Norepinephrine in chronic paranoid schizophrenia: above-normal levels in limbic forebrain.

In postmortem examination of brains of four patients with chronic paranoid schizophrenia, above-normal norepinephrine levels were measured in the ventral septum, the bed nucleus of the stria terminalis, the nucleus accumbens, and the mammillary bodies. No changes were detected in other limbic forebrain regions, including the hypothalamus and the medial olfactory (preoptic) area. The results point to the possibility of a malfunction of limbic noradrenergic mechanisms in schizophrenia, especially the paranoid variety.

[Coblation tonsillectomy. Results of a pilot study]. / Coblation-Tonsillektomie. Ergebnisse einer Pilotstudie.

BACKGROUND: The introduction of coblation tonsillectomy (CTE) may contribute to reduce the postoperative morbidity in terms of pain, delayed oral intake and bleeding. METHODS: A prospective pilot study was undertaken to evaluate the clinical course by inpatient observation (5 days) and telephone contact 6 months after CTE. The data from 61 patients (aged 44 months-69 years) were analyzed. The patients were grouped into those with surgical care of bleeding (A), non-surgical care of bleeding (B), and no bleeding event (C). RESULTS: The study was terminated early due to major bleeding complications in seven patients (A). Fifteen patients experienced minor (B) and 41 no (C) bleeding episodes. In the interview, 29 patients identified pain, lasting 16.7 (A), 11.6 (B) and 11 (C) days, as the most significant complication of surgery. CONCLUSIONS: The introduction of CTE was followed by a dramatic increase in major bleeding complications, including late bleeding episodes. Pain following tonsillectomy remains a problem to be solved by further techniques. We will continue to perform the cold dissection technique.

The Global Genome Biodiversity Network (GGBN) Data Standard specification.

Genomic samples of non-model organisms are becoming increasingly important in a broad range of studies from developmental biology, biodiversity analyses, to conservation. Genomic sample definition, description, quality, voucher information and metadata all need to be digitized and disseminated across scientific communities. This information needs to be concise and consistent in today's ever-increasing bioinformatic era, for complementary data aggregators to easily map databases to one another. In order to facilitate exchange of information on genomic samples and their derived data, the Global Genome Biodiversity Network (GGBN) Data Standard is intended to provide a platform based on a documented agreement to promote the efficient sharing and usage of genomic sample material and associated specimen information in a consistent way. The new data standard presented here build upon existing standards commonly used within the community extending them with the capability to exchange data on tissue, environmental and DNA sample as well as sequences. The GGBN Data Standard will reveal and democratize the hidden contents of biodiversity biobanks, for the convenience of everyone in the wider biobanking community. Technical tools exist for data providers to easily map their databases to the standard.Database URL: http://terms.tdwg.org/wiki/GGBN_Data_Standard.

Endothelial cell orientation on aortic valve leaflets.

Studies of the structure of blood vessels have commonly found that cells lining the vessels are lengthened in the direction of blood flow, presumably as an effect of shear stress. A study of aortic valves has, however, shown that endothelial cells covering both sides of aortic valve leaflets are arranged across the direction of flow. Aortic valve leaflets taken from seven adult mongrel dogs and fixed either open or closed with glutaraldehyde were studied with a scanning electron microscope after critical point drying. On both open and closed leaflets the endothelial cells tended to be aligned circumferentially with the free edge of the leaflet. The circumferential pattern was particularly unexpected on the leaflet surface facing the left ventricle because this surface could be expected to receive the full effect of shear stress from systolic blood flow. The finding suggested that surface cellular alignment on leaflets is determined by some force other than shear stress. The force apparently responsible for organising the collagenous layers in the leaflet, which are best adapted to bear stress, is diastolic blood pressure. Since the endothelium follows the same pattern of alignment as the layers of collagen it seems reasonable to conclude that endothelial orientation is also a response ultimately to pressure stress. The arrangement of the endothelium then serves as a readily observed indicator of those functional stresses that dominate and organise leaflet structure.

