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Biomedical subjects

M Atkins

Publications and source records attributed to M Atkins.

At least 37 records · Page 2Linked to original sources
PubMed1999

Dual efficacy of lamivudine treatment in human immunodeficiency virus/hepatitis B virus-coinfected persons in a randomized, controlled study (CAESAR). The CAESAR Coordinating Committee.

The efficacy and safety of lamivudine in persons coinfected with human immunodeficiency virus (HIV) type 1 and hepatitis B virus (HBV) were examined in the CAESAR study, a randomized placebo-controlled trial assessing the addition of lamivudine (150 mg 2x/day) or lamivudine (150 mg 2x/day) plus loviride (100 mg 3x/day) to zidovudine-containing background antiretroviral treatment. Baseline hepatitis B surface antigen (HBsAg) results were available for 1790 study subjects, of whom 122 (6.8%) tested positive. Retrospective analyses for serial HBV DNA, HBsAg, and hepatitis B e antigen (HBeAg) were performed on stored sera from 118 HBsAg-positive subjects. HBV DNA and HBeAg were present in 83% and 63%, respectively. At weeks 12 and 52, median log10 HBV DNA change was -2.0 and -2.7, respectively, in the lamivudine arms, compared with no reduction among placebo recipients (P<.001). A trend to lower alanine transferase level, and delayed progression of HIV-1 disease (relative hazard, 0.26; 95% confidence interval, 0.08-0.80) were also seen in the lamivudine arms, compared with the placebo group.

Acetamides↗
PubMed1998

Quantitative differences in the distribution of zidovudine resistance mutations in multiple post-mortem tissues from AIDS patients.

Replication of HIV introduces errors into the genome which are responsible for conferring a growth advantage over wildtype virus when drugs such as zidovudine (ZDV) exert a selective pressure. The molecular basis for HIV-1 resistance to ZDV has been mapped to codons 41, 67, 70, 215 and 219 of the reverse transcriptase gene both in vitro and in clinical samples of blood. This study has investigated the relationship between the quantitative prevalence of ZDV resistance in multiple organs of the same individual. Proviral HIV-1 load was measured by quantitative-competitive PCR in 90 samples from organs of 11 patients dying with AIDS. Nine of these patients had been prescribed zidovudine. The distribution of wildtype and mutant sequences at the positions 41, 67, 70, 215 and 219 of the reverse transcriptase was assessed using a point mutation assay. The results showed that the highest proviral loads were predominately found in lymph node, spleen and lung and there was a significant association between viral load and resistance to ZDV (P=0.008). Inter-organ distribution of wildtype and mutant sequences at codons 41, 67, 70, 215 and 219 was frequently not uniform and in some patients differed markedly between the lymphoreticular system and other organs. These results demonstrate that treatment of HIV-1 infection with zidovudine does not exert uniform selective pressures in multiple organs. These findings have implications for the interpretation of resistance data and design of treatment strategies for HIV, arguing in particular that alterations in therapeutic regimens should consider the likelihood of different resistance patterns being present in multiple sites within the same individual.

Acquired Immunodeficiency Syndrome↗
PubMed1998

A contextually relevant assessment of the impact of child maltreatment on the social competencies of low-income urban children.

OBJECTIVE: A developmental-ecological model was used to explore the psychological adjustment and peer social competencies of maltreated preschool children. METHOD: Enhanced research methods were used that included verification of maltreatment status, multiple-variable matching of comparison children, and contextually relevant assessment. One hundred eight Head Start children, of whom 54 were maltreated, participated. Assessment of social functioning included measurement of peer play interactions, global social skills, peer sociometrics, and teacher and parent ratings of behavior problems. RESULTS: Findings indicated that maltreated children were significantly less interactive in peer play and overall exhibited less self-control and interpersonal skill in social interactions than nonmaltreated children. In addition, maltreated children were more likely than their nonmaltreated peers to receive low sociometric ratings and were found by both teachers and parents to display more internalizing behavior problems than comparison children. CONCLUSIONS: These findings indicate the importance of using developmentally sensitive research methods to inform contextually relevant interventions.

Case-Control Studies↗
PubMed1997

Progression of HIV disease is associated with increased expression of Fc gammaRI and CR1 on alveolar macrophages.

