Quantification of hyaluronan in human fasciae: variations with function and anatomical site.

Recently, alterations in fascial gliding-like movement have been invoked as critical in the etiology of myofascial pain. Various methods have been attempted for the relief of this major and debilitating clinical problem. Paramount have been attempts to restore correct gliding between fascial layers and the movement over bone, joint, and muscular structures. One of the key elements that underlies such fascial movement is hyaluronan. However, until now, the precise content of hyaluronan within fasciae has been unknown. This study quantifies for the first time the hyaluronan content of human fascial samples obtained from a variety of anatomic sites. Here, we demonstrate that the average amount varies according to anatomic site, and according to the different kinds of sliding properties of the particular fascia. For example, the fascia lata has 35 µg of hyaluronan per gram of tissue, similar to that of the rectus sheath (29 µg g-1 ). However, the types of fascia adherent to muscle contain far less hyaluronan: 6 µg g-1 in the fascia overlying the trapezius and deltoid muscles. In the fascia that surrounds joints, the hyaluronan increases to 90 µg g-1 , such as in the retinacula of the ankle, where greater degrees of movement occur. Surprisingly, no significant differences were detected at any site as a function of age or sex (P-value > 0.05, t-test) with the sole exception of the plantar fascia. This work can provide a better understanding of the role of hyaluronan in fascia. It will facilitate a better comprehension of the modulation of the hyaluronan-rich layer that occurs in relation to the various conditions that affect fascia, and the diverse factors that underlie the attendant pathologies.

Transanal ileoproctostomy is feasible in human cadavers.

AIM: An ileorectal bypass performed entirely through a transanal route has recently been described in an animal model. The present study aimed to demonstrate its technical feasibility in four human cadavers. METHOD: A transanal endoscopic microsurgery (TEM) device and endoscopic instruments were used. The principal steps of the procedure included insertion of the TEM device, rectostomy above the peritoneal reflection, peritoneoscopy using a standard gastroscope and delivery of the small bowel through the proctostomy to perform an anastomosis. RESULTS: The procedure was successfully completed using transanal access in all cases. The mean procedure time was 90 min. The bypass was patent, and the anastomosis between the intraperitoneal rectum and the terminal ileum was leakproof. CONCLUSION: Transanal ileoproctostomy is technically feasible in human cadavers. The procedure may become an alternative to stoma formation in selected patients with colonic obstruction.

Development and aging are oxygen-dependent and correlate with VEGF and NOS along life span.

During development and aging, vascular remodeling represents a critical adaptive response to modifications in oxygen supply to tissues. Hypoxia inducible factor (HIF) has a crucial role and is modulated by oxygen levels, with an age-dependent response in neonates, adult, and aged people. ROS are generated under hypoxic conditions and the accumulation of free radicals during life reduces the ability of tissues to their removal. In this immunohistochemical study we investigated the presence and localization of VEGF and iNOS in human carotid bodies (CB) sampled at autopsy from three children (mean age - 2 years), four adult young subjects (mean age - 44.3 years), and four old subjects (mean age - 67.3 years). VEGF immunoreactivity was significantly enhanced in CB tissues from the children (7.2 ± 1.2%) and aged subjects (4.7 ± 1.7%) compared with the young adults (1.4 ± 0.7%). On the other hand, iNOS immunoreactivity was enhanced in CB tissues from the children (0.4 ± 0.04%) and young adult subjects (0.3 ± 0.02%) compared with the old subjects (0.2 ± 0.02%). Prevention of oxygen desaturation, reducing all causes of hypoxemia from neonatal life to aging would decrease the incidence of diseases in the elderly population with lifespan extension.

Cytoglobin and neuroglobin in the human brainstem and carotid body.

