Neglect and aphasia in the acute phase as predictors of functional outcome 7 years after ischemic stroke.

BACKGROUND AND PURPOSE: Visuospatial inattention (VSI) and language impairment (LI) are often present early after stroke and associations with an unfavorable short-term functional outcome have been reported. The purpose of this study was to investigate whether a screening of VSI and LI as indicators of cortical symptoms early after stroke could predict long-term functional outcomes. METHODS: A consecutive cohort of 375 patients with ischemic stroke was assessed for the occurrence of VSI at a median of 7 days after admission (interquartile range, 1-5 days) using the Star Cancellation Test and for LI (within the first 7 days) with the language item in the Scandinavian Stroke Scale. Seven years later, functional outcomes were assessed by the modified Rankin scale and Frenchay Activities Index in 235 survivors without recurrent stroke. Relationships between baseline predictors and functional outcome at 7 years were analyzed with bivariate correlations and multiple categorical regressions with optimal scaling. RESULTS: The regression model significantly explained variance in the modified Rankin scale (R2 = 0.435, P < 0.001) and identified VSI (P = 0.001) and neurological deficits (P < 0.001; Scandinavian Stroke Scale score without the language item) as the significant independent predictors. The model for Frenchay Activities Index was also significant (R2 = 0.269, P < 0.001) with VSI (P = 0.035) and neurological deficits (P < 0.001) as significant independent predictors. CONCLUSIONS: Visuospatial inattention at acute stroke has an independent impact on long-term functional outcomes. Early recognition may enable targeted rehabilitative interventions.

Anti-Mullerian hormone as a predictor of follicular reserve in ovarian insufficiency: special emphasis on FSH-resistant ovaries.

BACKGROUND: Anti-Müllerian hormone (AMH) is secreted by ovarian granulosa cells and its serum levels reflect ovarian follicle reserve. The main objective of this study was to test the use of AMH assay in identifying women with primary amenorrhea (PA) and existing follicles and to study follicle phase dependent AMH secretion. METHODS: Serum levels of AMH were measured in subjects with FSH-resistant ovaries (FSHRO, n= 12), primary ovarian insufficiency (POI) with PA (n= 11) or secondary amenorrhea (SA n= 20) of unknown etiology, and controls (n= 23), and in Turner syndrome (TS) [45,X (n= 18), mosaicism (n= 7), structural X chromosome abnormalities (SCA, n= 10)], and healthy controls (n= 34). RESULTS: Serum levels of AMH in women with FSHRO were comparable with those in control women (2.76 ± 2.37 versus 3.77 ± 2.36 ng/ml) and significantly higher than in women with PA (0.05 ± 0.04 ng/ml; P < 0.001) or SA of unknown origin (0.12 ± 0.20 ng/ml; P < 0.001). TS girls/women with 45,X or SCA had low serum AMH levels (0.13 ± 0.09 and 0.27 ± 0.19 ng/ml) compared with their controls (3.34 ± 2.23 ng/ml) or subjects with mosaicism (2.33 ± 2.81 ng/ml). AMH expression was detected in granulosa cells of women with FSHRO but not in any of the 45,X fetal ovarian specimens. CONCLUSIONS: A serum AMH assay could be used to identify patients with decreasing ovarian reserves and POI. Moreover, our results support the notion that AMH is secreted mainly by small non-selected follicles, since follicular granulosa cells were AMH-positive and serum AMH levels were normal/low normal in women with FSHRO, who lack follicle development beyond the small antral stage.

Somatosensory and auditory processing in opioid-exposed newborns with neonatal abstinence syndrome: a magnetoencephalographic approach.

OBJECTIVE: Opioid exposure during pregnancy is a potential risk factor for the developing central nervous system of the fetus. We studied evoked responses in buprenorphine-exposed newborns who displayed neonatal abstinence syndrome (NAS) to elucidate the possible alterations in functioning of the somatosensory and auditory systems. METHODS: We compared somatosensory (SEFs) and auditory evoked magnetic fields (AEFs), recorded with magnetoencephalography (MEG), of 11 prenatally buprenorphine-exposed newborns with those of 12 healthy newborns. Peak latencies, source strength and location of SEFs or AEFs were recorded. RESULTS: AEFs were present in all buprenorphine-exposed newborns without significant differences from those of healthy newborns. In contrast, though no group level differences in SEFs existed, at individual level the response deviated from the typical neonatal morphology in four buprenorphine-exposed newborns. CONCLUSIONS: Although buprenorphine exposure during pregnancy does not seem to cause constant deficiencies in somatosensory or auditory processing, in some newborns the typical development of somatosensory networks may be - at least transiently - disrupted.

