Spatially clustered type I interferon responses at injury borderzones.

Sterile inflammation after myocardial infarction is classically credited to myeloid cells interacting with dead cell debris in the infarct zone1,2. Here we show that cardiomyocytes are the dominant initiators of a previously undescribed type I interferon response in the infarct borderzone. Using spatial transcriptomics analysis in mice and humans, we find that myocardial infarction induces colonies of interferon-induced cells (IFNICs) expressing interferon-stimulated genes decorating the borderzone, where cardiomyocytes experience mechanical stress, nuclear rupture and escape of chromosomal DNA. Cardiomyocyte-selective deletion of Irf3 abrogated IFNIC colonies, whereas mice lacking Irf3 in fibroblasts, macrophages, neutrophils or endothelial cells, Ccr2-deficient mice or plasmacytoid-dendritic-cell-depleted mice did not. Interferons blunted the protective matricellular programs and contractile function of borderzone fibroblasts, and increased vulnerability to pathological remodelling. In mice that died after myocardial infarction, IFNIC colonies were immediately adjacent to sites of ventricular rupture, while mice lacking IFNICs were protected from rupture and exhibited improved survival3. Together, these results reveal a pathological borderzone niche characterized by a cardiomyocyte-initiated innate immune response. We suggest that selective inhibition of IRF3 activation in non-immune cells could limit ischaemic cardiomyopathy while avoiding broad immunosuppression.

Prevalence of mitral valve regurgitation in 102 asymptomatic Chinese Crested dogs.

INTRODUCTION: Mitral regurgitation (MR) is one of the main features of myxomatous mitral valve disease (MMVD), which is the most common heart disease in dogs. Myxomatous mitral valve disease affects many small breed dogs, and some breeds such as Cavalier King Charles Spaniels, Dachshunds, Yorkshire terriers, and Miniature Schnauzers have been studied more in detail. Breed-specific information regarding MMVD is valuable for providing appropriate advice on management and breeding. Data, based on insurance statistics in Sweden, show that Chinese Crested dogs (CCD) are twice as likely to visit the veterinarian for a heart-related problem than other breeds. ANIMALS: One-hundred two privately owned, healthy CCD were recruited via the Swedish CCD club. MATERIALS AND METHODS: This was a prospective observational study, in which clinical examinations, blood pressure measurements, and echocardiographic and Doppler examinations were performed in all dogs. Pulsed wave tissue Doppler imaging was performed in 87 dogs. RESULTS: Mitral regurgitation was present in 39 (38%) dogs, whereas a systolic murmur was present in 35 (34%) dogs. Mitral valve prolapse was present in 32 (31%) dogs. Tricuspid regurgitation was found in 29 (28%) dogs. Dogs in the MR group were older (median 9.5 years), and males were overrepresented compared with the non-MR group. Differences were also found between groups regarding left atrial size and transmitral E wave velocity. CONCLUSIONS: The prevalence of MR in CCD is similar to reports in other small breeds. Whether the MR detected in these dogs is a sign of MMVD is unknown.

Single-cell and spatial transcriptomics of the infarcted heart define the dynamic onset of the border zone in response to mechanical destabilization.

The border zone (BZ) of the infarcted heart is a geographically complex and biologically enigmatic interface separating poorly perfused infarct zones (IZs) from remote zones (RZs). The cellular and molecular mechanisms of myocardial BZs are not well understood because microdissection inevitably combines them with uncontrolled amounts of RZs and IZs. Here, we use single-cell/nucleus RNA sequencing, spatial transcriptomics and multiplexed RNA fluorescence in situ hybridization to redefine the BZ based on cardiomyocyte transcriptomes. BZ1 (Nppa + Xirp2 -) forms a hundreds-of-micrometer-thick layer of morphologically intact cells adjacent to RZs that are detectable within an hour of injury. Meanwhile, BZ2 (Nppa + Xirp2 +) forms a near-single-cell-thick layer of morphologically distorted cardiomyocytes at the IZ edge that colocalize with matricellular protein-expressing myofibroblasts and express predominantly mechanotransduction genes. Surprisingly, mechanical injury alone is sufficient to induce BZ genes. We propose a 'loss of neighbor' hypothesis to explain how ischemic cell death mechanically destabilizes the BZ to induce its transcriptional response.

