When should governments increase the supply of psychiatric beds?

Low numbers of hospital-based psychiatric beds create problems for people with severe mental illness (SMI), when they face extended emergency department (ED) waits, higher thresholds for admission to an acute bed, and short revolving-door stays with high rates of rehospitalisation. Limited access to inpatient treatment has been associated with higher suicide risk, premature mortality, homelessness, violent crime and incarceration. Ultimately, people with SMI can be transinstitutionalised to the criminal justice system. In the USA, for example, prisons have replaced mental hospitals as the largest institutions housing people with SMI. There is no international consensus on the safe minimum numbers of acute, forensic and rehabilitation beds needed to reduce these risks. As a consequence, Organisation for Economic Cooperation and Development (OECD) countries have wide variations in the mix of hospital beds with an average of 71 beds per 100 000 population. Policymakers face difficult choices with few studies to guide decisions on supplying beds. The UK Royal College of Psychiatrists offered a policy framework, which was adapted for Australia. The government of the State of South Australia increased the supplies of crisis, acute and forensic beds to meet a mandatory target to safely reduce mental health boarding in the EDs.

An unusual complication of hypertensive hemorrhage - delayed oculomotor palsy: case report and literature review.

We present a case of oculomotor palsy due to hypertensive hemorrhage in the caudate nucleus, with intraventricular extension. To our knowledge, this is the only instance of this complication occurring due to hypertensive hemorrhage. Our patient initially developed headache at the time of her hemorrhage; 8 days later, she developed complete third nerve palsy, which showed improvement at follow-up 4 months later. This was due to tracking of blood into the perimesencephalic cistern. The presence of hemorrhage in the basal cisterns was not visible on the initial CT scans and highlights the role of MRI in evaluating the brainstem for the presence of blood products.

Reproducibility of the high-performance liquid chromatographic fingerprints obtained from two soybean cultivars and a selected progeny.

Roots from soybean cultivars Williams 82 and Hartwig along with one of their progeny 14a, were extracted with non-polar, moderately polar, and highly polar solvent systems. Extracts were compared by thin-layer chromatography and by HPLC. Methanol extractions conducted at ambient temperature coupled with analysis by reversed-phase HPLC using UV detection provided the most representative sets of reproducible fingerprints. Further optimization of the overall protocol should allow for the profiling of different soybean cultivars when their roots are exposed to various environments and insults during early growth.

Case of unusual presentation of fusiform aneurysm of the basilar artery.

OBJECTIVE: To describe a case of a fusiform aneurysm of the basilar artery presented as a pontine infarct and 2 days later as a subarachnoid hemorrhage caused by the rupture of the same aneurysm. DESIGN: Case report. SETTING: Tertiary-care hospital. BACKGROUND: Fusiform aneurysm of cerebral vessels is a rare pathology that presents with ischemic stroke, subarachnoid hemorrhage, or mass effect. Ischemia and subarachnoid hemorrhage in the same patient 2 days apart, to our knowledge, was not reported before. SUBJECT: A 55-year-old Hispanic man with history of untreated hypertension and alcohol abuse presented with acute onset of right hemiparesis and dysarthria. On day 2 of his hospital admission, he developed arrhythmia and loss of consciousness. The patient expired from cardiac arrest on day 4 of his hospitalization. Initial head computed tomography scan showed dolichoectatic basilar artery and marked calcification of internal carotid arteries (ICA) and middle cerebral arteries (MCA). Brain magnetic resonance imaging showed left upper pons infarct 2 cm in diameter. Magnetic resonance angiography confirmed presence of a fusiform aneurysm of the basilar artery. Head computed tomography scan at the time of clinical deterioration on day 2 of hospital admission showed subarachnoid bleeding and significant brain edema. Autopsy revealed a ruptured basilar artery aneurysm with thrombus in the lumen and left pontine infarct. Microscopic examination of fusiform aneurysm showed atherosclerosis of the aneurysmal wall and attenuation and inflammation at the rupture site. CONCLUSIONS: We hypothesize that in our case, pontine infarct had developed because of occlusion of pontine perforators by a thrombus within an aneurysm, and subarachnoid hemorrhage had developed secondary to a rupture of weakened by inflammatory changes aneurysmal wall. We also hypothesize that in our case, ischemic stroke and subsequent subarachnoid hemorrhage may represent different stages of the same process of atherosclerosis and inflammation in an aneurysmal wall confirmed by autopsy. Origin as well as management of fusiform cerebral aneurysms are unclear. Antiplatelet agents and anticoagulation are recommended by some for stroke prophylaxis in patients with unruptured fusiform cerebral aneurysms. Our case shows that caution should be exercised in prescribing anticoagulants or even antiplatelet agents to a patient with fusiform aneurysm of cerebral arteries due to a possibility of rupture of an aneurysm. Randomized prospective study may be necessary to clarify this issue.

Ethics in managed care.