Refined mapping of the Cohen syndrome gene by linkage disequilibrium.

The Cohen syndrome is a rare autosomal recessively inherited disorder. Contrary to many case reports published elsewhere, the phenotype is uniform in Finland including nonprogressive mental and motor retardation, typical dysmorphic features, granulocytopenia and marked ophthalmological changes. By linkage analysis in five Finnish multiplex nuclear families, the COH1 locus for the Cohen syndrome was recently assigned to a 10-cM region between loci D8S270 and D8S521 on the long arm of chromosome 8. Here we present results of linkage disequilibrium and haplotype analysis in an extended panel of 16 Finnish COH1 families using new markers localized in the COH1 region. By inferring historical recombinations in conserved haplotypes the COH1 gene was assigned in the region of marker loci D8S1808, D8S1762 and D8S546. Calculations of genetic distances based on linkage disequilibrium suggest that the most likely localization of COH1 is in the immediate vicinity of marker locus D8S1762. Haplotype analysis suggests the occurrence of one main COH1 mutation and possibly one or two rare ones in Finland. This information will be useful in the positional cloning of the gene.

Imaging of head and neck tumors with positron emission tomography and [11C]methionine.

PURPOSE: To evaluate the value of positron emission tomography and [11C]methionine in imaging of malignant tumors of the head and neck region. METHODS AND MATERIALS: Forty-seven tumors of the head and neck were investigated with 11C-labeled methionine and positron emission tomography before treatment. Because of the resolution limits of the positron emission tomography scanner, all tumors selected for the study were larger than 1 cm in diameter. RESULTS: Forty-two (91%) of the 46 malignant tumors were clearly visible in the positron emission tomography image (squamous cell carcinoma, n = 26; lymphoma, n = 9; adenocystic carcinoma, n = 2; lymphoepithelioma, n = 1; adenocarcinoma, n = 1; transitional cell carcinoma, n = 1; esthesioneuroblastoma, n = 1; plasmocytoma, n = 1), while three (7%) squamous cell carcinomas were visible, but less easy to detect due to physiological accumulation of the tracer in the area under observation. Only one (2%) squamous cell carcinoma could not be delineated from the positron emission tomography image, and there was no uptake of [11C]methionine in a benign pleomorphic adenoma. No correlation was found between the uptake of [11C]methionine and the histological grade in the subset of squamous cell carcinoma (n = 30). High physiological uptake of [11C]methionine was observed in the salivary glands and the bone marrow. CONCLUSIONS: Malignant head and neck tumors can be effectively imaged with positron emission tomography using [11C]methionine as the tracer.

Evaluation of response to radiotherapy in head and neck cancer by positron emission tomography and [11C]methionine.

PURPOSE: To evaluate the usefulness of positron emission tomography (PET) and L-[methyl-11C]methionine in assessing treatment response to radiotherapy in head and neck cancer. METHODS AND MATERIALS: Fifteen patients with head and neck cancer (13 with squamous cell carcinoma, 1 with adenocystic carcinoma, and 1 with paranasal plasmocytoma) underwent a PET study with [11C]-methionine both before and after preoperative radiotherapy to the total tumor dose of 61-73 Gy. Twelve primary and 12 metastatic tumor sites were within the field of view. Nineteen of the 24 tumor sites were surgically explored after radiotherapy, and the tumor standardized uptake values (SUVs) of [11C]methionine were compared with histological findings. RESULTS: All 24 malignant lesions were detectable in the pretreatment study. In all but one case, the tumor SUV decreased after radiotherapy. The median SUV of the tumor site was smaller (1.9, range, 1.3-3.1, n = 7) in cases with histologically verified complete response than in cases with persistent cancer (median 4.1, range, 2.8-7.6, n = 12, p = 0.0008). A complete histological response was verified in none of the 9 cases with a postirradiation SUV larger than the median (3.1), whereas 7 of the 10 cases with a SUV of 3.1 or smaller had complete response (p = 0.003). The preirradiation uptake of [11C]methionine in tumors did not have significant association with histological response (p = 0.45). The PET findings correlated well with follow-up data in five cases with unoperated tumor sites. The [11C]methionine uptake of the submandibular salivary glands decreased after radiotherapy (p = 0.04). CONCLUSION: PET with [11C]methionine as a tracer may be useful in assessing response to radiotherapy in head and neck cancer. High uptake of [11C]methionine in the postirradiation scan suggests the presence of persistent disease.