Protective effects of glycoursodeoxycholic acid in Barrett's esophagus cells.

Barrett's esophagus (BE) is a premalignant condition associated with the development of esophageal adenocarcinoma (EAC). Previous studies have implicated hydrophobic bile acids and gastric acid in BE and EAC pathogenesis. In this study, we tested the hypothesis that DNA damage, cytotoxicity and oxidative stress induced by bile acids and gastric acid can be attenuated by the cytoprotective, hydrophilic bile acid glycoursodeoxycholic acid (GUDCA). Non-dysplastic BE cells were exposed for 10 min to pH 4 and/or bile acid cocktail or to pH 4 and a modified cocktail consisting of a mixture of bile acids and GUDCA. DNA damage was evaluated by the comet assay; cell viability and proliferation were measured by trypan blue staining and the MTS assay; reactive oxygen species (ROS) were measured using hydroethidium staining; oxidative DNA/RNA damage was detected by immunostaining with antibody against 8-OH-dG; thiol levels were measured by 5-chloromethylfluorescein diacetate (CMFDA) staining; and the expression of antioxidant proteins was evaluated by western blotting. DNA damage and oxidative stress were significantly increased, while thiol levels were decreased in BE cells treated with pH 4 and bile acid cocktail compared with cells treated with pH 4 alone or untreated cells. Bile acids and low pH also significantly decreased cell proliferation. Expression of the antioxidant enzymes, MnSOD and CuZnSOD, was elevated in the cells treated with bile acids and low pH. When GUDCA was included in the medium, all these effects of pH 4 and bile acids were markedly reduced. In conclusion, treatment of BE cells with acidified medium and a bile acid cocktail at physiologically relevant concentrations induces DNA damage, cytotoxicity, and ROS. The cytoprotective bile acid, GUDCA, inhibits these deleterious effects by inhibiting oxidative stress.

Anomalous patterns in cultured cell monolayers.

Gridlike patterns of differing cell density were observed in evenly seeded cell monolayers. Such patterns were obtained in five of six cell lines tested, suggesting widespread occurrence. The mechanism appears to involve small, transient temperature changes related to incubator tray structure. The very short time course of appearance of the patterns implicates attachment rather than growth as the critically affected factor. Impaired adhesion or directed sedimentation resulting from thermally induced microcurrents in the medium are the two most likely mechanisms.

Strategic location of calcium channels at transmitter release sites of frog neuromuscular synapses.

The localization of Ca2+ channels relative to the position of transmitter release sites was investigated at the frog neuromuscular junction (NMJ). Ca2+ channels were labeled with fluorescently tagged omega-conotoxin GVIA, an irreversible Ca2+ channel ligand, and observed with a confocal laser scanning microscope. The Ca2+ channel labeling almost perfectly matched that of acetylcholine receptors which were labeled with fluorescent alpha-bung-arotoxin. This indicates that groups of Ca2+ channels are localized exclusively at the active zones of the frog NMJ. Cross sections of NMJs showed that Ca2+ channels are clustered on the presynaptic membrane adjacent to the postsynaptic membrane.

Comparison of atazanavir with lopinavir/ritonavir in patients with prior protease inhibitor failure: a randomized multinational trial.

