Biomedical subjects
Publications and source records attributed to C Messa.
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We report four patients with progressive aphasia of the non-fluent type as the presenting clinical manifestation. The patients were included in a longitudinal study of focal progressive neuropsychological syndromes, and were periodically submitted to neuropsychological evaluations and neuroimaging studies (TC, MRI, SPET or PET). The pattern of neuropsychological impairment was in good agreement with the results of functional imaging studies, which indicated involvement of the anterior regions of the left hemisphere. The evolution of the clinical picture was extremely heterogeneous in the four patients, ranging from a relatively stable picture of transcortical motor aphasia to a severe progressive frontal lobe syndrome. Progressive non-fluent aphasia appears to be a reliable clinical marker of the localization of the pathological process; whether this is related to specific neuropathological conditions, such as Pick's disease, remains for the moment a matter of speculation.
The aim of this study was to evaluate, in 16 patients with drug-resistant partial epilepsy who were waiting to undergo surgical treatment, the relation between positron emission tomography (PET) findings with fluorine-18 fluorodeoxyglucose ([18F]FDG) in the interictal state and the different stereo-electroencephalography (SEEG) patterns that characterize: (a) the epileptogenic zone (low-voltage fast-activity discharge before or concurrent with ictal clinical symptoms), (b) the irritative zone (spikes, spikes and waves, isolated or grouped in short bursts) and (c) the lesional zone (continuous, sometimes polyrhythmic slow waves or continuous delta waves or very important voltage depression). SEEG was performed following an individually defined electrode implantation strategy. Whereas at least one area of hypometabolism was detected by visual interpretation of PET/[18F]FDG images in all the subjects in the study, there was poor agreement between PET/[18F]FDG quantitative measures of regional metabolism and SEEG findings. Normal metabolic rates were found in up to 62% of the areas with abnormal SEEG activity, independent of the type of electrical activity, i.e. epileptogenic, irritative, or lesional, while abnormal metabolic rates were found in up to 23% of the areas with normal SEEG activity. In conclusion, whereas the visual interpretation of interictal studies of glucose utilization in our series of drug-resistant epileptic patients consistently allowed the localization of an area of temporal hypometabolism, the quantitative and regional metabolic analysis demonstrated that such a finding is not specifically related to any of the three very different SEEG patterns (epileptogenic, irritative, lesional) or combinations thereof. These results complement those of previous interictal and ictal single-photon emission tomographic studies and of receptor studies in epileptics, suggesting functional and biochemical heterogeneity within the interictal hypoperfused/hypometabolic area in epileptic patients, and contribute to the debate on the use and interpretation of interictal PET/[18F]FDG studies in patients with medically refractory partial seizures.
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OBJECTIVE: To determine behavioural, dietary and other common factors associated with new cases of gallstones, diagnosed by ultrasonography, in a prospective cohort study conducted in southern Italy. SUBJECTS AND METHODS: Between May 1985 and June 1986, systematic sampling from the electoral register of Castellana, a small town in southern Italy, yielded 2472 subjects who had had their gallbladder checked for gallstones by ultrasonography. Between May 1992 and June 1993, 1962 out of the 2235 (87.7%) subjects without gallstones at baseline agreed to a further ultrasound examination. At the first survey a standardized questionnaire was administered, inquiring about medical history, diet, cigarette smoking and other behavioural characteristics. Height and weight were also measured, and blood levels of glucose, cholesterol, HDL-cholesterol and triglycerides were determined by standard methods. The same variables were measured at the second survey. The diagnosis of gallstones was made with the same echograph by echographists working in the same department. Multiple logistic regression was used to determine which factors measured at the first survey were associated with the incident cases of gallstones. RESULTS: One hundred and four subjects had developed gallstones, an incidence of 9.7 per 1000 persons per year. Age, body mass index (BMI), weight change, a history of diabetes, constipation (shown by use of laxatives), cigarette smoking, years of schooling, consumption of fried foods and excessive oil, and pregnancy in females, were positively associated with the incidence of gallstones. Consumption of wine, coffee, fish and wholemeal bread was inversely associated. Sex, family history of cholelithiasis, use of oral contraceptives and serum lipids were not independent risk factors for gallstones. CONCLUSION: The results of this study confirm many gallstone-associated factors reported in previous cross-sectional and case-control studies, as well as in other cohort studies based on the clinical diagnosis of gallstones, such as BMI, ageing and wine consumption. Furthermore, use of laxatives, considered a proxy of constipation, appears to be another important independent risk factor for gallstones.
