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Biomedical subjects

B Lee

Publications and source records attributed to B Lee.

At least 73 records · Page 4Linked to original sources

The study on the web-based Clinical Database Management System of Oriental Pulse Waveform.

There are many database-oriented sites on the web, which provide basic medical knowledge, hospital information, and medical counseling. However, there are only a few oriental pulse databases on the web. In this perspective, the goal of this study is to develop the Clinical Database Management System of Oriental Pulse Wave Form using the World Wide Web. Accordingly, this study has conducted researches in the Web-based diagnosis data management system of pulse waveform as well as the method of transmitting the data of pulse waveform. In order to set the standard for the documents of the pulse waveform of patients, the web-based clinical database management system has been developed.

Database Management Systems↗

Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome.

Basement membrane (BM) morphogenesis is critical for normal kidney function. Heterotrimeric type IV collagen, composed of different combinations of six alpha-chains (1-6), is a major matrix component of all BMs (ref. 2). Unlike in other BMs, glomerular BM (GBM) contains primarily the alpha 3(IV) and alpha 4(IV) chains, together with the alpha 5(IV) chain. A poorly understood, coordinated temporal and spatial switch in gene expression from ubiquitously expressed alpha 1(IV) and alpha 2(IV) collagen to the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains occurs during normal embryogenesis of GBM (ref. 4). Structural abnormalities of type IV collagen have been associated with diverse biological processes including defects in molecular filtration in Alport syndrome, cell differentiation in hereditary leiomyomatosis, and autoimmunity in Goodpasture syndrome; however, the transcriptional and developmental regulation of type IV collagen expression is unknown. Nail patella syndrome (NPS) is caused by mutations in LMX1B, encoding a LIM homeodomain transcription factor. Some patients have nephrosis-associated renal disease characterized by typical ultrastructural abnormalities of GBM (refs. 8,9). In Lmx1b(-/-) mice, expression of both alpha(3)IV and alpha(4)IV collagen is strongly diminished in GBM, whereas that of alpha1, alpha2 and alpha5(IV) collagen is unchanged. Moreover, LMX1B binds specifically to a putative enhancer sequence in intron 1 of both mouse and human COL4A4 and upregulates reporter constructs containing this enhancer-like sequence. These data indicate that LMX1B directly regulates the coordinated expression of alpha 3(IV) and alpha 4(IV) collagen required for normal GBM morphogenesis and that its dysregulation in GBM contributes to the renal pathology and nephrosis in NPS.

Animals↗

Efficient gene transfer of VSV-G pseudotyped retroviral vector to human brain tumor.

A retroviral vector constructed from the murine leukemia virus (MLV) can only express transgenes in cells undergoing mitosis, indicating its suitability as a delivery vehicle for cancer gene therapy. However, the transduction efficiency (TE) of retroviruses embedding endogenous envelope proteins in human cancer cells was found to be unsatisfactory. Recently, several research groups have demonstrated the feasibility of a retroviral vector pseudotyped with a vesicular stomatitis virus G (VSV-G) protein. In this study, the potential of VSV-G pseudotyped MLV-based retrovirus was examined as a delivery vehicle in a variety of human cancer cells including brain tumor cells in vitro and in vivo. The transduction efficiency of the 293T/G/GP/LacZ retrovirus in cell culture was superior in most cancer cells, particularly in brain tumor cells, compared with that of other retroviruses, such as PA317- or PG13-derived. The relative growth rate and phosphatidylserine expression level on the plasma membrane of target cells mainly influenced the transduction efficiency of VSV-G pseudotyped retrovirus, which suggested that both the relative growth rate and phosphatidylserine expression level were major determinants of TE. Furthermore, 293T/G/GP/LacZ could efficiently transduce human cancer cells regardless of the presence of chemical additives, whereas in other retroviruses, cationic chemical additives such as polybrene or liposomes were essential during virus infection. Finally, an average of 10% gene expression was routinely obtained exclusively in the tumor mass when 293T/G/GP/LacZ concentrated by simple ultracentrifugation was directly administrated to pre-established brain tumors in animal models (U251-N nu/nu mice or C6 Wistar rats). All told, the present study suggests that the VSV-G pseudotyped retrovirus is a suitable vector for brain tumor gene therapy.

Brain Neoplasms↗

Extraperitoneal approach reduces neutrophil activation, systemic inflammatory response and organ dysfunctionin aortic aneurysm surgery.

