Recognition of Dementia in General Practice: Comparison of General Practitioners' Opinions with Assessments Using the Mini-Mental State Examination and the Blessed Dementia Rating Scale

Mant A, Eyland E A, Pond D C, Saunders N A and Chancellor AH B. Recognition of dementia in general practice: comparisonof general practitioners' opinions with assessments using themini-mental state examination and the Blessed dementia ratingscale. Family Practice 1988; 5: 184–188. In a study of 226 elderly residents in a retirement villagein Sydney, Australia, general practitioners' opinions aboutdementia status had high positive and negative predictive valuesand high specificity, but low sensitivity when evaluated againstthe mini-mental state examination and the Blessed dementia ratingscale. General practitioners were found to disagree with thesetwo measures more often when patients were in advanced old age,and when they considered the patients to be depressed. We concludethat the general practitioner can increase his or her sensitivityto dementia in the elderly by use of either measure.     

Use of PC12 Cells as a Neurotoxicological Screen: Characterization of Anticyanide Compounds

A series of six biochemical markers of cyanide toxicity (dopaminerelease, hydroperoxide generation, cytosolic-free calcium levels,catalase activity, cytochrome oxidase activity, and superoxidedismutase activity) in cultured rat pheochromocytoma (PC12)cells were used to establish a screen for evaluation of potentialanticyanide compounds. Thirty-nine substances, including anticonvulsants,adrenergic blockers, antioxidants, and antipsychotics were testedand ranked according to the results. Based on the compositescoring in all six assays, carbamazepine, mannitol, allopurinol,and phenytoin were ranked as the most effective anticyanidecompounds. Additionally, known cyanide antidotes (e.g., pyruvate,mercaptopyruvate, -ketoglutarate, naloxone, and flunarizine)obtained relatively high ranking in the PC12 cell screen. Furthermore,a significant correlation was found between protective effects(based on LD50s) of cyanide antidotes in mice and ranking inthe in vitro screen. This study illustrates that by assayinga series of biochemical markers in a neuronal-type cell line,a rapid, cost-effective in vitro toxicological screen is possible.Several compounds have been identified which inhibit the biochemicaleffects of cyanide and may be used to enhance effectivenessof the standard cyanide antidotes.     

Immunotoxicological Profile of Morphine Sulfate in B6C3F1 Female Mice

This study was undertaken to investigate a number of immuneparameters which may be compromised with exposure to morphinesulfate. Mice were implanted subcutaneously with 8-, 25-, or75-mg morphine sulfate pellets. Placebo pellets of identicalmakeup to the 75-mg morphine pellet (without morphine of course)were used as a control. Twenty-four hours after implantationof a 75-mg morphine pellet, blood levels reached a peak of 1610ng/ml. Corticosterone increased in parallel with morphine andreached a peak level of 966 ng/ml 24 hr after implantation.The dose response of morphine to increase corticosterone, however,was fiat. The weight of the lymphoid organs, spleen and thymus,and the liver were significantly reduced in the morphine-treatedgroups. Morphine treatment was associated with an increase inserum albumin, SGPT, BUN, and alkaline phosphatase indicativeof hepatic damage. In contrast to increased serum proteins,the C3 component of complement was reduced in a dose-dependentmanner. Leukocyte number in the peripheral blood was significantlyreduced, while erythro-cyte number and hematocrit were bothincreased. The number of B cells and T cells was decreased inmorphine-treated animals. However, the percentage of T cellsrelative to B cells was increased. The primary IgM antibodyresponse to the T-depen-dent antigen, sheep red blood cells,was decreased. Natural killer cell activity was reduced in responseto morphine, as was the phagocytic capacity of Kupffer cells.Host-resistance models of Listeria monocytogenes or Streptococcuspneumoniae showed an increased resistance following administrationof morphine. This increased host resistance, however, was notdue to an increase in antimicrobial action of sera obtainedfrom mice treated with morphine. The majority of morphine'seffects on the immune system exhibited a flat dose response,suggesting that these effects may be mediated secondarily throughcorticosterone.     

