Neural functional correlates of emotional processing in patients with first-episode psychoses: an activation likelihood estimation (ALE) meta-analysis.

BACKGROUND: Early emotional recognition impairment characterises rst-episode psychoses (FEP) and remains stable thereafter. Patients with FEP consistently show brain activation changes during emotional processing in functional neuroimaging studies. AIM AND METHODS: To identify and compare cerebral activation correlates of FEP patients and healthy controls (HCs) during emotional task performances, we performed an Activation Likelihood Estimation (ALE) meta-analysis of peer-reviewed functional magnetic resonance imaging (fMRI) studies. RESULTS: Five studies included 71 patients with FEP and 75 HCs. Within-group analyses showed that HCs activated during emotional task performance the bilateral inferior parietal lobule (BAs 39 and 40), left inferior frontal gyrus (BAs 9 and 47), right amygdala, left middle frontal gyrus (BA 9), right cingulate gyrus (BA 32), and right middle temporal gyrus (BA 21). FEP activations correlating with emotional tasks included the right cuneus (BA 17) and right angular gyrus (BA 39). CONCLUSIONS: During emotional task performance, FEP patients fail to activate an extensive brain network comprising emotional processing-related areas, including both cortical and subcortical areas.

Modulation of LTP at rat hippocampal CA3-CA1 synapses by direct current stimulation.

Transcranial direct current stimulation (tDCS) can produce a lasting polarity-specific modulation of cortical excitability in the brain, and it is increasingly used in experimental and clinical settings. Recent studies suggest that the after-effects of tDCS are related to molecular mechanisms of activity-dependent synaptic plasticity. Here we investigated the effect of DCS on the induction of one of the most studied N-methyl-d-aspartate receptor-dependent forms of long-term potentiation (LTP) of synaptic activity at CA3-CA1 synapses in the hippocampus. We show that DCS applied to rat brain slices determines a modulation of LTP that is increased by anodal and reduced by cathodal DCS. Immediate early genes, such as c-fos and zif268 (egr1/NGFI-A/krox24), are rapidly induced following neuronal activation, and a specific role of zif268 in the induction and maintenance of LTP has been demonstrated. We found that both anodal and cathodal DCS produce a marked subregion-specific increase in the expression of zif268 protein in the cornus ammonis (CA) region, whereas the same protocols of stimulation produce a less pronounced increase in c-fos protein expression in the CA and in dentate gyrus regions of the hippocampus. Brain-derived neurotrophic factor expression was also investigated, and it was found to be reduced in cathodal-stimulated slices. The present data demonstrate that it is possible to modulate LTP by using DCS and provide the rationale for the use of DCS in neurological diseases to promote the adaptive and suppress the maladaptive forms of brain plasticity.

Detection and Management of Amyloid-Related Imaging Abnormalities in Patients with Alzheimer's Disease Treated with Anti-Amyloid Beta Therapy.

Amyloid-related imaging abnormalities (ARIA) are adverse events reported in Alzheimer's disease trials of anti-amyloid beta (Aß) therapies. This review summarizes the existing literature on ARIA, including bapineuzumab, gantenerumab, donanemab, lecanemab, and aducanumab studies, with regard to potential risk factors, detection, and management. The pathophysiology of ARIA is unclear, but it may be related to binding of antibodies to accumulated Aß in both the cerebral parenchyma and vasculature, resulting in loss of vessel wall integrity and increased leakage into surrounding tissues. Radiographically, ARIA-E is identified as vasogenic edema in the brain parenchyma or sulcal effusions in the leptomeninges/sulci, while ARIA-H is hemosiderin deposits presenting as microhemorrhages or superficial siderosis. ARIA tends to be transient and asymptomatic in most cases, typically occurring early in the course of treatment, with the risk decreasing later in treatment. Limited data are available on continued dosing following radiographic findings of ARIA; hence, in the event of ARIA, treatment should be continued with caution and regular monitoring. Clinical trials have implemented management approaches such as temporary suspension of treatment until symptoms or radiographic signs of ARIA have resolved or permanent discontinuation of treatment. ARIA largely resolves without concomitant treatment, and there are no systematic data on potential treatments for ARIA. Given the availability of an anti-Aß therapy, ARIA monitoring will now be implemented in routine clinical practice. The simple magnetic resonance imaging sequences used in clinical trials are likely sufficient for effective detection of cases. Increased awareness and education of ARIA among clinicians and radiologists is vital.

