Effectiveness of oral sildenafil for neonates with persistent pulmonary hypertension of newborn (PPHN): a prospective study in a tertiary care hospital.

INTRODUCTION: The prevalence of persistent pulmonary hypertension of newborn (PPHN) has been estimated 1.9/1000 live births. Although the efficacy of inhaled nitric oxide and extracorporeal membrane oxygenation in PPHN is well established but it is difficult to administer and monitor in resource limited countries. Owing to this, other treatment options need to be evaluated. METHOD: This is a prospective observational study conducted in the Pediatric Cardiology Department, NICVD, Karachi, from February 2020 to October 2020 after the approval from the Institutional Ethical Review Committee. All the neonates referred to our Unit were screened by echocardiography (echo) and those who fulfilled the inclusion criteria were included. Echo were done before starting sildenafil and after 72 h to assess the pressure gradient across tricuspid valve and right to left or bidirectional shunt across patent ductus arteriosus , patent foramen ovale , or both. Sildenafil was started with a dose of 1 mg/kg/dose thrice a day and increased to 2 mg/kg/dose after 48 h if partial pressure of oxygen (PO1] did not increase. In neonates who did not respond to increased dose of Sildenafil were added on oral Bosentan 1 mg/kg/dose twice a day. RESULTS: Total 82 newborns were enrolled. Fifty-two patients improved after 48 h so were continued on same treatment. Sildenafil dose was increased in 30 (37.9%) patients whose PO2 did not increase to at least 10% from baseline after 48 h of starting treatment. Three patients expired within 48-72 h. Out of 27 remaining patients, only four responded whereas 23 patients did not show any improvement. In these patients, Bosentan was supplemented along with sildenafil. CONCLUSION: The results of our study show effectiveness of oral Sildenafil in treating PPHN. The overall improvement observed in the patients was overwhelming. Combination of Sildenafil with Bosentan is beneficial in patients who did not respond on Sildenafil alone.

Overexpression of an insect virus encoded silencing suppressor does not enhance plants' susceptibility to its natural virus.

RNA silencing plays a key role in shielding plant and animal hosts against viral invasion and infection. Viruses encode RNA silencing suppressors (RSS) to block small RNA guided silencing of viral transcripts. The B2 protein encoded by Flock House virus (FHV) is a well-characterized RSS that facilitates infection in insects. It has been shown to act as a functional RSS in plants. FHVB2 over-expressing tobacco plants were used to study the effect of RSS on plant susceptibility to Tobacco mosaic virus (TMV), its natural pathogen. The major symptoms observed in TMV-infected transgenic plants were greenish mosaic, puckering and distortion of leaves, but the infected transgenic leaves were able to resist chlorophyll loss. The infected leaves of transgenic plants showed no significant difference in accumulation of virus when compared with that of the wild type plants. FHVB2 plants showed higher levels of H2O2 and the ROS scavenging enzymes, APX and SOD. This suggests that interference of FHVB2 with RNA silencing machinery may activate alternative defense pathways in the plants so that they are not overly sensitive to TMV infection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-020-00644-5.

Early and Intermediate-Term Outcome of Balloon Aortic Valvuloplasty in Children With Aortic Stenosis and Left Ventricular Dysfunction at Tertiary Care Hospital.

