Phospholipase C isozymes in the human brain and their changes in Alzheimer''s disease

OBJECTIVE: We compared the efficacy of bladder training, pelvic muscle exercise with biofeedback-assisted instruction, and combination therapy, on urinary incontinence in women. The primary hypothesis was that combination therapy would be the most effective in reducing incontinent episodes. STUDY DESIGN: A randomized clinical trial with three treatment groups was conducted in gynecologic practices at two university medical centers. Two hundred and four women diagnosed with genuine stress incontinence (n = 145) and/or detrusor instability (n = 59) received a 12-week intervention program (6 weekly office visits and 6 weeks of mail/telephone contact) with immediate and 3-month follow-up. Outcome variables included number of incontinent episodes, quality of life, perceived improvement, and satisfaction. Data analyses consisted of analysis of covariance using baseline values as covariates and chi2 tests. RESULTS: The combination therapy group had significantly fewer incontinent episodes, better quality of life, and greater treatment satisfaction immediately after treatment. No differences among groups were observed 3 months later. Women with genuine stress incontinence had greater improvement in life impact, and those with detrusor instability had less symptom distress at the immediate follow-up; otherwise, no differences were noted by diagnosis, incontinence severity, or treatment site. CONCLUSIONS: Combination therapy had the greatest immediate efficacy in the management of female urinary incontinence regardless of urodynamic diagnosis. However, each of the 3 interventions had similar effects 3 months after treatment. Results suggest that the specific treatment may not be as important as having a structured intervention program with education, counseling, and frequent patient contact.     

The neurobiology of apolipoproteins and their receptors in the CNS and Alzheimer''s disease

Relocation to a nursing home places frail elders at risk for developing depression and suicide ideation. This study followed two hundred and fifty-six newly relocated nursing home residents for five years. Using a Solomon Four research design, participants were divided into four groups, two control and two experimental, one each with pretesting and all with posttesting. Participants in the control groups received a friendly visit and those in the experimental groups received the intervention of life review. Immediate short-term results showed the life review to be an effective preventive intervention for clinical depression (p = .05). Additionally, when looking at long-term effects at one year, there were significant decrease in depression (p = .05), hopelessness (p = .01), and psychological well-being (p = .02) with measurable increases in life satisfaction (p = .08). These findings support the hypothesis that life review prevents despair in frail elders newly admitted to a nursing home.     

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.     

Loss of dopamine D2 receptors in Alzheimer''s disease with parkinsonism but not Parkinson''s or Alzheimer''s disease

Qualitative analyses of midfoot stabilization in triple arthrodeses utilizing bone staple versus 4.5-mm cannulated cancellous screw fixation, with and without washers, were performed in fresh cadaveric specimens. Twenty-two trials (11 matched-pair feet) were used for direct comparison. Stiffness, defined as force/displacement, was determined at each talonavicular and calcaneocuboid joint. Ultimate load failure points of each specimen were also calculated. Trial results showed no statistically significant difference in stiffness or ultimate failure between these two forms of midfoot fixation for triple arthrodeses.     

Predicting survival in patients with early Alzheimer''s disease

BACKGROUND: The indication for urgent cardiac surgical interventions in patients with active infective endocarditis has to be considered carefully following thromboembolic events, because of the high recurrence rate of such complications. In the case of brain embolisms the prognostic benefit of urgent surgery has been discussed controversially as effective anticoagulation during open heart surgery may result in secondary cerebral hemorrhages. PATIENTS AND METHODS: Between 1978 and 1993 infective endocarditis (IE) was proven in 288 consecutive and prospectively followed patients (131 females, 157 males; mean age 53.6 +/- 8.7 [9 to 81] years). To analyze potential benefits and risks of an urgent surgical intervention early after embolic cerebral infarction, cumulated survival rates were calculated for patients with and without surgical intervention with special reference to incremental risk factors and the timing of surgery. RESULTS: In 50 patients (17.4%) the clinical course was complicated by one, and in 58 patients (20.2%) by recurrent embolic events. In 80% the first embolism occurred within 33 days following the first manifestation of typical signs and symptoms of IE. 80% of recurrent events were observed within 32 days following the initial embolism. 71% of all embolic events were cerebral. In patients with cerebral embolism corroborated by computed tomography (CCT), the clinical course was complicated by intracranial hemorrhage in 12.5% while it was only 1.5% for patients without cerebral embolism. Because of a lack of therapeutic alternatives, 22 of 49 patients with recurrent embolic events, of which at least one was cerebral, underwent urgent cardiac surgery within 4 to 366 hours after the first cerebral manifestation. The cumulated survival rate of patients operated within 72 hours after the initial cerebral embolism was significantly more favorable (p < or = 0.000) than for unoperated patients or those who were operated after more than 8 days. CONCLUSION: An embolic event during IE carries a more than 50% risk of recurrence. In patients with short duration of signs and symptoms of IE and postembolic echocardiographic demonstration of persistent vegetations the probability is > 80%. At least for those patients urgent surgical intervention to remove the source of infection and embolic hazard seems to be beneficial. Surgical intervention using the heart-lung-machine should be performed within 72 hours. Such early timing results in a significant lower rate of secondary cerebral hemorrhages (p < or = 0.00) than a postponed operation. To exclude early reperfusion hemorrhage due to spontaneous thrombus fragmentation, CCT should be repeated directly preoperatively.     

