Medium term (> 12 months) outcomes after laparoscopic hiatal hernia repair without conventional fundoplication using PH4B-mesh implant (Phasix™) in 176 reflux patients: experience and technique.

BACKGROUND: Hiatal mesh repair remains a controversial topic among anti-reflux surgeons. Biosynthetic mesh cruroplasty may prevent early recurrence while avoiding late esophageal erosion and strictures associated with non-resorbable materials. So far, medium-term results on hiatal PH4B (Poly-4-Hydroxybutyrate) mesh repair from high-volume centers are lacking. METHODS: We analyzed the medium-term efficacy and safety of PH4B mesh cruroplasty in 176 consecutive patients (≥ 18 years) with symptomatic hiatal hernias. Treatment failure was defined as the clinical recurrence of reflux symptoms. Patients could choose between mesh augmented hiatal repair (combined with a modified anterior hemifundoplication and fundophrenicopexy), Nissen fundoplication, and magnetic sphincter augmentation at their discretion. We also describe the surgical approach to mesh augmented hiatal repair used at our center. RESULTS: On average, patients were 55 (± 14) years old and followed up for 22 (± 7; sum: 3931) months. Treatment failed in 6/176 (3%, 95% CI: 2-7%) patients. The 24-month Kaplan-Meier failure estimate was 2.8% (95% CI: 0.4-5%). Each centimeter in hernia size increased the risk of failure by 52% (p = 0.02). Heavier patients (BMI > 27) had an 11% higher probability of clinical symptom recurrence (p = 0.03). The dysphagia and bloating/gas rate were 13/176 (7%), each. 8 (5%) patients required endoscopy due to dysphagia but without intervention. No serious complications, including mesh infection and erosion, or fatalities, occurred. CONCLUSION: Augmented PH4B mesh cruroplasty without conventional fundoplication shows excellent intermediate-term results in patients with reflux disease due to hiatal hernia. Around one in thirty patients experience treatment failure within 2 years of surgery. Hernia size and overweight are key determinants of treatment failure.

Impaired heart rate variability in cervical dystonia is associated to depression.

Causes of cardiovascular autonomic dysfunction in cervical dystonia (CD) are poorly understood. Studies examining effects of botulinum neurotoxin (BoNT) therapy on heart rate variability (HRV) yielded contradictory results. There is compelling evidence that depression shifts autonomic balance towards sympathetic predominance. As depression is the most frequent non-motor symptom in CD, we sought to determine if it is associated to dysfunction of cardiovascular autonomic regulation. Standardized interviews, clinical examinations, self-rating forms, autonomic symptom questionnaire, and automated autonomic testing in outpatients with idiopathic CD were used. Cardiovascular autonomic screening encompassed five different analyses of HRV, and testing of orthostasis. 85 CD patients participated in the study. 21% of them had HRV impairment, 14% orthostatic hypotension. 30% of CD patients had symptoms of depression. In those, decreased HRV was more frequent than in CD patients without mood disturbance (40 vs. 13%; p = 0.008). CD patients with and without depression had no other significant differences, including demographics, dystonia severity, comorbidity, medication, or BoNT therapy. Cardiovascular autonomic imbalance with sympathetic predominance is a non-motor manifestation of CD, associated to depression. Impaired HRV is a cardiovascular risk factor, moreover, emphasizing the need to identify and treat depression in dystonia.

Association of CETP polymorphisms with the risk of vascular dementia and white matter lesions.

Cholesteryl ester transfer protein (CETP), a component of the high density lipoprotein (HDL), plays a central role in reverse cholesterol transport. We investigated the association of two putative functional CETP polymorphisms (C-629A and I405V) with the risk of vascular dementia (VD) and tested if this association is influenced by the presence of APOE4 allele. Our study included 163 VD patients (mean age: 74.25 +/- 7.9 years) and 452 cognitively healthy probands (mean age: 70.81 +/- 7.9 years). As a biological correlate, the association of CETP gene variants with white matter lesion (WML) load was investigated. Neither the C-629A (P = 0.169) nor the I405V (P = 0.840) polymorphism was associated with VD risk in the whole sample. However, in non-carriers of the APOE4 allele, homozygote carriers of the CETP C-629A A allele presented with an increased risk of VD (P = 0.01). Whereas in APOE4 carriers, no association of CETP polymorphisms with VD risk was detected. In addition, carriers of the CETP C-629A AA genotype presented with decreased WML load in the frontal brain (P = 0.009). Our results suggest that CETP gene polymorphisms might influence WML load and the risk of VD, the latter in non-carriers of the APOE4 allele.