Background Left ventricular (LV) dysfunction in patients with aortic valve stenosis (AVS) is seen in two scenarios: in neonates and in elderly patients. Neonatal AVS may present as a congestive cardiac failure (CCF), while older children rarely present with CCF if they have not been diagnosed early. Only a few reports of LV dysfunction with AVS have been described in the literature. However, there is a paucity of data regarding the safety and effectiveness of balloon aortic valvuloplasty (BAV) in children with AVS with LV dysfunction. Therefore, the aim of this study was to evaluate outcomes to establish the safety and effectiveness of BAV in children with AVS and LV dysfunction in improving LV function and survival. Methods A total of 160 BAVs were performed from 2004 to 2017; of these, 41 (25.6%) patients had LV dysfunction. We reviewed these cases, and data were obtained on clinical features, echocardiographic parameters including LV ejection fraction (LVEF) and LV dimensions, LV posterior wall, interventricular septal thickness, pressure gradient across the valve, aortic valve morphology and annulus and aortic insufficiency (AI), and angiographic parameters such as aortic and LV pressures, AI and annulus size, and balloon size. Echocardiography was done before the procedure, one day after intervention, at three months, at six months, and on regular follow-up. Mortality during and after the procedure and at follow-up was reported. Results Children who had undergone BAV for AVS and LV dysfunction within the age range of six to 192 months showed a significant reduction in peak-to-peak pressure gradient (PPG) from 73.5 ± 30 mmHg to 26.7 ± 6.7 mmHg and improvement in LVEF from 32.8 ± 11% to 54.3 ± 12.7% after 24 hours. Instantaneous gradient on echocardiography after three months showed PPG was 29.8 ± 7.7 mmHg and mean LVEF was 63 ± 8.6%. Mean LV end-diastolic pressure was 20.8 ± 4.7 mmHg and decreased to 13 ± 2.4 mmHg. Four patients died, all of whom had severe LV dysfunction - one died during the procedure and three died within six to 20 hours after successful BAV. On average follow-up of 6.4 ± 3.8 years, with a range of three months to 13 years, there was no mortality, pressure gradient increased to 40 ± 16.3 mmHg (range, 20 to 90 mmHg), and three had BAV after one, four, and six years, respectively. There was an increase in AI from mild to moderate in five patients, but they did not require any intervention. Four patients had aortic valve replacement (AVR) with two patients having an increase in pressure gradient and AI after eight and 13 years, respectively. One patient had AI (+3) after BAV had AVR after three years, and one patient who had a very thick and dysplastic aortic valve with LVEF of 20% and pulmonary hypertension (PH) had AVR after six months. Conclusion Patients with AVS who develop LV dysfunction deteriorate and die soon without treatment. Our data suggest that BAV in children with aortic stenosis and LV dysfunction is safe and effective in the normalization of LV function.

Incidence of Aortic Regurgitation in Association with Type of Ventricular Septal Defects and its Immediate and Intermediate Outcome after Surgical Closure.

Introduction Ventricular septal defect (VSD) is one of the more common congenital heart defects, and aortic regurgitation (AR) is its major complication if it remains unrepaired. We aim to determine the AR incidence in various types of VSD, its immediate and intermediate six to 12-month post-VSD repair outcomes of AR. Methods We conducted a retrospective review of medical records of all children aged 18 years or younger who were diagnosed with single VSD at our institution from 2016 to 2018. VSD was classified according to its location and relation to the tricuspid annulus and semilunar valve. AR severity grading was done according to the American Society of Echocardiography, and vena contracta width (VC) was taken as the main parameter for severity. We defined trivial-to-mild AR as VC width less than 0.3 cm, moderate AR was 0.3-0.6 cm VC width, and severe AR was VC width of more than 0.6 cm. Immediate and intermediate outcomes of surgical closure, such as residual VSD and AR, were observed. Results One hundred ninety patients with isolated single VSD were included in the study. Of those, 114 patients had perimembranous VSD (60.0%), 64 patients had muscular VSD (33.7%), and 12 patients had supracristal VSD (6.3%). The median age of our study cohort was six months, with a male to female ratio of 1.3:1. Aortic valve prolapse (28.9%; n = 55) and AR (23.2%; n = 44) were the most common findings on echocardiographic evaluation of VSD patients. Most cases of VSD with AR had trivial-to-mild AR, (68.2%; n = 30). AR was most commonly seen in supracristal VSD (83.3%; n = 10) followed by perimembranous VSD (28.9%; n = 33). VSD closed spontaneously in 34 patients (17.9%) and 98 patients (51.6%) patients underwent surgery. Residual VSD after surgical closure was present in 57.1% (56) and 17.3% (17) of the patients immediate postoperatively and six- to 12-month postoperative follow-up, respectively. Similarly, residual AR after surgical closure of VSD was present in 32.7% (32) and 15.3% (15) of the patients immediate postoperatively and six- to 12-month postoperative follow-up, respectively. Conclusion The incidence of AR with VSD was very high in our study; AR was most commonly associated with supracristal VSD. After surgical repair, mild AR decreased with time. Early corrective surgery of VSD can prevent this complication and help improve outcomes.

