Sleep related breathing disorders in older men: A search for underlying mechanisms

—The incidence of sleep-related breathing disorders (SRBDs) associated with hemoglobin desaturation was determined by nocturnal polygraphic evaluations in 26 healthy men, aged 55–70 years. Sixteen subjects (62%) had abnormal rates of at least 12 episodes per hour of sleep: 8 had occlusive, and 8 had central apnea or hypopnea. During waking ten of 16 SRBD subjects and only one subject without SRBDs exhibited either an elevated nasopharyngeal airway resistance (n=4) or a reduced ventilatory response to hypercapnia (n=4) and/or hypoxia (n=3). However, these abnormalities were not related to the type or severity of SRBDs, and 6 subjects with SRBDs demonstrated no respiratory defect. We conclude that SRBDs have a very high incidence in older males and are not usually secondary to pulmonary cardiac, neurological, or behavioral disorders. Additionally, we hypothesize that abnormalities in ventilatory control or upper airway resistance contribute to SRBDs, but depression of brain stem reticular formation activity during sleep plays a primary role in these disorders. Factors related to both aging and SRBDs are reviewed. These include reduced chemoreceptor responses, altered steroid hormone metabolism, and use and metabolism of hypnotic drugs and alcohol.     

Lipid transfer protein: a pan-allergen in plant-derived foods that is highly resistant to pepsin digestion

BACKGROUND: Lipid transfer proteins (LTPs) are small molecules of approximately 10 kD that demonstrate high stability. They have recently been identified as allergens in the Rosaceae subfamilies of the Prunoideae (peach, apricot, plum) and of the Pomoideae (apple). They belong to a family of structurally highly conserved proteins that are also present in non-Rosaceae vegetable foods. OBJECTIVE: The aim of this study was to investigate the cross-reactivity to non-Rosaceae LTPs, and to study the role of protein stability in allergenicity. METHODS: Thirty-eight patients with a positive SPT to Rosaceae fruit extracts enriched for LTP were characterized by interview and SPT. To investigate IgE cross-reactivity between Rosaceae and non-Rosaceae LTPs, RAST and RAST inhibition as well as ELISA and ELISA inhibition were performed, using whole food extracts and purified LTPs. Both purified natural LTPs (peach, carrot and broccoli) and Pichia pastoris recombinant LTPs (carrot and wheat) were included. Pepsin digestion was used to address the role of stability in the allergenicity of LTPs. RESULTS: IgE antibodies to Rosaceae LTPs reacted to a broad range of vegetable foods, including Gramineae (cereals), Leguminosae (peanut), Juglandaceae (walnut), Anacardiaceae (pistachio), Brassicaceae (broccoli), Umbelliferae (carrot, celery), Solanaceae (tomato), Cucurbitaceae (melon), and Actinidiaceae (kiwi). Binding and inhibition studies with purified natural and recombinant LTPs confirmed their role in this cross-reactivity. Many of these cross-reactivities were accompanied by clinical food allergy, frequently including systemic reactions. Antibody binding to LTP was shown to be resistant to pepsin treatment of whole extract or purified LTP. CONCLUSION: LTP is a pan-allergen with a degree of cross-reactivity comparable to profilin. Due to its extreme resistance to pepsin digestion, LTP is a potentially severe food allergen.     

Education modifies the effect of apolipoprotein epsilon 4 on cognitive decline

OBJECTIVES: To assess the influence of education on the association between apolipoprotein E and cognitive change. DESIGN: Prospective cohort. PARTICIPANTS: HMO-based sample of 2168 non-demented community-dwelling elderly followed over 6 years. MEASUREMENTS: Generalized estimating equations were used with the difference between baseline and follow-up cognitive abilities screening instrument (CASI) as the outcome variable. RESULTS: At follow-up, 6% of the sample had a decline of 1.5 S.D. or greater on the CASI. Compared to individuals without an APOE4 allele, individuals with a single APOE4 allele did not have greater CASI decline. By contrast, individuals with two APOE4 alleles experienced greater decline in cognitive performance and the magnitude of that decline decreased as years of educational attainment increased. These relationships held after adjusting for age, gender, ethnicity, depression, diabetes, and history of vascular disease. CONCLUSION: Lower education was associated with steep 4-year cognitive decline for APOE4 homozygotes but not for APOE4 heterozygotes. Potentially modifiable host factors such as education could influence the association of high-risk genotypes and cognitive decline.     

Performance of CHROMagar MRSA medium for detection of methicillin-resistant Staphylococcus aureus

CHROMagar MRSA was evaluated for its ability to identify methicillin-resistant Staphylococcus aureus (MRSA). A well-defined collection consisting of 216 MRSA strains and 241 methicillin-susceptible Staphylococcus aureus isolates was used. The sensitivity of CHROMagar MRSA after 24 h of incubation was 95.4%, increasing to 100% after 48 h. The specificity was already 100% after 24 h.     

Malformations of the axial skeleton in the museum Vrolik: II: craniosynostoses and suture-related conditions

