Varicose Segments Research Articles

Rac1 Pharmacological Inhibition Rescues Human Endothelial Dysfunction.

BackgroundEndothelial dysfunction contributes significantly to the development of vascular diseases. However, a therapy able to reduce this derangement still needs to be identified. We evaluated the effects of pharmacological inhibition of Rac1, a small GTPase protein promoting oxidative stress, in human endothelial dysfunction.Methods and ResultsWe performed vascular reactivity studies to test the effects of NSC23766, a Rac1 inhibitor, on endothelium‐dependent vasorelaxation of saphenous vein segments collected from 85 subjects who had undergone surgery for venous insufficiency and from 11 patients who had undergone peripheral vascular surgery. The endothelium‐dependent vasorelaxation of the varicose segments of saphenous veins collected from patients with venous insufficiency was markedly impaired and was also significantly lower than that observed in control nonvaricose vein tracts from the same veins. Rac1 activity, reactive oxygen species levels, and reduced nicotine adenine dinucleotide phosphate (NADPH) oxidase activity were significantly increased in varicose veins, and NSC23766 was able to significantly improve endothelium‐dependent vasorelaxation of dysfunctional saphenous vein portions in a nitric oxide–dependent manner. These effects were paralleled by a significant reduction of NADPH oxidase activity and activation of endothelial nitric oxide synthase. Finally, we further corroborated this data by demonstrating that Rac1 inhibition significantly improves venous endothelial function and reduces NADPH oxidase activity in saphenous vein grafts harvested from patients with vascular diseases undergoing peripheral bypass surgery.ConclusionsRac1 pharmacological inhibition rescues endothelial function and reduces oxidative stress in dysfunctional veins. Rac1 inhibition may represent a potential therapeutic intervention to reduce human endothelial dysfunction and subsequently vascular diseases in various clinical settings.

The Intimal Alteration of Human Varicose Veins Is Associated with Oxidative Stress and Cyclooxygenase‐2 Dependent Mechanisms

Chronic venous insufficiency (CVI) determinates high morbidity. Main varicose histological lesions include intimal fibrosis, luminal dilation and progressive vascular wall thickening. Plasma biomarkers of oxidative stress are increased in CVI patients. We evaluated histological changes and local inflammatory profile, particularly oxidative stress and prostanoids, in varicose saphenous veins (SV).10 distal and proximal segments of SV from patients with CVI were studied. In intimal layer, expression of smooth muscle actin (SMA), collagen I/III, and elastic fibers distribution were quantified by ImageJ sofware. NADPH oxidase subunit 4 (NOX‐4), cyclooxygenase‐2 (COX‐2), microsomal prostaglandin E synthase (mPGES‐1),MAC3, SMA, elastin, collagen I/III were studied by RT‐PCR. H2O2 production and NADPH oxidase activity were evaluated by commercial kits.Histological analysis showed higher intimal expression of SMA, collagen I/III and elastic fibers in proximal segments compared to distal segments. The progressive intimal vein thickness is inversely related to the ratio of SMA, collagen I/III and elastic fibers respect to intimal area. mRNA expression of SMA, collagen I/III, elastin, NOX‐4 and COX‐2 but not of mPGES‐1 or MAC3, H2O2 production and NADPH oxidase activity are upregulated at proximal varicose segments compared to distal segments. Our results suggest that oxidative stress and COX‐2 derived prostanoids might be implicated in the initial stages of the intimal fibrosis observed in varicose SV. Supported by PI13/01488 and SAF2012‐36400.