The current era of managed costs and care create ethical dilemmas based on economic constraints and incorporation of principles of distributive justice. Traditional ethical concerns related to confidentiality, conflicts of interest, double agentry, and honesty are complicated by interference in the doctor-patient relationship caused by intrusive utilization management. National health reform must take these issues seriously to ensure that the "cure" promised by such reform efforts is not worse than the disease. The challenge for psychiatrists is to adapt to these constraints without losing site of traditional medical ethical positions. Once the ethics become diseased, no cure may exist at all.

Infratentorial and supratentorial leukoencephalopathy associated with vitamin B12 deficiency.

BACKGROUND: Striking cerebral white matter abnormalities involving supratentorial regions seen on magnetic resonance imaging (MRI) scans have been described in patients with vitamin B12 deficiency. Severe involvement of infratentorial structures with partial reversibility has not been previously documented. OBSERVATION: A 54-year-old man experienced severe weight loss, associated with dementia and focal deficits. Laboratory analysis showed a severe vitamin B12 deficiency and elevated serum homocysteine. MRI scans showed a severe and diffuse white matter abnormal signal involving both the supra- and infratentorial compartments. Vitamin B12 supplementation resulted in a mild improvement in cognitive deficits and a marked resolution of imaging abnormalities. CONCLUSION: Leukoencephalopathy and dementia should raise the suspicion of a vitamin B12 deficiency because vitamin B12 supplementation may result in at least partial clinical improvement.

Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals.

Reporter genes (e.g. beta-galactosidase, chloramphenicol-acetyltransferase, green fluorescent protein, luciferase) play critical roles in investigating mechanisms of gene expression in transgenic animals and in developing gene delivery systems for gene therapy. However, measuring expression of these reporter genes requires biopsy or death. We now report a procedure to image reporter gene expression repetitively and non-invasively in living animals with positron emission tomography (PET), using the dopamine type 2 receptor (D2R) as a reporter gene and 3-(2'-[18F]fluoroethyl)spiperone (FESP) as a reporter probe. We use a viral delivery system to demonstrate the ability of this PET reporter gene/PET reporter probe system to image reporter gene expression following somatic gene transfer. In mice injected intravenously with replication-deficient adenovirus carrying a D2R reporter gene, PET in vivo measures of hepatic [18F] retention are proportional to in vitro measures of hepatic FESP retention, D2R ligand binding and D2R mRNA. We use tumor-forming cells carrying a stably transfected D2R gene to demonstrate imaging of this PET reporter gene/PET reporter probe system in 'tissues'. Tumors expressing the transfected D2R reporter gene retain substantially more FESP than control tumors. The D2R/FESP reporter gene/reporter probe system should be a valuable technique to monitor, in vivo, expression from both gene therapy vectors and transgenes.

Adult-onset MELAS presenting as herpes encephalitis.

OBJECTIVE: To report an unusual presentation of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) manifested in late life with a clinical picture of herpes simplex encephalitis. DESIGN: Case report. SETTING: Clinical neurology department in a tertiary care hospital. CASE DESCRIPTION: A 55-year-old woman developed aphasia and delirium during ophthalmic herpes zoster infection treated with oral prednisone and ophthalmic steroids, which was followed by progressive cognitive decline without acute neurologic events for 5 years. At age 60, the patient presented with new onset of seizures, hemiparesis, and hemianopsia. Subsequently she developed cortical blindness, multiple traumatic soft tissue injuries from falls, acute psychosis, and severe dementia with periods of agitation. She died in a nursing home in March 1997, 6 years after initial presentation. RESULTS: Magnetic resonance imaging scan of the brain showed hyperintensity on T2-weighted images involving temporal, parietal, and occipital lobes bilaterally as well as mild atrophy of brainstem and cerebellum. Single photon emission computed tomographic imaging showed hypoperfusion of temporal, parietal, and occipital lobes. Results of video electroencephalographic monitoring showed periodic lateralizing epileptiform discharges in temporal and occipital areas. The serum lactate level was normal in May 1996 and elevated in October 1996. The creatine kinase level was elevated with a 100% MM fraction in August 1991 and normal in March 1996. Results of repeated cerebrospinal fluid analyses indicated elevated protein levels. Analysis of DNA was diagnostic of MELAS by mitochondrial DNA point mutation at position 3243. The results of autopsy showed moderate cerebral, cerebellar, and brainstem atrophy with signs of infarction in temporal and parietal lobes bilaterally. CONCLUSIONS: The clinical presentation as well as age at onset of MELAS are highly variable. Onset of mitochondrial disorders can be provoked by febrile illness when there is mismatch between energy requirements and availability. In the differential diagnosis of herpes encephalitides, MELAS syndrome should be considered.

Stroke outcome in patients already taking aspirin.