Combined molecular and mathematical analysis of long noncoding RNAs expression in fine needle aspiration biopsies as novel tool for early diagnosis of thyroid cancer.

PURPOSE: In presence of indeterminate lesions by fine needle aspiration (FNA), thyroid cancer cannot always be easily diagnosed by conventional cytology. As a consequence, unnecessary removal of thyroid gland is performed in patients without cancer based on the lack of optimized diagnostic criteria. Aim of this study is identifying a molecular profile based on long noncoding RNAs (lncRNAs) expression capable to discriminate between benign and malignant nodules. METHODS: Patients were subjected to surgery (n = 19) for cytologic suspicious thyroid nodules or to FNA biopsy (n = 135) for thyroid nodules suspicious at ultrasound. Three thyroid-specific genes (TG, TPO, and NIS), six cancer-associated lncRNAs (MALAT1, NEAT1, HOTAIR, H19, PVT1, MEG3), and two housekeeping genes (GAPDH and P0) were analyzed using Droplet Digital PCR (ddPCR). RESULTS: Based on higher co-expression in malignant (n = 11) but not in benign (n = 8) nodules after surgery, MALAT1, PVT1 and HOTAIR were selected as putative cancer biomarkers to analyze 135 FNA samples. Cytological and histopathological data from a subset of FNA patients (n = 34) were used to define a predictive algorithm based on a Naïve Bayes classifier using co-expression of MALAT1, PVT1, HOTAIR, and cytological class. This classifier exhibited a significant separation capability between malignant and benign nodules (P < 0.0001) as well as both rule in and rule out test potential with an accuracy of 94.12% and a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 91.67%. CONCLUSIONS: ddPCR analysis of selected lncRNAs in FNA biopsies appears a suitable molecular tool with the potential of improving diagnostic accuracy.

Styrene enhances the noise induced oxidative stress in the cochlea and affects differently mechanosensory and supporting cells.

Experimental and human investigations have raised the level of concern about the potential ototoxicity of organic solvents and their interaction with noise. The main objective of this study was to characterize the effects of the combined noise and styrene exposure on hearing focusing on the mechanism of damage on the sensorineural cells and supporting cells of the organ of Corti and neurons of the ganglion of Corti. The impact of single and combined exposures on hearing was evaluated by auditory functional testing and histological analyses of cochlear specimens. The mechanism of damage was studied by analyzing superoxide anion and lipid peroxidation expression and by computational analyses of immunofluorescence data to evaluate and compare the oxidative stress pattern in outer hair cells versus the supporting epithelial cells of the organ of Corti. The oxidative stress hypothesis was further analyzed by evaluating the protective effect of a Coenzyme Q10 analogue, the water soluble Qter, molecule known to have protective antioxidant properties against noise induced hearing loss and by the analysis of the expression of the endogenous defense enzymes. This study provides evidence of a reciprocal noise-styrene synergism based on a redox imbalance mechanism affecting, although with a different intensity of damage, the outer hair cell (OHC) sensory epithelium. Moreover, these two damaging agents address preferentially different cochlear targets: noise mainly the sensory epithelium, styrene the supporting epithelial cells. Namely, the increase pattern of lipid peroxidation in the organ of Corti matched the cell damage distribution, involving predominantly OHC layer in noise exposed cochleae and both OHC and Deiters' cell layers in the styrene or combined exposed cochleae. The antioxidant treatment reduced the lipid peroxidation increase, potentiated the endogenous antioxidant defense system at OHC level in both exposures but it failed to ameliorate the oxidative imbalance and cell death of Deiters' cells in the styrene and combined exposures. Current antioxidant therapeutic approaches to preventing sensory loss focus on hair cells alone. It remains to be seen whether targeting supporting cells, in addition to hair cells, might be an effective approach to protecting exposed subjects.

Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory.

Non-fibrillar soluble oligomeric forms of amyloid-ß peptide (oAß) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAß initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aß, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAß levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAß to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Aß on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aß and tau pathology.

