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T McConnell

Publications and source records attributed to T McConnell.

At least 19 recordsLinked to original sources
PubMed2001

Marginal plafond impaction in association with supination-adduction ankle fractures: a report of eight cases.

In five years, approximately 800 ankle fractures were seen at the authors' institution, forty-four (5 percent) of which were of the supination-adduction pattern. Nineteen of these injuries had displaced vertical medial malleolus fractures, of which eight (42 percent) showed marginal impaction of the tibial plafond. All eight patients underwent open reduction and internal fixation with elevation of the impacted articular component and had good to excellent functional outcome with no arthritis on radiograph at the time of the most recent follow-up. The index of suspicion of marginal impaction of the tibial plafond should be high when treating supination-adduction pattern ankle fractures with displaced medial malleolus.

Adult↗
PubMed2000

Isolated tibial shaft fracture.

A nineteen-year-old otherwise healthy woman is seen in the emergency room after being struck by a car. The patient reports left lower extremity pain and has no other injuries. Exam shows a Tscherne grade I soft tissue injury with otherwise normal motor and sensory exam. There are no signs of compartment syndrome. A closed reduction was performed.

Adult↗
PubMed1997

Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study.

Compared with younger patients, elderly patients with acute myeloid leukemia (AML) respond poorly to conventional chemotherapy. To determine if this poor response is due to differences in the biologic characteristics of AML in the elderly, we studied 211 patients (161 de novo, 50 secondary AML) over 55 years of age (median, 68 years) registered to a single clinical trial for previously untreated AML (SWOG 9031, Phase III randomized trial of standard dose cytosine arabinoside and daunomycin + rhG-CSF). Pretreatment leukemic blasts were karyotyped and were also analyzed for intrinsic drug resistance by quantitating expression of the multidrug resistance glycoprotein MDR1 and functional drug efflux using sensitive flow cytometric techniques. Results were correlated with clinical variables and outcome. These elderly AML patients had a high frequency of unfavorable cytogenetics (32%), MDR1 protein expression (71%), and functional drug efflux (58%); each of these factors occurred at high frequencies in both de novo and secondary AML patients and was associated with a significantly poorer complete remission (CR) rate. In multivariate analysis, secondary AML (P = .0035), unfavorable cytogenetics (P = .0031), and MDR1 (P = .0041) were each significantly and independently associated with lower CR rates. Resistant disease was associated with unfavorable cytogenetics (P = .017) and MDR1 expression (P = .0007). Strikingly, elderly MDR1(-) de novo AML patients with favorable/intermediate cytogenetics had a CR rate of 81%; with increasing MDR1 expression, CR rate decreased in this cytogenetic group. MDR1(+) secondary AML patients with unfavorable cytogenetics had a CR rate of only 12%. Thus, AML in the elderly is associated with an increased frequency of unfavorable cytogenetics and MDR1 expression, both of which independently contribute to poor outcomes. The high frequencies of these features in both de novo and secondary elderly AML patients suggest a common biologic mechanism for these leukemias distinct from that in younger patients. Investigation of biologic parameters at diagnosis in AML in the elderly may help identify patients with a high likelihood of achieving CR with conventional regimens, as well as those who may require alternate regimens designed to overcome therapy resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Multidrug resistance-1 (MDR1) expression and functional dye/drug efflux is highly correlated with the t(8;21) chromosomal translocation in pediatric acute myeloid leukemia.