Effects of nicotine on response inhibition and interference control.

Nicotine is a cholinergic agonist with known pro-cognitive effects in the domains of alerting and orienting attention. However, its effects on attentional top-down functions such as response inhibition and interference control are less well characterised. Here, we investigated the effects of 7 mg transdermal nicotine on performance on a battery of response inhibition and interference control tasks. A sample of N = 44 healthy adult non-smokers performed antisaccade, stop signal, Stroop, go/no-go, flanker, shape matching and Simon tasks, as well as the attentional network test (ANT) and a continuous performance task (CPT). Nicotine was administered in a within-subjects, double-blind, placebo-controlled design, with order of drug administration counterbalanced. Relative to placebo, nicotine led to significantly shorter reaction times on a prosaccade task and on CPT hits but did not significantly improve inhibitory or interference control performance on any task. Instead, nicotine had a negative influence in increasing the interference effect on the Simon task. Nicotine did not alter inter-individual associations between reaction times on congruent trials and error rates on incongruent trials on any task. Finally, there were effects involving order of drug administration, suggesting practice effects but also beneficial nicotine effects when the compound was administered first. Overall, our findings support previous studies showing positive effects of nicotine on basic attentional functions but do not provide direct evidence for an improvement of top-down cognitive control through acute administration of nicotine at this dose in healthy non-smokers.

Neural effects of methylphenidate and nicotine during smooth pursuit eye movements.

INTRODUCTION: Nicotine and methylphenidate are putative cognitive enhancers in healthy and patient populations. Although they stimulate different neurotransmitter systems, they have been shown to enhance performance on overlapping measures of attention. So far, there has been no direct comparison of the effects of these two stimulants on behavioural performance or brain function in healthy humans. Here, we directly compare the two compounds using a well-established oculomotor biomarker in order to explore common and distinct behavioural and neural effects. METHODS: Eighty-two healthy male non-smokers performed a smooth pursuit eye movement task while lying in an fMRI scanner. In a between-subjects, double-blind design, subjects either received placebo (placebo patch and capsule), nicotine (7mg nicotine patch and placebo capsule), or methylphenidate (placebo patch and 40mg methylphenidate capsule). RESULTS: There were no significant drug effects on behavioural measures. At the neural level, methylphenidate elicited higher activation in left frontal eye field compared to nicotine, with an intermediate response under placebo. DISCUSSION: The reduced activation of task-related regions under nicotine could be associated with more efficient neural processing, while increased hemodynamic response under methylphenidate is interpretable as enhanced processing of task-relevant networks. Together, these findings suggest dissociable neural effects of these putative cognitive enhancers.

Atypical Presentation of Capillary Hemangioma in Oral Cavity- A Case Report.

Capillary Haemangioma is a benign vascular tumour characterized by proliferation of blood vessels that are primarily reported to be a developmental hamartomatous lesion of infancy and childhood. Pyogenic granuloma is a non-neoplastic benign lesion found in the oral cavity having a striking predilection for occurrence in the gingiva. The present case report is an atypical presentation of capillary haemangioma on gingiva which is considered to be extremely rare. The lesion in this case was clinically diagnosed as pyogenic granuloma but histopathologically as capillary haemangioma. These lesions present as a diagnostic dilemma to the clinician and can lead to serious complications if not carefully managed.

Evidence for genetic linkage between a polymorphism in the GNAS gene and malaria in South Indian population.

