Ethacrynic acid and furosemide alter Cl, K, and Na distribution between blood, choroid plexus, CSF, and brain.

Can loop diuretics like ethacrynic acid and furosemide, when administered intravenously, significantly alter ion transport and fluid dynamics in CNS? To shed light on this unresolved issue, we tested the ability of these agents to effect redistribution of Na, K and Cl in adult rat brain. Cl penetration into various CNS regions was assessed as the volume of distribution, i.e., uptake, of 36Cl from blood. Ethacrynic acid and furosemide (50 mg/kg IV) reduced by 20-30% the rate of permeation of 36Cl across the blood-CSF barrier, and they elevated [K] and [Cl] in choroid plexus (CP) by 15-25%. The loop diuretic-induced buildup of K and Cl in CP (lateral and 4th ventricle) was likely a reflection of decreased movement of these ions across the apical membrane into CSF. 36Cl activity in parietal cortex and pons-medulla decreased in treatment with furosemide and ethacrynic acid, due to slowing of Cl transport across blood-brain and/or blood-CSF barriers. Our inhibitory findings in intact rats are consistent with those from previous in vitro experiments demonstrating diminution by loop diuretics of Na, K and Cl transport across isolated CP membranes.


Effect of liposomes on lipid peroxidation and total phospholipids in rabbit ischemic spinal cord model.

The effect of spinal cord ischemia (induced by abdominal aorta ligation for 20 minutes) on lipid peroxidation and TPL composition was investigated and discussed in our previous articles. It is known, that partially reduced species of oxygen can be formed under aerobic conditions. For that reason, the effect of ligation release for 60 minutes was observed in experimental animals treated with the selected liposomes. Administration of CP, (CP+SA) and (CP+Chol) liposomes applied 30 minutes before 20 minutes ischemia revealed an ameliorating effect on in vivo and in vitro Fe-dependent peroxidation manifested by TBA-RS accumulation. Combined use of (CP+SA) liposomes with lipophylic form of stobadine (DP 1031) was not more effective. Application of CP liposomes directly before the ligation release slightly increased the antiradical capacity in spinal cord homogenates comparing with not-treated animals. Accumulation of TBA-RS was accompanied by TPL degradation during recirculation period but values of TPL after liposomal treatment were unaffected.


Long term regulation of nucleoside transport by thyroid hormone (T3) in cultured chromaffin cells.

The adenosine transport in cultured chromaffin cells was increased by the presence of triiodo-L-thyronine (T3) throughout the prolonged period studied. The Vmax values of this transport obtained in absence and presence of 1 microM T3 were 36.21 +/- 2.1 and 44.17 +/- 3.5 (means +/- SD) pmol/10(6) cells/min respectively for 26 hours incubation-time with the hormone. The Km values were not significantly modified. The number of adenosine transporters in cultured chromaffin cells, measured by [3H]nitrobenzylthioinosine (NBTI) binding, was increased by 1 microM T3 for 26 hours incubation-time. The values of binding sites per cell were 33,500 +/- 3,000 and 40,153 +/- 3,700 in absence and presence of T3 respectively, without changing the Kd constant. When the transport studies were carried out in presence of cycloheximide, an inhibitor of protein synthesis, the adenosine transport capacity decreased with a half-life values of 23.9 +/- 2.8 and 24.3 +/- 2.1 hours both in the presence or absence of T3 respectively. When cells were incubated in the presence of both T3 and cycloheximide, not only the activatory effect of T3 was completely abolished but also adenosine transport was decreased to the same extent as with cycloheximide alone. These results indicated that T3 activation of adenosine transport in chromaffin cells required the protein-synthesizing mechanism.


Norepinephrine, dopamine, and 5-HT release from perfused hypothalamus of the rat during feeding induced by neuropeptide Y.

In the unrestrained rat, the hyperphagic-like ingestion of food evoked by the sustained elevation of neuropeptide-Y (NPY) in the hypothalamus was correlated with the release and turnover of monoaminergic transmitters in this structure. A single guide tube was implanted stereotaxically in the perifornical region of the hypothalamus for localized push-pull perfusion of an artificial CSF vehicle or NPY1-36 in a concentration of 10, 50, or 100 ng/1.0 microliters. After the rat was fully satiated, a site reactive to NPY was perfused repeatedly at a rate of 20 microliters/min for 6.0 min with an interval of 6.0-12 min elapsing between each perfusion. Samples of perfusate were analyzed by HPLC with coulometric detection for DA, HVA, DOPAC, NE, MHPG, 5-HT, and 5-HIAA. Although control perfusions were without effect on feeding or monoamine activity, NPY evoked mean cumulative intakes of food of 14 +/- 2.4, 25.6 +/- 3.0 and 26.5 +/- 3.2 g in response to 10, 50, or 100 ng/microliter concentrations of NPY, respectively, over the 4.0-5.0 hr test interval. HPLC analyses showed that during feeding the release of both NE and DA was enhanced significantly. The turnover of both catecholamines likewise increased significantly as reflected by the elevated levels of MHPG, DOPAC and HVA. However, neither the basal efflux of 5-HT nor its turnover, as reflected by the output of 5-HIAA, was affected during feeding induced by NPY perfused in the hypothalamus. These results suggest that a sustained elevation of NPY in the hypothalamus causes a perturbation in the basal activity of NE and DA which are both implicated in the neuronal mechanism regulating normal eating behavior. Thus, these catecholamine neurotransmitters are envisaged to comprise an intermediary step in the functional role played by NPY in the hypothalamus in integrating the control of energy metabolism and caloric intake.


Regional effects of neurotensin on the electrically stimulated release of [3H]dopamine and [14C]acetylcholine in the rat nucleus accumbens.

This study has shown that neurotensin (NT) increases the electrically stimulated release of [3H]DA to a similar extent in all but the extreme caudolateral area of the rat nucleus accumbens and appears to modulate DA release equally in the medial and lateral zones of this brain area. The simultaneous release of ACh was not significantly affected by NT.


Mitochondrial factors involved in Parkinson's disease by MPTP toxicity in Macaca fascicularis and drug effect.

The maximal rates (Vmax) of some mitochondrial enzyme activities related to energy transduction (citrate synthase, succinate dehydrogenase, malate dehydrogenase, NADH-cytochrome c reductase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase, glutamate-pyruvate- and glutamate-oxaloacetate- transaminases) were evaluated in non-synaptic ("free") and intrasynaptic "light" and "heavy" mitochondria from hippocampus of Macaca fascicularis (Cynomolgus monkey). The different mitochondrial populations were isolated from the hippocampus of monkeys treated p.o. with dihydroergocryptine at a dose of 12 mg/kg/day before and during the induction of a Parkinson's-like syndrome by MPTP administration (i.v., 0.3 mg/kg/day for 5 days). The MPTP administration modified the activity of some enzymes related to the metabolism of glutamate and the activity of succinate dehydrogenase on selected types of mitochondria. Pharmacological treatment by dihydroergocryptine promoted return to the steady-state levels of most enzymes, demonstrating a protective effect on these biochemical parameters.


Soluble enkephalin-degrading enzymes released by lymphomic and erythroleukaemic cell lines.

The possible existence of soluble proteolytic enzymes released by cells of lymphomic (U937 and 1301) and erythroleukaemic (K562) lines was studied measuring the hydrolysis of 3H-leucine enkephalin in the presence of cell-free supernatants obtained from these lines. Results indicate that leu-enkephalin is rapidly degraded in the presence of these supernatants, and that enkephalin disappearance is paralleled by the formation of peptides that can be interpreted as its hydrolysis fragments. To characterize the factors involved in leu-enkephalin degradation, cell supernatants were analyzed by ion exchange and by steric exclusion chromatography. Data obtained indicate the presence of three groups of proteins active in leu-enkephalin degradation: aminopeptidases, dypeptidylaminopeptidases and dypeptidylcarboxypeptidases. In all three lines, these enzymes are represented by a considerable number of distinct activities. The sizable number of soluble enzymes identified and the significant total activity observed suggest a possible role in the regulatory degradation of informational peptides, as proposed by several groups for the membrane-bound proteolytic enzymes of immunocompetent cells.


Germanium-68 as a possible marker for silicon transport in rat brain.

Silicon (Si) is an essential trace element normally present in brain and cerebrospinal fluid, although the mechanism by which it enters and distributes in brain is largely unknown. Due to the short radioactive half-life of 31Si (156 min) we have investigated the use of 68Germanium (68-Ge, half-life 282 days) as a possible marker for Si transport in rat brain over longer periods than are possible with 31Si. Adult male anaesthetised rats were given a bolus of 68Ge I.V. and arterial blood samples taken during experiments that lasted between 5 min and 3 days. At termination, the brain was removed and analysed for radioactivity as were the plasma samples. Data were analyzed by Graphical Analysis which showed that the blood-brain barrier permeability to 68Ge (Kin approximately 10(-4) ml/min/g) is similar to that for many non protein-bound electrolytes in plasma and that 68Ge fluxes across cerebral capillaries are bidirectional. The autoradiographic distribution of 68Ge in brain was homogenous. Our results are in agreement with those of previous studies using 31Si or 68Ge, which suggest 68Ge may be a useful marker for Si when investigating the role of this element in conditions such as neurodegenerative diseases.


Enhanced GABA release in cerebral cortical slices derived from rats with thioacetamide-induced hepatic encephalopathy.

The release of newly loaded [3H]GABA was studied in slices of different brain regions derived from rats in which acute hepatic encephalopathy (HE) was induced with a hepatotoxin thioacetamide. HE increased both spontaneous and high (50 mM) ammonium chloride-evoked GABA release in cerebral cortical slices by 38% and 50%, respectively. No effects of HE were noted in cerebellar or striatal slices. An increased release of GABA in the cerebral cortex may contribute to the endogenous benzodiazepine-mediated enhancement of GABAergic tone, which is thought to be partly responsible for the pathophysiological mechanism of HE.


Velocity of Ellman's reaction and its implication for kinetic studies in the millisecond time range.

A detailed study of the velocity of the reaction between Ellman's reagent and thiocholine was undertaken, in order to test the possibilities of this reaction as a detection method for the earlier stages of cholinesterases reactions. Experiments were carried out on a stopped-flow apparatus with a built-in spectrophotometer. The obtained experimental data were analyzed by fitting the data to theoretical kinetic equations derived for the reaction. In this way, a complete kinetic characterization of the reaction was obtained. An important practical result derived from our investigations is the finding that, under most experimental conditions, the Ellman's reaction is more than sufficiently rapid as a detection method. However, in the case of reactions in the time scale of 200 milliseconds or less, this being 5 times the half life of Ellman's reaction at standard conditions, one has to consider the interference of this reaction with the enzyme reaction itself.