Improvements of Venous Tone with Pycnogenol in Chronic Venous Insufficiency: An Ex Vivo Study on Venous Segments

This study evaluated the stretching and dilatation of venous segments ex vivo in subjects with primary varicose veins in comparison with comparable segments from subjects that used the supplement Pycnogenol (150 mg/d) for 3 months before surgery. Subjects with varicose veins and chronic venous insufficiency voluntarily used Pycnogenol for a period of at least 3 months. The segments of veins removed with surgery (in 30 subjects that had used Pycnogenol and in 10 comparable control subjects that had not used the supplement) were compared with normal, unused vein segments harvested for bypass grafting. The segments were suspended and a weight was attached to the distal part of the veins for 3 minutes and dilated with pressurized water. Digital images were recorded; the veins were measured before and after stretching to evaluate elongation. The manipulation of the vein segment was minimal. Tests were completed within 20 minutes after harvesting the veins. All segments were 4 cm long. The stretching test indicated a significantly higher level of passive elongation in control, varicose segments (2.29; 0.65 mm) in comparison with 1.39; 0.2 mm in vein segments from Pycnogenol-using patients. The dilation test showed an average higher dilation (2.19; 0.3 mm) in control varicose veins in comparison with varicose veins from Pycnogenol-using patients (1.32; 0.7 mm) (p < 0.05). Stretching and dilatation were lower in veins from Pycnogenol-using subjects (p < 0.05). The measurement of destretching and the recovery after dilatation indicated a better tone and recovery of the original size/shape in varicose segments from patients using Pycnogenol. Varicose segments had a more significant persistent dilatation and elongation in comparison with normal vein segments. Pycnogenol seems to decrease passive dilatation and stretching and gives vein walls a greater tonic recovery and elasticity that allows the vein to recover its original shape after dynamic stresses.

The distribution and significance of varicosities in the saphenous trunks

The purpose of this study was to determine the prevalence, distribution, and extent of varicosities and focal dilatations in the saphenous trunks, their association with the sites of reflux, and their correlation with CEAP classes. This prospective study included patients belonging to different CEAP classes (2-6) and a control group of age- and gender-matched healthy volunteers (group C). Color-flow duplex scan imaging was used to evaluate the entire venous system from groin to ankle for reflux and obstruction. Varicose segments and focal dilatations of the great and small saphenous veins (GSV and SSV) were recorded, and the diameters throughout the length of the saphenous trunks were measured. The presence of varicosities in the tributaries and accessory veins were documented. From the 739 consecutive patients, 239 were excluded due to superficial venous thrombosis (SVT), deep venous thrombosis (DVT), both SVT and DVT, previous interventions, or C3-C6 presentation with no chronic venous disease (CVD). The included 500 patients (681 limbs) were divided into two groups based on CEAP class: group A (C2 + C3) and group B (C4-6). Group A had significantly more women than group B and a younger mean age (48 vs 56 years). Overall, GSV reflux (86%) was more prevalent than SSV reflux (17%), P < .0001. Saphenous trunk diameters, saphenofemoral junction (SFJ) and saphenopopliteal junction (SPJ) involvement were greater in group B, (P < .01). Group C had smaller saphenous diameters compared to group A in all locations (P < .05) but the malleoli. The prevalence of the saphenous varicose segments in both groups was small with the GSV in group B being the highest (4.3%) and the SSV in group A being the smallest (1.2%). Focal dilatations were significantly more prevalent than varicosities in the saphenous trunks (P < .0001). Varicosities of tributaries and accessory veins were more prevalent than those of saphenous trunks (P < .0001). The mean length of varicose segments in the saphenous trunks was short (3.8 cm, range, 2.1-6.4 for group A vs 4.1 cm, range, 2.3-8.3 for group B, P = .09). A novel definition for varicosities in the saphenous trunks was established. Using this definition, it was determined that focal dilatations are far more common than varicosities. Because both of these entities are more prevalent in the accessory saphenous veins and tributaries, and CEAP class correlates positively with the extent of reflux and saphenous trunk diameter, studies on earlier interventions are warranted to prevent CVD progression.

