Quantification of cerebral blood flow with 99mTc-ECD SPECT by a single arterial or venous blood sample

The purpose of the study is to develop a simple and less invasive method for quantifying regional cerebral blood flow (rCBF) using 99mTc-ECD and SPECT. By employing a microsphere model, a new method to measure rCBF was developed, which required a single arterial or venous sample instead of continuous withdrawal of arterial blood. Using a regression line, the integral of input function of arterial blood from 0 to 30 min was inferred by activity of arterial blood sampled at time t; A(t), by activity multiplied by its octanol extraction rate; AN(t), by activity of venous blood at time t; V(t), and by activity multiplied by its octanol extraction rate; VN(t). The optimum sampling time of arterial or venous blood was examined when mean % error for inference became minimum. Consequently, minimum error of AN(6 min) was 5.5%, A(3 min) was 8.9%, VN(6 min) was 5.9%, and V(20 min) was 10.0%. Quantitative measurement of rCBF using the value of VN(6 min) was performed on other 6 subjects with dementia etc. To validate the method, 133Xe inhalation SPECT studies were also performed on the same subjects. We found a good agreement between them (r = 0.851). The presented one-point sampling methods were simple and less invasive for quantifying rCBF.     

Regional cerebral blood flow measured by 99mTc-HMPAO SPECT differs in subgroups of Alzheimer's disease

Alzheimer's disease (AD) is a heterogeneous entity. Identifying AD subtypes might have impact in patients' response to different treatment strategies. We designed a study to examine regional cerebral blood flow (rCBF) in AD subtypes. To identify AD subtypes, we performed a cluster analysis including performance on memory, language, visuospatial, praxic, and executive functions. The rCBF measured by 99mTc-HMPAO SPECT was referred to the cerebellum. We examined 35 patients fulfilling the NINCDS-ADRDA criteria of probable AD and 13 age and sex-matched healthy cognitively intact controls. AD patients were at the early stage of the disease, their mean Mini-Mental Status (MMS) score (S.D.) was 22.5 (3.6). The cluster analysis revealed two AD subgroups: AD1 (N = 12) and AD2 (N = 23). The subgroups did not differ in age, sex, or global clinical severity as assessed by MMS and Brief Cognitive Rating Scale (BCRS). Both subgroups had equally impaired memory. The AD2 group was inferior to the AD1 group on verbal, visuospatial, praxic, and executive functions. The AD1 group showed reduced rCBF ratios in the temporal and parietal cortices and the amygdala compared to controls. The AD2 group differed from controls in the rCBF ratios of frontal, temporal, parietal, occipital, basal ganglia, and amygdaloid regions bilateral and from AD1 in the rCBF ratios of frontal and temporal cortices. In AD patients, the rCBF ratios did not correlate with MMS or BCRS scores. In contrast, several significant correlations were found between decreases rCBF ratios and impairment of memory and other cognitive functions. In conclusion, a cluster analysis on neuropsychological test performance identified two AD subgroups that differed on the neuropsychological profile and on the rCBF in spite of similar global clinical severity.     

Quantitative measurement of cerebral blood flow by the microsphere model with super-early 123I-IMP brain SPECT

Cerebral blood flow (CBF) was quantitatively measured in 6 healthy young volunteers based on "super-early" acquisition of N-isopropyl-p-[123I]iodoamphetamine (IMP) brain SPECT obtained 4-6 min after IMP injection with a three-head rotating gamma camera and the microsphere (MS) model. The ratio of radioactivity (count/pixel/min) in the conventional early SPECT image (taken 25-55 min after IMP injection) to that in the "super-early" image for each brain region negatively correlated with regional CBF value obtained with the "super-early" MS method. This indicates that wash-out of IMP from the regions with higher CBF is faster than that from the regions with lower CBF and that CBF values are underestimated with the conventional MS method in regions with higher CBF. Regional CBF was quantitatively measured with the "super-early" MS method and the ARG method, a recently developed method based on two-compartment model. The mean cortical CBF was 52.5 +/- 7.0 (ml/100 g/min, mean +/- SD) with the "super-early" MS method and 47.5 +/- 3.3 with the ARG method. The CBF values obtained with the "super-early" MS method agreed with those previously reported with positron emission tomography. Since the MS method is theoretically the simplest model, the "super-early" MS method can be applied various disorders of the central nervous system where the behavior of IMP is not fully understood.     

