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BACKGROUND: The prevalence of schizophrenia in the United States ranges between 0.5% and 1%. This difficult-to-treat disorder is marked by the presentation of symptoms that are both positive (i.e. hallucinations) and negative (i.e. blunted affect), as well as disturbances in cognition and affect. Several second-generation antipsychotics (i.e. olanzapine, risperidone, etc.) have been utilized for their varying effects on the symptoms of schizophrenia, yet 20% to 60% of patients with schizophrenia are considered treatment-resistant. While clozapine has been shown to be the most effective antipsychotic, negative symptoms commonly persist in clozapine-treated patients. Research shows that oxytocin has neuromodulatory effects on social perception and also enhances empathy and attentional engagement in individuals with schizophrenia, suggesting it has therapeutic effects on negative symptoms. The present study presents a series of cases suggesting the efficacy of combining clozapine and oxytocin for the reduction of positive and negative symptoms. This work contributes to schizophrenia treatment research by reporting a novel, integrated pharmacological approach to treatment-resistant schizophrenia. METHODS: Retrospective chart reviews were conducted on the charts of 15 patients with treatment-resistant schizophrenia. The patients were all admitted to the persistent psychotic disorder unit at a private hospital between May 2014 and September 2017. The average treatment duration was 2.7 months with a range between 1 and 9 months. All patients were 18 years or older and met the DSM-5 criteria for schizophrenia. The Positive and Negative Syndrome Scale (PANSS) was used to assess the efficacy of the combination treatment. Clozapine was prescribed to all 15 patients after they had failed to improve in three different trials of other antipsychotic medications. Intranasal oxytocin (10 IU 2x per day; 20 IU 3x per day) was prescribed to 11 of the patients only after the improvement in positive symptoms on the PANSS with clozapine had plateaued. Due to the risk of intranasal substance use in all the patients, oxytocin was administered sublingually to ensure adequate and less variable absorption of the neuropeptide. RESULTS: Over the course of treatment, PANSS scores reflected significant changes (p

Background The prevalence of schizophrenia in the United States ranges between 0.5% and 1%. This difficult-to-treat disorder is marked by the presentation of symptoms that are both positive (i.e. hallucinations) and negative (i.e. blunted affect), as well as disturbances in cognition and affect. Several second-generation antipsychotics (i.e. olanzapine, risperidone.) have been utilized for their varying effects on the symptoms of schizophrenia, yet 20% to 60% of patients with schizophrenia are considered treatment-resistant. While clozapine is shown to be the most effective antipsychotic, negative symptoms commonly persist in clozapine-treated patients. Research shows that oxytocin has neuromodulatory effects on social perception and enhances empathy and attentional engagement in individuals with schizophrenia, suggesting it may have therapeutic effects on negative symptoms. The present study presents a pilot prospective research study evaluating the efficacy of combining clozapine and sublingual oxytocin for the reduction of positive and negative symptoms. Methods Prospective research study evaluated 25 treatment resistant schizophrenic patients who were admitted to the persistent psychotic disorder unit at a private hospital, with an average treatment duration of 2.9 months with a range between 1 and 9 months. All have been followed as outpatient for up to 30 months after discharge. All patients were 18 years or older and met the DSM-5 criteria for schizophrenia. The Positive and Negative Syndrome Scale (PANSS) was used to assess the efficacy of the combination treatment. Clozapine was prescribed to all 25 patients after they had failed to improve in three different trials of other antipsychotic medications. Sublingual oxytocin (10 IU 2x per day; 20 IU 3x per day) was prescribed to 25 of the patients only after the improvement in positive symptoms on the PANSS with clozapine had plateaued. Due to a history of intranasal substance use in all the patients, oxytocin was administered sublingual to ensure adequate and less variable absorption of the neuropeptide. Results A time-series analysis demonstrated a significant decrease in PANSS scores across admission, stabilization of clozapine and stabilization of oxytocin (p Discussion The combined effect extends the current research of augmenting sublingual oxytocin and clozapine for individuals with previously treatment-resistant symptoms. Though each patient benefitted from clozapine alone, negative symptoms persisted. Patients, their families, and treatment program staff all observed a significant reduction in the patients’ anxiety and an improvement in the patients’ relatedness. While this case series cannot establish that oxytocin is responsible for the clinical improvements seen here, it does suggest that it may improve negative symptoms and social functioning in patients with treatment-resistant schizophrenia showing incomplete improvement with clozapine alone. The present study suggests the need for future research to explore the possibility that oxytocin can mitigate the negative symptoms of schizophrenia.

