Managing the behavioral problems of dementia in the home.

The majority of persons with dementia are cared for in the home by family and friends. The goals of treatment in this setting are to maximize the quality of life of the demented person and minimize burdens on the caregiver. Behavioral problems are common with dementia and can lead to significant caregiver burden. Behaviors that are most common or most serious to caregivers include behaviors related to memory disturbances, restlessness and agitation, catastrophic reactions, day/night disturbances, delusions, wandering, and physical violence. A general method for clinicians to manage these problems involves the identification of the behavior and its antecedent and consequent events. Stressors that may cause behavioral problems include fatigue, a change of routine, excessive demands, overwhelming stimuli, and acute illness or pain. Caregivers can be taught to identify these stressors in order to prevent or alleviate troublesome behaviors. When behavioral techniques are not successful and the behaviors are particularly dangerous or burdensome, therapy with low doses of high-potency neuroleptics has been suggested. Measures such as these to help caregivers in the management of dementia at home can be instrumental in improving the quality of life for the person with dementia.     

Monoclonal antibody direct immunofluorescence for the identification of Neisseria gonorrhoeae strains grown on selective culture media

Commercially available reagents for monoclonal antibody immunofluorescence, polyclonal antibody immunofluorescence, and coagglutination were employed in comparison with a rapid sugar fermentation test used for identifying clinical isolates of Neisseria gonorrhoeae recovered on modified Thayer-Martin media. Of 68 gonococcal strains, 68 were positive by the monoclonal immunofluorescent antibody. Of 16 nongonococcal gram-negative, oxidase-positive diplococci, all were negative by this reagent. Monoclonal antibody immunofluorescence was more specific and more sensitive than polyclonal antibody immunofluorescence and more sensitive than coagglutination.     

Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level, and relative body weight in normal and obese subjects

This study was undertaken to obtain further information on the mechanism by which blood fibrinolytic activity, a balance between plasminogen activators and inhibitors, is lowered in obese subjects. Fasting blood samples were collected from 35 subjects, aged 15 to 45 years, with normal glucose tolerance and a Body Mass Index (BMI) varying widely between 16 and 45 (normal, 19 to 25). Euglobulin Fibrinolytic Activity (EFA) did not correlate with the level of tissue type plasminogen activator (t-PA) related antigen but exhibited a negative correlation with the level of PA inhibitor (r = -.609, P less than 0.01). EFA was negatively and PA inhibitor positively correlated with both BMI (r = -.381, P less than 0.02 and .664, P less than 0.01, respectively) and plasma insulin level (r = .410, P less than 0.02 and .521, P less than 0.01, respectively). Stepwise analysis showed that these correlations were independent. As expected, plasma insulin was correlated with BMI (r = .512, P less than 0.01) and triglyceride level (r = .38, P less than 0.02), total cholesterol with age (r = .379, P less than 0.02). Ten obese subjects were submitted to a 24-hour fast. While body weight did not change appreciably, plasma insulin decreased from 22.3 +/- 2.2 to 16.3 +/- 1.1 microU/ml, EFA increased from 3.6 +/- .8 to 4.9 +/- .67 mm, and PA inhibitor decreased from 4.52 +/- .76 to 3.44 +/- .63 IU/mL. All these differences were significant. T-PA-related antigen did not change.(ABSTRACT TRUNCATED AT 250 WORDS)     

The increased plasma Lp(a): B lipoprotein particle concentration in angina pectoris is not associated with hypofibrinolysis

The structural homology between plasminogen and apolipoprotein (a), the specific glycoprotein of Lp(a) lipoprotein, raises the possibility of a relationship between this lipoprotein and the plasma fibrinolytic system. The present study examines this proposal by studying 66 patients with angina pectoris. As compared to normal controls, the patients had raised concentrations of Lp(a): B lipoprotein particles. No correlation was found between circulating Lp(a): B and the fibrinolytic system. The pathogenic role of Lp(a): B lipoprotein seems therefore not mediated by its effect on the plasma fibrinolytic system.     

Autoantibodies against bactericidal/permeability-increasing protein in patients with cystic fibrosis

Cystic fibrosis (CF), a genetic disorder, is characterized by chronic pulmonary infection/inflammation which leads to respiratory failure. The presence of anti-neutrophil cytoplasmic autoantibodies (ANCA) has previously been observed in the sera of patients with CF. In view of the known relationship of ANCA with primary vasculitis and of their putative pathogenetic role in these disorders, we studied the presence, specificity and isotype of ANCA and their clinical associations in 66 adult CF patients. None of the 66 CF samples had autoantibodies to the major ANCA antigens, proteinase 3 or myeloperoxidase. However, 60/66 (91%) CF samples contained IgG and 55/66 (83%) IgA, autoantibodies to bactericidal/permeability increasing protein (BPI), a recently characterized ANCA specificity. All the IgA anti-BPI-positive samples were also IgG anti-BPI-positive. The autoantibody specificity was confirmed by inhibition assay and immunoblotting of CF sera against a neutrophil granule preparation. Furthermore, in this cross-sectional study, anti-BPI levels were inversely correlated with the observed reductions in FEV1 and FVC (IgA anti-BPI and FEV1: r = 0.508, <it>p</it> &lt; 0.0001), and both IgG and IgA anti-BPI levels were higher in CF patients with secondary vasculitis (<it>n</it> = 6) than in those without (<it>p</it> &lt; 0.05). ANCA with specificity for BPI were present in the majority of CF sera in this study and autoimmune processes may be associated with the development of pulmonary injury in CF.      