Manejo nutricional de ascitis quilosa: Serie de casos y revisión de la literatura

RESUMEN Las ascitis quilosa (AQ) es una entidad poco común producida por el acúmulo de linfa en la cavidad peritoneal. Su incidencia se describe en aumento progresivo, asociándose a una mortalidad de 40-70%. Se incluyeron 3 pacientes con diagnóstico de AQ evaluados en la visita de asistencia nutricional del Hospital Clínico de la Universidad Católica (UC) durante el año 2019. Caso 1: Paciente mujer de 47 años, consulta por dolor abdominal agudo realizándose apendicectomía. Estudio de líquido peritoneal con triglicéridos (TG) de 1.362 mg/dL. Inicia Nutrición Parenteral Total (NPTC) progresando luego a régimen oral. Estudio no revela lesiones de vasos linfáticos ni otras causas. Caso 2: Paciente varón de 68 años con cirrosis por alcohol, Child Pugh B. Ingresa por disnea y ascitis refractaria. Estudio de líquido ascítico y pleural, con TG de 439 mg/dL y 592 mg/dL respectivamente. Se manejó con toracocentesis y paracentesis evacuadoras, tratamiento con régimen hipograso y aporte de triglicéridos de cadena media (MCT) vía oral. Evolución tórpida requiriendo apoyo con NPTC, realizándose drenajes sucesivos, por lo que se instala TIPS. Caso 3: Paciente mujer de 63 años consulta por dolor hipogástrico con masa palpable subcostal derecha. Estudio confirma masa pancreática por lo que se realiza Whipple. Reingresa por náuseas y vómitos profusos, evidenciándose líquido ascítico con TG de 251 mg/dl. Se inicia NPTC, escasos débitos del drenaje iniciándose realimentación progresiva por vía oral. El análisis del líquido tras la paracentesis establece el diagnóstico de AQ pues la clínica es inespecífica. Las principales complicaciones están dadas por la pérdida de quilo: desnutrición, infecciones y sepsis. Las opciones de tratamiento incluyen: medidas dietéticas, fármacos e intervenciones percutáneas o quirúrgicas; siempre orientadas al alivio sintomático, con foco en tratar la causa. Si la tolerancia oral es óptima la primera medida es la supresión de la grasa y la suplementación con MCT para evitar déficit energético. Con el empleo de estas medidas se ha reportado el cierre espontáneo de fístulas y/o defectos de vasos linfáticos en un 75%-80%. Se concluye que no hay guías de recomendación y los estudios se basan en series de pocos casos clínicos. La ascitis quilosa es una entidad patológica rara, que representa una situación clínica crítica con consecuencias inmunológicas y nutricionales; y el tratamiento debe ser etiológico y el paso clave inicial es optimizar el estado nutricional del paciente.

ABSTRACT Chylous ascites (CA) is an uncommon entity caused by the accumulation of lymph in the peritoneal cavity, its incidence has been gradually increasing; being associated with a mortality of 40-70%. This work includes 3 patients with CA diagnosis evaluated by the Nutritional Assistance team in the Hospital Clínico of the Universidad Católica, Chile during 2019. Case 1: 47-year-old female, with acute abdominal pain that resulted in an appendectomy. Peritoneal fluid study showed triglycerides (TG) of 1362 mg/dL. Total Parenteral Nutrition (TPN) was initiated with successive changes to an oral regimen. The case was negative for lymphatic vessel injuries or other causes of AQ. Case 2: 68-year-old male with alcoholic cirrhosis, Child-Pugh B. The patient was admitted for dyspnea and refractory ascites. Ascites and pleural fluid study showed TG of 439 mg/dL and 592 mg/dL, respectively, whichwas managed with thoracentesis and evacuating paracentesis, treatment with a low-fat regimen, and oral medium chain triglycerides (MCT). Case 2 had a poor evolution requiring TPN and successive evacuations, with TIPS installed. Case 3: A 63-year-old female patient with hypogastric pain and palpable right subcostal mass. Study confirmed a pancreatic tumor and Whipple Surgery was performed. Case 3 was readmitted for nausea and vomiting, showing ascitic fluid with TG of 251 mg/dl. TPN was started, with decrease in drainage fluids and successful progressive oral refeeding. The analysis of the paracentesis fluid established the diagnosis of CA since the symptoms were nonspecific. The main complications were due to the loss of chyle: malnutrition, infections and sepsis. Treatment options included: dietary measures, drugs, and percutaneous or surgical interventions; always oriented to symptomatic relief, focused on etiologic treatment. If oral tolerance is optimal, the first measure should be fat suppression and supplementation with MCT to avoid energy deficit. With the use of these measures, spontaneous closure of fistulas and / or lymphatic vessel defects has been reported in 75% -80% of patients. There are no recommendation guidelines for CA and studies are based on series of a few clinical cases. CA is a rare disease, representing a critical clinical situation with immunological and nutritional consequences. Etiologic treatment must be prioritized with a focus on optimization of the nutritional status of the patient

Down-regulation of non-L-, non-N-type (Q-like) Ca2+ channels by Lambert-Eaton myasthenic syndrome (LEMS) antibodies in rat insulinoma RINm5F cells.