Balloon sclerotherapy: A new method for the treatment of truncal varicose veins

Truncal varicose veins may be treated by conventional surgery or endovenous therapy. Endovenous ablation, such as laser or radiofrequency treatment, is less invasive but technically demanding, not cheap and has still the possibility of important side-effects. Moreover the treatment requires in the best case tumescent anesthesia. Catheter based endovenous sclerotherapy has the potential of systemic effects of sclerosing agent and air. We therefore aimed to develop a simple, minimal-invasive and cheap method for the treatment of truncal varicose veins reducing the potential risk of systemic effects of the sclerosing agent to a minimum. A double lumen double balloon catheter was developed. Thereby a treatment site within a vein can be isolated from blood for localized administration of a sclerotherapeutic agent. Later, a substantial portion of the therapeutic agent can be removed from the isolated segment thus minimizing the amount necessary. Occlusion of longer varicose segments is achieved by pointwise repetition of the manoeuvre or careful retraction of the expanded balloons with the "catched" sclerotherapeutic agent in between. The application was filed as United States Patent No. 6,726,67 B2. 18 balloon prototypes successfully passed an extensive test series (leak tests, dimension tests, mandrel--, guide wire--and introducer compatibility tests, destructive tests). Three patients with varicosity of the greater saphenous vein and the vena saphena accessoria lateralis, respectively, were successfully treated with complete occlusion of the vessels 10, 6 and 2 months after the intervention. Balloonsclerotherapy combines two well-established procedures (balloon catheter therapy and sclerotherapy, namely) and promises to be a minimal-invasive and cheap endovenous therapy of truncal varicose veins, requiring local anesthesia at the puncture site only and reducing possible systemic side effects of the sclerosing agent.

Expression of elastic components in healthy and varicose veins.

This study evaluates possible changes in the synthesis/degradation of elastic components of the vein wall in an attempt to explain the development of varicosis. Healthy and varicose saphenous veins were subjected to immunohistochemical analysis using anti-elastin, anti-fibrillin-1, anti-elastase, anti-transforming growth factor (TGF)-beta and anti-latent TGFbeta binding protein (LTBP)-2 monoclonal antibodies. In situ hybridization was performed using specific probes for tropoelastin and fibrillin-1. In healthy veins, elastin and fibrillin-1 showed even, overlapping distribution patterns indicating their particular abundance in the adventitia and at the intima/media interface. The expression of tropoelastin and fibrillin-1 was high in smooth muscle cells bordering the elastic laminae. Elastin, fibrillin-1, and cells expressing fibrillin-1 and tropoelastin mRNA showed a patchy disorganized pattern, particularly in the proximal varicose segments of patients under 50 years of age. Enhanced elastase activity was noted in both control and varicose specimens from elderly subjects. Varicose veins specimens showed greater LTBP-2 and TGF expression. Both molecules were detected in the subendothelium and the media, particularly in areas of marked injury. Our findings suggest that the development of the varicose condition involves a restructuring of the elastic component of the vein wall, perhaps as a consequence of changes in the transcription mechanisms of muscle layer cells.

8-Epi-PGF2alpha and 6-oxo-PGF1alpha in human (varicose) veins: influence of age, sex, and risk factors.

The isoprostane 8-epi PGF2alpha is a vasoconstrictive, mitogenic, proliferative, and mild proaggregatory agent. We examined 8-epi-PGF2alpha and 6-oxo-PGF1alpha from venous tissue derived from varicose (venous) surgery by means of a specific radioimmunoassay. A total of 336 samples from 82 patients (50 females, 32 males; aged 22-68 years) were examined. Tissue samples were classified according to normal, dilated, and varicose. Of these, 94 samples from 31 patients (20 females, 11 males; aged 29-64 years) with additional risk factors (cigarette smoking, hyperlipidemia, diabetes mellitus) were determined in the same way. Mean absolute values for 6-oxo-PGF1alpha are not significantly higher for dilated segments followed by varicose and intact samples. No significant age and sex differences can be monitored. Presence of risk factors, however, results in a significantly diminished 6-oxo-PGF1alpha, irrespective of morphology. 8-Epi-PGF2alpha again showed no age and sex dependence, its presence in varicose segments, however, was significantly (p<0.01) decreased. Risk factors resulted in a significantly increased 8-epi-PGF2alpha. These data indicate that the influence of risk factors on vasomodulatory (iso-)eicosanoids of human veins is more pronounced than the actual morphologic stage. Lower 8-epi-PGF2alpha in varicose veins may shift the venous tone toward vasodilatation and contribute to development and progression of varicosis.