The aim of the present study was to evaluate the presence of Neuroglobin (Ngb) and Cytoglobin (Cygb) in the solitary tract nucleus (STN) and in the carotid body of human subjects. Transverse serial sections of formalin-fixed, paraffin-embedded brainstems, taken from six subjects, were investigated. Ngb and Cygb are expressed in both the structures. Differences in expression of Ngb and Cygb among dorsal and ventral area of the STN may be related to their different functions and different metabolic demands. Because the STN plays an important role in the processing of cardiovascular and respiratory reflex inputs, Ngb and Cygb may play an integrative central modulatory action for the two systems.

Tullio Terni (1888-1946): The "column" of spinal cardiovascular regulation.

Tullio Terni (1888-1946) was a brilliant anatomist in the School of Medicine of Padova, Italy. He was a versatile scientist who gave fundamental and pioneering contributions in descriptive and experimental cytology, human and comparative morphogenesis, neuroanatomy, embryology and teratology, and regenerative biology. His most famous discovery, which bears his name, is the so-called "Terni's column." In embryos of chickens, he described the existence in the thoracolumbar region of the spinal cord of a preganglionic nervous center, constituting a longitudinal column of nervous cells between the first thoracic and the second lumbar segments. Tullio Terni embodied the ideal of free science without geographic boundaries. He used cutting-edge tools, demonstrating his very current approach. Terni studied the organization of tissues and organs and the spatial arrangement and the physical state of the tissues of living systems. He also practiced experimental embryology, which formed the basis of modern techniques in organ transplantation. Moreover, he studied multiple species in order to compare multiple organisms. Terni was a multifaceted scientist.

Sulci of the liver found after death: Their nature and potential teaching value.

Accessory sulci of the liver are more commonly found after death than in life, raising questions as to their causation and possible classification. We have analyzed a group of 180 livers sampled from un-embalmed (96) and embalmed cadavers (84). In un-embalmed cadavers, no accessory sulci were found on the diaphragmatic surface in 58 cases. Diaphragmatic sulci were found in the right lobe of 38 livers. When removed from the abdominal cavity and placed flat on the examination table (the "bench position") all 58 livers without sulci appreciable in the abdominal cavity showed the appearance of two sulci. The first ran from the right side of the inferior vena cava (IVC), curving anteriorly to the inferior border of the liver, at a point midway between the right extremity of the inferior border and the gallbladder fossa, concave towards the left. The second sulcus ran from the left side of the IVC, curving anteriorly to reach the inferior border of the liver at the level of the gallbladder fossa, concave towards the right. With progressive side-to-side manual compression, the sulci on the diaphragmatic surface become more evident. Division of the hepatic parenchyma along the two sulci exposed the right and middle hepatic veins respectively in more than 90% of cases. In embalmed cadavers, 24 livers showed antero-posterior sulci in the superior surface, visible and palpable on the liver examined in situ. When the livers with sulci had been removed from the abdomen for further examination, the appearance of the superior surface did not change. In a removed liver, accessory sulci can be divided into true, "diaphragmatic," sulci and "false" sulci due to the position of the free liver on the examination table. The "false" sulci may be considered as further morphological evidence of the functional anatomical division of the liver. Their demonstration may also be useful in teaching its topographical and surgical anatomy.

Hyaluronan within fascia in the etiology of myofascial pain.

The layers of loose connective tissue within deep fasciae were studied with particular emphasis on the histochemical distribution of hyaluronan (HA). Samples of deep fascia together with the underlying muscles were taken from neck, abdomen and thigh from three fresh non-embalmed cadavers. Samples were stained with hematoxylin-eosin, Azan-Mallory, Alcian blue and a biotinylated HA-binding protein specific for HA. An ultrasound study was also performed on 22 voluntary subjects to analyze the thickness of these deep fasciae and their sublayers. The deep fascia presented a layer of HA between fascia and the muscle and within the loose connective tissue that divided different fibrous sublayers of the deep fascia. A layer of fibroblast-like cells that stained prominently with Alcian blue stain was observed. It was postulated that these are cells specialized for the biosynthesis of the HA-rich matrix. These cells we have termed "fasciacytes", and may represent a new class of cells not previously recognized. The ultrasound study highlighted a mean thickness of 1.88 mm of the fascia lata, 1.68 mm of the rectus sheath, and 1.73 mm of the sternocleidomastoid fascia. The HA within the deep fascia facilitates the free sliding of two adjacent fibrous fascial layers, thus promoting the normal function associated with the deep fascia. If the HA assumes a more packed conformation, or more generally, if the loose connective tissue inside the fascia alters its density, the behavior of the entire deep fascia and the underlying muscle would be compromised. This, we predict, may be the basis of the common phenomenon known as "myofascial pain."