In 10 patients with Helicobacter pylori (HP) positive chronic gastritis, gastric mucosal content of interleukin (IL)-1 beta, IL-8, Transforming Growth Factor (TGF)-beta 1, Epidermal Growth Factor (EGF) and Polyamines (putrescine, spermine and spermidine) was evaluated before and after eradicating treatment. Histologically, in all patients eradication of HP was accompanied by a marked reduction of the inflammatory infiltrate. At the same time, at the end of the therapeutical regimen, elevated levels of IL-1 beta, IL-8, TGF-beta 1, putrescine and spermidine/spermine ratio significantly dropped, while EGF mucosal content, significantly increased. Results are discussed in terms of the reciprocal role of inflammatory cytokines, growth factors and polyamines in the evolution of the HP-associated chronic gastritis.
A recent survey of the knowledge and practice of both positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) of the brain among referring physicians in Europe (neurologists and psychiatrists) showed a disquieting lack of knowledge of the potential of these methodologies in the investigation and management of patients of their own specialities. The need to bring the knowledge of the potential of these techniques to the practicing physicians is paramount. It is imperative that the methodologies and concepts that preside over the application of these techniques in neurology and psychiatry must become more uniform if an impact is to be felt at a clinical level. There is clear improvement in the instrumentation available with the new state-of-the-art tomographic devices and with the development of new technetium-based radiopharmaceuticals for the study of cerebral perfusion. The constant progress made with ligands that permit the study of neurotransmission, tumor metabolism, and turnover do expand our capability to improve the knowledge concerning neurophysiology, neuropathology, and neuropharmacology of a variety of disease states. PET and SPECT will be progressively included in protocols aimed at stratifying patients with dementia, monitoring therapeutic trials, and improving our ability to determine outcome. Clinical usefulness of PET and SPECT begin to emerge in cerebral vascular disease, in the identification of cerebral death, in epilepsy, in cerebral trauma, in the investigation of HIV-positive patients with cerebral involvement, and in the monitoring of tumor recurrence and postirradiation damage. This review article outlines a current perspective of SPECT and PET as practiced in Europe, its potential, and its limitations.
Positron emission tomography with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG) has been used to assess the pattern of cerebral metabolism in different types of epilepsies. However, PET with [18F]FDG has never been used to evaluate drug naive patients with cryptogenic temporal lobe epilepsy, in whom the mechanism of origin and diffusion of the epileptic discharge may differ from that underlying other epilepsies. In a group of patients with cryptogenic temporal lobe epilepsy, never treated with antiepileptic drugs, evidence has been found of significant interictal glucose hypermetabolism in a bilateral neural network including the temporal lobes, thalami, basal ganglia, and cingular cortices. The metabolism in these areas and frontal lateral cortex enables the correct classification of all patients with temporal lobe epilepsy and controls by discriminant function analysis. Other cortical areas--namely, frontal basal and lateral, temporal mesial, and cerebellar cortices--had bilateral increases of glucose metabolism ranging from 10 to 15% of normal controls, although lacking stringent statistical significance. This metabolic pattern could represent a pathophysiological state of hyperactivity predisposing to epileptic discharge generation or diffusion, or else a network of inhibitory circuits activated to prevent the diffusion of the epileptic discharge.
Estrogen receptors have been found in normal and neoplastic gastrointestinal mucosa. The aim of our study was to verify whether the content of cytosolic estrogen receptor in normal and neoplastic tissue has a prognostic value in patients with colorectal adenocarcinoma. Eighty consecutive patients entered the study, and their follow-up was complete because none were lost to follow-up. Estrogen receptors were evaluated by an enzymatic immunoassay. Fifty-four percent of neoplastic samples and 84% of samples from surrounding mucosa showed an estrogen receptor content higher than 1.0 fmol/mg of cytosolic proteins (cut point for positive/negative hormone receptor status). Estrogen receptor levels were lower in neoplastic tissue than surrounding mucosa (1.2 +/- 1.05 fmol/mg protein vs 2.07 +/- 1.36 fmol/mg protein, respectively, t test P = 0.001). The survival of patients with estrogen receptor expression in uninvolved surrounding mucosa was longer than that of patients without estrogen receptor in the same type of mucosa (log rank test, P < 0.01). In the neoplastic tissue, receptor status had no prognostic value (log rank, P = 0.8). After taking into account the most important potential confounders by using the Cox proportional hazard model, the estrogen receptor status in normal mucosa samples maintained an independent prognostic value. These results support an association between the estrogen receptor status in normal mucosa and survival of patients with colorectal adenocarcinoma.