Thirty-three terminal cancer patients suffering from extremely severe drug-resistant pain were treated with Scrambler Therapy, a new bioengineering-based method for treating oncological/ neuropathic pain. Preliminary tests of the method’s effectiveness were performed by measuring pain intensity (visual analogue scale (VAS)) before and after each treatment session, and the duration of absence of pain in the hours following each single application, as well as by recording the variation in painkiller consumption. Each patient subsequently continued to receive treatment until the end point was reached, verifying whether the method retained the effectiveness displayed during the reference period. The VAS statistics before and after each treatment session, and of the baseline VAS prior to treatment and at the end of the reference cycle were subjected to a paired t-test (statistical significance). Both VAS references indicated a significant decrease in pain intensity, with p

Les auteurs rapportent deux observations de patients japonais souffrant de pancreatite chronique hereditaire : une femme de 46 ans atteinte de pancreatite chronique et son fils aine, qui fut symptomatique des l’âge de 18 ans et dont le diagnostic de pancreatite chronique calcifiante a ete pose a l’âge de 22 ans. Ces observations conduisent a une discussion de la prevalence de la pancreatite familiale dans la population japonaise.

The destruction by phagocytic cells of ingested microorganisms is best ensured by an intact respiratory burst with production of superoxide anion and other metabolites. The aim of the present study was to investigate the status of the reticulo-endothelial system, as assessed by superoxide anion generation of blood monocytes, in 18 patients with chronic pancreatitis (CP) as compared to 15 with chronic renal failure (CRF), 14 with diabetes mellitus (DM) and to 20 healthy volunteers. Macrophage suspensions (1 × 10 6 ) were prepared from blood samples withrawn after an overnight fast were tested for conventional phagocytosis function (carbon partical ingestion: percent and intensity) and for superoxide anion generation (chemiluminescent activation: cpm of light integrated intensity). Conventional phagocytosis function tests did not show any differemce among the groups examined. However, the peak value of generated susperoxide anion (× 10 4 cpm) was significantly lower in CP patients as compared to either healthy controls (14.9 ± 4.3 vs. 28.3 ± 4.7, P P P P

Huit cas de tumeurs insulaires (cinq insulinomes, deux gastrinomes et un glucagonome) ont ete diagnostiques au cours des onze dernieres annees au Centre National du Cancer a Tokyo. Un pancreatogramme a ete obtenu par CPRE dans quatre cas. Deux d’entre eux presentaient une interruption du canal pancreatique principal au niveau corporeal, un des patients avait une interruption et un aspect mouchete de la branche correspondant au processus incine. Un autre presentait, au niveau caudal, une dilatation irreguliere isolee du canal pancreatique. Les auteurs commentent les aspects caracteristiques des images pancreatographiques de ces tumeurs. Jusqu’a present, le diagnostic de ces tumeurs pancreatiques etait pose principalement sur base de donnees endocrinologiques et radiologiques. Neanmoins, a partir des donnees rapportees, il semble que dans la localisation des tumeurs insulaires, la CPRE presente une valeur diagnostique equivalente a celle de l’angiographie et de la tomodensitometrie computee.

We advocate the need to exploit formal methods in the development of critical applications on top of RT-CORBA, a recently defined real-time extension of CORBA. We illustrate our approach using the TRIO formal notation. First, we provide a model of the core features of RT CORBA and of the real-time event service. Then we formalize the requirements of a simple application for supervision and control, and we outline the object architecture of its implementation based on the RT-CORBA platform. Finally we show how the above model (RT-CORBA and service plus application objects) can be employed in the proof that the application requirements are actually fulfilled.

An Experimental Design technique applied for the training of Artificial Neural Networks is presented. The methodology is oriented to maximize the information achievable during experimental tests by guiding them in a structured way and to avoid the overtraining and the overfitting of the Network. The adopted technique is known as Active Learning and is based on the selection of the most significant training examples from an existing set of experimental data. Each experiment, feeding the Neural Network, is chosen as the one which brings the highest content of information through the maximization of an information functional based on the Shannon's Entropy concept. The results for the estimation of the Mechanical Efficiency and the Load Torque for a Spark Ignition Engine exhibit high precision levels with a lower number of experiments with respect to the use of conventional strategies for selecting the training data set.

SummaryLumboadrenal vein blood was continuously collected at min intervals from anesthetized dogs who were either made hypoxic or infused with ACTH or MEC. The secretions of 11-OHCS increased within the first min and attained peak rates between 5 and 10 min of exposure to these agents. Part of the increased secretory rates of the hypoxic and MEC groups could be accounted for by increases in adrenal blood flow. These data suggest that a min is sufficient time for hypoxia to (a) activate the hypothalamo–hypophyseal complex to release ACTH, (b) decrease the transit time for ACTH to reach the adrenal gland, and (c) increase adrenal blood and plasma flows. When occurring simultaneously, these 3 factors result in a rapid and sustained increase in adrenocortical secretory rates during hypoxia.The excellent technical assistance of E. Blomquist, C. Lau and L. Malasanos is greatly appreciated. Special thanks are due Dr. G. Courtney for encouragement, assistance and discussions during the course of this investigation.

SummaryAnesthetized dogs were subjected to 3–21 mm Hg CPPB or AbPB. Carotid and femoral arterial blood flow and mean carotid pressure decreased inversely proportional to increasing CPPB while femoral pressure remained essentially unaltered. Thus vascular resistance was significantly elevated only in the femoral circulation. In general, since all levels of AbPB were without effect except for the slight depression in femoral flow, the data suggest that elevations in abdominal pressure which occur during CPPB do not play a significant role in the restoration of circulatory parameters.