OBJECTIVES: To compare change from baseline in HIV RNA and fasting low-density lipoprotein (LDL) cholesterol levels in protease inhibitor (PI)-experienced patients receiving unboosted atazanavir 400 mg once daily versus lopinavir 400 mg boosted with ritonavir 100 mg twice daily, with two nucleoside reverse transcriptase inhibitors (NRTIs). Secondary objectives included virologic response, CD4 cell count changes, other lipid changes, safety, and tolerability. METHODS: Randomized, open-label, multinational, 48-week study in patients with one PI-regimen failure, HIV RNA > or = 1000 copies/mL, and CD4 count > or = 50 cells/mm3. RESULTS: Three hundred patients were randomized; 290 treated (144 atazanavir, 146 lopinavir/ritonavir). Lopinavir/ritonavir resulted in a significantly greater reduction in HIV RNA than unboosted atazanavir (-2.02 vs -1.59 log10 copies/mL, p < 0.001) at week 48. Secondary efficacy endpoints also favored lopinavir/ritonavir; the differences in efficacy between regimens were also observed in secondary analyses comparing those subjects who were susceptible and those subjects who were resistant to their respective PIs at baseline. However, both regimens were equally effective in subjects who had no baseline NRTI mutations. From baseline to week 48, atazanavir resulted in either no change or decreases in fasting LDL cholesterol, total cholesterol, and fasting triglycerides (-6%, -2%, and +1%), whereas lopinavir/ritonavir resulted in increases (+3%, +12%, and +53%) (p < 0.05, all between-treatment comparisons). Fewer patients were administered lipid-lowering therapy in the atazanavir arm (6% vs 20% for lopinavir/ritonavir). Both regimens were safe and well tolerated. CONCLUSIONS: While both treatments demonstrated good antiviral efficacy, relatively greater antiviral suppression was observed with lopinavir/ritonavir. In those patients with no NRTI mutations at baseline, both regimens demonstrated comparable virologic suppression. Atazanavir-treated patients demonstrated a superior lipid profile and required less frequent lipid-lowering treatment.

Cholestatic hepatic injury related to warfarin exposure.

Despite the widespread use of oral anticoagulants derived from 4-hydroxycoumarin, there have been only a small number of well-defined cases of hepatotoxicity. We report a well-defined case of cholestasis following exposure to warfarin sodium (Coumadin). Inadvertent rechallenge reproduced the syndrome. Cholestasis may occur in response to exposure to derivations of 4-hydroxycoumarin.

On the dissociation constants of BAPTA-type calcium buffers.

We have determined or redetermined the calcium dissociation constants of seven BAPTA-type buffers with KD's in the range from 0.4 microM to about 20 mM in 300 mM KCl. These include four newly synthesized ones: 5-nitro BAPTA; 5,5'-dinitro BAPTA; 5-methyl-5'-nitro BAPTA; and 5-methyl-5'-formyl BAPTA. Moreover, we tabulate dissociation constants or KD's for BAPTA and eleven BAPTA-type buffers, compare most of them with an empirical curve based upon so-called Hammett values, and predict KD's for several still unsynthesized but potentially valuable buffers.

Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum.

A cDNA fragment homologous to other G protein-coupled receptors was isolated from rat brain using the PCR method and demonstrated to be abundantly expressed in striatum. Using this fragment as a probe, a 2.1 kb full-length cDNA was isolated from a rat striatal cDNA library. This cDNA encodes a protein of 410 amino acids and is highly homologous to previously isolated adenosine receptor cDNAs. Expression of this cDNA in COS cells revealed high affinity (Kd = 38.6 nM) and saturable binding of the A2 adenosine receptor-selective ligand [3H]CGS 21680. Agonist displacement profile of [3H]CGS 21680 binding was consistent with an adenosine receptor of the A2 subtype (NECA greater than (R)-PIA greater than CPA greater than (S)-PIA). In situ hybridization demonstrated that rat A2 adenosine receptor mRNA was co-expressed in the same striatal neurons as D2 dopamine receptor mRNA, and never co-expressed with striatal D1 dopamine receptor mRNA. Several lines of evidence have previously suggested that dopamine-induced changes in motor behavior can be modulated by adenosine analogs acting at the A2 subtype of adenosine receptor in the forebrain. The co-expression of D2 dopamine and A2 adenosine receptors in a subset of striatal cells provides an anatomical basis for dopaminergic-adenosinergic interactions on motor behavior.

