Search PubMed⌕ Search

Biomedical subjects

K Smith

Publications and source records attributed to K Smith.

At least 37 records · Page 2Linked to original sources
PubMed1997

Immune reconstitution following T-cell depleted bone marrow transplantation: effect of age and posttransplant graft rejection prophylaxis.

Transplantation of T-cell depleted bone marrow has been associated with an increased risk of graft failure, requiring additional immunosuppression to prevent this complication. To determine the effect of graft rejection prophylaxis with posttransplant anti-thymocyte globulin and methylprednisolone on immune reconstitution, the lymphoid phenotype, function, and infectious complications of 170 recipients of a T-cell depleted bone marrow transplantation, 57 of whom received prophylaxis, were analyzed. Neutrophil recovery and normalization of T-cell numbers were more rapid in patients given anti-thymocyte globulin and methylprednisolone. Adults given graft rejection prophylaxis had prolonged inversion of their CD4/CD8 ratio, increased numbers of CD8+ CD11b+, HLA-DR+, CD57+, CD28- T cells, and delayed recovery of T-cell mitogen responses when compared to adults not given ATG and steroids. Even without posttransplant immunosuppression to prevent graft failure, adults experienced delayed recovery of total and CD45RA+ CD4+ cells, prolonged inversion of the CD4/CD8 ratio, and delayed recovery of T-cell mitogen responses when compared to children. During the first posttransplant year, Epstein-Barr Virus-Associated Lymphoproliferative disorders and opportunistic infections were increased in patients given prophylaxis. Patients who developed an opportunistic infection or EBV-LPD had significantly fewer circulating CD4+ T cells than those who did not. This study demonstrates that older age and graft rejection prophylaxis, rather than T-cell depletion alone, are associated with delayed immune reconstitution. In addition, it suggests that CD4 cell counts may be useful in predicting which patients are at increased risk of developing opportunistic infections following successful engraftment.

Adolescent↗
PubMed1997

Prediction of developmental patterns through 40 months from 6- and 12-month neurologic examinations in very low birth weight infants.

This study examines whether neurologic examinations at 6 and 12 months of age can predict developmental patterns in very low birth weight infants and fullterm controls through 40 months of age. We performed neurologic examinations at 6 and 12 months; the Bayley Scales of Infant Development at 6, 12, and 24 months; and the Stanford-Binet and the McCarthy Motor scale at 40 months. The very low birth weight infants were categorized on the basis of socioeconomic status and high or low risk for early medical complications. More abnormal neurologic scores predicted greater deceleration of cognitive development for high-risk infants only. The 12-month neurologic examination predicted the degree of deceleration in motor development. Medical risk was an independent predictor of curvature of the psychomotor development curve. We conclude that neurologic examinations during the 1st year of life might be used with other factors in decision concerning referrals to early-intervention programs.

Analysis of Variance↗
PubMed1997

Low seroprevalence of Toxoplasma gondii in feral pigs from a remote island lacking cats.

Serum samples from 1,264 feral pigs from Ossabaw Island, Georgia were initially screened for antibodies to Toxoplasma gondii by the modified agglutination test (MAT) using whole-formalinized tachyzoites and mercaptoethanol. Seropositive samples were also tested by the Sabin-Feldman dye test, the latex agglutination test (LAT), and the indirect hemagglutination test (IHAT). Ossabaw Island is a remote, barrier island located southeast of Savannah, Georgia. Antibodies to T. gondii were found in 11 (0.9%) of 1,264 pigs. The antibody titers were 1:20 (1 pig), 1:80 (2 pigs), 1:160 (2 pigs), 1:320 (4 pigs), and 1:640 (2 pigs) by the MAT, and 1:8 (2 pigs), 1:16 (3 pigs), 1:32 (1 pig), 1:64 (2 pigs), 1:128 (1 pig), and > or = 1:256 (2 pigs) by the Sabin-Feldman dye test. By the LAT, 5 pigs had a titer of > or = 1:64 and by the IHAT all 11 pigs had a titer of < 1:64. Antibodies (MAT titer, > or = 1:25) were found in 31 (18.2%) of 170 feral pigs from mainland Georgia. This seroprevalence on the mainland was significantly higher (P < 0.0001) as compared on Ossabaw Island. The markedly low prevalence of T. gondii on Ossabaw Island was attributed to the virtual absence of cats on the Island; only 1 domestic cat was known to be present.