Ca2+ mobilization in saphenous vein smooth muscle cells derived from patients with primary varicosity.

Human primary varicosity is associated with 'weakness' of the vein wall. We investigated whether the reduced responsiveness of varicose veins to physiological vasoconstrictors might result from impaired Ca2+ mobilization in venous smooth muscle. The hypothesis was tested in cells derived from phenotypically different vein segments that were obtained from the inguinal saphenous vein (tissue with incompetent valves), the distal portion of the long saphenous vein just above the medial ankle (clinically healthy tissue), and from a tributary to the long saphenous vein just below the knee (incompetent and overtly varicose tissue). Saphenous vein from patients undergoing cardiac surgery served as control. Cytosolic free Ca2+ levels ([Ca2+]i) were determined with the fura-2 method in cultured medial smooth muscle cells of third to sixth passage (21-23 measurements per tissue derived from five controls and seven patients). Angiotensin II (10 nmol L-1 to 10 mumol L-1) induced a significantly (P < 0.05) smaller rise in [Ca(2+)1i response in cells derived from incompetent or varicose segments (approximatley 70 nmol L-1) than in cells derived from clinically healthy vein (approximately 130 nmol L-1) or controls (approximately 170 nmol L-1). Likewise, the effect of endothelin-1 (100 nmol L-1) on [Ca2+]i was considerably less in cells derived from segments with incompetent valves or from varicose vessel segments than in cells derived from control patients (P < 0.05). In organ baths, endothelium-denuded strips of varicose vessels contracted significantly less in response to these agonists than clinically healthy segments from the same patient. The reduced contractility of diseased human varicose veins in response to angiotensin II and endothelin-1 involves impaired Ca2+ mobilization.

Responsiveness of human varicose saphenous veins to vasoactive agents.

To test in vitro the constrictor and relaxation responsiveness of variously diseased segments of human saphenous vein from patients with varicose vein disease. The vein segments were derived (i) from the inguinal saphenous vein (valvularly incompetent and slightly dilated; tissue A); (ii) from the distal end of the lower leg just above the medial ankle (competent; tissue B); (iii) from a tributary to the long saphenous vein just below the knee (dilated, incompetent and overtly varicose; tissue C). The contractile responses were tested with phenylephrine (an alpha-adrenergic receptor agonist) and aescin, a clinically used phlebotonic drug derived from horse chestnut extract. Relaxant responses were tested with acetylcholine and sodium nitroprusside. Both contractile agents contracted vein segments from the inguinal and ankle area with similar potency and efficacy, but were virtually without effect in the overtly varicose segments from the calf. EC50 values (molar concentration of the agonist that produces 50% of the maximum effect) in tissues A and B were 2.9 +/- 0.3 and 2.5 +/- 0.5 micromol l(-1) (phenylephrine) and 9.4 +/- 1.0 and 15.9 +/- 2.5 micromol l(-1) (aescin); the corresponding maximum effects (maximum effect, percent of KCl-induced contraction) were 76 +/- 3 and 70 +/- 4% (phenylephrine) and 70 +/- 2 and 71 +/- 3% (aescin) (P = NS in both cases for A vs B). In tissue C, the maximum effects were 5 +/- 5% (phenylephrine) and 10 +/- 7% (aescin) of KCl-induced contraction (not significantly different from zero). Acetylcholine-induced relaxation was similar for vein segments from locations A and B, whereas sodium nitroprusside was more effective in tissue B than A. These findings support the notion that abnormalities within the venous wall affect venous smooth muscle contractility. Since competent and incompetent clinically normal vessels show normal contractile responses, whereas varicose vessels are not responsive to vasoactive drugs, it is likely that pharmacological treatment regimens are effective in early, but not in late stages of the disease.