The complex imprinted GNAS locus which encodes G-alpha subunit (Gαs) is involved in a number of G-protein coupled signaling pathways in eukaryotic cells. Erythrocyte invasion by Plasmodium falciparum parasites is significantly regulated by protein of GNAS gene. This study was designed to evaluate the association between single nucleotide polymorphisms (SNPs) present in GNAS locus and susceptibility to malaria. In this case control study, individuals affected by P. falciparum malaria (n=230), Plasmodium vivax malaria (n=230) and normal controls (n=230) were tested for the association of eighteen (18) known SNPs to evaluate their role in the onset of the disease. There was no significant difference in genotype frequencies of all the SNPs tested between P. falciparum and P. vivax affected individuals. However, when Bonferroni correction for multiple comparisons were performed as a control, our results demonstrated alleles and genotypes of rs7121: C>T (NC_000020.10:g.57478807C>T), a silent polymorphism situated in the exon 5, were significantly (p<0.05) associated with susceptibility to malaria in the South Indians participants. Our results demonstrate that population specific polymorphisms that exist in GNAS gene may alter the risk of occurrence of malaria.

Secretion and signaling activities of lipoprotein-associated hedgehog and non-sterol-modified hedgehog in flies and mammals.

Hedgehog (Hh) proteins control animal development and tissue homeostasis. They activate gene expression by regulating processing, stability, and activation of Gli/Cubitus interruptus (Ci) transcription factors. Hh proteins are secreted and spread through tissue, despite becoming covalently linked to sterol during processing. Multiple mechanisms have been proposed to release Hh proteins in distinct forms; in Drosophila, lipoproteins facilitate long-range Hh mobilization but also contain lipids that repress the pathway. Here, we show that mammalian lipoproteins have conserved roles in Sonic Hedgehog (Shh) release and pathway repression. We demonstrate that lipoprotein-associated forms of Hh and Shh specifically block lipoprotein-mediated pathway inhibition. We also identify a second conserved release form that is not sterol-modified and can be released independently of lipoproteins (Hh-N*/Shh-N*). Lipoprotein-associated Hh/Shh and Hh-N*/Shh-N* have complementary and synergistic functions. In Drosophila wing imaginal discs, lipoprotein-associated Hh increases the amount of full-length Ci, but is insufficient for target gene activation. However, small amounts of non-sterol-modified Hh synergize with lipoprotein-associated Hh to fully activate the pathway and allow target gene expression. The existence of Hh secretion forms with distinct signaling activities suggests a novel mechanism for generating a diversity of Hh responses.

Heteropagus twins-a tale of two cases.

Heteropagus twinning is a rare occurrence. Parasitic and asymmetric conjoined twins are rarer anomalies of monochorionic monoamniotic twins; which consist of an incomplete twin attached to the fully developed body of the co-twin. We present here two such cases of Heteropagus twinning.

Sensorimotor gating is associated with CHRNA3 polymorphisms in schizophrenia and healthy volunteers.

Attentional gating deficits, commonly measured by prepulse inhibition (PPI) of the acoustic startle response (ASR), have been established as an endophenotype of schizophrenia. Prepulse inhibition is heritable and has been associated with polymorphisms in serotonin and dopamine system genes. Prepulse inhibition can be enhanced by nicotine, and therefore it has been proposed that schizophrenia patients smoke to ameliorate their early attentional deficits. The PPI-enhancing effects of nicotine in rodents are strain dependent, suggesting a genetic contribution to PPI within the nicotinic acetylcholine receptor (nAChR) system. Recent human genetic studies also imply that tobacco dependence is affected by polymorphisms in the alpha3/alpha5 subunits of the nAChR (CHRNA3/CHRNA5) gene cluster. We, therefore, investigated the impact of two common CHRNA3 polymorphisms (rs1051730/rs1317286) on PPI, startle reactivity, and habituation of the ASR in two independent samples of 107 healthy British volunteers and 73 schizophrenia patients hailing from Germany. In both samples, PPI was influenced by both CHRNA3 polymorphisms (combined p-value=0.0027), which were strongly linked. Moreover, CHRNA3 genotype was associated with chronicity, treatment, and negative symptoms in the schizophrenia sample. These results suggest that sensorimotor gating is influenced by variations of the CHRNA3 gene, which might also have an impact on the course and severity of schizophrenia.

