wide among chemo-resistant ovarian cancer. Tamoxifen is a standard palliative treatment in many centers. LH-RH (luteinizing hormone-releasing hormone) agonists have also demonstrated activity among patients with ovarian cancer in several studies with response rates of 9-12% and disease stabilization in 15-26% of these women. METHODS: In this retrospective study 32 patients with ovarian cancer who had relapsed after platinum/paclitaxel-based first-line chemotherapy and had exhausted all standard treatments received LH-RH analogue Leuprorelin depot 3.75 mg sc once a month until tumor progression. RESULTS: One patient (3%) had a complete response, with remission time over 3 years. Two patients (6%) reached partial response with remission time of 3 and 4 months. Four patients (12%) remained stable for a mean time of 7 months (range 4-12 months). The remaining 25 patients (78%) had progressive disease. The treatment was well tolerated, and no major toxicity has been reported. CONCLUSION: This study showed that LH-RH agonist Leuprorelin has only a limited effect in patients pretreated with platinum-based chemotherapy.     

IgG subclass antibody responses to alginate from Pseudomonas aeruginosa in patients with cystic fibrosis and chronic P. aeruginosa infection.

Chronic bronchopulmonary infection with alginate-producing, mucoid Pseudomonas aeruginosa is characteristically associated with cystic fibrosis (CF). A significant correlation between the antibody response to alginate and poor lung function has been reported. Enzyme-linked immunosorbent assays were developed for the quantitation of human IgG1, IgG2, IgG3, and IgG4 antibodies to P. aeruginosa alginate. We investigated the pattern of IgG subclass antibodies against P. aeruginosa alginate in serum of patients with CF, others with chronic P. aeruginosa infection, and healthy controls. Healthy controls and patients with CF, before they acquired P. aeruginosa infection, had no or very low titers of antibodies against P. aeruginosa alginate. The latter with chronic infection had significantly higher antibody levels than all others groups, including patients with chronic P. aeruginosa infection but no CF. CF with chronic P. aeruginosa infection led to an inverse correlation between lung function parameters and levels of IgG3 and IgG4. Fifty-seven patients with CF have been followed for an average of 12 years with multiple antibody assays covering the preinfection, early, and late stage of chronic infection. All of them developed IgG1 and IgG3 antibodies to alginate at the start of infection. IgG2 antibodies developed later and showed only a slow increase during the chronic infection. Patients who died had significantly higher IgG2 anti-alginate antibody levels than other investigated groups. Elevated levels of IgG2 and IgG3 antibodies to P. aeruginosa alginate are a sign of poor prognosis in CF.     

The burch colposuspension for urinary incontinence in patients with stable and unstable detrusor function

Eighty patients with urinary incontinence, 61 with stable and 19 with unstable detrusor function, were evaluated preoperatively and postoperatively after Burch colposuspension. The cure rate in the stable group was found to be 75% vs. 26% in the unstable group. This difference was highly significant (P < 0.0005). In the unstable group, the major cause of failure was persistent instability. The great controversy in the literature as to the prognostic significance of preoperatively demonstrated detrusor instability when treating urinary incontinence by conventional antiincontinence surgery is suggested to be due to: (1) differences in the cystometric techniques, hence the populations classified with detrusor instability; and (2) difficulties in identification of instability secondary to bladder neck incompetence. The cystometric technique described in this study is considered sufficiently physiologic to allow a reliable identification of true instability, thereby selecting patients who will not benefit from surgery. It is emphasized that there is a need for a thorough standardization of the cystometric technique for classifying true instability and as a basis for comparative studies.