Neuronal cell cultures: a tool for investigations in developmental neurobiology.

The aim of this review is to describe environmental requirements for survival of neuronal cells in culture, and secondly to survey the complex interplay between hormones, neurotrophic factors, transport- and extracellular matrix- proteins, which characterize the developmental program of differentiating neurons. An overall reconsideration of the literature in this vast field is above the limits of the present paper; since progress and refinement in the techniques of neuronal cell cultures have paralleled the advancement in Developmental Neurobiology, we will run instead through the main steps which form the conceptual framework of neuronal cell cultures.


Structure of hypothalamic coronaro-constrictory peptide factors.

The following peptide structure in 3 of 5 coronaro-constrictory peptide factors isolated from bovine hypothalamus was determined by amino acid analysis and Edman degradation: 1) (P1)--Val-Val-Tyr-Pro-Trp; 2) (P2)--Val-Val-Tyr-Pro-Trp-Thr; 3) (P3)--Leu-Val-Val-Tyr-Pro-Trp-Thr. A computer search for these amino acid sequences revealed that these peptides represent fragments 33-37; 33-38; 32-38 of the beta-chain of bovine hemoglobin. Solid phase peptide synthesis of 2 peptides (P2 and P3) was carried out. It was established that synthetic peptides had the properties of coronaro-constrictory peptides. The possibility of the formation of hypothalamic coronaro-constrictory peptides in vivo is discussed.


Evaluation of the mechanisms by which gamma-amino-butyric acid in association with phosphatidylserine exerts an antiepileptic effect in the rat.

The i.p. injection in rats of GABA (740 mg/Kg) after sonication with an equal amount of phosphatidylserine (PS) has an antiepileptic effect. The injection of plain GABA has no such an effect. Blood, brain and synaptosomal accumulation of exogenous labeled GABA under the two circumstances are evaluated. In the case of GABA/PS injection there is a higher passage of the exogenous labeled neurotransmitter into the blood and brain nerve endings (synaptosomes). A higher synaptosomal accumulation of the exogenous labeled neurotransmitter is found even when GABA and PS are injected separately. Since these accumulation increases occur at a time when there is the antiepileptic effect, they seem relevant to it. Our interpretation of the chain of the events resulting in the antiepileptic action is that the phospholipid facilitates from the beginning the first passage of the exogenous neurotransmitter form the peritoneum to the blood. Then a higher passage to the brain tissue and eventually to the GABA-ergic nerve endings ensues. The brisker accumulation of the exogenous neurotransmitter in the nerve endings could be at the basis of a more efficient GABA-ergic inhibitory control in the brain.


Muscarinic receptor subtypes in bovine adrenal medulla.

Catecholamine secretion in the bovine adrenal medulla is evoked largely by nicotinic receptor activation. However, bovine adrenal medulla also contain muscarinic receptors that mediate several cell responses. To understand the physiological role of muscarinic receptors in the bovine adrenal medulla it is important to identify the pharmacological subtypes present in this tissue. For this, we analyzed the abilities of different selective muscarinic antagonists in displacing the binding of the non-selective antagonist [3H] quinuclidinyl benzylate to an enriched plasma membrane fraction prepared from bovine adrenal medulla. All the selective antagonists bind at least two bindings sites with different affinities. The binding profile of the sites with high proportion is similar to the M2 subtype and those present in low proportion have a M1 profile. However, some variation in the proportion of the sites for the different ligands suggest the presence of the third pharmacological subtype (M3). We conclude that the sites in high proportion (60-80%) correspond to M2 muscarinic subtypes, and the rest is constituted by M1 plus M3 subtypes. The presence of multiplicity of subtypes in the adrenal medulla membranes suggests a diversity of functions of muscarinic receptors in the adrenal gland.


D-penicillamine affects lipid peroxidation and iron content in the rat brain cortex.

D-Penicillamine, a trifunctional amino acid known for its ability to form metal complexes and for being a radical scavenger, has been investigated "in vitro" and "in vivo" in the rat brain cortex. At 50 microM the drug facilitated lipid hydroperoxides and TBARS formation in brain cortex homogenates, while at higher concentrations a clear inhibition of the lipid peroxidative process was observed. The activity of the D-penicillamine (25 and 50 mg/Kg i.p.) was evaluated "in vivo" after a 7-day treatment in rats in whose brain cortex a slow process of lipid peroxidation was induced by iron-saccharate injection. Lipid hydroperoxides, lipid soluble fluorescent compounds and the iron content of both iron-injected and contralateral hemicortices showed a significant decrease in comparison to rats untreated with D-penicillamine. The higher dose also induced in normal rats a significant decrease in basal TBARS and iron content of the brain cortex. In the iron-injected cortex the observed Fe2+/Fe3+ ratio was significantly different from that of normal rats. On the contrary ratios obtained form D-penicillamine treated animals were higher in comparison to both normal and iron-injected animals. These results suggest that D-penicillamine, acting as a reducing agent, inhibits the iron redox system and, as a chelating agent, can remove metal from action sites where lipid peroxidation may occur.


A unique hydrophobic domain of rat brain globular acetylcholinesterase for binding to cell membranes.

Both salt-soluble and detergent-soluble rat brain globular acetylcholinesterases (SS- and DS- AChE EC 3.1.1.7) are amphiphiles, as shown by detergent dependency of enzymatic activity and binding to liposomes. Proteinase K and papain treatment transformed SS-AChE and DS-AChE into forms that, in absence of detergent, no longer aggregated nor bound to liposomes. In contrast, phosphatidylinositol-specific phospholipase C had no effect on these properties. Labeling DS-AChE with 3-(trifluoromethyl)-3-(m-(125I)-iodophenyl) diazirine ([125I]TID) revealed, by polyacrylamide gel electrophoresis under reducing conditions, one single band of 69 kD apparent molecular mass. The same pattern was previously obtained with Bolton and Hunter reagent-labeled enzyme. Proteinase K treatment transformed the 11 S [125I]TID labeled AChE into a 4 S form which no longer showed 125I-radioactivity and was unable to bind to liposomes. These results are compatible with the existence of a hydrophobic segment present both on salt-soluble and detergent-soluble 11 S AChE as well as on the minor forms 4 S and 7 S. This segment is not linked to the catalytic subunits by disulfide bounds in contrast to the 20 kD non-catalytic subunit described by Inestrosa et al.


New insights into the cause of Parkinson's disease.

Current concepts as to the cause of Parkinson's disease (PD) suggest an inherited predisposition to environmental or endogenous toxic agents. Study of the substantia nigra after death in PD has highlighted three major changes: (1) evidence of oxidative stress and depletion of reduced glutathione; (2) high levels of total iron, with reduced ferritin buffering; and (3) mitochondrial complex I deficiency. Which of these is the primary event, generating a secondary cascade of changes culminating in nigral cell death, is unknown. In presymptomatic Lewy body-positive control brains, the nigra shows depletion of reduced glutathione content and, possibly, a reduction of complex I activity. Whatever the significance of these various abnormalities, be they causal or secondary, they provide novel targets for the development of new strategies to treat the cause of PD.


[3H] cocaine labels a binding site associated with the serotonin transporter in guinea pig brain: allosteric modulation by paroxetine.

We studied the characteristics of [3H]cocaine binding to membranes prepared from whole guinea pig brain. Cocaine binding was specific and saturable. A one-site binding model fit the data adequately: the Kd value of [3H]cocaine was 44 nM with a Bmax value of 280 fmol/mg protein. The rank order of potency for the [3H]cocaine binding site was paroxetine > clomipramine > (-)-cocaine > fluoxetine > mazindol > desipramine > GBR12909 > phencyclidine > benztropine > GBR12935 > (+)-cocaine. The IC50 values of these drugs for inhibition of [3H]cocaine binding were highly correlated with their IC50 values for inhibition of [3H]5-HT uptake into synaptosomes prepared from whole guinea pig brain. High affinity 5-HT uptake inhibitors produced dose-dependent wash-resistant (pseudoirreversible) inhibition of [3H]cocaine binding. The wash-resistant inhibition produced by paroxetine was due to an increase in the Kd of [3H]cocaine binding sites, and was accompanied by an increase in the dissociation rate, consistent with an allosteric mechanism. These studies suggest that, using membranes prepared from whole guinea pig brain, [3H]cocaine labels a binding site associated with serotonin transporter and that paroxetine and cocaine bind to different sites on the serotonin transporter.


Arterial delivery of myoblasts to skeletal muscle.

One of the major limitations of myoblast implantation as a therapy for muscular disease is that multiple injections by intramuscular implantation may be required for widespread delivery of cells. Also, some sites (eg, the diaphragm) are relatively inaccessible to injection. As an alternative, we have undertaken intra-arterial administration of myoblasts. For these experiments, we used donor cell myoblasts from the immortal L6 cell line labeled with lacZ via the beta-gal-at-gal retrovirus. In our model, target rat skeletal muscle (tibialis anterior [TA]) was injured using 0.5 ml of 0.5% bupivacaine and 15 IU of hyaluronidase; saline was injected into the contralateral side as a control. We infused 3 x 10(6) lacZ-positive cells into the abdominal aorta of previously injured, immunosuppressed (cyclosporine A) rats. At 7, 14, and 28 days, TA, liver, heart, lung, and spleen were examined for lacZ staining. In both the injured and control muscles, a few differentiated, lacZ-positive muscle cells were present, both singly and in groups, at each time point. These studies demonstrate that genetically labeled, transformed myoblasts may migrate from the arterial circulation to muscle and fuse there to form differentiated muscle cells. It is conceivable that intra-arterial delivery of myoblasts may have a role in the therapy of selected diseases of skeletal muscle.


Hemimasticatory spasm: clinical and electrophysiologic observations.

Hemimasticatory spasm is a rare disorder of the trigeminal nerve that produces involuntary jaw closure due to paroxysmal unilateral contraction of jaw-closing muscles. We report three patients with this disorder. Electrophysiologic studies demonstrated normal blink and masseter reflexes. The masseter inhibitory reflex was absent during periods of spasm. Needle electromyography demonstrated irregular bursts of motor unit potentials that were identical to the pattern observed in hemifacial spasm. The electrophysiologic findings suggest ectopic excitation of the trigeminal motor root or its nucleus, an abnormality that is analogous to ectopic excitation of the facial nerve in hemifacial spasm. One patient improved temporarily with surgery, one improved while on treatment with carbamazepine, and another responded favorably to botulinum toxin injection.


