A model of the natural history of screen-detected prostate cancer.
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Biomedical subjects
Publications and source records attributed to J A Lane.
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BACKGROUND: Helicobacter-pylori-related duodenal ulcer (DU) is an important cause of dyspepsia. AIM: To determine the relationship between the pattern of H. pylori infection and the epidemiology of duodenal ulcer in a single population. DESIGN: Prospective two-part study of (i) patients with DU referred for endoscopy because of dyspepsia, and (ii) the incidence of H. pylori infection in the general population of the same area. METHODS: Details of 533 DU patients were recorded, and related to the pattern of H. pylori infection among 10 537 adults in the same community, determined by the (13)C-urea breath test. RESULTS: In patients with DU, birth year was more important than age in determining the rate of presentation for endoscopy (the 'birth cohort' effect). H. pylori infection showed a similar birth cohort effect, and the prevalence decreased steadily in those born in successive years, from 28.8% in the 1930s to 3.5% in the 1970s. The proportion of dyspeptic patients who had duodenal ulcers also fell progressively, from 22.2% in 1979 to 5.7% in 1998. H. pylori prevalence and duodenal ulcer incidence were closely correlated at all ages. DISCUSSION: Duodenal ulcer prevalence (as judged by the rate of referral of duodenal ulcer patients for endoscopy) is determined principally by the distribution of H. pylori infection in the local population. The birth cohort effect seen in adult duodenal ulcer patients reflects the acquisition of H. pylori in childhood. In Bristol, H. pylori prevalence and duodenal ulcer incidence are both declining to very low levels.
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PURPOSE: The onset of dry eye is very common during menopause and may result from the loss of hormonal support. The purpose of this study was to assess the effect that changes in sex hormone and prolactin levels have on tear function in premenopausal and menopausal woman. METHODS: Women between the ages of 30 and 60 were solicited to participate in a study concerning menopause and tear function. One-hundred and ten women were given tear function tests (osmolarity, tear volume, tear flow, Schirmer's test) and serum levels were measured for total testosterone, estradiol, prolactin, and follicle stimulating hormone. RESULTS: For all women on hormone replacement therapy, we found a strong negative correlation between serum prolactin level and tear function. For women in menopause, total testosterone correlated positively with tear function, whereas for premenopausal women there was a negative correlation between total testosterone and tear function. Serum estradiol levels correlated positively with tear function for women 30-39 years of age, whereas for menopausal women the correlation was negative. CONCLUSIONS: This is the first demonstration in humans that tear production is correlated with serum prolactin and sex hormone levels prior to and during the menopause.
AIM: A seasonal variation was noted in the incidence of amoeba-like keratitis in Iowa. The level of contamination of amoeba in surface water has been found previously to vary on a monthly basis for Tulsa, Oklahoma, a region with a similar climate. It was hypothesised that this seasonal variation in amoeba-like keratitis correlated with the concentration of amoeba in surface water. METHODS: The monthly variation in the onset of symptoms was determined and date of diagnosis in 137 cases of amoeba-like keratitis, in Iowa, from January 1993 to the end of December 1996. RESULTS: Over a 4 year period a significant variation was found, on a monthly basis, in the onset of symptoms as reported by the patient. There were two peak periods per year when the onset of symptoms was most frequent: June and November. This corresponded closely with the concentration of amoeba in the ground water reported for a similar region in the mid-west (Tulsa, Oklahoma). A yearly increase was found in the number of cases diagnosed from January 1993 to the end of December 1996. CONCLUSIONS: This study supports the hypothesis that the concentration of amoeba in surface water may influence the rate of an amoeba-like keratitis infection.