Neurotensin receptor 1 immunoreactivity in the peripheral ganglia and carotid body.

In the present study we investigated, through immunohistochemistry, the presence and location of neurotensin receptor 1 (NTR1) in the peripheral ganglia and carotid body of 16 humans and 5 rats. In both humans and rats, NTR1 immunostained ganglion cells were found in superior cervical ganglia (57.4+/-11.6% and 72.4+/-11.4%, respectively, p0.05), enteric ganglia (51.9+/-10.4% and 64.6+/-6.1, p<0.05), sensory ganglia (69.2+/-10.7% and 73.0+/-13.1%, p>0.05) and parasympathetic ganglia (52.1+/-14.1% and 59.4+/-14.0%, p>0.05), supporting a modulatory role for NT in these ganglia. Positivity was also detected in 45.6+/-9.2% and 50.8+/-6.8% of human and rat type I glomic cells, respectively, whereas type II cells were negative. Our findings suggest that NT produced by type I cells acts in an autocrine or paracrine way on the same cell type, playing a modulatory role on chemoception.

Anatomic distribution of apoptosis in medulla oblongata of infants and adults.

The aim of the study was to evaluate the distribution of apoptosis in the medullary nuclei of infants and adults who died of hypoxic-ischaemic injury. Apoptosis was studied by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) in brainstems from 22 adults (7 subjects who died of opiate intoxication, 15 who died of other hypoxic-ischaemic injury) and 10 infants. The nuclei examined included the hypoglossal, dorsal motor nucleus of the vagus, nucleus tractus solitarii, nucleus of the spinal trigeminal tract, cuneate, vestibular and inferior olivary nuclei. A morphometric analysis with the optical disector method was performed to calculate the mean percentages (+/- standard deviation) of TUNEL-positive neuronal and glial cells for the sample populations. Opiate deaths did not have higher apoptotic indices than other adult hypoxic-ischaemic deaths. Statistically significant differences between adults and infants were found in the neuronal apoptotic indices of the cuneate (28.2 +/- 16.3% vs. 6.9 +/- 8.7%), vestibular (24.7 +/- 15.0% vs. 11.3 +/- 11.4%), nucleus tractus solitarii (11.2 +/- 11.2% vs. 2.3 +/- 2.4%), dorsal motor nucleus of the vagus (6.8 +/- 8.5% vs. 0.1 +/- 0.2%) and hypoglossal (6.6 +/- 5.7% vs. 0.1 +/- 0.2%), indicating higher resistance of the neuronal populations of these infant medullary nuclei to terminal hypoxic-ischaemic injury or post-mortem changes. Differences in neuronal apoptotic index were also statistically significant among nuclei, suggesting differential characteristics of survival. Nuclei with higher neuronal apoptotic indices were the cuneate, vestibular and nucleus of the spinal trigeminal tract, which are located in the lateral medullary tegmentum and share the same vascular supply from the posterior inferior cerebellar artery.

The gracilis muscle and its use in clinical reconstruction: an anatomical, embryological, and radiological study.