Resistance to chemotherapy is a major problem in acute myeloid leukemia (AML). An important resistance mechanism in adult AML is active drug efflux mediated by the multidrug resistance protein-1 (MDR1). To determine if MDR1 is important in childhood AML, we examined MDR1 expression and functional dye/drug efflux in 20 pediatric/adolescent AML patients; results were correlated with cytogenetics and clinical outcome. Using flow cytometry, MDR1 protein expression on the leukemic blasts was measured with the antibody MRK16, while efflux was measured by extrusion of the fluorescent dye DiO(C2)3 in the presence/absence of cyclosporin A (CsA). Six of 20 cases expressed MDR1. While all six MDR1+ cases were efflux+, three of 14 MDR1- cases also demonstrated efflux. Both MDR1 and efflux were strongly correlated with the t(8;21). All six MDR1 +/efflux+ cases and 2/3 MDR1 -/efflux+ cases had a t(8;21), while no MDR1-/efflux- cases had a t(8;21) (P < 0.0005). This correlation between MDR1, efflux, and the t(8;21) in pediatric AML was not found in 11 adult t(8;21) cases similarly studied. Although the clinical relevance of MDR1 in pediatric AML awaits larger studies, our results suggest a biologic subset of pediatric AML patients may benefit from regimens which include MDR1-reversing agents or non-MDR1 substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Increase in enkephalin-like immunoreactivity in hippocampi of adults with generalized epilepsy.

The changes of opioid peptide reactivity in seizure activity have been well studied in animals. Increased enkephalin and dynorphin immunoreactivity in the hippocampi of animals are interpreted as the result of seizure induced mossy fibre sprouting. We studied the hippocampi of six patients with a history of long-standing grand mal seizures and six age-matched control patients with no history of epilepsy or neurologic disease, using frozen sections which were immunostained with antibodies against Leu-enkephalin and Met-enkephalin. The staining intensity in the CA3, CA4 and internal molecular layer of the dentate fascia in each case was quantified using optical densitometry image analysis. The CA3 and CA4 of the epileptic hippocampi showed highly significant increase in Leu-enkephalin-like immunoreactivity compared to the controls (P < 0.005) while the inner molecular layer showed only significant increase (P < 0.05). Met-Enkephalin-like immunoreactivity was only significantly increased in CA4 of the epileptic hippocampi (P < 0.05).

Adult↗
PubMed1994

Signet ring cell adenocarcinoma of prostate.

Primary signet ring cell adenocarcinoma of the prostate is a rare malignancy with a total of 13 cases reported to date in the English literature. We report a very unusual case of signet ring adenocarcinoma of the prostate occurring in a patient who presented initially with irritative voiding symptoms and a bladder mass. Results of immunohistochemical, flow cytometric, and cytogenetic analyses of the tumor are presented.

Carcinoma, Signet Ring Cell↗
PubMed1994

Confidentiality and the law.

Codes of medical ethics issued by professional organizations typically contain statements affirming the importance of confidentiality between patients and health-care practitioners. Seldom, however, is the confidentiality obligation depicted as absolute. Instead, exceptions are noted, the most common of which is that health-care professionals are justified in breaching the confidence of a patient if required by law to do so. Reasons that might be given to support this exception are critically discussed in this paper. The conclusion argued for is that this is not a legitimate exception to the confidentiality rule.

Codes of Ethics↗
PubMed1993

Dense microspheres in the human hippocampus.

Dense microspheres (DMS) are structures found within neuronal processes of the adult human brain. Although best known as a feature of the neocortex, they are also found in the hippocampal formation. We describe a characteristic pattern of DMS distribution in the human hippocampus. The functional significance of this pattern is unknown, but it casts doubt on the proposed relationship of DMS to senile plaques. We also present evidence that DMS are composed of protein, but without a significant component of carbohydrate or neutral glycoprotein.

Adult↗
PubMed1992

Prenatal diagnosis of transient myeloproliferative disorder via percutaneous umbilical blood sampling. Report of two cases in fetuses affected by Down's syndrome.

Since its initial description in 1982, percutaneous umbilical blood sampling has become useful in diagnosing, monitoring, and even treating a variety of fetal disorders. Recently two percutaneous umbilical blood samples were evaluated in which the white blood cell count was markedly elevated with many circulating blasts. Both samples exhibited the morphologic features of a transient myeloproliferative disorder, characteristically seen in neonates and infants with Down's syndrome. In both cases, antenatal clinical and ultrasound abnormalities also were suggestive of Down's syndrome, which was confirmed by cytogenetic studies. Although the peripheral blood abnormalities persisted at birth, both patients experienced spontaneous remission of the transient myeloproliferative disorder by 5 weeks of age. To our knowledge, these two cases of Down's syndrome represent the first reported examples of the intrauterine diagnosis of transient myeloproliferative disorders.