Age Factors↗
PubMed1996

Interaction of mouse adenovirus type 1 early region 1A protein with cellular proteins pRb and p107.

We demonstrated functional associations between mouse adenovirus type 1 (MAV-1) early region 1A (E1A) protein and both the mouse retinoblastoma protein (pRb) and the mouse pRb-related protein, p107. Interactions between MAV-1 E1A and mouse pRb or mouse p107 proteins were examined in infected cell lysates using a mouse embryonic fibroblast cell line infected with wild-type and mutant MAV-1 viruses. Using a polyclonal antibody to MAV-1 E1A, exogenously added mouse pRb or mouse p107 was coimmunoprecipitated from wild-type, dIE105 (CR1 delta)-, and dIE106 (CR3 delta)-infected cell lysates. No coimmunoprecipitation was seen with cell lysates from dIE102 (CR2 delta) or pmE109, a mutant virus that produces no detectable E1A protein due to an ATG to TTG point mutation in the initiator methionine. Introduction of mouse pRb into SAOS-2 cells resulted in a flat and enlarged cell phenotype, whereas cotransfection of mouse pRb and MAV-1 E1A resulted in a significant reduction of flat cells, presumably due to E1A binding pRb. CR1 delta and CR2 delta E1A proteins were less effective at reducing the number of flat, enlarged cells induced by pRb expression than were the CR3 delta or wild-type E1A proteins. The reduced ability of these mutants to inactivate pRb relative to wild-type E1A correlated with their reduced ability to bind pRb in the in vitro coimmunoprecipitation experiments. As a measure of p107/MAV-1 E1A complex formation in MAV-1-infected cells, we used mobility shift assays to examine cell extracts for the presence of p107-containing E2F protein-DNA complexes. Mock-, dIE102-, and pmE109-infected cell extracts formed a p107-containing complex, whereas wild-type-infected cell extracts did not. Thus the formation of a p107-E2F complex in wild-type- or these mutant-infected extracts inversely correlated with the presence of E1A-p107 complexes identified in the vitro coimmunoprecipitation experiments. This is consistent with E1A-p107 complexes forming in wild-type MAV-1-infected cells.

Adenovirus E1A Proteins↗
PubMed1996

Compartment switching of WNT-2 expression in human breast tumors.

WNT-2 is a secreted polypeptide with mitogenic effects in murine mammary epithelial cells, but its role in human cancer is unknown. Using RNase protection analysis of primary cell preparations and in situ hybridization analysis, we report that WNT-2 is expressed at low levels in normal human breast fibroblasts but not in epithelial cells. WNT-2 was found to be expressed at high levels in both the epithelium and stroma of 5 of 11 infiltrating carcinomas and 2 of 6 fibroadenomas. The high level of WNT-2 expression in tumor epithelium suggests that tumorigenesis may involve the ectopic expression of WNT-2 and the creation of an autocrine Wnt signaling loop.

Breast↗
PubMed1996

Ancient single origin for Malagasy primates.

We report new evidence that bears decisively on a long-standing controversy in primate systematics. DNA sequence data for the complete cytochrome b gene, combined with an expanded morphological data set, confirm the results of a previous study and again indicate that all extant Malagasy lemurs originated from a single common ancestor. These results, as well as those from other genetic studies, call for a revision of primate classifications in which the dwarf and mouse lemurs are placed within the Afro-Asian lorisiforms. The phylogenetic results, in agreement with paleocontinental data, indicate an African origin for the common ancestor of lemurs and lorises (the Strepsirrhini). The molecular data further suggest the surprising conclusion that lemurs began evolving independently by the early Eocene at the latest. This indicates that the Malagasy primate lineage is more ancient than generally thought and places the split between the two strepsirrhine lineages well before the appearance of known Eocene fossil primates. We conclude that primate origins were marked by rapid speciation and diversification sometime before the late Paleocene.

Animals↗
PubMed1996

Accuracy and precision of a new, portable, handheld blood gas analyzer, the IRMA.