OBJECTIVES: to compare the effects of transperitoneal and extraperitoneal approaches on systemic inflammatory response, neutrophil activation and organ dysfunction in elective abdominal aortic aneurysm (AAA) repair. PATIENTS AND METHODS: twenty patients admitted for elective infrarenal AAA repair were prospectively randomised into transperitoneal (n =10) or extraperitoneal ( n =10) groups. Neutrophil activation was assessed by measuring the plasma levels of neutrophil elastase/alpha(1)-anti-trypsin complexes before surgery, intraoperatively and at 6 h, 12 h, 24 h and then daily after surgery. Venous blood samples for estimation of liver function tests, full blood counts, urea and electrolytes and arterial samples for blood gas analysis were taken daily from preoperatively to day 5 after surgery. Multiple organ dysfunction (MOD) and systemic inflammatory response (SIR) scores were calculated daily. RESULTS: the concentrations of neutrophil elastase/alpha(1)-anti-trypsin complexes were significantly higher in the transperitoneal group at 6 h after surgery compared to the extraperitoneal group (799(455-921) ng/ml (median(i.q.r.)) vs 307(171-395) ng/ml, p<0.005), and at 12 h (397(364-936) ng/ml vs 319(134-352) ng/ml, p <0.05). The MOD scores were significantly higher in the transperitoneal group in comparison to the extraperitoneal group at day 1 (2.5(2-3.3) vs 1(0-1), p<0.001) and day 2 (2.5(2-3.3) vs 1(0-1), p <0.001). The SIR scores were also significantly higher at day 1 (1(0-2) vs 0, p <0.01), day 2 (1.5(0-2.3) vs 0, p <0.01), and day 3 (1(0-1) vs 0, p <0.05). CONCLUSIONS: neutrophil activation, systemic inflammatory response and organ dysfunction are increased in elective AAA repair when a transperitoneal approach is used. This may be related to intestinal manipulation and mesenteric traction which are reduced in the extraperitoneal approach.

APACHE↗

The role of mutant Apc in the development of dysplasia and cancer in the mouse model of dextran sulfate sodium-induced colitis.

BACKGROUND & AIMS: Differences in genetic background may play a role in the development of ulcerative colitis (UC)-related neoplasia. Loss of heterozygosity (LOH) of APC has been reported in human UC-associated neoplasia. To investigate the role of genetic differences in UC-associated neoplasia, we compared differences in dextran sodium sulfate (DSS) colitis-associated neoplasia between wild-type C57BL/6J mice (WT-DSS) and C57BL/6J mice with a germline mutation in Apc (Min-DSS). METHODS: DSS colitis was induced in female wild-type and Min mice. Age- and sex-matched non-DSS-treated Mins were also studied. Animals were sacrificed after 1 and 2 cycles of DSS. The cecums and large intestines were studied for numbers of dysplasias/cancers. Dysplasias were studied for LOH of Apc. RESULTS: No WT-DSS, 100% of Min-DSS, and 50% of non-DSS-treated Mins had dysplasia. The mean numbers of lesions per mouse were 0 (WT-DSS), 15.6 and 29.3 (1 and 2 cycles Min-DSS, respectively), 1.2 and 1.9 (age-matched control Min, 1 and 2 cycle equivalents, respectively; P < 0.0002, Min-DSS vs. WT-DSS and non-DSS-treated Min; P = 0.03, Min-DSS 2 cycle vs. Min-DSS 1 cycle). Cancers were seen in 0%, 22%, and 40% of non-DSS Min, Min-DSS-1 cycle, and Min-DSS-2 cycle animals, respectively. LOH of Apc was observed in 90.6% of dysplasias and 6% of nondysplastic mucosa. CONCLUSIONS: A germline mutation in Apc contributes significantly to the development of colitis-associated neoplasia. Colitis markedly accelerates the development of dysplasia and cancer in the Min mouse. Dysplasia in Min-DSS occurs through LOH of Apc.

Adenoma↗

Mitochondrial-encoded gene regulation in rat pancreatic islets.

