Pharmacological specificity of the increase in neurotensin concentrations after antipsychotic drug treatment.

Neurotensin is an endogenous neuropeptide that produces many CNS effects that are similar to the behavioral and physiological alterations seen after administration of antipsychotic drugs to laboratory animals. As previously reported, sub-chronic (3 week) and acute (single injection) treatment with haloperidol (1 mg/kg), a clinically effective antipsychotic drug increases neurotensin concentrations in the nucleus accumbens and the caudate nucleus. In contrast, a tricyclic antidepressant (desipramine, 10 mg/kg), an anxiolytic (chlordiazepoxide, 25 mg/kg) and a histamine H1 receptor antagonist (diphenhydramine, 20 mg/kg) did not alter neurotensin concentrations in these brain regions after sub-chronic or acute treatment. These data demonstrate pharmacologic specificity to the antipsychotic drug-induced increases in regional brain neurotensin concentrations, and support the hypothesis that these changes may contribute to the clinical efficacy of these drugs.     

Optometry research. Part 2: Grants received.

Part 1 showed that the dominant provider of ophthalmic research funding (85%) was the National Eye Institute (NEI) and that on the average optometry faculty members had received about 3% of that funding over the years. Part 2 shows how this 3% of NEI funding has been distributed among the 16 U.S. schools in existence during the period studied and why 3% is a rational result under current conditions.     

Artifacts due to stimulus correlated motion in functional imaging of the brain

To assess the effect of stimulus correlated motion on the appearance of functional magnetic resonance images, conventional visual and motor protocols were each performed by four normal volunteers and an image co-registration technique was used to retrospectively monitor subject motion. In three studies synthetic data sets were constructed from single baseline images using the positional information obtained from the co-registration procedure. Cumulative difference images were then created from both the synthetic and functional image sets. Stimulus correlated motion was detected in all eight studies and the synthetic cumulative difference images showed striking similarities to the equivalent functional images in each case.     

Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails.

Monocyte chemoattractant protein 1 (MCP-1) is a member of the chemokine family of cytokines that mediate leukocyte chemotaxis. The potent and specific activation of monocytes by MCP-1 may mediate the monocytic infiltration of tissues in atherosclerosis and other inflammatory diseases. We have isolated cDNAs that encode two MCP-1-specific receptors with alternatively spliced carboxyl tails. Expression of the receptors in Xenopus oocytes conferred robust mobilization of intracellular calcium in response to nanomolar concentrations of MCP-1 but not to related chemokines. The MCP-1 receptors are most closely related to the receptor for the chemokines macrophage inflammatory protein 1 alpha and RANTES (regulated on activation, normal T expressed and secreted). The identification of the MCP-1 receptor and cloning of two distinct isoforms provide powerful tools for understanding the specificity and signaling mechanisms of this important chemokine.     

Non-obstructive colonic dilatation in the trauma patient: an analysis of six patients.

Non-obstructive colonic dilatation was diagnosed in six of 13,641 patients admitted to a Level I trauma centre over a 70-month period (incidence, less than 0.05 per cent). Four were older than 60 years, and five required long-term support on a ventilator. Successful treatment depends on expeditious decompression of the dilated colon. Fibreoptic colonoscopy is the recommended method.     

Evaluation of myocardial function in patients with end-stage heart failure during support with the Jarvik 2000 left ventricular assist device.

In 2 patients with the Jarvik 2000 left ventricular assist device (LVAD), we assessed left ventricular systolic function through pressure-volume loops and E(max) at the beginning and end of the support period to potentially predict the possibility of pump removal without transplantation. Immediately before LVAD implantation and explantation, pressure and volume measurements were made with catheters and echocardiography, respectively, the E(max) being calculated from the slope of the pressure-volume loops, and the left ventricular ejection fraction (LVEF) being estimated by echocardiography. Transplantation was performed after 14 and 62 days, respectively, during which the LVEF increased by 75% (from 12% to 21%) in Patient 1 and remained unchanged (from 16% to 18%) in Patient 2, whereas the E(max) increased from 0.63 and 0.42 mm Hg/ml, respectively, to 1.31 and 1.07 mm Hg/ml, reflecting a 107% and 155% improvement. In these 2 cases, the E(max) was a more reliable indicator of intrinsic myocardial contractility than was the LVEF.     

Minimal volume,hypotense resuscitation

Large volume fluid resuscitation attempting to normalise physiological parameters in hypovolaemic shock has become the accepted management practice during the last 30 years. This doctrine, based on research in the 1950s, teaches that shock increases mortality, aggressive resuscitation improves outcome and normalisation of vital signs protects against multiple organ dysfunction. The wide acceptance of this doctrine is demonstrated by the central role it plays in the American College of Surgeons Advanced Trauma Life Support (ATLS) course and its Australian equivalent the Early Management of Severe Trauma (EMST) course. During the late 1980s, a number of animal research papers demonstrated severe limitations to the earlier work performed in the 1950s and proposed an alternative approach using hypotense or minimal fluid resuscitation. Controlled haemorrhagic shock is hypovolaemic shock in which the source of the bleeding is easily controlled without operation and hence aggressive fluid resuscitation can be pursued with minimum risk. Uncontrolled haemorrhagic shock is hypovolaemic shock due to bleeding which cannot be controlled without surgery. The restoration of blood pressure towards normal levels may lead to dislodgement of thrombus and loss of vascular spasm in damaged vessels, with a subsequent increase in blood loss. It is in this situation that hypotense resuscitation is thought to be of most value. Hypotense resuscitation is defined as the use of fluid resuscitation to maintain blood pressure at lower than normal levels which are sufficient to maintain life, but minimise the risk of exacerbating internal bleeding. Prompted by animal research a number of human studies have been undertaken to clarify the role of fluid resuscitation in uncontrolled haemorrhage. At present, there is wide acceptance of the use of hypotense or minimal volume resuscitation for ruptured abdominal aortic aneurysm and a recent demonstration that morbidity and mortality are decreased by the use of hypotense resuscitation in penetrating truncal trauma. There are however many other clinical situations that may produce uncontrolled haemorrhagic shock about which we have little clinical data to predict appropriate levels of fluid resuscitation. These include ectopic pregnancy, gastro-intestinal haemorrhage and blunt multi-system trauma. This paper will analyse the animal studies that demonstrate the physiological effects of the various fluid resuscitation regimes and discuss all the clinical papers on the subject of hypotense resuscitation. An attempt will then be made to integrate this data into current Australian practice and give broad guidelines on the modern management of uncontrolled haemorrhagic shock, based on minimal volume or hypotense resuscitation.