The incidence of dementia: a meta-analysis

OBJECTIVE: To carry out a meta-analysis of the age-specific incidence of all dementias, including AD and vascular dementia. BACKGROUND: Several meta-analyses have been carried out on dementia prevalence, but none on its incidence. METHODS: We used loess-curve fitting to analyze data from 23 published studies reporting age-specific incidence data. RESULTS: The incidence of both dementia and AD rose exponentially up to the age of 90 years, with no sign of leveling off. The incidence rates for vascular dementia varied greatly from study to study, but the trend was also for an exponential rise with age. There was no sex difference in dementia incidence (p = 0.21), but women tended to have a higher incidence of AD in very old age, and men tended to have a higher incidence of vascular dementia at younger ages. East Asian countries had a lower incidence of dementia than Europe (p = 0.0004), and also tended to have a lower incidence of AD. CONCLUSIONS: The incidence of dementia rises exponentially to the age of 90 years. Any sex differences are small, and incidence is lower in East Asia than in Europe.     

Doppler grid surface scanning applications for pulmonary subsurface parenchymal perfusion assessment

Subsurface perfusion to lung parenchyma underlying the pleura is difficult to assess in live ventilated animals. The purpose of this study was to assess applicability of a newly developed laser Doppler grid scanning imaging technology that measures perfusion of pleural subsurface lung regions in intact normal and abnormal animal lungs. Eighty-six Doppler grid perfusion measurements were performed in five New Zealand White Rabbits (3-5 kg); four with unilateral bullous lung disease, one normal control. Left upper lobe lung surface was exposed to 10 1-sec spot Nd:YAG exposures (70 W/cm2). One week following laser exposure, all rabbits underwent sequential bilateral open thoracotomy. Unaffected left lower lobes in these animals and all four lobes of a previously untreated rabbit were used as controls. Pleural subsurface perfusion measurements were recorded over a contiguous 900-pixel square surface grid using quantitative noncontact laser Doppler imaging during open thoracotomy procedures. Scans were obtained in a normal volume ventilation mode, at 30 cm of inspiratory hold airway pressure, and postinflation. A perfusion-pressure response curve was obtained in normal lung at 10-, 20-, and 30-cm static airway pressure. Post mortem measurements were used as 0 flow controls. Normal lung tissue was found to have relatively high pleural subsurface perfusion (1362 +/- 328 corrected units on a scale of 0-4095). Areas of atelectasis had decreased perfusion (659 +/- 512 U., 48.4 +/- 12.5% compared to normal lung, p < 0.02), but returned to normal levels after inflation of the lung (1253 +/- 363 U., p = 0.21 compared to normal). Pleural subsurface perfusion decreased uniformly and progressively as lung inflation pressure increased (p < 0.0001). Perfusion increased immediately to supranormal values following release of high inspiratory inflation pressure holds (1603 +/- 626 U., 117 +/- 18% compared to normal lung, p = 0.03). Bullae had markedly decreased perfusion (541 +/- 68 U.) that was not further reduced by increased inflation pressures. Noncontact laser Doppler grid perfusion imaging appears to provide a new tool for measuring pleural subsurface perfusion over a large area of lung surface in clinical experimental settings. Results are rapid, reproducible, and consistent. Sampling errors inherent in current point sampling Doppler flow techniques are reduced by the multiple contiguous measurements. We have used this technique to demonstrate inspiratory pressure-related reduction in pleural subsurface perfusion in normal lung, reversible decreased perfusion in atelectatic regions, and reduced perfusion in bullous and laser-treated lung regions.     

Involvement of the Fas/Fas ligand pathway in activation-induced cell death of mycobacteria-reactive human gamma delta T cells: a mechanism for the loss of gamma delta T cells in patients with pulmonary tuberculosis

Although the identity of T cells involved in the protection against Mycobacterium tuberculosis (Mtb) in humans remain unknown, patients with pulmonary tuberculosis (TB) have reduced numbers of Mtb-reactive, V gamma 9+/V delta 2+ T cells in their blood and lungs. Here we have determined whether this gamma deltaT loss is a consequence of Mtb Ag-mediated activation-induced cell death (AICD). Using a DNA polymerase-mediated dUTP nick translation labeling assay, 5% or less of freshly isolated CD4+ alpha beta or gamma delta T cells from normal healthy individuals and TB patients were apoptotic. However, during culture Mtb Ags induced apoptosis in a large proportion of V gamma 9+V delta 2+ peripheral blood T cells from healthy subjects (30-45%) and TB patients (55-68%); this was increased further in the presence of IL-2. By contrast, anti-CD3 did not induce any significant level of apoptosis in gamma delta T cells from healthy subjects or TB patients. Mtb Ag stimulation rapidly induced Fas and Fas ligand (FasL) expression by gamma delta T cells, and in the presence of metalloproteinase-inhibitors >70% of gamma delta T cells were FasL+. Blockade of Fas-FasL interactions reduced the level of Mtb-mediated gamma delta T cell apoptosis by 75 to 80%. Collectively, these findings demonstrate that Mtb-reactive gamma delta T cells are more susceptible to AICD and that the Fas-FasL pathways of apoptosis is involved. AICD of gamma delta T cells, therefore, provides an explanation for the loss of Mtb-reactive T cells during mycobacterial infection.     