The Relationship between Use of the Maximum Tolerated Dose and Study Sensitivity for Detecting Rodent Carcinogenicity

The relationship between maximum tolerated dose (MTD) and studysensitivity for detecting rodent carcinogenicity was evaluatedfor 216 chemicals found to be carcinogens in laboratory animalstudies conducted by the National Cancer Institute (NCI) andthe National Toxicology Program (NTP). Approximately two-thirdsof these rodent carcinogens would have been detected even withoutthe top dose (estimated MTD), but in many of these studies,some site-specific carcinogenic effects would have been missed.Among the remaining one-third of the rodent carcinogens thatrequired the top dose for statistical significance, approximately80% had numerically elevated rates of the same site-specifictumors at lower doses as well. Only 13 of the NCI/NTP rodentcarcinogens had increased tumor rates limited to the top dosefor all sites of carcinogenicity. Alternatively, of the 838site-specific carcinogenic effects observed in the NCI/NTP studies,447 (53%) would have been detected even without the top dose.Of the remaining effects, 75% (294/391) showed numerically elevatedsite-specific tumor rates at lower doses. Our evaluation indicatesthat most carcinogenic effects ob served at the top dose inrodent studies are also present (with reduced incidence thatmight or might not be statistically significant) at the lowerdoses typically employed (MTD, MTD).     

Anthropometric Characteristics of Mohawk Children Aged 6 to 11 Years: A Population Perspective

OBJECTIVE: Recent studies have concluded that Native North American children have higher proportions of overweight and obesity than children from the general North American population. This study presents anthropometric data on a representative sample of children from the Mohawk Nation that can be used for comparison with other Native American populations. DESIGN: This is a cross-sectional study comparing distributions of anthropometric characteristics of Mohawk children to the corresponding age and gender data from the Second National Health and Nutrition Examination Survey (NHANES II). Weight, height, triceps and subscapular skinfold thickness, and waist and hip circumferences were measured in 527 children. SUBJECTS/SETTING: All children in grades 1 to 6 (aged 6 to 11 years) in the 3 elementary schools of 2 Mohawk communities in Canada, for whom parental consent was obtained, were enrolled in the present study. There were no exclusion criteria. With a participation rate of 83%, the 527 children enrolled in this study represent an unbiased sample of the population from 2 Mohawk territories. RESULTS: Compared with children studied in NHANES II, Mohawk children were similar in height and triceps skinfolds but were generally heavier, had thicker subscapular skinfolds, and had greater waist and hip circumferences. These differences were greater in older children. Mohawk children who had extreme-high weight values compared with their population means were heavier than their NHANES II counterparts. APPLICATIONS/CONCLUSIONS: Results indicated that, on average, Mohawk children seem to be slightly heavier than children in NHANES II. Except for those with extreme overweight values, Mohawk children show less variation of weight and body mass index than children in NHANES II. Finally, overweight Mohawk children seem to be more likely to carry their excess body fat truncally, compared with overweight children from NHANES II. Health practitioners working with Native American populations should be careful when assessing childhood obesity. Simple comparisons of weight or body mass index with NHANES standards may lead to inappropriate risk assessments.     

Pulmonary Immunotoxicity of Inhaled Ammonium Metavanadate in Fisher 344 Rats

Male Fisher 344 rats were exposed to 2 mg vanadium(V)/m³ (asammonium metavanadate NH⁴VO³, 0.32 µm MMD) atmospheresfor 8 hr/day for 4 days in a nose-only exposure system. In exposedrats, lung V burdens increased in a time-dependent fashion.Analysis of lung cells and lavage fluid 24 hr after the finalexposure suggested that tissue damage and a strong inflammatoryresponse was elicited; numbers of neutrophil and small macrophages(M), as well as levels of lavageable protein and lactate dehydrogenase,were significantly elevated as compared with levels observedwith air-exposed rats. Vanadium also affected pulmonary alveolarM (PAM) capacities to produce and respond to immunoregulatingcytokines. Inducible PAM production of tumor necrosis factor-awas significantly inhibited, as was the ability to increasecell surface Class II/I-A molecule expression in response tointerferon- (rFN-). PAM from V-exposed hosts were also inhibitedin their ability to be primed by EFN- to produce superorideanion and hydrogen peroxide in response to stimulation withopsonized zy-mosan. These studies indicate that short-term repeatedexposure of rats to atmospheric V, at levels encountered inan occupational setting, can alter host pulmonary immunomocompetence,with one major effect occurring at the level of cytokine-relatedfunctions. These alterations may be underlying mechanisms forthe well-documented increases in bronchopulmonary infectionsand cancers in workers chronically exposed to V-containing atmospheres.