Severe erythroblastopenia and hemolytic anemia during a hepatitis A infection

A 41-year-old woman had acute hepatitis A infection complicated with severe anemia due to selective erythroblastopenia and hemolysis. A mechanism involving a cellular immune reaction is suggested. The hematological complications resolved during steroid treatment. She later developed a transient seropositive arthritis.     

Advanced diabetic glomerulopathy. Quantitative structural characterization of nonoccluded glomeruli

Quantitative ultrastructural data were obtained from kidney biopsy material of 12 long-term insulin-dependent diabetics. All patients had overt diabetic nephropathy with increased urinary albumin excretion and reduced glomerular filtration rate. Renal clearance of 51Cr-EDTA was in the range of 16-50 ml X min-1 X 1.73 m-2. All patients received antihypertensive treatment. A combined light- and electron-microscope study was performed. A significant proportion of the glomeruli was totally occluded (mean 36%, range 24-67%). Structural data presented relate only to the open, still-functioning glomeruli. Comparison with data previously obtained showed that the thickness of the peripheral basement membrane [647 nm, coefficient of variation (C.V.) 0.22] was more than twice the normal value (310 nm, C.V. 0.08); the width of epithelial foot processes (352 nm, C.V. 0.07) was significantly greater than in normal biopsies (224 nm, C.V. 0.06); and the mean volume of the open glomeruli was markedly increased compared with normal and clearly exceeded that in the early diabetic hypertrophy. Total mesangial volume and total basement membrane material per open glomerulus were increased by 277 and 614%, respectively. However, capillary length and surface per open glomerulus were similar to those observed in early diabetic hypertrophy. These findings suggest that a late glomerular hypertrophy with preservation of capillary surface occurs as a compensatory phenomenon, prolonging renal survival for diabetic nephropathy patients.     

Quantitative changes of cerebral neocortical structure in insulin-treated long-term streptozocin-induced diabetes in rats

The brains of rats with streptozocin-induced diabetes treated with a low-dose insulin regimen (1 IU/day) were studied with morphometric techniques. After 1 yr of diabetes, brain weight decreased slightly (1350 +/- 71 vs. 1521 +/- 55 mg, 2P less than .01) as did the volume of the neocortex (498 +/- 36 vs. 567 +/- 40 mm3, 2P less than .05). A significant loss of neocortical neurons occurred (38 +/- 2 X 10(6) vs. 46 +/- 3 X 10(6), 2P less than .01), and the length of the capillary network in the neocortical tissue shortened disproportionately (405 +/- 102 vs. 631 +/- 47 m, 2P less than .01), leading to increased diffusion distance. The mechanisms underlying cerebral loss in this model are unknown, but abnormalities of the vascular supply with prolongation of the route of diffusion might play a role.     

Interference reflection microscopic study of dorsal root growth cones on different substrates: assessment of growth cone-substrate contacts

The contact between dorsal root growth cones and substrates of type IV collagen, fibronectin, poly-L-lysine, and laminin were studied using interference reflection microscopy (IRM) coupled with detaching growth cones from these substrates and observing substrate-associated membrane (SAM). IRM images of growth cones on collagen and fibronectin indicate substantial dark areas of close association between the substrate and basal region of the growth cone. The thin membranous veils and lamellapodia appear bright, indicating a greatly decreased association with the substrate. Filopodia can appear either entirely dark or light but usually are dark interspersed with brighter areas indicating varying degrees of contact. IRM images of growth cones on polylysine and laminin suggest a decreased association between the basal region of the growth cone and the substrate. The appearance of veils and lamellapodia was similar to that observed on collagen and fibronectin. Observations of SAM indicate an increased degree of contact between growth cones and substrates of collagen and fibronectin compared to laminin and polylysine. Collectively these data indicate that simple increases in adhesion are not adequate to explain substrate preference and enhancement of neurite elongation. Overall decreases in adhesion may accomplish the same phenomena, suggesting that it is perhaps more important to consider the regional distribution of adhesive contacts in relation to growth cone movement.     

