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Biomedical subjects

M Adams

Publications and source records attributed to M Adams.

At least 109 records · Page 6Linked to original sources
PubMed2000

Outcome of pediatric thromboembolic disease: a report from the Canadian Childhood Thrombophilia Registry.

The outcome for children with deep vein thrombosis (DVT) and pulmonary embolism (PE) is unknown. An understanding of morbidity and mortality of DVT/PE is crucial to the development of rational treatment protocols. The Canadian Childhood Thrombophilia Registry has followed 405 children aged 1 mo to 18 y with DVT/PE for a mean of 2.86 y (range, 2 wk to 6 y) to assess outcome. The all-cause mortality was 65 of 405 children (16%). Mortality directly attributable to DVT/PE occurred in nine children (2.2%), all of whom had central venous line-associated thrombosis. Morbidity was substantial, with 33 children (8.1%) having recurrent thrombosis, and 50 children (12.4%) having postphlebitic syndrome. Recurrent thrombosis and postphlebitic syndrome were more common in older children, although deaths occurred equally in all age groups. The incidence of recurrent thrombosis and postphlebitic syndrome are likely underestimated because of difficulties in diagnosis, especially in younger children. The significant mortality and morbidity found in our study supports the need for international multicenter randomized clinical trials to determine optimal prophylactic and therapeutic treatment for children with DVT/PE.

Adolescent↗
PubMed2000

Pediatric cervical spine injuries: report of 102 cases and review of the literature.

OBJECT: To evaluate and review their experience with pediatric cervical injuries and factors affecting outcome, the authors conducted a retrospective clinical study of 102 cases (65% boys, 35% girls) of pediatric cervical spine injuries treated in the last decade. This study is an extension of and comparison with their earlier experience. METHODS: Patients were divided into two age groups-birth to 9 years (Group I) and 10 to 16 years of age (Group 2)- and managed according to status at presentation and type of injury. Thirty patients were managed surgically and 72 non-surgically (42 wore a halo brace and 30 wore hard collars or custom-molded braces). Motor vehicle accidents were the most common cause of injury, and 40% were associated with head injury. Patients in the younger-age group (Group 1) sustained more neurological injuries than the older patients in Group 2, and most injuries were in the upper cervical spine. Of the 38 children in Group 1, in 39% a subluxation was present and in 29% a fracture or fracture/subluxation was demonstrated. Of the patients in Group 2, 80% had sustained fractures or fracture/subluxations. Vertebral fractures were the most common radiological findings (32%). At late follow-up review (mean 5 years), solid fusions were demonstrated in all patients. Neurological deterioration did not occur in any patient. The mortality rate was 16%. Compared with the authors' earlier report, the incidence of cases with pediatric cervical injuries increased, as did the number managed surgically. Various fusion techniques were used, and neurological and fusion outcomes improved as compared with the previous report. CONCLUSIONS: The prognosis of neurological recovery from pediatric cervical spine injuries is related to the severity of the initial neurological injury. Management must be tailored to the patient's age, neurological status, and type and level of injury. Compared with our earlier experience, fusion and instrumentation procedures were used more frequently. Different types of fusion and instrumentation procedures can be performed safely in children and produce good outcomes.

Adolescent↗
PubMed2000

Unraveling the realities of vascular access: the Network 11 experience.

Arteriovenous (AV) fistulae are well recognized as the preferred vascular access for hemodialysis, yet national data show that only 23% of patients used an AV fistula in 1997. To identify barriers to the placement of native AV fistulae, the Renal Network of the Upper Midwest, Inc. (End-Stage Renal Disease [ESRD] Network 11) initiated a vascular access project to look at the process of referral for patients beginning hemodialysis in the first 6 months of 1999. Of these patients, 63% began hemodialysis with a catheter as the only access, 22% had an AV fistula placed (but only 14% used an AV fistula for their first dialysis treatment), and 15% began with a graft. About 40% of patients were referred to a nephrologist less than 1 month before dialysis, allowing little chance for permanent access placement. Yet 27% of patients used a catheter on the first hemodialysis treatment and were seen by a nephrologist more than 1 month before starting dialysis, indicating the presence of an opportunity to improve. At 6 months after initiation of dialysis, 25% of patients who began dialysis using a catheter were using an AV fistula and 35% were using a graft. Network 11 plans to use this information to promote early referral of patients to a nephrologist and subsequent prompt referral of such patients to a vascular surgeon. Other activities to improve vascular access management are also indicated.