Factors associated with psychotic symptoms in Alzheimer''s disease

BACKGROUND: The incidence of abdominal aortic aneurysm (AAA) has increased steadily during the past 30 years. METHODS: Trends in the incidence and surgical intervention for AAA in Western Australia were reviewed for the interval 1985-1994. A population-based health database was used to link morbidity and mortality records of all patients aged 55 years or more who died from rupture or were admitted and treated surgically for AAA. Three groups were separated for analysis: patients with a ruptured AAA, those admitted for elective repair and those admitted as an emergency with an acute (non-ruptured) aneurysm. RESULTS: There was a decline in the incidence of both emergency and elective procedures for AAA after 1992. While the mortality rate from ruptured AAA has also fallen since 1991, the overall case fatality rate for ruptured AAA has fallen by only 1.3 per cent (from 80.7 to 79.3 per cent). CONCLUSION: The decline in mortality rate and emergency procedures may result from a fall in the incidence of ruptured AAA, due to an increasing rate of elective surgery before 1992. The decline in elective procedures from 1992 may be due to a fall in the prevalence of AAA owing to high rates of elective surgery, or to a fall in the incidence of the disease itself.     

Histopathologic correlates of white matter changes on MRI in Alzheimer''s disease and normal aging

Human lipoproteins after their intestinal or hepatic synthesis undergo within vascular compartment important remodeling through the agency of endothelial lipases, Lecithin: Cholesterol Acyl Transferase and lipid transfer proteins, Cholesteryl Ester Transfer Protein (CETP) and Phospholipid Transfer Protein (PLTP). Following CETP and PLTP characteristics presentation, transfer proteins activities and role were described specifying notably mechanism and kinetic models of cholesteryl ester transfer reaction (shuttle and ternary collision complex mechanisms). Comparative study of Phospholipid Transfer Activities mediated by CETP and PLTP has shown that phospholipid transfer activities of PLTP and CETP are different and might rely on distinct mechanisms. PLTP mediated phospholipid transfers modulate cholesteryl ester transfer activity of CETP. In vivo PLTP is responsible for the net mass transfer of phospholipid from triglyceride rich lipoprotein towards HDL. Whereas PLTP has no intrinsic cholesteryl ester transfer activity, it enhances the transfer of cholesteryl ester from HDL to VLDL and LDL. Thus PLTP might be a determinant factor in modulating the CETP mediated redistribution of cholesteryl esters between pro-(LDL) and anti-(HDL) atherogenic lipoproteins.     

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.     

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.     

Anosognosia and procedural learning in Alzheimer''s disease

Biochemical modulation of 5-fluorouracil (5-FU) by folinic acid (FA) increases the response rate in patients with metastatic colorectal cancer compared to 5-FU alone. Phase II trials also demonstrated increased efficacy when interferon was added to 5-FU. In two consecutive trials, 76 patients were treated on days 1-5 with FA 200 mg/m2 plus interferon 5 x 10(6) U/m2 and 5-FU 350 mg/m2 as intravenous bolus injection (n = 33, regimen A) or 5-FU 500 mg/m2 as 2-hour infusion (n = 43, regimen B), repeated every 3 weeks with individual 5-FU dose escalation in steps of 50 (regimen A) or 100 mg/m2 (regimen B). In regimen A 5-FU dose reduction to 300 mg/m2 due to toxicity was necessary in 49% of the patients; in regimen B a 5-FU dose of 600 mg/m2 or above was tolerated by 70% of the patients. Dose-limiting toxicity was severe mucositis and/or diarrhea. Objective responses were observed in 5 of 33 patients (15%) in regimen A (3-28%, 95% confidence interval) and 7 of 41 patients (17%) in regimen B (5-29%, 95% confidence interval). Median time to progression was 4.7 and 4.8 months, and median survival 9.9 and 11.4 months for regimens A and B, respectively. Prolonged 5-FU administration over 2 h allows the administration of a higher 5-FU dose compared to bolus injection with no apparent improvement in antineoplastic efficacy. The addition of interferon to the combination of 5-FU plus FA in this dose and schedule does not seem to improve the response rate but appears to increase treatment toxicity.     

