Posterior cortical brain dysfunction in cognitively impaired patients with Parkinson's disease--a rCBF scintigraphy study.

OBJECTIVES: The aim of the study was to visualize cortical function in Parkinson's patients with various degrees of cognitive impairment. MATERIALS AND METHODS: Thirty-seven patients with Parkinson's disease and three with Parkinson plus syndromes underwent cognitive assessment and rCBF using (99m)TC-HMPAO-SPECT. RESULTS: Almost no regional reductions in cerebral blood flow were seen in patients without cognitive impairment (n = 16). Limited, mainly posterior, blood flow reductions were seen in patients with mild cognitive impairment (n = 14), whereas the reductions were extensive and bilaterally symmetric, involving both anterior and posterior brain regions in patients with dementia (n = 10). CONCLUSIONS: The findings suggest a widespread cortical, mainly posterior type of dysfunction and a relationship between the degree of cognitive impairment and the magnitude of the dysfunction.

Short-term memory dysfunction in Kleine-Levin syndrome.

BACKGROUND: A previous investigation at our department of a young man with typical Kleine-Levin syndrome revealed short-term memory dysfunction as well as hypoperfusion of the temporal lobes on single photon emission tomography (SPECT) (CERETEC) examination, 6 and 7 years after recovery, suggesting long lasting or even permanent cerebral dysfunction. PATIENTS AND METHODS: We investigated four cases with classical adolescent Kleine-Levin syndrome characterized by hypersomnia and typical associated symptoms. We used neuropsychological testing and SPECT (CERETEC) of the brain. The results from the previous report related to above is included. RESULTS: Examination with SPECT (CERETEC) during remission revealed hypoperfusion of the temporal lobes and fronto-temporal region in two of four cases. There were normal findings in two. Neuropsychological testing performed during remission showed reduction in the short-term memory capacity in all four cases. CONCLUSION: It is striking that all the cases investigated showed short-term memory dysfunction. One patient who had recovered from paroxysmal symptoms (hypersomnia attacks and bulimia) 6 years earlier showed progress in the short-term memory dysfunction. A pathologic condition in the temporal lobes may be suspected in Kleine-Levin syndrome.

A case of Kleine-Levin syndrome examined with SPECT and neuropsychological testing.

A case of Kleine-Levin syndrome with typical periodic hypersomnia and bulimia was diagnosed. On examination with single photo emission tomography (SPECT) (CERETEC) during a relapse period and 2 weeks later there was marked cortical hypoperfusion of the frontal and temporal lobes, especially on the left side as well as in the right parietal lobe. Neuropsychological testing performed 1 week after a relapse showed a reduction in encoding to memory function of verbal learning indicating neocortical damage of the left fronto-temporal region. A follow-up 2 months later after the patient had spontaneously recovered showed only a slight left fronto-temporal disturbance. CT and MRI of the brain were normal although the MRI showed a large and asymmetric mamillary body. Neuropsychological testing 6 years after recovery showed pronounced reduction in short-time verbal and visual memory. Seven years after recovery SPECT demonstrated a normalized frontal perfusion but still a slight hypoperfusion in the left temporal lobe. Our results correlate to autopsy findings in two cases described previously.

Neuronal storage of histamine in the brain and tele-methylimidazoleacetic acid excretion in portocaval shunted rats.

Rats with portocaval anastomosis (PCA), an animal model of hepatic encephalopathy (HE), have very high brain histamine concentrations. Our previous studies based on a biochemical approach indicated histamine accumulation in the neuronal compartment. In this study, immunohistochemical evidence is presented which further supports the amine localization in histaminergic neurons. These neurons become pathological in appearance with cisternae frequently seen along histaminergic fibres in many brain areas, including the hypothalamus, amygdala, substantia nigra and cerebral cortex. Such formations were not observed in sham-operated animals. The neuronal deposition is predominant, and unique for histamine. It serves as a mechanism to counterbalance excessive brain neurotransmitter formation evoked by PCA. However, there are other mechanisms. The data provided here show that there is also a significant increase in histamine catabolism in the shunted rats, as reflected by both the higher brain N-tele-methylhistamine (t-MeHA) concentration and urinary excretion of N-tele-methylimidazoleacetic acid (t-MelmAA), a major brain histamine end product. The stomach, in addition to the brain, is a site of enhanced histamine synthesis in portocavally shunted subjects. After gastrectomy or food deprivation to eliminate the contribution of the stomach, shunted rats excrete significantly more t-MelmAA, implying the role of the CNS. This last finding suggests that under strictly defined conditions, namely in parenterally fed HE patients with abnormal plasma L-histidine, the measurement of urinary t-MelmAA might provide valuable information concerning putative brain histaminergic activity.

