Wolfram syndrome: a neuropathological study

Neuropathological examination was carried out on a patient aged 37 years who had suffered from Wolfram syndrome. Atrophy of the olfactory bulbs and tracts, atrophy of the optic nerves and chiasm, loss of neurons in the lateral geniculate nuclei mainly affecting the small cell layers, atrophy of the superior colliculus, loss of fibers in the cochlear nerve and mild loss of neurons in the cochlear nuclei and inferior colliculus, mild olivopontocerebellar atrophy, and demyelination of the pyramidal tracts were the main neuropathological findings. These correlated with anosmia, loss of vision, loss of hearing, cerebellar symptoms and signs, Babinski sign, and clonus, respectively, clinically observed in this patient. Mild neuron loss and gliosis in the preoptic and paraventricular area of the hypothalamus and mild motor neuron loss in the spinal cord did not reach thresholds of impaired function, although loss of neurons in discrete bulbar nuclei might have accounted for the late episode of food aspiration and suffocation. The relationship between memory loss, personality disturbances, and signs of prefrontal release and mild loss of neurons in the anterior and dorso-medial nuclei of the thalamus remains unclear.     

Delusions in Alzheimer''s disease: a review

To understand the developing processes of gamma-aminobutyric acid (GABA)-containing chromaffin cells and nerve fibers in the mouse adrenal gland, we examined the tissues in various postnatal stages by immunohistochemistry using a GABA antibody. From birth until postnatal week 1, GABA-immunoreactivity was seen in very few nerve fibers, and in none of the chromaffin cells. At postnatal week 2, GABA-immunoreactivity appeared weakly in clusters of chromaffin cells and strongly in relatively numerous varicose nerve fibers. The immunoreactive nerve fibers were densely distributed in the small immunonegative chromaffin cells and large ganglion cells, but only sparsely so in the weak immunoreactive chromaffin cells. At postnatal week 3, the number of the immunoreactive chromaffin cells and nerve fibers further increased compared to that at postnatal week 2. The staining pattern of GABA-immunoreactive nerve fibers in the medullas was similar to that at postnatal week 2. From postnatal week 4 until postnatal week 8, the distribution and frequency of the immunoreactive chromaffin cells and nerve fibers were also similar to those at postnatal week 3. These results suggest that the expression of GABA in the chromaffin cells and in the nerve fibers of the mouse adrenal gland may be completed by postnatal week 3.     

Alzheimer''s syndrome, not Alzheimer''s disease

The defibrillation thresholds of both first-phase polarities of a biphasic waveform were tested using an endocardial defibrillation electrode system. Despite differences in defibrillation thresholds in the individual patient, both tested electrode polarities lead to a comparable overall defibrillation efficacy.     

Word reading in Alzheimer''s disease: cross-sectional and longitudinal analyses of response time and accuracy data

Injection of Fluoro-Gold (FG) into the whiskerpad muscles of rats yields a permanent retrograde labeling of motoneurons in the facial nucleus. Following subsequent resection of 10 mm of the facial nerve, one-third of the facial motoneurons die and the microglia phagocytize the dead FG-labeled neurons, take up FG, and get labeled in vivo. The resulting identification of all FG-labeled cells allows long-term comparative investigations on the behavior of neuronophages. In this study, we used two groups of rats to test whether the quantified expression of five immune-related antigens by neuronophages was related to quantified decline in neuron number (counts after immunostaining for neuron-specific enolase) 3 to 224 days after resection of the facial nerve. Rats of the first group received standard food and those of the second group, pellets containing 1,000 ppm of the calcium channel blocker nimodipine. Image analysis of the number of FG-containing cells and the number and projection area of immunopositive neuronophages in serial sections for each antigen showed that nimodipine significantly attenuated the immunostaining for CR3, MHC class I, and class II antigens (monoclonal antibodies [MAbs] OX-42, OX-18, and OX-6); enhanced the expression of monocyte-macrophage-specific antigen (MAb ED1); and did not change the expression of rat macrophage differentiation antigen (MAb ED2). The altered expressions, however, had no effect on the loss of motoneurons in the lesioned facial nucleus. We conclude that the degree of expression of immune-related antigens by neuronophages has no influence on the delayed neuronal cell death induced by permanent target deprivation.     