Uptake of carbon-11-methionine and fluorodeoxyglucose in non-Hodgkin's lymphoma: a PET study.

Uptake of L-[methyl-11C]methionine (11C-methionine) and [18F]-2-fluoro-2-deoxy-D-glucose (FDG) was studied with PET in 14 patients with non-Hodgkin's lymphomas. The low molecular weight fraction of venous plasma separated by fast gel filtration was used as the input function for 11C-methionine studies, and tracer accumulation was analyzed according to Patlak and Gjedde. The average uptake rate of 11C-methionine was 0.0775 +/- 0.0245 min-1 (s.d.) and of FDG 0.0355 +/- 0.0293 min-1, 11C-methionine uptake rate being significantly higher than that of FDG (p less than 0.01). Carbon-11-methionine accumulated strongly in all but one of the lymphomas. FDG accumulated clearly in lymphomas of high-grade malignancy, whereas two intermediate- and three low-grade malignant lymphomas had a poor uptake rate. The tumor/plasma ratio of both 11C-methionine and FDG increased faster in high and intermediate-grade lymphomas than in low-grade lymphomas, but there was considerable overlap between the histologic grades. Carbon-11-methionine seems to be preferable in detecting tumors, while FDG was superior to 11C-methionine in distinguishing the high-grade malignant lymphomas from the other grades.

Carbon-11-methionine and PET is an effective method to image head and neck cancer.

Methionine metabolism is altered in cancer, and methionine labeled with 11C has been successfully used for imaging of brain, lung, and breast cancer and lymphoma. Uptake of L-[methyl-11C]methionine (11C-methionine) in head and neck cancer of 23 patients was studied with PET. Accumulation of 11C-methionine in the tumors was assessed by two different methods: the influx constant, Ki, and the standardized uptake value (SUV). All 23 cancers accumulated 11C-methionine. The mean Ki was 0.147 +/- 0.070 min-1 and the mean SUV 8.5 +/- 3.5. There was a strong correlation between the two measures of tumor uptake (r = 0.92, p less than 0.0001). There was no correlation between the uptake of 11C-methionine and the histological grade of cancer. Head and neck cancer can thus be effectively imaged with 11C-methionine. Carbon-11-methionine PET imaging may be useful in delineating tumors for therapy planning.

Influence of the blood glucose concentration on FDG uptake in cancer--a PET study.

Radiolabeled [11F]-2-fluoro-2-deoxy-D-glucose (FDG) is a glucose analogue widely used to study tumor metabolism by means of positron emission tomography (PET). Little is known about the effect of hyperglycemia on FDG uptake and PET imaging of tumors. Five patients with head and neck cancer underwent two PET studies prior to cancer therapy, first in the fasting state and then 2-5 days later after oral glucose loading. FDG uptake was measured with standardized uptake values (SUV) and Ki values according to Patlak et al. The fasting SUVs ranged from 4.1 to 10.9 and Kis from 0.021 min-1 to 0.067 min-1, whereas after loading both the SUVs (range 2.2-5.9, p < 0.02) and Ki values (range 0.006-0.042 min-1, p < 0.05) decreased significantly, and the quality of the PET images became markedly poorer. The FDG metabolic rate (Ki x P-Gluc) remained similar in different plasma glucose concentrations in tumors, but increased clearly in muscles after loading. Therefore, patients entering PET-FDG studies should fast and their blood glucose concentration needs to be taken into account when evaluating FDG accumulation.

Imaging of uterine carcinoma by carbon-11-methionine and PET.