Pathology of olfactory mucosa in patients with Alzheimer''s disease

Radiographs of hand and hip joints of 15 hemodialysis patients taken annually over at least 15 years were evaluated in this retrospective study. We looked for signs of A beta 2M-amyloidosis such as lucencies, erosions, and soft tissue swelling. The femoral head-soft tissue distance (FHSTD) was used to estimate the soft tissue swelling of the hips. The number and size of lucencies, the number of erosions, and the FHSTD increased during dialysis. Both hyperparathyroidism and failure of renal allograft transplantation influenced the development of lucencies and erosions after 15 years. The FHSTD at the start of the dialysis appeared to be an independent prognostic factor for the lucencies of the hips and hands. We conclude that the radiological signs of A beta 2M-amyloidosis are influenced not only by the duration of dialysis, but also by age, failure of renal transplantation, hyperparathyroidism and the FHSTD at the start of dialysis.     

Object decision priming in Alzheimer''s disease

The ability to effectively define disease status in ovarian cancer after initial therapy or to selectively screen high-risk populations remains a major challenge for in vivo monoclonal antibody (mAb)-targeted approaches. Antitumour murine mAbs (HMFG1, HMFG2, H317, and H17E2) and the reshaped human antibody Hu2PLAP (against placental alkaline phosphatase; PLAP), labelled with indium-111 and iodine-123, were evaluated for their ability to localise ovarian tumours in sequential studies of our group. Thirty patients with ovarian cancer, aged 40-78 years (median 60 years) were studied with HMFG1/G2: 11, and H317/H17E2: 19 murine mAbs. Six patients with ovarian cancer aged between 36 and 65 years (median 49 years) were studied with the reshaped human Hu2PLAP mAb (5 patients) or the murine H17E2 mAb (2 patients) labelled with 111In via a new macrocyclic chelating agent (DOTA). One of these was imaged twice, with H17E2- and Hu2PLAP-DOTA-111In, respectively. In 20 out of 22 patients with radiologically measurable ovarian cancer, the presence of tumour was confirmed by the murine mAb scan and correlated well with the findings of conventional radiology diagnostic methods. One of these patients with a negative H17E2 scan and a large abdominal mass at laparotomy was found to have a PLAP-negative tumour on immunohistochemistry. Additionally, the antibody scan revealed the presence of active disease, confirmed at laparotomy/laparoscopy, in 6 out of 8 patients considered to be in clinical complete remission. Best images were obtained at 24 and 48 h after the 123I and 111In mAbs, respectively. Successful imaging with the reshaped human antibody, Hu2PLAP, was seen in 2 patients with PLAP-positive tumours. Antibodies to DOTA developed in 2 patients. In conclusion, immunolocalisation of ovarian tumours is feasible with both murine and reshaped human mAbs. The sensitivity and specificity of the method appear very high in this pilot study, and in view of the absence of toxicity, the diagnostic contribution of this approach should be evaluated prospectively. Given the low number of patients without surgically detectable disease in the present study, future investigations should include more patients with no evidence of disease in order to provide more meaningful estimates of specificity.     

Mitochondrial DNA mutations in Alzheimer''s disease

A rapid, simple, and efficient chloroform/methanol-free method of isolating gangliosides is described. The nonionic polyoxyethylene detergent, hexaethyleneglycol mono-n-tetradecyl ether (C14EO6), forms clear micellar solutions in water, but two-phase separation can be achieved by centrifugation in the presence of ammonium sulfate at room temperature. A mixture of pure gangliosides, metabolically labeled gangliosides obtained from cultured hippocampal neurons, and gangliosides from rat cerebellar tissue were quantitatively recovered in the detergent-rich upper (coacervate) phase, with a partition coefficient K > 60. Gangliosides were subsequently separated from the detergent using an Iatrobead column prior to analysis by thin-layer chromatography. The procedure described here is as efficient as other methods of ganglioside extraction, such as that using chloroform/methanol/water/pyridine, but is less time-consuming inasmuch as extraction, purification, and TLC analysis can be completed within 1 day.     