PURPOSE: To evaluate the confocal microscopic appearance of the tear film by correlating the interference pattern created by the lipid surface with physiologic measurements of tear function and with clinic diagnosis. METHODS: A series of 53 patients was examined with a battery of tests to evaluate the tear film and with confocal microscopy to evaluate the interference pattern created by the lipid surface of the tear film. Assessment of the tear-film appearance involved five nonparametric scales: degree of debris in the tear film, variability of the interference pattern over time, linearity of the interference pattern, number of dry spots seen, and relative thickness of the lipid layer. For 10 other subjects, the confocal appearance of the tear film and evaporation from the ocular surface was tested for before and after meibomian gland expression. RESULTS: The confocal appearance correlated with multiple physiologic variables and clinical diagnosis. Patients with seborrheic meiboman gland dysfunction had a thicker lipid layer, greater variability, and more debris than did patients with obstructive meibomiam gland dysfunction. After meibomian gland expression, lipid thickness and linearity increased, whereas pattern variability and evaporation decreased significantly. The mean reduction in evaporation was 48%. CONCLUSIONS: Confocal microscopy can be used to examine the tear film, and its appearance correlates significantly with physiologic variables in normal-individuals and in disease states. The confocal appearance of the lipid interference patterns and evaporation from the ocular surface are altered after lipid expression from meibomian glands.
A tandem scanning confocal microscope (TSCM) is currently being used to obtain high-resolution images of the human cornea in vivo. Advantages of confocal microscopy for in vivo imaging include optical sectioning and increased contrast through removal of scattered light. We have adapted to TSCM to view the retina in vivo by constructing an applanating lens and fitting the microscope with an imaging-intensifying camera of increased sensitivity. The microscope uses a spinning disc with 40,000 holes, each of 30 microns diameter, and a 100 W mercury arc lamp light source with a 455 nm long pass filter. The applanating lens is composed of three elements, two of which are movable for focusing. Images of a rabbit retina were obtained in vivo revealing the nerve fiber layer and blood vessels around the optic disc. The power density at the retina was calculated to be 3 mW/cm2, which is well below the power levels of a direct or indirect ophthalmoscope. Magnification of the retinal image was approximately 60 x and a 1 mm wide area of retina was in view. This prototype TSCM system demonstrates that images of a retina in vivo are obtainable with confocal microscopy and that the sharpness is comparable to standard fundus camera photography. Further modifications to improve the light level and alterations in the design of the objective should improve the quality of the images obtained and achieve the enhanced resolution of which, in theory, the confocal microscope is capable.
Blepharitis patients have a number of disturbances in their tear film associated with meibomian gland dysfunction that affect evaporation and tear osmolarity. We tested a series of 156 consecutive patients, with a presumed diagnosis of blepharitis, dry eye, or allergic disease, and a series of 72 normals. We compared their tear film characteristics using tear osmolarity, tear volume, tear production (fluorophotometric and Schirmer test), tear turnover (decay constant), tear evaporation, and meibomian gland function evaluated by gland drop-out, expressed lipid viscosity, and volume. Of the 156 patients tested, we found 37 had dry eye, 10 had only allergic disease, 73 had meibomian gland dysfunction and dry eye, and 36 had only meibomian gland dysfunction. We created a model of the relative influence some of these factors had on each other using their correlation coefficients. The highest correlations for osmolarity were Schirmer test (-0.44), lipid volume low (-0.44), lipid viscosity high (0.39), gland drop-out (0.39), and tear evaporation (0.36). With regression analysis we accounted for 47% of the total variation in osmolarity, but only 17% of the variation in tear evaporation. We also present our classification system for blepharitis and dry eye patients based on our measurable physiologic parameters.
We examined a group of normal subjects to evaluate the tear film function by measuring reflex tear capacity using the Schirmer test without anesthetic, steady state tear flow using fluorophotometry, meibomian gland function based on gland drop-out, expressible lipid volume and viscosity, tear loss from evaporation, and tear osmolarity. We found the average tear flow to be 0.19 +/- 0.19 microliters/min, lower than previously measured. The average tear volume was also correspondingly less, 2.74 +/- 2.0 microliters. We found there was a decline associated with advancing age for all parameters except the decay constant and lipid volume. The highest correlations with aging were tear volume (-0.64), Schirmer test (-0.63), and tear osmolarity (0.59). Our results indicate that there is a decline in tear film function throughout life and that tear flow is considerably less than previously estimated.