OBJECTIVE: The accuracy and precision of the new IRMA (Immediate Response Mobile Analysis System, Diametrics, Inc., St. Paul, MN) handheld blood gas analyzer was compared with that of two benchtop blood gas analyzers. The IRMA consists of a notebook-sized machine and disposable cartridges, each containing a pH, a CO2 and an O2 electrode, and provides bedside (point-of-care) blood gas analysis. METHODS: A total of 172 samples (arterial and mixed venous) were obtained from 25 informed, consenting patients undergoing cardiopulmonary bypass. The pH, PCO2 and PO2 of each sample was determined on four blood gas analyzers: NOVA Statlabs Profile 5 (NOVA Biomedical, Waltham, MA), the ABL-50 (Radiometer, West Lake, OH), and two IRMA machines. Linear regression and bias +/- precision were determined, comparing each of the analyzers with the NOVA. RESULTS: All three machines showed a similar, high degree of correlation with the NOVA for pH, PCO2, and PO2. The bias and precision of the IRMA machines compared with the NOVA was similar to that of the ABL compared with the NOVA for pH (NOVA:ABL -0.005 +/- 0.011; NOVA:IRMA 1 = 0.0026 +/- 0.025; NOVA:IRMA 2 = 0.0021 +/- 0.025), for PCO2 (NOVA:ABL = -1.4 +/- 1.3 mmHg; NOVA: IRMA 1 = -1.3 +/- 1.9 mmHg; NOVA: IRMA 2 = -1.2 +/- 2.1 mmHg) and PO2 (NOVA:ABL = 3.6 +/- 21.1 mmHg; NOVA:IRMA 1 = 3.4 +/- 19.9 mmHg; NOVA:IRMA 2 = 6.3 +/- 20.9 mmHg). The bias found for pH, PCO2, and PO2 was not affected by extremes of temperature (range 25.5-40 degrees C) or hematocrit (range 11-44%) for any machine. CONCLUSIONS: The new technology incorporated in the IRMA blood gas analyzer provides results with an accuracy that is similar to that of benchtop analyzers, but with all of the advantages of point-of-care analysis.

Blood Gas Analysis↗
PubMed1996

Delayed diagnosis in a rural trauma center.

BACKGROUND: The rapid and accurate diagnosis of all injuries is critical in trauma surgery. Injuries not diagnosed after the secondary survey are not without serious consequences. Therefore, in an effort to decrease this problem a policy was initiated to perform an ongoing serial exam during the entire course of each patient's involvement with the trauma team at Saint Francis Medical Center. METHODS: Prospective identification and evaluation of patients admitted to a single trauma service with delayed diagnosis was done from July 1, 1993, to October 31, 1995. RESULTS: Sixty-eight delayed diagnoses were identified in 56 patients, for an incidence of 3% of the total 1876 patients evaluated. The vast majority were nonspinal orthopedic injuries (63%). Of seven missed spinal fractures, only one resulted in permanent paralysis. The remaining injuries missed were 11 injuries located in the head and neck area, 3 arterial injuries, 3 pneumothoraces, and 2 small bowel injuries. Thirty-four percent of the patients required surgical intervention for these injuries and one patient died because of the delay. There was a high association of delayed diagnosis in victims with altered mental status, victims intubated in the field, and individuals requiring immediate operation. Twenty percent of our total missed injuries could have been avoided if a thorough evaluation of initial films had been done. CONCLUSIONS: Delayed diagnosis remains a problem in all trauma centers. This study demonstrates that to keep this problem at a reasonable rate, we must: (1) carefully review initial x rays; (2) repeat any study that is not clear; and (3) continue serial examinations of each patient for the entire clinical course. Objective and thoughtful discussion of missed injuries on a routine basis will also keep this problem minimal.

Abdominal Injuries↗
PubMed1996

The measurement of tissue protein turnover.

