An overview of systematic reviews on cannabis and psychosis: Discussing apparently conflicting results

Issues . Cross‐sectional surveys have revealed that cannabis is the most widely used illicit substance in Western countries. Cannabis intoxication can lead to acute, transient psychotic symptoms and the short‐term exacerbation of pre‐existing psychotic symptoms. However, controversy exists about whether cannabis can actually cause long‐term psychosis. Approach . We summarised the findings of systematic reviews on the association between cannabis use and psychosis, searching MEDLINE, EMBASE and CINAHL up to August 2007. We assessed the methodological quality, selected the better quality reviews and analysed reasons for discordant results. Key Findings . We included five systematic reviews. Four of the reviews performed a meta‐analysis and showed a consistent association between cannabis use and psychosis; the fifth review considered psychological problems more broadly, did not perform a meta‐analysis and reported an inconsistent association. The reasons for discordance were: different outcomes (psychosis vs. psychological problems), different inclusion criteria for primary studies and different methods for summarising the results. Implications . This overview shows a consistent association between cannabis use and psychotic symptoms, though it is not possible to draw firm conclusions about a causal relationship. Reverse causality and residual confounding cannot be excluded. An interaction with other environmental and genetic factors is difficult to ascertain. Conclusion . We conclude that there is insufficient knowledge to determine the level of risk associated with cannabis use in relation to psychotic symptoms and that more information is needed on both the risks of cannabis use and the benefits of preventive interventions to support evidence‐based approaches in this area.[Minozzi S, Davoli M, Bargagli AM, Amato L, Vecchi S, Perucci CA. An overview of systematic reviews on cannabis and psychosis: Discussing apparently conflicting results. Drug Alcohol Rev 2009]     

Influence of class I and II HLA alleles on inhibitor development in severe haemophilia A patients from the South of Brazil

Summary. Congenital haemophilia A is a chromosome‐linked recessive disorder caused by the deficiency or reduction of factor VIII (FVIII) pro‐coagulant activity. During treatment, some patients develop alloantibodies (FVIII inhibitors) that neutralize the action of exogenously administered FVIII. Currently, the presence of these inhibitors is the most serious adverse event found in replacement therapy. Some studies have suggested that genetic factors influence the development of the FVIII coagulation inhibitors. To identify the class I and II alleles that may be influencing the formation of inhibitors in severe haemophilic patients. Genotyping of the class I (HLA‐A, ‐B and ‐C) and class II (HLA‐DRB1, ‐DQA1 and ‐DQB1) alleles of 122 patients with severe haemophilia A, including 36 who had developed antibodies to factor VIII, was performed. After the comparison of the group without inhibitors and the group with inhibitors, HLA‐C*16 [Odds ratio (OR) = 7.73; P = 0.0092] and HLA‐DRB1*14 (OR = 4.52; P = 0.0174) were found to be positively associated with the formation of the inhibitors. These results confirm that HLA alleles are involved in inhibitor production and could be used as a tool for recognition of groups at high risk of possible inhibitor development in Southern Brazilian haemophilic patients.     

Current management of ovarian carcinosarcoma

Ovarian carcinosarcomas (OCS), also known as malignant mixed müllerian tumors, are uncommon malignancies that carry a poor prognosis. The presentation of OCS is usually indistinguishable from that of epithelial ovarian cancer. Due to its low frequency, prospective trials have been difficult to perform, but there is evidence that OCS are sensitive to platinum-based chemotherapy. Recent studies have shown encouraging results with platinum-ifosfamide and platinum-taxane schedules, which are usually considered the treatment of choice. However, poor performance status at presentation is also a common problem, so that many patients may be unsuitable for combination chemotherapy but may still benefit from single-agent platinum or ifosfamide or, occasionally, from nonplatinum schedules such as ifosfamide plus paclitaxel. Aggressive cytoreductive surgery appears to have a positive impact on outcome and should probably be offered to most patients. However, this procedure has been associated with higher rates of complication in OCS and should only be attempted by experienced (gynecological) surgeons in centers with expertise in the management of gynecological malignancies.     

Manifestation of Left Atrial Events and Interatrial Frequency Gradients in the Surface Electrocardiogram During Atrial Fibrillation: Contributions from Posterior Leads

Background: In most patients, atrial fibrillation (AF) is initiated and maintained by pulmonary vein foci, but the relationship between left atrial (LA) events and the surface electrocardiogram (ECG) is largely unknown. We investigated whether LA events are reflected in the surface ECG and whether additional information can be obtained from recording posterior leads in patients with AF.
Methods and Results: In 10 patients undergoing radiofrequency ablation of AF, we identified 103 5-second segments with a significant frequency gradient between right (RA) and left (LA) intraatrial electrograms, or with frequency changes from segment to segment in the same patient. QRS-T cancellation methods were used to isolate atrial activity in the surface ECG and peak frequencies were computed. Peak frequencies of different posterior leads were very similar (6.0 ± 1.3 Hz for V10, 6.0 ± 0.9 Hz for V9, 5.9 ± 1.4 Hz for V8, 6.0 ± 1.3 Hz for V7). We found a strong correlation between V1 and RA and between V9 and LA, 0.89 and 0.88, respectively, while the lowest correlation was found between lead V1 and LA, 0.62, P < 0.0001. Magnitude-squared coherence values were highest between V1 and RA and between V9 and LA.
Conclusion: We have demonstrated that, by recording additional surface ECG leads from posterior locations, RA and LA electrical events and interatrial frequency gradients can be monitored noninvasively.     