Estrogen and Progesterone Receptors in Normal and Varicose Saphenous Veins

The presence of estrogen and progesterone receptors was investigated in the walls of normal and varicose veins. Cryostat sections from the saphenous veins of 29 normal individuals, and varicose and normal vein segments of 32 patients with varicose veins, were stained with anti-estrogen or anti-progesterone receptor antibodies. Nuclear stain intensity was scored by three independent observers. Receptors to both hormones were detected in the nuclear regions of the intima and media in females and males. In the adventitia, estrogen and the progesterone receptors were found only in nuclei of the vasa vasorum. Estrogen receptor levels were lower in non-varicose segments of varicose veins compared with normal veins. In varicose segments, estrogen receptors were more abundant than in the non-varicose parts of the same vein, especially in females. Similarly, progesterone receptor levels in the non-varicose portions were higher in females. These gender differences may be related to hormonal action. However, these differences may also be age related. These findings may be related to the involvement of sex-hormones in varicosis, by mechanisms as yet unknown.

Estrogen and progesterone receptors in normal and varicose saphenous veins

The presence of estrogen and progesterone receptors was investigated in the walls of normal and varicose veins. Cryostat sections from the saphenous veins of 29 normal individuals, and varicose and normal vein segments of 32 patients with varicose veins, were stained with anti-estrogen or anti-progesterone receptor antibodies. Nuclear stain intensity was scored by three independent observers. Receptors to both hormones were detected in the nuclear regions of the intima and media in females and males. In the adventitia, estrogen and the progesterone receptors were found only in nuclei of the vasa vasorum. Estrogen receptor levels were lower in non-varicose segments of varicose veins compared with normal veins. In varicose segments, estrogen receptors were more abundant than in the non-varicose parts of the same vein, especially in females. Similarly, progesterone receptor levels in the non-varicose portions were higher in females. These gender differences may be related to hormonal action. However, these differences may also be age related. These findings may be related to the involvement of sex-hormones in varicosis, by mechanisms as yet unknown.

Was ist ein Nozizeptor?

Nociceptors can be defined as sensory receptors that are activated by noxious stimuli that damage or threaten the body's integrity. Nociceptors belong to the slowly conducting afferent A delta and C fibres. They are classified according to their responses to mechanical, thermal, and chemical stimuli. In the skin, high-threshold mechano-nociceptors (HTMs) and mechano-heat nociceptors of A and C fibres (AMHs and CMHs) are frequently found. CMHs are usually called polymodal C fibres (CPMs) if they also show chemosensitive properties. Sensations of sharp pain are evoked by intraneural microstimulation of nociceptive A delta fibres, whereas stimulation of C fibres causes dull pain sensations. NOCICEPTORS OF DEEP TISSUES AND VISCERA: Slowly conducting afferents of deep tissues (muscles, joints) are primarily classified according to their mechanosensitivity. High-threshold afferents in somatic and visceral tissues are specifically activated by noxious mechanical stimuli. Many visceral afferents, however, are already activated by peristaltic contractions encoding the stimulus intensity over a wide range. High proportions of somatic and visceral nociceptors can be excited or sensitised by various irritants and inflammatory mediators such as capsaicin, bradykinin, prostaglandins, leukotrienes, serotonin, histamine, and free radicals. As a special class of nociceptors, mechano-insensitive or "silent" afferents have been found in nearly all tissues. Silent afferents become mechanosensitive only after long noxious stimulation, e.g., during an inflammation. "Free nerve endings", which are regarded as the morphological correlatives of nociceptors, usually consist of bundles of unmyelinated fibres. With electron microscopy varicose segments of the sensory axon are visible that are characterised by free areas of axolemma, accumulations of mitochondria and vesicles, and a modified axoplasm. These presumptive receptive sites are periodically arranged along the whole course of the sensory endings at a length of up to several hundred microns. Additionally, the fine sensory endings are branched, forming tree-like structures, and frequently innervate different types of tissues. Studies correlating structure and function of articular afferents provide evidence for a close relationship between topographical and functional properties of sensory endings. High-threshold afferents (nociceptors) seem to terminate in structures of dense connective tissue. Proportions of nociceptors contain neuropeptides such as substance P and calcitonin gene-related peptide, which are released from the activated nociceptive terminals and cause neurogenic inflammation, including precapillary vasodilatation and postcapillary plasma extravasation. Experimental and clinical progress has been achieved in using the nociceptor as a target for chemical anti-nociception and treatment of pain. Substances that act directly or indirectly on the nociceptor are steroidal and non-steroidal analgesics, capsaicin analogs, bradykinin antagonists, opioids, and (in the trigeminal system) 5-hydroxytryptamine agonists.

