Proteinuria in benign nephrosclerosis.

Benign nephrosclerosis seldom is associated with significant proteinuria or reduced renal function. This study demonstrated that, despite the finding of benign nephrosclerosis on a renal biopsy specimen, concomitant proteinuria is predictive of a poor prognosis. Twelve patients, ranging in age from 24 to 59 years, with hypertension, proteinuria (greater than 1 g/d), and findings of benign nephrosclerosis on renal biopsy specimens were studied retrospectively. In three of these patients, the hypertension and proteinuria were diagnosed during pregnancy. Follow-up was possible in 11 patients. Nine patients became nephrotic in the course of their disease. Two patients had endstage renal disease and required maintenance dialysis treatment. Seven patients had decreased renal function as shown by the increase in serum creatinine levels. Thus, the combination of hypertension, proteinuria (greater than 1 g/d), and benign nephrosclerosis may be indicative of a progressive condition with a high percentage of patients having renal failure.

The effect of withaferin A on human peripheral blood lymphocytes. An electron-microscope study.

Cultures of normal human peripheral blood lymphocytes stimulated by phytohaemagglutinin (PHA) were treated with withaferin A and examined by an electron microscope. The compound was found to affect the spindle microtubules of cells in metaphase. There were no intact pole-to-pole microtubules or pole-to-kinetochore microtubules found in the treated cells; the centrioles were located in the center. Furthermore, cells at interphase were also affected, the membrane system of the cells being damaged.

The effect of withaferin A, a natural steroidal lactone, on the fine structure of S-180 tumor cells.

Mouse sarcoma 180 (S-180) solid and ascites tumor cells were treated in vivo and in vitro with withaferin A and observed with the electron microscope. The compound was found to effect this spindle microtubules of cells in metaphase. An interesting finding was the double membranes surrounding the chromosomes in the treated cells; probably the nuclei were reconstructed directly from the metaphase stage in the in vivo withaferin A-treated cells. In addition the membranes of the cells in interphase were affected by in vivo or in vitro treatment with the compound.

Lupus nephritis. Electron-dense and immunofluorescent deposits and their correlation with proteinuria and renal function.

Thirteen patients who had systemic lupus erythematosus were studied for the purpose of correlating the findings of light and electron microscopy and immunofluorescent studies with renal function and the presence of proteinuria. Subendothelial deposits of electron-dense material were found in all biopsy specimens, whereas mesangial and subepithelial deposits were not always present. IgG and beta 1c were constant findings in the glomerular membrane. The seven patients who were found to have extensive subendothelial deposits had moderate to massive proteinuria, and four of these patients had decreases in renal function. Most of the patients who had smaller subendothelial deposits had slight or insignificant proteinuria. Massive subendothelial deposits were mainly found in specimens showing histologic evidence of active lesions. Correlation was also found between proteinuria and the overall amount of deposits and their distribution. The prognosis was dependent on the severity of subendothelial deposits, the overall amount of deposits, and the morphologic form of lupus nephropathy.

IgA-IgG nephropathy: a clinicopathologic entity with slow evolution and favorable prognosis.

Renal biopsy specimens were obtained from nine patients with proteinuria and persistent macroscopic or microscopic hematuria. Histologic examination either disclosed no abnormality or showed moderate mesangial thickening and occasionally, evidence of focal segmental glomerulonephritis. Immunofluorescent studies revealed diffuse generalized mesangial deposits of IgA, IgG and betalc in all specimens. Fibrinogen deposits were present in the mesangial space in four specimens only, while IgM was uniformly absent. Serial sections of identical glomeruli allowed the localization of betalc within both IgA and IgG deposits. Ultrastructural studies of the renal biopsy specimens showed accumulation of electron-dense material in the subendothelial region of the capillary loops and the mesangium, with thickening of its matrix. Follow-up data indicated a generally good prognosis.

The clinicopathologic features of cryoglobulinemic nephropathy.