The gracilis muscle is used widely in reconstructive surgery, as a pedicled or as a free microsurgical flap, for soft tissue coverage or as a functioning muscle transfer. Many studies, based on cadaver dissections, have focused on the vascular anatomy of the gracilis muscle and provided different data about the number, origin, and caliber of its vascular pedicles. Computed tomographic (CT) angiography of both thighs of 40 patients (35 males and 5 females, mean age: 63 years) have been analyzed to provide a detailed anatomical description of the arterial supply of the gracilis muscle. The gracilis muscle had a mean length of 41 +/- 2.1 cm. The principal pedicle enters the gracilis muscle at a mean distance (+/-SD) of 10 +/- 1 cm from the ischiopubic attachment of the muscle. Its caliber shows a mean value of 2.5 +/- 0.5 mm, and it is statistically larger when originating directly from the deep femoral artery (45%) than from its muscular branch supplying the adductors, i.e., the "artery to the adductors" (46%) (P < 0.01). A significant correlation between the caliber of the artery of the main pedicle and the volume of the gracilis muscle was found (P < 0.01). The mean number of distal accessory pedicles is 1.8 (range, 1-4,) and the artery of the first of these pedicles shows a mean caliber of 2.0 mm. There is no correlation between either the number or the caliber of the artery of the accessory pedicles and the volume of the gracilis muscle. CT angiography, providing detailed images of the muscular and vascular structures of the thigh of each patient, could be a useful preoperative study for the reconstructive surgeon. It would allow a personalized planning of a gracilis flap, reducing the risk of iatrogenic damage.

Tendinous muscular insertions onto the deep fascia of the upper limb. First part: anatomical study.

We examined 30 upper limbs in order to study the tendinous muscular insertions into the deep fascia and to verify whether they have a specific anatomical arrangement and to measure their resilience to traction. We have found that the fascia receives many tendinous muscular insertions, which are always present and exhibit a constant anatomical structure. In particular, the pectoralis major fascia always continues with the brachial fascia in two distinct ways: the fascia overlying the clavicular part of pectoralis major had an expansion towards the anterior brachial fascia, whereas the fascia covering its costal part extended into the medial brachial fascia and the medial intermuscular septum. The lacertus fibrosus was also composed by two groups of fibres: the main group was oriented downwards and medially, the second group longitudinally. The palmaris longus opened out into a fan-shape in the palm of the hand and sent some tendinous expansions to the flexor retinaculum and fascia overlying the thenar eminence muscles. In the posterior region of the arm, the fascia of the latissimus dorsi sent a fibrous lamina to the triceps brachial fascia. The triceps tendon inserted partially into the antebrachial fascia, while the extensor carpi ulnaris sent a tendinous expansion to the fascia of the hypothenar eminence. It is hypothesized that the tendinous muscular insertions maintain the fascia at a basal tension and create myofascial continuity between the different muscles actuating flexion and extension of the upper limb, stretching the fascia in different ways according to the different motor directions.

Anatomy of the deep fascia of the upper limb. Second part: study of innervation.

Analysis of specimens taken from different areas of the deep fascia in 20 upper limbs was made in order to establish which kind of nerve fibres and endings are present in the deep muscular fascia. The flexor retinaculum and the lacertus fibrosus were also evaluated because they are anatomically hardly separable from the deep muscular fascia, although they have different functions. In particular, specimens were taken at the level of: (a) the expansion of pectoralis major onto the bicipital fascia, (b) the middle third of the brachial fascia, (c) the lacertus fibrosus, (d) the middle third of the antebrachial fascia, (e) the flexor retinaculum. This study demonstrated an abundant innervation of the fascia consisting in both free nerve endings and encapsulated receptors, in particular, Ruffini and Pacini corpuscles. However, differences in innervation were verified: the flexor retinaculum was resulted the more innervated element whilst lacertus fibrosus and the pectoralis major expansion the less innervated. These results suggest that the retinaculum has more a perceptive function whereas the tendinous expansions onto the fascia have mostly a mechanical role in the transmission of tension. The hypothesis that the fascia plays an important role in proprioception, especially dynamic proprioception, is therefore advanced. In fact, the fascia is a membrane that extends throughout the whole body and numerous muscular expansions maintain it in a basal tension. During a muscular contraction these expansions could also transmit the effect of the stretch to a specific area of the fascia, stimulating the proprioceptors in that area.

