Surgical treatment of acute respiratory failure caused by mediastinal goiter. Clinical experience and results

In the regions where goitre is endemic, onset of the disease with acute respiratory insufficiency caused by thyroid compression is an uncommon situation requiring a rapid diagnosis and urgent surgical treatment. From January 1997 to December 2000 we observed 81 patients with thyroid pathologies, (69 males and 12 females; mean age 64 years). We found colloid-cystic goitre in 39 cases, adenomatous goitre in 26, carcinoma in 12, Hürthle's cell tumours in 3 and inflammatory disease in 1. All patients underwent thyroidectomy. Nine patients (11%) presented acute respiratory insufficiency caused by thyroid compression, with various associated phonesis disorders; in these cases we performed emergency surgery with postoperative maintenance of tracheal intubation or tracheotomy or the possible positioning of a self-expanding tracheal stent. In these 9 patients there were 4 deaths (44%), 3 in the immediate postoperative period and one after 10 months. We also observed one hydropneumothorax. Functional recovery was achieved in the remaining 5 patients. The treatment of this clinical picture requires urgent tracheal intubation, before the use of diagnostic tools, and it is important to maintain it after the surgical procedure for as long as is necessary for the tracheal wall to be reconstituted. In the severest cases a temporary tracheotomy is needed or the positioning of a tracheal stent, which offers a valid and effective alternative.     

Psychiatric pharmacogenetics: personalizing psychostimulant therapy in attention-deficit/hyperactivity disorder

There is a substantial amount of variation in response and adverse drug reactions to psychostimulant therapy in attention-deficit/hyperactivity disorder (ADHD). Psychiatric pharmacogenetics is a rapidly developing field, which can be applied to identify genetic predictors of this variability in outcome to psychostimulant medications. This article will briefly review ADHD and its pharmacotherapy. This will be followed by an overview of the pharmacokinetics and pharmacodynamics of methylphenidate, the most commonly used psychostimulant in the US. Then the field of psychiatric pharmacogenetics will be introduced and its methodology will be described. This will be followed by a discussion about how pharmacogenetics can be applied to children afflicted with ADHD. The future of psychiatric pharmacogenetics will then be presented with an emphasis being placed on developing prospects that will ensure the continued advancement of this field.     

Hereditary nephritis with macrothrombocytopenia: phenotypic variety and the genotypic defect

A number of patients present to nephrologists with end-stage renal failure of unknown cause and many have small kidneys, making renal biopsy inadvisable. A small number may have clues to the diagnosis of hereditary nephritis, as in the patient we present here. The propositus was a 22-year-old man, who was admitted to our nephrology ward because of recently discovered renal insufficiency. Ultrasound examination revealed bilateral small kidneys. He was severely hypertensive; audiometry and ophthalmic examinations were normal. Thrombocytopenia with giant platelets was observed in peripheral blood smears. Basophilic cytoplasmic inclusions (D?hle-like bodies) were present in neutrophil and basophilic granulocytes. A family history of nephropathy associated with macrothrombocytopenia was obtained. Epstein syndrome was diagnosed, a rare autosomal dominant disorder. He started hemodialysis and subsequently received a living donor kidney transplant (from his mother). Molecular genetics has considerably clarified the field of hereditary nephritis associated with macrothrombocytopenia by demonstrating that these syndromes involve a similar molecular defect. It was first shown that these syndromes were linked to the same locus on chromosome 22q. Then the gene involved--encoding non-muscle myosin heavy chain 9 (MYH9)--was identified. This entity ("MYH9 disease") must be clearly differentiated from Alport syndrome (type IV collagen disease). In conclusion, this case serves to remind us: 1) that in patients presenting late to nephrologists with bilateral small kidneys, the diagnosis can still be made in some instances on the basis of other clinical signs known to be associated with recognized inherited syndromes; 2) that there are various types of inherited thrombocytopenia associated with nephritis; screening for nephritis is mandatory in all of them.     