Evidence for a role of progesterone in menstrual cycle-related variability in prepulse inhibition in healthy young women.

Prepulse inhibition (PPI) of the startle response is sensitive to sex, with healthy young women showing less PPI compared with age-matched men, and varies according to the menstrual cycle phase in women. Relatively less is known regarding sex and hormonal influences in prepulse facilitation (PPF). Menstrual phase-related variability in PPI is suggested to be mediated by fluctuating estrogen level, based on the observations of more PPI in women during the follicular, relative to the luteal, phase. No study has directly assessed the relationship between fluctuating hormones and PPI or PPF levels over the human ovarian cycle. To examine the roles of circulating ovarian hormones in PPI and PPF, 16 non-smoking regularly menstruating healthy women were tested during both the follicular and luteal phases on PPI and PPF and provided saliva samples for measurement of 17beta-estradiol (estrogen), progesterone and testosterone. The results showed higher levels of 17beta-estradiol and progesterone during the luteal, relative to the follicular, phase; and more PPI during the follicular phase and more PPF during the luteal phase with comparable startle amplitude and habituation during the two phases. A larger increase in progesterone was associated with a smaller decrease in PPI from the follicular to the luteal phase. No significant associations were found between changes in PPI/PPF and estrogen levels. The findings confirm lower PPI during the luteal, compared with the follicular, phase and suggest a role for progesterone, more specifically an antipsychotic-like PPI-restoration action of progesterone, during the luteal phase in PPI of young women.

Effects of acute nicotine on brain function in healthy smokers and non-smokers: estimation of inter-individual response heterogeneity.

The present study used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms of nicotine effects on antisaccades (an oculomotor measure of the conflict between a reflexive response and a spatially complex volitional response) and prosaccades (involving reflexive overt attentional shifts). Given the known inter-individual variability in drug response we aimed to identify oculomotor variables and brain areas in which significant inter-individual heterogeneity in response to nicotine is observed. To do so we calculated within-session intraclass correlation (ICC) coefficients over measurements obtained before and after nicotine/placebo administration and reasoned that a significant reduction in ICC with nicotine compared to placebo would reflect the operation of significant inter-individual response heterogeneity. Thirteen light-to-moderate smokers and 11 non-smokers completed fMRI during antisaccades before and after subcutaneous injection of 12 microg/kg nicotine or saline placebo in a double-blind, randomised, cross-over design. All participants were healthy, right-handed males. Nicotine and placebo were given on separate occasions approximately 1 week apart with time of injection kept constant. Nicotine significantly reduced antisaccade latencies in both groups. At the level of brain function, during antisaccades the blood oxygen level dependent (BOLD) response in the left frontal eye field was non-significantly reduced by nicotine while it significantly increased following placebo in non-smokers, but there was no discernible effect in smokers. During prosaccades, it was found that deactivation areas (posterior cingulate gyrus and precuneus; right superior temporal gyrus) showed enhanced deactivations following nicotine administration in both groups. ICC analysis identified significant inter-individual response heterogeneity in antisaccade reflexive errors in smokers, and in a number of brain regions, particularly in non-smokers. These findings suggest that nicotine has beneficial effects at the cognitive level and leads to reductions in task-related activations and further decreases of BOLD in deactivation areas. The comparison of within-session ICCs across drug conditions suggests that the effects of nicotine are subject to inter-individual variability at behavioural and neural levels.

A comparison of prepulse inhibition in pre- and postmenopausal women and age-matched men.

