Principles for using combination vaccines.
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Family Practice↗
Biomedical subjects
R Zimmerman
Publications and source records attributed to R Zimmerman.
Prolonged allograft survival but no tolerance induction by modulating CD28 antibody JJ319 after high-responder rat heart transplantation.
BACKGROUND: Allograft rejection depends on T cell immune responses requiring antigen recognition and costimulatory signals through accessory T cell receptors, including CD28. Inhibition of CD28 signaling with a CTLA-4-immunoglobulin (Ig) fusion protein has resulted in immunosuppression and occasional T cell anergy in mouse transplant models, but not in rats. Because this approach also inhibits a potentially tolerizing signal through CTLA-4, selective blockade of CD28 ligation might induce more profound immunosuppression and transplant tolerance. METHODS: The effects of escalating doses of the rat CD28 monoclonal antibody JJ319 on allograft survival were studied after vascularized heterotopic heart transplantation in a high responder strain combination (DA to Lewis). CD28 antigen modulation and circulating antibody levels were monitored by flow cytometry. RESULTS: CD28 antibody JJ319 markedly prolonged cardiac graft survival compared with untreated controls (7 days, range: 6-8). A strictly dose-dependent increase in median graft survival time was demonstrated with a maximum of 36 days (range: 30-40; p <0.001) after the administration of 8 x 1 mg JJ319 i.p. (days -1 to +6 before/after transplantation). However, indefinite graft survival and tolerance could not be induced by JJ319 treatment. At the maximal dose, flow cytometry showed complete down modulation of the CD28 receptor for 10-14 days without T cell depletion in close temporal relation to antibody presence in serum. In vitro, CD28-modulated T cells showed significantly reduced responses to activation. CONCLUSIONS: CD28 antibody JJ319 induces profound immunosuppression after rat heart transplantation, however without development of transplant tolerance. The underlying mechanism seems to be receptor modulation during primary alloantigen recognition. While still potentially applicable clinically, there are no qualitative or quantitative differences to the treatment with CTLA-4/lg or the blockade of CD2 or LFA-1, as reported elsewhere. Thus, a CD28-modulating approach seems not to allow therapeutic exploitation of a tolerizing signal delivered by CTLA-4 but may still be clinically applicable, especially in combined immune interventions.
Abatacept↗
Association of diabetes mellitus and chronic hepatitis C virus infection.
While patients with liver disease are known to have a higher prevalence of glucose intolerance, preliminary studies suggest that hepatitis C virus (HCV) infection may be an additional risk factor for the development of diabetes mellitus. To further study the correlation of HCV infection and diabetes, we performed a retrospective analysis of 1,117 patients with chronic viral hepatitis and analyzed whether age, sex, race, hepatitis B virus (HBV) infection, HCV infection, and cirrhosis were independently associated with diabetes. In addition, a case-control study was conducted to determine the seroprevalence of HCV infection in a cohort of 594 diabetics and 377 clinic patients assessed for thyroid disease. In the former study after the exclusion of patients with conditions predisposing to hyperglycemia, diabetes was observed in 21% of HCV-infected patients compared with 12% of HBV-infected subjects (P =.0004). Multivariate analysis revealed that HCV infection (P =.02) and age (P =.01) were independent predictors of diabetes. In the diabetes cohort, 4.2% of patients were found to be infected with HCV compared with 1.6% of control patients (P =.02). HCV genotype 2a was observed in 29% of HCV-RNA-positive diabetic patients versus 3% of local HCV-infected controls (P <.005). In conclusion, the data suggest a relatively strong association between HCV infection and diabetes, because diabetics have an increased frequency of HCV infection, particularly with genotype 2a. Furthermore, it is possible that HCV infection may serve as an additional risk factor for the development of diabetes, beyond that attributable to chronic liver disease alone.
Adult↗
Safer sex strategies for women: the hierarchical model in methadone treatment clinics.
Women clients of a methadone maintenance treatment clinic were targeted for an intervention aimed to reduce unsafe sex. The hierarchical model was the basis of the single intervention session, tested among 63 volunteers. This model requires the educator to discuss and demonstrate a full range of barriers that women might use for protection, ranking these in the order of their known efficacy. The model stresses that no one should go without protection. Two objections, both untested, have been voiced against the model. One is that, because of its complexity, women will have difficulty comprehending the message. The second is that, by demonstrating alternative strategies to the male condom, the educator is offering women a way out from persisting with the male condom, so that instead they will use an easier, but less effective, method of protection. The present research aimed at testing both objections in a high-risk and disadvantaged group of women. By comparing before and after performance on a knowledge test, it was established that, at least among these women, the complex message was well understood. By comparing baseline and follow-up reports of barriers used by sexually active women before and after intervention, a reduction in reports of unsafe sexual encounters was demonstrated. The reduction could be attributed directly to adoption of the female condom. Although some women who had used male condoms previously adopted the female condom, most of those who did so had not used the male condom previously. Since neither theoretical objection to the hierarchical model is sustained in this population, fresh weight is given to emphasizing choice of barriers, especially to women who are at high risk and relatively disempowered. As experience with the female condom grows and its unfamiliarity decreases, it would seem appropriate to encourage women who do not succeed with the male condom to try to use the female condom, over which they have more control.
Acquired Immunodeficiency Syndrome↗
Adverse health experiences, environmental attitudes, and pesticide usage behavior of farm operators.