Cerebellar diaschisis revisited: pontine hypometabolism and dentate sparing.

A unilateral supratentorial lesion may cause hypometabolism in the contralateral cerebellar hemisphere (crossed cerebellar diaschisis). We analyzed glucose metabolism, measured by PET-FDG, in the posterior fossa in 67 patients (78 PET studies) with primary unilateral supratentorial brain tumors selected for visually obvious metabolic asymmetry in the cerebellar hemispheres. We found that glucose utilization was 17% lower in the contralateral cerebellar cortex (compared with the ipsilateral one), consistent with the selection criterion, and 19% lower in the ipsilateral pons, wherein lie the first order synapses of the corticopontocerebellar pathway. This finding helps to validate the prevalent view that cerebellar diaschisis is due to interruption of afferent input from the corticopontocerebellar pathway. However, glucose metabolism in the contralateral dentate nucleus was relatively preserved--only 2% less than the ipsilateral dentate. This "dentate sparing" suggests preservation of afferent input to the largest of the deep cerebellar nuclei from the Purkinje cells in the cortex, despite interruption of the major excitatory input to the Purkinje cells.


Vertigo and the anterior inferior cerebellar artery syndrome.

We present two patients with clinical features of infarction in the distribution of the anterior inferior cerebellar artery (AICA) who had vertigo as an isolated symptom for several months prior to infarction. Both had risk factors for cerebrovascular disease and other episodes of transient neurologic symptoms not associated with vertigo. At the time of infarction they developed vertigo, unilateral hearing loss, tinnitus, facial numbness, and hemiataxia. MRI identified hyperintense lesions in the lateral pons and middle cerebellar peduncle on T2-weighted images. Audiometry and electronystagmography documented absent auditory and vestibular function on the affected side. Since the blood supply to the inner ear and the vestibulocochlear nerve arises from AICA, a combination of peripheral and central symptoms and signs is characteristic of the AICA infarction syndrome. The vertigo that preceded infarction may have resulted from transient ischemia to the inner ear or the vestibular nerve.


Accuracy and interobserver reliability of scalp ictal EEG.

We studied the accuracy and reliability of scalp ictal EEG in 137 complex partial seizures (119 temporal and 18 extratemporal) in 35 patients in whom we knew the correct site of seizure origin because all patients had been seizure-free for more than 2 years after seizure surgery. Three electroencephalographers independently determined side of seizure origin based on activity at onset of electrographic seizure (ASO), rhythmic theta and alpha (RTA), postictal findings (PIF), and the electrographic seizure as a whole. When all seizures were analyzed, including those with generalized features or obscured by artifact, we determined side of seizure onset correctly in 76% to 83% of temporal seizures and 47% to 65% of extratemporal seizures. In most of the remainder, a lateralization judgment was impossible. When analysis was confined to those seizures in which lateralization was possible, we correctly lateralized 93% to 99% of temporal seizures and 89% to 100% of extratemporal seizures. Interobserver reliability was excellent. RTA and PIF were more accurate than ASO. RTA was significantly more common in temporal seizures. Our data indicate that lateralization by scalp EEG is highly accurate and reliable.


A clinical staging classification for type C Niemann-Pick disease.

Analysis of the temporal sequence of neurologic events, neurophysiologic abnormalities, and longevity in 36 Niemann-Pick type C patients revealed two clinical subgroups with five stages of severity within each group. Patients with a preschool onset (group I; n = 18) had a higher mortality than did patients with a school-age onset (group II; n = 18). An asymptomatic phase (stage 0) was defined by biochemical and histopathologic evidence of disease. The initial manifestations of stage 1 were a movement disorder (group I) and cognitive difficulties (group II) accompanied by impaired vertical saccadic eye movements and abnormal acoustic reflexes. Stage 2 was characterized by the sequential occurrence of vertical supranuclear gaze palsy (VSGP), cognitive difficulties, and dysarthria in group I and a movement disorder, VSGP, and dysarthria in group II. Pyramidal tract signs and abnormal brainstem auditory evoked responses defined stage 3 in both groups. Stage 4 culminated in a nonambulant, vegetative state.


Possible use of CSF glycosphingolipids for the diagnosis and therapeutic monitoring of lysosomal storage diseases.

We used a high-performance liquid chromatography method to measure CSF gangliosides, neutral glycolipids, and sulfatides in patients with lysosomal storage disorders. These measurements could be done on less than 1 milliliter of CSF. In patients with GM1 gangliosidosis, GM1 ganglioside was increased, and in GM2 gangliosidosis patients, GM2 ganglioside was increased in CSF. Sulfatides were variably increased in CSF early in the course of the disease and appeared to be a means of monitoring patients, following bone marrow transplantation. Fabry's disease patients showed an increase in globotriaosylceramide, but Krabbe's disease patients did not demonstrate an increase in galactosylceramide. This study suggests that CSF glycosphingolipid measurements may prove helpful in the diagnosis and monitoring of lysosomal storage diseases.


Trisomy 17p associated with Charcot-Marie-Tooth neuropathy type 1A phenotype: evidence for gene dosage as a mechanism in CMT1A.

Charcot-Marie-Tooth neuropathy type 1A (CMT1A) is associated with a DNA duplication on chromosome 17, band p11.2, resulting in partial trisomy for this region in CMT1A patients. The 17p11.2 duplication may lead to the CMT1A phenotype either through disruption of a gene at the duplication breakpoint junction or by trisomic dosage and overexpression of a gene within the duplication. To test the latter model, we evaluated a patient with complete translocation trisomy 17p for signs of CMT1A. In addition to the dysmorphic features seen in trisomy 17p, a neurologic examination and electrophysiologic studies detected a demyelinating neuropathy, compatible with CMT1A. A karyotype on the patient's father found a balanced translocation [t(14;17)] with breakpoints on chromosome 17 in either band p11.1 or proximal p11.2. An analysis of the patient's DNA confirmed trisomy 17p and mapped the translocation breakpoint to a region in 17p11.2, proximal to the duplication breakpoint in CMT1A. Our observations in this patient with trisomy 17p are relevant to an understanding of the genetic mechanism in CMT1A and provide strong evidence that gene dosage through segmental trisomy for 17p11.2 results in the CMT1A phenotype.


Strong correlation between the number of CAG repeats in androgen receptor genes and the clinical onset of features of spinal and bulbar muscular atrophy.

X-linked spinal and bulbar muscular atrophy (SBMA), a motor neuron disease associated with androgen insensitivity, is caused by androgen receptor gene mutations with an increased number of tandem CAG repeats in exon 1. We investigated the increased number of CAG repeats in androgen receptor genes of 19 SBMA patients and found that this correlated strongly with the age at onset of muscle weakness. Thus, SBMA is the first genetic disease in which a strong correlation between the degree of genetic abnormality (number of CAG tandem repeats) and clinical phenotypic expression is demonstrable. The results further indicate that androgen gene mutation is directly involved in the degeneration of motor neurons.


[Protective action of 21-aminosteroids in post-ischemic shock (splanchnic artery occlusion). Experimental model].

In anesthetized Wistar female rats a post-ischemic shock have been induced by splanchnic artery occlusion (S.A.O.). In these condition all animals died at 90 min., past release of occlusion and splanchnic reperfusion. 100% of pretreated rats with 21-Aminosteroids (U74389F) at doses of 1.5 mg.kg-1 survive over 3-6 hours, and 50% over 12 hours. Moreover, TNF alpha in these animals decrease significantly (p < 0.05). These results shown that 21-Aminosteroids can cause protective activity on lipoperoxidative damage in post-ischemic shock.


[Inotropic treatment in heart transplantation].

The safe conduct of anesthesia and intensive care for heart transplant recipient requires a sound understanding of the pathophysiology of advanced cardiac failure through knowledge of anesthetic and cardiovascular pharmacology and an appreciation of the altered physiologic and pharmacologic responses of acutely denervated and transplanted heart. The most serious dysfunction is acute distension and failure of the transplanted heart's right ventricle. Hemodynamic monitoring and TEE are useful in the management of inotropic support during heart transplantation.


[Different anaesthetic technique: conduction and outcome from multidisciplinary procedures].

Different anesthetic techniques in perioperative times (intraoperative induction and maintenance of anaesthesia, recovery and 24 and 48 postoperative hours) were evaluated in 100 patients underwent general surgery. After randomization, 4 groups were clinically and statistically compared according to anesthesia technique (propofol + fentanyl in air/O2; isoflurane + fentanyl in air/O2; propofol + fentanyl in N2O/O2; isoflurane in N2O/O2). The results show that conduction of anesthesia without N2O is difficult; but the adequacy of induction and maintenance of anesthesia, the speed of recovery and the quality in the postoperative period show no difference in the anesthesia techniques used.


Critically ill patients and fat emulsions.

In critically ill patients, lipid tolerance may be impaired. In ICU, patients are usually given TPN including fat emulsions. If sedation with propofol is given simultaneously the fat load increases and may exceed the maximal clearing capacity of exogenous fat emulsion unless the administration of the parenteral fat is adjusted to take account of the lipid contained in propofol. An accumulation of fat may result in the so-called 'fat overload syndrome'. Close monitoring of serum triglyceride concentration is therefore recommended to avoid fat overload.


[Esophageal achalasia: cardiomyotomy or pneumatic dilatation?].

Sixty-four patients with achalasia of the esophagus were surgically treated during the period 1973-1990. They were analyzed a late follow-up (mean = 78 months) by means of subjective and objective parameters. The Authors emphasize the efficiency of the diagnostic approach so that surgical treatment offers better results. The surgical technique of choice consists of an anterior esophagomyotomy (extending from 6 cm above the esophagogastric junction down to 1-2 cm below it) with the addition of an anterior Dor antireflux procedure through a laparotomy. The other therapeutic approach to achalasia is pneumatic dilatation of lower esophageal sphincter. A retrospective comparison of two different treatments is made through the analysis of the literature (medlars 1986-1990). Relief of dysphagia is reported in 92.78% of patients treated by myotomy and in 78.71% of those treated by forceful dilatation. The morbidity rate is greater after pneumatic dilatation (6% vs 5%) and the mortality rate is 1.1% after myotomy and 0.2% after dilatation. There are not rigorous criteria of choice between the two treatment methods but the Authors indicate that Heller's myotomy with an antireflux procedure achieve better and lasting results.


[Carcinoma of the surgically treated stomach. Our experience].