UNLABELLED: L-[methyl-11C]methionine ([11C]methionine) is probably one of the most useful positron-emitting tracers for metabolic imaging of human cancer. In this study, we investigated whether human uterine cancer can be imaged with [11C]methionine and PET. METHODS: Fourteen patients with primary uterine malignancy participated in the study. Eight patients had endometrial carcinoma and six had cervical carcinoma. The normal endometrium was analyzed in four additional patients with no uterine malignancy and in one patient with cervical cancer. Tracer uptake was quantitated by calculating both the standardized uptake values (SUVs) and the kinetic influx constants (Ki values) for the tracer. RESULTS: All patients with either cervical or endometrial carcinoma had increased uptake of [11C]methionine in the PET image. The mean SUV of the carcinomas was 8.4 (n = 13; s.d., 1.5) and the mean Ki was 0.15 min-1 (n = 12; s.d., 0.08 min-1), whereas the mean SUV of the normal endometrium was only 4.6 (n = 5; s.d., 0.8). Histologically poorly (Grade III) or moderately (Grade II) differentiated endometrial carcinomas accumulated more [11C]methionine than the well-differentiated (Grade I) ones (p = 0.04 for the SUVs, and p = 0.05 for the Ki values). There were also variable physiological accumulations of [11C]methionine in the pelvis. CONCLUSIONS: Uterine carcinoma accumulated [11C]methionine more than the normal endometrium. However, the physiological accumulations of [11C]methionine in the pelvis may confuse the interpreter of the PET image; thus, morphological imaging also needs to be performed as a reference to localize the tumor accurately. We conclude that human uterine carcinoma can be effectively imaged with [11C]methionine and PET.

Metabolic imaging of ovarian tumors with carbon-11-methionine: a PET study.

UNLABELLED: This study examines the potential of 11C-methionine as a PET tracer in metabolic imaging of benign and malignant ovarian tumors. METHODS: Four patients with one or two benign ovarian tumors (endometriomas or cystadenomas), two patients with a tumor of borderline malignancy and seven patients with ovarian cancer were studied with 11C-methionine and PET before laparotomy. CT or MRI were performed as a reference. Tracer uptake was quantitated by calculating tracer standardized uptake values (SUVs) and the kinetic influx constants (Ki values). RESULTS: Benign or borderline malignant tumors did not accumulate 11C-methionine, whereas all carcinomas had significant uptake. The mean SUV of the primary carcinomas was 7.0 (s.d., 2.2) and the mean Ki was 0.14 min-1 (s.d., 0.1 min-1), but the distribution of tracer uptake was highly heterogenous in four of six tumors. CONCLUSION: Ovarian cancer can be imaged with 11C-methionine and PET. This method also may be of value in the differential diagnosis between benign and malignant ovarian neoplasms. Due to physiological accumulations and methodological limitations, the value of 11C-methionine PET in the staging of ovarian cancer appears to be limited.

Comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine in head and neck cancer.

The positron emission tomography (PET) tracer 2-18F-fluoro-2-deoxy-D-glucose (FDG) is the most widely used tracer in oncology. PET tracer. Another radiotracer, L-methyl-11C-Methionine (11C-methionine), also has been used successfully for PET imaging of brain and lung tumors, non-Hodgkin's lymphoma, breast cancer and head and neck cancer. This study compared FDG and 11C-methionine as tumor-detecting agents in head and neck cancer. Prior to cancer therapy, fourteen patients underwent a PET study with FDG and one with 11C-methionine. Nineteen of 21 malignant lesions that could be evaluated were visible with both tracers. Tracer uptake was measured as standardized uptake values (SUV) and Ki values according to Patlak et al. The mean SUV in FDG studies was 7.7 +/- 4.2 and in 11C-methionine studies 7.7 +/- 2.5, whereas the Ki values in 11C-methionine studies (mean, 0.128 +/- 0.068 min-1) were always higher than in FDG studies (mean, 0.036 +/- 0.023 min-1). A good correlation was found between the SUVs (r = 0.79, p < 0.0001) and the Ki values (r = 0.82, p < 0.001) between the two tracers. Both FDG and 11C-methionine are effective in PET imaging of head and neck cancer, and the uptake rates of the tracers seem to be closely related.

Cohen syndrome: essential features, natural history, and heterogeneity.