The expression of receptors for complement and the Fc region of immunoglobulin by alveolar macrophages (AM) constitutes a valuable aid to effector function of these cells. However, during HIV infection such expression may also act to increase binding of immune complexes, thus facilitating viral infection of these cells. This study was designed to determine whether changes in the expression of these receptors occurs in situ during HIV infection. Lung macrophages were isolated by bronchoalveolar lavage in groups of HIV+ subjects segregated on the basis of peripheral CD4 count. A group of normal subjects was also investigated. Expression of CR1 and Fc gammaRI was quantified by measuring the optical density of reaction product following controlled immunoperoxidase staining with MoAbs CD35 and CD64. Both CR1 and Fc gammaRI were increased over normal in all HIV+ subjects. This increase was progressive with advancing disease as determined by correlation with declining peripheral CD4 count. Comparison of asymptomatic and symptomatic subjects with HIV infection showed no difference in CR1 expression but a rise in Fc gammaRI expression in the latter group. An overall inverse correlation was also found between peripheral CD4 count and Fc gammaRI expression, but not CR1 expression. These data demonstrate a significant increase in the expression of these receptors on AM from HIV+ subjects, and show that this increase may occur before any symptoms in these patients.

Adult↗
PubMed1997

Domestic violence and children: prevalence and risk in five major U.S. cities.

OBJECTIVE: Children witnessing domestic violence is a major national concern. The present study provided data on the prevalence of children's exposure to substantiated cases of adult female assaults in five U.S. cities. METHOD: Data for this study were drawn from the Spouse Assault Replication Program (SARP) database, collected from police officers and female victims of misdemeanor domestic violence. In addition, household demographic data and data on involvement of children in the violent incidents were collected. Data from the SARP households were compared with census data from each city. RESULTS: Results indicated that children were disproportionately present in households with domestic violence and that young children were disproportionately represented among these children. Moreover, these children were exposed to excessive levels of additional developmental risk factors and they were involved in the incidents to varying degrees. CONCLUSIONS: These findings underscore the importance of establishing a more rigorous interdisciplinary, scientific research agenda to inform assessment and treatment efforts for a very vulnerable group of children who witness domestic violence, children aged 0 through 5 years.

Adolescent↗
PubMed1997

War pensions.

Explore the source record for details and available documents.

Humans↗
PubMed1997

Interleukin-2-based therapy for metastatic renal cell cancer: the Cytokine Working Group experience, 1989-1997.

PURPOSE: This article reviews long-term follow-up data from three phase II studies conducted by the Cytokine Working Group from 1989 to 1995 that evaluated various recombinant interleukin-2 (rIL-2) -based regimens in patients with metastatic renal cell cancer. Response rates, long-term response duration, and toxicity are compared. PATIENTS AND METHODS: The Cytokine Working Group studies reviewed here investigated the safety and efficacy of two high-dose intravenous rIL-2-based regimens and two moderate-dose outpatient subcutaneous rIL-2-based regimens in patients with progressive metastatic renal cell cancer. A randomized phase II study, initiated in 1989, investigated the safety and efficacy of high-dose intravenous rIL-2 alone and high-dose intravenous rIL-2 plus recombinant interferon-alpha (rIFN-alpha). A second phase II study, initiated in 1992, tested the safety and efficacy of moderate-dose subcutaneous rIL-2 plus subcutaneous rIFN-alpha in the outpatient setting. The third trial, initiated in 1995, investigated a regimen consisting of the previous subcutaneous rIL-2 plus rIFN-alpha regimen alternating with intravenous bolus 5-fluorouracil (5-FU) plus subcutaneous rIFN-alpha. Median follow-up for these studies is 72 months, 48 months, and 24 months, respectively. RESULTS: The overall response rates observed with each of these regimens were similar (17% with high-dose rIL-2 alone, 11% with high-dose rIL-2/rIFN-alpha, 17% with outpatient subcutaneous rIL-2/rIFN-alpha, and 16% with outpatient rIL-2/rIFN-alpha, plus 5-FU/rIFN-alpha). However, the high-dose rIL-2 regimen produced a 7% complete response rate, compared with 0%, 4%, and 4%, respectively, with each of the other regimens. Median response duration was also much longer with high-dose intravenous rIL-2 alone (53 months), compared with 7 months, 12 months, and 9 months, respectively, with each of the other regimens. CONCLUSION: Complete response rate and response duration appear to favor the high-dose intravenous rIL-2 regimen. This will require verification in a randomized study comparing the best high-dose arm (rIL-2 alone) with the best outpatient regimen (rIL-2/IFN-alpha). The Cytokine Working Group is currently conducting such a study.

