Motor and somatosensory evoked potentials in hereditary spastic paraplegia.

Motor evoked potentials (MEPs) from the arms and legs to transcranial stimulation of the motor cortex and somatosensory evoked potentials (SSEPs) from stimulation of the nerves of the arms and legs, were recorded in 11 patients with hereditary spastic paraplegia. Electrophysiological abnormalities were found to be distributed differently among the systems examined; the longer the pathway, the higher the incidence and severity of impairment. MEPs from the leg were either absent or clearly reduced or prolonged in all patients. Eight patients showed abnormal cortical SSEPs on stimulation of the leg (absent or reduced responses in four, slowed central conduction velocity in seven), but only two of these patients had abnormal MEPs from the arm (absent responses). Cortical SSEPs on stimulation of the median nerve were reduced in two patients. Mean values of amplitude and central conduction velocity for MEPs and SSEPs from the leg were significantly different between patients and controls. Such differences were not found for either MEPs or SSEPs from the arm. This distribution of abnormalities, which suggests a differential involvement of the spinal pathways, parallels the reported pathological pattern in which degeneration of axons is more common and severe in the motor and sensory fibres supplying the leg.     

Effect of prone positioning on the survival of patients with acute respiratory failure

BACKGROUND: Although placing patients with acute respiratory failure in a prone (face down) position improves their oxygenation 60 to 70 percent of the time, the effect on survival is not known. METHODS: In a multicenter, randomized trial, we compared conventional treatment (in the supine position) of patients with acute lung injury or the acute respiratory distress syndrome with a predefined strategy of placing patients in a prone position for six or more hours daily for 10 days. We enrolled 304 patients, 152 in each group. RESULTS: The mortality rate was 23.0 percent during the 10-day study period, 49.3 percent at the time of discharge from the intensive care unit, and 60.5 percent at 6 months. The relative risk of death in the prone group as compared with the supine group was 0.84 at the end of the study period (95 percent confidence interval, 0.56 to 1.27), 1.05 at the time of discharge from the intensive care unit (95 percent confidence interval, 0.84 to 1.32), and 1.06 at six months (95 percent confidence interval, 0.88 to 1.28). During the study period the mean (+/-SD) increase in the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen, measured each morning while patients were supine, was greater in the prone than the supine group (63.0+/-66.8 vs. 44.6+/-68.2, P=0.02). The incidence of complications related to positioning (such as pressure sores and accidental extubation) was similar in the two groups. CONCLUSIONS: Although placing patients with acute respiratory failure in a prone position improves their oxygenation, it does not improve survival.     

K-ras gene mutational analysis supports a monoclonal origin of biphasic pleomorphic carcinoma of the lung.

We investigated 27 pleomorphic carcinomas of the lung for exon 1 K-ras gene mutations using polymerase chain reaction-single-strand conformation polymophism analysis and direct sequencing. All pleomorphic carcinomas were biphasic, that is, composed of an adeno-, squamous- or large-cell-carcinomatous component associated with a spindle- and/or giant-cell component. Of 27 cases, six (22%) showed K-ras codon 12 mutations, which is a figure higher than that previously reported on in pure sarcoma-like pleomorphic carcinomas. Five tumors displayed the same mutation in both the epithelial and the sarcomatoid components, whereas in one tumor the mutation was restricted to the epithelial component. All mutations occurred in smokers, and were transversions, including GGT (glycine) to TGT (cysteine) change in two cases, to GCT (alanine) in two and to GTT (valine) in two. No significant relationships were found between the occurrence and type of mutations and patients' survival or any other clinicopathological variable, suggesting that K-ras mutations are early events in the development of these tumors. Our results indicate that most, though not all, biphasic pleomorphic carcinomas of the lung are monoclonal in origin, and that cigarette smoking may have a causative role in the development of K-ras alterations in these tumors, as all mutations are transversions.     

The paraventricular nucleus of hypothalamus mediates the pressor response to noradrenergic stimulation of the medial prefrontal cortex in unanesthetized rats

The medial prefrontal cortex (MPFC) is a structure that is also involved in cardiovascular modulation. The injection of norepinephrine (NE) into the prelimbic (PL) area of the MPFC of unanesthetized rats evokes a pressor response which is mediated by acute vasopressin release. Vasopressin is synthesized by magnocellular cells of the paraventricular (PVN) and supraoptic nucleus (SON) of the hypothalamus. In the present study, we endeavored to determine which vasopressin-synthesizing hypothalamic nucleus is involved in the pressor pathway activated after NE injection into the PL area of the MPFC. We report here that lidocaine microinjection into the SON did not change the pressor response evoked by NE injection into the PL. However, the response to NE was blocked by prior injection of lidocaine or CoCl₂ into the PVN, indicating that this area is responsible for the mediation of this pressor response. A neuroanatomic experiment in which the neuronal tracer biotinylated dextran amine (BDA) was microinjected into the MPFC showed a lack of axons or neuronal cell bodies in the PVN, indicating that there are no direct connections between the PL area of the MPFC and the PVN. The results suggest that the PVN is involved in the mediation of the pressor response to NE in the PL area and that this pathway must relay in other brain structures before reaching the PVN.     