Intellectual performance in multi-infarct dementia and Alzheimer''s disease a replication study

A comparative study was conducted to evaluate the efficacy of a metal or flexible plastic 8 mm cannula for artificial abortion by vacuum aspiration for patients at six to 10 weeks' gestation. Complication rates, amounts of retained tissue (obtained with a curette check), frequencies of cannula obstructions and procedure times were used as criteria for determining the efficacy of the two types of cannulae. Two physicians participated in the study: one was responsible for the preliminary examination and performance of the abortion, and the other physician, who was kept unaware of the type of cannula used, was responsible for patient care after completions of the abortion to the time of the follow-up visit. Paracervical block anesthesia was used in all cases. Differences in complication rates (controlled for gestational age) between groups of subjects aborted with either the metal or flexible plastic cannula were not significantly different (p less than .05). For both patient groups shock was the most frequently reported immediate complication (2.7% in the metal cannula group, 4,7% in the flexible plastic cannula group), and leukorrhea was the most frequently reported complication at the time of follow-up (3.3% metal, 5.3% flexible plastic). Amounts of retained tissue and frequency of cannulae obstruction were similar for both groups. Procedure times were also similar for both groups (means of 5.7 minutes and 5.5 minutes, respectively, for procedures performed with the metal and flexible plastic cannulae).     

Deleterious network: a testable pathogenetic concept of Alzheimer''s disease

Cumulative evidence has indicated that a deleterious network is formed on the basis of close interactions among abnormal amyloid precursor protein (APP) metabolism, oxidative damage, compromised energy metabolism and impaired calcium homeostasis. A unifying hypothesis-the deleterious network hypothesis of Alzheimer's disease (AD)-proposes that the deleterious network, not any single factor, is the common pathway of AD. Aging and multiple genetic or environmental factors could trigger the network by promoting the occurrence of one or more of the key detrimental factors, leading to a number of pathological changes of the disorder. This new hypothesis appears to unify some major theories of AD, providing a sound basis for consistent explanations to a large variety of the observations about the disorder. In this article upto-date delineation of the novel theory is given. Three types of studies are also proposed for further determining the validity of the new hypothesis. Based on this theory, it is suggested that combinative applications of the approaches which can reduce the incidence of the four key pathological factors could become a new therapeutic strategy of AD.     

Assessment of the pathological stages of Alzheimer''s disease in thin paraffin sections: a comparative study

In 20 minipigs an osteotomy of the lumbar spine was done at L3 and fixed with resorbable implants (plate and screws) made of poly-L-lactide. For 24 months postoperatively the cancellous bone surrounding the screws was examined histologically. Specimens from the body of lumbar spine L2 and L4, carrying the screws, were fixed in a series of ethanol immersions and then embedded in methylmethacrylate. Longitudinal and transverse sections were cut with a microtome at 4-5 microns and stained by the Masson-Goldner and Giemsa method for light microscopy. Our investigation confirmed a long degradation period of poly-L-lactide and little inflammatory reaction within the bone during the whole period of observation. For poly-L-lactide the degradation time exceeded the longest follow-up time in this study, 24 months. Polymorphonuclear granulocytes and mononuclear round cells were scarce in all follow-up groups. Osteolytic changes or the emergence of seroma was not observed. Textured bone was evident early close to a thin fibrous capsule surrounding the screws. The remodelling of the bone close to the screws ensues by the formation of osteons.     

Tau in Alzheimer''s disease

The effects on goats of Calotropis procera latex given by different routes of administration were investigated. The administration of latex at 1 ml/Kg body weight via the oral route or at 0.005 ml/Kg body weight/day via the intravenous or intraperitoneal route caused death of the goats between 20 minutes and 4 days. When the small dose of latex (0.005 ml/Kg body weight/day) was given by the oral route or intramuscular route no death among the goats occurred. Nervous signs, frequent urination, frothing at the mouth, dyspnoea and diarrhoea were the main features in goats given latex by the oral, intravenous or intraperitoneal route. Lameness was observed in goats given latex via the intramuscular route. Lesions were widespread congestion and haemorrhage, pulmonary cyanosis, enterohepatonephropathy, peritonitis (in goats receiving latex via i.p. route) and haemorrhagic myositis at the site of latex injection. These changes were accompanied by increases in the activities of serum GDH, LDH, ALP, GGT and AST and in the concentrations of cholesterol, urea and creatinine and decreases in the level of total protein.     

