Serotonin modifies the spontaneous spiking activity of gracile nucleus neurons in rats: role of 5-HT1A and 5-HT2 receptors.

We tested the effects of microiontophoretic application of serotonin (5-HT) on the firing rate of neurons located in the gracile nucleus (GN) of rats. Application of 5-HT1A and 5-HT2 agonists and antagonists respectively mimicked/ modulated and blocked the effects produced by the amine, respectively. Among the tested neurons, 88.2% modified their background firing activity in the presence of 5-HT. Responsive neurons decreased their mean firing activity (MFA) in 56.7% of cases and increased it in the remaining 43.3%. To ascertain the specificity of the effects induced by 5-HT, we utilized 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and alpha-methyl-5-hydroxytryptamine (α-MET-5-HT), agonists for 5-HT1A and 5-HT2 receptors, respectively. The microiontophoresis of 8-OH-DPAT modified the background firing rate of all GN neurons (100% of tested neurons) mimicking the decrease of MFA evoked by 5-HT. The application of a-MET-5-HT modified the MFA in 76.9% of tested neurons, decreasing it in 61.5% of cases and increasing in the remaining 23.1%. The decrease of MFA induced by 8-OH-DPAT was antagonized by application of the 5-HT1A receptor antagonist N-[2-[-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY100635), while application of 5-HT2 receptor antagonist ketanserine tartrate (KET) antagonized only the increase of MFA induced by a-MET-5-HT. These results indicate that 5-HT is able to modulate the background firing activity of GN neurons by 5-HT1A and 5-HT2 receptors.

Effects of bicuculline application on the somatosensory responses of secondary vestibular neurons.

Limb somatosensory signals modify the discharge of vestibular neurons and elicit postural reflexes, which stabilize the body position. The aim of this study was to investigate the contribution of the γ-amino-butyric-acid (GABA) to the responsiveness of vestibular neurons to somatosensory inputs. The activity of 128 vestibular units was recorded in anesthetized rats in resting conditions and during sinusoidal foreleg rotation around the elbow or shoulder joints (0.026-0.625Hz, 45° peak amplitude). None of the recorded units was influenced by elbow rotation, while 40% of them responded to shoulder rotation. The selective GABAA antagonist receptor, bicuculline methiodine (BIC), was applied by microiontophoresis on single vestibular neurons and the changes in their activity at rest and during somatosensory stimulation was studied. In about half of cells the resting activity increased after the BIC application: 75% of these neurons showed also an increased response to somatosensory inputs whereas 17% exhibited a decrease. Changes in responsiveness in both directions were detected also in the units whose resting activity was not influenced by BIC. These data suggest that the responses of vestibular neurons to somatosensory inputs are modulated by GABA through a tonic release, which modifies the membrane response to the synaptic current. It is also possible that a phasic release of GABA occurs during foreleg rotation, shaping the stimulus-elicited current passing through the membrane. If this is the case, the changes in the relative position of body segments would modify the GABA release inducing changes in the vestibular reflexes and in learning processes that modify their spatio-temporal development.

Noradrenergic modulation of neuronal responses to n-methyl-d-aspartate in the vestibular nuclei: an electrophysiological and immunohistochemical study.

Excitatory responses evoked by N-methyl-d-aspartate (NMDA) in the vestibular nuclei (VN) of the rat were studied in vivo during microiontophoretic application of noradrenaline (NA) and/or its agonists and antagonists. Ejection of NA-modified excitatory responses mediated by NMDA receptors (NMDAR) in all neurons tested; the effect was enhancement in 59% of cases and depression in the remaining 41%. Enhancements prevailed in all VN with the exception of the lateral vestibular nucleus, where both effects were recorded in an equal number of cases. The enhancing action of NA on NMDAR-mediated responses was mimicked by the noradrenergic beta-receptor agonist isoproterenol, the beta1 specific agonist denopamine and the alpha2 agonist clonidine. These effects were blocked respectively by the generic beta-receptor antagonist timolol, the beta1 antagonist atenolol and the alpha2 antagonist yohimbine. In contrast, application of the alpha1 receptor agonist cirazoline and the specific alpha1 antagonist prazosin respectively mimicked and partially antagonized the depression of NMDAR-mediated excitations induced by NA. Double-labeling immunohistochemical techniques demonstrated broad colocalization of NMDAR (specifically NR1 and NR2 subunits) with noradrenergic receptors (alpha1, alpha2 and beta1) in many VN neurons; only minor differences were found between nuclei. These results indicate that NA can produce generalized modulation of NMDAR-mediated excitatory neurotransmission in VN, which may in turn modify synaptic plasticity within the nuclei.