Megestrol acetate versus aminoglutethimide for metastatic breast cancer

In this prospective, randomized study the clinical response and toxicity of megestrol acetate (MA) and aminoglutethimide (AG) as second-line treatment in patients with metastatic breast cancer was compared. 176 patients were included, and 150 received treatment greater than 8 weeks and are evaluable for treatment response. The two groups did not differ with regard to prognostic factors. Response rate for the AG and MA groups were 34% and 31% respectively, with duration of response of 13.1 and 13.0 months. Stable disease was obtained in 33% and 35% respectively. No difference was observed in survival. Side effects occurred more frequently in the AG group (42%) than in the MA group (18%).     

Some new, simple and efficient stereological methods and their use in pathological research and diagnosis

Stereology is a set of simple and efficient methods for quantitation of three-dimensional microscopic structures which is specifically tuned to provide reliable data from sections. Within the last few years, a number of new methods has been developed which are of special interest to pathologists. Methods for estimating the volume, surface area and length of any structure are described in this review. The principles on which stereology is based and the necessary sampling procedures are described and illustrated with examples. The necessary equipment, the measurements, and the calculations are invariably simple and easy.     

Reproducibility of histomorphologic diagnoses with special reference to the kappa statistic

Systems for classification and grading used in pathology should ideally be biologically meaningful and at least be reproducible from one pathologist to another. A statistical method to evaluate reproducibility (non-chance agreement) for several observers using nominal or ordinal categories has been developed and refined over the past few decades--the kappa statistic. A high level of observed agreement among different pathologists can either signify a high level of reproducibility, if agreement by chance is low, or express a low level of reproducibility, if agreement by chance is almost as high as the observed agreement. Therefore, the observed agreement says nothing in itself, unless it is low. The kappa value, however, indicates how much better the observers are compared to a throw of the dice, and therefore gives the real credit to the agreement which was found. We have developed a user-friendly computer program for calculating inter- and intra-observer agreement of 2 or more observers. By calculating associations between different categories and different observers, the statistic furthermore obtains a function close to the parameter of accuracy. We recommend the use of the above method before a set of nominal or rank scale parameters are used for deciding prognosis and treatment of patients. By submitting a diskette the computer program will be available at no cost.     

Cyclical use of tamoxifen and high-dose medroxyprogesterone acetate in advanced estrogen receptor positive breast cancer

Summary One-hundred and seventy patients with estrogen receptor positive (10 pmol/g protein) advanced breast cancer have been treated in a prospective randomized study either with continuous tamoxifen 30 mg × 1 daily (TAM), or with TAM 30 mg × 1 daily for 8 weeks alternating with medroxyprogesterone acetate 500 mg × 2 daily for 8 weeks (TAM/HD-MPA). The response rate was 62% in the group treated with cyclic TAM/HD-MPA versus 41% in the TAM alone group (p = 0.02). There was no significant difference in duration of remissions or survival.     

Optic nerve head sector analysis recognizes glaucoma most effectively around disc poles

PURPOSE: To analyze the topography of normal and glaucomatous discs with the goal of developing improved strategies to discriminate between normal and glaucomatous eyes. SUBJECTS AND METHODS: Raster tomography was performed in both eyes of 225 healthy subjects and in 296 eyes of 214 glaucoma patients. Cup area, average cup radius, rim area and minimal rim width were measured in 24 sectors around the optic nerve head at nine different depths from the reference plane. Receiver Operating Curves (ROC) for numerous combinations of parameter, sector and depth were calculated and compared. RESULTS: Discrimination between glaucomatous and normal eyes varied widely between single sectors of the optic disc, and was best at the vertical poles of the disc, intermediate in nasal sectors and worst in temporal sectors. When single sectors or combinations of sectors at the superior pole were combined with their counterparts at the inferior pole of the optic nerve, the gain in sensitivity exceeded the loss in specificity, and discrimination improved. Separation declined dramatically if any of the 8 temporal sectors were involved in such analysis. Depth influenced discrimination only slightly. CONCLUSION: Single sectors located close to the vertical meridian yielded better discrimination than global measurements. When two or more sectors at the superior pole were combined with each other, as well as with their counterparts at the inferior pole, discrimination improved even further. Localized changes concurred frequently, but asymmetrically at both poles of the disc. The depth from reference plane used to define the cup was not critical for separation between normal and glaucomatous eyes.