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Non-osseous bone scan abnormalities in multiple myeloma associated with hypercalcemia.

Uptake of Tc-99m MDP by extraskeletal tissues is a rare, serendipitous finding during bone scanning studies. It can be clinically correlated with the presence of hypercalcemia in association with renal failure, as may occur in multiple myeloma. While the precise mechanism of non-osseous uptake of MDP is not certain, it may represent metastatic calcification based upon histological examination. A critical calcium-phosphate ion product appears to be requisite for deposition within soft tissues, and all cases in the literature for which data were available exceeded this ion product value. While MDP bone scanning is not generally useful in the diagnosis or staging of multiple myeloma, these findings may indicate secondary effects of the disease. The authors report the first case of liver, spleen, and lung uptake by MDP in a patient with hypercalcemia secondary to multiple myeloma, with a review of the literature.

Aged↗

Tests of the precedence effect in sound localization reveal abnormalities in multiple sclerosis.

The precedence effect in sound localization involves presenting identical sounds (e.g., clicks) from pairs of matched speakers situated on opposite sides of a subject's head, with the clicks from one speaker preceding those from the other by a short interval. With appropriate delays, normal subjects perceive a fused image which originates from the side of the leading speaker. This test was administered to 24 patients with multiple sclerosis (MS). Separate tests involving speaker delays ranging from 0 msec (simultaneous presentation) to 8 msec were presented. At 0 msec delay, normal subjects perceived the fused image to be located halfway between the two speakers; at progressively longer delays, the image was perceived closer to the leading speaker. In contrast to normal subjects, a large proportion of the MS subjects exhibited difficulties with the task. The discrimination deficit was limited to delays below 1 msec, suggesting a problem involving an increased threshold for lateralizing the fused image away from midline toward the side of the leading speaker. The neural instability produced by demyelination in MS patients might account for this pattern of results.

Adult↗

Multiple molecular abnormalities in Ph1 chromosome positive acute lymphoblastic leukaemia.

The Ph1 chromosome is present in 95% of patients with chronic myelogenous leukaemia (CML). The Ph1 chromosome also occurs in 5-25% of children and adults with acute lymphoblastic leukaemia (ALL). This observation raises questions as to whether these diseases are similar or identical. In patients with CML the c-abl and bcr genes are translocated and abnormally expressed. We studied molecular events related to bcr and c-abl in five patients with ALL to determine its relationship to CML. Four had the Ph1 chromosome; the fifth a probable Ph1 chromosome. c-abl and bcr abnormalities identical to CML were detected in four suggesting a common molecular basis. One patient with the Ph1 chromosome and c-abl translocation lacked these molecular changes but had abnormal c-abl gene transcription apparently unrelated to bcr. These data suggest that Ph1 chromosome positive ALL is heterogeneous; in some patients the molecular abnormality is identical to CML; in others c-abl is likewise involved but via a different mechanism.

Adolescent↗

Multiple spuriously abnormal thyroid function indices due to heterophilic antibodies.

A 57-year-old man with a history of liver fibrosis, portal hypertension and hypersplenism had thyroid function assessed because of weight loss. Free T4 (FT4), total T4 (TT4), total T3 (TT3) and TSH were all assayed by enhanced chemiluminescent immunoassay. This demonstrated elevation of all three hormones. Because of the atypical profile obtained and because the patient appeared to be euthyroid, re-assay of the patient's serum was performed following immunoglobulin precipitation with 50% polyethylene glycol. The levels of T4 and T3 were then found to be within the reference ranges suggesting that the serum contained interfering immunoglobulins. Anti-immunoglobulin antibodies also neutralized the interfering substances present in the patient's serum. These observations indicate that non-specific immunoglobulins present in the patient's serum cross-reacted with the antibodies employed in the assays used, giving rise to spurious results. To our knowledge, this is the first report of artefactual elevation of results obtained by T4, T3 and TSH assays of a serum occurring as a result of interfering immunoglobulins. Their presence became apparent only because of the very rare coincidence of antibodies interfering with more than one assay giving rise to an atypical hormone pattern. The frequency of this phenomenon affecting a single assay and therefore more likely to go undetected, is unknown and is a cause for concern.

Antibodies, Heterophile↗

Developmental abnormalities in multiple proliferative tissues of Apc(Min/+) mice.