The triangles of Grynfeltt and Petit and the lumbar tunnel: an anatomo-radiologic study.

PURPOSE: Lumbar hernias are protrusions of intra-abdominal contents classically through the superior (Grynfeltt) and inferior (Petit) lumbar triangles. The anatomy of the triangles is variable and quantitative data are few. No radiological data on the anatomy of the triangles are available. METHODS: Fifty computed tomography angiography of the upper abdomen (M25, F25, mean age 72.5-year-old) were analyzed. The dimensions and the contents of the lumbar triangles were analyzed. The characteristics of the space between the two triangles were also documented. RESULTS: The superior lumbar triangle showed a mean surface area of 5.10 ± 2.6 cm2. In the area of the triangle, the 12th intercostal pedicle and the 1st lumbar branches of the iliolumbar vessels were found in 42 and 46 %, respectively. The inferior lumbar triangle had a mean surface of area 18.7 ± 8.4 cm2. In this area, the 2nd, 3rd, and 4th lumbar branches were found in 9, 67, and 8 %, respectively. On oblique coronal images, a direct tunnel between the superior and the inferior lumbar triangles was found, showing an oblique course, with a postero-anterior direction (mean length 36.5 ± 5.8 mm, mean caliber 7.4 ± 3.1 mm). CONCLUSIONS: Among the anatomical factors of weakening of the abdominal wall, the course of branches of the lumbar vessels was documented not only in the superior but also in the inferior lumbar triangle. A real musculoaponeurotic tunnel between the superior and the inferior lumbar triangles located in the oblique coronal plane was found, that could play a role in the development of incarceration or strangulation of lumbar hernias.

Selective stroke of the solitary tract nuclei in two cases of central sleep apnoea.

Central sleep apnoea (CSA) is a breathing disorder characterized by repetitive central apnoeas with hypoxia interrupted by hyperventilation phases. In the literature, there are reports of CSA caused by brainstem infarcts. We report two patients (38 and 53 years old) with longstanding history of central sleep apnoea who died during sleep. In both cases the autopsy revealed acute bilateral hypoxic lesions at the level of the solitary tract nuclei. In one case, symmetrical selective neuronal necrosis was found in the dorsal part of the solitary tract nuclei. A chronic obstructive vasculopathy was also found, with thickening and fibrosis of the smallest vessels of the medullary tegmentum. In the other case, bilateral infarctions were found with the base at the ependymal lining of the 4th ventricle floor and the apex towards the solitary tract. An acute intramural hemorrhagic lesion in the premedullary segment of the left vertebral artery was also found. Episodes of hypoxemic hypoxia during sleep may worsen the effects of focal oligohemic hypoxia in the medullary tegmentum. Selective stroke of the solitary tract nuclei may be the acute fatal lesion in patients with both central sleep apnoea and lesions of the vertebro-basilar system. To the best of our knowledge, this is the first neuropathologic report of acute medullary ischemic-hypoxic lesions which may not be considered the cause of the CSA because of their recent onset. Our findings suggest that CSA, besides being caused by ischemic events at the level of the medulla, may also contribute to pathogenesis of strokes, through hypoxia or hemodynamic oscillations.

ECRG4 expression in normal rat tissues: expression study and literature review.