ECT in Parkinson's disease-dopamine transporter visualised by [123I]-beta-CIT SPECT.

Parkinson's disease (PD) is characterised by a loss of dopaminergic neurones in the basal ganglia. These neurones may be visualised by single photon emission computed tomography (SPECT) with the cocaine analogue 2beta-carboxymethyl-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT), which labels the dopamine reuptake sites in the nerve terminals. In order to evaluate the possibility to predict the outcome of ECT a prospective study was performed with six PD patients in whom the [123I]beta-CIT uptake was measured before and after an electroconvulsive therapy (ECT) series. The side-to-side difference in the radiotracer uptake was found to be significantly lower in striatum located contralaterally to the part of the body with the most pronounced symptomatology. No significant change in uptake of the radioligand was seen after ECT. Patients with best uptake and thus with less advanced PD improved most after ECT. The possibility to use the [123I]beta-CIT uptake to predict the outcome of ECT treatment has to be further evaluated.

[Examination of gastric emptying with gamma camera. Clinically useful, uniform method now established]. / Undersökning av ventrikeltömning med gammakamera. Kliniskt användbar, enhetlig metod nu fastställd.

Although more than 30 years have passed since the introduction of scintigraphic testing of gastric emptying there has been no well-defined standard. Eight Swedish hospitals have established a nationally standardized method for scintigraphic testing of gastric emptying of solids. 160 healthy subjects participated. The meal consisted of a 99mTc-labeled omelet (1300 kJ) and 150 ml unlabeled soft drink (290 kJ). There were no differences in calculated variables between the centers. Premenopausal women showed slower emptying than postmenopausals and men of any age, making separate reference values for younger women necessary.

Consensus report on quality control of quantitative measurements of renal function obtained from the renogram: International Consensus Committee from the Scientific Committee of Radionuclides in Nephrourology.

Among all the physiological indices that can be quantified using renography, measurement of renal function is the most basic. These measurements are used to make critical clinical management decisions and, as such, their reliability needs to be quality assured. This article seeks to address each aspect of the renography procedure, with particular emphasis on the effect on measurement of relative renal function. Estimation of individual kidney function is mentioned, but only briefly. A consensus approach was adopted, overseen, and directed by a chairman appointed by the Scientific Committee of the International Radionuclides in Nephro-Urology Group. The chairman selected the panel of experts from eight different countries based on their practical experience in the field. Where evidence exists to support the various recommendations it is given. Otherwise, the stated guidance represents the considered opinion of a body of experts, based on long experience and unpublished data. Some necessary compromises were made to account for the fact that renography is seldom performed solely with the purpose of measuring relative renal function. The technicalities of renography have always been a source of debate in nuclear medicine, which is reflected by the fact that a consensus could simply not be reached on a small number of issues. The structure of the report ensures that these are clearly indicated. This should serve to highlight gaps in our current knowledge, thus helping to direct future research. It is envisaged that the recommendations will be revised on a 2-year cycle to ensure that they remain up to date. An "open" process will be used to encourage participation and ownership. It is hoped that promotion of these guidelines, suitably complemented by audit processes, will raise standards in the practice of gamma camera renography.

Consensus on renal cortical scintigraphy in children with urinary tract infection. Scientific Committee of Radionuclides in Nephrourology.