The action exerted on non-L-, non-N-type (Q-like) Ca 2+ channels by immunoglobulins G (IgGs) obtained from two patients with Lambert-Eaton myasthenic syndrome (LEMS) was investigated in the rat insulinoma RINm5F cell line. LEMS IgGs reduced by 30-36% the whole-cell Ba2+ currents through Q-like Ca2+ channels at +10 mV without significantly modifying their voltage dependence and activation kinetics. Single- and multiple-channel recordings in cell-attached and outside-out patches of cells treated with LEMS IgGs showed no significant changes of the channel elementary properties but rather a decreased number of active channels per patch. This suggests that Q-like current depression by LEMS autoantibodies is mostly due to a down-regulation of functioning Ca2+ channels. In agreement with previous observations, LEMS IgGs also reduced by 20-33% the dihydropyridine-sensitive (L-type) Ba2+ current. The suggested down-regulation of Q-like channels by LEMS IgGs in RINm5F cells may have a functional correlation with the depressive action of LEMS autoantibodies on the P/Q-type Ca2+ channels controlling acetylcholine release from mammalian neuromuscular junctions.

Lomefloxacin versus amoxicillin in the treatment of acute exacerbations of chronic bronchitis: an Italian multicenter study.

Nine centers in Italy participated in a worldwide, multicenter study comparing the effectiveness and safety of lomefloxacin and amoxicillin in patients with acute exacerbations of chronic bronchitis caused mainly by gram-negative pathogens. The 157 enrolled patients received either 400 mg lomefloxacin once daily (n = 78) or 500 mg amoxicillin every 8 hours (n = 79) for 7-10 days. A total of 131 patients were evaluable for bacteriologic efficacy and 154 for clinical efficacy. At 2-4 days after the conclusion of treatment, the bacterial eradication rate was 84.8% for lomefloxacin-treated patients and 64.6% for amoxicillin-treated patients (p = 0.0065); the clinical success rate (cure plus improvement) for lomefloxacin was 94.7% and for amoxicillin was 83.3% (p = 0.0212). The reinfection rate was lower in the lomefloxacin group than in the amoxicillin group (3.0% vs 13.8%, p = 0.0382). Both drug regimens were well tolerated. Once-a-day treatment with 400 mg lomefloxacin was more effective than 500 mg amoxicillin three times daily for the treatment of acute exacerbations of chronic bronchitis caused by gram-negative pathogens.

Glutathione S-transferase M1 genotype and age-related cataracts. Lack of association in an Italian population.

PURPOSE: To investigate possible associations between the gene number and allelic forms of glutathione S-transferase M1 (GSTM1) and the occurrence of nucleic and cortical age-related cataracts. METHODS: Patients with cortical cataract, nuclear cataract, mixed and cortical cataract, and no cataract were sytematically selected from subjects evaluated in the Italian-American Study of the Natural History of Age-Related Cataract. The patients were typed for the A, B, and null alleles of GSTM1 using a variation of the amplification refractory mutation system. RESULTS: Forty-nine percent of patients (50/102) with cortical cataracts, 45% (13/29) with nuclear cataracts, 51% (36/71) with mixed nuclear and cortical cataracts, and 50% of controls (49/98) were homozygous for the null GSTM1 allele. Twenty-five percent of patients (26/102) with cortical cataracts, 24% (7/29) with nuclear cataracts, 31% with mixed nuclear and cortical cataracts, and 27% of controls (26/98) displayed only the A allele for GSTM1. Twenty-four percent of patients (24/102) with cortical cataract, 24% (7/29) with nuclear cataracts, 14% (10/71) with mixed nuclear and cortical cataract, and 18% of controls showed only the B allele for GSTM1. Two percent of patients (2/102) with cortical cataracts, 7% (2/29) with nuclear cataracts, 4% (3/71) with mixed nuclear and cortical cataracts, and 5% of controls (5/98) showed both A and B alleles for GSTM1. CONCLUSIONS: No associations between the GSTM1 alleles, including the null allele, and cataracts were detected in this study.