Long-Term Follow-Up and Outcome of a Large Cohort of Patients with Common Variable Immunodeficiency

Common Variable Immunodeficiency belongs to the group of rare diseases encompassing antibody deficiency syndromes of highly variable clinical presentation and outcome. The multicenter prospective study on a cohort of 224 patients with Common Variable Immunodeficiency provides an updated view of the spectrum of illnesses which occurred at the clinical onset and over a long period of follow-up (mean time: 11 years) and information on the effects of long-term immunoglobulin treatment. The mean age at the time of diagnosis was 26.6 years. Seventy-five patients were younger than 14 years of age. The mean age at the onset of symptoms was 16.9 years. This implicates with a mean diagnostic delay of 8.9 years. Respiratory tract infections were the most prominent clinical problem observed at diagnosis and during the follow-up. Intravenous immunoglobulin administration induced a significant reduction in the incidence of acute infections, mainly acute pneumonia and acute otitis. However, a progressive increase in the prevalence of patients with chronic diseases, mainly sinusitis and lung disease, was observed in all age groups, including the pediatric population. The morbidity of Common Variable Immunodeficiency due to all associated clinical conditions increased over time despite an adequate replacement with intravenous immunoglobulins. Our data stressed the need to develop international guidelines for the prevention and therapy of chronic lung disease, chronic sinusitis, chronic diarrhoea, and chronic granulomatosis in patients with humoral immunodeficiencies. WITHIN THE IPINET (Italian Primary Immunodeficiency Network) IPINET: De Mattia D, Martire B, Bari, Cossu F, Cagliari, Schirilló G, Catania, Castagnola E, Genova, Pietrogrande MC, Delle Piane RM, Milano, Putti C, Padova, Trizzino A, Amato GM, Palermo, Bertolini P, Parma, Zecca M, Pavia, Consolini R, Pisa, Moschese V, Rossi P, Cancrini C, Roma, Cazzola GA, Verona     

Interactions between suxamethonium and non-depolarizing neuromuscular blocking drugs

In anaesthetized cats, we have confirmed that previously injectedsuxamethonium potentiates non-depolarizing neuromuscular blockingdrugs whereas, when injected during the block, suxamethoniumantagonizes the paralysis. We have attempted to explain theseinteractions by studying the effects of suxamethonium on extracellularlyrecorded nerve ending waveforms that correspond to the ioniccurrents in the mouse triangularis sterni isolated nerve-musclepreparation. The preparations were paralysed with µ-conotoxin(obtained from the cone snail), which is believed to act byselectively blocking sodium channels in muscle, and which thereforeshould not interfere with currents at the nerve endings. Suxamethonium,in concentrations of 0.5-300 µmol litre^–1, produceda concentration-dependent increase in the amplitude of the waveformcorresponding to the inward calcium current evoked by a nerveimpulse. This effect did not occur in the presence of tubocurarine,suggesting that suxamethonium, which is a nicotinic agonist,may have been acting on a nicotinic receptor on the nerve endingsthat is coupled to the voltage-operated calcium channels. Theinward calcium current is believed to be responsible for neurotransmitter(acetylcholine) release. It is concluded, therefore, that itsenhancement by suxamethonium contributes to the ability of thisdrug to reverse non-depolarizing block. Suxamethonium also exertedcomplex effects on the waveform corresponding to the outwardflowing calcium-activating potassium current at the nerve endings,but no effect was observed in this isolated nerve-muscle preparationthat could obviously explain the ability of suxamethonium topotentiate subsequently injected non-depolarizing blocking drugs.     

Hand movements at 3 months predict later hemiplegia in term infants with neonatal cerebral infarction

Aim The aim of this study was to explore the predictive value of quantitative assessment of hand movements in 3‐month‐old infants after neonatal stroke. Method Thirteen infants born at term (five females, eight males; mean gestational age 39.4wks, SD 1.19, range 37–41wks; mean birthweight 3240g, SD 203, range 2900–3570g) with neonatal arterial ischaemic cerebral infarction, and 13 healthy infants (mean gestational age 39.1wks, range 37–41wks, SD 1.26; mean birthweight 3190g, SD 259, range 2680–3490g) were enrolled in the study. The absolute frequency and the asymmetry of global hand opening and closing, wrist segmental movements, and independent digit movements were assessed from videotapes recorded at around 12 weeks. Neurological outcome was assessed when the infants were at least 18 months old using Touwen’s neurological examination. Results Five of the 13 infants with neonatal stroke had normal neurological development, and eight had hemiplegia. Asymmetry of wrist segmental movements and the absolute frequency of independent digit movements were significantly different between infants with and without hemiplegia (p=0.006 and p=0.008, respectively). No differences were found in global hand movements. Interpretation We propose that the observed abnormalities of hand movements are the result of two different mechanisms: direct disruption of the corticospinal projection to the spinal cord, and altered modulation of the central pattern generators of general movements.