Between 1977 and 1991, 12 patients (11 males and 1 female; median age of 62.7 years) with gastric stump cancer were observed. All patients were previously operated for benign gastric (4) or duodenal (8) ulcer disease. Median duration interval between first operation and the diagnosis of gastric carcinoma was 22.0 years (range 7-39 years). Only in 5 patients total gastrectomy was carried out. Two out of these 5 patients are still alive at 2 and 24 months after surgery, while the median survival of remaining patients was about 9 months. The usefulness of close follow-up and digestive endoscopy in peptic ulcer patients who had surgical treatment is considered in order to detect an early gastric stump cancer.


[Leiomyoma of the esophagus].

In this paper the Authors report a review of the clinical records from 1972 to 1985 of the Institut of IV Clinica Chirurgica of Rome of esophageal leiomyoma. We report on 7 cases: three males and four females. Their ages ranged from 37 to 78 years (mean 54 years). The most frequent symptoms were dysphagia (71.4%), loss weight (57.1%) and slight epigastralgia (42.8%). Barium meal, esophagoscopy, esophageal manometry, TAC are the most sensitive procedures for a correct preoperative diagnosis. The therapy of choice is surgical treatment. However surgery is conservative: extramucosal enucleation of the leiomyoma is the procedures of choice. The postoperative course was free of complications, the long-term results were excellent.


[Acute disorders of the biliary tract in geriatric patients].

Acute pathologies of the biliary tract in geriatric patients were examined in this study taking into account the major causes, treatment used and results obtained. All patients aged over 65 who had been hospitalised during the past 17 years for acute pathologies of the biliary tract (564 cases, equivalent to 34.2% of all in-patients suffering from acute biliary pathologies) were included in the study. These patients were then subdivided into 3rd and 4th age groups (65-74 and < 75 years respectively). The results obtained in the 3rd age group (267 patients, 60%) showed the greatest number of cases of inflammatory lithiasic disease of the cholecystus (61.2%) and VBP (17.7%), whereas 45 patients, equivalent to 49.5%, presented tumours with jaundice. Out of a total of 179 cases in patients in the 4th age group, equivalent to 39.3%, 119 (66.5%) were suffering from lithiasic cholecystitis and 16 (8.9%) from calcolosis of the VBP with jaundice. Cancer of the pancreas head was diagnosed in 27 patients (58.7%), whereas 9 (19.6%) had obstruent cancer of the biliary tract. The Authors conclude that both the preoperative preparation, the choice of operation and postoperative treatment give satisfactory results with a very low early mortality (0.8% in non-tumour cases and 6.9% in tumour cases).


[Endoscopic and intraoperative ultrasonography in staging of stomach neoplasms].

In Japan a better prognosis of gastric cancer has been achieved by early diagnosis and wide, careful lymphectomy. This is not true in western countries. Thus the Authors believe that rational surgical strategy and the careful use of advanced diagnostic tools would produce a better outcome. The Authors report the new diagnostic methods that they adopt in every case of gastric neoplasm: endoscopic ultrasonography, which also proved useful in submucosal tumors, like lymphomas; parenteral nutrition, immune status assessment for a possible use of immune response modulators, single-dose antimicrobial prophylaxis, antithrombotic prophylaxis, autologous blood storage, in order to reduce transfusion-linked risks. Surgical strategy is also reported, which includes wide resection with adequate margins, R2 lymphectomy and intraoperative assessment of disease extension by ultrasonography.


[Permanent expanders in esthetic, corrective and reconstructive surgery of the breast].

Since 1986 we used the permanent expandable implant (PEI) as the first choice of prosthesis in breast surgery. The possibilities offered by multiple over-expansions and deflations have been explored: 224 PEI were utilized in 162 patients for aesthetic (38 with bilateral hypoplasia), corrective (20 with asymmetry, tubular breasts or Poland's Syndrome) and reconstructive breast surgery (104 patients for immediate and delayed reconstruction following radical, modified radical, partial and subcutaneous mastectomy). All implants were positioned submuscularly; a latissimus dorsi flap was transposed when pectoralis major was absent or damaged. Either the Becker or the Gibney implant was used. All PEI were immediately or progressively overinflated by 25-80% and then deflated to the planned volume. Twenty-two patients developing capsular contracture were treated by overinflations and deflations with subjective and objective improvement. Many of augmentation mammaplasty patients refused implant deflation to the planned preoperative volume. The over-expansion/deflation process proved to be effective in obtaining ptosis, in maintaining permanent volume symmetry and in keeping the base of tubular breast unfolded.


[Latero-terminal anastomosis in colorectal surgery using a mechanical stapler. Technical note].

Following a discussion of the various methods of colorectal anastomosis in cancer surgery, the Authors describe a technical variant using a mechanical stapler in a high rectal location. The rapidity of anastomosis as well as the decreased risk of dehiscence, fistula and stenosis are underlined.


[Clamping the suprahepatic inferior vena cava in emergency surgery. Technical note].

In major hepatic surgery the temporary exclusion of the vena cava may be achieved using a variety of more or less complex procedures. Alternatively, for use above all in emergency surgery, the paper illustrates a method of clamping the suprahepatic inferior vena cava using a left lateral route, which is quick to carry out and undoubtedly efficient.


[Deep vein thrombosis in surgery].

Deep vein thrombosis is still an underestimated and often unrecognised diseases both in Italy and abroad despite being far from rare and in spite of its severe complications and often disabilitating sequelae. It is a disease which is becoming more frequent due to increased life expectation, the larger number of operations on elderly patients, and the increased frequency of limb injuries. General and specialised surgery is often hampered by this complication. This has raised interest in a more detailed knowledge of the mechanisms leading to DVT, and the correct employment of the latest equipment which enable diagnosis to be made and daily monitoring of the disease during its evolution. But the greatest efforts must be reserved for preventive measures in order to achieve a statistically significant reduction in the incidence of the disease in operated patients. It is to be hoped that a greater awareness of thromboembolic diseases will allow this to be achieved in the future.


[Optimal dose of amino acids administered in total parenteral nutrition (TPN) of malnourished patients].

A plasmatic concentration for each aminoacid, between 1 and 1.5 times the normal value in fasting healthy subjects, is considered as an optimal target during total parenteral nutrition (TPN) in malnourished patients. We have analyzed the correlation between the aminoacid input and the aminoacid plasmatic concentration during TPN at different aminoacid composition. By exponential regression curves we then calculated the input required to keep each aminoacid plasma concentration in the optimal range.


[Primary carcinoma of the cystic duct. A rarity in surgery].

The Authors describe a case of primary carcinoma of the cystic duct as reported in the data od another 29 cases described in literature. The subjects it generally strikes are elderly men and its symptomatology is rather non specific. A preoperative diagnosis is as difficult as ever even with the aid of the most modern diagnostic techniques. The postoperative survival time is comparatively superior to other tumors of gallbladder and biliary tract, independently of the type of the surgical treatment adopts: cholecystectomy with the resection of the cystic duct associated less with lymphadenectomy and partial resection of the hepato-choledochus.


[Cholestatic jaundice secondary to distention of the gallbladder caused by cystic duct syndrome].

The Authors describe a rare case of cholestatic jaundice which persisted due to compression of the biliary tract by a hugely swollen gallbladder due to cystic duct syndrome.


[Isolated neurofibroma of the stomach. Case report and review of the literature].

An uncommon case of gastric neurofibroma is described: it was an incidental finding during assessment for abdominal pain, possibly due to pancreatitis, in a 58 year old man, with no sign of von Recklinghausen's disease. The generic diagnosis of gastric wall neoplasia was made by CT scanning; the neoplasm was resected with wedge resection of gastric wall. Histological and ultrastructural examination revealed a neurofibroma. Gastrointestinal stromal tumors are rare occurrence and usually are of smooth muscle derivation: a small percentage arises from nerve sheet, but such a distinction is never sharp. Neurogenic gastric tumors are usually benign and only 10% of von Recklinghausen associated neurofibromas can undergo malignant transformation. Wide excision of the tumor appears therefore the treatment of choice.


[Pseudo-acute abdomen in familial Mediterranean fever. A case report].

The Authors report a case of familial mediterranean fever with pseudo-acute abdomen recently observed and emphasize how a careful anamnesis can avoid unnecessary surgical intervention.


[Lipoprotein(a): structure, metabolism and atherosclerotic disease].

Lipoprotein(a) was discovered by chance by Berg in 1963; after twenty years of research, the chemical, physical and metabolic characteristics of Lp(a) are now known. This lipoprotein forms the missing link between the lipid metabolism and the coagulation-fibrinolysis process. The A. describe its similarity to plasminogen, its capacity to delay coagulum or embolus destruction and highlight its structural and functional similarity to lipid metabolism. To day, a total of 6 Lp(a) isoforms have been identified with different molecular weights: in addition, the inverse proportion between the isoforms' molecular weight and Lp(a) plasma concentration has been demonstrated. Lp(a) is not the product of the metabolism of other lipoproteins nor is it a catabolite of LDL; it is produced ex-novo and does not apparently exchange its proteic fraction with other lipoproteins. The paper also examines the question of whether Lp(a) is a plasma marker which increases during the formation of atherosclerotic plaque or whether it should not be considered an atherogenetic factor. To this end the possible mechanisms by which Lp(a) is deposited in plaque are examined. Lastly, the paper reviews all studies concerning the relationship between Lp(a), ischemic cardiopathy and cerebrovascular disease.


[Chronic hepatitis and liver cirrhosis].

The Authors consider 349 liver biopsies; 32 of these showed cirrhosis. Patients with chronic hepatitis are at high risk for evolution to cirrhosis. Our aim is to establish the markers HBsAg and HBcAg comparing this with the risk groups and with the possible causes of cirrhosis.


[Gastric and hematologic changes in patients with gastric parietal cell autoantibodies and non-insulin-dependent diabetes mellitus].

Gastric abnormalities are more common in diabetics than in the normal population. They seem to be related to gastric parietal cell autoantibodies (GPCA). We have studied 168 patients affected with non-insulin-dependent diabetes mellitus (NIDDM), and assessed the GPCA in the serum and haematologic disorders. We have also assessed the endoscopic and histological findings of atrophic gastritis in patients with GPCA. GPCA were found in 15.74% of diabetic patients and in 2% of a control group of blood donors. 80% of GPCA positive patients showed signs of atrophic gastritis. Such presence of GPCA seems to be a good marker to identify patients affected by atrophic gastritis and its complications.


[Influence of nutrition, age and vitamin D status on fasting urinary excretion of calcium in postmenopausal women].