Prepulse inhibition (PPI) of the startle response is sensitive to sex with women showing less PPI compared with age-matched men and varies according to the menstrual cycle in women. Relatively less is known about sex differences in prepulse facilitation (PPF). To examine further the roles of sex and circulating sex hormones, pre- (n=20) and postmenopausal women (n=20) were compared with men of similar ages (n=17, 18-40 years; n=18, 55-69 years). All participants were assessed on PPI and PPF, and provided saliva samples for measurement of 17beta-estradiol (estrogen) and testosterone. Premenopausal women showed less PPI compared with age-matched men, with no significant difference in PPF. Postmenopausal women did not differ in PPI but showed more PPF than age-matched men. There was less PPI and PPF in older, relative to young, men; pre- and postmenopausal women did not differ significantly. PPI showed no association with the levels of sex hormones. PPF showed small positive associations with both the levels of estrogen and testosterone, especially in young men. The present findings extend recent observations in mice showing less PPI in premenopausal, but not postmenopausal, female compared with male mice of similar ages (Ison and Allen, Behav Brain Res, 2007) to humans. There appear to be no substantial relationships between individual differences in endogenous levels of sex hormones and PPI; fluctuations within an individual may have a stronger role.

Cognitive effects of adjunctive 24-weeks Rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind investigation.

Cognitive impairment has the greatest impact on illness outcome in schizophrenia. The most significant challenge in schizophrenia therapeutics, thus, is to develop an efficacious treatment for cognitive impairments. Acetylcholinesterase inhibitors, such as Physostigmine and Rivastigmine, are considered effective treatments for cognitive decline in Alzheimer's Disease, where the loss of cholinergic neurons is thought to be responsible for various cognitive deficits. The current study investigated the cognitive effects of Rivastigmine given as an add-on therapy to antipsychotic-treated schizophrenia patients in a placebo-controlled double-blind design. The study initially involved 40 patients, of which 21 patients (11 assigned to Rivastigmine and 10 assigned to placebo) agreed to continued participation, remained on the study drug, and underwent assessment of executive functioning, verbal skills, verbal and spatial working memory, attention and psychomotor speed on three occasions: (i) at baseline, and then (ii) after 12 weeks and (iii) 24 weeks of treatment with placebo or Rivastigmine. The results failed to reveal significant improvement on any cognitive measure with Rivastigmine treatment, compared with the placebo treatment. Some cognitive variables showed significant practice effects in both the placebo and Rivastigmine groups. No effects were noted in symptoms or side effects ratings. The beneficial cognitive effects of Rivastigmine seen in an open-label preliminary study are not substantiated by this study. Future studies should investigate the effects of other procholinergic drugs, such as Galantamine, which also act on the nicotine receptors and may produce stronger cognitive effects in schizophrenia.

A behavioural and functional neuroimaging investigation into the effects of nicotine on sensorimotor gating in healthy subjects and persons with schizophrenia.

RATIONALE: Schizophrenia patients display an excessive rate of smoking compared to the general population. Nicotine increases acoustic prepulse inhibition (PPI) in animals as well as healthy humans, suggesting that smoking may provide a way of restoring deficient sensorimotor gating in schizophrenia. No previous study has examined the neural mechanisms of the effect of nicotine on PPI in humans. OBJECTIVES: To investigate whether nicotine enhances tactile PPI in healthy subjects and patients with schizophrenia employing a double-blind, placebo-controlled, cross-over design and, if so, what are the neural correlates of nicotine-induced modulation of PPI. MATERIALS AND METHODS: In experiment 1, 12 healthy smokers, 12 healthy non-smokers and nine smoking schizophrenia patients underwent testing for tactile PPI on two occasions, 14 days apart, once after receiving (subcutaneously) 12 microg/kg body weight of nicotine and once after receiving saline (placebo). In experiment 2, six healthy subjects and five schizophrenia patients of the original sample (all male smokers) underwent functional magnetic resonance imaging (fMRI) under the same drug conditions and the same tactile PPI paradigm as in experiment 1. RESULTS: Nicotine enhanced PPI in both groups. A comparison of patterns of brain activation on nicotine vs placebo conditions showed increased activation of limbic regions and striatum in both groups after nicotine administration. Subsequent correlational analyses demonstrated that the PPI-enhancing effect of nicotine was related to increased hippocampal activity in both groups. CONCLUSIONS: Nicotine enhances tactile PPI in both healthy and schizophrenia groups. Our preliminary fMRI findings reveal that this effect is modulated by increased limbic activity.