Adult↗
PubMed1990

Cloning and characterization of the t(15;17) translocation breakpoint region in acute promyelocytic leukemia.

A reciprocal chromosomal translocation, t(15;17)(q22;q11.2-12), is characteristic of acute promyelocytic leukemia (APL) of French-American-British (FAB) subtype M3, and is not associated with any other human malignancy. The non-random pattern of the APL translocations suggests that specific genes on chromosomes 15 and 17 are somehow altered or deregulated as a consequence of the rearrangement. Translocation breakpoints in APL patients provide physical landmarks that suggest an approach to isolating the APL gene(s). Genetic and physical maps constructed for the APL breakpoint region on chromosome 17 have indicated that two fully-linked DNA markers, defining loci for THRA1 and D17S80, map to opposite sides of an APL breakpoint yet reside on a common 350-kb Clal fragment. Cosmid-walking experiments to clone this APL breakpoint have revealed a 38-kilobase deletion on chromosome 17. Studies in additional APL patients have shown that the breakpoint region on chromosome 17 spans at least 80 kilobases.

Chromosome Walking↗
PubMed1990

Megalencephaly in the epileptic chicken: a morphometric study of the adult brain.

The epileptic chicken is a genetic model of generalized epilepsy in which epilepsy is combined with megalencephaly. We have performed a morphometric study of the brains of adult epileptic hens, using heterozygous carrier hens as controls. There is no obvious disorder of cell form or of architectural arrangement in the megalencephalic brains. We have found that the enlargement of the epileptic brain is not uniform: it is most marked in the telencephalon, and is present to a lesser degree in the cerebellum, but neither the optic tectum nor the diencephalic nucleus rotundus shows a significant increase in size. The enlarged regions are characterized by a decrease in the packing density of neurons. There is an increase in the total neuron population in some of the enlarged areas (archistriatum), despite the lower density per unit volume, but in other enlarged areas (hippocampus) there is no difference in total neuron numbers. The glial cells, by contrast, show no significant alteration in packing density. These findings suggest that the megalencephaly of the epileptic chicken is due to an increase in neuron size, with a contribution from increased numbers of neurons and glial cells. The epileptic chicken may provide a valuable model for further dynamic studies of aberrant neuronal development, and of structural-functional relationships in epilepsy.

Animals↗
PubMed1989

Localization of preferential sites of rearrangement within the BCR gene in Philadelphia chromosome-positive acute lymphoblastic leukemia.

The Philadelphia chromosome associated with acute lymphoblastic leukemia (ALL) has been linked to a hybrid BCR/ABL protein product that differs from that found in chronic myelogenous leukemia. This implies that the molecular structures of the two chromosomal translocations also differ. Localization of translocation breakpoints in Philadelphia chromosome-positive ALL has been impeded due to the only partial characterization of the BCR locus. We have isolated the entire 130-kilobase BCR genomic locus from a human cosmid library. A series of five single-copy genomic probes from the 70-kilobase first intron of BCR were used to localize rearrangements in 8 of 10 Philadelphia chromosome-positive ALLs. We have demonstrated that these breakpoints are all located at the 3' end of the intron around an unusual restriction fragment length polymorphism caused by deletion of a 1-kilobase fragment containing Alu family reiterated sequences. This clustering is unexpected in light of previous theories of rearrangement in Philadelphia chromosome-positive chronic myelogenous leukemia that would have predicted a random dispersion of breakpoints in the first intron in Philadelphia chromosome-positive ALL. The proximity of the translocation breakpoints to this constitutive deletion may indicate shared mechanisms of rearrangement or that such polymorphisms mark areas of the genome prone to recombination.