Gene variations in GSTM3 are a risk factor for Alzheimer's disease.

Oxidative stress is a relevant pathomechanism in Alzheimer's disease (AD) and gene variations in the glutathione S-transferase M3 gene (GSTM3), involved in the detoxification of oxygen radicals, might influence the risk of AD. We investigated the effect of three polymorphisms in GSTM3: rs1332018 (C/A); rs1799735 (del/AGG); rs7483 (G/A), on the risk of AD in 363 AD patients and 358 healthy controls. Single marker association analyses revealed that the AGG/AGG genotype of the GSTM3 rs1799735 (del/AGG) polymorphism was associated with an increased risk of AD (p=0.05), especially in the group of APOE4-allele non-carriers (p=0.004; OR=2.07). Examination of the haplotypes identified a two-marker haplotype (C/AGG) consisting of rs1332018 (C/A) and rs1799735 (del/AGG) to increase the risk of AD (p=0.029), this effect was also most prevalent in APOE4-allele non-carriers (p=0.009; OR=1.95). The population attributable risk of this haplotype in APOE4-allele non-carriers was 32.2%. Our results suggest that there is a group of AD patients in which variations in metabolism of oxidative stress play an important role.

Brain imaging and neuropsychology in late-onset dementia due to a novel mutation (R93C) of valosin-containing protein.

Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD, MIM 167320) is a recently identified autosomal dominant disorder due to mutations in the valosin-containing protein (VCP) that affects muscle, bone and brain. Brain involvement and neuropsychological findings of IBMPFD have not been described in detail. A patient carried a novel heterozygous base pair change, 47832C>T, in the VCP gene that resulted in substitution of an arginine residue by cysteine at position 93 (R93C). He presented first with myopathy while bone involvement remained subclinical. The patient developed behavioral abnormalities in his 60s and showed frank personality change with fluent empty speech at the age of 74 years. This syndrome was best classified as semantic dementia. Magnetic resonance imaging disclosed slight but progressive cerebral atrophy with prominent callosal and frontal white matter loss. Positron emission tomography demonstrated glucose hypometabolism of the frontal and temporal lobes disproportionate to their structural involvement. This first comprehensive clinical and neuroimaging study in IBMPFD may raise the awareness among clinicians as well as basic scientists for this exemplary genetic model of dementia.

White matter lesions - age-adjusted values for cognitively healthy and demented subjects.

OBJECTIVES: To develop age-adjusted norms for white matter lesions (WML) and to differentiate dementia from mild cognitive impairment and normal aging. MATERIALS AND METHODS: 240 patients underwent a comprehensive clinical, neuropsychological and MRI examination. A scale was developed quantify WML in anatomically defined regions by rating size and frequency. FLAIR sequences were used to determine a global and a frontal score. The scores were correlated with the psychometric test results and the final clinical diagnosis: cognitively normal (CN), mild cognitive impairment (MCI), Alzheimer's Disease (AD), vascular dementia (VD). Age-adjusted curves for WML scores were calculated by means of a non-parametic smoothing method. RESULTS: WML scores of the whole cerebrum and the frontal lobe were significantly increased in vascular dementia as compared to CN, MCI and AD. Individual WML scores correlated significantly with age and neuropsychological test results. For the age range 55-72, the WML scores of VD were significantly different from those of CN, MCI and AD. CONCLUSIONS: Age-corrected WML load was significantly higher in vascular dementia as compared to MCI, AD and cognitively normals over a wide age range.

[Management of incidental findings in neuroimaging in diagnosis and pathophysiological research]. / Management inzidenter Befunde in der bildgebenden Diagnostik und Forschung.

Structural, quantitative and functional neuroimaging has contributed greatly to the advancement in clinical diagnosis and research into pathophysiology of psychiatric disorders. In diagnostic investigations, the frequency of "incidental" findings, i. e. potentially pathological findings, which are unexpected with regards to the primary diagnostic question and which cannot be related to the presenting clinical symptomatology, amounts up to 30 %. Approximately 2 - 5 % of these unexpected findings have immediate clinical consequences. The analysis of incidental findings in the context of clinical diagnostic procedures allows to extrapolate on their prevalence in experimental studies, because here, such findings are not systematically documented. Several medical, ethical and legal problems arise related to the detection, evaluation and documentation of incidental findings in clinical experimental studies. These problems and resulting obligations will be discussed and solutions with respect to the management of incident findings will be proposed.