Comparative efficacy of two angiotensin II receptor antagonists, irbesartan and losartan in mild-to-moderate hypertension. Irbesartan/Losartan Study Investigators.

The primary objectives of this double-blind study were to compare the antihypertensive efficacy and tolerability of irbesartan and losartan, two angiotensin II (AT1 subtype) receptor antagonists with different pharmacokinetic profiles in patients with mild-to-moderate hypertension. Both drugs are approved for once-daily use (although losartan may also be prescribed twice-daily). After a placebo lead-in, 567 patients were randomized (1:1:1:1) to once-daily therapy with placebo, 100 mg losartan, 150 mg irbesartan, or 300 mg irbesartan for 8 weeks. Treatment groups had comparable demographic and baseline characteristics. After 8 weeks of treatment, reductions from baseline in trough seated diastolic blood pressure (SeDBP) and trough seated systolic blood pressure (SeSBP) with 300 mg irbesartan were greater than with 100 mg losartan (P < .01 for both comparisons), by 3.0 and 5.1 mm Hg, respectively; larger reductions were also demonstrated at weeks 1 and 4 (P < .01 and P = .017, respectively, for SeDBP). Throughout the study, the antihypertensive effect of 150 mg irbesartan did not differ significantly from that of 100 mg losartan. All therapies were well tolerated. The 300 mg dose of irbesartan was associated with the lowest incidence of adverse events (AE) and discontinuations because of AE. This study demonstrates that the maximally effective once-daily doses of two different AT1 receptor antagonists may result in clinically significant differences in blood pressure reductions, and therefore highlights the potential importance of the pharmacokinetic and pharmacodynamic differences between these two members of this class.

Calcium channels and calcium-gated potassium channels at the frog neuromuscular junction.

Two mechanisms which regulate transmitter release by regulating Ca2+ entry in the presynaptic nerve terminal were studied at the frog neuromuscular junction (nmj). First, the location of Ca2+ channels in relation to transmitter release sites and, second, the regulation of Ca2+ entry by Ca(2+)-gated potassium (gKca) channels. Ca2+ channels were disclosed using fluorescent omega-conotoxin GVIA (omega-CgTX) which blocks transmitter release and Ca2+ entry at the frog nmj. Ca2+ channels were located in bands spaced at regular intervals of 1 micron. The omega-CgTX labeling was removed following mechanical displacement of the presynaptic terminal after collagenase digestion. The bands of omega-CgTX staining matched almost perfectly the staining of cholinergic receptors with fluorescent alpha-bungarotoxin (alpha-BuTX) and therefore must be located at the active zone. The role of gKca channels in the regulation of transmitter release was assessed using charybdotoxin (ChTX) which blocks gKca channels of large and intermediate conductances. Application of ChTX (2-20 nM) induced a two-fold increase in transmitter release which was prevented when a membrane permeant Ca2+ buffer (DMBAPTA-AM) was introduced prior to the toxin application. The Ca2+ buffer by itself caused a reduction in transmitter release. Nerve-evoked Ca2+ entry in the presynaptic terminal, detected with the fluorescent indicator fluo3, was increased following gKca channel blockade by ChTX. The Ca(2+)-gated K+ channels may function to limit the duration of the presynaptic action potential and thus limit Ca2+ entry.

Presynaptic calcium signals during neurotransmitter release: detection with fluorescent indicators and other calcium chelators.