Adult↗
PubMed1997

Prospective randomized trial of lisofylline for the prevention of toxicities of high-dose interleukin 2 therapy in advanced renal cancer and malignant melanoma.

The therapeutic application of high-dose interleukin (IL) 2 in human malignancy is limited by severe multiorgan toxicities that are mediated, in part, by tumor necrosis factor (TNF) and IL-1. CT1501R (lisofylline; LSF) is one of several methyl xanthine congeners that inhibit the effects of TNF by the interruption of specific signal transduction pathways. This randomized, placebo-controlled trial was designed to assess the activity of LSF in reducing the toxicities of high-dose IL-2 therapy. Fifty-three patients with metastatic renal cancer or malignant melanoma were treated with i.v. bolus IL-2, 600, 000 IU/kg every 8 h for 5 days (14 doses), followed by 9 days of rest and another 5-day course of IL-2. Patients were randomly assigned to LSF, 1.5 mg/kg i.v. bolus, or placebo every 6 h during IL-2 therapy. All patients were to be treated to individual maximum tolerance of IL-2 at the intensive care unit level of support. The end points for statistical analysis were the number of IL-2 doses administered during the first cycle of treatment (maximum, 28) and the toxicities experienced by each group after the first 8 planned IL-2 doses. There was no difference between the LSF and placebo groups in the mean number of IL-2 doses tolerated in the entire first cycle of therapy (19.6 +/- 5.4 versus 19.5 +/- 5.8, P = 0.86) or in the first or second 5-day course of IL-2. The only significant difference in toxicities occurring through the eighth dose of IL-2 was in the maximum elevation of serum creatinine (mean, 1.7 +/- 0.8 for placebo versus 1.5 +/- 0.6 mg/dl for LSF, P = 0.013). A Monte Carlo analysis of major toxicities over the first 14-dose course of therapy showed a statistically significant difference favoring the LSF-treated group (P = 0.025). LSF was well tolerated, associated only with mildly increased nausea (P = 0.006 after eight IL-2 doses, but not significant for the entire first cycle). The antitumor activity was comparable in both groups (objective responses, 2 of 28 with LSF versus 4 of 24 with placebo). The mean peak plasma concentrations of LSF on days 1, 5, and 19 were 6.24, 3.83, and 5.04 micromol/liter, respectively. In conclusion, with this dose and schedule, LSF did not alter the toxicities of high-dose i.v. IL-2 sufficiently to impact the overall dose intensity of IL-2. Successful IL-2 toxicity modulation may require the use of higher doses of LSF, the development of agents with more potent anti-TNF activity, and/or combined modulating agents that function via distinct mechanisms to interrupt cytokine-mediated signaling.

Adult↗
PubMed1996

Community-based resilient peer treatment of withdrawn maltreated preschool children.

The purpose of the present study was to evaluate differences in the social play of maltreated and nonmaltreated preschool children and the effectiveness of a resilient peer treatment (RPT) for socially withdrawn victims of physical abuse and neglect. RPT is a peer-mediated classroom intervention based on a developmental-ecological model. It involves pairing withdrawn children with resilient peers in the natural classroom under the supervision of a parent assistant. Forty-six Head Start children, of whom 22 were maltreated, were randomly assigned to RPT and control conditions. Outcome variables were observational categories of social play and standardized teacher ratings. Before treatment, maltreated children were significantly more isolated and less interactive in peer play than nonmaltreated children. RPT resulted in a significant increase in positive interactive peer play and a decrease in solitary play for maltreated and nonmaltreated, socially withdrawn children. Moreover, treatment gains in social interactions were validated 2 months following treatment. Findings are discussed in terms of a developmental-ecological model.

Child Abuse↗
PubMed1995

Breath-holding time in normal subjects, snorers, and sleep apnea patients.