Effects of scatter and attenuation correction on quantitative assessment of regional cerebral blood flow with SPECT

The pyruvate dehydrogenase complex (PDC) plays a key role in the anaerobic mitochondrial metabolism of the parasitic nematode Ascaris suum. A cDNA coding for an A. suum pyruvate dehydrogenase kinase (APDK) has been cloned and sequenced from poly(A)+ RNA isolated from adult A. suum muscle.2 APDK exhibited significant sequence identity to mammalian PDKs. Nucleotide sequence analysis of the APDK cDNA revealed a 22-nucleotide spliced leader, characteristic of many nematode mRNAs, a 5'-UTR of 6 nucleotides, an open reading frame of 1197 nucleotides, and a 3'-UTR of 101 nucleotides that included a putative polyadenylation signal. The open reading frame predicted a protein of 399 amino acids with a molecular weight of 45,402 that included a putative 18-aminoacid leader peptide. Recombinant APDK (rAPDK) was functionally expressed in Escherichia coli with a his tag at its N-terminus and purified to apparent homogeneity on Ni-NTA-agarose. Recombinant APDK was a dimer and was not autophosphorylated and its activity was stimulated in the presence of APDK-deficient adult A. suum muscle PDC presumably by the binding of APDK to the dihydrolipoyl transacetylase (E2) core of the complex. After binding to the core, rAPDK activity was stimulated by elevated NADH/NAD+ and acetyl CoA/CoA ratios within the same ranges as observed for the native APDK. Immunoblotting suggested that native APDK focused as a series of 43-kDa spots (pI 6.1-6.8) on two-dimensional gels of the purified adult A. suum muscle PDC.     

Chronic schizophrenia: validity of the study of regional cerebral blood flow through cerebral SPECT

OBJECTIVE: To check the validity of the diagnostic test in schizophrenia. MATERIAL AND METHODS: The cerebral blood flow (CBF) characteristics were assessed by means of single photon emission tomography (SPECT) in 24 patients with schizophrenia and 20 normal control subjects. Analysis of sensitivity, specificity and the Youden rate was made of certain RCBF patterns chosen in terms of the cerebral regions between which the greatest differences were observed according to the diagnosis, schizophrenia vs control. RESULTS: Schizophrenia vs control: sensitivity = 58.33%; specificity = 95%; positive predictive value = 93.33% and overall efficiency = 53.33%. CONCLUSIONS: Cerebral SPECT is valid in the discrimination between patients diagnosed with schizophrenia and control subjects, taking the diagnostic judgement of the psychiatrist as the gold standard, and the RCBF pattern that displays the best coefficient is hypoperfusion, in one or several of the regions: right frontal/left frontal/right parietal/thalamus: sensitivity = 58.33%; specificity = 95%; positive predictive value = 93.33% and overall efficiency = 53.33%.     

Comparison of technetium-99m-ECD to Xenon-133 SPECT in normal controls and in patients with mild to moderate regional cerebral blood flow abnormalities

Technetium-99m-1,1-ethyl cysteinate dimer (ECD) has been proposed as a "chemical microsphere" for SPECT measurement of regional cerebral blood flow (rCBF). However, its distribution has not yet been compared in humans to an established rCBF measure. Therefore, we compared the uptake and distribution of ECD with rCBF measured by 133Xe SPECT in subjects with mild to moderate flow abnormalities and in normal volunteers. Blood and urine chemistries and vital signs were unchanged from pre-ECD values up to seven days postinjection. Profile plots demonstrated pattern agreement between rCBF ratios (133Xe) and ECD count density ratios. A significant correlation of rCBF ratios to ECD count density ratios was observed (r = 0.77), with a slope of 0.64 and intercept of 0.36. To explore whether or not the relationship between rCBF and ECD was dependent on absolute flow, ECD region of interest data were expressed in units of ml/min/100 g by equating global CBF (133Xe) and ECD global count density. A closer correlation (r = 0.88) was found for these data than for the count ratio data. The slope was closer to one (m = 0.83) and the intercept was closer to zero (b = 8.2). Also, a significant correlation was observed between ECD-derived rCBF and 133Xe rCBF in the lesion area (r = 0.92) for patients with well-demarcated rCBF lesions. The slope (0.80) suggested a slight underestimation of lesion flow by ECD. Finally, ECD clearance from cortical gray matter ROIs derived from high-resolution scans from 1 to 4 hr postinjection was slow (2.4%/hr). In summary, ECD is a safe and effective marker of regional cerebral perfusion. The distribution of ECD is linearly related to rCBF measured by 133Xe SPECT, although our data suggest a mild underestimation of flow at the high end of the normal range.     