Nitric oxide synthase-immunoreactive axons innervating the guinea-pig lingual artery: an ultrastructural immunohistochemical study using elastic brightfield imaging.

The ultrastructure of nitric oxide synthase-immunoreactive (NOS-IR) axons innervating the guinea-pig lingual artery was investigated by means of pre-embedding immunohistochemistry using an indirect peroxidase technique and diaminobenzidine. Sections ranging in thickness from 60 to 500 nm were ultrastructurally evaluated in elastic brightfield imaging mode. Thick sections (optimum at 300 nm) were advantageous for enhancement of the labelling intensity, whilst some subcellular details were better revealed by thin sections. NOS-IR axon terminals often contained aggregations of large, dense-cored vesicles, consistent with a previous light microscopical report on colocalization of NOS and vasoactive intestinal peptide-immunoreactivity in these fibres. NOS-IR axons formed direct neuro-muscular junctions (width less than 50 nm) at the outer surface of the tunica media, thus providing a structural basis for "nitrergic" vasodilation. In addition, NOS-IR axons made direct contacts with non-varicose and varicose segments of non-reactive axons, suggesting interneuronal communication between these elements.

Terminal processes of serotonin neurons in the caudal spinal cord of the molly, Poecilia latipinna, project to the leptomeninges and urophysis.

The caudal neurosecretory complex of poeciliids has previously been shown to be innervated by extranuclear and intrinsic serotonergic projections. In the present study, immunohistochemical techniques were used to characterize fibers originating from serotonin neurons intrinsic to the caudal spinal cord. Bipolar and multipolar neurons were oriented ventromedially, and contained numerous large granular vesicles. Three types of serotonergic fibers were distinguished based on their distribution and morphology. Intrinsic Type-A fibers branched into varicose segments near the ventrolateral surface of the spinal cord and contacted the basal lamina beneath the leptomeninges. Type-B fibers coursed longitudinally to enter the urophysis, where they diverged and terminated around fenestrated capillaries. Labelled vesicles in Type-A and Type-B terminals were the same size as those in labelled cells and in unlabelled neurosecretory terminals in the urophysis. Type-C small varicose fibers branched within the neuropil of the caudal neurosecretory complex. Serotonin may be secreted into the submeningeal cerebrospinal fluid, the urophysis, and the caudal vein by Type-A and Type-B fibers, whereas, Type-C fibers may be processes of serotonergic interneurons in the neuroendocrine nucleus. The possibility that urotensins I and II or arginine vasotocin were colocalized in the processes of the intrinsic serotonin neurons was investigated immunohistochemically. The negative results of these experiments suggest that serotonin-containing neurons may represent a neurochemically distinct subpopulation in the caudal neurosecretory complex.

Immunocytochemical study of GABAergic neurons containing the calcium-binding protein parvalbumin in the rat hippocampus.

