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Clinical and hormonal response to general anaesthesia in patients affected by different degrees of mental retardation.

BACKGROUND: Poor or no clinical signs of psychological distress are usually observed in patients affected by severe or profound mental retardation (MR). The aim of this study was to use clinical and hormonal parameters in order to compare the amount of stress in patients affected by different degrees of MR undergoing general anaesthesia for dental care. METHODS: Nine patients affected by mild or moderate MR (group A: intellective quotient > 35) and 12 affected by severe or profound MR (group B: intellective quotient < 36), undergoing general anaesthesia for dental care, were studied. The reaction to venipuncture before anaesthesia induction and the recovery from anaesthesia were assessed by clinical scores. Cardiac rate and arterial pressure were recorded before and after venipuncture and after removing the endotracheal tube. Cortisol and prolactin, two hormones affected by stress, were determined in plasma the day prior to surgery (1), after anaesthesia induction (2), and after removing the endotracheal tube (3). RESULTS: During venipuncture, group B was significantly less reactive than group A (p < 0.05) and showed no arterial pressure increase while group A presented a significant increase of systolic pressure; conversely, the groups shared the same hormonal pattern at time 2 (cortisol did not change, prolactin increased significantly). Postoperatively A and B groups did not differ regarding cardiac rate and arterial pressure, while a wider range of postoperative scores was observed in group A in which a further prolactin increase was registered at time 3. CONCLUSIONS: Clinical evaluation can underestimate the stress to which patients affected by severe or profound MR are subjected during anaesthesia induction.

Adolescent↗

Functional and biochemical analysis of a sodium channel beta1 subunit mutation responsible for generalized epilepsy with febrile seizures plus type 1.

Generalized epilepsy with febrile seizures plus type 1 is an inherited human epileptic syndrome, associated with a cysteine-to-tryptophan (C121W) mutation in the extracellular immunoglobin domain of the auxiliary beta1 subunit of the voltage-gated sodium channel. The mutation disrupts beta1 function, but how this leads to epilepsy is not understood. In this study, we make several observations that may be relevant for understanding why this beta1 mutation results in seizures. First, using electrophysiological recordings from mammalian cell lines, coexpressing sodium channel alpha subunits and either wild-type beta1 or C121Wbeta1, we show that loss of beta1 functional modulation, caused by the C121W mutation, leads to increased sodium channel availability at hyperpolarized membrane potentials and reduced sodium channel rundown during high-frequency channel activity, compared with channels coexpressed with wild-type beta1. In contrast, neither wild-type beta1 nor C121Wbeta1 significantly affected sodium current time course or the voltage dependence of channel activation. We also show, using a Drosophila S2 cell adhesion assay, that the C121W mutation disrupts beta1-beta1 homophilic cell adhesion, suggesting that the mutation may alter the ability of beta1 to mediate protein-protein interactions critical for sodium channel localization. Finally, we demonstrate that neither functional modulation nor cell adhesion mediated by wild-type beta1 is occluded by coexpression of C121Wbeta1, arguing against the idea that the mutant beta1 acts as a dominant-negative subunit. Together, these data suggest that C121Wbeta1 causes subtle effects on channel function and subcellular distribution that bias neurons toward hyperexcitabity and epileptogenesis.

Animals↗

Generalized immune response to Pneumocystis carinii infection in the lung.

We studied inflammatory cells retrieved by bronchoalveolar lavage (BAL) from immunocompromised patients with or without Pneumocystis carinii pneumonia (PCP). Twenty-four patients with PCP, and 20 patients without PCP underwent lavages of both an uninvolved lobe and the lobe involved in pulmonary infection. Patients without P. carinii, had a significant increase (p less than 0.02) in the percentages of neutrophils (22 +/- 7.1%, mean +/- SEM) and lymphocytes (16 +/- 3.8%) in the involved lobe compared to those in the uninvolved area (neutrophils: 9 +/- 4.8%; lymphocytes: 10 +/- 2.4%). Patients with PCP, had no differences between the % neutrophils or % lymphocytes in the involved vs. uninvolved lobes. Patients with PCP had more (p less than 0.01) P. carinii in the upper lobe (23 +/- 4.6 P. carinii clusters/500 cells) than the middle lobe (11 +/- 3.6). In PCP, despite regional infections, there was a diffuse inflammatory response.

Bronchoalveolar Lavage Fluid↗