A comparative cerebral blood flow study in a baboon model with acetazolamide provocation: 99mTc-HMPAO vs 123I(IMP)

Pharmacological interactions are important when nuclear medical procedures are applied to patients under drug therapy, or drug provocation. This study compares in baboon models (regional) cerebral blood flow [(r)CBF] results from 99mTc-HMPAO and 123I-iodoamphetamine [123I(IMP)] each with and without acetazolamide, the latter a suggested drug for testing cerebrovascular reserve. Expected differences in cerebral uptake were observed between the two radio-tracers without acetazolamide. The increase in tracer uptake resulting from acetazolamide is significantly enhanced for 123I(IMP), which could have diagnostic implications.     

Quantification of cerebral blood flow and partition coefficient using iodine-123-iodoamphetamine

The aim of this study was to develop a simple, noninvasive method for quantifying both regional cerebral blood flow (rCBF) and the partition coefficient (lambda) using N-isopropyl-p[123I]iodoamphetamine and SPECT. METHODS: By employing a two-compartment model (influx, K1: outflux, k2), a new method was introduced that requires two serial SPECT scans at 30 min and 60 min, and a single arterial sample 5 min after tracer injection. The integral of the arterial input function is inferred from the sample by using the correlation obtained from 25 subjects. Two original mathematical functions, phi for K1 and gamma for lambda (= K1/k2), were obtained from the input functions of 12 subjects. The values of K1 and lambda are determined from the two scans and the single arterial sample by using these functions. The values obtained for K1 (= rCBF) and lambda were compared with those obtained by nonlinear least-squares fitting analysis and the 133Xe inhalation SPECT method. RESULTS: K1 and lambda were in good agreement with the values obtained by nonlinear least-squares fitting analysis (r = 0.873 in K1 and r = 0.825 in lambda), and rCBF values were closely correlated with those obtained by the 133Xe method (r = 0.843). CONCLUSION: The proposed method has three advantages: (a) accurate, simultaneous quantification of both rCBF and the partition coefficient; (b) simplicity and noninvasiveness; and (c) a relatively short period (approximately 70 min) for the study.     

Stepwise analysis of cerebral blood flow SPECT imaging on standard brain atlas in patients with dementia of Alzheimer''s type

In 1994 the first human parvovirus B19 (B19) epidemic to be documented in Denmark was recorded from February 2 to September 30. In total, 10,333 serum samples were tested for specific B19 IgM and IgG antibodies, using IDEIA Parvovirus B19 IgM and IgG kits. The prevalence of B19 IgM positivity was 11% for the whole period and 29% at the peak of the epidemic in week 14, declining from week 39 and onwards to 1-3%. The prevalence of B19 IgG (IgM-negative samples) was 60%, indicating an earlier infection, and the same for men and women. The gender distribution of tested patients was the same at the beginning of the epidemic as at the end of the epidemic and a year after its peak, i.e. 86% of samples were from women and only 14% from men. Age distribution for women was the same for the three periods (median age 34 years). For men the median age was 32 years, 39 years and 31 years, respectively. Only a few samples from children were tested. No change in test pattern was observed during the three periods. Approximately 75% of all samples tested were from women of childbearing age (18-45 years old), suggesting a fear of fetal complications in an actual or future pregnancy, rather than a serological verification of clinical symptoms. From the sparse clinical information that accompanied the serum sample we were not able to demonstrate that women were more likely than men to have a symptomatic B19 infection. With reservations we estimate that 14% of adverse pregnancy outcome is correlated with a B19 infection.     

Quantitative cerebral blood flow and metabolism determination in the first 48 hours after severe head injury with a new dynamic SPECT device