Clinical efficacy of ofloxacin in lower respiratory tract infections. A multicentre study.

A multicentre clinical trial was carried out to determine the activity and tolerability of ofloxacin in the treatment of lower respiratory tract infections. 667 patients were randomly allocated to 1 of 3 different twice daily dosage regimens: 400 mg (245 patients), 600 mg (211) or 800 mg (211). The mean duration of treatment was 8.77 +/- 2.62 days. Satisfactory overall clinical results (i.e. cured or improved) were obtained in 612 of 667 patients (91.8%). Eradication of pathogens was achieved for 279 of 354 isolated strains (78.8%). Side effects were observed in 31 patients and consisted of gastrointestinal disturbance (22), skin rash (1), neurological disturbance (3) and others (5). No significant alteration of haematological parameters was reported.

Can prolonged treatment improve the prognosis in adults with focal segmental glomerulosclerosis?

Eighty nephrotic adults with focal segmental glomerulosclerosis (FSGS) and plasma creatinine lower than 3 mg/dL were given corticosteroids (53 patients) or immunosuppressive agents (27 patients) for a median of 16 and 75 weeks, respectively. Forty-two patients responded with complete remission (29 patients, 36%) or partial remission (13 patients, 16%). Twenty-six patients who did not respond were treated again. Two patients obtained complete remission and 13 partial remission. The probability of remission was associated with treatment with corticosteroids (P = 0.0001; RR, 3. 93; 95% CI, 2.00 to 7.72), absence of arterial hypertension (P = 0. 0023; RR, 2.59; 95% CI, 1.41 to 4.79), and a percentage of hyaline glomeruli lower than 5% (P = 0.0152; RR, 2.04; 95% CI, 1.15 to 3.64). The probability of being alive at 110 months without doubling of plasma creatinine was 69%. The risk of renal insufficiency was correlated with mesangial proliferation (P = 0.0025; RR, 5.50; 95% CI, 1.82 to 16.60) and with interstitial fibrosis (P = 0.0231; RR, 4. 44; 95% CI, 1.23 to 16.08) at initial biopsy. Considering partial or complete remission as a time-dependent variable, only the lack of remission (P = 0.0027; RR, 7.23; 95% CI, 1.98 to 26.33) and mesangial proliferation (P = 0.0069; RR, 4.59; 95% CI, 1.52 to 13. 88) were correlated with renal failure. Major side effects were observed in 11 patients (5 infections, 1 peptic ulcer, 2 diabetes, 3 neoplasias). This study shows that 70% of nephrotic adults with FSGS may obtain complete or partial remission and maintain stable renal function for about 10 years when given a prolonged therapy with corticosteroids or immunosuppressive drugs.

Ioversol. Double-blind study of a new low osmolar contrast agent for peripheral and visceral arteriography.

The new low-osmolar contrast agent ioversol was compared with the conventional ionic contrast agent diatrizoate in 60 patients undergoing routine abdominal (21 patients) and peripheral (39 patients) arteriography. The effects on hemodynamics, various laboratory parameters, and patient comfort were evaluated. In peripheral arteriography, there was less discomfort with ioversol as well as decreased magnitude and incidence of hypotension (P less than .001) after injection. In visceral arteriography, there was no significant difference between the two agents. Overall, the incidence of ECG changes was small in both groups (ioversol 2%, diatrizoate 8%). The two media were equivalent in incidence of adverse reactions (eg, nausea, vomiting, urticaria), the effect on laboratory parameters, and in the diagnostic adequacy of the radiographs. We conclude that ioversol is safe and efficacious for peripheral and visceral arteriography. In peripheral arteriography it causes less patient discomfort and, perhaps more importantly, fewer hemodynamic alterations than diatrizoate. These differences in hemodynamic effects may be important in patients with hemodynamic instability or limited cardiovascular reserve.

Atherosclerosis, peripheral arterial disease and the vascular response to ketanserin.