Adolescent↗
PubMed1999

Limitation of Tat-associated transcriptional processivity in HIV-infected PBMC.

The ability of HIV to match levels of viral mRNA to the activation state of the host cell may play a role in its ability to persist as well as to replicate. This linkage depends on the function of the viral transcriptional regulatory protein, Tat, which increases the efficiency of RNA elongation (transcriptional processivity) in response to cellular activation. To quantify levels of Tat function in vivo, a quantitative competitive RT-PCR assay was developed that reflects levels of TAR leader fragments (nonprocessive transcripts) and viral mRNA (processive transcripts), indicating low or high levels of Tat function, respectively. The abundance of these RNA species was measured in peripheral blood mononuclear cells (PBMC) of 22 HIV-1-positive individuals (CD4(+) T cell counts 63-934/mm3) and in established cell line models of HIV constitutive replication (H9IIIB) and reversible latency (U1 and ACH-2). In PBMC, the level of total viral transcripts ranged over four orders of magnitude; however, nonprocessive transcription predominated: 70% of PBMC samples had a ratio of processive to total transcripts of <0.3 and none of the samples had 100% processivity. The cell line studies revealed that, even in activated H9IIIB cells, nonprocessive transcription dominates and that latently infected cells can have different transcriptional responses to activation. This is the first study that enumerates degrees of transcriptional processivity in the circulating mononuclear cell compartment and the results suggest that limitation of Tat function may be a common phenotype throughout the course of the disease.

Cell Line↗
PubMed1999

Acute torsion of the renal transplant after combined kidney-pancreas transplant.

BACKGROUND: Surgical complications after combined kidney and pancreas transplantation are a major source of morbidity and mortality. Complications related to the pancreas occur with greater frequency as compared to renal complications. The occurrence in our practice of two cases of renal infarction resulting from torsion about the vascular pedicle led to our retrospective review of similar vascular complications after combined kidney and pancreas transplantation. METHODS: Charts were reviewed retrospectively, and two patients were identified who experienced torsion about the vascular pedicle of an intra-abdominally placed renal allograft. RESULTS: Two patients who had received combined intraperitoneal kidney and pancreas transplantation presented at 16 and 11 months after transplant, respectively, with abdominal pain and decreased urine output. One patient had radiological documentation of abnormal rotation before the graft loss; unfortunately, the significance of this finding was missed. Diagnosis was made in both patients at laparotomy, where the kidneys were infarcted secondary to torsion of the vascular pedicle. Both patients underwent transplant nephrectomy and subsequently received a successful second cadaveric renal transplant. CONCLUSIONS: The mechanism of this complication is a result of the intra-abdominal placement of the kidney, length of the vascular pedicle, excess ureteral length, and paucity of adhesions secondary to steroid administration. These factors contribute to abnormal mobility of the kidney. Technical modifications such as minimizing excess ureteral length and nephropexy may help to avoid this complication.

Adult↗
PubMed1999

Residency application statements can predict postresidency training.

We sought to evaluate whether residency application statements regarding expected career paths are accurate predictors of early postresidency career paths. We evaluated 162 residents who completed a categorical medicine residency at Georgetown University Hospital between 1990 and 1998 to determine if their stated career plans (generalist practice, subspecialization, or undecided) at application predicted activity immediately after residency. Of 130 residents with defined postresidency plans at application, most 78 (60%) followed those career paths after graduation; 18 (67%) of 27 pursued their initial interest in generalist practice, and 60 (58%) of 103 pursued their stated interest in subspecialty training. We also noted a movement of residents toward generalism (79 [49%] of 162), despite low initial interest (27 [17%] of 162).

Career Choice↗
PubMed1999

Motor feedback physiological control for a continuous flow ventricular assist device.

The response of a continuous flow magnetic bearing supported ventricular assist device, the CFVAD3 (CF3) to human physiologic pressure and flow needs is varied by adjustment of the motor speed. This paper discusses a model of the automatic feedback controller designed to develop the required pump performance. The major human circulatory, mechanical, and electrical systems were evaluated using experimental data from the CF3 and linearized models developed. An open-loop model of the human circulatory system was constructed with a human heart and a VAD included. A feedback loop was then closed to maintain a desired reference differential pressure across the system. A proportional-integral (PI) controller was developed to adjust the motor speed and maintain the system reference differential pressure when changes occur in the natural heart. The effects of natural heart pulsatility on the control system show that the reference blood differential pressure is maintained without requiring CF3 motor pulsatility.