Effects of body to head rotation on the labyrinthine responses of rat vestibular neurons.

Vestibulospinal reflexes elicited by head displacement in space depend on the direction of body displacement, because the neuronal responses to labyrinthine stimulation are tuned by neck displacement: a directional tuning takes place in the medial cerebellum and in spinal motoneurons, while a gain and a basal activity tuning can be observed in the reticular formation, a target structure of the medial cerebellum. In the present study, we investigated whether also the response of vestibular nuclear neurons (another target of the medial cerebellum) to labyrinthine stimulation is tuned by neck displacement and which parameters of the response are modulated by it. In urethane-anaesthetized Wistar rats, single-unit activity was recorded from the vestibular nuclei at rest and during wobble of the whole animal at 0.156 Hz. This stimulus tilted the animal's head by a constant amplitude (5°), in a direction rotating at a constant velocity over the horizontal plane, either in clockwise or counter clockwise direction. The gain and the direction of neuronal responses to wobble were evaluated through Fourier analysis, in the control position (with coincident head and body axes) and following a body-to-head rotation of 5-30° over the horizontal plane, in both directions. Most of the vestibular neurons modified their response gain and/or their basal activity following body-to-head rotation, as it occurs in the reticular formation. Only few neurons modified their response direction, as occurs in the cerebellum and in spinal motoneurons. The different behaviour of cerebellar neurons and of their vestibular and reticular target cells, suggests that the role played by the cerebellum in the neck tuning of vestibulospinal reflexes has to be reconsidered.

Non-enhanced MR angiography of renal arteries: comparison with contrast-enhanced MR angiography.

BACKGROUND: The main causes of renal artery stenosis (RAS) are atherosclerosis and fibromuscular dysplasia. Despite contrast-enhanced magnetic resonance angiography (CE-MRA) being a safe and reliable method for diagnosis of RAS especially in young individuals, recently it has been possible to adopt innovative technologies that do not require paramagnetic contrast agents. PURPOSE: To assess the accuracy of steady-state free-precession (SSFP) non-contrast-enhanced magnetic resonance angiography (NC-MRA) by using a 1.5 T MR scanner for the detection of renal artery stenosis, in comparison with breath-hold CE-MRA as the reference standard. MATERIAL AND METHODS: Sixty-three patients (33 men, 30 women) with suspected renovascular hypertension (RVHT) were examined by a 1.5T MR scanner; NC-MRA with an electrocardiography (ECG)-gated SSFP sequence was performed in 58.7% (37/63) of patients; in 41.3% (26/63) of patients a respiratory trigger was used in addition to cardiac gating. CE-MRA, with a three-dimensional gradient echo (3D-GRE) T1-weighted sequence, was performed in all patients within the same session. Maximum intensity projection (MIP) image quality, number of renal arteries, and the presence of stenosis were assessed by two observers (independently for NC-MRA and together for CE-MRA). The agreement between NC-MRA and CE-MRA as well as the inter-observer reproducibility were calculated with Bland-Altman plots. RESULTS: MIP image quality was considered better for NC-MRA. NC-MRA identified 143 of 144 (99.3%) arteries detected by CE-MRA (an accessory artery was not identified). Fourteen stenoses were detected by CE-MRA (11 atherosclerotic, 3 dysplastic) with four of 14 (28.5%) significant stenosis. Bland-Altman plot demonstrated an excellent concordance between NC-MRA and CE-MRA; particularly, the reader A evaluated correctly all investigated arteries, while over-estimation of two stenoses occurred for reader B. Regarding NC-MRA, inter-observer agreement was excellent. CONCLUSION: NC-MRA is a valid alternative to CE-MRA for the assessment of renal arteries.

A new technique to investigate vestibulo-spinal reflexes.