Renal biopsy specimens from eight patients with cryoglobulinemic nephropathy were examined by light, electron, and immunofluorescence microscopy. The light microscopic features were not diagnostic. Characteristic ultrastructural findings were observed in all except one specimen and consisted of glomerular electron-dense deposits, which had a coarse, granular appearance at low-power magnifications and revealed tubular, annular and in a few cases, also fibrillar structures at high-power magnifications. Subendothelial deposits were a constant finding. The presence of intravascular thrombi (deposits), osmiophilic bodies, and crystals within the cytoplasm of the glomerular cells are also helpful for the diagnosis of this entity. Because of these specific findings, cryoglobulinemic nephropathy should be recognized as a clinicopathologic entity.

Pure squamous cell carcinoma and mixed adenosquamous cell carcinoma of the thyroid gland.

Four cases of pure squamous cell carcinoma and two cases of mixed squamous cell and glandular carcinoma are reported. Obviously, there is a possibility that squamous cell carcinoma of the thyroid gland develops from the existing squamous cells or as a result of metaplasia of follicular cells. Metastases and direct extension of squamous cell carcinoma in the thyroid gland are much more frequent and must be excluded before the diagnosis can be established. Although the gross and microscopic pathology of these lesions presents no unusual features, follicles lined by metaplastic squamous cells offer strong presumptive evidence of a primary thyroid neoplasm. These tumors are comparatively radioresistant and biologically highly malignant. The treatment of choice is radical surgical resection, and these neoplasms must be treated more aggressively in the initial stage.

Instability of leukocyte aggregation: lack of evidence for leukoembolization during various states of inflammation.

This study centers on the question of whether the phenomenon of leukocyte aggregation, which is typical to inflammatory conditions, is pathogenic per se. We examined patients and laboratory animals in whom the presence of aggregated leukocytes in the peripheral blood was documented by direct visualization and where, despite the presence of aggregated leukocytes, neither the patients nor the laboratory animals showed clinical or pathological evidence for leukoembolization. Our in vitro findings about the reversibility of the phenomenon of leukocyte aggregation help to explain the above-mentioned observations as well as the well-known daily clinical experience that, despite complement activation and other aggregatory stimuli, there is no clinical or pathological evidence for leukoembolization.

Leydig's and sertoli cells. Their fine structures in three cases of Klinefelter's syndrome.

Testicular biopsy specimens obtained from three patients with Klinefelter's syndrome were studied by light and electron microscopy. Of note in the ultrastructural findings were the absence of annulate lamellae in the Sertoli cells and the abnormal mitochondria, the presence of microcrystalline formations, and the absence of the crystals of Reinke in Leydig's cells. It is suggested that the impaired hormonal function of the testes in Klinefelter's syndrome may be related to the absence of annulate lamella in the Sertoli cells and the presence of microcrystal formations in Leydig's cells.

Unusual renal deposit in mixed connective tissue disease.

We describe a patient with clinical signs of mixed connective tissue disease who developed nephrotic syndrome. The kidney biopsy revealed glomerular and vascular deposits that stained positive with Congo red and showed a green birefringence. The Congo red positivity became negative in sections treated with potassium permanganate. Peroxidase-antiperoxidase staining with anti-AA antibodies was strongly positive. Ultrastructurally, although the deposits were similar to amyloid, they were about twice the size of amyloid fibrils. To our knowledge, the deposition of an amyloidlike material that shows the histochemical and immunohistochemical features of amyloid AA but is lacking the distinctive ultrastructural characteristics of amyloid fibrils has not been described.

On the sensitivity of the probability of error rule for feature selection.