Mitochondrial adenosine triphosphate (ATP) generation plays a major role in insulin secretion in pancreatic islet beta cells. The relationship between age and nutritional status of the islet and mitochondrial gene messenger RNA (mRNA) expression was investigated. Three animal groups were studied: infant (12-day-old) rats fed either mother's milk or a high carbohydrate (HC) diet; young (2 to 4-month-old) rats; and old (12 to 14-month-old) rats. The expression of mitochondrial cytochrome oxidase (CYO) (subunits I, II, and III), beta-nicotinamide adenine dinucleotide, reduced form dehydrogenase subunit 4 (NADH-DH4), and ATP synthase (subunit 6) (ATP-SYN6) mRNAs was characterized by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The mitochondrial gene mRNAs were identified in each of the groups of rat islets and in RINm5F cells. CYO-II mRNA expression in young and old rat pancreatic islets was 12.7- and 8.2-fold higher, respectively, compared with the level in infant rat islets. The expression of NADH-DH4 and ATP-SYN6 mRNAs was 47% and 40% lower, respectively, in young rat islets compared with the level in infant rat islets. CYO-I, CYO-III, and cytoplasmic glyceraldehyde-3-phosphate dehydrogenase (GPDH) mRNA expression did not differ between experimental groups. Artificial rearing of infant rat pups on a HC diet for 8 days lead to a 3.3-fold increase in islet CYO-II mRNA expression compared with mother-fed pups. However, glucose (11 mmol/L) stimulation of cultured isolated islets from young and old rats for 4 days failed to affect the expression level of mitochondrial gene mRNAs. Thus, aging affected the differential expression of CYO-II, NADH-DH4, and ATP-SYN6 mRNAs in rat islets. CYO-II mRNA expression was modulated only in infant rat islets after in vivo administration of carbohydrate.

Aging↗

Long-term correction of urea cycle disorders.

Long-term correction of urea cycle disorders is achieved by correction of the enzymatic defect in hepatocytes. Currently, orthotopic liver transplantation is the primary means of achieving this correction. In the United States most liver transplantations for urea cycle disorders have been restricted to patients with ornithine transcarbamylase deficiency and argininosuccinic aciduria. However, patients with citrullinemia have also received transplants, but more so in Europe and Japan. Recent advances in organ procurement, surgical technique, and immunosuppression have significantly decreased morbidity and mortality. However, unique short-term complications associated with surgery and long-term complications associated with chronic immunosuppression have spurred continued efforts to develop gene replacement therapies for management of acute metabolic decompensations as intercurrent therapy until liver transplantation, and ultimately, for long-term correction. The pathophysiology of urea cycle disorders requires gene vector delivery systems that are highly efficient for liver transduction and transgene expression. To date, adenoviral vectors are unique in fulfilling these criteria, and significant data have been gained in both animal and human studies with early versions of adenoviral vectors. Ultimately, the development of helper-dependent adenoviral vectors may offer the long-term expression and increased margin of safety necessary for adjunctive therapies.

Adenoviridae↗

Endovascular stent-graft repair of primary aortocaval fistula with an abdominal aortoiliac aneurysm.

A primary aortocaval fistula is present in less than 1% of all abdominal aortic aneurysms. Until recently, surgical repair was the only method of treatment and was associated with a high incidence of morbidity and mortality. With the rapid development of aortic stent-graft technique, endovascular stent-graft repair may offer an alternative to the management of this often fatal condition. We report a case of an aortoiliac aneurysm with an aortocaval fistula successfully treated with endovascular stent-grafting. The unique hemodynamic changes, technical problems, and complications associated with this case are discussed, and the literature is reviewed.

Aortic Aneurysm, Abdominal↗

Circularly permuted proteins in the protein structure database.

Some proteins are homologous to others after their sequence is circularly permuted. A few such proteins have been recognized, mainly by sequence comparison, but also by comparing their three-dimensional structures. Here we report the result of a systematic search for all protein pairs in the SCOP 90% id domain database that become structurally superimposable when the sequence of one of the pairs is circularly permuted. Using a reasonable set of criteria, we find that 47% of all protein domains are superimposable to at least one other protein domain in the database after their sequence is circularly permuted. Many of these are symmetric proteins, which superimpose to another protein both with and without a circular permutation of the sequence. However, 412 of the total 3035 domains are nonsymmetric, and these become structurally superimposable to another protein only after a circular permutation of the sequence. These include most known and many previously undetected circularly permuted proteins with remote homology.

Amino Acid Sequence↗

Cavities of alpha(1)-antitrypsin that play structural and functional roles.