The Esophageal Cancer Related Gene 4 (ECRG4) is a highly conserved tumour suppressor gene encoding various peptides (augurin, CΔ16 augurin, ecilin, argilin, CΔ16 argilin) which can be processed and secreted. In the present work, we examined ECRG4 expression and location in a wide range of rat organs and reviewed the available literature. ECRG4 mRNA was identified in all examined tissues by quantitative PCR (qPCR). ECRG4 immunoreaction was mainly cytoplasmic, and was detected in heart and skeletal muscles, smooth muscle cells showing only weak reactions. In the digestive system, ECRG4 immunostaining was stronger in the esophageal epithelium, bases of gastric glands, hepatocytes and pancreatic acinar epithelium. In the lymphatic system, immunoreactive cells were detectable in the thymus cortex, lymph node medulla and splenic red pulp. In the central and peripheral nervous systems, different neuronal groups showed different reaction intensities. In the endocrine system, ECRG4 immunoreaction was detected in the hypothalamic paraventricular and supraoptic nuclei, hypophysis, thyroid and parathyroid glands, adrenal zona glomerularis and medulla and Leydig cells, as well as in follicular and luteal cells of the ovary. In the literature, ECRG4 has been reported to inhibit cell proliferation and increase apoptosis in various cell types. It is down-regulated, frequently due to hypermethylation, in esophageal, prostate, breast and colon cancers, together with glioma (oncosuppressor function), although it is up-regulated in papillary thyroid cancer (oncogenic role). ECRG4 expression is also higher in non-proliferating cells of the lymphatic system. In conclusion, our identification of ECRG4 in many structures suggests the involvement of ECRG4 in the tumorigenesis of other organs and also the need for further research. In addition, on the basis of the location of ECRG4 in neurons and endocrine cells and the fact that it can be secreted, its role as a neurotransmitter/neuromodulator and endocrine factor must be examined in depth in the future.

Spontaneous involution of diffuse fibrous dysplasia of paranasal sinuses.

We report the case of a 25-year-old patient, diagnosed at age 10, with diffuse fibrous dysplasia of the paranasal sinuses, an extremely rare idiopathic condition. This diagnosis is possible only by cerebral computed tomography (CT), cerebral and anterior skull base magnetic resonance imaging (MRI), and histopathology. Surgical treatment is common. This boy had mild symptoms: moderate headache in the morning that did not affect his daily activity, and rhinitis, partially responsive to medication. The neurologic examination was abnormal. Radiographs, CT, and MRI showed a diffuse mass in the paranasal sinuses which had a histopathological diagnosis of fibrous dysplasias. The family refused to refer the patient to surgery. The boy has been monitored annually for 15 years. He has remained asymptomatic without headache since age 11, with normal, general and neurologic examinations. Serial MRIs showed a spontaneous partial involution of the mass.

How was the Turin Shroud Man crucified?

As the literature is not exhaustive with reference to the way the Turin Shroud (TS) Man was crucified, and it is not easy to draw significant information from only a "photograph" of a man on a linen sheet, this study tries to add some detail on this issue based on both image processing of high resolution photos of the TS and on experimental tests on arms and legs of human cadavers. With regard to the TS Man hands, a first hypothesis states that the left hand of the TS Man was nailed twice at two different anatomical sites: the midcarpal joint medially to the pisiform between the lunate/pyramidal and capitate/uncinate bones (Destot's space) and the radiocarpal joint between the radio, lunate and scaphoid; also the right hand would have been nailed twice. A second hypothesis, preferred by the authors, states that the hands were nailed only once in the Destot's space with partial lesion of the ulnar nerve and flexion of the metacarpophalangeal joint of the thumbs. With regard to the TS Man feet, the imprint of the sole of the right foot leads to the conclusion that TS Man suffered a dislocation at the ankle just before the nailing. The entrance hole of the nail on the right foot is a few inches from the ankle, and excludes a double nailing. The nail has been driven between the tarsal bones. The TS Man suffered the following tortures during crucifixion: a very serious and widespread causalgia due to total paralysis of the upper right limb (paradoxical causalgia); a nailing of the left wrist with damage to the ulnar nerve; a similar nailing of the right wrist; and a nailing to both feet using one only nail that injured the plantaris medialis nerves. The respiratory limitation was probably not sufficient to cause death by asphyxiation. Also considering the hypovolemia produced by scourging and the many other tortures detectable on the TS, the principal cause of death can be attributed to a myocardial infarction.