Platelet activation releases thromboxane A2 and serotonin, which acts on blood vessels through a specific, 5-hydroxytryptamine (5-HT2) receptor. The development of ketanserin, the selective 5HT2 receptor blocker, has made it possible to explore the role of serotonin in patients with advanced atherosclerotic disease. Ketanserin in low doses (3 to 30 micrograms/kg) was administered intra-arterially to 23 patients with symptomatic peripheral occlusive vascular disease during peripheral angiography: an additional seven patients received a placebo. The angiographic response was evaluated by coded reading and by computer-assisted measurement of arterial segments in four anatomical regions (pelvis, thigh, knee, and lower leg). Hemodynamic changes were assessed by mercury strain gauge plethysmography and Doppler pressure measurement. Unequivocal vasodilatation was observed in zero of seven placebo-treated patients and in 13 of 23 (57%) treated patients primarily at the level of collateral vessels. Dilation of the geniculate arteries, a major source of collaterals to the calf, was associated with a significant increase in the blood flow delivery to the calf. There was a moderate drop of systemic blood pressure in patients who failed to respond with peripheral vasodilatation. Ketanserin induces hemodynamically significant vasodilatation in some patients with peripheral vascular disease, suggesting that serotonin may contribute to ischemia in some patients with advanced atherosclerosis.

Sister chromatid exchange analysis in familial groups of malignant melanoma patients.

Sister chromatid exchange (SCE) analysis was carried out on peripheral blood lymphocytes of 20 familial malignant melanoma (FMM) and 39 sporadic malignant melanoma (SMM) untreated patients, belonging to 10 and 39 families, respectively. The study was extended to 39 unaffected close relatives of FMM patients, to 187 unaffected close relatives of SMM patients, and to 20 unaffected unrelated individuals (control group), all examined under the same conditions. The mean SCE rates/cell were significantly higher in MM families than in the control group, and in melanoma patients than in their close relatives. The mean SCE levels of FMM and SMM patients, (8.4 +/- 0.8 and 8.0 +/- 0.3, respectively) were similar, and so were the distributions of individuals in classes of increasing SCE values (with a modal value at 7-8 SCEs/cell). The mean SCE levels of close relatives of FMM and SMM patients were also similar (5.4 +/- 0.2 and 5.4 +/- 0.1, respectively, with a modal value at 4-5 SCEs/cell), and slightly higher than in the control group (4.7 +/- 0.2 SCEs/cell). More than 7 SCEs/cell were observed in the majority (41 of 59) of FMM or SMM patients, in a smaller fraction (25 of 227) unaffected relatives, and in none of 20 unrelated unaffected individuals. These observations favor the hypothesis that higher SCE levels may be an expression of constitutional lesions predisposing to this neoplastic disease.

Respiratory infections: clinical evaluation.

A review of clinical studies of piperacillin shows that it is valuable for the treatment of respiratory infections due to Enterobacteriaceae, Pseudomonas sp, anaerobes, and mixed flora including anaerobes. Various studies of a total of 420 patients treated with piperacillin for lower respiratory tract infections found that 97% of the patients were cured or markedly improved. Piperacillin has also been found as effective as combination therapy (gentamicin or tobramycin plus carbenicillin or ticarcillin) in the treatment of serious infections, including pneumonia and several caused by gram-negative organisms and anaerobic organisms. A review of the literature on bacteriological responses to piperacillin shows that 126 of 153 (82%) of the susceptible strains could be eradicated. Streptococcus pneumoniae, beta-hemolytic streptococci, Haemophilus influenzae, Peptostreptococcus sp, Bacteroides sp, and Fusobacterium sp have been completely eradicated by treatment with piperacillin. Most of the published studies indicate that therapy with the drug is usually well tolerated.

Tension development in lumbrical muscles and concomitant increase of activity in A alpha and A beta afferents during sympathetic stimulation in the cat.

In anaesthetized and curarized cats electrical stimulation of the lumbar sympathetic trunk, at frequencies within the physiological range, induces the development of a small tension in superficial lumbrical muscles (50-100 mg in different preparations). This effect can be reproduced in anaesthetized and curarized cats by stimulating the peripheral stump of the tibial nerve with parameters adequate to activate the entire C-fibre group, and therefore postganglionic sympathetic fibers. The collision technique was used to evaluate in the tibial nerve possible changes in afferent activity from the skinned foot. It was found that an increase of non-cutaneous activity consistently occurs in A beta and, occasionally, in A alpha fibre groups. Secondary and primary spindle afferents, respectively, belong to these fibre groups. It was also found that: (1) the tension development in lumbrical muscles and the increase of the afferent activity of non-cutaneous origin exhibit similar time courses; (2) the two events are affected in parallel by the same stimulus parameters; (3) both events are abolished by alpha-adrenoceptor antagonists. Therefore the possibility of a sympathetic fusimotor action affecting mainly secondary afferents is suggested and discussed.