Positron emission tomography (PET) with 2-deoxy-2[18F]fluoro-D-glucose (FDG) was used to study 9 children who demonstrated complete or partial agenesis of the corpus callosum (ACC) on magnetic resonance imaging (MRI). Of the 7 patients with epilepsy, FDG-PET clearly localized areas of cortical metabolic abnormality in 6 patients; in 5 of these, localization of the metabolic abnormalities on PET corresponded to electroencephalographic localization of epileptogenicity. MRI documented focal cortical abnormalities in only 2 of the 7 children with epilepsy. In 1 patient, the abnormality observed on MRI was confined to a frontal lobe, whereas the FDG-PET study revealed hypometabolism of the entire hemisphere. One patient with infantile spasms exhibited bilateral multifocal epileptiform discharges on electroencephalography, whereas both the PET and MRI revealed only left hemispheral cortical abnormalities. Another patient with infantile spasms had prominent brainstem glucose metabolic activity on FDG-PET in the absence of any MRI or PET cortical abnormality. Two children underwent surgery because of refractory seizures; the resected cortical tissue in both patients consisted of cortical microdysgenesis. Seizure control improved significantly in both patients. FDG-PET studies in the 2 highest functioning patients (i.e., only minor learning disabilities and no epilepsy) did not reveal any focal cortical hypometabolism; therefore, there appears to be an association between the presence of focal metabolic abnormalities on PET and the presence of seizures in ACC patients.(ABSTRACT TRUNCATED AT 250 WORDS)
We have studied seven patients with Spielmeyer-Vogt disease (SV), aged 11-29 years, using PET and 2-deoxy-2[18F]fluoro-D-glucose. Five patients showed a distinctive age-related progression with decreased metabolic activity starting in the calcarine area and spreading rostrally to the entire cortex, leaving normal uptake only in the basal ganglia and brainstem of the oldest patients. Calcarine hypometabolism was mild in the youngest patient. All patients, including the youngest when the study was repeated 2 years later, had significantly decreased calcarine metabolic activity (P = 0.002). Two patients had PET patterns markedly different from the five others, with significantly decreased metabolic activity in most brain areas. Both patients may represent a new SV variant. An adult pathological control with congenital amaurosis showed normal cerebral metabolic activity in all areas. Two patients had older sisters, one now deceased, the other not available for study, who presented a rapid regression associated with epilepsy. Phenytoin and carbamazepine probably caused increased seizure activity and faster regression. The younger siblings treated with phenobarbital monotherapy had few seizures and maintained motor functions 5-8 years longer compared with their respective sisters. While the clinical course made obvious that some areas, such as the macula, are damaged before others, the progression from the calcarine area to the more anterior regions (but sparing the basal ganglia) provides unexpected insights into selective vulnerability of neurons that will allow a more precise way of monitoring individual patients.
The epidermal growth factor receptor (EGFR) was investigated by an enzyme immunoassay in neoplastic tissue and surrounding mucosa from 43 patients with colorectal cancer. This study found a positivity of 86% in normal samples and a positivity of 93% in neoplastic ones. In normal tissue samples, EGFR levels were 162 +/- 129 ng Ab B/mg protein, while in colorectal neoplastic samples EGFR levels were 228 +/- 135 ng Ab B/mg protein. This difference was statistically significant (p < 0.01). There was a significant correlation between the EGFR levels in neoplastic tissue and those in surrounding mucosa (r = 0.75). In 5 of 43 patients, the EGFR was evaluated also by Western blotting with three different anti-EGFR antibodies, of which one was biotin-conjugated. The presence of a 170-kDa band was detected. Moreover, by using the anti-EGFR mAb biotin conjugate a 90-kDa band was also detected.
We evaluated polyamine (putrescine, spermidine, and spermine) levels, estrogen receptor concentrations, and their relationship in neoplastic tissue and surrounding mucosa from 30 patients with gastric adenocarcinoma. Cytosolic estrogen receptors were measured with an immunoenzymatic assay. Polyamine levels were evaluated with high-performance liquid chromatography. Estrogen receptor concentrations were statistically higher in surrounding mucosa than in neoplastic tissue (p = 0.023). Putrescine and spermidine levels and the spermidine to spermine ratio were statistically higher in neoplastic tissue than in surrounding mucosa (p < 0.004). Significant correlations were found between the levels of spermidine and total polyamines in neoplastic tissue and surrounding mucosa (r = 0.48, p = 0.014, and r = 0.45, p = 0.021, respectively). Polyamine levels were lower in estrogen-receptor-positive tumors than in estrogen-receptor-negative ones, although this decrease was statistically significant only in the case of spermine (p = 0.02). The significance of these findings is that the cellular activity of normal and neoplastic gastric mucosa may be partly controlled by estrogens.