Diagnostic accuracy of serological assays in pediatric inflammatory bowel disease

BACKGROUND & AIMS: Accurate serological assays are desirable for the diagnosis of inflammatory bowel disease (IBD) types in the pediatric age group. The aim of this study was to test the diagnostic accuracy of modified assays for perinuclear (p) antineutrophil cytoplasmic antibodies (ANCAs) and anti-Saccharomyces cerevisiae antibodies (ASCAs) in patients with pediatric ulcerative colitis (UC) and Crohn's disease (CD) and in those without IBD. METHODS: With observers blinded to patients' diagnoses, serum specimens were analyzed for immunoglobulin (Ig) A and IgG ASCAs and ANCAs by enzyme-linked immunosorbent assay. The perinuclear location of ANCAs visualized by indirect immunofluorescence was confirmed by its disappearance after administration of deoxyribonuclease. RESULTS: IgA and IgG ASCA titers were significantly greater and highly specific for CD (95% for either, 100% if both positive). pANCA was 92% specific for UC and absent in all non-IBD controls. The majority of patients with CD positive for pANCA had a UC-like presentation. Disease location, duration, activity, complications, and treatment with immunosuppressive drugs did not have an impact on the ASCA or pANCA assay results. After resection, UC patients remained pANCA positive, in contrast to patients with CD, in whom ASCA titers decreased toward normal values postoperatively. CONCLUSIONS: ASCA and pANCA assays are highly disease specific for CD and UC, respectively. These serological tests can assist clinicians in diagnosing and categorizing patients with IBD and may be useful in making therapeutic decisions.     

Update on Alzheimer''s disease

The nation's health care system is undergoing a period of rapid change that will profoundly affect women's health care services and, ultimately, women's health. Although managed care is quickly becoming the predominant mode of health care delivery in the United States, a new, more consumer-focused, and accountable model known as organized systems of care (OSC) is emerging. OSC development has been driven by large private and public employers seeking to purchase the highest quality health care for the best price. The changes in health care delivery encouraged by these innovative employers will provide women with optimal care and attention, which will in turn help them attract and retain a competitive and productive workforce.     

Alzheimer''s disease: the advent of effective therapy

PURPOSE: To investigate the astigmatic keratotomy effect of a modified single-hinge cataract incision. SETTING: Department of Ophthalmology, San Juan de Dios Hospital, Tenerife, Spain. METHODS: This prospective study evaluated the astigmatic changes resulting from preincision grooves of less than 40, 45, and 55 degrees in arc length used with a single-hinge, self-sealing cataract incision in 144 eyes that had against-the-rule corneal astigmatism preoperatively. The intended 90% depth preincision was centered on the steep meridian and lengthened according to the amount of preoperative astigmatism. Outcome measurements were obtained by calculating the surgically induced astigmatism vectors and the postoperative keratometry changes 1 day, 1 week, and 1, 3, and 6 months after surgery. RESULTS: Three months postoperatively, astigmatism decreased by 0.03, 0.30, and 0.68 diopter in the less than 40, 45, and 55 degree incision length groups, respectively. The differences between the 45 and 55 degree groups and the less than 40 degree group was statistically significant (P < .05). Similar results were observed 6 months after surgery. CONCLUSION: The astigmatic preincision modification produced statistically significant increasing reductions in preoperative astigmatism according to preincision length.     

Biological markers of Alzheimer''s disease

A 49-year-old woman presented with splenic lymphoma with villous lymphocytes (SLVL) that showed a clonal abnormality of del(7)(q22q32) in addition to inv(10)(p13q23), the latter being a previously undescribed abnormality in chronic lymphoproliferative disorders. A review of the literature on cytogenetic abnormalities of SLVL indicates that del(7q) is strongly associated with SLVL and may be important in the pathogenesis of this disorder.     

Neurochemical studies of Alzheimer''s disease

Age differences in the representation of semantic information may underlie the cognitive decline observed in aging. The objective of the present study was to determine to what extent elderly and young subjects agreed in the representations of semantic categories. Ninety elderly (77 women, 13 men) and 90 young (74 women, 16 men) participants wrote down the first four associations evoked by each of 30 semantic category names. Results showed differences between the two groups in items selected as most common responses (MCRs); frequency of occurrence of the MCRs differed between the two groups in 21 semantic categories. Results suggest that young and elderly subjects hold different representations of semantic categories and also highlight the importance of using age-appropriate norms in the evaluation of cognitive functions in aging.     

Postprandial hypotension in Alzheimer''s disease

The degree of postprandial hypotension in patients with Alzheimer's disease (AD) is not known. We therefore studied ten AD patients and 23 controls before and after a meal. Seven AD patients but only six controls showed a fall in blood pressure (BP) of 20 mmHg or more. Maximum BP fall in AD patients was observed between 20 and 120 min after food ingestion. This differed from the time course in other groups with primary chronic autonomic failure. Postural hypotension occurred in two controls, but not in AD patients. Abnormalities in cardiac vasomotor regulation, gut peptide liberation or both could be responsible for postprandial hypotension in AD.     