The purpose of the present study was to evaluate the influence of nutrition, age, and Vitamin D status on fasting urinary calcium (Ca) as a function of creatinine excretion (Ca/Cr) and of glomerular filtration rate (Ca/GFR) in postmenopausal women. Fasting urinary calcium, urinary Cr and GFR were measured in 18 women aged 54 to 91 years before and after six days of a calcium (400 mg/die) and sodium (100 mEq/die) restricted diet with a controlled content of proteins, lipids and glucides. Aged (over 64 y.) women having an adequate vitamin D status showed fasting urinary Ca/Cr and Ca/GFR after the controlled diet significantly lower than those showed before. It is concluded that fasting Ca/Cr and Ca/GFR may be nutrition-dependent. A revision of the significance of the fasting urinary Ca excretion is consequently suggested.


[Gynecomastia].

Gynecomastia is a benign pathology due to the increased volume of the mammary glands. The various etiological factors lead to an imbalanced estrogen/androgen ratio or to a greater local receptivity to the former with consequent hypertrophy of the mammary stromal gland components. Although the majority of cases are benign and/or transient, gynecomastia must be carefully examined using thorough anamnesis, hormone assays and instrumental tests in order to exclude local or further removed pathology. At present, medical or surgical therapy is reserved for those cases in which this condition is painful and/or psychologically damaging. In this study, following a review of the literature, the Authors focus on the etiological, diagnostic and therapeutic aspects of gynecomastia and illustrate the cases they have observed.


[Neurological changes in aged patients with fractures of the femur: prevalence and clinical aspects].

This study evaluates the prevalence and clinical significance of the main neurological diseases in 246 hospitalized elderly patients with hip fracture, who have to undergo rehabilitative treatment. Eighty-three patients already had clinically noticeable neurological diseases before fracture; they were compared to other components the survey. As for the type of fracture and surgical treatment, differences have not been found. Medical conditions have proved worse among neurological disease bearers; the same patients also had to run into more complications. What results from the study, considering the high prevalence of neurological diseases in patients with hip fractures, suggests that these neurological diseases are important risk factors for accidental falls and it's necessary to provide these patients with careful, continuous hospital assistance.


[Reactive arthritis HLA B27 correlated in hospital patients in a general medicine department].

We examined 14 cases of reactive arthritis seen during the four year period 1982/1985 out of a total of 7,380 admissions. The average age of the patients was 40.1 years, while hospitalisation averaged 15.6 days. More than half the patients presented oligoarthritis manifestations which were also characterized by asymmetry and migratory behavior. Visceral manifestations were noted in 10 of 14 patients (71.4%). Etiological diagnosis was arrived at in only two cases, whereas half the cases showed no positive enteral or urogenital infectious antecedents. The HLA B-27 determination resulted positive in 25% of the cases. This is highly significant (p < 0.01) when compared to the control group 4% positivity. The follow-up was carried out medially for 4 years in all patients and evidenced only one case of persistent joint inflammation at the knee level and another case of relapsing uveitis. This study, performed on a random group of patients hospitalized in a General Medicine Department, confirms for the most part data appearing in the literature.


[Use of ultrafiltration in refractory cardiac decompensation].

Traditional therapy for heart failure (diuretics, digitalic compound, vasodilators, inodilatory ACE-inhibitors) cannot arrest the progressive overloading of the circulatory system so that it is inevitable that a refractory stage to all forms of treatment will be reached when more specialised techniques, such as heart transplant and ultrafiltration will be needed. The paper reports the results obtained in 13 patients in ultrafiltration treatment for refractory heart failure: in the majority of these, a marked improvement in general conditions (edema, dyspnea) was recorded together with a regression from class 5 to class 3 NYHA in 5 patients, and to class 2 for others. The ultrafiltration method in spite of not altering the prognosis which remains negative in these patients, allow those waiting for heart transplant to survive and may improve their chances of surviving heart surgery.


[Prevention of Pneumocystis carinii pneumonia with intermittent trimethoprim-sulfamethoxazole].

To evaluate efficacy and toxicity of intermittent trimethoprim-sulfamethoxazole (T/S) prophylaxis for Pneumocystis carinii pneumonia (PCP) our HIV-positive patients were given T/S (160 mg, 800 mg) twice daily for 3 consecutive days per week. Patients were included only if they met the CDC criteria for PCP prophylaxis, did not have intolerance to T/S, and if follow-up was 3 or more months. Thirty-eight patients received primary prophylaxis (Group I) for a mean period of 18.1 months and 26 patients received secondary prophylaxis (Group II) for a mean period of 15.5 months. Seventeen patients had adverse reactions (14 minor and 3 major reactions). PCP occurred in 1 patient in Group I after 20 months of T/S, and in 2 patients in Group II after 11 and 18 months of T/S. This pilot study suggests that intermittent T/S treatment is efficacious and relatively safe in the prophylaxis for PCP in HIV-positive patients.


[Idiopathic hypereosinophilia syndrome: description of a clinical case and review of the literature].

Idiopathic hypereosinophilia is a disease with an unknown etiology and pathogenesis and uncertain nosographic classification, although there is now tendency to group a number of syndromes under this name which were previously classified separately, although having similar hematological symptoms and clinical manifestations. The paper examines these aspects and reports the case of a patient with idiopathic hypereosinophilia to steroid treatment.


[Asymptomatic bilateral occipital calcifications. A possible atypical form of Sturge-Weber-Krabbe syndrome?].

Sturge-Weber-Krabbe syndrome is a rare congenital neuro-cutaneous disease which is characterized, in its full clinical expression, by facial naevus flammeus and epilepsy with mental retardation. Different atypical cases in which one or more symptoms are missing and clinical course is benign, have been reported in the literature in recent years. In the present paper a possible case of this syndrome radiologically diagnosed, without neurological and cutaneous symptoms, is reported; the importance of a more comprehensive study of this complex disorder, with particular attention to the incomplete forms, is stressed.


[Clinical evaluation of a selective inhibitor of cholesterol synthesis: pravastatin].

The recent introduction in clinical practice of a new class of drugs able to reduce the endogenous synthesis of cholesterol has undoubtedly made a noteworthy contribution to the treatment of hypercholesterolaemia which, as is well known, is one of the greatest risk factors in the natural history of atherosclerotic disease and of its cardiovascular complications. A last generation drug belonging to this family is pravastatin which differs from the other substances inhibiting the activity of the key enzyme of cholesterol metabolism, HMGCaA reductase, because of certain features of the molecule, such as hydrophilia and the fact it is already pharmacologically active at the moment of oral administration. Pravastatin, which is probably a special category of HMGCoA reductase inhibitor, has shown, in numerous experimental studies and controlled clinical trials, a notable effectiveness in reducing in a highly selective fashion the synthesis of cholesterol in the liver cells and consequently the number of cholesterol-rich lipoproteins in the systemic circulation, without also determining significant biologically negative side-effects.


[Changes in lipid status during pravastatin treatment].

Reduced cholesterolemia lowers the risk of ischemic cardiopathy, especially if LDL cholesterol levels are reduced. Today this effect can be achieved using drugs following the discovery of a new class of molecules: statins are specific inhibitors of HMG-CoA-reductase, a key enzyme in cholesterol biosynthesis. These molecules act by modifying the intracellular quota of cholesterol, especially at a hepatocytic level, thus enabling an enhanced expression of those genes responsible for forming receptors for membrane LDL with an increased number of receptors. This leads to a modulation of receptor activity which interferes with LDL uptake, promoting more rapid clearance. The aim of this study was to confirm the efficacy and tolerability of pravastatin when used for long periods in patients with high cholesterol levels, and to compare its activity to that of gemfibrozil.


[Salivary and serum beta 2-microglobulin in the diagnosis of primary Sjögren's syndrome].

beta 2-microglobulin (beta 2m) serum and salivary levels and total protein salivary levels were determined in 15 patients with primary Sjögren's syndrome (pSS), 14 patients with sicca syndrome and 11 healthy subjects. beta 2m serum and salivary levels were higher (p < 0.005) in the patients with pSS than in the healthy subjects and in the patients with sicca syndrome. The bioptic focus scores of minor salivary glands were correlated to beta 2m salivary levels with a high significance (p < 0.001) but were not correlated to beta 2m serum levels. The assessment of beta 2m serum and salivary levels is a non-invasive clinical investigation, which may be easily repeated. It is a very sensitive and highly specific test for the diagnosis of pSS. It may be therefore a useful mean to follow the natural course of pSS and to evaluate the effects of therapy.


[Determination of serum procollagen-III peptide in chronic liver diseases. Clinical usefulness].

Liver fibrosis determines the course and prognosis of chronic liver disease. Histological examination of liver biopsy is essential for diagnosing hepatic disease. Evaluation of serum concentration procollagen III peptides (sPIIIP) by radioimmunoassay (RIA) is a biochemical test useful for evaluating a fibrotic process. We have investigated 20 healthy subjects and 50 patients with chronic liver disease, histologically diagnosed by percutaneous liver biopsy: steatosis (8), fibrosteatosis (7), chronic persistent hepatitis (10), chronic active hepatitis (7), cirrhosis (18). SPIIIP levels were increased in patients with cirrhosis and chronic active hepatitis and in these groups of patients such levels were well correlated with histological activity of hepatic disease. Evaluation of serum concentration of PIIIP by RIA seems to be a useful test for evaluating a fibrotic process in chronic liver diseases evolving towards cirrhosis.


[Hormonal markers of early-stage osteitis fibrosa in patients on hemodialysis].

The diagnosis of renal osteodystrophy is straightforward when the disease has reached an advanced stage and the pathology is extremely difficult to treat, whereas it is considerably more complex during the early stages. A study was carried out to assess the sensitivity of some biochemical, hormonal and instrumental markers in the early diagnosis of osteitis fibrosa in patients undergoing hemodialysis due to chronic renal insufficiency. Of these markers, the assay of whole molecule PTH appeared to be the most sensitive and specific biological marker.


[Efficacy and tolerability of nicardipine retard and captopril in hypertension in the aged. Results of a multicenter study].

The efficacy and tolerability of nicardipine retard and captopril were assessed in 174 over-60-year-olds suffering from slight or moderate essential hypertension. After 2-3 weeks of wash out the patients were randomly assigned to calcium antagonist (40 mg twice a day) or ace-inhibitor (25 mg twice a day) treatment which continued for 180 days. Monotherapy was combined with hydrochlorothiazide (12.5 mg/day) after 2 months in the event of an unsatisfactory reduction of arterial pressure in relation to basal values. Systolic and diastolic blood pressure was measured (1st and 5th Korotkoff's tone) at monthly intervals while lying and standing; heart rate was also measured using a palpatory method. Both nicardipine retard (no. 86) and captopril (no. 88) caused a significant reduction of clino- and orthostatic systolic and diastolic arterial pressure during the first two months of treatment. Respectively 70% and 51% of patients responded to treatment and the blood pressure reductions achieved using monotherapy remained unchanged during the course of the study. The association of hydrochlorothiazide resulted in a significant decrease in arterial pressure in non-responders, an effect which was observed with both nicardipine retard and captopril. No significant variation in heart rate was recorded between the two groups. Twenty-one patients in the nicardipine retard group and 16 in the captopril group suffered from slight to moderate side effects. Six patients dropped out of the nicardipine retard group and 15 patients out of the captopril group, an event for which side-effects were responsible in 1 and 3 cases respectively. In conclusion, nicardipine retard and captopril represent an efficacious form of treatment for geriatric hypertension and possess a satisfactory level of tolerability.