Synthetic calcium buffers, including fluorescent calcium indicators, were microinjected into squid 'giant' presynaptic nerve terminals to investigate the calcium signal that triggers neurotransmitter secretion. Digital imaging methods, applied in conjunction with the fluorescent calcium indicator dye fura-2, reveal that transient rises in presynaptic calcium concentration are associated with action potentials. Transmitter release terminates within 1-2 ms after a train of action potentials, even though presynaptic calcium concentration remains at micromolar levels for many seconds longer. Microinjection of the calcium buffer, EGTA, into the presynaptic terminal has no effect on transmitter release evoked by single presynaptic action potentials. EGTA injection does, however, block the change in calcium concentration measured by fura-2. Therefore, the calcium signal measured by fura-2 is not responsible for triggering release. These results suggest that the rise in presynaptic calcium concentration that triggers release must be highly localized to escape detection with fura-2 imaging. Unlike EGTA, microinjection of BAPTA--a calcium buffer with an equilibrium affinity for calcium similar to that of EGTA--produces a potent, dose-dependent, and reversible block of action-potential evoked transmitter release. The superior ability of BAPTA to block transmitter release apparently is due to the more rapid calcium-binding kinetics of BAPTA compared to EGTA. Because EGTA should bind calcium within a few tens of microseconds under the conditions of our experiments, the inability of EGTA to block release indicates that transmitter release is triggered within a few tens of microseconds after the entry of calcium into the presynaptic terminal.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency-dependent action of phenytoin on lamprey spinal axons.

The effect of the antiepileptic drug phenytoin (diphenylhydantoin, DPH) was tested on the conduction of intracellularly recorded action potentials in lamprey giant reticulospinal axons. When the isolated spinal cord was exposed to 80 microM DPH for up to 4 h, no significant effect was seen on the amplitude or conduction velocity of the action potential, although the maximum rate of rise was reduced from 247.8 to 149.6 V/s after 1 h. However, at higher stimulus frequencies both the amplitude and conduction velocity of the action potential were reduced progressively during a 500 stimulus train. The reduction was greater the higher the stimulus frequency, and was reversed upon return to 1 Hz stimulation. At frequencies greater than 40 Hz an all-or-none block developed. This also developed sooner the higher the stimulus frequency. Axons bathed in drug-free solutions did not show this effect at stimulus frequencies up to 100 Hz. Similar effects were seen in 16 microM DPH when the spinal cord was exposed to the drug overnight. This is close to the human therapeutic CSF level. The frequency-dependent depression of the action potential was greatly potentiated by increasing the extracellular potassium concentration from 2.1 to 5 mM. Under these conditions the axons rapidly developed block at stimulus frequencies as low as 2 Hz, and this was not reversible during a 5 h wash. In the absence of DPH, 5 mM potassium produced a 4-5 mV depolarization, but did not induce a frequency-dependent block. This effect of potassium may be important to the therapeutic effect of DPH because during epileptiform activity the extracellular K+ increases several fold.

Zinc elevates neuropeptide Y levels in rat pheochromocytoma cells by a mechanism independent of L-channel mediated inhibition of release.

Both zinc and neuropeptide Y (NPY) have been implicated as playing a role in seizures and feeding behavior. We investigated the hypothesis that zinc could regulate levels of NPY, and found that chronic exposure to 50-100 microM zinc increased levels of cellular NPY in cultured PC12 cells grown in the presence of nerve growth factor. Zinc's effect on NPY was specific, time- and concentration-dependent, and independent of inhibition of NPY release secondary to blockade of dihydropyridine-sensitive calcium channels. These results are consistent with a role for zinc in regulating hippocampal NPY following high-frequency neuronal activity.

Oil bioremediation using insoluble nitrogen source.