The clinical utility of structural neuroimaging with MRI for diagnosis and differential diagnosis of dementia: a memory clinic study.

OBJECTIVES: The individual contribution to the final comprehensive clinical diagnosis of neuropsychology (NP) and magnetic resonance imaging (MRI), respectively, was quantified in a specialized tertiary care setting to investigate the added clinical value of routine MRI. METHODS: In 106 patients referred to a university memory clinic for the work-up of cognitive disturbances the primary care diagnosis, the initial clinical neuropsychiatric diagnosis, the neuropsychological and MRI diagnoses, and the final comprehensive clinical diagnosis were documented. The neuropsychological investigation was performed using the CERAD test battery. MRI was performed using T1, double echo and FLAIR sequences without contrast medium. The change of the final comprehensive clinical diagnosis in relation to the initial neuropsychiatric diagnosis was used to determine the diagnostic contribution of both, MRI and NP. RESULTS: NP and MRI led to a significant change of the final comprehensive diagnosis in 26% of patients (CI: 0.26 +/- 0.09; p < 0.05). In addition, three cases of secondary dementias, and six cases of vascular encephalopathy without dementia were recognized by MRI. Sensitivity, specificity, and the positive predictive value were higher for NP and MRI, respectively, than for the initial clinical diagnosis alone. CONCLUSION: MRI as well as neuropsychological testing improves early detection and differential diagnosis of dementia and additionally supplies clinically relevant findings. MRI carries added clinical value in the investigation of dementias.

[Alzheimer's disease versus vascular dementia -- dichotomy or interaction?]. / Alzheimer Demenz versus vaskuläre Demenz -- Dichotomie oder Interaktion?

Alzheimer's dementia (AD) and vascular dementia (VD) are the two major forms of dementia in the elderly. They have been separated categorically on the basis of pathophysiological findings and clinical operationalized criteria. However, this strict separation has to be reevaluated in the light of recent data. The risk to develop a neurodegenerative dementia in old age is determined by various susceptibility genes and correlated with aging. In AD, the current understanding of pathophysiology focuses on the amyloid cascade hypothesis as the major endpoint of the complex cellular pathology. In VD, incomplete microangiopathic infarcts due to fibrohyalinosis are regarded as the major pathophysiological event. A controversial discussion exists about the coincidence or interaction of genetically determined risk factors of AD and/or VD. Further interactions between AD and VD exist with regard to perivascular mediators and those factors which impair cerebral blood flow. Based on these and other recent neuropathological and therapeutic findings the hypothesis is proposed that the two specific etiopathologies of AD and VD interact to precipitate clinical dementia in the individual and that the individual phenomenology of these dementias is modified by vascular risk factors. Neither, a categorical separation of AD and VD nor the recent idea to regard AD as a distinct form of vascular dementia, do appear convincing.

[Quantification of microangiopathic lesions in brain parenchyma and age-adjusted mean scores for the diagnostic separation of normal from pathological values in senile dementia]. / Quantifizierung mikroangiopathischer Hirnparenchymläsionen zur Abgrenzung altersnormaler gegenüber pathologischer Ausprägung bei Altersdemenzen.

PURPOSE: To quantify microangiopathic lesions in the cerebral white matter and to develop age-corrected cut-off values for separating normal from dementia-related pathological lesions. MATERIALS AND METHODS: In a memory clinic, 338 patients were investigated neuropsychiatrically by a psychological test battery and by MRI. Using a FLAIR sequence and a newly developed rating scale, white matter lesions (WMLs) were quantified with respect to localization, number and intensity, and these ratings were condensed into a score. The WML scores were correlated with the mini-mental state examination (MMSE) and clinical dementia rating (CDR) score in dementia patients. A non-linear smoothing procedure was used to calculate age-related mean values and confidence intervals, separate for cognitively intact subjects and dementia patients. RESULTS: The WML scores correlated highly significantly with age in cognitively intact subjects and with psychometric scores in dementia patients. Age-adjusted WML scores of cognitively intact subjects were significantly different from those of dementia patients with respect to the whole brain as well as to the frontal lobe. Mean value and confidence intervals adjusted for age significantly separated dementia patients from cognitively intact subjects over an age range of 54 through 84 years. CONCLUSION: A rating scale for the quantification of WML was validated and age-adjusted mean values with their confidence intervals for a diagnostically relevant age range were developed. This allows an easy to handle, fast and reliable diagnosis of the vascular component in senile dementia.