Base Sequence↗
PubMed1987

Genetic risk for recombinant 8 syndrome and the transmission rate of balanced inversion 8 in the Hispanic population of the southwestern United States.

A rec(8) dup(q) syndrome, secondary to a pericentric inversion--inv(8)(p23q22)--has been identified in 26 probands from Hispanic kindreds in the southwestern United States. The clinical phenotype of the Hispanic rec(8) syndrome includes a dysmorphic facies, cardiovascular and urinary-tract malformations, and mental retardation. Segregation analysis utilizing pedigree and cytogenetic data from 31 kindreds including five additional kindreds from additional sources has provided computation of genetic risks for counseling. An inv(8) carrier parent has a 6.2% risk of having a rec(8) child. The transmission rate of the inv(8) was significantly higher for inv(8) carrier mothers (59%) than for carrier fathers (42%). The combined transmission rate for both sexes was 53%. Risk for spontaneous abortion or stillbirth (11.3%) was not higher than the general population frequency of 13%-15%. It is significant that all kindreds identified to date are of Hispanic background with ancestors traced to the southern Colorado/northern New Mexico region. By means of extended pedigree information, three independently ascertained kindreds have been linked through common ancestry 4 generations in ascendance. The Hispanic background, geographic localization, and common ancestry in three kindreds suggest a single founder of the Hispanic inv(8) in the Southwest.

Chromosome Inversion↗
PubMed1984

Coronary myointimal hyperplasia in freshwater Lake Michigan salmon (genus Oncorhynchus). Evidence for lipoprotein-related atherosclerosis.

The relationship between plasma lipoprotein concentration and histologic myointimal proliferative lesions in the coronary vessels was examined in 37 freshwater Chinook salmon (Oncorhynchus tshawytscha). The fish were obtained during the migrating, schooling, and spawning periods of the fourth year of life. Plasma apoB polypeptides were maximally elevated in the migrating fish in correlation with a high degree of coronary vascular disease. Both the relative incidence and the severity of lesions were greater in migrating salmon as compared with spawning fish. In contrast, plasma apoA polypeptides were maximally elevated in association with reduced levels of plasma apoB in spawning fish in which coronary lesions were reduced in severity and incidence. Simultaneous observations confirmed the relative decrease in circulating thyroid hormone and increase in adrenal cortical hormones characteristic of the maturation process. These data in the mature freshwater Lake Michigan Chinook salmon provide direct support for the hypothesis that coronary proliferative atherogenesis proceeds in parallel with excessive exposure to apoB-containing lipoproteins and that reversal is associated with excessive exposure to apoA-containing lipoproteins. The temporal relationship to altered hormone status is described, but the pathophysiologic significance for atherogenesis cannot be determined from these data.

Adrenal Cortex Hormones↗
PubMed1982

Gastric parietal cell and other autoantibodies in the BB rat.

A longitudinal study of circulating autoantibodies in the sera of 48 BB rats was performed by indirect immunofluorescence. No pancreatic islet cell, adrenocortical, or thyroid microsomal autoantibodies were found. However, autoantibodies reactive to gastric parietal cells (PCA), smooth muscle, and thyroid colloidal antigens were identified, PCA were not detected in Wistar-Furth or BB x Wistar-Furth F1 hybrid rats. The range of ages at the time of first appearance of PCA was the same as that of onset of insulin-dependent diabetes (IDD) in the BB rats, suggesting that the processes leading to PCA and IDD were occurring at the same time of life in these animals. The presence of PCA was associated with degrees of lymphocytic gastritis and with squamous metaplasia of the gastric mucosa in the oldest BB rats (9 mo of age). Levels of serum iron and vitamin B12 did not differ between PCA-positive and PCA-negative BB rats, nor was achiorhydria found in any rat studied. The identification of PCA (and chronic gastritis) and other autoantibodies in the BB rat suggests that these animals have an underlying autoimmune diathesis. These findings thus provide indirect support for an autoimmune pathogenesis for IDD in the BB rat.

Achlorhydria↗