Oil bioremediation is limited by the availability of nitrogen and phosphorous, which are needed by the bacteria and not present in sufficient amounts in hydrocarbons. The supply of these two essential elements as water-soluble salts presents several problems. These include the rapid dilution of the salts in the large volumes of polluted land or water and their utilization by other bacteria that do not degrade oil. In addition, increasing the concentration of mobile nitrogen creates further environmental problems. The use of hydrophobic sources of nitrogen and phosphorous that have a low water solubility can overcome these problems. We have studied one such compound. F-1, that is not used by most bacteria but serves as a good nitrogen and phosphorous source for those bacterial strains that are capable of utilizing it. We have shown that bacteria using F-1 do not cross-feed other bacterial strains. Moreover, when the concentration of the pollutant is sufficiently reduced, the multiplication of the bacteria slows down until they become a negligible fraction of the bacterial population. Chemical analysis indicated that following a 28-day treatment of Alaskan crude oil, most of the hydrocarbons, including polycyclic aromatics, are degraded to undetectable levels. The C34 and C35 components were also degraded, although their degradation was not completed within this time period. In treatment of a sandy beach that was accidentally polluted with crude heavy oil, about 90% degradation was obtained within about 4 months at an outside average temperature of 5 -10 degrees C.

Analysis of frozen sections of intraoperative specimens obtained at the time of reoperation after hip or knee resection arthroplasty for the treatment of infection.

BACKGROUND: Despite the effectiveness of a two-stage exchange protocol for the treatment of deep periprosthetic infection, infection can persist after resection arthroplasty and treatment with antibiotics, leading to a failed second-stage reconstruction. Intraoperative analysis of frozen sections has been shown to have a high sensitivity and specificity for the identification of infection at the time of revision arthroplasty; however, the usefulness of this test at the time of reoperation after resection arthroplasty and treatment with antibiotics is, to our knowledge, unknown. METHODS: The medical records of sixty-four consecutive patients who had had a resection arthroplasty of either the knee (thirty-three patients) or the hip (thirty-one patients) and had had intraoperative analysis of frozen sections of periprosthetic tissue obtained at the time of a second-stage operation were reviewed. The mean interval between the resection arthroplasty and the attempted reimplantation was nineteen weeks. The results of the intraoperative analysis of the frozen sections were compared with those of analysis of permanent histological sections of the same tissues and with those of intraoperative cultures of specimens obtained from within the joint. The findings of the analyses of the frozen sections and the permanent histological sections were considered to be consistent with acute inflammation and infection if a mean of ten polymorphonuclear leukocytes or more per high-power field (forty times magnification) were seen in the five most cellular areas. RESULTS: The intraoperative frozen sections of the specimens from two patients (one of whom was considered to have a persistent infection) met the criteria for acute inflammation. Four patients were considered to have a persistent infection on the basis of positive intraoperative cultures or permanent histological sections. Overall, intraoperative analysis of frozen sections at the time of reimplantation after resection arthroplasty had a sensitivity of 25 percent (detection of one of four persistent infections), a specificity of 98 percent, a positive predictive value of 50 percent (one of two), a negative predictive value of 95 percent, and an accuracy of 94 percent. CONCLUSIONS: A negative finding on intraoperative analysis of frozen sections has a high predictive value with regard to ruling out the presence of infection; however, the sensitivity of the test for the detection of persistent infection is poor.

Selected risk factors in pediatric adenotonsillectomy.

OBJECTIVE: To evaluate the ability of a set of cost-effective criteria to identify before surgery the pediatric patients in whom perioperative respiratory compromise is most likely to develop after adenotonsillectomy. SETTING: A children's hospital medical center. DESIGN: Prospective study using preoperative parental questionnaires and perioperative respiratory status documentation. PATIENTS: All patients scheduled at the outpatient clinic were eligible. MAIN OUTCOME MEASURE: The development of respiratory compromise as defined by at least 1 of the following occurring more than 2 hours after surgery: an oxygen desaturation level of less than 90%, an obstructive breathing pattern, or respiratory distress requiring intervention. RESULTS: The risk of respiratory compromise was significantly increased in patients who were younger than 3 years (P < .001) and in those who had neuromuscular disorders (P < .05), chromosomal abnormalities (P < .005), difficulty in breathing during sleep (P < .005), restless sleep (P < .01), loud snoring with apnea (P < .05), or an upper respiratory tract infection within 4 weeks of surgery (P = .005). Respiratory compromise did not develop in any patients who did not snore (P < .05). CONCLUSIONS: A complete history that includes symptoms suggestive of sleep apnea will assist in the preoperative identification of pediatric patients most at risk for perioperative respiratory compromise after undergoing adenotonsillectomy. Such patients might benefit from overnight observation in a hospital setting. However, when snoring is absent, outpatient surgery is appropriate, as the risk of respiratory compromise is minimal.