Procedural memory stimulation in Alzheimer''s disease: impact of a training programme

The operative results of 23 patients with a specific or unspecific spondylodiscitis were documented over 2 years after the focus of the inflammation had been eradicated, bone chip had been interposed and a CDH instrumentation had been performed by an anterior approach only. These outcomes were compared with the results of 32 patients in whom the focus had been removed and the defect had been filled with bone graft from an anterior approach, followed by stabilisation with CD instrumentation through an additional dorsal approach. In the cases where CDH instrumentation was applied, the range of fusion averaged 1.3 segments. This was clearly less extensive than in dorsoventral stabilisation, in which on average 3.5 segments were fused. In 47 of 55 cases mobilisation was achieved without orthesis. Eight months after the operations bony fusion could be observed radiologically in all patients. The mean preoperative kyphotic angle of the affected segments was 14.4 degrees, compared to 4 degrees after the operation. The mean loss of reposition was measured to be about 2.7 degrees in both groups. Average operation time and blood loss were about 50% higher in the patients treated dorsoventrally. We conclude that even in the case of florid spondylodiscitis, a short-range anterior fusion of the affected spinal segment may be performed by use of a stable-angle implant without an increased risk of infection-related loosening.     

Visual evoked potentials in Alzheimer''s disease: investigations in a PET-defined collective

Evidence indicates that the lipoxygenase (LO) pathway of arachidonic acid is a key mediator of angiotensin II (AII)-induced aldosterone synthesis in adrenal glomerulosa cells. Although protein kinase C (PKC) may play a role in AII action, the precise PKC isoforms involved and whether LO products can activate PKC is not clear. We therefore evaluated the effect of AII and LO products such as 12- and 15-hydroxyeicosatetraenoic acids (HETEs) on PKC activation in isolated rat adrenal glomerulosa cells. PKC activity was measured by the phosphorylation of a PKC specific peptide while the PKC isoforms were identified by Western immunoblotting using antibodies that recognize the alpha, beta, gamma or epsilon isoforms of PKC. Treatment of the cells for 15 min with AII (10[-8]M) or the LO products 12- or 15-HETE caused a marked increase in PKC activity in membrane fractions with reciprocal decreases in the cytosolic PKC activity. Rat glomerulosa cells expressed only the alpha, and epsilon isoforms of PKC. AII increased membrane bound levels of both PKC-alpha and -epsilon (1.9- and 1.5-fold, respectively), whereas the LO products predominantly activated PKC-epsilon. Reciprocal decreases in immunoreactive cytosolic PKC levels were seen. AII-induced aldosterone synthesis was blocked by H-7 and retinal as well as by a PKC-specific pseudosubstrate inhibitor, PKC(19-36). These results suggest that AII and LO pathway-induced actions in the adrenal glomerulosa may be mediated by specific PKC isoforms.     

Motor performance in Alzheimer''s disease

A 47-year-old man with Hirayama's disease who developed cervical spondylotic amyotrophy (CSA) is presented. The patient had noted weakness and atrophy of hand and forearm muscles bilaterally at the age of 16. At the age of 40, he developed proximal muscle atrophy and weakness bilaterally after 20 years of a non-progressive state. Myelography and computed tomography (CT)-myelography revealed that ventral cord compression at multiple levels of C4-7 vertebral bodies was increased when the neck was extended. The clinical diagnosis was CSA associated with Hirayama's disease. To our knowledge, this is the first such case to be reported.     

Diagnostic items and treatment of Plummer''s disease: a study on 180 patients

OBJECTIVE: To evaluate the impact of operator caseload on the sampling efficiency for early and standard, midtrimester amniocentesis. STUDY DESIGN: Prospective ascertainment of genetic amniocenteses performed during 36 months, grouped into early (13-14 weeks' gestation) and standard procedures (15-20 weeks' gestation). Details of each amniocentesis were recorded immediately after sampling, and pregnancy outcomes were retrieved via questionnaires completed by the delivering physician. Sampling efficiency was evaluated separately in the early and standard cohorts in relation to operator caseload. RESULTS: In total, 193 and 707 patients underwent early and standard amniocentesis, respectively. Forty of 46 physician-operators performed < 50 total procedures during the study interval (group A). When compared to operators performing > or = 50 cases (group B, n = 6), a higher rate of single-pass success was noted among group B physicians for both early and standard procedures (A vs. B, early: 40/45 vs. 145/148, P = .018; standard: 243/295 vs. 384/412, P < .0001). Logistic regression confirmed an independent effect of physician caseload on sampling efficiency and a significant interaction between physician caseload and simultaneous ultrasound guidance in predicting single-attempt success. CONCLUSION: Operator caseload directly influenced sampling efficiency for both early and standard, midtrimester amniocentesis.