This article elucidates the clinical picture in Cohen syndrome (MIM 216550), an autosomal recessive disorder that is overrepresented in Finland. The diagnosis is based on the typical clinical picture: nonprogressive psychomotor retardation, motor clumsiness and microcephaly, typical facial features, childhood hypotonia and hyperextensibility of the joints, ophthalmologic findings of retinochoroidal dystrophy and myopia in patients over 5 years of age, and granulocytopenia. In a nationwide study, 29 Finnish patients were investigated. Magnetic resonance images of the brain with quantitative structure analyses revealed a relatively enlarged corpus callosum (CC). The youngest patients had normal EEGs, while all others had low-voltage EEGs. Of the patients, 22% had profound, 61% severe, 6% moderate, and 11% mild retardation. In an adaptive behavior scale (AAMD), patients had high scores in the positive domains (self-direction, responsibility, and socialization), whereas maladaptive behavior was almost lacking. Only the youngest patients had unimpaired visual function. Vision started to deteriorate early but slowly. Progressive myopia and retinochoroidal dystrophy were found in all of the patients over 5 years of age. All of the patients had isolated granulocytopenia. The heart anatomy was normal. However, decreased left ventricular function with advancing age was found. No significant endocrine abnormalities were discovered. Fingers were slender but short, with a typical metacarpophalangeal pattern profile. The manifestations vary at different ages. The Finnish Cohen patients are clinically highly homogeneous, their disease gene being located on chromosome 8. Heterogeneity probably exists among other patients claimed to have Cohen syndrome.

The MMN amplitude increases in hypnosis: a case study.

The neural mechanisms associated with hypnosis were investigated in a single highly hypnotizable subject by measuring the mismatch negativity (MMN) component of auditory ERP, reflecting the preattentive discrimination of change in stimulus flow, in normal baseline state and under hypnosis. It has been proposed that the frontal inhibition associated with hypnosis can be measured as a decrease in MMN. ERPs were elicited using the passive oddball paradigm with standard and deviant sine tone stimuli of 500 and 553Hz, respectively. The measurement was repeated in five separate sessions. In hypnosis the MMN was significantly larger compared to baseline. The results indicate that hypnosis can give rise to altered information processing in the brain even at a relatively early, i.e. preattentive level and that the larger MMN measured under hypnosis does not support frontal inhibition theory.

A new triphenylethylene compound, Fc-1157a. II. Antitumor effects.

The antitumor effects of a new antiestrogen, Fc-1157a have been studied in vitro and in vivo. In vitro the effect of Fc-1157a was comparable to that of tamoxifen. The effect was dose-dependent, and at concentrations higher than 10(-6) mol/1 Fc-1157a induced real cell death of the MCF-7 cells. In DMBA-induced mammary cancer in rats Fc-1157a decreased the number of new tumors and inhibited the growth of existing tumors, these effects being statistically highly significant. The ratio of growing tumors to stable and regressing tumors was significantly decreased. Although these effects were slightly stronger with Fc-1157a than with tamoxifen, the difference between these two compounds was not statistically significant. Murine uterine sarcoma, an estrogen receptor-negative tumor, was resistant to tamoxifen, but was statistically significantly inhibited by high doses (100 and 200 mg/kg-1 day-1 for 5 days) of Fc-1157a. The antitumor effects of Fc-1157a are due mainly to the antiestrogenic activity. At high concentrations in vitro and at high doses in vivo Fc-1157a exerts antitumor effects some of which are different from those of tamoxifen and are directed even against estrogen receptor-negative tumors. The exact mechanism of the observed cytolytic effect at high doses is unknown.

A new triphenylethylene compound, Fc-1157a. I. Hormonal effects.

The basic pharmacological and biochemical properties of a new antiestrogen, Fc-1157a, are described. Fc-1157a is bound specifically and with high affinity to estrogen receptors. The binding is competitive with estradiol. Fc-1157a treatment induces translocation of estrogen receptors from cytoplasm to nucleus. The turnover rate of nuclear estrogen receptors is markedly lower than with estradiol, but is more rapid than after tamoxifen. Fc-1157a is an almost pure antiestrogen in rat uterus, but has intrinsic estrogenic activity in mouse uterus. In animal experiments Fc-1157a has shown antitumor properties, which are described in the companion paper.

Effects of dietary supplementation with sea buckthorn (Hippophaë rhamnoides) seed and pulp oils on atopic dermatitis.