ACE I/D polymorphism is a risk factor of Alzheimer's disease but not of vascular dementia.

Different studies have investigated the effect of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism on the risk of Alzheimer dementia (AD). However, results on the association of the ACE-I allele with AD have been inconclusive. A recent meta-analysis reported an association of the I-allele with the risk of AD. A few small studies also investigated the effect of ACE polymorphism on the risk of vascular dementia (VD). We have investigated the effect of ACE I/D polymorphism in 351 AD and 155 VD patients and 348 healthy controls. We found the I/I genotype to be associated with an increased risk of AD, but not with the risk of VD. Cell-specific effects of ACE polymorphism are suggested, additional studies on neuronal cells might help to understand the role of this polymorphism in AD.

[Reliability of quantifying vascular white matter brain lesions -- a contribution to reproducible quantitative diagnosis]. / Reliabilität der Quantifizierung von vaskulären Läsionen der weissen Hirnsubstanz -- ein Beitrag zur replizierbaren quantitativen Diagnostik.

PURPOSE: Microangiopathic lesions of the brain tissue correlate with the clinical diagnosis of vascular subcortical dementia. The "experience-based" evaluation is insufficient. Rating scales may contribute to reproducible quantification. MATERIALS AND METHODS: In MRI studies of 10 patients, 9 neuroradiologists quantified vascular white matter lesions (WMLs) at two different points in time for 12 anatomically defined regions with respect to number, size and localization (score). For 9 observers and 10 studies, 90 intra-observer differences were obtained for each of the 12 WML scores. To calculate the inter-observer reliability, rating pairs were formed. Furthermore, 360 differences were computed for each score and rating for 12 anatomically defined WML scores, and the intraclass correlation (ICC) was calculated as a measure of agreement (reliability). RESULTS: As to the intra-observer reliability, the median of the differences was 1.5 for the entire brain as opposed to 0 for defined brain regions. The corresponding values for the inter-observer reliability were 3 and 1, respectively. The mean intra-class correlation coefficient for the 10 studies was 0.88, whereas the mean interclass correlation concerning the inter-observer reliability was 0.70, with the first and second rating being averaged. The rating of each study took about 6 minutes. CONCLUSION: The rating scale with high intra- and inter-observer reliability can dependably quantify WMLs and correlates with the clinical diagnosis of vascular dementia. Using a reliable rating scale, the diagnostic distinction of age-associated physiological vs. pathological size of the WML can make a contribution to the reproducible quantifiable diagnostic evaluation of vascular brain tissue lesions within the framework of dementia diagnostics.

Polymorphisms in glutathione S-transferase omega-1 and AD, vascular dementia, and stroke.

BACKGROUND: Glutathione S-transferase omega-1 (GSTO1) protects from oxidative stress, a risk factor for Alzheimer disease (AD), vascular dementia (VaD), and stroke. Polymorphisms in GSTO1 might influence the function of the protein and thus the risk of AD, VaD, and stroke. METHODS: The GSTO1 gene was screened for variations. The effect of the detected polymorphisms on the risk of AD, VaD, and stroke was evaluated. CSF levels of cholesterol and plasma homocysteine levels were compared according to the GSTO1 genotype. RESULTS: Two missense polymorphisms in exon 4 of GSTO1 (Ala140Asp and Glu155DeltaGlu) were detected and tested for their association with AD, VaD, and stroke. The Asp/Asp and Ala/Asp genotypes increased the risk of stroke (p = 0.003, OR = 2.1), and the Asp/Asp genotype increased the risk of VaD (p = 0.02, OR = 2.2). GSTO1 polymorphisms did not influence the risk of AD, but the Asp allele influenced the age at onset (p = 0.05). In nondemented probands CSF levels of cholesterol were increased in carriers of the Asp/Asp genotype (p = 0.004); however, in patients with manifest dementia the authors found decreased CSF levels of cholesterol in carriers of the Asp/Asp genotype (p = 0.028). Serum homocysteine levels in stroke patients were higher in carriers of at least one Asp allele (p = 0.011). CONCLUSION: The GSTO1 Asp allele may be a genetic risk factor for cerebrovascular diseases, and might influence the course of Alzheimer disease, even though effects vary in different studies.