Structure, stress, and tissue repair in aortic valve leaflets.

During the normal cyclic operation of the aortic valve its leaflets are subjected to continual bending, shearing, and membrane stresses. In vivo studies of marked leaflets have shown that the bending stresses are greatest where leaflets are attached to the aortic wall. Pressure stresses during diastole also appear to be high in this region. The internal shearing stresses are difficult to predict because of the semifluid nature of the tissue in the attachment zone. In the present study a model of the attachment region incorporated measurements of leaflet motion from dogs in vivo and from histological sections. From these measurements bending and membrane stresses were derived in order to estimate the total stresses. In this region the total stresses in systole were negligible because membrane stresses are essentially zero, but those in diastole ranged from 76 to 95 g.mm-2 in the circumferential direction and from 37 to 44 g.mm-2 in the radial direction. The calculated stress suggests that excessive tissue wear and valve failure could occur in the absence of tissue replacement. From radioautographic studies of rat valves, proteins and complex sugars of the valve connective tissues were found to be regularly replaced in patterns predictable from the level of stresses.

Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is the term used to describe children who are inattentive, impulsive, and hyperactive. The cause is unknown and is thought to be multifactorial. Based on the work of others, we hypothesized that some children with ADHD have altered fatty acid metabolism. The present study found that 53 subjects with ADHD had significantly lower concentrations of key fatty acids in the plasma polar lipids (20:4n-6, 20:5n-3, and 22:6n-3) and in red blood cell total lipids (20:4n-6 and 22:4n-6) than did the 43 control subjects. Also, a subgroup of 21 subjects with ADHD exhibiting many symptoms of essential fatty acid (EFA) deficiency had significantly lower plasma concentrations of 20:4n-6 and 22:6n-3 than did 32 subjects with ADHD with few EFA-deficiency symptoms. The data are discussed with respect to cause, but the precise reason for lower fatty acid concentrations in some children with ADHD is not clear.

Post-herpetic neuralgia: further post-mortem studies of cases with and without pain.

The pathological features associated with post-herpetic neuralgia require further study. We report here 5 cases, 3 with severe post-herpetic neuralgia (PHN) and 2 with no persistent pain. The findings of dorsal horn atrophy and cell, axon and myelin loss with fibrosis in the sensory ganglion were found only in patients with persistent pain. Marked loss of myelin and axons in the nerve and/or sensory root were found in cases with and without pain. Some evidence is presented for a more generalized subacute or chronic inflammatory process which may explain the clinical features of some patients. Further studies will be necessary to fully describe the morbid anatomy of this disorder.

Post-herpetic neuralgia: post-mortem analysis of a case.

The morphological and biochemical substrates of the severe pain in post-herpetic neuralgia (PHN) are unclear. This report is an autopsy study of a 67-year-old male with severe PHN during the last 5 years of his life over the right T7-8 dermatomes. The dorsal horn of the thoracic spinal cord of the affected side was atrophic from T4 to T8, with loss of both myelin and axons. Despite this, only the T8 ganglion was affected by fibrosis and cell loss and only the nerve roots at that level appeared affected. Markers of unmyelinated afferents (substance P), substantia gelatinosa neurons (opiate receptors), glial cells (glial fibrillary acidic protein), and descending spinal projections (dopamine-beta-hydroxylase and serotonin) were not different at affected versus non-affected spinal cord levels. The pain of PHN may result from the uninhibited activity of unmyelinated primary afferents as a result of the loss of myelinated afferent fibers and the possible presence of hypersensitive neurons in the dorsal horn.

Intramural stress as a causative factor in atherosclerotic lesions of the aortic valve.