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UNLABELLED: The liver plays an important role in glucose homeostasis. PET studies with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) of the liver (e.g., in neoplasms) require an understanding of the effects of dietary conditions on hepatic FDG uptake. METHODS: Twenty studies were performed on 10 normal volunteers (ages 24 +/- 4) after fasting 4 to 19 hr and again after oral consumption of 100 g of dextrose to investigate tracer kinetic model configurations of FDG in the normal liver and to evaluate the impact of oral glucose on liver in normal subjects. Dynamic PET images were acquired for about 1 hr using a Siemens/CTI 931 tomograph. RESULTS: A three-compartment model with an input function delay time parameter was the statistically preferred model configuration. The model estimated transport rate constant from plasma to liver, K1, increased significantly (p < 0.05) from 0.864 +/- 0.136 ml/min/g in fasting studies to 1.058 +/- 0.269 ml/min/g in postglucose studies. Glucose loading also significantly increased (p < 0.01) the rate constant for FDG phosphorylation, k3, from 0.005 +/- 0.003 min-1 in fasting studies to 0.013 +/- 0.007 min-1 in postglucose administration and, consequently, significantly increased both the phosphorylation fraction (k3/(k2 + k3)) and the influx constant (K1k3/(k2 + k3)). No significant differences in the liver-to-plasma transport rate constant, k2, dephosphorylation constant, k4, or distribution volume of FDG (K1/(k2 + k3)) were observed. CONCLUSION: Dynamic FDG-PET studies can be used to evaluate kinetics of liver glucose metabolism. The results indicate that dietary conditions have a significant effect on hepatic FDG kinetics. Because of the higher net FDG uptake by normal liver after glucose loading, fasting conditions are preferred for FDG liver tumor studies to increase the tumor-to-background contrast.
UNLABELLED: SPECT studies of regional cerebral perfusion with a high-resolution system were compared to PET studies of regional cerebral glucose utilization (rCMRglc) in 21 patients with probable Alzheimer's disease (AD). Ten normal subjects were also evaluated with SPECT and 10 with PET. METHODS: rCMRglc (for PET) and counts (for SPECT) in the associative cortices were normalized to the average rCMRglc, and counts in the calcarine cortex and basal ganglia were considered as a "reference area" to obtain a ratio. The ratio differences between patients and controls were tested with ANOVA performed separately for PET and SPECT. RESULTS: The difference between probable AD patients and controls was significant for both PET (p < 0.00001) and SPECT (p < 0.005); this difference was significant for the frontal, temporal and parietal cortices (p < 0.0001) for PET, and for the temporal (p < 0.005) and parietal (p < 0.001) cortices for SPECT. Temporo-parietal defects were detected in all subjects with PET and in 90% with SPECT. CONCLUSION: PET and SPECT are able to detect characteristic temporo-parietal abnormalities in probable AD. However, the presence of abnormalities in other associative areas is better evaluated with PET.
This study examined the presurgical 2-deoxy-2[18F]-fluoro-D-glucose positron emission tomography (PET) patterns of regional cerebral glucose metabolism in the non-resected hemisphere of 13 children who underwent hemispherectomy for early-onset intractable seizures. These patterns were compared with the rate of change in the children's non-verbal communication scores, measured before and after surgery. Irrespective of the side of surgery, the pre-operative glucose metabolism in the non-resected prefrontal cortex correlated significantly with the postoperative rate of change in the children's ability to focus the attention of an adult on an object or event (joint attention). These preliminary findings suggest that pre-operative PET patterns might be associated with certain aspects of the developmental outcome of children undergoing hemispherectomy.
The pattern of regional cerebral blood flow was assessed by single photon emission tomography and (99mTc)HM-PAO in 28 patients with clinical diagnosis of non-refractory cryptogenic temporal lobe epilepsy on chronic treatment with carbamazepine. Each patient underwent a magnetic resonance imaging study of the brain. An EEG was performed concurrently with the assessment of cerebral blood flow. Areas of focal hypoperfusion were observed in 8/28 patients, and a concurrent EEG focus was identified in 10/28 patients. Areas of hypoperfusion and the EEG foci were consistent in 6 of the 10 patients with EEG abnormalities; in 2 patients hypoperfusion and the EEG abnormalities were on opposite sides, though in homologous areas; in 2 patients the perfusion pattern was normal in spite of the EEG abnormalities. The number of clinical seizures and EEG abnormalities was higher for the patients presenting with cerebral hypoperfusion than for those with normal perfusion. It is concluded that the evaluation of cerebral blood flow may provide useful information for both diagnostic and prognostic assessment of these patients.