OBJECTIVE: To determine cerebral blood flow (CBF) and metabolism in the acute phase after severe head injury by a new dynamic SPECT device using 133Xenon and to evaluate a possible role of CBF and metabolism in the determination of prognosis. DESIGN: Prospective study. SETTING: General intensive care unit in a universitary teaching hospital. SUBJECTS: 23 severely head injured patients having CT scan and CBF determination, intracranial pressure (ICP) and jugular bulb oxygen saturation monitoring in the first 48 hours. MEASUREMENTS AND MAIN RESULTS: CBF varied from 18.0 to 60.0 ml/100 g/min. No correlation was found between early CBF and severity of trauma evaluated with the Glasgow Coma Score (GCS) (F = 2.151, p = 0.142) and between CBF and prognosis at 6 months evaluated with Glasgow outcome score (GOS) (F = 0.491, p = 0.622: rs = 0.251, p = 0.246). CMRO2 was depressed in relation to the severity of injury, specifically ranging from 0.9 +/- 0.5 ml/100 g/min in patients with GCS 3 to 1.7 +/- 0.8 ml/100 g/min in patients with GCS 6-7. In no patient with CMRO2 less than 0.8 ml/100 g/min was a good outcome observed. A significant correlation was found between GCS and GOS (rs = 0.699, p = 0.0002), between CMRO2 and GOS (F = 4.303, p = 0.031; rs = 0.525, p = 0.013) and between AJDO2 and GOS (F = 3.602, p = 0.046; rs = 0.491, p = 0.017). Fronto-occipital ratio (F/O) of CBF distribution was significantly lower than normal values (chi 2 = 18.658, p = 0.001) but did not correlate either with prognosis (chi 2 = 1.626, p = 0.443) or with severity (chi 2 = 1.913, p = 0.384). CONCLUSIONS: CBF in the first 48 hours after trauma varies within a large range of values and is not correlated with severity and prognosis. Clinical evaluation with GCS and CMRO2 are much more reliable indicators of severity of head trauma and have a significant role in the determination of prognosis. F/O ration is significantly altered from normal values confirming "post-traumatic hypofrontalism" but does not correlate with severity and prognosis.     

Cerebral blood flow study using SPECT in patients with memory disorders

INTRODUCTION: Global amnesia (AG) is a dysfunction of memory, in which there is a sudden incapacity to remember recent events and assimilate new information. The aetiology is currently under discussion. The main hypotheses under consideration are an ischemic mechanism and an epileptic mechanism. OBJECTIVE: To study the cerebral blood flow in patients with temporary global amnesia (AGT) or permanent global amnesia (AGP) using functional neuroimaging techniques. MATERIAL AND METHODS: Four patients were studied. Two had severe alterations of fixation memory which had been present for months. The other two had a sudden loss of recent memory, although space-person orientation and immediate memory remained normal. In all cases the cerebral blood flow (FSC), was assessed by single photon emission tomography (SPECT), using Tc-HMPAO as the radio tracer. RESULTS: We describe 4 patients, 2 men and 2 women aged between 42 and 64.2 with AGT and the others with AGP. On SPECT there was temporal hypoperfusion in all 4 patients. In 2 cases there was associated parietal hypoperfusion and in 1 case there was frontal hypoperfusion. CONCLUSIONS: These findings suggest that AGT and AGP are of vascular origin and that SPECT is a useful diagnostic technique in patients with AG.     

SPECT cerebral blood flow, MR imaging, and neuropsychological findings in traumatic head injury.

Investigated 16 patients with diffuse or contusional brain damage and 8 patients with focal lesions 5–22 mo postinjury, using single proton emission computed tomography (SPECT) cerebral blood flow (CBF) measurements and neuropsychological examination. All Ss were aged 16–64 yrs. Compared with 16 controls, the diffuse group showed significant differences on 13 of 24 measures after correction for premorbid differences, whereas the focal group was significantly impaired on only 3 tests after correction. SPECT apparently identified abnormalities not demonstrated on magnetic resonance (MR) imaging and vice versa. Abnormal regional CBF seemed to be related to neuropsychological defects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparative study of simple methods to measure regional cerebral blood flow using iodine-123-IMP SPECT

The aim of this study was to compare the accuracy and reliability of simple methods of quantifying regional cerebral blood flow (rCBF) with 123I-labeled N-isopropyl-p-iodoamphetamine (IMP) and SPECT and to determine which method was best. METHODS: Four methods were examined: (a) the microsphere method with continuous withdrawal of arterial blood, which was based on a microsphere model using the SPECT image obtained 5 min after tracer injection, (b) the microsphere method with one-point sampling, which was the same as the first method except that one-point sampling was used instead of continuous withdrawal, (c) the modified microsphere method with one-point sampling, which was the same as the second method except that a later SPECT image (30-min postinjection) with correction was used and (d) a table look-up method based on a two-compartment model with one-point arterial blood sampling and two SPECT scans obtained 40- and 180-min postinjection. The accuracy of these methods was validated by comparing the rCBF values with those obtained by nonlinear least squares fitting analysis based on the two-compartment model in 15 subjects. RESULTS: Regional cerebral blood flow values obtained by the first method correlated most closely with those obtained by nonlinear least squares fitting analysis (error, 6.8%). The second method estimated rCBF with a mean error of 10.4%. The third method estimated rCBF with a mean error of 13.1%, even though it tended to slightly overestimate rCBF. The fourth method was inclined to underestimate rCBF with a mean error of 17.1%, and it greatly overestimated regional distribution volume. CONCLUSION: The first method was the most accurate and reliable. For less invasiveness, the first method should be combined with one-point sampling instead of continuous withdrawal, which was used in the second method. When using a delayed SPECT image with a conventional SPECT scanner, the third method was considered to be superior to the fourth method.     