Compartmental Analysis of Breathing in the Supine and Prone Positions by Optoelectronic Plethysmography

Optoelectronic plethysmography (OEP) has been shown to be a reliable method for the analysis of chest wall kinematics partitioned into pulmonary rib cage, abdominal rib cage, abdomen, and right and left side in the seated and erect positions. In this paper, we extended the applicability of this method to the supine and prone positions, typically adopted in critically ill patients. For this purpose we have first developed proper geometrical and mathematical models of the chest wall which are able to provide consistent and reliable estimations of total and compartmental volume variations in these positions suitable for clinical settings. Then we compared chest wall (CW) volume changes computed from OEP( V _CW) with lung volume changes measured with a water seal spirometer (SP) ( V _SP)in 10 normal subjects during quiet (QB) and deep (DB) breathing on rigid and soft supports. We found that on a rigid support the average differences between V _SP and V _CW were –4.2% ± 6.2%, –3.0% ± 6.1%, –1.7% ±7.0%, and –4.5% ± 9.8%, respectively, during supine/QB, supine/DB, prone/QB, and prone/DB. On the soft surface we obtained –0.1% ± 6.0%, –1.8% ± 7.8%, 18.0% ± 11.7%, and 10.2% ± 9.6%, respectively. On rigid support and QB, the abdominal compartment contributed most of the V _CW in the supine (63.1% ± 11.4%) and prone (53.5% ± 13.1%) positions. V _CW was equally distributed between right and left sides. In the prone position we found a different chest wall volume distribution between pulmonary and abdominal rib cage (22.1% ± 8.6% and 24.4% ± 6.8, respectively) compared with the supine position (23.3% ± 9.3% and 13.6% ± 3.0%). © 2001 Biomedical Engineering Society. PAC01: 8763Lk, 8719Uv     

The inverse association of salmonellosis in infancy with allergic rhinoconjunctivitis and asthma at school-age: a longitudinal study

BACKGROUND: Respiratory allergies are inversely related to early acquisition of food-borne and fecal-oral infections, consumption of unpasteurized milk, early exposure to stables and high endotoxin concentrations in a farming environment. We tested therefore if infection by Salmonella in early life can protect from development of respiratory allergies later in life. METHODS: During 2003, we studied two groups of Sardinian children (age 6-18 years) who had been hospitalized before 4 years of age (during 1989-2001) with non-typhoid salmonellosis (n = 148) or acute enteritis of nonbacterial etiology (NB-enteritis) (n = 167). Allergic rhinoconjunctivitis (AR) and asthma were evaluated by telephonic interview with a ISAAC questionnaire; participants reporting AR and/or asthma were further examined through a complete diagnostic work-up to objectively confirm or exclude current disease. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the role of different types of enteritis on the risk of developing allergic rhinoconjunctivitis or asthma over time. RESULTS: Children who had been hospitalized with salmonellosis had a lower prevalence of allergic rhinoconjunctivitis (eight of 148, 5.4%vs 23 of 167, 13.8%; P = 0.019) or asthma (five of 148, 3.4% vs 21 of 167, 12.6%; P = 0.006) than those who had been hospitalized with NB-enteritis. The proportional hazard of salmonellosis for asthma was 0.23 (95% CI: 0.08-0.67; P < 0.01) and for allergic rhinoconjunctivitis was 0.40 (95% CI: 0.17-0.95; P = 0.04), after adjusting for confounders. DISCUSSION: The strength of the observed associations suggests that Salmonella may contribute to shape the natural history of respiratory allergies. However, further studies are needed to test in other settings the association observed in Sardinian children. We speculate that clinical or subclinical infection by Salmonella may contribute to the atopy protective influence of a traditional farming environment or of areas endemic for food-borne and fecal-oral infections. Food hygiene and prevention of salmonellosis must remain however a public health priority.     

Pressor effects of the injection of noradrenaline into different cerebroventricular spaces in unanesthetized rats

Injection of noradrenaline (NA) into the lateral cerebral ventricle (i.c.v.) was reported to cause blood pressure increase in unanesthetized rats, blocked by i.v. injection of vasopressin antagonists. We report similar responses to NA injection into the III or IV ventricles, suggesting multiple sites of action for i.c.v. NA. These responses were blocked by i.v. pretreatment with vasopressin antagonist, suggesting a common mediation by vasopressin release into circulation. Selected ventricular spaces were occluded with Nivea^® cream plugs to identify ventricular areas responding to i.c.v. NA. III ventricle or aqueduct occlusions markedly reduced pressor responses to i.c.v. NA. Microinjection of NA into the periaqueductal gray matter (PAG) caused pressor responses that were similar to those of i.c.v. NA, reinforcing the idea of a site of action in the aqueduct. IV ventricle occlusion only partially blocked the response to i.c.v. NA. The results suggest at least two sites of action for i.c.v. NA in unanesthetized rats. A primary site located in the PAG and another on the IV ventricle wall.     

Positive end expiratory pressure in anesthesia

It is well established that general anesthesia, with or without paralysis, causes profound changes in respiratory function. From a clinical point of view, the more important consequence of this impairment is a decreased efficiency of gas exchange, with a decreased blood oxygenation. The main reason of this respiratory embarrassment is the intraoperative occurrence of atelectasis, mainly in the dependent lung regions. The amount of atelectasis, computed through Computerized Tomography, correlates with the amount of intrapulmonary shunt; thus, alveolar collapse and ventilation/perfusion mismatching are considered the most important factors for poor respiratory function. This deterioration seems also to play a crucial role in obese patients, who have poorer respiratory function and gas exchange than normal subjects already in physiological conditions. Different ventilatory approaches have been tried to resolve and eventually prevent the anesthesia-induced atelectasis. In normal subjects, the sole application of positive end-expiratory pressure (PEEP) seems to be an useless tool for improving gas exchange, probably because of changes in hemodynamics functions. The only effective application of PEEP seems to be in association to an alveolar recruitment manoeuvre. As the anesthesia-induced atelectasis are also present in the postoperative period, this ventilatory approach may also be used to prevent this condition. In obese patients PEEP seems to have a major effectiveness than in normal subjects, with an improvement of lung volumes, respiratory mechanics, gas exchange and an occurrence of recruitment. However, further studies are necessary to define optimal value of PEEP and tidal volume for different types of patients.