Germ-line mutation of the Apc gene has been linked to familial adenomatous polyposis (FAP) that predisposes to colon cancer. Apc(Min/+) mice, heterozygous for the Apc gene mutation, progressively develop small intestinal tumours in a manner that is analogous to that observed in the colon of patients with FAP (Su et al. 1992; Fodde et al. 1994; Moser et al. 1995). We have studied the effects of Apc gene mutation on murine intestinal and extra-intestinal, proliferatively active tissues. We have contrasted the histology to that of the age- and sex-matched wild-type C57BL/6 mice. Histological assessment of the normal appearing intestinal mucosa demonstrates minimal change in size of crypts. In contrast, villi are longer in the ileum of Apc(Min/+) mice relative to C57BL/6 mice at 12 and 15 weeks of age. Vigorous splenic haematopoiesis in Apc(Min/+) mice was seen at 12 and 15 weeks of age, as reflected by marked splenomegaly, increased splenic haematopoietic cells and megakaryocytes. Peripheral blood counts, however, did not differ between C57BL/6 and Apc(Min/+) mice at 15 weeks of age. Lymphoid depletion in Apc(Min/+) mice was characterized by diminished numbers of splenic lymphoid follicles and small intestinal Peyer's patches. The ovaries of 12- and 15-week-old Apc(Min/+) mice exhibited increased numbers of atretic follicles, and estrous cycling by serial vaginal smears showed tendency of elongation in the mutant mice during these age ranges. The testicles of 10-week-old Apc(Min/+) mice showed increased numbers of underdeveloped seminiferous tubules. Collectively, these data suggest that, in addition to its obvious effects upon intestinal adenoma formation, Apc gene mutation causes impairment of developmental and apparent differentiation blockade in proliferative tissues, including those of the haematopoietic system, lymphoid and reproductive tract.

Adenomatous Polyposis Coli↗

Multiple growth abnormalities in vascular smooth muscle from spontaneously hypertensive rats.

1. In tissue culture the growth characteristics of aortic smooth muscle cells isolated from spontaneously hypertensive rats (SHR) were compared with those of normotensive Wistar-Kyoto (WKY) rats. 2. Aortic smooth muscle cells from SHR exhibit enhanced proliferation when grown in the presence of low (1%) and moderate (5%) concentrations of fetal calf serum. 3. Cell quiescence in cultures of smooth muscle from SHR becomes apparent at cell densities approximately 20% higher than in cultures from WKY rats. 4. These different growth characteristics of smooth muscle between the two strains of rats may contribute to the early pre-hypertensive development of vascular hypertrophy in the SHR.

Animals↗

Platelet function in myeloproliferative disorders: characterization and sequential studies show multiple platelet abnormalities, and change with time.

Bleeding and thrombosis are well known major causes of morbidity and mortality in patients with myeloproliferative disorders (MPD) but the relationship between these clinical events and the commonly found platelet function abnormalities have not been established. In this study we performed simultaneous laboratory evaluations in 54 patients with MPD to investigate abnormalities in platelet aggregation and cyclooxygenase activity, the latter by using an in vitro aspirin inhibition test; the studies were repeated in 22 patients 1-27 months later. We have found platelet hyper- and hypofunction co-existing in some patients (9/54), and change of platelet function during the course of the disease (7/22) with platelet hypofunction being the only constant abnormality over time. These results may explain the lack of correlation between the clinical events and the limited assessment of platelet function in the hitherto published studies, and also suggest the need for repeated evaluations to properly assess the relative risk for bleeding and thrombosis.

Aged↗

Multiple congenital abnormalities in a newborn boy associated with maternal use of fluphenazine enanthate and other drugs during pregnancy.

A boy was born with a short sloping forehead, wide metopic suture, persistent metopic fontanelle, telecanthus, ocular hypertelorism, nystagmoid eye movements, bilateral cleft lip and palate, imperforate anus, rectourethral fistula, bifid scrotum and an unusual penis with hypospadias. The neutrophil polymorphs had numerous nuclear projections. The pregnancy was complicated by chronic maternal schizophrenia, severe toxaemia and maternal use of fluphenazine enanthate, dicyclomine hydrochloride, doxylamine succinate, pyridoxine hydrochloride and other drugs. Details of mother's illness, pregnancy and drug usage are presented with the clinical findings and investigations.

Abnormalities, Drug-Induced↗

Renal vein thrombosis: an underdiagnosed complication of multiple renal abnormalities.

Thirty-one cases of renal vein thrombosis (RVT) were reviewed retrospectively for clinical laboratory, and radiographic findings. An underlying renal disorder was present in 28 cases, absent in only 3. This supports other evidence that RVT is usually a complication of renal disease rather than a primary event, and that nephrotic syndrome may be due to renal disease rather than RVT. The findings also confirmed the large spectrum of urographic appearances in RVT, and were used as a basis for developing specific and liberal indications for renal venography.

Humans↗