Vestibulospinal reflexes can be elicited in humans by low amplitudes direct (galvanic) currents lasting tens of milliseconds and applied across the two mastoids bones, which can be delivered by particular stimulators. The stimulus induces a perception of body sway and a postural response appropriate to counteract the perceived sway. Both the direction of the perceived and induced body sway are modulated by the orientation of the head with respect to the body. This phenomenon is due to the fact that integration of vestibular and neck signals allows to correctly infer the direction of body sway from the labyrinthine input, which is instead related to direction of head motion. The modulation of stimulus-elicited body sway by neck rotation could be utilised for testing the effectiveness of neck proprioceptive signals in modifying the reference frame for labyrinthine signals from the head to the body. In the present experiments we showed that labyrinthine stimulation can be performed also by using train of pulses of 1 msec duration, which can be delivered by virtually all stimulators allowed for human use. Moreover, we developed a simple technique for visualising the time course of the changes in the direction of the postural response, based on the evaluation of the velocity vector of subject's centre of pressure. This method could be exploited in order to the test the efficacy of neck proprioceptive information in modifying the reference frame for processing vestibular signals in both physiological and pathological condition.

Pharmacogenomic update on multiple sclerosis: a focus on actual and new therapeutic strategies.

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of central nervous system comprising several subtypes. Pharmacological treatment involves only few drugs. Among these, interferon beta (IFN-ß) and glatiramer acetate were the most used. Although evidence supports the efficacy of these agents in treating MS symptoms, actual studies allowed to introduce new innovative drugs in clinical practice. Applying pharmacogenetic approach to MS, IFN-ß and several other immune pathways were abundantly investigated. Numerous reports identified some promising therapy markers but only few markers have emerged as clinically useful. This may be partially due to differences in clinical and methodological criteria in the studies. Indeed, responder and non-responder definitions lack standardized clinical definition. The goal of this review is to treat advances in research on the pharmacogenetic markers of MS drugs and to highlight possible correlations between type of responses and genetic profile, with regard to clinical and methodological discrepancies in the studies.

Effects of trunk-to-head rotation on the labyrinthine responses of rat reticular neurons.

Vestibulospinal reflexes elicited by head displacement become appropriate for body stabilization owing to the integration of neck input by the cerebellar anterior vermis. Due to this integration, the preferred direction of spinal motoneurons' responses to animal tilt rotates by the same angle and by the same direction as the head over the body, which makes it dependent on the direction of body displacement rather than on head displacement. It is known that the cerebellar control of spinal motoneurons involves the reticular formation. Since the preferred directions of corticocerebellar units' responses to animal tilt are tuned by neck rotation, as occuring in spinal motoneurons, we investigated whether a similar tuning can be observed also in the intermediate station of reticular formation. In anaesthetized rats, the activity of neurons in the medullary reticular formation was recorded during wobble of the whole animal at 0.156 Hz, a stimulus that tilted the animal's head by a constant amplitude (5°), in a direction rotating clockwise or counter clockwise over the horizontal plane. The response gain and the direction of tilt eliciting the maximal activity were evaluated with the head and body axes aligned and during a maintained body-to-head displacement of 5-20° over the horizontal plane, in either direction. We found that the neck displacement modified the response gain and/or the average activity of most of the responsive neurons. Rotation of the response direction was observed only in a minor percentage of the recorded neurons. The modifications of reticular neurons' responses were different from those observed in the P-cells of the cerebellar anterior vermis, which rarely showed gain and activity changes and often exhibited a rotation of their response directions. In conclusion, reticular neurons take part in the neck tuning of vestibulospinal reflexes by transforming a head-driven sensory input into a body-centred postural response. The present findings prompt re-evaluation of the role played by the reticular neurons and the cerebellum in vestibulospinal reflexes.

"Full metal jacket" with direct stenting of complete chronic occlusions of the superficial femoral artery.

PURPOSE: This study evaluated the short- and midterm patency of complete total occlusions of the superficial femoral artery (SFA) treated with direct stenting. MATERIALS AND METHODS: Fifty-two consecutive patients (36 men and 16 women; mean age 73.6 years; range 58-85) with chronic complete SFA occlusion and good distal run-off (two or three patent vessels) underwent endovascular recanalisation by direct stenting. All patients were symptomatic (severe claudication or critical ischaemia). Recanalisation was achieved by using a contralateral approach in 44 patients and an ipsilateral antegrade access in eight patients. A total of 152 nitinol stents were used: three stents in 32 cases, four stents in eight cases and two stents in 12 cases. Follow-up consisted of clinical evaluation and colour Doppler ultrasound at 6, 12, 18 and 24 months. RESULTS: The immediate technical success rate was 100%, with complete SFA recanalisation documented on postprocedural angiography. Four cases of distal embolism occurred, which were treated successfully with intra-arterial thrombolysis. During the follow-up, 12 reocclusions were observed: eight were treated with mechanical thrombectomy and in-stent angioplasty, and four were converted into femoropopliteal bypasses. The primary patency rates at 6, 12, 18 and 24 months were 92.3%, 76.9%, 69.2% and 69.2%, respectively. The secondary patency rates at 6, 12, 18 and 24 months were 100%, 100%, 92.3% and 92.3%. CONCLUSIONS: The percutaneous treatment of chronic complete SFA occlusions yielded good primary and secondary patency rates in the short and medium term, with few periprocedural complications. Reocclusions were treated using the percutaneous technique, which guarantees a good secondary patency rate.