A placebo-controlled, double-blind study was conducted to investigate the effects of seed and pulp oils of sea buckthorn (Hipphophae rhamnoides) on atopic dermatitis. Linoleic (34%), alpha-linolenic (25%), and oleic (19%) acids were the major fatty acids in the seed oil, whereas palmitic (33%), oleic (26%), and palmitoleic (25%) acids were the major fatty acids in the pulp oil. The study group included 49 atopic dermatitis patients who took 5 g (10 capsules) of seed oil, pulp oil, or paraffin oil daily for 4 months. During follow-up dermatitis improved significantly in the pulp oil (P < 0.01) and paraffin oil (P < 0.001) groups, but improvement in the seed oil group was not significant (P = 0.11). Supplementation of seed oil increased the proportion of alpha-linolenic acid in plasma neutral lipids (P < 0.01), and increases of linoleic, alpha-linolenic, and eicosapentaenoic acids in plasma phospholipids were close to significant (0.05 < P < 0.1). Pulp oil treatment increased the proportion of palmitoleic acid (P < 0.05) and lowered the percentage of pentadecanoic acid (P < 0.01) in both plasma phospholipids and neutral lipids. In the seed oil group, after 1 month of supplementation, positive correlations were found between symptom improvement and the increase in proportions of alpha-linolenic acid in plasma phospholipids (Rs = 0.84; P = 0.001) and neutral lipids (Rs = 0.68; P = 0.02). No changes in the levels of triacylglycerols, serum total, or specific immunoglobulin E were detected. In the pulp oil group, a significant (P < 0.05) increase in the level of high density lipoprotein cholesterol, from 1.38 to 1.53 mmol/L was observed.

Periodontal findings in Cohen syndrome with chronic neutropenia.

Radiographic periodontal status and microbiological findings of periodontal pockets in subjects with Cohen syndrome are presented in this report. This hereditary disorder causes mental retardation, and neutropenia is one feature of the syndrome. Fifteen patients with Cohen syndrome and 15 controls matched for age and sex and, as far as possible, according to the degree of mental retardation were examined. Alveolar bone loss was evaluated from the panoramic radiographs. Two subgingival samples were obtained from the most affected anterior and posterior periodontal sites in each dentate subject and examined for the occurrence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia/nigrescens, Peptostreptococcus micros, Bacteroides forsythus, and Campylobacter rectus. Subjects with Cohen syndrome had alveolar bone loss more frequently and the bone loss was more extensive (Mann-Whitney U-test: P < 0.05) than in the controls. They also harbored one or several of the putative periodontal pathogens (Mann-Whitney U-test: P < 0.001) more often than the controls. We conclude that subjects with Cohen syndrome have increased susceptibility to early periodontal breakdown which is likely to be associated with neutropenia.

Finnish norms for the Harvard Group Scale of Hypnotic Susceptibility, Form A.

Finnish norms of the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A) are presented. The aggregate sample of 285 subjects consisted of 3 groups (n = 129, n = 116, and n = 40) that were tested during 1996 and 1997. Comparisons are made with the original normative American sample, an Australian sample, and 3 translated adaptations of HGSHS:A in Danish, German, and Spanish. In the Finnish sample, Items 2 (eye closure), 11 (posthypnotic suggestion), and 12 (amnesia) received high passing percentage in comparison with the reference data, but generally the Finnish normative data were congruent with these index studies.

Anterior brain functions and hypnosis: a test of the frontal hypothesis.

Neuropsychological frontal lobe tests were used to compare individuals with high (n = 8) and low (n = 9) hypnotizability during both baseline and hypnosis conditions. Subjects were assessed on two hypnotic susceptibility scales and a test battery that included the Stroop test, word fluency to letter- and semantic-designated categories, tests of simple reaction time and choice reaction time, a vigilance task, and a questionnaire of 40 self-descriptive statements of focused attention. Effects for hypnotic susceptibility and hypnosis/control conditions were scant across the dependent variables. High hypnotizables scored higher on the questionnaire at baseline, and their performance on the word-fluency task during hypnosis was reduced to a greater extent than lows. Findings indicate that although the frontal area may play an important role regarding hypnotic response, the mechanisms seem to be much more complex than mere general inhibition.