The native form of inhibitory serine protease inhibitors (serpins) is strained, which is critical for their inhibitory activity. Previous studies on stabilizing mutations of alpha(1)-antitrypsin, a prototype of serpins, indicated that cavities provide a structural basis for the native strain of the molecule. We have systematically mapped the cavities of alpha(1)-antitrypsin that play such structural and functional roles by designing cavity-filling mutations at residues that line the walls of the cavities. Results show that energetically unfavorable cavities are distributed throughout the alpha(1)-antitrypsin molecule, and the cavity-filling mutations stabilized the native conformation at 8 out of 10 target sites. The stabilization effect of the individual cavity-filling mutations of alpha(1)-antitrypsin varied (0.2-1.9 kcal/mol for each additional methylene group) and appeared to depend largely on the structural flexibility of the cavity environment. Cavity-filling mutations that decreased inhibitory activity of alpha(1)-antitrypsin were localized in the loop regions that interact with beta-sheet A distal from the reactive center loop. The results are consistent with the notion that beta-sheet A and the structure around it mobilize when alpha(1)-antitrypsin forms a complex with a target protease.

Amino Acid Substitution↗

A frontal plane model of the lumbar spine subjected to a follower load: implications for the role of muscles.

Compression on the lumbar spine is 1000 N for standing and walking and is higher during lifting. Ex vivo experiments show it buckles under a vertical load of 80-100 N. Conversely, the whole lumbar spine can support physiologic compressive loads without large displacements when the load is applied along a follower path that approximates the tangent to the curve of the lumbar spine. This study utilized a two-dimensional beam-column model of the lumbar spine in the frontal plane under gravitational and active muscle loads to address the following question: Can trunk muscle activation cause the path of the internal force resultant to approximate the tangent to the spinal curve and allow the lumbar spine to support compressive loads of physiologic magnitudes? The study identified muscle activation patterns that maintained the lumbar spine model under compressive follower load, resulting in the minimization of internal shear forces and bending moments simultaneously at all lumbar levels. The internal force resultant was compressive, and the lumbar spine model, loaded in compression along the follower load path, supported compressive loads of physiologic magnitudes with minimal change in curvature in the frontal plane. Trunk muscles may coactivate to generate a follower load path and allow the ligamentous lumbar spine to support physiologic compressive loads.

Humans↗

DC-SIGN interactions with human immunodeficiency virus type 1 and 2 and simian immunodeficiency virus.

Dendritic cells (DCs) efficiently bind and transmit human immunodeficiency virus (HIV) to cocultured T cells and so may play an important role in HIV transmission. DC-SIGN, a novel C-type lectin that is expressed in DCs, has recently been shown to bind R5 HIV type 1 (HIV-1) strains and a laboratory-adapted X4 strain. To characterize the interaction of DC-SIGN with primate lentiviruses, we investigated the structural determinants of DC-SIGN required for virus binding and transmission to permissive cells. We constructed a panel of DC-SIGN mutants and established conditions which allowed comparable cell surface expression of all mutants. We found that R5, X4, and R5X4 HIV-1 isolates as well as simian immunodeficiency and HIV-2 strains bound to DC-SIGN and could be transmitted to CD4/coreceptor-positive cell types. DC-SIGN contains a single N-linked carbohydrate chain that is important for efficient cell surface expression but is not required for DC-SIGN-mediated virus binding and transmission. In contrast, C-terminal deletions removing either the lectin binding domain or the repeat region abrogated DC-SIGN function. Trypsin-EDTA treatment inhibited DC-SIGN mediated infection, indicating that virus was maintained at the surface of the DC-SIGN-expressing cells used in this study. Finally, quantitative fluorescence-activated cell sorting analysis of AU1-tagged DC-SIGN revealed that the efficiency of virus transmission was strongly affected by variations in DC-SIGN expression levels. Thus, variations in DC-SIGN expression levels on DCs could greatly affect the susceptibility of human individuals to HIV infection.

Amino Acid Sequence↗

CD4-independent use of Rhesus CCR5 by human immunodeficiency virus Type 2 implicates an electrostatic interaction between the CCR5 N terminus and the gp120 C4 domain.

