Naturalistic follow-up of co-morbid substance use in schizophrenia: the West London first-episode study.

BACKGROUND: The impact of co-morbid substance use in first-episode schizophrenia has not been fully explored. METHOD: This naturalistic follow-up of a cohort of 152 people with first-episode schizophrenia examined substance use and clinical outcome in terms of symptoms and social and neuropsychological function. RESULTS: Data were collected on 85 (56%) of the patient cohort after a median period of 14 months. Over the follow-up period, the proportion of smokers rose from 60% at baseline to 64%. While 30% reported lifetime problem drinking of alcohol at baseline, only 15% had problem drinking at follow-up. Furthermore, while at baseline 63% reported lifetime cannabis use and 32% were currently using the drug, by the follow-up assessment the latter figure had fallen to 18.5%. At follow-up, persistent substance users had significantly more severe positive and depressive symptoms and greater overall severity of illness. A report of no lifetime substance use at baseline was associated with greater improvement in spatial working memory (SWM) at follow-up. CONCLUSIONS: Past substance use may impede recovery of SWM performance in people with schizophrenia in the year or so following first presentation to psychiatric services. The prevalence of substance use other than tobacco tends to diminish over this period, in the absence of specific interventions. Persistent substance use in first-episode schizophrenia is associated with more severe positive and depressive symptoms but not negative symptoms, and should be a target for specific treatment intervention.

Effort and work of breathing in neonates during assisted patient-triggered ventilation.

OBJECTIVE: This study compares patient-ventilator synchrony, work of breathing and patient effort in neonates during different modes of patient-triggered ventilation. DESIGN: Clinically stable neonates received intermittent mandatory ventilation (IMV), synchronized intermittent mandatory ventilation (SIMV), pressure assist/control ventilation (A/C), and pressure support ventilation (PSV) in a random order for 20 mins. With each mode patient-ventilator synchrony, work of breathing, and patient effort were evaluated. SETTING: Neonatal level III intensive care unit of a university hospital. Measurements and RESULTS: Seven clinically stable neonates (31.4 +/- 2 wks gestation, weighing 1.49 +/- 0.38 kg) were randomly ventilated with the above four modes using a Bird VIP ventilator. Esophageal pressure, airway pressure, and flow were measured using a CP-100 neonatal monitor (Bicore). Data for five consecutive breaths in each mode were analyzed. Patient effort and work of breathing differed significantly among modes of ventilation. The inspiratory pressure time product was least with A/C (0.54 +/- 0.29 cm H(2)O.sec) and increased with PSV (0.60 +/- 0.39 cm H(2)O.sec), SIMV (1.46 +/- 0.55 cm H(2)O.sec), and IMV (2.74 +/- 1.05 cm H(2)O.sec) (p <.05). A similar trend was observed for work of breathing, with work least during A/C (0.07 +/- 0.04 joules per liter [J/L]), followed by PSV (0.17 +/- 0.14 J/L), SIMV (0.33 +/- 0.13 J/L), and IMV (0.41 +/- 0.16 J/L) (p <.05). Marked dyssynchrony between patient-initiated and ventilator-initiated inspiration occurred only during IMV. CONCLUSION: Asynchrony can be avoided by the use of assisted, patient triggered modes of ventilation and, of the available modes, pressure A/C results in the least effort and work of breathing for clinically stable neonates.

Blockade of acute hypertensive response does not prevent changes in behavior or in CSF acetylcholine (ACH) content following traumatic brain injury (TBI).

There is evidence that the blood-brain barrier (BBB) is breached following traumatic brain injury (TBI), allowing the unregulated entry of circulating neuroactive substances into the central nervous system. As the traumatic episode is typically associated with an acute hypertensive event, which in itself may alter BBB status, the effects of the blockade of TBI-associated hypertension on injury-associated behavioral and cerebrospinal fluid (CSF) neurochemical changes were assessed in rats. Animals were injected with either saline or hexamethonium 15 min prior to a moderate fluid percussion injury while under light methoxyflurane anesthesia. This dose of hexamethonium was demonstrated to block the hypertensive response to TBI. Pretreatment with hexamethonium prevented neither acute nor more enduring behavioral deficits observed after TBI. Hexamethonium did not prevent TBI-associated increases in CSF acetylcholine (ACh) content in separate group of rats sampled 12 min following TBI. Furthermore, histological inspection indicated that hexamethonium did not prevent TBI-induced disruption of the BBB, as assessed by intravascular horseradish peroxidase (HRP). Thus, blockade of the hypertensive response to TBI does not afford behavioral protection nor does it prevent changes in the BBB or CSF ACh content following TBI. TBI is in itself sufficient to modify behavior, neurochemistry and BBB function in the absence of hypertension.

Moderate hypothermia reduces blood-brain barrier disruption following traumatic brain injury in the rat.

The effects of moderate hypothermia on blood-brain barrier (BBB) permeability and the acute hypertensive response after moderate traumatic brain injury (TBI) in rats were examined. TBI produced increased vascular permeability to endogenous serum albumin (IgG) in normothermic rats (37.5 degrees C) throughout the dorsal cortical gray and white matter as well as in the underlying hippocampi as visualized by immunocytochemical techniques. Vascular permeability was greatly reduced in hypothermic rats cooled to 30 degrees C (brain temperature) prior to injury. In hypothermic rats, albumin immunoreactivity was confined to the gray-white interface between cortex and hippocampi with no involvement of the overlying cortices and greatly reduced involvement of the underlying hippocampi. The acute hypertensive response in normothermic rats peaked at 10 s after TBI (187.3 mm Hg) and returned to baseline within 50 s. In contrast, the peak acute hypertensive response was significantly (P < 0.05) reduced in hypothermic rats (154.8 mm Hg, 10 s after TBI) and returned to baseline at 30 s after injury. These results demonstrate that moderate hypothermia greatly reduces endogenous vascular protein-tracer passage into and perhaps through the brain. This reduction may, in part, be related to hypothermia-induced modulation of the systemic blood pressure response to TBI.

The susceptibility of elastin-fatty acid complexes to elastolytic enzymes.

Elastin in vivo is likely to be complexed with amphipathic ligands such as lipids. The susceptibility of stable [3H] elastin-fatty acid complexes to the action of porcine pancreatic elastase (PPE) and to human neutrophil lysates over time was assessed. Elastolysis by PPE of substrates prepared with oleic or linoleic acids was initially higher (for up to 2 hours) than that of uncomplexed elastin. Stearic acid and elaidic acid (the trans isomer of oleic acid) did not enhance the elastolytic rate above control. The stimulatory effect of oleic and linoleic acids appeared to derive from increased adsorption of PPE onto elastin; the loss of stimulatory activity over time occurred in parallel with a progressive decrease in adsorption. All fatty acids tested inhibited elastolysis by neutrophil lysates, the effect being particularly marked with oleic and elaidic acids. These results indicate that 1). Complexed fatty acids can modulate the rate of elastin breakdown by elastases; 2). The effects observed with PPE are due to differences in adsorption of enzyme onto substrate, possibly as a result of steric considerations; 3). Since elastolysis by neutrophil lysates is inhibited by all fatty acids, the properties of different elastolytic enzymes should be considered in in vitro model systems of connective tissue breakdown.

Wide variations in the night visiting rate.

The night visit record of an out-of-hours rota service of a large health centre which includes 10 group practices was examined. The mean annual night visiting rate for the health centre was 35.2 per 1000 patients, ranging from 25.8 to 43.5 between individual practices. The organization of medical care at night was the same for all the practices, and no major demographic differences between practices were identified. It is argued that the doctor-patient relationship may have an influence on differences in night visiting rates.