R. De Caro

The human area postrema and other nuclei related to the emetic reflex express cAMP phosphodiesterases 4B and 4D

Phosphodiesterase 4 (PDE4) inhibitors, i.e. rolipram, are being extensively investigated as therapeutic agents in several diseases. Emesis is one of the most common side effects of PDE4 inhibitors. Given the fact that the area postrema is considered the chemoreceptor trigger zone for vomiting, the present study investigates the regional distribution and cellular localization of the four gene transcripts of the PDE4 subfamily (PDE4A, PDE4B, PDE4C and PDE4D) in human brainstem. In situ hybridization histochemistry was used to locate the mRNA distribution of the four PDE4 subfamilies in the area postrema and related nuclei of human postmortem brainstem. We have found that in the brainstem PDE4B and PDE4D mRNA expression is abundant and distributed not only in neuronal cells, but also in glial cells, and on blood vessels. The hybridization signals for PDE4B and PDE4D mRNAs in the area postrema were stronger than those in any other nuclei in the brainstem. They were also found in vomiting-related nuclei such as the nucleus of the solitary tract and the dorsal vagal motor nucleus. These findings suggest that cAMP signaling modification in the area postrema could mediate the emetic effects of PDE4 inhibitors in human brainstem.

Pectoral and femoral fasciae: common aspects and regional specializations

The aim of this study was to analyse the organization of the deep fascia of the pectoral region and of the thigh. Six unembalmed cadavers (four men, two women, age range 48–93 years old) were studied by dissection and by histological (HE, van Gieson and azan-Mallory) and immunohistochemical (anti S-100) stains; morphometric studies were also performed in order to evaluate the thickness of the deep fascia in the different regions. The pectoral fascia is a thin lamina (mean thickness ± SD: 297 ± 37 μm), adherent to the pectoralis major muscle via numerous intramuscular fibrous septa that detach from its inner surface. Many muscular fibres are inserted into both sides of the septa and into the fascia. The histological study demonstrates that the pectoral fascia is formed by a single layer of undulated collagen fibres, intermixed with many elastic fibres. In the thigh, the deep fascia (fascia lata) is independent from the underlying muscle, separated by the epimysium and a layer of loose connective tissue. The fascia lata presents a mean thickness of 944 μm (±102 μm) and it is formed by bundles of collagen fibres, arranged in two to three layers. In each layer, the fibres are parallel to each other, whereas the orientation of the fibres varies from one layer to the adjacent one. The van Gieson elastic fibres stain highlights the presence of elastic fibres only in the more external layer of the fascia lata. In the thigh the epimysium is easily recognizable under the deep fascia and presents a mean thickness of 48 μm. Both the fascia lata and pectoral fascia result innerved, no specific differences in density or type of innervations is highlighted. The deep fascia of the pectoral region is morphologically and functionally different from that of the thigh: the fascia lata is a relatively autonomous structure with respect to the underlying muscular plane, while the pectoralis fascia acts as an additional insertion for the pectoralis major muscle. Different portions of the pectoralis major muscle are activated according to the glenohumeral joint movements and, consequently, selective portions of the pectoral fascia are stretched, activating specific patterns of proprioceptors. So, the pectoralis muscle has to be considered together with its fascia, and so as a myofascial unit, acting as an integrated control motor system.

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. Clin. Anat. 21:696–704, 2008.

The course of the posterior inferior cerebellar artery may be related to its level of origin.