Algorithms↗
PubMed1999

Two novel genes in the center of the 11p15 imprinted domain escape genomic imprinting.

We previously reported the isolation of a 2.5 Mb tumor-suppressing subchromosomal transferable fragment (STF) from human chromosome 11p15 and the identification of nine known genes and four novel genes within this STF. We now report the isolation of two novel cDNAs, designated here as TSSC4 and TSSC6 (tumor-suppressing STF cDNA 4 and 6), located within the STF. TSSC4 and TSSC6 encode predicted proteins of 329 and 290 amino acids, respectively, with no close similarity to previously reported proteins. TSSC4 and TSSC6 are both located in the center of a 1 Mb imprinted domain, which contains the imprinted genes TSSC3, TSSC5, p57(KIP2), KVLQT1, ASCL2, IGF2 and H19. However, we found that neither TSSC4 nor TSSC6 was significantly imprinted in any of the fetal or extra-embryonic tissues examined. Based on this result, the imprinted gene domain of 11p15 appears to contain at least two imprinted subdomains, between which TSSC4 and TSSC6 substantially escape imprinting, due either to lack of initial silencing or to an early developmental relaxation of imprinting.

Alleles↗
PubMed1999

Aromatase and estrogen receptor immunoreactivity in the coronary arteries of monkeys and human subjects.

OBJECTIVE: The objective of this study was to determine whether estrogen could be formed locally in the coronary arteries. DESIGN: Coronary arteries were examined from monkeys (Macaca fascicularis, one male and one female) and human subjects (one premenopausal woman, one postmenopausal woman, and one man) by immunocytochemistry, using purified antisera against human placental estrogen synthetase (aromatase) and ER alpha. The arteries were graded for the amount of atherosclerosis. RESULTS: There was clear immunopositivity for both aromatase and estrogen receptors in all arteries studied. Although all endothelial cells (CD31 positive) stained for both antigens, the staining in macrophages, fibroblasts, and smooth muscle cells was irregular. CONCLUSION: The present results provide the first evidence for the local formation of estrogen in the coronary arteries. In addition to complementing the evidence of a cardioprotective effect of estrogen on the coronary circulation, our results highlight the potential importance of local regulation of estrogen formation and the role of available precursor androgens in maintaining the cardiovascular system.

Animals↗
PubMed1998

Myocardial nuclear factor-kappaB activity and nitric oxide production in rejecting cardiac allografts.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a rapid response transcription factor for genes whose products are critical for inflammation and immunity. In a rat model of heterotopic cardiac transplantation, we studied NF-kappaB DNA binding activity and nitric oxide (.NO) production in untreated allografts and whether inhibition of NF-kappaB suppresses .NO production and prolongs graft survival. METHODS: In allograft recipients and isograft controls, NF-kappaB was assayed by electrophoretic mobility shift assay, daily from transplant until rejection. Myocardial .NO was directly detected in explanted allografts by electron spin resonance spectroscopy on day 6 after transplant. The potent inhibitor of NF-kappaB, pyrrolidine dithiocarbamate (PDTC; 250 mg/kg s.c.) was administered daily from transplant until day of rejection. The extent of graft lymphocytic infiltrate was assessed by routine hematoxylin and eosin staining. Immunohistochemical staining of NF-kappaB was per formed to identify the cell type responsible for NF-kappaB activity. RESULTS: A time-dependent increase in myocardial NF-kappaB activity was seen in untreated allografts as compared with isografts as determined by PhosphorImage analysis. Peak NF-kappaB activity occurred in allografts on day 4 with a ninefold increase as compared with isografts (24.0+/-3.7% vs. 2.7+/-0.5; P<0.05). On posttransplant day 6, electron spin resonance spectroscopy analysis of allografts demonstrated .NO identified by a triplet nitrogen signal centered at g=2.012 with hyperfine splitting of 17.5 Gauss, which is consistent with nitrosoheme formation and low-field signals at g=2.08 and g=2.03 consistent with nitrosomyoglobin. These signals were not seen in native hearts of allograft recipients. With PDTC administration, a threefold decrease in NF-kappaB activity within the transplanted heart was observed on posttransplant day 5 as compared with untreated allografts (9.7+/-1.6% vs. 23.5+/-2.5%; P<0.01). PDTC prolonged graft survival as compared with untreated allografts (11.7+/-0.3 vs. 6.6+/-0.2 days; P<0.05) and reduced the intensity of the nitrosoheme and nitrosomyoglobin signals. Allograft mononuclear cell infiltrate correlated with peak NF-kappaB activity with peak infiltrate on posttransplant day 4. PDTC treatment had no effect on the extent of infiltrate. Immunohistochemical staining localized NF-kappaB to the infiltrating mononuclear cells on posttransplant day 5. CONCLUSION: These data support a role for NF-kappaB in allograft rejection.

