Lice, damned lice, and statistics.
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Biomedical subjects
Publications and source records attributed to R Robinson.
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Experimental designs in ophthalmologic research frequently treat both eyes of a subject in the same fashion: e.g., therapy with a specific drug or control. In these two-eye designs, observations from the same subject are often positively correlated. Failure to account for this correlation is a serious error which overstates the precision of studies, resulting in falsely significant results. This paper reviews the statistical methods appropriate for studies where endpoints are quantitative. We present: (1) the use of analysis of variance (t-test when there are 2 treatment conditions) to estimate differences between all experimental treatments, (2) the use of contrasts to estimate differences between specific treatments, and (3) methods for analysis of data from multiple experiments. Because of the ubiquity of incorrect analysis of data from two-eye designs in the ophthalmologic research literature and the serious consequences of this error, we propose a limited statistical review of manuscripts to ascertain if the statistical analysis matched the experimental design.
A middle aged woman referred for an abdominal mass was found to have large amounts of dopa (3-4-dihydroxyphenylalanine) metabolites in her urine. At operation a tumour affecting almost the entire left lobe of the liver was removed. Histologically the tumour was a metastatic carcinoid. After operation the excretion of dopa metabolites fell substantially, confirming that the tumour was the source. Apparently, owing to an enzyme defect the tumour had been unable to decarboxylate dopa. These findings are further evidence of a neural origin for the endocrine system of the gut.
Fifteen patients with advanced hematopoietic and other malignancies were treated with recombinant DNA produced Alpha 2 Interferon (IFN) (Schering) by intravenous (IV) and intramuscular (IM) routes at weekly intervals in escalating doses from 1 X 10(6) IU to 100 X 10(6) IU in order to determine the tolerance and pharmacokinetics. The most common side effects included fever, chills, myalgia, and arthralgia. At doses of 60 X 10(6) or above, severe but reversible hypotension was observed in five patients receiving interferon by intravenous route. Patients receiving interferon by intramuscular route had fever, chills, and myalgias but did not develop hypotension at the same dosage. Two patients with non-Hodgkin lymphoma showed objective evidence of regression. Our data suggest a biphasic pattern of elimination with terminal half-life ranging from 1.9 to 2.9 hours and peak titer of 16,000 units and under for IV interferon, and terminal half-life of 6 hours with peak titers of 600 units for intramuscular interferon. However, interpatient variability precludes a definite conclusion. Although the areas under the serum concentration vs time curves were similar, the intravenous route provided higher but unsustained levels of interferon than the intramuscular route.
A new anaerobic, mesophilic, spore-forming cellulolytic bacterium is described. Cellulose is cleared within 24 to 48 h around colonies formed in cellulose agar roll tubes. Cells stain gram negative and are nonmotile rods which form oblong spores either centrally or subterminally in a clostridial swelling. Colonies are irregular with an opaque edge and a center devoid of both vegetative cells and spores. Cellulose, xylan, pectin, cellobiose, glucose, maltose, galactose, sucrose, lactose, and mannose serve as substrates for growth. H(2), CO(2), acetate, butyrate, formate, and lactate are produced during fermentation of cellulose or cellobiose. The temperature and pH for optimum growth are 37 degrees C and 7.0, respectively. The DNA composition is 26 to 27 mol% guanine plus cytosine. This bacterium resembles "Clostridium lochheadii" in morphological and some biochemical characteristics but is not identical to it. The name Clostridium cellulovorans sp. nov. is proposed. The type strain is 743B (ATCC 35296).
Previous work from this laboratory described an association, based on genetic evidence, between a 68 000 dalton protein (p68) and corticotropin (ACTH) sensitive adenylate cyclase activity among variants of the Y1 mouse adrenocortical tumor cell line. To study the nature of this association further, we have purified p68 and raised a polyclonal anti-p68 serum in rabbits. A variant subclone of the Y1 line, in which p68 comprised approximately 10% of total soluble protein, was used as starting material. Purification of p68 was achieved by passage of a 100 000 X g supernatant fraction over DEAE-cellulose, fractionation with ammonium sulfate, and chromatography on hydroxylapatite. The purified protein had an isoelectric point of 7.3, a polarity value of 46%, and a blocked amino terminal end group. A rabbit antiserum raised against the purified p68 had a titer of 1:16 000 and specifically precipitated p68 from extracts of Y1 cells labeled with L-[35S]methionine. Using this antiserum, p68 also was detected in other cell lines including mouse erythroleukemia and Sertoli cells; rat Leydig, ovary, and glioma cells; and Chinese hamster ovary cells. The presence of p68 in a variety of cell types suggests that the function of p68 is not restricted to adrenal cells or to specific actions of ACTH.
The influence of topical corticosteroid on the efficacy of five topical antifungal agents was evaluated in a standardized rabbit model of Candida keratitis using a quantitative mycologic technique. Topical 1% prednisolone acetate worsened the disease when given alone and adversely influenced the efficacy of 5% natamycin, 1% flucytosine, and 1% miconazole when given in combination. The efficacy of amphotericin B appeared unaffected when the antifungal agent was administered in concentrations of 0.5% and 0.15%. The adverse effect of the topical corticosteroid appeared to be inversely related to the efficacy of the antifungal agent in vivo.
