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Biomedical subjects

C E Alexander

Publications and source records attributed to C E Alexander.

17 recordsLinked to original sources
PubMed2007

Evidence for the receipt of DNA damage stimuli by PML nuclear domains.

Promyelocytic leukaemia nuclear domains (PML-NDs) comprise a shell of PML protein and many labile cargo proteins. The nature of their cargo, their juxtaposition to foci of damaged DNA following ionizing radiation (IR), and the altered DNA damage responses in PML null cells all implicate PML-NDs in the DNA damage response. In this work, the propensity of PML-NDs to increase in number and decrease in size following IR has been studied. Serial quantitative studies of endogenous PML-NDs prove that the PML-ND response to IR is not the result of the asymmetry in cell cycle distribution that can follow IR, but reflects more directly the process of DNA damage. The response is swift, sensitive (evident after 1 Gy), and potentially reversible in untransformed fibroblasts. In these cells and in HCT116 colon cancer cells, failure to restore PML-ND number within 24 h correlates with later loss of growth potential--in fibroblasts, through prolonged cell cycle arrest and in HCT116 cells, through apoptosis. Failure to express an intact ATM/CHK2 DNA damage signalling pathway in either cell type leads to a delay in the PML-ND response to IR. Conversely, cell cycle progression following IR in cells that detect damaged DNA accelerates PML-ND reorganization. Collectively, these data show that the increase in PML-ND number seen after irradiation is, in part, triggered by the receipt of the DNA damage stimulus. The senescent cell state is also associated with chronic DNA damage and Hayflick-limited fibroblasts were found to express nuclei with elevated numbers of PML-NDs before IR that remained unresponsive to IR. Though the underlying reasons for damage-induced PML alteration remain obscure, it is noteworthy that significant numbers of PML-NDs juxtapose with ionizing radiation-induced foci after IR. The co-regulation of these structures may necessitate the stereotyped increases in PML-ND number following damage.

Apoptosis↗
PubMed2001

CD95 is required for the early control of parasite burden in the liver of Leishmania donovani-infected mice.

In this study we show an increased incidence of T cell apoptosis in the liver and spleen of mice infected with Leishmania donovani. T cells from L. donovani-infected mice were found to be increasingly susceptible to CD95-mediated apoptosis in vitro, compared to controls. To test if suboptimal T cell function resulting from CD95-mediated apoptosis contributes to sustained parasite burden in L. donovani parasitized mice, B6.gld mice (lacking functional CD95 ligand) were infected with L. donovani. Surprisingly, at four different time points no difference in levels of T cell apoptosis in the spleen and liver was found between these mice and controls following intravenous delivery of L. donovani amastigotes, indicating that the CD95 / CD95L interaction is not essential for T cell apoptosis in the L. donovani-infected liver and spleen. However, B6.gld mice were increasingly susceptible to L. donovani infection, associated with less efficient granuloma formation in the liver and uncontrolled parasite growth in the spleen. Late in infection (day 56 post-infection), B6.gld mice had higher numbers of IFN-gamma-producing CD4(+) T cells in the liver and spleen, indicating a role for CD95 signaling in the homeostasis of this subset of cytokine-producing T cells in L. donovani-parasitized mice. Adoptive transfer of CD4(+) and CD8(+) T cells into recombinase activating gene 1 knockout (RAG-1(- / -)) recipients, revealed that CD95L expressed on CD4(+) T cells contributes to early control of L. donovani infection in the liver via mechanisms that are independent of granuloma formation and induction of apoptosis. These results indicate important roles for CD95 and CD95L that are unrelated to regulation of apoptosis in the early control of L. donovani infection.

Animals↗
PubMed1995

Repeat Russe bone grafting after failed bone graft surgery for scaphoid non-union.

We report the long-term outcome of repeat Russe bone grafting after failure of a previous Russe graft for scaphoid non-union. 15 patients were followed for a mean of 71 months after their last surgical procedure. 11 patients had undergone a single previous Russe graft and four patients had two previous graft attempts. Internal fixation was used in only three patients. Eight out of 15 (53%) patients achieved union after a single repeat graft and one out of four united after a third attempt. When union was achieved, range of motion was unchanged, grip strength was increased 10% and pain was slight to none, allowing return to full employment in seven out of the nine patients. All patients who did not achieve union have either undergone a salvage procedure or are contemplating one. Based on the literature and our relatively low rate of union without internal fixation (53%), we recommmend supplementary internal fixation if repeat Russe bone grafting is undertaken. When union is achieved, satisfactory results can be expected.