The course of the posterior inferior cerebellar artery (PICA) was analyzed with reference to its origin and relationships with the medullary and cerebellar surfaces and the adjacent cranial nerves in 40 brains after the injection with acrylic resins of the vertebrobasilar system. In 42.5% of instances, the PICA originated from the lateral medullary segment of the vertebral artery (VA), in 32.5% from its premedullary segment, in 22.5% from the basilar artery (BA), and in 2.5% it was absent. With reference to the level of origin, three patterns of course for the lateral medullary segment of the PICA can be outlined. (1) When it arises from the lateral medullary segment of the VA, it passes below the hypoglossal nerve, and the lateral medullary segment may form a loop with an anterosuperior convexity towards the pontomedullary sulcus (41%), or it may follow a rectilinear course (41%). It passes at the level of the accessory nerve. The tonsillomedullary (TM) segment shows a caudal loop and the telovelotonsillary (TVT) has a cranial loop. (2) When the PICA arises from the BA, it passes above the hypoglossal nerve. The lateral medullary segment forms a loop with lateral convexity (78%) and passes above or through the glossopharyngeal nerve, frequently showing a recurrent course among the roots of the IX, X, or XI cranial nerve. The TM and the TVT segments do not have loops. (3) When the PICA arises from the premedullary segment of the VA, it passes above, below, or through the rootlets of the hypoglossal nerve. In the lateral medullary segment, it follows a rectilinear course (54%) and passes the plane formed by the IX, X, and XI cranial nerves at an intermediate level with respect to the other two patterns. The TM and the TVT segments show caudal and cranial loops. The different origins and courses of the PICA derive from the selection of different branches of the primitive vertebrobasilar plexus during the development of the cerebellum. The existence of an embryologic correlation between the course of the PICA and its level of origin may be useful in the evaluation of its angiographic anatomy.

Decellularized omentum as novel biologic scaffold for reconstructive surgery and regenerative medicine

Homologous tissues, such as adipose tissue, may be an interesting source of acellular scaffolds, maintaining a complex physiological three-dimensional (3D) structure, to be recellularized with autologous cells. The aim of the present work is to evaluate the possibility of obtaining homologous acellular scaffolds from decellularization of the omentum, which is known to have a complex vascular network. Adult rat and human omenta were treated with an adapted decellularization protocol involving mechanical rupture (freeze-thaw cycles), enzymatic digestion (trypsin, lipase, deoxyribonuclease, ribonuclease) and lipid extraction (2-propanol). Histological staining confirmed the effectiveness of decellularization, resulting in cell-free scaffolds with no residual cells in the matrix. The complex 3D networks of collagen (azan-Mallory), elastic fibers (Van Gieson), reticular fibers and glycosaminoglycans (PAS) were maintained, whereas Oil Red and Sudan stains showed the loss of lipids in the decellularized tissue. The vascular structures in the tissue were still visible, with preservation of collagen and elastic wall components and loss of endothelial (anti-CD31 and -CD34 immunohistochemistry) and smooth muscle (anti-alpha smooth muscle actin) cells. Fat-rich and well vascularized omental tissue may be decellularized to obtain complex 3D scaffolds preserving tissue architecture potentially suitable for recellularization. Further analyses are necessary to verify the possibility of recolonization of the scaffold by adipose-derived stem cells in vitro and then in vivo after re implantation, as already known for homologus implants in regenerative processes.

FENESTRATION OF THE VERTEBROBASILAR JUNCTION

SummaryA fenestration of the vertebrobasilar junction was found in an 80-year-old man during autopsy. It was associated with thrombosis of the vertebral arteries which had caused a left Wallenberg syndrome. The left limb of the fenestration presenting the same transverse diameter as that of the remaining part of the basilar artery appeared to be its direct (true) origin. The right limb had a lesser transverse diameter and appeared to bridge the lateral surface of the rostral end of the right vertebral artery and the basilar trunk. According to the authors, this fenestration could have been caused by the persistence of the cranial part of a primitive lateral vertebrobasilar anastomosis, rather then by the usual incomplete fusion of the primitive paired basilar arteries.

Surgical anatomy of the radial nerve at the elbow.

An anatomical study of the brachial portion of the radial nerve with surgical implications is proposed. Thirty specimens of arm from 20 fresh cadavers (11 male, 9 female) were used to examine the topographical relations of the radial nerve with reference to the following anatomical landmarks: acromion angle, medial and lateral epicondyles, point of division between the lateral and long heads of the triceps brachii, lateral intermuscular septum, site of division of the radial nerve into its superficial and posterior interosseous branches and entry and exit point of the posterior interosseous branch into the supinator muscle. The mean distances between the acromion angle and the medial and lateral levels of crossing the posterior aspect of the humerus were 109 (±11) and 157 (±11) mm, respectively. The mean length and calibre of the nerve in the groove were 59 (±4) and 6 (±1) mm, respectively. The division of the lateral and long heads of the triceps was found at a mean distance of 126 (±13) mm from the acromion angle. The mean distances between the lateral point of crossing the posterior aspect of the humerus and the medial and lateral epicondyles were 125 (±13) and 121 (±13) mm, respectively. The mean distance between the lateral point of crossing the posterior aspect of the humerus and the entry point in the lateral intermuscular septum (LIS) was 29 (±6) mm. The mean distances between the entry point of the nerve in the LIS and the medial and lateral epicondyles were 133 (±14) and 110 (±23) mm, respectively. Our study provides reliable and objective data of surgical anatomy of the radial nerve which should be always kept in mind by surgeons approaching to the surgery of the arm, in order to avoid iatrogenic injuries.