Tissue protein turnover can be assessed by a number of semi-, quantitative and qualitative methods. There are a number of static indices of the state of turnover of protein, for example amount of RNA per DNA or protein, the state of aggregation of ribosomes (i.e. the polyribosome index), the abundance of mRNA for particular proteins, and the enzymatic activity of proteins such as proteases, ribonuclease, etc. In addition, the concentration of particular amino acids such as glutamine or non-re-utilizable amino acids, formed post-translationally, such as 3-methylhistidine or hydroxyproline, are able to provide snapshot indices. However, since turnover is a dynamic process it should, ideally, be probed using methods such as the incorporation of tracer amino acids into protein or the dilution of tracer amino acids in the free pool by protein breakdown. The combination of tracer and tissue or limb balance methods is especially powerful since all the dynamic processes can potentially be quantified. The use of stable isotopes to label metabolic tracers has dramatically increased the feasibility of carrying out measurements of protein synthesis and breakdown and there has been a substantial growth in the application of the methods to a wide variety of tissues sampled by biopsy or at operation. Summaries of a number of currently feasible methods are provided, together with commentary on the relative efficacy of the methods and of the instrumental techniques required. There is also a discussion of suitable tracer labels and amino acids, plus a summary of the most reliable current values for protein turnover in a variety of tissues. The review also contains descriptions of potential methods which have not yet been applied in human beings but which are feasible, given the current recent increases in the accuracy and sensitivity of instrumentation for measurement of stable isotope labelling.

Amino Acids↗
PubMed1996

The benefits of a shared-care prostate clinic.

OBJECTIVE: To establish a hospital based shared-care clinic to investigate and manage benign prostatic hyperplasia (BPH) with general practitioners (GPs). PATIENTS AND METHODS: During one year, 330 patients referred with suspected prostatic obstruction were investigated in an outreach clinic in a rural cottage hospital by urology department nurses according to a protocol. After this, they were referred directly back to their GPs with recommendations for their management or seen in the urologist's clinic. A questionnaire was completed by the GPs to assess their satisfaction with and attitudes to the clinic. RESULTS: One-third of the patients were referred directly back to their GP, a third were seen routinely and a third seen urgently in the urologist's clinic, usually because a prostate-specific antigen assay indicated the possibility of latent prostatic cancer. A survey confirmed that GP support for the clinic was unanimous whilst patients were reassured by the thoroughness and sensitivity of the clinic's nursing staff. CONCLUSION: The clinic reduced the workload of the GPs and urologists whilst providing a speedy and comprehensive assessment of patients presenting with suspected prostatic obstruction.

Clinical Protocols↗
PubMed1996

Titanium aneurysm clips: Part II--Seizure and electroencephalographic studies in implanted rabbits.

Because titanium is widely used in neurosurgical procedures, we compared spontaneous and induced epileptiform activity in 12 rabbits with titanium clips implanted in the subarachnoid space with 12 rabbits with cobalt alloy clips and 6 rabbits that were not operated on that served as controls. Beginning 1 week after surgery, 30-minute electroencephalographic recordings were made at monthly intervals for 6 months. Recordings were scored by an electroencephalographer unaware of which treatment group was being recorded. In 48 recordings made during 6 months, no epileptiform activity was observed in any animal. Seizure threshold was evaluated by continuous intravenous injection of the convulsant drug, pentylenetetrazole (2 mg/kg/min), with continuous electroencephalographic recording. Time to spiking for the nonsurgical control group was 327 mean seconds +/- 181 standard deviation (SD), 216 mean seconds +/- 135 SD for the titanium group, and 389 mean seconds +/- 290 SD for the cobalt group. There were no significant differences among the groups (P = 0.17). Latency to behavioral tonicoclonic seizure was 1031 seconds +/- 537 SD for the group not operated on, 875 seconds +/- 334 SD for the titanium group, and 1267 seconds +/- 764 SD for the cobalt group. This study suggests that titanium clips are well tolerated within the brain and will not induce seizures.

Animals↗
PubMed1996

A randomised trial comparing mesalazine and prednisolone foam enemas in patients with acute distal ulcerative colitis.