99Tcm-DMSA as a dynamic imaging agent for estimating renal blood flow. A comparison with 99Tcm-DTPA

A technique for estimating fractional renal blood flow (RBF) from the early part of the 99Tcm-diethylenetriaminepentaacetate (DTPA) renogram has been described previously and its reproducibility validated in the pig model. The technique is assumed to be applicable to any recirculating gamma-emitting tracer compound. The aim of this study was to determine whether the same method could be applied to 99Tcm-dimercaptosuccinic acid (DMSA) which has been largely neglected as a dynamic imaging agent. Paired estimates of fractional RBF were obtained in Large White (n = 16) and G?ttingen miniature pigs (n = 6) in three groups: group 1, paired 99Tcm-DTPA studies; group 2, paired 99Tcm-DMSA studies; group 3, alternate 99Tcm-DTPA and 99Tcm-DMSA studies. The results showed good agreement between paired results independent of whether 99Tcm-DTPA or 99Tcm-DMSA was used, supporting the assumption that the technique is applicable to any recirculating gamma-emitting tracer compound. The demonstration that fractional RBF can be reliably estimated from the DMSA renogram means that, if required, it may be combined in a single nuclear medicine procedure with conventional static DMSA renal imaging.     

A case of meningioma with non-accumulation of 99mTc-ECD and increased accumulation of 99mTc-HMPAO in the tumor]

99mTc-ECD SPECT and 99mTc-HMPAO SPECT with or without Matas test were performed in a 62-year-old woman with meningioma in the left anterior cranial fossa. After injection of 740 MBq 99mTc-ECD or HMPAO, 64 projection images were collected with a rotating Gamma camera. Matas test was carried out by compressing the left common carotid artery for about one minute immediately after RI injection. Although 99mTc-ECD SPECT showed non-accumulation in the tumor, 99mTc-HMPAO SPECT demonstrated increased accumulation in it. This area of increased accumulation disappeared on 99mTc-HMPAO SPECT with Matas test which causes decrease in blood flow of the tumor. These findings suggest 99mTc-ECD and 99mTc-HMPAO have a different mechanisms of accumulation in the meningioma.     

Preictal SPECT in temporal lobe epilepsy: regional cerebral blood flow is increased prior to electroencephalography-seizure onset

Peri-ictal SPECT provides unique information on the dynamic changes in regional cerebral blood flow (rCBF) that occur during seizure evolution and, thus, could be useful in clarifying the poorly understood interplay of the interictal and ictal states in human focal epilepsy. The regional hyperperfusion observed on ictal SPECT is generally believed to be a consequence of electrical seizure activity. However, recent studies using invasive long-term cortical CBF monitoring have demonstrated that rCBF changes occur up to 20 min prior to ictal electroencephalography (EEG) onset. Because of apparent technical difficulties, no preictal SPECT studies have been reported so far. Therefore, we present our results on two patients with temporal lobe epilepsy in whom preictal SPECT scans were performed fortuitously under continuous video-EEG monitoring control. METHODS: Technetium-99m-hexamethyl propyleneamine oxime was injected 11 min (Patient 1) and 12 min (Patient 2) before clinical and EEG seizure onset, as documented from simultaneous video-EEG monitoring in two patients with temporal lobe epilepsy. We obtained accurate anatomical reference of CBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. RESULTS: Whereas interictal SPECT showed a hypoperfusion of the temporal lobe ipsilateral to the seizure focus, on preictal SPECT, a significant increase in rCBF in the epileptic temporal lobe could be observed. These rCBF changes were not accompanied by any significant changes of the ongoing EEG. CONCLUSION: Our study provides evidence that rCBF is increased in the epileptic temporal lobe several minutes before EEG seizure onset. Thus, rCBF changes observed on peri-ictal SPECT scan cannot be considered a mere consequence of EEG seizure activity but may rather reflect a change in neuronal activity precipitating the transition from the interictal to the ictal state.     