Tuning of human vestibulospinal reflexes by leg rotation.

Changing the foot position modifies the mechanical action exerted by the ankle extensor and flexor muscles over the body. We verified, in two groups of healthy subjects standing with the heels touching or apart, whether a 90° external rotation of the right leg and foot also changes the pattern of vestibulospinal reflexes elicited by electrical stimulation of the labyrinth. With the head oriented forward, leg rotation did not modify the labyrinthine-driven displacements of the center of pressure (CoP). When the head was rotated in the horizontal plane, either to the right or to the left, the CoP displacement increased along the y axis in all subjects. Changes in the x component in most instances appropriate to preserve unmodified the direction of body sway elicited by the stimulus were observed. Right leg rotation increased the basal EMG activity of ankle extensors and flexors on the left side, while the right side activity was unaffected. The EMG responses to labyrinthine stimulation were modified only on the left side, in a way appropriate to correct the effects of the altered torque pattern exerted on the body by right leg muscles. It appears, therefore, that somatosensory signals related to leg rotation and/or copy of the corresponding voluntary motor commands modify the pattern of vestibulospinal reflexes and maintain the postural response appropriate to counteract a body sway in the direction inferred by labyrinthine signals.

Comparative study of jaws with multislice computed tomography and cone-beam computed tomography.

PURPOSE: The aim of this study was to compare the dosimetric and diagnostic performance of multislice computed tomography (MSCT) and cone-beam computed tomography (CBCT) in the study of the dental arches. MATERIALS AND METHODS: Effective dose and dose to the main organs of the head and neck were evaluated by means of thermoluminescent dosimeters (TLDs) placed in an Alderson Rando anthropomorphic phantom and using a standard CBCT protocol and an optimised MSCT protocol. Five patients with occlusal plane ranging from 54 cm to 59 cm who needed close follow-up (range 1-3 months) underwent both examinations. Image quality obtained with CBCT and MSCT was evaluated. RESULTS: Effective dose and dose to the main organs of the head and neck were higher for MSCT than for CBCT. Image quality of CBCT was judged to be equivalent to that of MSCT for visualising teeth and bone but inferior for visualising soft tissues. Beam-hardening artefacts due to dental-care material and implants were weaker at CBCT than at MSCT. CONCLUSIONS: When panoramic radiography is not sufficient in the study of the teeth and jaw bones, CBCT can provide identical information to MSCT, with a considerable dose reduction. MSCT is, however, indicated when evaluation of soft tissue is required.

Percutaneous treatment of complete chronic occlusions of the superficial femoral artery.

PURPOSE: This study was done to evaluate the mid-and long-term patency rates of complete (from the origin to Hunter's duct) chronic occlusions of the superficial femoral artery (SFA) treated by angioplasty and/or stenting. MATERIALS AND METHODS: From February 2002 to March 2005, 21 patients with complete occlusion of the SFA and good distal runoff (two or three patent vessels) were treated with endovascular recanalisation. All patients had severe claudication or critical limb ischaemia. In all cases, recanalisation was performed with a contralateral approach by percutaneous transluminal angioplasty (PTA), with stenting only when PTA provided unsatisfactory results (due to elastic recoil and complications such as dissection). In the case of calcified occlusions and when the true lumen of the SFA could not be crossed, subintimal angioplasty was performed. Follow-up was done at 6 and 12 months and annually thereafter (range 6-55 months, mean 23 months) with clinical evaluation and colour-Doppler ultrasound. RESULTS: Immediate technical success was achieved in all cases (100%), with post-procedural angiography demonstrating complete recanalisation of the SFA. Two distal embolisation (9.5%) occurred, both treated successfully by local thrombolysis. Primary patency rates at 6, 12, 24, 32 and 44 months were 93.3%, 69.2%, 72.7%, 62.5% and 40%, respectively; secondary patency rates at 6, 12 and 24 months were 100%, 84.6% and 81.8%, respectively. CONCLUSIONS: Percutaneous treatment of complete chronic occlusions of the SFA showed good mid-and long-term primary patency rates, with few periprocedural complications. Re-occlusions can be treated by a percutaneous technique, which ensures a good secondary patency rate.