[Efficacy of L-thyroxine (L-T4) therapy on the volume of the thyroid gland and nodules in patients with euthyroid nodular goiter (ENG)].

The efficacy of treatment with TSH suppressive doses of L-thyroxine was evaluated by echography in 35 patients with euthyroid nodular goiter. Patients have been subdivided in two groups comparable for sex age and size of the goiter. Sixteen patients were treated for nine months with suppressive doses of thyroxine and nineteen were followed without therapy as control. Patients in treatment were then followed up for additional 9 months without therapy. The mean decrease of thyroid volume at nine months was 25% (27 +/- 10 ml vs 20 +/- 8 ml; p < 0.01). After discontinuation of treatment thyroid volume increased and had returned to base line values after nine months of follow up. In the control group mean thyroid volume had increased by 17.7% at nine months (28 +/- 17 vs 33 +/- 19 ml; p < 0.001). Thyroid nodules in response to thyroid hormone treatment showed a variable behaviour: 30.7% (4/13) of the nodules responded to the therapy with a reduction > to 25% at the ninth month; the remaining nodules were insensitive to the therapy. In conclusion suppressive thyroxine treatment is effective in reducing the goiter, nodules instead are only in part sensitive to the treatment. Thyroxine therapy of euthyroid nodular goiter must be followed for long term since upon thyroxine discontinuation there is a prompt reappearance of the goiter.


[Imaging diagnosis, echography and CAT in mechanical jaundice].

In a review of 70 cases of extra-hepatic cholestasis of different origin, the great diagnostic value of imaging techniques, echography and computed tomography, was demonstrated in distinguishing the type of jaundice, and in defining the cause and site of obstruction.


[High resolution electrophoresis of serum aand amniotic fluid].

In a sample group of 92 women undergoing prenatal echo-guided transabdominal amniocentesis between the 12th and 23rd week of pregnancy the Authors analysed amniotic fluid and maternal serum using the recently developed method of high resolution protein electrophoresis in order to identify the presence of particular proteins in the amniotic fluid which are pathognomonic for a number of maternofetal pathologies. The results obtained in normal and pathological pregnancies or in the case of twins showed a marked dispersion in amniotic fluid of total protein concentrations depending on the period of gestation; in addition, albumin, alpha 1-antitrypsin, alpha 2-glycoprotein acid, alpha 2-macroglobulin and beta 2-protein were also found. Plasma levels of prealbumin, albumin, alpha 1-glycoprotein acid and IgG were slightly reduced, whereas there was a marked increase in ceruloplasmin, transferrin and fibrinogen; C3 and haptoglobin levels were normal. It is therefore possible to ascertain that amniotic fluid proteins analysed by high-resolution 15-band electrophoresis did not vary qualitatively or quantitatively until the 23rd week of gestation and in those cases of twin or pathological pregnancies examined no anomalous band was found in the protein electrophoresis of maternal serum or amniotic fluid which might prove useful in prenatal diagnosis.


[Evaluation of a new method for cervical cytology].

An adequate sample is the most important factor for successful cervical cytology. In this study a conventional method is compared to a new method of biopsy in a group of 40 patients undergoing tests in June 1991. A quantitative and qualitative evaluation of esocervical and endocervical cells was made; similar percentages were obtained for floor cells using both using systems, whereas higher percentage values (82.5% vs 67.5%) were obtained for cylindrical cells using the new method. Compared to the conventional method the new method also possessed an inadequacy rate of below 50% in post-menopausal patients. Therefore, although the new method is similar to the conventional one in terms of quality, it is thought to be more appropriate due to the greater number of endocervical cells collected, especially in post-menopausal patients.


[Decisional analysis in the diagnosis of Chlamydia trachomatis].

The aim of this work is the use of decisional analysis for the clinical diagnosis of Chlamydia trachomatis, to verify the utility of making a routine direct immunofluorescence test with a strategy of no routine direct immunofluorescence test with a strategy of no routine test in women during gynecologic escannations. Patients eligible for this analysis were sexually active woman, who are not pregnant, woman in reproductive age who do not have evidence of a clinical syndrome associated with or known to be caused by Chlamydia trachomatis. Our results show that the decision as to the use of the test involves 0.87 utility, while the decision of no routine test involves a 0.80 utility. We can therefore deduce that the best strategy for a woman who subjects herself to routine gynecologic care is to use this test, because the Chlamydia trachomatis has been implicated as the etiologic agent of acute salpingitis, chronic and tubal infertility.


[Screening of endometrial carcinoma].

The Authors analyse the characteristics of the carcinoma of the endometrium concluding that this neoplasia has the necessary requirements to undergo a screening by means of endometrial cytology. The Authors believe that this test should be combined with those carried out to prevent cervical and mammary neoplasia, applying a total screening to the gynaecological neoplasia.


[Treatment of premenstrual syndrome. Experience and considerations].

The Authors review the scientific literature on premenstrual syndrome (PMS), focusing on the diagnostic standards and the complex symptomatologic pattern. They report, furthermore, the results of a study of 4 groups of patients affected by PMS and treated with different therapeutic programs. The data obtained confirm that treatment of PMS must be personal and valued on the ground of dominant group of symptoms.


[Evaluation of the efficacy and tolerability of nimesulide in the treatment of mastodynia].

In a double blind clinical trial 40 female patients, aged between 14 and 65 years, affected by mastodynia associated with benign non neoplastic disease of the breast, underwent oral treatment with nimesulide (200 mg/day) or placebo for a period of 15 consecutive days, during which no other drug therapy was assumed. The administration of nimesulide produced a clinically significant attenuation of mammary tenseness and mastodynia, in most cases up to complete remission of the symptoms. No adverse reaction was observed.


[Pain control during the expulsion period in labor using bupivacaine and fentanyl].

The association of extremely diluted concentrations of opioids and local anesthetics appears to be highly promising for pain control during labour. This study examined the efficacy of the association of Fentanyl 100 mcg and Bupivacaine 10 mg in second-stage labour pain and perineal pain. The study which was carried out in 20 patients confirmed the lack of collateral effects on the fetus, mother (except for slight itching in 25% of cases) and the progress of labour. A virtually total elimination of pain was obtained in all cases during the dilatation and expulsion stages. During the second stage of labour pain was completely abolished in 50% of cases, whereas in the remaining 50% it lasted on average for 13 minutes. Perineal analgesia was sufficient to allow episiorrhaphy in 50% of patients without resorting to the use of local anesthetic.


[Treatment of dysfunctional metrorrhagia with GnRH analogs].

Thirty patients diagnosed as affected by dysfunctional metrorrhagia were treated with goserelin in a registered formulation of 3.6 mg injected subcutaneously into the anterior abdominal wall. These patients suffered from hypochromic anemia secondary to metrorrhagia with asthenic symptoms. After six months' treatment there was a significant improvement in hemocrasia and symptoms resolved without collateral effects requiring the suspension of treatment. The 10 patients who subsequently underwent surgery were in excellent condition and did not require blood transfusions.


[Sexuality of the aging male].

The paper discusses data reported in the literature concerning the sexual behaviour of elderly males and examines the role played by anatomical alterations to the genital tract, erection physiology and psycho-physical performance. The Authors review the current possibilities of treatment for sexual therapy in elderly males.


[Research on the understanding of the relation between patient, gynecologist and breast disease].

The aim of our work was to identify the most important aspects of the relationship between gynecologist and patient who presents himself during our observation because of breast pathology. In order to evaluate all that said above we asked patients to compile a questionnaire characterized by different questions. The results obtained were very satisfactory and at the same time they lead us to a greater engagement towards the prevention of breast neoplasia, especially for those women predisposed to such disease.


[HELLP syndrome. Discussion of a case].

The HELLP syndrome is the most severe variant of pre-eclampsia. A case is reported in a primigravida patient at 25 weeks of gestation. The lack of response to medical treatment and the deterioration of maternal indices necessitated a Cesarean section with intensive neonatal care at a very premature stage. The physiopathological grounds and the various methods of treating this syndrome are discussed and the paper concludes that rapid birth is the only solution capable of preventing severe maternal complications.


[Mondor syndrome. Etiopathogenesis and case report].

The Authors observed and report a case of Mondor's syndrome in a male. In the attempt to identify the real origin in this peculiar thrombophlebitis they reviewed the recent literature. It is apparently impossible to drawn definitive conclusions from the different studies on this subject. Anyway Mondor's syndrome looks suitable for inclusion in the group of jumping thrombophlebitis. Therefore the real cause of the venous accident should be a pathologic situation next to the venous branch where the thrombophlebitis has broken out.


1S,3R-ACPD-sensitive (metabotropic) [3H]glutamate receptor binding in membranes.

Metabotropic glutamate receptors are selectively activated by 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD). [3H]Glutamate binding sites in rat brain membranes were characterized in the presence of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, and N-methyl-D-aspartate (NMDA) to block binding to ionotropic glutamate receptors. 1S,3R-ACPD displaced a single population of [3H]glutamate binding sites and was mimicked by other metabotropic glutamate agonists with a potency order of L-glutamate > 1S,3R-ACPD > ibotenate > 1R,3S-ACPD. Quisqualate interacted at two populations of binding sites. 1S,3R-ACPD-sensitive [3H]glutamate binding was saturable (Bmax = 2.50 +/- 0.27 pmol/mg protein), reversible, and had high-affinity (KD = 187 +/- 60 nM). 1S,3R-ACPD-sensitive [3H]glutamate binding likely represents labeling of metabotropic glutamate receptors in rat brain membranes.


Alteration of delta-6 desaturase by vitamin E in rat brain and liver.

delta-6 Desaturase, measured at substrate saturation using linoleic acid, was found to be increased by more than two-fold when the content of vitamin E in brain microsomal membrane suspension was increased (up to 7.5 micrograms/mg membrane protein, i.e. 100 micrograms/g tissue from which microsomes were prepared). In contrast, this activity was reduced by 25% in the liver. This raises the question of the multiple role of vitamin E in membranes, the control of membrane polyunsaturated fatty acids through synthesis, and their protection against peroxidation.