[Does magnetization transfer ratio (MTR) contribute to the diagnosis and differential diagnosis of the dementias?]. / Leistet die Magnetization-Transfer-Ratio (MTR) einen Beitrag zur Diagnostik und Differenzialdiagnostik der Demenzen?

PURPOSE: The magnetization transfer ratio (MTR) is a MR-based neuroimaging procedure aiming at the quantification of the structural integrity of brain tissue. Its contribution to the differential diagnosis of dementias was examined and discussed in relation to the pathogenesis of age-related dementias. MATERIALS AND METHODS: Sixty-one patients from a memory clinic were diagnosed by general physical and neuropsychiatric examination, and underwent neuropsychologic testing and neuroimaging using MRI. Their clinical diagnoses were based on standard operational research criteria. Additionally, the MTR in 10 defined regions of interest (ROI) was determined. This investigation was performed using a T1-weighted SE sequence. Average MTR values were determined in the individual ROI and their combinations and correlated with the age, gender, cognitive impairment and clinical diagnosis. Sensitivity, specificity, positive and negative predictive value were determined, as well as the rate of correct classifications. RESULTS: For cognitive healthy subjects, the MRT values correlate only mildly, though significantly, with age in the hippocampus and with gender in the dorsal corpus callosum. In contrast, the MTR in the frontal white matter correlates strongly and highly significantly with cognitive impairment in patients with dementia. The differential diagnostic assignment of Alzheimer's disease versus vascular dementia by MTR provides a correct classification of approximately 50 % to 70 %. PPV for no dementia vs. vascular dementia or the NPV for vascular vs. Alzheimer's disease are considerably higher exceeding 80 %. For no dementia vs. Alzheimer's disease, the NPV was over 90 %. CONCLUSION: MTR values indicate functional changes in the brain tissue between cognitive healthy and demented patients, and correlate with the cognitive loss, but not with age and gender. In principle, the MTR is suitable for the diagnosis of age-related dementias, but does not contribute substantially to the differential diagnosis of vascular dementia vs. Alzheimer's disease. The present results support the assumption of a synergy between vascular and degenerative components of age-related dementias.

[Effects of extended clinical diagnostics on the diagnostic spectrum of an outpatient memory clinic]. / Auswirkungen der erweiterten klinischen Diagnostik auf das Diagnosespektrum einer Gedächtnisambulanz.

OBJECTIVES: In an outpatient memory clinic, the methods of extended clinical diagnostics pertaining to imaging and neuropsychology were changed but the modus of assignment to the clinic remained unchanged at different times. Expected changes in the diagnostic spectrum can be attributed to the changed diagnostics. Consistent with reports from the literature regarding the consequences of such changes, the associated costs have to be taken into consideration as well. METHODS: The clinical final diagnoses of 174 patients referred in 2000/2001 for the diagnostics and differential diagnostics of dementia ("current population") were compared with those of 169 patients who visited the same outpatient clinic in 1998/1999 ("former population"). The diagnostic spectra of the two populations were compared. The diagnoses were differentiated in "no dementia" (XD), "neurodegenerative dementia" (ND), "vascular dementia" (VD), and "dementia of the mixed type" (MIXD). For all patients, the same clinical diagnostic criteria (ICD-10) and laboratory tests were implemented. Only the neuroradiological and neuropsychological methods changed from 1998/1999 to 2000/2001: The current population was examined with MRI instead of CT and underwent an expanded neuropsychological test battery with additional power and speed tests. RESULTS: The diagnoses of the two populations differed significantly in their frequency distribution. A dementia was excluded in 51.1% of the "current" patients vs 19.5% of the "former" patients. The frequencies of the dementia diagnoses were significantly different for the diagnoses ND (29.9 vs 47.9%) and MIXD (1.1 vs 7.7%), but not for VD (13.2 vs 12.4%). Beside other independent modalities, the improvement of imaging with MRI is discussed as recording atrophy size and vascular lesions better than CT. The improvement of the neuropsychological test battery containing additional speed tests is discussed as being able to differentiate even minimal cognitive disturbances. CONCLUSION: Using optimized imaging and neuropsychological methods, the diagnostic spectrum of an outpatient memory clinic changed. The clinical diagnosis was improved by the more sensitive, extended clinical diagnostics. Through optimized differential diagnostic allocation and the exclusion of dementia, expenses can be reduced by early and indication-related medication and by the resulting delay of institutionalized care.