A questionnaire related to cortical scintigraphy in children with urinary tract infection was submitted to 30 experts. A wide consensus was reached on several issues related to planar images: 99mTc dimercapto succinic acid (DMSA) appears as the most appropriate tracer for renal imaging; dynamic tracers are considered to be inferior, in particular 99mTc diethylenetriaminepentaacetate, which is not recommended. The general opinion is that DMSA scintigraphy is not feasible with a minimal dose below 15 MBq, whereas the maximum dose should not be higher than 110 MBq. The dose schedule generally is based on body surface area, and sedation is only exceptionally given to children. Images are obtained 2 to 3 hours after injection, preferably with high resolution collimators; pinhole images are used by only half of the experts. Posterior and posterior oblique views are used by most of the experts, and the posterior view is acquired in supine positions. At least 200.000 kcounts or 5 minute acquisition is required for nonzoomed images. As a quality control, experts check the presence of blurred or double outlines on the DMSA images. Color images are not used and experts report on film or directly on the computer screen. As far as normal DMSA images are concerned, most experts agree on several normal variants. Hydronephrosis is not a contraindication for DMSA scintigraphy but constitutes a pitfall. Differential renal function generally is measured, but no consensus is reached whether or not background should be subtracted. Most of the experts consider 45% as the lowest normal value. A consensus is reached on some scintigraphic aspects that are likely to improve and on some others that probably represent persistent sequelae. There is a wide consensus for the systematic use of DMSA scintigraphy for detection of renal sequelae, whereas only 58% of the experts are systematically performing this examination during the acute phase of infection.

Determination of the histamine metabolite tele-methylimidazoleacetic acid and of creatinine in urine by the same HPLC system.

OBJECTIVE AND DESIGN: To develop an HPLC method with UV detection for determination of tele-methylimidazoleacetic acid (t-MelmAA) in urine of man or animals, which is reliable, simple and less expensive than existing GC/MS techniques. METHOD: The elaborated procedure enables separation of t-MelmAA from its pros-isomer (p-MelmAA) as well as from imidazoleacetic acid. As an internal standard tele-ethylimidazoleacetic acid (t-EtlmAA) is used. The acids, after being converted to their stable isopropylesters, are extracted at pH 6.0-6.5. The further separation prior to HPLC utilises a small cellulose phosphate column. The HPLC system is isocratic with a C18 column and mobile phase consisting of an aqueous solution of SDS at pH 3.5 mixed with acetonitrile (65:35). An advantage of this system is that it can be used to determine the urine creatinine concentration to express excreted t-MelmAA in mmol/mol creatinine. RESULTS AND CONCLUSIONS: The method applicability is demonstrated in repeated studies in mastocytosis patients. The broad range of excretion values, from normal up to a high level (0.9 to 30 mmol/mol creatinine), indicates that it can be satisfactorily used for evaluation of histamine turnover under various clinical conditions. The method appears to be a good alternative to GC/MS based ones.

Serum tryptase measured with B12 and G5 antibody-based immunoassays in mastocytosis patients and its relation to histamine turnover.

Serum tryptase was measured with the B12 and G5 antibody-based immunoassays in 25 adult patients with mastocytosis and in 18 controls. Twelve patients had uncomplicated cutaneous mastocytosis (urticaria pigmentosa) and 13 had urticaria pigmentosa with systemic symptoms. Tryptase levels were compared with histamine turnover estimated as urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid. Elevated B12 tryptase levels (> 20 microg/L) were found in most mastocytosis patients, including five of eight patients with only cutaneous manifestations who had a low urinary histamine metabolite excretion. This indicated a higher sensitivity for diagnosing mild mastocytosis on the basis of levels of serum tryptase as opposed to urinary methylimidazoleacetic acid. However, the serum B12 tryptase assay could not differentiate between urticaria pigmentosa patients with and without systemic disease: the measurement of histamine metabolite excretion probably reflects the mast cell burden more accurately. Serum G5 tryptase levels were generally low in both controls and mastocytosis patients.

Clinical symptoms, hormone profiles, treatment, and prognosis in patients with gastric carcinoids.