Controlled and automatic memory process in Alzheimer''s disease

Treatment of cultured rat hepatocytes with cyclosporin A (0.01-1 microM) for 24, 48, or 72 h in the presence of insulin and epidermal growth factor induced an inhibition on cell proliferation in a time- and concentration-dependent manner, with an IC50 = 0.05 microM CsA corresponding to 48-h treatment. The inhibitory effect of CsA at < or = 0.1 microM doses for 48 h on [3H]thymidine uptake was reversed after withdrawal of the drug and subsequent addition of insulin plus EGF or serum; however, at 1 microM CsA the effect was irreversible and numerous bright small vesicles were observed. The molecular mechanism involved in CsA action in hepatocytes seems to be independent on cAMP and pertussis-toxin sensitive G proteins.     

Prevalence and correlates of anxiety in Alzheimer''s disease

Short-lived occupational skin symptoms of irritant or urticarial nature were commonly reported among 253 attendants in a clinical study on occupational dermatitis in Danish gardeners and greenhouse workers. Aimed prick or scratch-patch testing for immediate skin and mucosal symptoms was performed in 105 persons with plants as is. 35 persons (33%) had at least 1 positive reaction and a family history of, or personal, atopy was significantly more prevalent among these compared to attendants with negative reactions. Positive histamine release tests made immunologic etiology probable in Schlumbergera cacti, Stephanotis floribunda, Euphorbia pulcherrima and Gerbera reactions. Other new species implicated in immediate-type reactions included Ficus pumila, Gardenia jasminoides, Hibiscus rosa-sinensis, Campanula, Columnea, Epipremnum aureum, Pelargonium and Primula vulgaris. Because of the high prevalence of short-lived skin symptoms and because contact urticaria may present itself as a dermatitis, it is recommended that one supplement patch tests with tests for immediate reactions.     

Imidazoline receptor proteins in brains of patients with Alzheimer''s disease

Experiments have been carried out to investigate the chemical substrate in the rostral ventrolateral medulla (RVLM) underlying the depressor responses induced by activation of the greater splanchnic nerve (GSPL) afferent fibres of the rat. In anaesthetised rats with urethane and alpha-chloralose, microinjection of bicuculline, a GABA(A) receptor antagonist, into the RVLM, attenuated largely the depressor responses elicited by electrical stimulation of the GSPL afferent fibres, while strychnine or saline had no effect. In 18 RVLM neurons (including seven identified cardiovascular neurons), iontophoresis of bicuculline also significantly blocked the inhibition evoked by stimulation of the GSPL afferent inputs. We suggest that the depressor responses induced by stimulation of the GSPL afferent fibres involve a GABA(A)-receptor-mediated mechanism in the RVLM in rats.     

Frontal lobe hypometabolism and depression in Alzheimer''s disease

PURPOSE: It is speculated that the susceptibility to urothelial cancer in dye workers who are exposed to aromatic amines is affected not only by occupational environmental factors but by host specific factors. We evaluated the interaction between glutathione S-transferase M1 gene deficiency and the occupational environmental factors associated with urothelial cancer. MATERIALS AND METHODS: The study included 137 workers who had prior exposure to dyestuff intermediates, of whom 36 had urothelial cancer. The prevalence of a glutathione S-transferase M1 gene polymorphism was investigated using polymerase chain reaction. The relationship between the glutathione S-transferase M1 0/0 gene and occupational environmental factors in the onset of urothelial cancer was examined by multivariate analysis. RESULTS: The prevalence of glutathione S-transferase M1 gene deficiency did not differ significantly between the urothelial cancer (21 cases, 58.3%) group and the cancer-free (47, 46.3%) group. It was estimated that 29.6% of the urothelial cancers in these dye workers was attributable to the glutathione S-transferase M1 0/0 gene. Analysis using multiple logistic models showed low predictive ability for urothelial cancer due to glutathione S-transferase M1 gene deficiency (p = 0.084, odds ratio 2.260, 95% confidence interval [CI] 0.904 to 5.652). A history of working in small factories (p = 0.000, odds ratio 7.404, 95% CI 2.854 to 19.206) and a long period of exposure (p = 0.016, odds ratio 5.051, 95% CI 1.371 to 18.612) significantly predicted cancer. CONCLUSIONS: We demonstrated a strong trend using the multiple logistic analysis of the contribution of glutathione S-transferase M1 gene polymorphism and occupational environmental factors. Therefore, the glutathione S-transferase M1 enzyme might have an important role in the detoxification of aromatic amine derived carcinogens. Occupational environmental factors, however, might contribute more than a glutathione S-transferase M1 gene deficiency to the occurrence of urothelial cancer among individuals exposed to aromatic amines, because of the extremely potent carcinogenicity of some occupational environmental factors.