Distal ulcerative colitis can be treated with oral or rectal mesalazine, or both. A foam enema preparation has been developed and its efficacy investigated. The aim of this study was to evaluate the efficacy and safety of mesalazine foam enemas compared with prednisolone foam enemas in the treatment of patients with acute distal ulcerative colitis. Patients aged over 18 years presenting with a relapse of distal ulcerative colitis were randomly allocated treatment with mesalazine foam enema (n = 149 evaluable patients) and prednisolone foam enema (n = 146 evaluable patients) for four weeks. A randomised multicentre investigator blind parallel group trial was conducted. It was found that after four weeks of treatment, clinical remission was achieved by 52% of mesalazine treated patients and 31% of patients treated with prednisolone (p < 0.001). There was a trend in favour of more patients in the mesalazine group achieving sigmoidoscopic remission (40% v 31%, p = 0.10). Histological remission was achieved by 27% and 21% of patients receiving mesalazine and prednisolone respectively. Symptoms improved in both treatment groups. Significantly more mesalazine patients had no blood in their stools after four weeks of treatment (67% v 40%, p < 0.001). Prednisolone treated patients had significantly fewer days with liquid stools than mesalazine patients, with a median of 0 and 1 days respectively by week 4 (p = 0.001). In this study mesalazine foam enema was superior to prednisolone foam enema with regards to clinical remission, this was supported by favourable trends in sigmoidoscopic and histological remission rates. Both treatments were well tolerated.

Acute Disease↗
PubMed1996

Total hip and knee replacement treatment programs: a report using consensus.

Physical therapists may use varied treatment protocols for the acute care of patients with to hip or knee replacements. The purpose of this study was to develop, via consensus, a standardized treatment program for patients receiving total hip or knee replacement for primary osteoarthritis. Eighteen clinicians nationwide participated in a three-round consensus process. In Round 1, over 80% of the panel identified exercise, transfers, ambulation, and discharge criteria as the important treatment categories. In Round 2, they reviewed the preliminary physical therapy treatment program and recommended additional exercise regimes. In Round 3, 76% of the panel accepted the final total hip replacement program while 70% of the panel accepted the total knee replacement program. Using the consensus development process, physical therapists may begin to define their treatment programs which is fundamental to establishing a baseline standard of care.

Hip Prosthesis↗
PubMed1996

Coronary artery bypass graft surgery and its impact on erectile function: a preliminary retrospective study.

Erectile function is markedly affected by acute alterations in circulatory homeostasis of which coronary artery bypass graft surgery is an excellent model. A group of consecutive patients who had undergone coronary artery bypass surgery 6-12 months previously were selected for detailed review by questionnaires that scored their pre-operative and post-operative sexual function and erectile ability and aspects of the quality of life. Thirty patients were evaluable. 10 men (33.3%) had poor erectile function before surgery. Eleven out of 30 men reported an improvement in erectile function while 10 men experienced a decrease or cessation of erectile function. Four of the five patients reporting new post-operative erectile function had had good pre-operative function suggesting that the surgery was directly associated with the impotence in these men. This pilot study suggests that coronary artery bypass surgery can have a significant impact in erectile function.

Coronary Artery Bypass↗
PubMed1996

In vivo treatment with interleukin 2 reduces parasitemia and restores IFN-gamma gene expression and T-cell proliferation during acute murine malaria.

In this study, we describe the functional alterations in the host immune system that occur following acute infection with Plasmodium yoelii. Further, we have addressed the question whether the transient condition of altered immune responsiveness can be restored by a cytokine therapy. The lymphoproliferative response towards concanavalin A (Con A) or to cross-linked anti-CD3 mAb was significantly diminished in acutely infected mice compared to immune and normal animals. This condition was associated with poor production of IL-2. In vivo treatment with recombinant IL-2 (rIL-2) resulted in marked diminution of parasitemia (from 24% +/- 6% to 8% +/- 3%) in mice during the acute phase of infection. Despite this diminution in parasitemia, 70% of the IL-2 treated mice died by day 17 post infection. In vivo treatment with rIL-2 led to a partial but significant restoration in lymphoproliferative response to TCR-mediated (cross-linked anti-CD3 mAb) or to Con A-induced stimulation in acutely infected mice. The transcripts for IL-4, IL-5, GM-CSF, and TNF-alpha were expressed in the splenocytes from acutely infected mice not treated with rIL-2. mRNAs for IL-2, IFN-gamma, IL-6, IL-10 which were not detected in acutely infected mice could be reversed by administration of rIL-2 in vivo. We suggest that some of the hyporesponsive T-cells in the acute phase of infection have the potential to be reversed, and this reversal is manifested also at the level of cytokine gene expression.

Animals↗