ALTHOUGH recovery of function following brain damage has long been known to occur, the mechanisms involved are not completely understood1. Of relevance to this problem are reports of pharmacological facilitation of recovery from brain damage in humans2 and from experimentally-induced nervous system lesions in animals3–9. We have previously reported that L-dopa injections produce a dramatic and apparently permanent abolition of the hyper-reactivity or rage syndrome that results from surgical damage to the septal nuclei of the rat forebrain10. Independent confirmation of this finding has also appeared11. We report here that other dopamine agonists share this ability to attenuate or abolish the septal rage syndrome (SRS).

SummaryEighteen experiments were performed on 8 conscious and anesthetized dogs in which the dorsal roots (T11-L3) had been severed and a glass cannula inserted in the lumbo-adrenal vein. Decompression to 17,000 feet simulated altitude for 2 hours while breathing ambient air (pO2 78 mm Hg) caused marked elevations in 17-OHCS secretions in both conscious and anesthetized dogs.

Mental disturbances associated with acquired immunodeficiency syndrome (AIDS) are related not only to profound psychosocial stress, systemic diseases, and neoplasms or opportunistic infections within the central nervous system (CNS); they are also related to the direct neurotoxicity of the etiologic human immunodeficiency virus (HIV), producing an array of both insidious and acute affective, cognitive, and behavioral dysfunction that can mimic many neuropsychiatric disorders. The precise mechanism of this direct neurotoxicity is not known, nor have the frequency, clinical course, or methods of early diagnosis been clearly established; however, a critique of 56 clinical reviews or case reports regarding approximately 800 subjects suggest that at some point following infection an HIV-induced dementia is extremely common, as are marked histopathological changes throughout the CNS. Treatment strategies are discussed.

The human immunodeficiency virus (HIV), the etiological agent of acquired immunodeficiency syndrome (AIDS), directly affects the central nervous system (CNS) and often causes cognitive, motor, and behavioral changes and eventually a dementia prior to death. Suggestive evidence for the early onset of HIV-induced mental changes is derived from numerous case reports, the nature of subcortical CNS postmortem findings, and early abnormalities seen in cerebrospinal fluid, on brain computed tomography, magnetic resonance imaging, and electroencephalography, and on neuropsychological tests administered to patients with AIDS and AIDS-related complex. However, whether clinically significant cerebral impairment can precede symptoms of immunosuppression is unclear. A few studies have shown poorer performance on neuropsychological tests by asymptomatic HIV-infected subjects compared with uninfected controls, but several studies have not found this difference. To address this controversy, the current literature is reviewed, methodological problems are discussed, and recommendations are made for evaluation and treatment when early HIV-induced mental changes are suspected.

Various circulatory functions were measured in anesthetized dogs subjected to 18.5 mm Hg positive pressure breathing. Immediately upon raising the intrapulmonary pressure there occurred a five- to sixfold increase in venous pressure as well as a decrease in mean arterial pressure. Accompanying these pressure changes was a progressive decrease in circulating plasma volume as measured by the T-1824 method. A 30% decrease in plasma volume was recorded after 160 minutes of increased intrapulmonary pressure. Hemoconcentration was also indicated by the increased hematocrits, although calculated fluid loss was only 13%. All circulatory changes returned to prepressure breathing levels upon release of pressure breathing. Other changes, such as oliguria, periods of apnea and an alkaline urine accompanied positive pressure breathing. The data suggest that the decrease in plasma volume is the result of venostasis caused by the rapid increase in venous pressure. Submitted on April 27, 1959

SummaryExperiments on acutely prepared anesthetized dogs revealed that 17-OHCS secretion after adrenal vein cannulation reached a low baseline level within one hour and remained relatively stable for the next 3.5 hours during which time the adrenal cortex was responsive to exogenous ACTH. Using this preparation, 17-OHCS secretory rates were significantly increased during hyperoxia, hypoxia and continuous positive pressure breathing. No significant positive correlations between steroid concentration and plasma flow were observed. The possible mechanism (s) for stimulation of the adrenal cortex during these stresses are discussed.

Femoral arterial blood flow and related cardiopulmonary parameters were ascertained in 95 anesthetized dogs during exposure to heat, cold, altitude, hypoxia at two different times, and various combinations of these environments. Cold (1 C) and decompression (17,300 ft) without hypoxia at room temperature (24 C) each depressed arterial blood flow significantly the same amount, while the combination of decompression and cold caused a significant depression in flow less than either acting alone. Heat (38 C) alone produced slight increases in arterial pressure and heart rate; however, heat in combination with altitude depressed the flow less than did altitude alone. Hypoxia (Po2 75 mm Hg), whether from decompression or breathing 10% O2 at ground level, increased blood flow while depressing femoral vascular resistance in all animals in cold, hot, or room temperatures. The greatest hypoxic increases in blood flow were noted immediately after decompression both at 24 and 38 C, while the smallest increase was noted with hypoxic exposure during the second period at a cold, simulated altitude. circulation and stress Submitted on June 19, 1963