The Museum Vrolik collection of anatomical specimens in Amsterdam, The Netherlands, comprises over 5,000 specimens of human and animal anatomy, embryology, pathology, and congenital anomalies. Recently, we rediagnosed a subset of the collection comprising dried infantile, juvenile, and adult human skulls with congenital and acquired conditions. On external examination and additional radiography, we found 58 skulls with craniosynostosis (CS) involving one or more sutures and 40 skulls with a presumed suture related condition. Most of these were part of the material collected and described by Louis Bolk (1866-1930). Analysis of his observations suggests that skull deformation because of premature suture closure depends not only on the identity of the sutures involved but also on the timing and progression of their closure and the extent of their involvement. Moreover, premature closure of the sagittal suture after 3-6 years of age appeared to be much more common than expected because it is not accompanied by skull deformation. Many of the skulls with single-suture CS were microcephalic, which may be the cause of the premature synostosis. By contrast, microcephaly may be a resulting phenomenon in multi-suture CS. We noticed that the quotient between height of the cranial vault (vertex-porion distance) and head circumference, multiplied by 100, was 26 or higher only in those CS cases with multi-suture involvement. We therefore consider this parameter, which we named "acrocephalic index", to be an indicator of multi-suture involvement in individual CS cases. In two adult skulls, the skull had a quadrangular shape, which we assumed to be correlated to the presence of an unusually interdigitated open metopic suture. We propose to name this anomaly: tetragonocephaly. Another presumed suture-related condition, bathrocephaly, was found concomitantly with basilar invagination in several cases. We hypothesize that the chronically raised intracranial pressure in these cases caused the still open lambdoidal sutures to distend and the occipital bone to protrude.     

Intelligence indices in people with a high/low risk for developing Huntington''s disease.

Intelligence in 20 presymptomatic subjects with an increased risk (> 95%) for carrying the gene for Huntington's disease (HD) was studied in a prospective, case-control, single blind study. No significant differences between the groups were detected for intelligence indices and subtest scores (Wechsler Adult Intelligence Scale). The high level of the performance IQ and the significant discrepancy between performance IQ and verbal IQ found in both the high risk and the low risk groups contrasted with our expectations based on anamnestic information, general clinical opinion, and the results of previously conducted studies. We propose that psychosocial circumstances could explain the test results and discuss the consequences of our findings for clinical genetics practice.     

Chronic unpredictable stress causes attenuation of serotonin responses in cornu ammonis 1 pyramidal neurons

In the present study, serotonin (5-HT) responses of hippocampal pyramidal cornu ammonis 1 (CA1) neurons were studied in rats subjected twice daily for 21 days to unpredictable stressors. In hippocampal tissue from thus stressed rats mRNA expression of the 5-HT(1A) receptor and mineralo- as well as glucocorticoid receptors were examined with in situ hybridization. On average, stressed rats displayed increased adrenal weight and attenuated body weight gain compared with controls, supporting that the animals had experienced increased corticosterone levels due to the stress exposure. One day after the last stressor, under conditions that corticosterone levels were low (predominant mineralocorticoid receptor activation), the 5-HT(1A) receptor mediated hyperpolarization of CA1 neurons in response to 10 microM 5-HT was significantly reduced compared with controls. Basal membrane properties of CA1 cells in stressed rats were comparable to those of controls. The 5-HT(1A) receptor mRNA expression was not changed after chronic stress exposure, in any of the hippocampal areas. A small but significant increase in mineralocorticoid receptor mRNA expression was observed after stress in the dentate gyrus, while glucocorticoid receptor expression was unchanged. The data indicate that unpredictable stress exposure for 3 weeks results in suppression of 5-HT(1A) receptor-mediated responses, possibly due to posttranslational modification of the receptor.     

Colonization of in vitro-formed cervical human papillomavirus- associated (pre)neoplastic lesions with dendritic cells: role of granulocyte/macrophage colony-stimulating factor

The purpose of this study was to investigate the ability of CD1a+ Langerhans/dendritic cells (LCs/DCs) to infiltrate human papillomavirus (HPV)-associated (pre)neoplastic lesions of the uterine cervix. Migration of LCs/DCs in the presence of keratinocytes derived from normal cervix and HPV-transformed cell lines was evaluated in Boyden chambers and in organotypic cultures and correlated with granulocyte/macrophage colony-stimulating factor (GM-CSF) production by the cells, as determined by ELISA. Conditioned media of HPV-transformed keratinocytes contained lower amounts of GM-CSF and induced a decreased motile response of LCs/DCs in the Boyden chamber assay compared with those of normal cervical keratinocytes. The migration of LCs/DCs in the presence of conditioned media from normal keratinocytes could be blocked by an anti-GM-CSF antibody, and the migration of LCs/DCs in the presence of conditioned media from HPV-transformed keratinocytes could be increased by supplementing the media with recombinant GM-CSF. GM-CSF was also a potent factor in enhancing the colonization of LCs/DCs into organotypic cultures of HPV-transformed keratinocytes, as the infiltration of LCs/DCs in the in vitro-formed (pre)neoplastic epithelium was minimal under basal conditions and dramatically increased after the addition of GM-CSF to the cultures. These results suggest that GM-CSF could play an important role in the recruitment of LCs/DCs into the HPV-transformed (pre)neoplastic cervical epithelium and be useful as a new immunotherapeutic approach for cervical (pre)cancers.     

Determination of total body water by multifrequency bio-electric impedance: development of several models

Multifrequency bio-electronic impedance analysis (MF BIA) measurements are taken from a heterogeneous group of patients, varying in size between obese and slim. The measuring system uses four electrodes: two current and two potential electrodes. Three new models are developed to calculate total body water (TBW) from the BIA data, and the resulting TBW values are compared with TBW determined by D₂O dilution. The results demonstrate that the most simple model provides the best TBW values. For individual patients, TBW can be determined by means of bioimpedance measurement with an accuracy of 3 litres. In the most simple model (model 1), the body is electrically represented by a cylinder, and corrections are made for the amount of fat. This is an extension of the model used by Xitron. In the more advanced models (2 and 3), the body is represented by a cylinder for the trunk, and truncated cones represent the arms and legs. In model 2, ΔTBW amounts to 3 litres. It is shown that the resistance of the trunk is proportional to the square root of the length. In model 3, it is assumed that subcutaneous fat is a poor conductor if electric current. An equation is developed that describes the partition of subcutaneous fat, and the fat layer is then removed from the cones representing arms and legs and from the cylinder that models the trunk.