Treatment of Felty's syndrome with the haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF)

Felty's syndrome (FS) (rheumatoid arthritis with neutropenia and splenomegaly) has a poor prognosis, largely because of the high risk of severe infection. Granulocyte colony-stimulating factor (G-CSF) is an emerging treatment for chronic neutropenia. We prospectively monitored its use in eight patients with recurrent infections or who required joint surgery. Significant side-effects were documented in five, including nausea, malaise, generalized joint pains, and in one patient, a vasculitic skin rash. In two patients treatment had to be stopped, and in these cases G-CSF had been started at full vial dosage (300 micrograms/ml filgrastim or 263 micrograms/ml lenograstim) alternate days or daily. G-CSF treatment was continued in three patients by restarting at reduced dose, and changing the proprietary formulation. G- CSF raised the neutrophil count, reduced severe infection, and allowed surgery to be performed. A combined clinical and laboratory index suggested that long-term treatment (up to 3.5 years) did not exacerbate the arthritis. Once on established treatment, it may be possible to use smaller weekly doses of G-CSF to maintain the same clinical benefit. One of the three patients whose FS was associated with a large granular T-cell lymphocytosis showed a reduction in this subset of lymphocytes during G-CSF treatment.      

The effect of sterilization on transforming growth factor beta isolated from demineralized human bone

Growth factors have been identified as the primary cause of osteoinduction in bone healing. Transforming growth factor beta (TGF- beta) has been shown to promote bone formation and is present in bone in high quantities. The aims of the present study were to isolate TGF- beta from human bone, demonstrate its biologic activity, and analyze the effects of conventional sterilization techniques on activity. Bone, obtained from femoral heads of five patients (mean age, 70 years) was ground, demineralized, and freeze-dried, and samples from each patient were divided into three groups: no treatment, sterilization with 1.60 to 1.94 Mrad of 60Co irradiation, and sterilization with ethylene oxide (ETO). Carrier-free recombinant TGF-beta control was also treated and was totally inactivated by ETO but not by irradiation (p < 0.01). TGF- beta activity in demineralized bone was not significantly diminished (p > 0.1) by either sterilization procedure, and substantial amounts of active TGF-beta were recovered in all bone samples: 1.04 +/− 0.77 ng per mg of protein in irradiated samples, 0.67 +/− 0.26 ng per mg in ETO- treated samples, and 1.04 +/− 0.33 in untreated samples, respectively (mean +/− SD). Although a recent report demonstrated that the osteoinductive activity of bone morphogenetic protein in bone powder is diminished considerably by ETO and by 2.5 Mrad of irradiation sterilization of bone powder, these data demonstrate that TGF-beta activity, with its osteoinductive properties, was not destroyed in more coarsely ground, demineralized bone by ETO or by lower doses of irradiation. These findings support the use of human bone allografts in clinical instances involving impaired bone formation.     

The plasminogen activator inhibitor-1 −675 4G/5G genotype influences the risk of myocardial infarction associated with elevated plasma proinsulin and insulin concentrations in men from Europe: the HIFMECH Study

Summary. Although the potential role of plasminogen activator inhibitor‐1 (PAI‐1) in the development of coronary artery disease is strongly supported by its biological characteristics, results of clinical studies remain controversial. Objectives: To investigate whether plasma PAI‐1 concentrations and the ?675 4G/5G polymorphism located in the PAI‐1 gene could constitute risk markers for myocardial infarction (MI). Patients and methods: We used a European case–control study, the HIFMECH study, comparing 598 men with MI and 653 age‐matched controls. Results: Insulin resistance explained a major part of the variation in PAI‐1 (24%) whereas inflammation had only a minor contribution (0.01%). For both cases and controls plasma PAI‐1 concentrations were significantly higher in the North than the South, and in both regions were higher in individuals with MI compared with control subjects [overall odds ratio (OR) for a 1 SD increase = 1.54, 95% confidence interval (CI) 1.34, 1.77]. This difference was observed in all the centers studied. Overall, the difference between cases and control subjects remained significant after controlling for inflammation variables (OR = 1.30, 95% CI 1.08, 1.57), but lost significance after controlling for insulin resistance variables (OR = 1.17, 95% CI 0.98, 1.40). The 4G allele was associated with significantly higher PAI‐1 levels in cases but not controls and, taken independently, did not modify the risk of MI (P = 0.9). However, a significant interaction was observed with both insulin or proinsulin and the risk of MI (P = 0.05 and 0.02, respectively), but not with triglycerides or body mass index (BMI). The insulin or proinsulin effect on risk was observed only in the carriers of the 4G/4G genotype. This interaction appeared not to be mediated by plasma PAI‐1 antigen concentrations (P = 0.01 and 0.02 after adjustment for PAI‐1 plasma levels). The interaction with proinsulin but not insulin remained statistically significant after further adjustment for other factors associated with insulin resistance (triglycerides and BMI) and C‐reactive protein (P = 0.01). Conclusion: This study suggests that PAI‐1 has a role in risk of MI in the presence of underlying insulin resistance. A significant interaction between insulin or proinsulin and the ?675 4G/5G polymorphism was observed in risk for MI. The mechanisms for these interactions remain to be determined.