The structural features of PV-immunoreactive (PV-I) neurons, a particular subpopulation of GABAergic neurons, in the hippocampus were studied by immunocytochemistry. The PV-I cell bodies were concentrated within the stratum pyramidale (SP) and stratum oriens (SO) in the hippocampus. PV-I puncta were frequent in SP, while they were rarely seen in other layers. The dendritic arborization of PV-I neurons resembled that of some of the nonpyramidal cells observed after Golgi-impregnation. The most commonly observed PV-I neurons had their perikarya located in SP with dendrites extending into SO and the stratum radiatum (SR). Most of the dendrites in SR had typical beaded or varicose segments. The dendrites extending into SO had few beaded parts. There were many bipolar and multipolar neurons with smooth dendrites in SO, but only a small number of such multipolar neurons in SR. An electron microscopic analysis revealed that PV-I products were located to perikarya, dendrites, myelinated axons and synaptic boutons. The perikarya of PV-I neurons exhibited several ultrastructural features of nonpyramidal cells, e.g., abundant cisternae of endoplasmic reticulum, mitochondria and other perikaryal organelles, an infolded nuclear envelope and intranuclear inclusions. They received many asymmetric synapses with round presynaptic vesicles. There were numerous PV-I boutons, presumably axonal endings, covering the pyramidal cell bodies. The PV-I boutons also contacted the axon initial segments and proximal dendrites of the pyramidal cells. In addition PV-I terminals were found on somata and dendrites of both PV-I or PV-negative nonpyramidal cells. The results suggest that PV-containing neurons include basket and axo-axonic cells.

The organization and hypothalamic projections of the tuberomammillary nucleus in the rat: An immunohistochemical study of adenosine deaminase-positive neurons and fibers

The intense immunohistochemical reaction for the enzyme adenosine deaminase displayed by neurons in the tuberomammillary nucleus in the rat was used to study the distribution and morphology of cells comprising this nucleus, their fiber fields within the posterior hypothalamus and their projection pathways from the hypothalamus. Neurons immunoreactive for adenosine deaminase were found along ventricular and basal aspects of the hypothalamus from the level of the dorsomedial nucleus to the caudal pole of the mammillary body. Approximately 4500 neurons were seen on each side of the brain. Positive neurons showed a complex distribution, largely avoiding nuclear boundaries within the posterior basal hypothalamus and mammillary body. This distribution is mapped in detail and a nomenclature based on topography is introduced so that different regions of the cell distribution may be discussed more easily. Reactive neurons showed a Golgi-like staining which allowed careful study of their morphology. In general, neurons were large, with major axes of from 22 to 30 μm, and bipolar in shape. A second, smaller cell type, 14–16 μm in diameter was also seen and, although often less intensely stained, it was considered a constituent of tuberomammillary nucleus of the hypothalamus as well. Stained dendritic arbours extended considerable distances from the parent cell bodies and branched regularly. Dendrites showed very sparse spines and had an apparently scalloped surface. Features suggestive of varicose segments of dendrites were also noted. The long, smooth dendrites of positive neurons were often seen to aggregate into bundles which avoided nuclear boundaries and tended to collect adjacent to basal and ventricular surfaces of the posterior hypothalamus. Varicose fibers immunoreactive for adenosine deaminase formed a dense network within the hypothalamus. These fibers were considered to derive from the positive neurons in the tuberomammillary nucleus and were similar to adenosine deaminase-immunoreactive fibers seen throughout much of the rest of the brain. The density of this type of positive fiber was, however, much greater within the hypothalamus. The region of the posterior basal hypothalamus also contained relatively sparse populations of adenosine deaminase-positive fibers, apparently distinct from this network. These consisted of a field of fine fibers in the median division of the medial mammillary nucleus and a few large varicosities in the dorsolateral part of the median eminence. As the most recent addition to the list of neuronal groups recognized to have projections to widespread regions of the neuraxis, it is anticipated that the tuberomammillary nucleus will be of interest to investigators in a variety of disciplines. The detailed anatomical observations presented here are expected to assist in the determination of the anatomical and functional relationships of the tuberomammillary nucleus with its global terminal field.

Varicography in the management of recurrent varicose veins.

Forty lower extremities in 29 patients with recurrent varicose veins have been investigated by varicography. In 29 lower extremities the recurrent varicosities were on the long saphenous venous system and in 11 lower extremities on the short saphenous system. The recurrences consisted of varicose segments or tributaries of the long or short saphenous veins, varicose tributaries at the sites of previous ligations of varicose veins, and varicosities associated with incompetent perforating veins in the midthigh and calf. It is suggested that varicography is a useful method for demonstrating the sites of recurrent varicose veins and for enabling definitive surgery to be performed.