[Evaluation of the contribution of the importance of neuroimaging for the diagnostics of dementias--comparison to the psychological diagnostics]. / Evaluation des Beitrages der radiologischen bildgebenden Diagnostik bei demenziellen Erkrankungen--ein Vergleich mit der psychologischen Diagnostik.

OBJECTIVE: While psychology is accepted as a necessary component of the dementia diagnostics, the extended clinical diagnostics with neuroimaging is differently estimated. The goal of the study is the quantification of the individual contribution of the two different methods. METHODS: Of 100 patients the diagnosis of entrance, the neurological, the psychological, and the final clinical diagnosis were documented. For both imaging and psychology the sensitivity, specificity, and the positive predictive value were computed. The diagnostic of each method was determined from the change of the final in relation to the initial clinical diagnosis. The neuroradiological investigation took place with MRI, the psychological examination used both usual power and special speed tests. RESULTS: The extended clinical diagnostics led for 26 % of the patients to the change of the clinical diagnosis. Imaging and psychology supplied different own but supplementing contributions. In the case of annihilation imaging contributed with 73.3 %, psychology with 54.1 % to the diagnosis of a neurodegenerative dementia, whereas the contributions to the diagnosis of a vascular dementia were 83.3 % and 70.8 %, respectively. However psychology diagnosed and quantified the dementia. The contribution of neuroimaging consisted in the differential diagnosis of the dementias. Organic causes of symptomatic dementias and vascular encephalopathy without dementia but with consequences for a secondary prophylaxis were additional information also. CONCLUSION: Psychology improves the diagnostic accuracy of dementias. Neuroimaging improves the differential diagnosis of dementias and supplies additional clinically relevant findings. In the qualified diagnostics and differential diagnostics of the dementias both methods are indispensable.

[Is there a referral bias in the diagnoses of patients of a memory clinic?]. / Unterscheiden sich die Diagnosen der Patienten einer Gedächtnisambulanz nach dem Uberweisungsmodus?

In a recent study addressing the contribution of neuropsychology and neuroradiology to the improvement of the dementia diagnoses of a memory clinic more than 45% of the patients (45 out of 101) did not meet the criteria for dementia. This finding was unexpected because all patients had been referred for the diagnosis and differential diagnosis of dementia. The aim of the present study was to examine whether the proportion of nondemented patients varies with the "modus of referral". This was not found to be true. The frequency of the diagnosis "no dementia" was not significantly different for the two patient groups "general practitioner" vs. "neuropsychiatrist" referred patients (p=0.859). In conclusion, there is no difference between the two groups of physicians in the reliability judging whether a "cognitive complainer" needs to be referred to a specialized memory clinic.

[Microangiopathic lesions of white matter. Quantitation of cerebral MRI findings and correlation with psychological tests]. / Mikroangiopathische Läsionen der weissen Hirnsubstanz. Quantifizierung im MRT und Korrelation mit psychologischen Testergebnissen.

AIM: The importance of vascular lesions in the white matter of the brain (WML) is viewed differently. Diagnostic evaluation is determined by experience and age-associated normal values are not available. MATERIAL AND METHODS: One hundred fifty-two patients aged 68.8 years (range 50-89) were examined at a memory clinic using a magnetic resonance FLAIR sequence,which is sensitive for WML. The WMLs were entered with respect to size, localization, laterality, and density. The WML scores of 76 clinically and psychologically normal subjects with microangiopathic lesions and 27 patients with vascular dementia were correlated with psychological test results. The contribution of local WML scores to the differentiation between age-associated microangiopathy and vascular dementia was calculated using logistic regression analysis. Nonparametric monotonic regression was used to analyse the age-associated WML scores of both groups, taking individual age into account. RESULTS: The WML scores correlated linearly with the age of psychologically normal subjects but with degree of dementia for those with vascular dementia, and it allowed differentiation between these two groups with an accuracy of up to 88% and specificity of approximately 95% with reference to the right frontal region. The odds ratios of the general and frontal WML scores were significantly different (1,102 and 1,400, respectively). Statistical significance of the age-associated WML scores varied for different age ranges. CONCLUSION: It is possible to differentiate psychologically normal subjects with microangiopathic brain lesions from patients with vascular dementia on MRI when referring to frontal WML scores.