Envelope glycoproteins (Envs) of human immunodeficiency virus type 2 (HIV-2) are frequently able to use chemokine receptors, CXCR4 or CCR5, in the absence of CD4. However, while these Envs are commonly dual-tropic, no isolate has been described to date that is CD4 independent on both CXCR4 and CCR5. In this report we show that a variant of HIV-2/NIHz, termed HIV-2/vcp, previously shown to utilize CXCR4 without CD4, is also CD4 independent on rhesus (rh) CCR5, but requires CD4 to fuse with human (hu) CCR5. The critical determinant for this effect was an acidic amino acid at position 13 in the CCR5 N terminus, which is an asparagine in huCCR5 and an aspartic acid in rhCCR5. Transferring the huCCR5 N terminus with an N13D substitution to CCR2b or CXCR2 was sufficient to render these heterologous chemokine receptors permissive for CD4-independent fusion. Chimeric Envs between HIV-2/vcp and a CD4-dependent clone of HIV-2/NIHz as well as site-directed Env mutations implicated a positively charged amino acid (lysine or arginine) at position 427 in the C4 region of the HIV-2/vcp env gene product (VCP) gp120 as a key determinant for this phenotype. Because CD4-independent use of CCR5 mapped to a negatively charged amino acid in the CCR5 N terminus and a positively charged amino acid in the gp120 C4 domain, an electrostatic interaction between these residues or domains is likely. Although not required for CD4-dependent fusion, this interaction may serve to increase the binding affinity of Env and CCR5 and/or to facilitate subsequent conformational changes that are required for fusion. Because the structural requirements for chemokine receptor use by HIV are likely to be more stringent in the absence of CD4, CD4-independent viruses should be particularly useful in dissecting molecular events that are critical for viral entry.

Amino Acid Sequence↗

cis Expression of DC-SIGN allows for more efficient entry of human and simian immunodeficiency viruses via CD4 and a coreceptor.

DC-SIGN is a C-type lectin expressed on dendritic cells and restricted macrophage populations in vivo that binds gp120 and acts in trans to enable efficient infection of T cells by human immunodeficiency virus type 1 (HIV-1). We report here that DC-SIGN, when expressed in cis with CD4 and coreceptors, allowed more efficient infection by both HIV and simian immunodeficiency virus (SIV) strains, although the extent varied from 2- to 40-fold, depending on the virus strain. Expression of DC-SIGN on target cells did not alleviate the requirement for CD4 or coreceptor for viral entry. Stable expression of DC-SIGN on multiple lymphoid lines enabled more efficient entry and replication of R5X4 and X4 viruses. Thus, 10- and 100-fold less 89.6 (R5/X4) and NL4-3 (X4), respectively, were required to achieve productive replication in DC-SIGN-transduced Jurkat cells when compared to the parental cell line. In addition, DC-SIGN expression on T-cell lines that express very low levels of CCR5 enabled entry and replication of R5 viruses in a CCR5-dependent manner, a property not exhibited by the parental cell lines. Therefore, DC-SIGN expression can boost virus infection in cis and can expand viral tropism without affecting coreceptor preference. In addition, coexpression of DC-SIGN enabled some viruses to use alternate coreceptors like STRL33 to infect cells, whereas in its absence, infection was not observed. Immunohistochemical and confocal microscopy data indicated that DC-SIGN was coexpressed and colocalized with CD4 and CCR5 on alveolar macrophages, underscoring the physiological significance of these cis enhancement effects.

CD4 Antigens↗

A new therapeutic target in Alzheimer's disease treatment: attention to butyrylcholinesterase.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly, characterised by widespread loss of central cholinergic function. The only symptomatic treatment proven effective to date is the use of cholinesterase (ChE) inhibitors to augment surviving cholinergic activity. ChE inhibitors act on the enzymes that hydrolyse acetylcholine (ACh) following synaptic release. In the healthy brain, acetylcholinesterase (AChE) predominates (80%) and butyrylcholinesterase (BuChE) is considered to play a minor role in regulating brain ACh levels. In the AD brain, BuChE activity rises while AChE activity remains unchanged or declines. Therefore both enzymes are likely to have involvement in regulating ACh levels and represent legitimate therapeutic targets to ameliorate the cholinergic deficit. The two enzymes differ in location, substrate specificity and kinetics. Recent evidence suggests that BuChE may also have a role in the aetiology and progression of AD beyond regulation of synaptic ACh levels. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine, MF-8622) and ChE inhibitors such as rivastigmine, which have a dual inhibitory action on both AChE and BuChE, indicate potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. The development of specific BuChE inhibitors and the continued use of ChE inhibitors with the ability to inhibit BuChE in addition to AChE should lead to improved clinical outcomes.

Alzheimer Disease↗

Proteasomal activation mediates down-regulation of inositol 1,4,5-trisphosphate receptor and calcium mobilization in rat pancreatic islets.