Topographic distribution of atherosclerotic lesions of the aortic valve was investigated in rabbits on a 2%-cholesterol-enriched diet and related to distribution of intramural stress in the valve. Initially the lesions appeared at the base of the leaflet on the aortic face and with time spread further out into the leaflet and up the wall of the aortic sinus. In the leaflet, the lesion occurred only in the pressure-bearing part and was primarily composed of a mass of foam cells. By 10 weeks primary fatty plaques were still confined to the aortic face but fibroblasts within the leaflet had also taken up fat. Even after 33 weeks, the atheromatous plaque had not spread beyond the pressure-bearing part of the leaflet. From silicone rubber casts of the valve it was observed that only part of the leaflet was under pressure and the remaining leaflet sustained no pressure gradient. The maximum intramural stress occurred during diastole on the pressure-bearing part. In systole, the blood flow produced shear stress on the entire leaflet. Hence, occurrence of atherosclerotic lesions only in the area of maximum intramural stress suggests that intramural stress and not shear stress plays an important role in accelerating the process of atherosclerosis.

Nodular regenerative hyperplasia of the liver associated with macroglobulinemia. A clue to the pathogenesis.

Nodular regenerative hyperplasia of the liver is an infrequent condition characterized by transformation of the hepatic parenchyma into nodules with only mild fibrosis. Little is known about the etiology except that there is usually an underlying chronic disease, such as Felty's syndrome, which antedates the development of clinical liver disease. It is poorly understood how the associated diseases contribute to the pathogenesis of nodular regenerative hyperplasia. Presented are four cases of nodular regenerative hyperplasia in which macroglobulinemia was also present. This new association suggests to us a hypothesis for the pathogenesis of nodular regenerative hyperplasia. Histologic examination of the livers in these and other cases of nodular regenerative hyperplasia reveals widespread obliteration of the small portal veins. Postmortem angiography of one liver in the present series demonstrated that the nodules were well perfused and that the atrophic areas were poorly perfused with portal blood. This supports the view that atrophy of lobules results from a lack of portal blood supply and that nodules develop from lobules well supplied with portal blood. In each of the clinical conditions associated with nodular regenerative hyperplasia, including macroglobulinemia, inflammatory or thrombotic vascular lesions are found in many organs. Therefore, nodular regenerative hyperplasia may be the hepatic expression of a more widespread vascular disease.

Selective active site inhibitors of human lactate dehydrogenases A4, B4, and C4.

Human lactate dehydrogenases (LDH-A4, -B4, and -C4) are highly homologous with 84-89% sequence similarities and 69-75% amino acid identities. Active site residues are especially conserved. Gossypol, a natural product from cotton seed, is a non-selective competitive inhibitor of NADH binding to LDH, with K(i) values of 1.9, 1.4, and 4.2 microM for LDH-A4, -B4, and -C4, respectively. However, derivatives of gossypol and structural analogs of gossypol in the substituted 2,3-dihydroxy-1-naphthoic acid family exhibited markedly greater selectivity and, in many cases, greater potency. For gossypol derivatives, greater than 35-fold selectivity was observed. For dihydroxynaphthoic acids with substituents at the 4- and 7-positions, greater than 200-fold selectivity was observed. Inhibition was consistently competitive with the binding of NADH, with dissociation constants as low as 30 nM. By comparison, a series of N-substituted oxamic acids, which are competitive inhibitors of the binding of pyruvate to LDH, exhibited very modest selectivity. These results suggest that substituted dihydroxynaphthoic acids are good lead compounds for the development of selective LDH inhibitors. Selective inhibitors of LDH-C4 targeted to the dinucleotide fold may hold promise as male antifertility drugs. Selective inhibitors of LDH-A4 and -B4 may be useful for studies of lactic acidemia associated with ischemic events. More broadly, the results raise the question of the general utility of drug design targeted at the dinucleotide binding sites of dehydrogenases/reductases.

Familial Dandy-Walker malformation associated with macrocephaly, facial anomalies, developmental delay, and brain stem dysgenesis: prenatal diagnosis and postnatal outcome in brothers. A new syndrome?