Adolescent↗
PubMed1993

Palmar midcarpal instability: results of surgical reconstruction.

We reviewed the cases of 13 patients who underwent 15 surgical procedures for palmar midcarpal instability from 1981 to 1989. Six patients had a limited midcarpal arthrodesis, and nine patients had one of four different soft tissue reconstructive procedures. One hundred percent clinical follow-up was obtained at an average of 48 months. All six of the limited midcarpal arthrodeses were successful. Six of the nine soft tissue reconstructions failed. However, one procedure, a distal advancement of the ulnar arm of the arcuate ligament combined with a dorsal capsulodesis, restored stability in three of five wrists. We concluded that patients with palmar midcarpal instability may have significant disability that may be refractory to nonsurgical management. Limited midcarpal arthrodesis provides definitive treatment.

Activities of Daily Living↗
PubMed1992

Aspirin usage and its influence on femoro-popliteal vein graft patency. The Femoro-popliteal Bypass Trial Participants.

As part of the Femoro-popliteal Bypass Trial patients undergoing femoro-popliteal vein bypass were randomised to aspirin 300 mg and dipyridamole 150 mg twice daily or identical placebo tablets. Blood was taken from a subgroup of 145 patients (mean age 66.3 years) with patent grafts at 6 months. Serum salicylate analysis revealed that of the 65 randomised to receive placebo 18 (28%) had evidence of salicylate in their sample (greater than 50 ng ml-1). Similarly, in those randomised to active treatment and considered to be good compliers 16/61 (26%) had no evidence of salicylate in their serum sample (less than 50 ng ml-1). Analysis of primary graft patency by "intention to treat" failed to detect a difference by life table, the risk being slightly higher in the group assigned to placebo (RR = 1.33, 95% confidence internal C.I. 0.64-2.78, p = 0.438). When comparing patients with no detectable serum concentration (less than 50 ng ml-1) with patients with serum salicylate over 50 ng ml-1 there was a significant difference in graft patency at 66 versus 83% respectively at 3 years (RR = 2.38, 95%C.I. 1.08-5.26, p = 0.024). When corrected for a number of possible risk factors this significant difference was maintained (RR = 2.78, 95%C.I. 1.15-6.67, p = 0.017). Although these findings are based on observational data they provide indirect evidence of an improvement in graft patency with aspirin. This result combined with the finding of a significant reduction in cardiovascular events in the main trial results support the use of aspirin and dipyridamole in patients undergoing femoro-popliteal vein bypass.

Aged↗
PubMed1990

Lunate silicone replacement arthroplasty in Kienböck's disease: a long-term follow-up.

We report a long-term follow-up (average, 5 years) of 10 patients who had lunate silicone replacement arthroplasty for treatment of Kienböck's disease. Clinical results were assessed on relief of pain, return to normal occupation, and range of motion. At 18- to 20-months follow-up, eight patients had satisfactory results, whereas at final follow-up only five of the patients had satisfactory results. Three of five patients with radiographs averaging 57 months after operation had evidence of particulate synovitis. Contrary to our previous publications on silicone replacement arthroplasty, it was concluded that the success rate for silicone replacement arthroplasty and the incidence of particulate synovitis do not warrant the continued use of silicone replacement arthroplasty as a primary treatment modality for Kienböck's disease.

Adolescent↗
PubMed1985

Congenital syphilis revisited.

Despite decades of experience with congenital syphilis, problems still arise in case definition, diagnostic evaluation, treatment, and follow-up. We reviewed all 50 cases of early congenital syphilis reported to the State of Texas in 1982. A large proportion of the infants were premature (39%), of low birth weight (38%), and symptomatic at birth (62%). Because of these findings, we believe that possible cases of asymptomatic congenital syphilis in Texas may be under-reported. Laboratory and/or roentgenographic findings were important to confirm the diagnosis of congenital syphilis. Over half of the asymptomatic infants had positive results of cerebrospinal fluid VDRLs. After diagnosis, the treatment of infants with penicillin varied considerably. While all 47 living infants were treated with penicillin, 21 different regimens were used. We urge all physicians to perform complete diagnostic evaluations on suspected infants consisting of a quantitative serum test for syphilis, serum IgM levels, a cerebrospinal fluid VDRL, roentgenographs of the long bones, and dark-field microscopy where indicated. Additionally, infants and their families need appropriate follow-up after treatment.