Fractal organization of the pointwise correlation dimension of the heart rate.

OBJECTIVE: To depict and quantify the degree of organization of the heart rate variability (HRV) in normal subjects. METHODS: A modified algorithm was created to estimate series of 'point-dimensions' (PD2) from interbeat (R-R) interval series of 10 healthy subjects (21-56 years). Our innovation is twofold: (i) we quantified instances of low-dimensional chaos, random fluctuations, and those for which our method failed to provide either (due to poor statistics); (ii) consecutive subepochs of PD2s underwent a relative dispersion (RD) analysis, yielding an index (D) which quantifies the dynamical organization of the heart rate generator. RESULTS: The mean values of PD2 series varied between 4.58 and 5.88 (mean+/-SD= 5.21+/-0.41, n = 10). For group 1 (21-30 years, n = 6) we found an averaged PD2 of 5.49+/-0.27, while for group 2 (47-56 years, n = 4) PD2 averaged 4.79+/-0.17. The RD analysis performed for subepochs of PD2s yielded both instances obeying fractal scaling (D < 1.5) and stochasticity (D > 1.5). The average D for group 1 was 1.39+/-0.04 (14 subepochs) and for group 2, 1.20+/-0.008 (8 subepochs). Paired t-test and Hartley F-max test for comparison between D values and homogeneity of variance between the two groups were performed, yielding P-values 0.004 and 0.02, respectively. CONCLUSIONS: The complexity of the HRV seems to be modulated by a non-random fractal mechanism of a 'hyperchaotic' system, i.e. it can be hypothesized to contain more than one attractor. Also, our results support the 'chaos hypothesis' put forth recently, namely, the complexity of the cardiovascular dynamics is reduced with aging. The index of relative dispersion of the dimensional complexity has to be tested in various clinico-pathological settings, in order to corroborate its value as a potential new physiological measure.

Naso- and oropharyngeal dimensions in children with obstructive sleep apnea.

Sixty children (3-11 years) were evaluated to determine variations in naso- and oropharyngeal dimensions associated with tonsil and adenoid hypertrophy. The subjects were grouped according to tonsil size and a clinical history of chronic upper airway obstruction. Intraoperative measurements included oropharyngeal diameter, length of the hard and soft palates, width and arch of the hard palate, nasopharyngeal volume, as well as tonsil and adenoid weights and volumes. A significantly larger oropharyngeal diameter was found in children with small, non-obstructing tonsils (P less than 0.01). Children with large, non-obstructing tonsils had a similar oropharyngeal diameter to those children with large, obstructing tonsils. However, tonsil volume, not weight, was increased in the children with large obstructing tonsils as compared to those with large non-obstructing tonsils and small non-obstructing tonsils (P less than 0.04). A shorter soft palate was associated with larger, obstructing tonsils (P less than 0.004). The length of the hard palate was similar in all patients, however, a trend towards a higher arched palate was seen in patients with larger, obstructing tonsils. The distance from the soft palate to the posterior pharyngeal wall was greater in obstructed patients with adenotonsillar hypertrophy (P less than 0.003). In patients requiring adenoidectomy, the nasopharyngeal volume prior to adenoidectomy was significantly smaller in patients with obstructive symptoms (P less than 0.001). Postadenoidectomy, no significant difference was found in the nasopharynx volume amongst all subjects. These data indicate that subtle differences in oropharyngeal dimensions exist which along with increased lymphoid tissue volume, lead to the development of obstructive symptoms. Etiologic considerations are discussed.