Inositol 1,4,5-trisphosphate receptor (IP3R) protein levels in isolated rat pancreatic islets were investigated in response to carbachol (CCh) and sulfated cholecystokinin 26-33 amide stimulation. Within 2 h, CCh reduced IP3R-I protein levels by 22% and IP3R-II and -III levels to 65% or more below basal. Sulfated cholecystokinin 26-33 amide decreased the levels of IP3R-I, -II, and -III by 34%, 60%, and 66% below basal, respectively. The effect of CCh was concentration- and time-dependent, with a persistent decline in IP3R levels for up to 6 h after the onset of stimulation. CCh-pretreated islets also showed an inhibition of glucose-stimulated insulin secretion. Proteasome inhibition completely blocked the down-regulatory effects of CCh on IP3Rs and significantly increased the insulin secretory response to glucose stimulation in the presence of CCH: Islet stimulation by glucose, alpha-ketoisocaproic acid, and tolbutamide completely protected IP3Rs against the down-regulatory effects of CCH: 2-deoxyglucose and 3-O-methyl glucose failed to affect CCh-induced IP3R down-regulation. The protective effects of glucose on IP3R down-regulation were completely inhibited by the Ca(2+) channel-blocking agent nimodipine. Intracellular Ca(2+) ([Ca(2+)](i)) levels in Fura-2 (fluorescent Ca(2+) indicator)-loaded islets, in the absence of extracellular Ca(2+), increased in response to glucose stimulation; but in islets pretreated with CCh, glucose did not increase [Ca(2+)](i) above basal levels. However, in islets pretreated with CCh and the proteasomal inhibitor MG-132 (carbobenzoxyl-leucinyl-leucinyl-leucinyl-H), the glucose-stimulated increase in [Ca(2+)](i) was significantly higher than the change observed for glucose-stimulated [Ca(2+)](i) in the absence of MG-132. The results suggest that muscarinic receptor stimulation modulates IP3R protein levels in islets through a proteasomal activation pathway, and that down-regulation of IP3Rs has a profound effect on Ca(2+) mobilization in islets that may relate to insulin secretory responsiveness.

Animals↗

Statistical optimization of bioluminescence of Photobacterium phosphoreum KCTC2852.

In this study, media optimization by statistically designed experiments stimulated an increase in the intensity and stability of bioluminescence of Photobacterium phosphoreum KCTC 2852 during continuous cultivation. The Plackett-Burman design method selected two components (NaCl, yeast extract) among nine components of the seawater complete (SC) medium. The response-surface design method calculated the optimum concentration of NaCl (31.1 g/l) and yeast extract (5.1 g/l). In the optimized medium, bioluminescence per cell increased twofold. During continuous cultivation in a stirred tank reactor, bioluminescence decreased rapidly in the SC medium, whereas the optimized medium could maintain bioluminescence for more than 80 h, resulting in an increased bioluminescence. Upon contact with 0.1 ppm Hg2+, a sharp decrease in bioluminescence was observed, which was reproducible in the measuring chamber. This shows the possibility that P. phosphoreum could be cultivated continuously with enhanced bioluminescence stability and that on-line water toxicity could be monitored continuously.

Journal Article↗

Impact of menopause on the prevalence and severity of sleep apnea.

STUDY OBJECTIVES: To compare the prevalence and severity of sleep apnea between premenopausal and postmenopausal women, and to determine whether these differences are affected by the body mass index (BMI) and neck circumference. DESIGN: Cross-sectional study utilizing a sleep clinic patient database. SETTING: University hospital. PATIENTS: A total of 1,315 women, classified into premenopausal and postmenopausal groups based on age (< 45 years and > 55 years, respectively). MEASUREMENTS: Anthropometric measurements included height, weight, and neck circumference. Sleep measurements included full nocturnal polysomnography. Sleep apnea was defined as an apnea-hypopnea index (AHI) > 10/h. RESULTS: There were 797 premenopausal and 518 postmenopausal women. The latter group was more obese (mean +/- SE BMI, 32.2 +/- 0.4 kg/m(2) vs 30.2 +/- 0.4 kg/m(2); p < 0.0001) and had larger neck circumference (37.1 +/- 0.2 cm vs 35.8 +/- 0.2 cm; p < 0.0001). The prevalence of sleep apnea was greater in postmenopausal women than premenopausal women (47% vs 21%; chi(2) < 0.0001). There were proportionately more postmenopausal than premenopausal women in all ranges of apnea severity (AHI, 10 to 30/h, 30 to 50/h, and > 50/h). Postmenopausal women had a significantly higher mean AHI compared to premenopausal women (17.0 +/- 0.9/h vs 8.7 +/- 0.6/h; p < 0.0001); this significant difference persisted even after adjusting for BMI and neck circumference. CONCLUSION: There may be functional, rather than anatomic, differences in the upper airway between premenopausal and postmenopausal women, which may account for the observed differences in apnea prevalence and severity.

Adult↗