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Serum dopamine-beta-hydroxylase (DBH) activity has been reported to be raised in some patients with neuoblastoma but this has been challenged. We have studied serum DBH levels on 26 children with neuroblastoma and 58 age-matched controls. Only in 2 patients were the levels higher than in the controls, and then only transiently. In both, the rise in DBH levels could be accounted for by the transfusion of adult blood. Serum DBH levels in children with neuroblastoma were unrelated to the response of this neoplasm to treatment or to urinary catecholamine output and thus are unlikely to have any value in diagnosis or as a marker of tumour activity.
A standardized model of Candida albicans keratitis was developed in pigmented rabbits using a quantitative mycologic technique to evaluate the disease at intervals throughout the course. In this model, using two different infecting strains, the efficacy of five antifungal agents was compared. Amphotericin B, in concentrations of 0.5% to 0.075%, was superior to all other agents tested. Natamycin 5% ranked next, followed by 1% flucytosine, and 1% miconazole. Ketoconazole 1% was ineffective.
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A multicentre study to evaluate the activity of amoxycillin when combined with clavulanic acid against clinical bacterial isolates was performed in South Africa. Minimum inhibitory concentrations for amoxycillin alone and in combination with clavulanic acid were determined by agar dilution. The majority of amoxycillin-resistant Klebsiella and Escherichia coli strains became sensitive to amoxycillin in the presence of low concentrations of clavulanic acid. Beta-lactamase-producing strains of Staphylococcus aureus showed increased susceptibility to amoxycillin in the presence of clavulanic acid. Minimum bactericidal concentrations indicated that amoxycillin retains bactericidal activity in the presence of clavulanic acid. Enterobacter and Serratia species and Pseudomonas aeruginosa remained amoxycillin-resistant in the presence of clavulanic acid.
Serum uric acid levels were measured in 133 dehydrated patients admitted with diarrhea. Elevated levels were found in 80% of the patients; the highest was 38 mg/dL. Serum uric acid was correlated with serum urea nitrogen and the levels tended to be higher in patients with hypernatremia. The serum uric acid levels returned toward normal with rehydration, and no specific therapy was necessary.
Eleven cDNA clones identified from a cDNA library prepared from the mRNA fraction of SV40 transformed cells detected, by hybridization, higher levels of cellular mRNA in SV40-transformed cells than in nontransformed cells. Three of these cDNA clones detected levels of cellular mRNA that were more than 100-fold greater in SV40tsA transformed cell lines grown at the permissive temperature than in those grown at the nonpermissive temperature. Northern blot hybridizations confirmed these results and in some cases detected RNA species of multiple sizes that were regulated in a temperature-dependent fashion in SV40tsA transformed cell lines. Infection of 3T3 cells with SV40 stimulated the levels of RNAs complementary to these cDNA clones. The results demonstrate that the SV40 large T antigen can regulate the steady state levels of some cellular RNA species.
This investigation examined the continued self-destructive behaviors of adolescent suicide attemptors treated at Childrens Hospital of Los Angeles from 1972 through 1978. A total of 235 questionnaires were mailed to subjects who were hospitalized as a result of an accident, illness, or suicide attempt. The questionnaire was designed to elicit data with respect to the occurrence, frequency of occurrence and medical consequences of various self-destructive behaviors. The results suggest that certain continued self-destructive behaviors may be manifested by adolescents who have attempted suicide. Implications of the findings of this pilot study are discussed with regard to developing a theoretical model of self-destructive behaviors in adolescent suicide attemptors and the clinical prediction of adolescent suicide.
Adolescent suicide has become an increasingly important problem in today's society. In an effort to understand the precipitating factors in adolescent suicide attempts and the professional response to the adolescent attempting suicide, a comprehensive review was undertaken at the Children's Hospital of Los Angeles (CHLA). A total of 232 subjects admitted to CHLA from January 1972 through July 1978 were included in a retrospective chart analysis. Data on adolescents who had attempted suicide were extracted from their medical records and compared with those of matched groups of adolescents admitted for reasons other than suicide attempt. Comparisons were made of demographic data, family background, hospital admissions, and professional involvement. Our findings confirmed that most attemptors are female midadolescents and are likely to use drugs in the attempt. In addition, our results underscored the importance of the family with respect to the precipitation of an adolescent suicide attempt and the subsequent treatment approach.
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Antibody to the major purified cytochrome P-450 induced by 3-methylcholanthrene in rat liver strongly inhibits aryl hydrocarbon hydroxylase activity of uninduced and benz[a]anthracene-induced human monocytes and lymphocytes. Antibody to the cytochrome P-450 induced by phenobarbital has relatively little or no effect on the aryl hydrocarbon hydroxylase activity of the same human cells.