Auditory steady-state responses to click trains from the rat temporal cortex.

In order to investigate the mechanisms underlying the generation of steady-state responses (SSRs), auditory evoked potentials elicited by click trains presented at several stimulation rates (30, 40, 50, 60 Hz) were recorded in 7 awake rats by means of epidural electrodes placed over the temporal cortex. Mean amplitude-rate function calculated on the recorded responses appeared almost flat and showed the maximum value at 50 Hz, while mean phases showed a linear increase when increasing the stimulation rate. In each rat, predictions of the recorded responses at 30, 40, 50 and 60 Hz were synthesized by superimposing middle-latency auditory evoked potentials (MAEPs) at suitable time intervals at each rate. Mean amplitudes calculated on the predicted curves decreased linearly when increasing the stimulation rate and appeared higher in comparison to those obtained from the recorded SSRs. Predicted phases showed a linear increase when increasing the stimulation rate and were leading with respect to corresponding phase values calculated for recorded SSRs. Our findings indicate that the MAEP superimposition mechanism does not adequately predict the generation of temporal recorded SSRs in rats. This was explained by admitting that phenomena related to the recovery cycle and, to a lesser extent, to rate-dependent facilitating effects come into play.

Possible modulation of auditory middle latency responses by nitric oxide in the inferior colliculus of anaesthetized rats.

Nitric oxide (NO) is a short-lived radical species endowed with intercellular signalling functions in the mammalian brain. In the present study we have investigated the effects of focal injection into one inferior colliculus of N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, on the acoustic middle latency responses (MLRs) evoked by click stimuli and recorded from the auditory cortex in anaesthetized rats. Microinfusion of L-NAME (1.0 mM) did not alter the latency of MLRs nor did it affect the evoked brain stem responses (ABRs). By contrast, L-NAME reduced P1a-N1 amplitude of MLRs by 51.7 +/- 6.6% (mean +/- SEM; n = 5) and almost complete recovery to background amplitude was obtained 15-25 min after treatment. The less active isomer, D-NAME (1.0 mM; n = 5), failed to produce consistent effects on the evoked MLRs. A higher concentration of L-NAME (5.0 mM; n = 5) yielded a 69.0 +/- 13.3% inhibition whereas maximum inhibition produced by 0.5 mM (n = 3) L-NAME was approximately equal to 10% of control value. The inhibitory effect typically evoked by 1.0 mM L-NAME was prevented by treating rats with L-arginine (5.0 mM; n = 5), the endogenous precursor of NO synthesis. Reduction of MLR amplitude was also obtained in rats receiving intracollicular injection of dizocilpine (MK801; 1.0 microM) and LY274614 (1.0 mM), two selective N-methyl-D-aspartate (NMDA) receptor antagonists. In conclusion, the present data support a role for intracollicular NO in the processing and transmission of the acoustic input to the auditory cortex in the rat.

Inhibition of low- and high-threshold Ca2+ channels of human neuroblastoma IMR32 cells by Lambert-Eaton myasthenic syndrome (LEMS) IgGs.

IgGs from two LEMS patients applied to human neuroblastoma IMR32 cells reduced the density of low- (LVA; T) and high-threshold (HVA; L and N) Ba2+ currents by different percentages: 36% (LVA) and 56% (HVA) for one and 48% and 45% for the other. A pharmacological assay of IgGs action based on the block of L-type channel by nifedipine and on the delayed activation of N-type channel by noradrenaline, indicated a preferential inhibition of the N-type current in IMR32 cells (55% and 47% for the two patients). The L-type current, contributing to approximately one-third of the total, was also depressed by LEMS IgGs but to a minor degree (49% and 30%). Except for an increase of single N-type channel inactivation, LEMS antibodies preserved the elementary properties of single HVA channels, suggesting that the macroscopic current reduction after IgGs treatment is likely due to a decrease in the number of active HVA Ca2+ channels.