Circulating leptin levels during acute experimental endotoxemia and antiinflammatory therapy in humans

Leptin, a newly discovered adipose tissue-derived weight-reducing hormone, is increased in acute inflammation and may be involved in the anorexia and wasting syndrome associated with infection. To determine whether this hormone responds to an acute inflammatory stimulus, plasma leptin concentrations were measured in 12 healthy subjects after intravenous administration of endotoxin. These subjects were randomized to receive concurrently ibuprofen or placebo normal saline (6 in each group). Endotoxin administration resulted in fever, leukocytosis, and an increase in plasma levels of the stress hormones adrenocorticotropic hormone (3.2 +/- 0.3 to 132.6 +/- 75.5 pmol/L, P = .001) and cortisol (431.6 +/- 44 to 796.9 +/- 99 mmol/L, P = .001). Plasma leptin levels, however, did not change significantly from baseline values after administration of endotoxin (0 h: 6.9 +/- 3.1 ng/mL; 6 h: 6.0 +/- 2.2; 24 h: 6.5 +/- 2.8). While ibuprofen suppressed fever and symptoms associated with endotoxemia, it had no effect on the plasma levels of leptin. In conclusion, acute experimental human endotoxinemia is not associated with acute changes in circulating leptin levels.     

Regression of childhood Barrett's esophageal mucosa by antireflux surgery and bipolar electrocoagulation

The authors report a case of a 13-year-old girl with Barrett's esophagus who underwent antireflux surgery and was subsequently treated with endoscopic thermal coagulation using bipolar electrocoagulation. Follow-up endoscopy 15 months after completion of the endoscopic therapy showed normal esophageal mucosa without intestinal metaplasia. Longer follow-up is needed to assess the long-term effects of endoscopic treatment of the Barrett's mucosa with thermal coagulation, and this procedure should still be considered under investigation.     

Peroral anticoagulant therapy--are the TT-values reliable?

As part of the Norwegian Medical Association's quality assurance programme for the primary health care sector we have investigated the lasting quality of the specimens drawn for determination of Thrombotest. Blood drawn into siliconated glass tubes resulted in varying Thrombotest values, depending on the time of analysis after specimen collection. Reliable Thrombotest values are needed to be able to administer the correct dosage of warfarin. Thrombotest analysis should therefore be performed within two hours, or after 48 hours of specimen collection.     

Distribution and diversity of halophilic bacteria in a subsurface salt formation

A macromolecular prodrug of the known antiretroviral agent zidovudine and alpha, beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) was synthesized. A succinic spacer was present between the polymer and the drug, and 1,1'-carbonyldiimidazole was used as the coupling agent. In vitro drug release studies at pH 1.1, 5.5 and 7.4 indicated that limited amounts of intact drug were released from the conjugate. At pH 1.1 and 7.4 succinylzidovudine was released, and this was hydrolysed to give free zidovudine. In the presence of alpha-chymotrypsin, zidovudine was released preferentially in comparison with the succinyl derivative. The amounts of released zidovudine and succinylzidovudine were greater in plasma than in aqueous buffer solutions. These results show that after i.v. administration this drug-polymer conjugate can release zidovudine into the blood circulation for prolonged periods.     

Fatal rhino-orbital-cerebral zygomycosis

Rhinocerebral zygomycosis is usually an aggressive, fulminant and, at times, fatal disease most often affecting poorly controlled diabetics of all ages. We report the case of a 13-month-old white boy, a previously undiagnosed diabetic. He came to our hospital with recurrent epistaxis, decreasing consciousness, and a small visible infection at the inner canthus of the left eye. Initial evaluation revealed that the patient was in diabetic ketoacidosis. Despite aggressive medical and surgical treatment, his condition deteriorated rapidly, including the development of diabetes insipidus, and he died 4 days after admission. At autopsy, he was found to have fungal cerebritis (Rhizopus) with multiple areas of infarction and massive cerebral edema.     

Comparative effects of enteric-coated pancreatin microsphere therapy after conventional and pylorus-preserving pancreatoduodenectomy

BACKGROUND: A comparative study was performed between patients with exocrine pancreatic insufficiency after conventional pancreatoduodenectomy (Whipple's procedure) and pylorus-preserving pancreatoduodenectomy (PPPD). In these patients the pharmacodynamics of 2-mm enteric-coated pancreatin microspheres (ECPMs) and their gastric transit time in relation to that of a solid meal were investigated. The efficacy of ECPM preparations may differ after Whipple's procedure compared with PPPD, because the latter procedure does not include gastrectomy. METHODS: Gastric transit was assessed by double-isotope scintigraphy. A pancake meal was labelled with 99mTc. ECPMs were cold-labelled with 170Er and neutron activated shortly before ingestion to enable imaging with a gamma camera. Intraluminal pancreatic enzyme activity was assessed during a 6-h period with two indirect tests: the cholesteryl [14C]octanoate breath test and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid-p-aminosalicylic acid (NBT-PABA-PAS) test. RESULTS: In patients who had Whipple's procedure, the gastric transit time of ECPMs and of the pancake meal was not significantly different. The outcome of the indirect pancreatic function tests during enzyme supplementation was comparable, and not significantly different, from that in healthy volunteers. In patients who had PPPD, however, the gastric transit time of microspheres was greatly delayed compared with that of the pancake meal (P < 0.05). Improvement in the outcome of the indirect pancreatic function tests during enzyme supplementation was much less and remained well below that of healthy volunteers (P < 0.05). CONCLUSION: In cases of exocrine pancreatic insufficiency after Whipple's procedure, 2-mm ECPM treatment adequately restores pancreatic enzyme activity. Following PPPD, however, ECPM treatment is often ineffective because the microspheres are retained in the stomach. In these patients, use of conventional powdered pancreatin enzyme preparations may improve the efficacy of treatment.