BACKGROUND: Type 1 gastric carcinoids are associated with hypergastrinaemia and chronic atrophic gastritis, type 2 occur in patients with multiple endocrine neoplasia type 1 combined with Zollinger-Ellison syndrome, and type 3 lack any relation to hypergastrinaemia. Type 1 tumours are usually benign whereas type 3 are highly malignant. AIMS: To identify possible tumour markers in patients with gastric carcinoids. PATIENTS/METHOD: Nine patients with type 1, one with type 2, and five with type 3 were evaluated with regard to symptoms, hormone profile, and prognosis. RESULTS: Plasma chromogranin A was increased in all patients but was higher (p < 0.01) in those with type 3 than those with type 1 carcinoids. All patients with type 3 carcinoids died from metastatic disease, but none of the type 1 patients died as a result of their tumours. One type 1 patient with a solitary liver metastasis received interferon alpha and octreotide treatment. Nine months later, the metastasis was no longer detectable. She is still alive eight years after diagnosis, without recurrent disease. This represents the only reported case of foregut carcinoid with an unresectable liver metastasis that seems to be have been cured by biotherapy. CONCLUSIONS: Plasma chromogranin A appears to be a valuable tumour marker for all types of gastric carcinoid. Combination therapy with interferon alpha and octreotide may be beneficial in patients with metastasising type 1 gastric carcinoids.

Studies on renal function in patients with cystinuria.

Total and separate renal functions were evaluated in 40 patients with cystinuria. The average duration of the renal stone disease was 26 years (range 1-53). The patients had been subjected to a stone-preventing regimen composed of increased fluid intake, urinary alkalinization and treatment with a sulphydryl compound, tiopronin or D-penicillamine, for an average of 11.7 years (range 1-24). Urinary cystine concentration was determined regularly to monitor the treatment. All patients were examined with gamma camera renography and an assessment of glomerular filtration rate (GFR), and early and late renographic results could be compared in 30 patients. The early renographic evaluation showed that 43% of binephric patients (13/30) had an abnormal relative renal function (RRF) before the start of the stone-preventing treatment. At the late evaluation, 50% of binephric patients (17/34) had an abnormal RRF, while 30% of all patients (12/40) had a GFR below the age-related normal range. Thirty percent of 74 evaluated kidneys (22/74) had a separate GFR below an estimated age-related normal range. At the late evaluation only 30% of the patients had functionally unaffected kidneys with both normal GFR and bilateral normal renography. There was, however, no case with terminal renal failure. The separate GFR of kidneys with a history of staghorn stones was significantly lower than for kidneys without that special type of stones, but otherwise there was no relationship between renal functional impairment and other estimates of the activity of the renal stone disease. In conclusion, impairment of renal function is common in patients with stone-forming cystinuria. Stone-preventive treatment appears to be effective in preserving renal function. The high frequency of renal functional impairment justifies close surveillance of this group of patients. By renographic examination, unilateral changes in renal function can be detected at an early stage and patients at risk for further deterioration of renal function can be identified.

Histidine decarboxylase expression and histamine metabolism in gastric oxyntic mucosa during hypergastrinemia and carcinoid tumor formation.

Histamine is an important stimulator of gastric acid secretion. In experimental animals, inhibition of acid secretion by long term histamine2 receptor blockade causes hypergastrinemia, proliferation of enterochromaffin-like (ECL) cells, and formation of histamine-producing gastric carcinoids. The aim of this study was to examine the role of gastrin in histamine synthesis and metabolism of the oxyntic mucosa of normal, hyperplastic, and carcinoid-bearing Mastomys natalensis. Administration of exogenous gastrin to normal animals increased histidine decarboxylase (HDC) messenger RNA (mRNA) expression in the oxyntic mucosa within 30 min, indicating that gastrin stimulates histamine synthesis by regulating HDC mRNA abundance. Endogenous hypergastrinemia, induced by short term histamine2 receptor blockade (loxtidine) for 3-29 days, did not induce tumors, but enhanced the expression of HDC mRNA (2- to 4-fold elevated) and histamine contents (2-fold elevated) in the oxyntic mucosa. Long term histamine2 receptor blockade (7-21 months) resulted in sustained hypergastrinemia and ECL tumor formation. Tumor-bearing animals had a 4-fold increase in HDC mRNA expression and histamine contents of the oxyntic mucosa. Urinary excretion of the histamine metabolite methyl-imidazole-acetic acid was 2-fold elevated. Tumor-bearing animals recovering from histamine2 receptor blockade were normogastrinemic and had normal levels of HDC mRNA and histamine in the oxyntic mucosa as well as normal excretion of methyl-imidazole-acetic acid. The results indicate that ECL cell carcinoids developing during hypergastrinemia are well differentiated tumors that respond to high gastrin levels with increased histamine synthesis and secretion.