A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia

Tardive dyskinesia (TD) is a common and potentially irreversible side effect associated with long-term treatment with typical antipsychotics. Approximately, 80% or more of patients with schizophrenia are smokers. Smoking is a potent inducer of the CYP1A2 enzyme, and is known to cause a significant decrease in plasma concentrations of some antipsychotics. Therefore, person-to-person differences in the extent of CYP1A2 induction by smoking may contribute to risk for the development of TD. Recently, a (C-->A) genetic polymorphism in the first intron of the CYP1A2 gene was found to be associated with variation in CYP1A2 inducibility in healthy volunteer smokers. The aim of this study was to test the clinical importance of the (C-->A) polymorphism in CYP1A2 in relation to TD severity. A total of 85 patients with schizophrenia were assessed for TD severity using the Abnormal Involuntary Movement Scale (AIMS), and were subsequently genotyped for the (C-->A) polymorphism in CYP1A2. The mean AIMS score in patients with the (C/C) genotype (associated with reduced CYP1A2 inducibility) was 2.7- and 3.4-fold greater than in those with the (A/C) or (A/A) genotype, respectively (F[2,82] = 7.4, P = 0.0007). Further, a subanalysis in the 44 known smokers in our sample, revealed a more pronounced effect. The means AIMS score in smokers was 5.4- and 4. 7-fold greater in (C/C) homozygotes when compared to heterozygotes and (A/A) homozygotes, respectively (F[2,41] = 3.7, P = 0.008). These data suggest that the (C-->A) genetic polymorphism in the CYP1A2 gene may serve as a genetic risk factor for the development of TD in patients with schizophrenia. Further studies in independent samples are warranted to evaluate the applicability of our findings to the general patient population receiving antipsychotic medications.     

Evidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHD)

A recent study demonstrated that treatment of hyperactive mice with psychostimulants and serotonergic agents produced a calming effect that was dependent on serotonergic neurotransmission and was not associated with any changes in extracellular dopamine levels. The complex interaction between the serotonergic and dopaminergic neurotransmitter systems suggests that a balance between the two systems may be necessary for mediating hyperactive behaviour. Defects in serotonin system genes, therefore, may disrupt normal brain serotonin function causing an imbalance between these neurotransmitter systems leading to the development of attention deficit hyperactivity disorder (ADHD). Using the transmission disequilibrium test (TDT), the current study assesses for linkage disequilibrium between polymorphisms in the serotonin HTR2A receptor gene and ADHD. One hundred and fifteen families with a total of 143 children diagnosed with ADHD (DSM-IV) were genotyped for the His452 Tyr and the T102C polymorphisms in the serotonin HTR2A receptor gene. TDT analysis revealed a preferential transmission of the 452Tyr allele to the affected offspring (P = 0.03), suggesting linkage disequilibrium of this polymorphism with ADHD. This may open a new door in ADHD molecular genetics research, expanding the existing view of a catecholaminergic hypothesis to include a serotonergic hypothesis and should help elucidate the complex interplay among the neurotransmitter systems in the etiology of ADHD.     

Clinically relevant cognitive impairment after cardiac surgery: a 6-month follow-up study

BACKGROUND AND PURPOSE: The majority of studies on neuropsychological complications after cardiac surgery used the raw variation of selective tests scores to define the occurrence of cognitive decline. We prospectively estimated the frequency of cognitive impairment after cardiac surgery, with a particular emphasis on persistent and clinically relevant cognitive decline. Possible baseline and operative predictors were also evaluated. METHODS: An extensive neuropsychological battery was administered to 110 patients (mean age 64.1+/-9.4 years; 70.9% males) undergoing cardiac surgery before and 6 months after the operation. After evaluating the variations in the cognitive performances, two independent neuropsychologists ranked the patients as unchanged-improved, mildly-moderately deteriorated, or severely deteriorated, using a global and functionally oriented judgement. The degree of the impairment was determined in relation to its impact on everyday life activities. RESULTS: Ten patients (9.1%) were ranked as severely deteriorated, 22 (20%) as mildly-moderately deteriorated, and 78 (70.9%) as unchanged-improved. Cognitively impaired patients were older (p=0.031), more often females (p=0.005), with a low education level (p=0.013). At multivariate analysis, female gender (odds ratio (OR) 6.14, 95% confidence interval (95% CI) 2.16-17.50), baseline use of beta-blockers (OR 4.55, 95% CI 1.30-15.92), and PaO2 at arrival in intensive care unit (OR for 1 mm Hg increment 1.012, 95% CI 1.004-1.020) were significant predictors of cognitive impairment of any degree. Positive predictors of severe cognitive impairment were history of hypertension (OR 5.33, 95% CI 1.03-27.64) and PaO2 at arrival intensive care unit (OR for 1 mm Hg increment 1.020, 95% CI 1.006-1.035), while education was protective (OR per year of increment 0.53, 95% CI 0.31-0.90). CONCLUSIONS: A considerable proportion of cardiac surgery patients may undergo clinically relevant cognitive impairment. The knowledge of variables influencing cognitive outcome is essential for the adoption of preventive measures.