Do we really need new medical information about the Turin Shroud

Image processing of the Turin Shroud (TS) shows that the Man represented in it has undergone an under glenoidal dislocation of the humerus on the right side and lowering of the shoulder, and has a flattened hand and enophthalmos; conditions that have not been described before, despite several studies on the subject. These injuries indicate that the Man suffered a violent blunt trauma to the neck, chest and shoulder from behind, causing neuromuscular damage and lesions of the entire brachial plexus. The posture of the left claw-hand is indicative of an injury of the lower brachial plexus, as is the crossing of the hands on the pubis, not above the pubis as it would normally be, and are related to traction of the limbs as a result of the nailing to the patibulum. The disappearance of the thumbprints is because of entrainment of the flexor pollicis longus tendons while the nails were driven through the wrists. The blunt chest trauma, which resulted in the body falling forwards, was the direct cause of a lung contusion and haemothorax, confirmed by the post-mortem leakage of clots and serum from the chest caused by the stabbing with the spear, and was a likely cause of cardiac contusion. All the evidence is in favour of the hypothesis that the TS Man is Jesus of Nazareth.

pPKCα mediated-HIF-1α activation related to the morphological modifications occurring in neonatal myocardial tissue in response to severe and mild hyperoxia.

In premature babies birth an high oxygen level exposure can occur and newborn hyperoxia exposure can be associated with free radical oxygen release with impairment of myocardial function, while in adult animal models short exposure to hyperoxia seems to protect heart against ischemic injury. Thus, the mechanisms and consequences which take place after hyperoxia exposure are different and related to animals age. The aim of our work has been to analyze the role played by HIF-1α in the occurrence of the morphological modifications upon hyperoxia exposure in neonatal rat heart. Hyperoxia exposure induces connective compartment increase which seems to allow enhanced blood vessels growth. An increased hypoxia inducible factor-1α (HIF-1α) translocation and vascular endothelial growth factor (VEGF) expression has been found upon 95% oxygen exposure to induce morphological modifications. Upstream pPKC-α expression increase in newborn rats exposed to 95% oxygen can suggest PKC involvement in HIF-1α activation. Since nitric oxide synthase (NOS) are involved in heart vascular regulation, endothelial NOS (e-NOS) and inducible NOS (i-NOS) expression has been investigated: a lower eNOS and an higher iNOS expression has been found in newborn rats exposed to 95% oxygen related to the evidence that hyperoxia provokes a systemic vasoconstriction and to the iNOS pro-apoptotic action, respectively. The occurrence of apoptotic events, evaluated by TUNEL and Bax expression analyses, seems more evident in sample exposed to severe hyperoxia. All in all such results suggest that in newborn rats hyperoxia can trigger oxygen free radical mediated membrane injury through a pPKCα mediated HIF-1α signalling system, even though specificity of such response could be obtained by in vivo administration to the rats of specific inhibitors of PKCα. This intracellular signalling can switch molecular events leading to blood vessels development in parallel to pro-apoptotic events due to an immature anti-oxidant defensive system in newborn rat hearts.

Traumatic primary brain stem haemorrhage. A clinical and experimental study.

SummaryWe report 36 cases of post-traumatic “primary brain stem haemorrhage” visualized by the CT scan and confirmed at autopsy.Clinical experience shows that many technical factors influence the inability to visualize brain stem haemorrhages. Experimental injection of fresh blood into the pons and midbrain of cadavers shows that lesions as small as 0.25 ml in volume may be visualized.The volume and the anatomical configuration of traumatic lesions of the brain stem extended over a rostro-caudal direction, and their proximity to bony structures at the base of the skull are obstacles to the visualization of brain stem haemorrhages.