Neural correlates of adjunctive rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind fMRI study.

Facilitation of central cholinergic activity may form a potential treatment strategy for cognitive impairment in schizophrenia. In a randomized, placebo-controlled, double-blind, parallel-group design, we investigated the neural correlates of cognitive effects of rivastigmine, an acetylcholinesterase inhibitor, given as an add-on therapy to antipsychotic-treated schizophrenia patients. Thirty-six chronic schizophrenia patients with mild cognitive impairment took part. After 1 week on placebo (baseline), all patients entered a double-blind protocol; 18 were allocated to receive rivastigmine and 18 placebo for the next 12 weeks (final sample with usable imaging data: 11 patients on rivastigmine, 10 on placebo). All patients underwent functional magnetic resonance imaging during a parametric 'n-back' task, involving monitoring of dots in particular locations on a screen at a given delay from the original occurrence, twice: at baseline and 12 weeks post-rivastigmine/placebo treatment. Compared to placebo, rivastigmine produced only a small and non-significant improvement in task accuracy across all conditions with no change in response latency, and increased activity in the extrastriate visual cortex in areas associated with visual and spatial attention but not in any region within the working memory network. Our observations suggest that cholinergic enhancement with rivastigmine at doses known to be effective in Alzheimer's disease does not produce strong and clinically meaningful cognitive and neural changes in schizophrenia patients treated with atypical antipsychotics although the neural effects in terms of enhanced neuronal activity in regions associated with visual and spatial attention are consistent with those reported previously with cholinergic enhancement in healthy subjects.

Nicotine use in schizophrenia: the self medication hypotheses.

The behavioural and cognitive effects of nicotine in schizophrenia have received much interest in recent years. The rate of smoking in patients with schizophrenia is estimated to be two- to four-fold the rate seen in the general population. Furthermore such patients favour stronger cigarettes and may also extract more nicotine from their cigarettes than other smokers. The question has been raised whether the widespread smoking behaviour seen in this patient group is in fact a manifestation of a common underlying physiology, and that these patients smoke in an attempt to self-medicate. We present an overview of the explanations for elevated rates of smoking in schizophrenia, with particular emphasis on the theories relating this behaviour to sensory gating and cognitive deficits in this disorder that have been viewed as major support for the self-medication hypotheses.

Influence of cigarette smoking on prepulse inhibition of the acoustic startle response in schizophrenia.

The prevalence of tobacco smoking is known to be higher in patients with schizophrenia than other psychiatric disorders and general population. These patients also show reduced prepulse inhibition (PPI) of the startle response. PPI refers to a reduction in response to a strong startling stimulus if preceded shortly by a stimulus of sub-threshold intensity. PPI is thought of as an objective index of sensorimotor gating. Nicotine administered subcutaneously or via cigarette smoking enhances PPI in healthy human beings. It also enhances PPI at low, but not high, doses in the rat. We examined the influence of smoking on PPI of the acoustic startle response in 46 male patients with chronic schizophrenia. In a naturalistic design, patients (n = 9) who smoked a cigarette less than 10 min prior to being tested on PPI were compared with other smoking (n = 23) and non-smoking patients (n = 14). We found that the group of patients who smoked a cigarette prior to being tested had significantly greater PPI than other two groups. These observations suggest a PPI-enhancing effect of cigarette smoking on PPI in patents with schizophrenia. Higher prevalence of cigarette smoking in schizophrenic patients may reflect an attempt to improve sensorimotor gating deficits. Copyright 2001 John Wiley & Sons, Ltd.