A twin study of genetic contributions to hippocampal morphology in schizophrenia

Our goal was to establish whether altered hippocampal morphology represents a trait marker for genetic vulnerability in schizophrenia. We outlined the hippocampi on high-resolution MR images obtained from matched samples of control and discordant monozygotic and dizygotic co-twins (N = 40 pairs). Hippocampal measures were used in statistical tests specifically designed to identify disease-associated genetic and nongenetic influences on morphology. 3D surface average maps of the hippocampus were additionally compared in biological risk groups. Smaller hippocampal volumes were confirmed in schizophrenia. Dizygotic affected co-twins showed smaller left hippocampi compared to their healthy siblings. Disease-associated effects were not present between monozygotic discordant co-twins. Monozygotic, but not dizygotic, unaffected co-twins exhibited smaller left hippocampi compared to control twins, supporting genetic influences. Surface areas and posterior volumes similarly revealed schizophrenia and genetic liability effects. Results suggest that hippocampal volume reduction may be a trait marker for identifying individuals possessing a genetic predisposition for schizophrenia.     

Use of growth factors in the elderly patient with cancer: a report from the Second International Society for Geriatric Oncology (SIOG) 2001 meeting

Over 70% of the total incidence of cancer recorded in Europe in 1996 was in the elderly population (> or =60 years). Despite such high statistics, elderly cancer patients have often been denied the treatment that younger patients routinely receive. The response of elderly cancer patients to full-dose chemotherapy treatment in several neoplasms is similar to that of younger patients, demonstrating that age should not be a barrier to the administration of potentially curative or palliative chemotherapy. In order to provide optimal treatment to elderly cancer patients, management guidelines are recommended which take into account various factors, such as the physical well-being of the patient, the type of malignancy and any conditions that may hamper compliance with chemotherapy. The evidence-based guidelines of the National Comprehensive Cancer Network (NCCN) in the US recommend that the safest and most effective treatment of cancer in older individuals may be achieved by proper patient selection based on comprehensive geriatric assessment, dose adjustment of renally excreted drugs, prophylactic use of haematopoietic growth factors in patients treated with chemotherapy of dose-intensity comparable to cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) and maintenance of haemoglobin levels > or =12 g/l. The objective of this article is to report the conclusions of the meeting of the International Society of Geriatric Oncology (SIOG) in September 2001, including the need for geriatric assessment to tailor the management of patients to their personal circumstances and general health and the importance of evidence-based guidelines for the management of elderly cancer patients cannot be over-estimated.     

Treatment of acute rhinosinusitis diagnosed by clinical criteria or ultrasound in primary care. A placebo-controlled randomised trial

OBJECTIVES: To compare antibiotics and placebo in patients with clinically diagnosed acute maxillary sinusitis (AMS). To study whether sinus ultrasound examination would help to detect those patients who benefit from antibiotic therapy. DESIGN: A double-blind, randomised, placebo-controlled multicentre trial. SETTING: Nine primary care sites in Finland. SUBJECTS: 150 adult patients (mean age 39.7 years) with a clinical diagnosis of sinusitis. INTERVENTION: Antibiotics (amoxicillin 750 mg x 2, doxycycline 100 mg x 2 or penicillin V 1500 mg x 2) or placebo twice daily for 7 days; all patients were examined with sinus ultrasound after randomisation. MAIN OUTCOME MEASURE: Clinical success (patients' report of recovery) in telephone interview at 2 weeks. RESULTS: A total of 146 patients completed the 2-week follow-up. Patients receiving antibiotics achieved a slightly higher rate of clinical success than patients receiving placebo (80% vs 66%; p = 0.068). CONCLUSIONS: Antibiotics hasten symptom relief in AMS. Yet many patients recover in 2 weeks without antimicrobial treatment. Only half of patients with a clinical diagnosis of AMS have sinusitis in ultrasound examination.     

Bordetella pertussis protein pertactin induces type-specific antibodies: one possible explanation for the emergence of antigenic variants?

Divergence has been found between Bordetella pertussis vaccine strains and circulating strains. Polymorphism in pertactin (Prn) is essentially limited to region 1, which is made up of repeats. Today, the 3 most prevalent Prn variants are Prn1-3. Vaccine strains produce Prn1, whereas Prn2 is the predominant type found in circulating strains. We investigated how variation in region 1 affects the production of human serum antibodies. Individuals infected by Prn2 strains had significantly fewer antibodies to Prn1 did than those infected by Prn3 strains and those immunized with a booster dose of acellular vaccines containing Prn1. Moreover, in contrast to vaccine recipients and subjects infected by Prn3 strains, individuals infected by Prn2 strains had hardly any antibodies specific to the variable region of Prn1. These results indicate that conformational changes have occurred in the variable region of Prn, which may offer a possible explanation for the emergence of Prn2 strains in certain countries.     

High levels of luteinizing hormone analog stimulate gonadal and adrenal tumorigenesis in mice transgenic for the mouse inhibin-alpha-subunit promoter/Simian virus 40 T-antigen fusion gene

Transgenic (TG) mice expressing the Simian virus 40 T-antigen under the control of the murine inhibin-alpha promoter (Inhalpha/Tag) develop granulosa and Leydig cell tumors at the age of 5-6 months, with 100% penetrance. When these mice are gonadectomized, they develop adrenocortical tumors. Suppression of gonadotropin secretion inhibits the tumorigenesis in the gonads of intact animals and in the adrenals after gonadectomy. To study further the role of luteinizing hormone (LH) in gonadal and adrenal tumorigenesis, a double TG mouse model was generated by crossing the Inhalpha/Tag mice with mice producing constitutively elevated levels of LH (bLHbeta-CTP mice). Our results show that in double TG mice (bLHbeta-CTP/Inhalpha/Tag), gonadal tumorigenesis starts earlier and progresses faster than in Inhalpha/Tag mice. Both ovarian and testicular tumors were histologically comparable with the tumors found in Inhalpha/Tag mice. In addition, adrenal tumorigenesis was found in intact double TG females, but not in Inhalpha/Tag females. Inhibin-alpha and LH receptor (LHR) were highly expressed in tumorigenic gonadal tissues, and the elevated LH levels were shown to be associated with ectopic LHR and high inhibin-alpha expression in the female adrenals. We conclude that in the Inhalpha/Tag tumor mouse model, elevated LH levels act as a tumor promoter, advancing gonadal and adrenal tumorigenesis.