Brothers are reported with an apparently new constellation of manifestations including Dandy-Walker complex (DWC), migrational brain disorder, macrocephaly, and facial anomalies. The first brother presented at birth, the second was detected prenatally with DWC and the pregnancy terminated. Fetal brain histopathology showed DWC associated with brainstem dysgenesis. Inheritance is likely autosomal or X-linked recessive. An extensive review of the differential diagnosis of DWC is provided.

Phrenic involvement in Charcot-Marie-Tooth disease. A pathologic documentation.

A 69-year-old woman diagnosed as having Charcot-Marie-Tooth disease (CMT) for 30 years' duration died of respiratory failure secondary to diaphragmatic weakness. At autopsy, identical neuropathic changes were found in phrenic and other affected somatic peripheral nerves. We conclude that the phrenic nerve may be involved by the neuropathy of at least some forms of CMT.

Role of mechanical stress in calcification of aortic bioprosthetic valves.

Calcification of bioprostheses used for heart valve replacement is a serious problem, since it causes bioprosthetic dysfunction. In vivo, bioprostheses are subjected to large mechanical stresses during each cardiac cycle. We investigated whether stresses play a major role in calcification of bioprostheses. Previous studies of Carpentier-Edwards porcine, Hancock porcine, and Ionescu-Shiley pericardial bioprostheses indicated that the highest stresses occurred in the areas of greatest flexion of the leaflet. In porcine bioprostheses, stresses were greater in the commissural region than at the base, and were compressive on the aortic surface of the leaflet. The pericardial tissue showed shear deformation in the zone of flexion. In the present study, the three types of bioprostheses were implanted in the aortic position in calves to investigate the development, location, and distribution of calcification. Visual, radiographic, and histologic techniques were used. All bioprostheses showed calcification which began in the area of leaflet flexion. In porcine bioprostheses, calcification occurred earlier in the commissural region than at the base. The earliest calcific deposits were localized within collagen cords on the aortic surface of the leaflets. In pericardial bioprostheses, calcification occurred at multiple foci along the zone of leaflet flexion and was located between and within layers of collagen along planes parallel to the leaflet surface. Hence calcification in all bioprostheses began in the areas of greatest stress. In porcine bioprostheses, calcification was present where collagen fibers are likely to have been damaged by compressive stresses. In pericardial bioprostheses, calcification was found along the planes of shear where structural integrity is likely to have been disrupted by the sliding of individual layers of collagen over each other. It is concluded that mechanical stresses initiate calcification by damaging the structural integrity of the leaflet tissue. Therefore, calcification of bioprostheses can be inhibited by reducing functional stresses through the modification of design and tissue properties to duplicate those of the natural aortic valve.

The dynamic aortic root. Its role in aortic valve function.

By attaching appropriate measuring devices to the wall of an intact aortic root at the level of leaflet coaptation, we have measured a 16 per cent diameter change during each cardiac cycle. The dimensional changes observed can by themselves explain aortic valve function and obviate the postulation that the leaflets shorten and lengthen during each cardiac cycle. The tissue composition of the aortic root and leaflets is more compatible with this theory than with other postulations. Such a dynamic aortic root may explain the longevity of the actual aortic leaflets, in that leaflet fatigue stress is minimized by changes in aortic root dimension.

Visceral infarction caused by cocaine abuse: a case report.

Cocaine abuse is now known to result in a wide variety of medical illnesses. We report our experience with one patient who had abdominal pain and was found to have near-total infarction of all abdominal viscera. The cause of this and other medical complications of cocaine abuse (i.e., extreme vasoconstriction) is discussed in detail. Physicians should maintain a high index of suspicion when dealing with complaints of abdominal pain by cocaine users.

Evidence for the role of 2-hydroxychromene-2-carboxylate isomerase in the degradation of anthracene by Sphingomonas yanoikuyae B1.