Birth Weight↗
PubMed1984

Inadequate treatment of syphilis in pregnancy.

Pregnant women with untreated syphilis have high rates of adverse pregnancy outcome. Early syphilis in pregnancy, if not treated, results in 40% loss either by spontaneous abortions, stillbirth, or perinatal death. Another 40% of such pregnancies result in an infant born with congenital syphilis. Only 20% of such pregnancies result in a normal infant. Currently recommended treatment of early syphilis in pregnant women uses a dosage of 2.4 million U of benzathine penicillin G. Because of the potentially disastrous effect syphilis has on pregnancy outcome, the occurrence of any treatment failure must be considered seriously. In this brief report we present clinical summaries of four pregnant women treated for syphilis who represent probable treatment failures.

Adult↗
PubMed1984

Congenital syphilis. Why is it still occurring?

A total of 159 cases of early congenital syphilis were reported in the United States during 1982, with Texas reporting 50 cases. We reviewed these Texas cases to identify the most important characteristics on which to focus control efforts. Thirty-eight mothers were 25 years of age or younger; 33 were unmarried. All were from minority groups. No congenital syphilis occurred in whites. Blacks were twice as likely as Hispanics to have an infected infant. Foreign-born Hispanic women were three times more likely to be delivered of an infected child than Hispanics born in the United States. Attendance at prenatal care facilities significantly affected the risk of being delivered of an infected child in both black and Hispanic women; 31 women received no prenatal care. Based on these findings, congenital syphilis in Texas can be reduced primarily through improving prenatal care for high-risk populations and by refining casefinding efforts to control infectious syphilis in the community.

Female↗
PubMed1984

Dynamic triquetrolunate instability: case report.

A case is reported that demonstrates dynamic triquetrolunate instability with the additional finding of obstruction to smooth intercarpal motion by a tag of torn interosseous triquetrolunate ligament. The patient was successfully treated with excision of the ligamentous tag accompanied by triquetrolunate fusion.

Adult↗
PubMed1984

Ulnar carpal instabilities.

Ulnar carpal instabilities are more common than previously suspected. To date, instability patterns have been described at the triquetrolunate and triquetrohamate joints. In this article, the pathomechanics, diagnosis, and treatment of these instability patterns are reviewed and several pertinent case reports are presented.

Adult↗
PubMed1983

Limb salvage procedure for neoplasms about the knee by spherocentric total knee arthroplasty and autogenous autoclaved bone grafting.

Spherocentric total joint arthroplasty was performed for treatment of neoplasm in 15 patients. The average follow-up period was 30 months. In nine of the patients concomitant autoclaved autologous bone implants were also prepared from the resected specimens. The results were satisfactory in ten patients and unsatisfactory in five. One patient had an infection that required amputation. One patient with osteosarcoma had a recurrence at 20 months and was treated by amputation. Poor results were caused by stem failure in two patients and by component loosening in one patient. Total joint arthroplasty combined with autoclaved bone implantation is a useful limb salvage procedure for resected neoplasms about the knee.

Adolescent↗
PubMed1976

Viral hepatitis in the United States Navy and Marine Corps.

Two analyses of the Navy and Marine Corps experience with viral hepatitis are reported. The first is longitudinal in nature and shows that over the past 100 years the syndrome has been common and at a relatively steady rate of 100-400 cases/100,000 average strength/year. The second is an examination of cases in calendar year 1974 for demographic, geographic, and occupational patterns. There is a strong inverse relationship between disease occurrence and age. Each type of viral hepatitis shows a distinct geographic distribution. Navy personnel in health-related occupations had a greater risk of acquiring viral hepatitis than did other persons on active duty. Differences among other occupational groups were found, but valid interpretations could not be made because of the small numbers of cases in each category.

Adult↗
PubMed1968

Sulfadiazine-resistant group A Neisseria meningitidis.

A meningitis epidemic due to Group A meningococci was unusual in that most of the strains isolated from patients were generally resistant to sulfadiazine. This is the first report of sulfonamide resistance in an epidemic strain of Neisseria meningitidis Group A.

Drug Resistance, Microbial↗