Large-scale isolation of sinusoidal endothelial cells from pig and human liver.

OBJECTIVE: Hepatic in vitro studies, like those on hypoxia/reperfusion injury in liver transplants, demand large numbers of cultivated sinusoidal endothelial cells (SECs). In this article, we present and evaluate a new method for the isolation of SECs from porcine and human livers. METHODS: SECs were isolated employing a four-step collagenase perfusion. The sinusoidal character of the cells was validated by transmission and scanning electron microscopy, exclusion of Weibel-Palade bodies and factor VIII-related antigen, expression of scavenger receptor, and incorporation of latex beads. RESULTS: In 23 pigs, an average of 9 x 10(4) SECs were harvested from each liver. Cells were cultivated under standard conditions, as well as in multilayer cocultures of isolated SECs and hepatocytes in a "sandwich" configuration. Standard cultures showed an average of 90% SECs in primary cultures and 100% SECs after the first passage. The possibility of isolation of SECs from human livers was demonstrated in eight cases. CONCLUSION: With the four-step collagenase perfusion it is possible to easily isolate large numbers of viable and pure SECs from one organ. A further advantage is the possibility of isolating hepatocytes from the same organ.

Primary hyperparathyroidism--early diagnosis in patients referred for thyroid surgery.

BACKGROUND AND AIMS: From 1986 to 1998, 190 patients presented for first-time operations for sporadic, non-malignant, non-multiple endocrine neplasia primary hyperparathyroidism. Of these patients, 54% had been classified as "asymptomatic", 41% as symptomatic and 5% as acute. One hundred and thirty-five patients (71%) were referred to us for parathyroid surgery. Fifty-five patients (29%) were referred for thyroid surgery with hitherto unknown hyperparathyroidism. This corresponds to a prevalence of primary hyperparathyroidism of 1% in patients referred for thyroid surgery (5450 patients during the same period of time). PATIENTS/METHODS: Patients referred for parathyroid surgery (group I, n=135) were compared with patients originally referred for thyroid surgery (group II, n=55). Group II was divided into group IIa: hyperparathyroidism preoperatively biochemically evident (n=26), and group IIb: borderline biochemistry, parathyroid enlargement evident at the operation (n=29). The groups were compared regarding clinical manifestations, serum calcium and parathyroid hormone, pathologic-anatomical substrates, operative complications and outcome. RESULTS: Renal, osseous and gastrointestinal manifestations were more frequent in group I than in groups IIa and IIb (P<0.05). However, cardiovascular and neuromuscular symptoms were present in groups IIa and IIb in more than one-third of patients. Patients from group IIb were younger (49+/-12 years) than patients from groups IIa (60+/-13 years) and I (60+/-14 years). Adenomas were found in 85% of group I patients, in 45% of group IIa patients and in 21% of group IIb patients (P<0.01). In all other cases, hyperplasia was confirmed histologically. Serum calcium was higher in group I (3.0+/-0.42 mmol/l) than in groups IIa (2.63+/-0.16 mmol/l) and IIb (2.46+/-0.14 mmol/l) (P<0.01). Serum PTH was higher in group I (median 11.0 pmol/l) than in groups IIa and IIb (median 7.1 and 6.4 pmol/l, respectively) (P<0.05). Postoperatively, hypercalcemia persisted in two patients (1.1%) belonging to group I, with mediastinal adenomas. Serum calcium at discharge showed no differences between groups (group I: 2.22+/-0.16; group IIa: 2.22+/-0.15; group IIb: 2.20+/-0.11 mmol/l). Recurrent laryngeal nerve paralysis occurred early (4.2% of "nerves at risk") and remained permanent (0.8% of "nerves at risk") without significant differences between groups. CONCLUSION: Diagnostic efforts regarding parathyroid function should be mandatory before thyroid operations. "Asymptomatic" patients frequently (more than 30%) present with cardiovascular and neuromuscular, "unspecific" symptoms. Simultaneous parathyroid exploration is obvious in cases with biochemically evident primary hyperparathyroidism, but should also be performed in patients with borderline biochemistry.