Animals↗
PubMed1998

Prothrombotic disorders in infants and children with cerebral thromboembolism.

BACKGROUND: To our knowledge, the contribution of prothrombotic conditions to cerebral thromboembolism has never been prospectively studied in a large series of pediatric patients. METHODS: The Hospital for Sick Children, Toronto, Ontario, established a program in January 1992 to diagnose and treat children (term newborn to 18 years old) with arterial ischemic stroke or sinovenous thrombosis. The routine evaluation for prothrombotic conditions included plasminogen, antithrombin, protein C, free protein S, activated protein C resistance, IgG and IgM anticardiolipin antibody, and lupus anticoagulant. We analyzed samples taken within 2 years of the event. We report results on patients seen from January 1, 1992, to January 1, 1997. RESULTS: Ninety-two patients (47 males and 45 females) entered the program during the study interval. Patients ranged from newborn to 18 years in age. Arterial ischemic stroke occurred in 78% of patients while sinovenous thrombosis occurred in 22%. All were tested for prothrombotic disorders. One or more abnormal results were present in 35 (38%) of the 92 patients. The majority (21/35) had multiple abnormal test results. The abnormal test results were anticardiolipin antibody (33%), plasminogen (9.5%), activated protein C resistance (9%), protein C (7%), antithrombin (12.5%), lupus anticoagulant (8%), and free protein S (11.5%). Male sex predicted the presence of prothrombotic abnormalities (relative risk, 1.7; 95% confidence interval, 1.2-2.5), but stroke type (relative risk, 0.8; 95% confidence interval, 0.7-1.1), age group, and presence of other risk factors did not predict abnormal testing. CONCLUSIONS: A significant proportion (38%) of children with cerebral thromboembolism had evidence of prothrombotic conditions. In particular, there was a predominance of children with anticardiolipin antibody (33%). These data support a recommendation that children with cerebral thromboembolism be evaluated for prothrombotic disorders.

Adolescent↗
PubMed1998

Elucidation of the exon-intron structure and size of the human protein kinase C beta gene (PRKCB).

As part of a transcriptional mapping project on human chromosome 16p12, a genomic contig was constructed that spanned the alternatively spliced human protein kinase C beta gene (PRKCB). PRKCB was determined to consist of 18 exons covering approximately 375 kb, with a particularly large intron of over 150 kb between exons 2 and 3. PRKCB is nearly 19 times larger than the highly homologous Drosophila melanogaster protein kinase C gene (dPKC), which has a similar-sized open reading frame but only 13 exons. This increase in size has occurred mostly as a result of expansion of introns, with intron size in the human gene averaging 22 kb compared with 1.5 kb in dPKC. The difference in gene size correlates with the difference in genome size, with the human haploid genome being nearly 18 times larger than the 170 Mb Drosophila haploid genome.

Blotting, Southern↗
PubMed1998

Phase behavior of mixtures of rods (tobacco mosaic virus) and spheres (polyethylene oxide, bovine serum albumin).

Aqueous suspensions of mixtures of the rodlike virus tobacco mosaic virus (TMV) with globular macromolecules such as polyethylene oxide (PEO) or bovine serum albumin (BSA) phase separate and exhibit rich and strikingly similar phase behavior. Isotropic, nematic, lamellar, and crystalline phases are observed as a function of the concentration of the constituents and ionic strength. The observed phase behavior is considered to arise from attractions between the two particles induced by the presence of BSA or PEO. For the TMV/BSA mixtures, the BSA adsorbs to the TMV and bridging of the BSA between TMV produces the attractions. For TMV/PEO mixtures, attractions are entropically driven via excluded volume effects known alternatively as the "depletion interaction" or "macromolecular crowding."

Animals↗