Quantitative assessment of cerebral blood flow by 123I-IMP SPECT: venous sampling method with hand warming in the water bath

In order to establish a noninvasive, quantitative method for measuring regional cerebral blood flow (rCBF) by N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPECT, we attempted to employ continuous venous sampling instead of arterial sampling. Forty two patients with cerebrovascular diseases were classified into two groups, with (group II: n = 35) and without (group I: n = 7) hand warming. In group II, either hand was warmed, wrapping in a hot blanket (group IIA) or immersed in a 44 degrees C water bath (group IIB). In each patient, immediately after intravenous bolus injection of 222 MBq IMP, arterial and venous blood samples were collected continuously for 5 min from the radial artery and the cubital vein, respectively. By octanol extraction, IMP was divided into the unmetabolized and metabolized fraction. The ratio of 123I-IMP radioactivity of venous blood compared to arterial blood (pass ratio, referred as %PR) was calculated in three fractions, whole blood, unmetabolized, and metabolized fraction. By using these parameters, we assessed the possibility to estimate the amount of unmetabolized IMP fraction of arterial blood, usually used as an input function, from venous samples. In group I, %PR demonstrated a considerable variation between individuals (whole IMP, 47.5 +/- 24.6% (mean +/- SD): unmetabolized IMP, 46.0 +/- 24.5%: metabolized IMP, 51.8 +/- 27.4%). In group II, especially in group IIB, both increase of %PR value and the decrease in variation (whole, 77.9 +/- 5.6%: unmetabolized, 75.7 +/- 5.7%: metabolized, 86.7 +/- 8.7%) were observed, which permitted the further calculation based on the assumption that %PR value was constant in each IMP fraction (whole blood and unmetabolized fraction).(ABSTRACT TRUNCATED AT 250 WORDS)     

Carotid arterial blood flow in the ovine fetus as a continuous measure of cerebral blood flow

Principles derived from a group of 46 ML of the mantle zone are presented: Mantle pattern of a ML and its cytological structure are mostly sufficient for positive basic diagnosis. Diffuse mantle zone ML need detection of BCL-1 and CD5 hyperexpression which are characteristic for small-cell and centrocytoid forms when compared with BCL-2 positive centrofollicular lymphomas. B monocytoid lymphomas from the parafollicular subgroup as well as plasmacytoid ML from the marginal subgroup retain faint BCL-1 positivity but lose CD5 positivity. That may results in attempt of problematic narrowing of mantle zone definition because of existence of the mixed cellularity forms of mantle zone ML. Nodular mantle zone ML are clinically recognized late and are unsensitive to treatment which is opposite to the original idea of their relative benignity. M-coding of mantle zone ML is very defective because the codes do not separate nodular (perifollicular) and diffuse variants.     

Technetium-99m hexamethylpropylene amine oxime single-photon emission tomography of regional cerebral blood flow in insulin-dependent diabetes

The experience of major paediatric trauma presenting both directly and indirectly over ten years to a Paediatric Teaching Hospital is presented. Of the 185 patients assessed and treated in the Resuscitation Room, 131 were considered to have sustained significant trauma: 99 being admitted to the Intensive Therapy Unit and 32 transferred to the regional Neurosurgical centre. Road traffic accidents were responsible for the majority of serious injuries and eight of the 11 deaths, emphasising the need for further preventative measures. There were 95 interhospital transfers amongst the 131 patients judged to have sustained significant trauma. The potential benefits of centralisation of services to manage major paediatric trauma, in terms of both a reduction in interhospital transfers and early involvement of experienced staff, are proposed.     

SPECT imaging of normal subjects with technetium-99m-HMPAO and technetium-99m-ECD

This study describes an adaptation of hydrophobic interaction chromatography (HIC) that can be used to estimate protein solubility optima. The method does not support determination of absolute, e.g. quantitative solubility, however it does provide a basis for identifying the salt concentration, pH, or additive concentrations that support the highest relative solubility. The magnitude of a given salt's effects are consistent with its ranking in the Hofmeister series. IgG in solutions of strong 'precipitating' salts exhibits a classical salting-in/salting-out curve, described by a solubility minimum at low ionic strength, increasing to a well-defined maximum, and then losing solubility with further elevation of salt concentration. The direct effect of pH on protein solubility, as well as its indirect effect via modification of the ionic equilibria of dissolved salts, can also be tracked. Cooperative effects of solubility modifiers such as amino acids can likewise be assessed. The technique can be a useful tool in the development of liquid formulations for protein pharmaceuticals.