Rhythmic activities in the rat solitary complex in vitro.

In adult rat brainstem slices, rhythmic discharge of action potentials occurred spontaneously in 10 out of 197 cells of the solitary complex. In 6 neurones, fast rhythms (2-6 per min) were characterized by volleys of synaptic activity presenting abrupt onset denoting synchronized discharge of presynaptic elements. Synchronizing signals may be generated by cells discharging bursts of high-frequency action potentials and presenting extensive axonal arborization, as observed in one cell. Slower rhythms (0.3-0.8 per min) monitored in three cells did not involve synchronizing processes and could be evoked in non-rhythmic cells by 15-30 min bath application of the cholecystokinin octapeptide (100 nM). These results suggest distinct operating mechanisms of fast and slow rhythms in the solitary complex in vitro.


The effect of halothane on cultured fibroblasts and neuroblastoma cells.

Halothane exposure over the cultured cells (100 and 1,000 ppm) caused a disruption of the pattern of actin distribution in both fibroblasts and neuroblastoma cells. Neuroblastoma cells exposed to halothane also lost microspikes; however, neurite elongation was not affected by halothane. The present study suggests that halothane induces the functional disruption of actin, resulting in an interference of normal neural development in vivo.


Mutations in genes for acetylcholinesterase intensify lethality by acrylamide in Caenorhabditis elegans.

Acrylamide inhibits growth and results in death in the nematode Caenorhabditis elegans. The lethargic effect is marked in the mutants defective in genes for acetylcholinesterase (AChE) and the effect is approximately parallel with the decrease in AChE activity by mutations. Although neither the activity nor the localization of the enzyme is affected by acrylamide, the acetylcholine level was significantly elevated.


Activation of D1 receptors stimulates accumulation of gamma-aminobutyric acid in slices of the pars reticulata of 6-hydroxydopamine-lesioned rats.

D1 dopamine receptors are present on terminals of striatal neurons to the pars reticulata of the substantia nigra in the rat. Here we have studied the effect of the activation of these receptors on the synthesis of gamma-aminobutyric acid (GABA) in slices of the pars reticulata of the substantia nigra isolated from 6-hydroxydopamine-lesioned rats. The synthesis was judged by the accumulation of GABA after inhibiting GABA transaminase with aminooxyacetic acid. Both dopamine and SCH 23390, a D1 agonist, stimulated the synthesis. The effect of both compounds was blocked by SCH 23390, a D1 antagonist, but not by sulpiride, a D2 antagonist. In the absence of receptor activation, the synthesis was very slow. The results suggest a trophic influence of dopamine upon the synthesis of GABA via D1 receptors.


Formation of muscle spindles in the absence of motor innervation.

Whether muscle spindles can form in muscles innervated only by afferents was investigated by removing the lumbosacral segment of the spinal cord immediately after crushing the nerve to the medial gastrocnemius (MG) muscle in newborn rats, and administering nerve growth factor for 10 days afterwards. The nerve-crushed MG muscles reinnervated by afferents in the absence of motor innervation were examined at postnatal (P) days 7, 9 and 30 for the presence of spindles by light and electron microscope. Reinnervated MG muscles contained spindle-like encapsulations of 1-4 fibers at 7, 9 and 30 days after the nerve crush. The number of spindles exceeded that of normal MG muscles, suggestive of de novo formation of spindles. All nerve-muscle contacts in the spindles had features of sensory endings, and intrafusal fibers expressed the spindle-specific slow-tonic myosin heavy chain (MHC) isoform at P30. No motor endplates were visible on any muscle fibers and extrafusal fibers were atrophied, as would be predicted in the absence of motor innervation. Thus, efferents are not essential for the formation and differentiation of muscle spindles in reinnervated muscles of neonatal rats.


Serotonin modulates auditory information processing in the cochlear nucleus of the rat.

The effect of iontophoretic application of serotonin (5-HT) was studied in neurons of the cochlear nucleus in the rat. 5-HT inhibited the spontaneous activity in 71%, and the tone-evoked activity in 32% of the neurons. We also observed an excitatory effect, with a longer latency than that of the inhibition, in 40% of the neurons. In some neurons 5-HT had both inhibitory and excitatory effects. Neurons with different response types seem to have different sensitivities to 5-HT. As the effects of 5-HT were generally weaker than those of other putative neurotransmitters, it probably has only a small modulatory influence on auditory processing.


Pattern of electroencephalographic activity during light induced seizures in genetic epileptic chicken and brain chimeras.

Genetic epilepsy was studied in Fayoumi epileptic (F.Epi) chickens and in neural chimeras obtained by selective substitution of embryonic brain vesicles of F.Epi donors in normal recipient chickens. Typical motor seizures accompanied by convulsions were evoked by intermittent light stimulation in F.Epi and in chimeras having embryonic substitution of the prosencephalon and the mesencephalon. The motor seizure was less severe in chimeras receiving only the prosencephalon. In the F.Epi, as well as in all the chimeras, the EEG during seizures was characterized by a desynchronized (or a flattening) pattern of activity. F.Epi and chimeras had a lower threshold to Metrazol induced seizures than control chickens. The experimental animals show that, in this model, large prosencephalic and mesencephalic areas are involved in the epileptic disease. The epileptic character of this genetic dysfunction is discussed.


Ricinus communis agglutinin I reacting and non-reacting butyrylcholinesterase in human cerebrospinal fluid.

Differences in glycosylation of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in human brain, plasma and cerebrospinal fluid (CSF) have been investigated by means of their interaction with agarose-immobilized lectins. Most of the AChE in brain and CSF was associated to concanavalin A (Con A), Lens culinaris (LCA) and Triticum vulgaris (WGA) agglutinins, but little activity was adsorbed to Ricinus communis agglutinin I (RCAI). Brain, plasma and CSF BuChE was almost fully bound to Con A, LCA and WGA-agarose. Brain BuChE was unable to react with RCA (RCA-BuChE), the plasma enzyme was completely bound to the lectin (RCA+BuChE) and BuChE from CSF of normal children was partially fixed to RCA (RCA +/- BuChE). BuChE in CSF of children with meningitis fully reacts with the lectin. The data suggest that the proportion of RCA+BuChE in CSF of children with meningitis is increased, this enzyme probably coming from plasma.


Cross-linking of 125I-alpha-bungarotoxin to Drosophila head membranes identifies a 42 kDa toxin binding polypeptide.

The nicotinic acetylcholine receptor (nAChR) antagonist alpha-bungarotoxin (alpha-Btx) binds to two different classes of high affinity binding sites from the Drosophila central nervous system. We have used the bivalent reagent 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDAC) to cross-link 125I-alpha-Btx (M(r) = 8 kDa) to Drosophila head membranes. Upon sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), one major adduct of M(r) approximately 50 kDa was identified, suggesting that a 42 kDa polypeptide binds the toxin. Adduct formation was inhibited by other cholinergic ligands. Detergent-solubilized receptor complexes containing the cross-linked products were immunoprecipitated by antisera against two nAChR subunits previously identified by molecular cloning, the ALS and ARD proteins, suggesting that the 42 kDa toxin binding polypeptide constitutes a component of the previously described class 1 alpha-Btx binding site.


A neuroprotective effect of adenosine A1-receptor agonists on ischemia-induced decrease in 2-deoxyglucose uptake in rat hippocampal slices.

The effects of adenosine (A) receptor agonists on ischemia-induced impairment of 2-deoxyglucose (2-DG) uptake by rat hippocampal slices was evaluated. Hippocampal slices were exposed to 20-min hypoxia + hypoglycemia (ischemia) and then returned to oxygenated and glucose-containing Krebs-Ringer solution for 6 h. Ischemia reduced 2-DG uptake in the hippocampal slices. The ischemia-induced reduction in 2-DG uptake was attenuated by pretreatment with A1 receptor agonists but not with A2 receptor agonists. 8-Phenyltheophylline, an A1 receptor antagonist, exacerbated the ischemia-induced decrease. The A1 receptor agonist-induced neuroprotective effect was blocked by co-treatment with 8-phenyltheophylline. The present study suggests that the A1 receptor-mediated function has a protective role in ischemia-induced decreases in glucose metabolism in hippocampal slices.


Postnatal development of neuropeptide Y-containing neurons in the visual cortex of normal- and dark-reared rats.

The postnatal development of neuropeptide Y (NPY)-immunoreactive neurons in the visual cortical areas (17, 18 and 18a) has been studied in Wistar rats reared under normal lighting conditions or in complete darkness. Immunohistochemistry on paraffin sections at postnatal days (P)7, 14, 21, 30 and 60 showed an overall similarity in laminar distribution of NPY neurons in all 3 visual areas of both normal- and dark-reared animals. The pattern of development of NPY neurons was characterized by an increase in their density from P7 to reach a peak at P21 followed by a decline to 37-47% of peak levels at P60. However, this diminution was not so great in dark-reared rats as in the normal, since the density only decreased to 62-78% of peak levels. At P60 the resulting differences in neuron density were marked in areas 17 and 18, where the dark-reared had 75% more cells than normal, and moderate in area 18a (30% more than normal). These results suggest that the normal decline in NPY neurons is not entirely mediated by visual experience since it takes place, albeit to a modified extent, in its total absence.


Presence of functional vasopressin V1 receptors in rat vagal afferent neurones.

The nucleus of the solitary tract (NTS) is one of the brain regions by which arginine vasopressin (AVP) influences blood pressure. This series of experiments in adult male rats was designed to determine whether the AVP binding sites which have been demonstrated in the NTS by in vitro autoradiography might be presynaptic on vagal afferents from the nodose ganglion; whether the AVP binding sites on vagal afferent neurones are functional receptors; and whether vagal transport of AVP receptors to other organs also occurs. High affinity binding sites (using the selective V1 antagonist radioligand [125I][d(CH2)5,Sar7]AVP and in vitro autoradiography) with characteristics of V1 receptors in the medial subnucleus of the NTS were reduced by 40% ipsilateral to nodose ganglionectomy. The nodose ganglion itself also contained high affinity V1 AVP binding sites that localised over cell bodies of vagal sensory neurones. That these binding sites were functional receptors was apparent when low concentrations of AVP but not oxytocin were found to depolarize the isolated nodose ganglion utilizing the 'silicone grease gap' technique. Furthermore, the actions of AVP were antagonised by low concentrations of a selective V1 receptor antagonist. However, there was no accumulation of AVP binding sites adjacent to either the proximal or distal vagal ligations suggesting that peripheral vagal transport of AVP receptors may not occur. Therefore these results are consistent with functional AVP V1 receptors occurring in the nodose ganglion. These receptors may occur on central terminals of vagal sensory neurones in the medial subnucleus of the NTS, but there was no evidence for peripheral transport of AVP V1 receptors.