Sphingomonas yanoikuyae B1 is extremely versatile in its catabolic ability. An insertional mutant strain, S. yamoikuyae EK504, which is unable to grow on naphthalene due to the loss of 2-hydroxychromene-2-carboxylate isomerase activity, was utilized to investigate the role of this enzyme in the degradation of anthracene by S. yanoikuyae B1. Although EK504 is unable to grow on anthracene, this strain could transform anthracene to some extent. A metabolite in the degradation of anthracene by EK504 was isolated by high-pressure liquid chromatography (HPLC) and was identified as 6,7-benzocoumarin by UV-visible, gas-chromatographic, HPLC/mass-spectrometric, and 1H nuclear magnetic resonance spectral techniques. The identification of 6,7-benzocoumarin provides direct chemical and genetic evidence for the involvement of nahD in the degradation of anthracene by S. yanoikuyae B1.

Stresses of natural versus prosthetic aortic valve leaflets in vivo.

During normal function of the aortic valve, the aortic leaflets undergo not only cyclic loading and unloading but also cyclic reversal of their curvature. The stresses induced in the leaflet due to these variations have been computed using a new concept based on the structure of the leaflet. Membrane stresses have been related to the pressure difference across the leaflet and bending stresses to the leaflet curvature. Total stresses were obtained by adding the two stresses. Total stresses in bioprosthetic and synthetic leaflets also were computed using the same approach. In systole, the natural leaflet is subjected to much lower total stress than a bioprosthetic or a synthetic leaflet. The natural leaflet is not subjected to compressive stresses during the cardiac cycle, whereas bioprosthetic and synthetic leaflets must sustain compressive stresses during systole. The differences in stress patterns of these leaflets indicate that there is a difference in their longevity.

Stress sharing between the sinus and leaflets of canine aortic valve.

A knowledge of the behavior of the aortic valve sinuses is necessary to the understanding of stress sharing between the sinuses and the leaflets. Radiopaque markers were placed on the sinuses and the leaflets of dogs during cardiopulmonary bypass, and the movement of the markers was studied using fluoroscopy. The center of the sinus moved radially during each cardiac cycle, but in an inconsistent manner. The sinus was under a dual influence: the passive influence of aortic pressure and the active influence of myocardial contraction. The longitudinal curvature of the sinus showed no dimensional change, whereas the radius of the circumferential curvature decreased by 15.7% from systole to diastole. In diastole, the stress in the sinus was 6.1 g/mm2 and was 24.3 g/mm2 circumferentially and 12.1 g/mm2 radially in the leaflet. Histologically, the main stress-bearing component of the leaflet was made up of thick, dense, collagenous fibers oriented circumferentially. These fibers curved into the sinus wall instead of inserting straight into the aortic wall, thereby suggesting that the high stress in the leaflet is shared with the sinus and that continuity of the circumferential stress exists between the leaflet and the sinus. The leaflet does not pull inwardly on the aortic wall. In diastole, the sinus adapts to the new stress conditions in the leaflet by reducing its radius of circumferential curvature. This stress sharing is important for the longevity of the aortic valve.

[3H]vesamicol binding in human brain cholinergic deficiency disorders.

We measured the binding of the vesicular acetylcholine transport blocker [3H]vesamicol (2-[4-phenylpiperidino] cyclohexanol; AH-5183) to autopsied frontal cortex and amygdala of patients from 4 disorders having a marked brain cholinergic reduction, namely Alzheimer's disease, Parkinson's disease with dementia, dominantly inherited olivopontocerebellar atrophy and Down's syndrome. Although mean activity of the specific cholinergic marker enzyme choline acetyltransferase (ChAT) was markedly reduced by about 60% in frontal cortex in the 4 patient groups and by 80% or greater in amygdala of the Alzheimer's and Down's syndrome patients, [3H]vesamicol binding density was, on average, either normal or only slightly reduced as compared with the controls. This discrepancy suggests that in human brain [3H]vesamicol binding is either not preferentially localized to cholinergic nerve endings or, in these cholinergic deficiency syndromes, a substantial proportion of the vesamicol binding sites persist on cholinergic nerve terminals despite loss of ChAT activity.