The low sensitivity of the probability of error rule (Pe rule) for feature selection is demonstrated and discussed. It is shown that under certain conditions features with significantly different discrimination power are considered as equivalent by the Pe rule. The main reason for this phenomenon lies in the fact that, directly, the Pe rule depends only on the most probable class and that, under the stated condition, the prior most probable class remains the posterior most probable class regardless of the result for the observed feature. A rule for breaking ties is suggested to refine the feature ordering induced by the Pe rule. By this tie-breaking rule, when two features have the same value for the expected probability of error, the feature with the higher variance for the probability of error is preferred.

Contextual template matching: a distance measure for patterns with hierarchically dependent features.

Contextual template matching refers to situations where the feature sets of the two templates under consideration may not be identical, but are rather contingent on the context within which these templates are observed. This paper addresses context-dependent template matching where the relevancy of certain features to a given object is contingent on the value of higher level features. In such situations portions of the patterns for two objects X and Y may not be comparable, and therefore classical distance measures are not applicable. A framework for describing pattern spaces with hierarchically dependent features-named conditional pattern spaces (CPS)-is presented, and a distance measure for comparing objects in a CPS is developed and illustrated on archaeological objects. This measure satisfies several desired properties of distance measures, such as the metric requirements.

Sensitivity analysis in bayesian classification models: multiplicative deviations.

The sensitivity of Bayesian pattern recognition models to multiplicative deviations in the prior and conditional probabilities is investigated for the two-class case. Explicit formulas are obtained for the factor K by which the computed posterior probabilities should be divided in order to eliminate the deviation effect. Numerical results for the case of binary features indicate that the Bayesian model tolerates large deviations in the prior and conditional probabilities. In fact, the a priori ratio and the likelihood ratio may deviate within a range of 65-135 percent and still produce posterior probabilities in accurate proximity of at most ±0.10. The main implication is that Bayesian systems which are based on limited data or subjective probabilities are expected to have a high percentage of correct classification despite the fact that the prior and conditional probabilities they use may deviate rather significantly from the true values.

Evaluating Multimembership Classifiers: A Methodology and Application to the MEDAS Diagnostic System.

Performance evaluation measures for multimembership classifiers are presented and applied in a retrospective study on the diagnostic performance of the MEDAS (Medical Emergency Decision Assistance System) system. Admission and discharge diagnoses for 122 patients with one or more of 26 distinct disorders in five major disorder categories were gathered. The average number of disorders per patient was 2 with 36 (29.5 percent) patients having 3 or more disorders simultaneously. The features (symptoms, signs, and laboratory data) available at admission were entered into a multimembership Bayesian pattern recognition algorithm which permits for diagnosis of multiple disorders. When the top five computer-ranked diagnoses were considered, all of the correct diagnoses for 86.1 percent of the patients were displayed by the fifth position. In 71.6 percent of these cases, no false diagnosis preceded any correct diagnosis. In ten cases a discharge diagnosis which was suggested by the available findings was omitted by the admitting physician. In six of these ten cases, the overlooked diagnoses appeared at the computer ranked list above all false diagnoses. Considering the urgency of diagnosis in the Emergency Department, the high uncertainty involved due to the limited availability of data, and the high frequency with which multiple disorders coexist, this limited study encourages our confidence in the MEDAS knowledge base and algorithm as a useful diagnostic support tool.

Pattern-Based Interactive Diagnosis of Multiple Disorders: The MEDAS System.

A knowledge-based interactive sequential diagnostic system is introduced which provides for diagnosis of multiple disorders in several body systems. The knowledge base consists of disorder patterns in a hierarchical structure that constitute the background medical information required for diagnosis in the domain under consideration (emergency and critical care medicine, in our case). Utilizing this knowledge base, the diagnostic process is driven by a multimembership classification algorithm for diagnostic assessment as well as for information acquisition [1]. A key characteristic of the system is congenial man-machine interface which comes to expression in, for instance, the flexibility it offers to the user in controlling its operation. At any stage of the diagnostic process the user may decide on an operation strategy that varies from full user control, through mixed initiative to full system control. Likewise, the system is capable of explaining to the user the reasoning process for its decisions. The model is independent of the knowledge base, thereby permitting continuous update of the knowledge base, as well as expansions to include disorders from other disciplines. The information structure lends itself to compact storage and provides for efflcient computation. Presently, the system contains 53 high-level disorders which are diagnosed by means of 587 medical findings.