Generality of vertebrate developmental patterns: evidence for a dermomyotome in fish.

The somitic compartment that gives rise to trunk muscle and dermis in amniotes is an epithelial sheet on the external surface of the somite, and is known as the dermomyotome. However, despite its central role in the development of the trunk and limbs, the evolutionary history of the dermomyotome and its role in nonamniotes is poorly understood. We have tested whether a tissue with the morphological and molecular characteristics of a dermomyotome exists in nonamniotes. We show that representatives of the agnathans and of all major clades of gnathostomes each have a layer of cells on the surface of the somite, external to the embryonic myotome. These external cells do not show any signs of terminal myogenic or dermogenic differentiation. Moreover, in the embryos of bony fishes as diverse as sturgeons (Chondrostei) and zebrafish (Teleostei) this layer of cells expresses the pax3 and pax7 genes that mark myogenic precursors. Some of the pax7-expressing cells also express the differentiation-promoting myogenic regulatory factor Myogenin and appear to enter into the myotome. We therefore suggest that the dermomyotome is an ancient and conserved structure that evolved prior to the last common ancestor of all vertebrates. The identification of a dermomyotome in fish makes it possible to apply the powerful cellular and genetic approaches available in zebrafish to the understanding of this key developmental structure.

Effects of 5-hydroxytryptamine on the neuronal firing rate of bulbar reticular neurons.

The effects of 5-hydroxytryptamine (5-HT) on neuronal firing rate were studied in the reticular gigantocellular nucleus (GRN) and, for a comparison, in the interstitial (IRN), the parvicellular (PRN) and the lateral (LRN) nuclei, sharing some of GRN functional characteristics. Unitary extracellular recordings performed in anesthetized rats demonstrated that microiontophoretic application of 5-HT modulated the background firing rate in 92% of GRN, in 100% of IRN and LRN, and in 77% of PRN tested neurons. In GRN, 5-HT application induced excitatory responses in 49% of the neurons tested and inhibitions in 43% of them. Both types of effects were dose dependent and appeared scattered throughout the nucleus. Enhancements and decreases of firing rate in response to 5-HT application were also recorded in IRN (58% and 42% respectively), LRN (43% and 57%) and PRN (36% and 41%). The 5-HT(1A) receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) mimicked 5-HT evoked inhibitions in all the nuclei tested and induced weak inhibitory responses also in neurons excited by 5-HT. The 5-HT2A receptor agonist alphamethyl-5-hydroxytryptamine (alpha-me-5-HT) mimicked excitatory as well as inhibitory responses to 5-HT, the former prevailing in GRN and the latter in the remaining reticular nuclei. Both excitatory and inhibitory responses to 5-HT were partially or totally blocked by the application of 5-HT2 receptor antagonist ketanserin. It is concluded that an extended, strong and differentiated control is exerted by 5-HT on the electrical activity of bulbar reticular neurons. Both 5-HT(1A) and 5-HT(2A) receptors mediate these effects, but the involvement of other receptors appears probable.

Distinct mechanisms regulate slow-muscle development.

Vertebrate muscle development begins with the patterning of the paraxial mesoderm by inductive signals from midline tissues [1, 2]. Subsequent myotome growth occurs by the addition of new muscle fibers. We show that in zebrafish new slow-muscle fibers are first added at the end of the segmentation period in growth zones near the dorsal and ventral extremes of the myotome, and this muscle growth continues into larval life. In marine teleosts, this mechanism of growth has been termed stratified hyperplasia [3]. We have tested whether these added fibers require an embryonic architecture of muscle fibers to support their development and whether their fate is regulated by the same mechanisms that regulate embryonic muscle fates. Although Hedgehog signaling is required for the specification of adaxial-derived slow-muscle fibers in the embryo [4, 5], we show that in the absence of Hh signaling, stratified hyperplastic growth of slow muscle occurs at the correct time and place, despite the complete absence of embryonic slow-muscle fibers to serve as a scaffold for addition of these new slow-muscle fibers. We conclude that slow-muscle-stratified hyperplasia begins after the segmentation period during embryonic development and continues during the larval period. Furthermore, the mechanisms specifying the identity of these new slow-muscle fibers are different from those specifying the identity of adaxial-derived embryonic slow-muscle fibers. We propose that the independence of early, embryonic patterning mechanisms from later patterning mechanisms may be necessary for growth.