BACKGROUND: The onset of irregular inspiratory muscle activity has been observed toward the breakpoint of the breath-holding maneuver. We wondered if this was similar to the increased respiratory effort with paradoxical breathing seen during the resolution of an apnea in obstructive sleep apnea syndrome (OSAS). STUDY OBJECTIVE: To compare the breakpoint of breath holding in normal subjects, OSAS patients, and snorers. METHODS: Thirty normal subjects, 30 patients with OSAS, and 16 snorers performed serial breath-holding maneuvers at functional residual capacity (FRC) under standardized pretest conditions using the rebreathing method of Read. RESULTS: Intergroup comparisons were carried out by analysis of variance with post hoc Tukey's Highest Significant Difference tests. Basal end-tidal carbon dioxide (EtCO2) was significantly higher in OSAS than in normal subjects and snorers. Basal breath-holding time (BHT) was shorter in OSAS as compared with that in normal subjects and snorers (p < 0.05). The maximal EtCO2 level attained was higher in OSAS as compared with normal subjects (p < 0.05) and snorers (p = 0.052). The maximal BHT in OSAS was shorter than in normal subjects (p < 0.05) but not in snorers. The slope of BHT/EtCO2 differed significantly in OSAS compared with normal subjects and snorers (p < 0.05). No significant correlation was found between slope BHT/EtCO2 and age or body mass index using multiple regression analysis. The FRC of OSAS patients and snorers were similar (p = 0.792). CONCLUSION: We conclude that BHT and slope of BHT/EtCO2 are different in OSAS subjects as opposed to those in normal subjects and snorers.

Carbon Dioxide↗
PubMed1994

Parvovirus B19 outbreak on an adult ward.

In November and December 1992, an outbreak of parvovirus B19 infection occurred among patients and staff on an adult mixed surgical ward at a large hospital in London. Three patients and 15 staff members were serologically confirmed as acute cases. The attack rate among susceptible members of staff was 47%. In those infected, arthralgia (80%) and rash (67%) were the most common symptoms. Of six susceptible in-patients on the ward, three became infected. One of the in-patients who had carcinoma of the mouth was viraemic for more than 10 days with marrow suppression resulting in the postponement of chemotherapy until intravenous immunoglobulin was given and he was no longer viraemic. Control measures taken included closure of the ward to new admissions, transfer of only immune staff to the ward, and restriction of the ward nursing staff to working only on that ward. Although no specific exposure was conclusively identified as a risk factor, there was a suggestion of an increased risk of acquiring parvovirus B19 infection among those staff who did not adopt strict hand washing procedures after each physical contact with a patient (RR = 2.33; P = 0.07). Knowledge of parvovirus B19 among interviewed health care workers was poor: only 42% reported knowing about parvovirus B19 and only 38% could name a patient category at risk of a severe outcome following infection. This is the first report of a nosocomial outbreak affecting an adult ward and of possible transmission of parvovirus B19 infection from staff to in-patients. Hospital control of infection teams should include parvovirus B19 in their outbreak containment plans.

Adult↗
PubMed1994

Nasal resistance in obstructive sleep apnea.

BACKGROUND: Acute increases in nasal resistance are known to induce upper airway occlusion in predisposed subjects. With the limited efficacy of nasal surgery alone in the treatment of obstructive sleep apnea (OSA), the relevance of chronically increased nasal resistance in the pathophysiologic features of OSA remains undetermined. METHODS: Seventy-one patients with OSA (apnea+hypopnea index > 15 [AHI]) and 70 antisocial snorers (ASS [AHI < 15]) referred for routine assessment of sleep-disordered breathing had concomitant measurement of combined (CNR) and highest unilateral (HUNR) nasal resistance by anterior rhinomanometry. RESULTS: Nine individuals (five of 71 in the OSA group and 4 of 70 in the ASS group, 0.5 < p < 0.75) had an abnormally elevated CNR. The HUNR was increased in 21 individuals (11 of 70 in the ASS group and 10 of 71 in the OSA group, 0.25 < p < 0.5). There was no significant difference between CNR in OSA (1.5[0.5]) (mean [SE]) and ASS (1.6 [0.2]) groups. No correlation was found between CNR and the AHI in OSA or in ASS. The Mean HUNR in the OSA group was 5.5 (0.9) (mean [SE]) and in ASS was 5.3(0.6), which were not significantly different (p = 0.89). The HUNR also did not correlate with the AHI in either OSA or ASS. CONCLUSION: Chronic changes in nasal resistance are not a significant risk factor for the development or severity of OSA.

Airway Resistance↗
PubMed1993

Cytomegalovirus mononucleosis: risk for fathers of young children.

A case of pyrexia of unknown origin in a 35-year-old man, who had become a father nine months earlier, is presented. A diagnosis of cytomegalovirus mononucleosis was achieved only after extensive investigations. It is suggested that cytomegalovirus mononucleosis should be added to the differential diagnosis when investigating pyrexia of unknown origin in fathers of young children.

Adult↗