Effects of lipopolysaccharide on food-motivated behavior in the rat are not blocked by an interleukin-1 receptor antagonist.

To investigate the role of interleukin-1 (IL-1) in the decrease in food-motivated behavior after peripheral administration of lipopolysaccharide (LPS), rats trained to press a lever for food on a fixed ratio 10 schedule were pre-treated with a recombinant human IL-1 receptor antagonist (IL-1ra). This endogenous cytokine has been shown to block most of the inflammatory and immune effects of IL-1 both in vitro and in vivo. Intraperitoneal (i.p.) injection of LPS (400 micrograms/kg) decreased operant responding for food to 30-60% of baseline for 1-4 h. Response rates gradually recovered, but were still below control levels 8 and 24 h post-injection. Neither i.p. (8 mg/kg) nor intracerebroventricular (288 micrograms/kg) administration of IL-1ra blocked the effects of peripherally administered LPS on food-motivated behavior. These results suggest that the effects of LPS on this behavior are not mediated by the release of IL-1.


Expression of c-fos protein in lumbosacral spinal cord in response to vaginocervical stimulation in rats.

The pattern of vaginocervical stimulation-evoked expression of the proto-oncogene c-fos in lumbar 5-sacral 1 segments of the spinal cord of ovariectomized adult rats was mapped using immunocytochemistry. A calibrated force of mechanostimulation was applied to the vaginal cervix of experimental animals and to the perineum of control animals while they were gently restrained. The number of cells expressing c-fos was significantly greater in the experimental than the control animals in laminae I, IV, V-VI and X. The implications of the present findings for elucidating the spinal pathways mediating the various behavioral, neuroendocrine and autonomic effects of vaginocervical stimulation (VS) are discussed.


Review article: venous thromboembolism in trauma patients.

The increased coagulability in multiple injured patients results in increased risk for deep venous thrombosis and pulmonary embolism. The authors discuss etiology, diagnosis, treatment, and prophylaxis of venous thromboembolism in trauma patients.


Omeprazole in the treatment of peptic ulcers and gastroesophageal reflux disease.

Omeprazole blocks the final step of gastric acid secretion by blocking the proton pump (the hydrogen and potassium ATPase) in gastric parietal cells. Due to this direct action, omeprazole is the most potent, clinically available suppressor of gastric acidity.


General surgery: is there a future?

General surgery may not survive in an age of superspecialization unless the emphasis of general surgical training shifts from broad competence to defined areas of expertise. The author presents suggestions for restructuring general surgery residency requirements.


Completeness of case ascertainment of the State Cancer Registry.

The authors evaluated the ability of the New Jersey State Cancer Registry to detect known cancer cases during an investigation of a cancer cluster occurring in professional football players. The Registry was found to be a valuable tool for the detection of cancer cases for New Jersey residents.


The New Jersey health care delivery structure--a clarification.

Recent SBME rules were developed from issues raised by a previous commissioner of health. SBME received comments on these issues at two public hearings. SBME drafted the rules to incorporate the substance and the principles of the state's Health Care Cost Reduction Act.


CLIA-88 final rule: Part 2.

Physicians performing moderate or high complexity tests will need to prepare their office laboratories to meet CLIA-88 government standards. Doctors who have not applied for their registration certificate should do so immediately. This is the second in a three-part series.


Children's preferences for high-fat foods.

Many high-fat foods are highly preferred by adults, and children soon acquire these preferences. The circumstances and mechanisms that contribute to establishing children's preferences for high-fat foods are the subject of this review.


Body weight, fat storage, and alcohol metabolism.

Ethanol account for a significant fraction of the energy intake of persons consuming even moderate amounts of alcohol. A recent study has shown that although alcohol does not reveal itself as a layer floating at the top of a drink, metabolically it behaves more like oil than sugar.


Retinoids and carotenoids as inhibitors of carcinogenesis and inducers of cell-cell communication.

In cell cultures of carcinogen-initiated fibroblasts, a number of retinoids and carotenoids can reversibly inhibit progression to the transformed state. The anticarcinogenic action of retinoids and carotenoids is closely correlated with enhanced gap-junction cell-to-cell communication and with increased synthesis of the gap-junction protein, connexin.


Directional coronary atherectomy in lesions unfavourable for balloon angioplasty: initial Green Lane and Mercy Hospitals experience.

directional coronary atherectomy is a new percutaneous interventional technique in which coronary arterial stenotic material is shaved off to alleviate stenosis. This study presents the initial outcome of coronary atherectomy at Green Lane and Mercy hospitals where the major indications for atherectomy are lesions with angiographic appearances unfavourable for balloon angioplasty or where balloon angioplasty had been unsuccessful. data on patients undergoing coronary atherectomy between February 1990 and December 1991 were analysed. No patient or procedure was excluded. for the first 28 lesions in 25 patients, procedural success, improvement in lumen diameter to less than 50% diameter loss stenosis, but freedom from myocardial infarction, death or emergency bypass surgery, was achieved in 27 of 28 lesions. In one patient there was acute thrombotic coronary arterial closure treated successfully by balloon angioplasty. Another patient developed an asymptomatic fistulous connection with an adjacent coronary vein which resolved spontaneously. although technically more difficult than balloon angioplasty, directional coronary atherectomy can be carried out in selected patients with a high initial success rate and low complication rate. The technique has allowed percutaneous treatment of a number of selected patients unsuitable for balloon angioplasty, and has turned an unsuccessful angioplasty into an initial procedural success in others.


Pneumococcal bacteraemia in south Auckland: a five year review with emphasis on prescribing practices.

to determine incidence, predisposing factors, management and outcome of pneumococcal bacteraemia in south Auckland. medical records were reviewed retrospectively of patients identified as having pneumococcal bacteraemia at Middlemore Hospital during five years 1986-90. records were available for 143 of 149 episodes. The incidence of pneumococcal bacteraemia was 12.1/10,000 admissions. The male to female ratio was 1.2:1, 61.5% were over the age of 50 years, 76% had underlying medical conditions, and the mortality was 16.1%. Twenty of the 23 who died were over the age of 60 years. Just over half attended hospital within 48 hours of becoming unwell, while 10.5% had had symptoms for more than one week. Pneumonia was seen in 85% and meningitis in 7%. Initial treatment was with a single antibiotic in 94%. Following microbiological diagnosis, 54% were treated with penicillin G, but in over one-third, an unnecessarily broad spectrum antibiotic was continued as definitive treatment. the incidence, age distribution, predisposing factors and mortality of pneumococcal bacteraemia in south Auckland is similar to those reported elsewhere. Inappropriately broad spectrum antibiotics are used too often in definitive treatment.


Adolescence and sun protection.

to examine adolescents' sun behaviours and use of sun protection measures, attitudes to tanning, and awareness of melanoma, in the light of the Cancer Society's Sun-smart campaign in the summer of 1990-1. a sample of 345 fourth formers from schools in Auckland, Wellington and Christchurch was surveyed regarding their experiences and beliefs about tanning, and their use of sun protection measures including sunblock lotions, hats and clothing; their knowledge of melanoma and risks for melanoma; and their exposure to the educational campaign and its message. despite relatively high awareness of melanoma as a dangerous form of cancer, a significant proportion of the sample showed high positive attitudes towards tanning and high levels of sun exposure without adequate sun protection. On the positive side, reports of exposure to sources of information about melanoma were correlated with melanoma awareness, which in turn predicted use of sun protection measures. the findings suggest that campaigns such as those of the Cancer Society have an important role to play in reducing high levels of sun exposure among adolescents. Continued efforts need to be directed at adolescents to increase the acceptability and use of sun protection measures.


General practitioners' views on the role of the community pharmacist.

to determine the views of general practitioners on the roles and activities of community pharmacists. the views of 137 general practitioners in Otago and Southland were canvassed by postal questionnaire. one hundred and three completed questionnaires were returned. All of the general practitioners reported that their professional contact with pharmacists was useful. Seventy-five percent expressed a desire for greater cooperation. Nearly all respondents (99%) accepted that pharmacists have a role in screening prescriptions for possible problems and preparing and dispensing medicines. They also accepted that pharmacists were capable of treating and advising in the management of minor illnesses. Providing drug information to general practitioners, information about previously diagnosed conditions to patients, and advice on personal and home hygiene were less widely accepted activities. The majority indicated that they considered it inappropriate for pharmacists to undertake screening programmes (blood pressure (70.6%), cholesterol (70.6%), glucose (60.8%), haemoglobin (72.5%)). Younger general practitioners objected more often than older general practitioners to reclassification of Acetopt eye drops from prescription only to availability through pharmacies (p < 0.05). Female general practitioners were more often in favour of reclassification of Gyno-Daktarin than their male colleagues (p < 0.05). this study shows that general practitioners accept several aspects of the current role of pharmacists in providing primary health care. However, there is room for improved communication between general practitioners and pharmacists to ensure optimum patient care.


Age and ethnicity as prognostic factors influencing overall survival in breast cancer patients in the Auckland region. Auckland Breast Cancer Study Group.

to assess the effect of age at diagnosis and ethnicity on overall survival from breast cancer. information was collected from 2706 breast cancer patients in the Auckland region, diagnosed between 1976 and 1985. Age at diagnosis was categorised into four groups: < 35 years, 35-49 years, 50-74 years and 75 years or older. Ethnicity was self reported in three categories: European, Maori and Pacific Island Polynesian. Independent effects were assessed by controlling for extent of disease, specifically metastases at presentation, nodal status and size of tumour. age and ethnic group were both significantly related to overall survival in univariate analyses. In multivariate analysis, age had an independent effect on survival mainly due to a significant survival difference between women aged less than 35 years and those aged 35 to 49 years (p < 0.0001; RR = 2.02). Survival was not significantly different between other age groups when adjustments were made for extent of disease. There was no significant effect of ethnicity on survival in the reduced dataset used for the multivariate analysis. Separate analyses suggested that ethnic differences in the extent of disease at diagnosis may be the cause of the apparent initial effect of ethnicity on survival. women < 35 years at diagnosis have a significantly poorer prognosis than women aged 35-49 years. Other differences between age groups were not significant when stage of disease was taken into account. Ethnicity was not an independent factor influencing survival after controlling for extent of disease but numbers in the Maori and Pacific Island groups were too small to conclusively evaluate any effect of ethnic group on prognosis.