Somite development in zebrafish.

A full understanding of somite development requires knowledge of the molecular genetic pathways for cell determination as well as the cellular behaviors that underlie segmentation, somite epithelialization, and somite patterning. The zebrafish has long been recognized as an ideal organism for cellular and histological studies of somite patterning. In recent years, genetics has proven to be a very powerful complementary approach to these embryological studies, as genetic screens for zebrafish mutants defective in somitogenesis have identified over 50 genes that are necessary for normal somite development. Zebrafish is thus an ideal system in which to analyze the role of specific gene products in regulating the cell behaviors that underlie somite development. We review what is currently known about zebrafish somite development and compare it where appropriate to somite development in chick and mouse. We discuss the processes of segmentation and somite epithelialization, and then review the patterning of cell types within the somite. We show directly, for the first time, that muscle cell and sclerotome migrations occur at the same time. We end with a look at the many questions about somitogenesis that are still unanswered.

The zebrafish slow-muscle-omitted gene product is required for Hedgehog signal transduction and the development of slow muscle identity.

Hedgehog proteins mediate many of the inductive interactions that determine cell fate during embryonic development. Hedgehog signaling has been shown to regulate slow muscle fiber type development. We report here that mutations in the zebrafish slow-muscle-omitted (smu) gene disrupt many developmental processes involving Hedgehog signaling. smu(-/-) embryos have a 99% reduction in the number of slow muscle fibers and a complete loss of Engrailed-expressing muscle pioneers. In addition, mutant embryos have partial cyclopia, and defects in jaw cartilage, circulation and fin growth. The smu(-/-) phenotype is phenocopied by treatment of wild-type embryos with forskolin, which inhibits the response of cells to Hedgehog signaling by indirect activation of cAMP-dependent protein kinase (PKA). Overexpression of Sonic hedgehog (Shh) or dominant negative PKA (dnPKA) in wild-type embryos causes all somitic cells to develop into slow muscle fibers. Overexpression of Shh does not rescue slow muscle fiber development in smu(-/-) embryos, whereas overexpression of dnPKA does. Cell transplantation experiments confirm that smu function is required cell-autonomously within the muscle precursors: wild-type muscle cells rescue slow muscle fiber development in smu(-/-) embryos, whereas mutant muscle cells cannot develop into slow muscle fibers in wild-type embryos. Slow muscle fiber development in smu mutant embryos is also rescued by expression of rat Smoothened. Therefore, Hedgehog signaling through Slow-muscle-omitted is necessary for slow muscle fiber type development. We propose that smu encodes a vital component in the Hedgehog response pathway.

Transcutaneous PCO2 level as an index of tissue resistance to ischemia.

The authors performed a retrospective study on a data base of 525 patients with peripheral arterial disease, to analyze the pathophysiologic meaning of resting transcutaneous pressure of carbon dioxide (PCO2) and of CO2 production during three minutes of local ischemia. The resting and postischemic PCO2 and its maximum increase related to rest (PCO2 production) were measured with Kontron 7640 equipment. The results show a significant increase of PCO2 production in the Fontaine stage 2A (183 patients, 4.61 mmHg, P < 0.0001), in stage 2B (194 patients, 5.22 mmHg, P < 0.0001), in the third stage (83 patients, 6.10 mmHg, P < 0.0001), and in the fourth stage (53 patients, 8.66 mmHg, P < 0.0001). Only the patients at the first stage showed an insignificant increase, perhaps because of the small number (12) in this group. The authors feel that the measurement of tcPCO2 production during local ischemic stress can be a very important parameter for evaluating peripheral arterial disease as an expression of metabolic tissue performance and, overall, of the tissue resistance to ischemia.

Postmenopausal bone density and milk consumption in childhood and adolescence.

Skeletal mass is a major determinant of susceptibility to osteoporotic fracture in menopause. At menopause, the skeletal mass is the resultant of the Peak Skeletal Mass (PSM) reached early adulthood minus the bone mass lost through the process of Adult Bone Loss (ABL). Current interventions for the maintenance of skeletal resilience in advanced age address the ABL peri- or postmenopausally. This study indicates that the effects of milk consumption in childhood and adolescence on bone density may manifest as higher bone density decades later in menopause. The assumed mechanism of the reported effect is through augmentation of the PSM, and acquisition of favorable nutritional habits which may influence the extent of ABL.