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We have used genetic engineering to obtain secretion of anti-human CD5 antibody fragments from Escherichia coli for conjugation to the 30-kDa form of ricin A chain (RTA30). This was accomplished by introducing stop codons at two positions in the hinge region of the human IgG1 gene so that coexpression of the truncated heavy-chain genes (Fd') with a light chain would result in Fab' and/or F(ab')2 proteins containing either one or two interheavy-chain cysteines. An Fd' gene encoding both interheavy-chain cysteines yielded a mixture of F(ab')2 and Fab', which could be separated by size-exclusion chromatography. An Fd' gene encoding only one interheavy-chain cysteine yielded primarily Fab'. Purified F(ab')2 protein was equivalent to unlabeled chimeric IgG in competing for binding of IgG with CD5 antigen, while the molar concentration of the monovalent Fab' required for 50% binding inhibition was 4- to 5-fold higher than IgG. An immunoconjugate was prepared with Fab' by direct coupling to the unique free cysteine on RTA30. The bivalent F(ab')2 was conjugated to RTA30 after derivatization with the crosslinking agent 5-methyl-2-iminothiolane. These immunoconjugates efficiently killed a CD5+ T-cell line and human peripheral blood T cells.
Although Catholic nursing education in the United States has traditionally instilled Gospel values in students, pressures from a secular culture are making it increasingly difficult to sustain this heritage. As the twenty-first century approaches, Catholic educators and healthcare administrators need to ask themselves whether Christian values still serve as the explicit basis of nursing service and education at their institutions. They must also ask what distinguishes graduates of Catholic nursing programs from those of other programs. The percentage of schools that are Catholic has remained roughly the same during the past 30 years, but in many cases these schools no longer instill Christian values. Although most programs offer courses in ethics, philosophy, and religion, few provide the value-laden experiences of the past. In fact, many instructors avoid addressing questions of values or ethics because they believe doing so would be a form of indoctrination. Catholic nursing education, like Catholic higher education in general, is becoming increasingly secular. To return Christian values to nursing practice and education, leaders need first to instill a sense of self-worth in nursing staff by letting them know they are valued and their efforts are appreciated. Leaders also need to emphasize the good their institutions do for their communities and make explicit the values on which their practices are based.
Successful immunotoxin therapy may depend upon reduction of the size of the components in order to decrease antigenicity and rate of clearance. In initial attempts to modify the A chain of ricin by deletion analyses within a prokaryotic expression system, coding sequences were modified by the insertion of unique restriction endonuclease sites and by the removal of 22 codons near the 5' terminus. The work presented here examines the expression, solubility, and activity of these mutant proteins and demonstrates that while amino acid residues may be altered in this region, the deletion of residues 19 through 40 yields an insoluble and inactive toxin molecule.
Linkage of ricin A chain (RA) to a cell surface binding antibody or other ligand can result in a potent cytotoxic agent. We expressed the primary sequence for RA in Escherichia coli to facilitate production and to obtain protein free of naturally occurring contaminants, i.e. ricin B chain. Differences in the level of expression and in the characteristics of the expressed protein were noted when several different host/vector systems were tested. Recombinant RA (rRA) was expressed directly under control of the phage lambda major leftward promoter (PL) and the E. coli trp promoter. It was also expressed fused to E. coli alkaline phosphatase sequences, both in the same reading frame for secretion and out-of-reading frame for expression in a cistron-like arrangement. Expression in the PL promoter system, which is temperature-regulated, was achieved at 37 degrees C as well as at 42 degrees C. The protein expressed at these different temperatures had grossly different properties. Whereas rRA expressed at 37 degrees C was soluble and fully active, that produced at 42 degrees C was aggregated, insoluble, and reduced in activity. Soluble rRA could be converted to the insoluble form by incubation at 42 degrees C in vivo, but not in vitro. Hence, this difference in properties does not simply reflect an inherent thermal instability of the protein. Conditions present in vivo, including the possible association with other proteins, are apparently required for this effect on rRA.
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