UNLABELLED: Background Although aspirin (ASA) has been shown to be effective for secondary (but not primary) stroke prevention and to have some beneficial influence on outcome when taken early after stroke onset, studies regarding the impact of prior use of ASA on stroke severity are conflicting. OBJECTIVES: To determine whether ASA therapy begun before stroke onset lessens the severity of stroke. METHODS: Prospective clinical information was collected for all patients admitted with their first acute ischemic stroke between July 1996 and July 1998. National Institutes of Health Stroke Scale (NIHSS) scores were noted on admission and at discharge. Barthel Index (BI), Modified Rankin Scale (MRS), and Glasgow Outcome Scale (GOS) scores were also noted at discharge. Stroke severity was classified as severe if the NIHSS score was 9 or greater, BI score was 55 or less, the MRS score was 4 or greater, or the GOS score was 3 or greater. Group comparisons were performed by using the X(2) tests. RESULTS: 178 patients were evaluated. Forty-two were taking ASA and 136 were not taking ASA or any other anti-thrombotic drug. There were no differences between the 2 groups in terms of age, gender, baseline hematocrit or blood glucose, history of hypertension, diabetes, atrial fibrillation, smoking, or stroke subtype. There were no significant differences between the 2 groups on any of the scales, either on admission or at discharge. CONCLUSION: Our data do not suggest that ASA use before stroke onset lessens the severity of first stroke. Until this question is definitively settled, however, it would be prudent to ensure balanced distribution of recent ASA use in acute stroke treatment trials.

Imaging of adenoviral-directed herpes simplex virus type 1 thymidine kinase reporter gene expression in mice with radiolabeled ganciclovir.

UNLABELLED: We are developing procedures to repeatedly and noninvasively image the expression of transplanted reporter genes in living animals and in patients, using PET. We have investigated the use of the Herpes Simplex Virus type 1 thymidine kinase gene (HSV1-tk) as a reporter gene and [8-14C]-ganciclovir as a reporter probe. HSV1-tk, when expressed, leads to phosphorylation of [8-14C]-ganciclovir. As a result, specific accumulation of phosphorylated [8-14C]-ganciclovir should occur almost exclusively in tissues expressing the HSV1-tk gene. METHODS: An adenoviral vector was constructed carrying the HSV1-tk gene along with a control vector. C6 rat glioma cells were infected with either viral vector and uptake of [8-3H]-ganciclovir was determined. In addition, 12 mice were injected with varying levels of either viral vector. Adenovirus administration in mice leads primarily to liver infection. Forty-eight hours later the mice were injected with [8-14C]-ganciclovir, and 1 hr later the mice were sacrificed and biodistribution studies performed. Digital whole-body autoradiography also was performed on separate animals. HSV1-tk expression was assayed, using both normalized HSV1-tk mRNA levels and relative HSV1-TK enzyme levels, in both the cell culture and murine studies. RESULTS: Cell culture, murine tissue biodistribution and murine in vivo digital whole-body autoradiography all demonstrate the feasibility of HSV1-tk as a reporter gene and [8-14C]-ganciclovir as an imaging reporter probe. A good correlation (r2 = 0.86) between the [8-14C]-ganciclovir percent injected dose per gram tissue from HSV1-tk positive tissues and HSV1-TK enzyme levels in vivo was found. An initial study in mice with [8-18F]-fluoroganciclovir and microPET imaging supports further investigation of [8-18F]-fluoroganciclovir as a PET reporter probe for imaging HSV1-tk gene expression. CONCLUSION: These results demonstrate the feasibility of using [8-14C]-ganciclovir as a reporter probe for the HSV1-tk reporter gene, using an in vivo adenoviral mediated gene delivery system in a murine model. The results form the foundation for further investigation of [8-18F]-fluoroganciclovir for noninvasive and repeated imaging of gene expression with PET.

Noninvasive methods for quantitating blood time-activity curves from mouse PET images obtained with fluorine-18-fluorodeoxyglucose.

UNLABELLED: The mouse model is currently being explored for various applications with PET imaging. Low resolution of current animal scanners relative to mouse size leads to difficulty in quantitating data from mouse PET images. We have, therefore, investigated methods for determining blood time-activity curves (TACs) from mouse PET studies done with fluorine-18-fluorodeoxyglucose (FDG). METHODS: Eight mice were fasted, the tail vein was injected with 150-300 microCi of FDG and dynamic images were acquired with a CTI/Siemens (Knoxville, TN) animal tomograph for 64.5 min. Concurrently, 11-14 left ventricle (LV) blood samples were drawn directly from the LV chamber. Organ TACs were obtained by drawing circular regions of interest (ROIs) of various sizes on images of the heart, liver and brain. For each mouse, the FDG model parameter K = (K1 x k3)/(k2 + k3) was estimated by a Patlak algorithm with various estimates of the blood TAC and, as a reference tissue TAC, the brain TAC. RESULTS: Most partial-volume-corrected heart ROI TACs overestimated the LV samples. Blood TACs from heart images produced statistically different estimates of K than did the LV samples. The liver image-derived blood TACs yielded estimates of K that were comparable to those yielded by the LV samples. Estimates of K determined with two directly sampled LV points in conjunction with the liver image-derived TAC were not statistically different from the estimates obtained with the LV samples. The size and location of ROIs on images of the liver minimally affected the TACs. CONCLUSION: We have shown that it is experimentally possible to obtain a blood TAC from mouse studies by repeatedly sampling from the LV. We have also shown that images of the liver can be used to reliably estimate the blood TAC. Future FDG PET studies with the mouse model will benefit from this demonstrated ability to noninvasively quantitate blood TACs directly from FDG PET images.