The state of leucocyte adhesiveness/aggregation (LAA) in the peripheral blood of burned mice: an early and sensitive inflammatory indicator and a marker of pulmonary leukostasis.

The inflammatory response during thermal injury increases the adhesiveness of white blood cells. A direct slide test was used to compare the state of leucocyte adhesiveness/aggregation (LAA) in the peripheral blood of mice subjected to a thermal injury with the findings in control animals. The state of LAA in the peripheral blood increased from baseline values of 1.1 +/- 1.1 per cent to 6.5 +/- 1.3 per cent within 1 h and to 11.0 +/- 1.2 per cent and 14.8 +/- 4 per cent after 3 and 6 h respectively following thermal injury. The respective leucocyte counts were 3075 +/- 277/mm3 (baseline), 3871 +/- 359, 3840 +/- 687 and 6395 +/- 1152 cells/mm3. The LAA values had subsided by 5 days following burning and correlated with the degree of pulmonary leukostasis. Our study suggests that the LAA is an early and sensitive marker of inflammation and that it can be used as a marker for the presence of pulmonary leukostasis during thermal injury.

Persistent hyponatremia and inappropriate antidiuretic hormone secretion in children with extensive burns.

Three children aged 2 1/2 to 5 1/2 yr, with burns covering 30%--45% of body surface area, developed hyponatremia and serum hypotonicity on the 5th--6th day following the burn injury. The hyponatremia persisted for 10--15 days. During this period, all three passed inappropriately concentrated urines. One child also demonstrated marked and inappropriate thirst. All three children demonstrated persistent respiratory alkalosis, which appeared and disappeared concomitantly with the hyponatremia. There were no signs of dehydration, and plasma volumes, measured in two children, were normal to high. These children are believed to show evidence of inappropriate antidiuretic hormone (ADH) secretion. In the absence of those conditions known to produce this syndrome, it is postulated that in these children it may have resulted from prolonged pain, anxiety, and/or pyrexia.

The CO2 laser in pediatric surgery.

The CO2 laser has found its place in surgery and is now an accepted modality in many fields. Its application in pediatric surgery is well based and it is our opinion that its use in this field should be more widespread.

Mechanical, biochemical, and structural effects of vitamin D deficiency on the chick heart.

The effects of vitamin D deprivation on the chick heart were investigated from three aspects: cardiac contractility (+/- dP/dT), intracellular high-energy phosphorus compounds, and structural differences. Four-week-old vitamin D-deficient chicks were divided into four groups: Group A served as the normal group and received subcutaneous injections of cholecalciferol; Groups B and C were vitamin D-deficient hearts but perfused differently; Group D received daily subcutaneous injections of 5 micrograms of 1,25(OH)2D3. When the isolated spontaneously beating hearts (modified Langendorff preparation) were perfused with Krebs-Henseleit (KH) solution containing a calcium concentration of 2.5mM, the myocardial contractility of the vitamin D-deficient hearts was significantly increased when compared with group A. After the isolated heart had beaten for one hour, the myocardial contractility in the vitamin D-deficient hearts was found to decline to significantly lower values. Presacrifice administration of 1,25(OH)2D3 improved cardiac performance. Vitamin D deficiency resulted in an enhanced rate of decline of the intracellular high-energy phosphorus compounds. No differences were found in the microscopic study. These observations suggest that vitamin D has a role in cardiac function.

Multiple plasmocytomas of the liver and the spleen.

Imaging in a patient with multiple myeloma and Gaucher's disease showed space-occupying lesions in the liver and spleen. These were found to be plasmocytomas on histologic examination.