Water pollution from agricultural pesticides continues to be a public concern. Given that the use of such pesticides on the farm is largely governed by voluntary behavior, it is important to understand what drives farmer behavior. Health belief models in public health and social psychology argue that persons who have adverse health experiences are likely to undertake preventive behavior. An analogous hypothesis set was tested here: farmers who believe they have had adverse health experiences from pesticides are likely to have heightened concerns about pesticides and are more likely to take greater precautions in dealing with pesticides. This work is based on an original survey of a population of 2700 corn and soybean growers in Maryland, New York, and Pennsylvania using the U.S. Department of Agriculture data base. It was designed as a mail survey with telephone follow-up, and resulted in a 60 percent response rate. Farm operators report experiencing adverse health problems they believe are associated with pesticides that is equivalent to an incidence rate that is higher than the reported incidence of occupational pesticide poisonings, but similar to the reported incidence of all pesticide poisonings. Farmers who report experiencing such problems have more heightened concerns about water pollution from fertilizers and pesticides, and illness and injury from mixing, loading, and applying pesticides than farmers who have not experienced such problems. Farmers who report experiencing such problems also are more likely to report using alternative pest management practices than farmers who do not report having such problems. This implies that farmers who have had such experiences do care about the effects of application and do engage in alternative means of pest management, which at least involve the reduction in pesticide use.
Agriculture↗
Project DARE: no effects at 10-year follow-up.
The present study examined the impact of Project DARE (Drug Abuse Resistance Education), a widespread drug-prevention program, 10 years after administration. A total of 1,002 individuals who in 6th grade had either received DARE or a standard drug-education curriculum, were reevaluated at age 20. Few differences were found between the 2 groups in terms of actual drug use, drug attitudes, or self-esteem, and in no case did the DARE group have a more successful outcome than the comparison group. Possible reasons why DARE remains so popular, despite the lack of documented efficacy, are offered.
Adolescent↗
Risky sex behavior and substance use among young adults.
Many young adults, despite widespread prevention and education efforts that target this age group, engage in behaviors that place them at risk of HIV infection. These behaviors include frequent experimentation with alcohol and other drugs before sex, sexual activity with different partners, and inconsistent safe-sex practices. The combination of these risky behaviors causes increased concern about the spread of HIV among this age group. The study discussed in this article examined the relationship between substance use during adolescence and HIV risk behavior among young adults ages 19 to 21 with and without a college education. Results indicated that increased use of alcohol and marijuana at younger ages is related to riskier sexual activity and increased use of alcohol and marijuana as young adults. Recommendations for interventions are made.
Adolescent↗
Semiquantitative assessment of c-erbB-2 (HER-2) status in cytology specimens and tissue sections from breast carcinoma.
OBJECTIVE: To determine whether various methods of fixation of surgical pathology specimens from breast carcinomas would influence the outcome of evaluation of the expression levels of c-erbB-2 (HER-2). For this, comparisons were made between (1) alcohol-fixed (95%) and air-dried smears from fresh surgical pathology specimens of breast carcinomas, and (2) formalin-fixed, paraffin-embedded tissue sections of the same specimens. STUDY DESIGN: Alcohol-fixed and air-dried smears or touch preparations were made from 30 fresh mastectomy/lumpectomy surgical pathology specimens from breast carcinomas. Immunohistochemistry was performed using the c-erbB-2 primary antibody against the extracellular domain of the c-erbB-2 gene product. Staining was simultaneously performed on formalin-fixed, paraffin-embedded tissue sections of the same specimens. A semiquantitative approach was used for evaluation of immunostaining by three independent investigators, and a consensus was reached. RESULTS: A total of 30 cases were reviewed. Tissue positivity was determined for c-erbB-2 in: 73% of alcohol-fixed specimens (n = 13 [3+] and n = 9 [2+]), 67% of air-dried smears (n = 9 [+3] and n = 11 [+2]) and 47% (n = 8 [+3]) and n = 6 [+2]) of formalin-fixed, paraffin-embedded tissue specimens. All formalin-fixed tissue specimens that were determined to positively express c-erbB-2 were also found to be positive on the alcohol-fixed smears. CONCLUSION: The incidence of c-erbB-2 expression in fresh cytologic material is significantly higher (P < .05) than in formalin-fixed, paraffin-embedded tissue. Alcohol-fixed smears demonstrate a slightly higher percentage of cell staining and stronger intensity of c-erbB-2 expression than the matched, air-dried smears. This is a sensitive and simple processing method that can be routinely applied in surgical pathology or fine needle aspiration biopsy specimens for the detection of c-erbB-2 (HER-2), with clinical implications.
Adenocarcinoma↗
Clueless: parental knowledge of risk behaviors of middle school students.
OBJECTIVES: To determine parental knowledge of risk behaviors of their middle-school-aged children and to compare that knowledge with behaviors reported by the students. DESIGN: Confidential surveys were administered to 194 poor and middle-class middle school students and their parents. INTERVENTION: None. MAIN OUTCOME MEASURE: Compare parental awareness and student admission of risk behaviors. RESULTS: Students and parents agree on the prevalence of some risk behaviors, including use of a seat belt, use of a bicycle helmet, arrest by police, use of diet pills, and attempts to lose weight through dieting and exercise. Small differences in perception, which were not statistically significant but which could be defined as trends, were found relating to the prevalence of dieting, exercising, or vomiting to lose weight. Statistically significant differences were found in the perceptions of the prevalence of the following risk behaviors: carrying a weapon to school (P<.001), LSD (lysergic acid diethylamide) or cocaine use (P=.02), suicide attempt (P<.001), sexual intercourse (P<.001), alcohol use (P<.001), tobacco use (P<.001), and marijuana use (P<.001). In many cases, parents dramatically underestimated the prevalence of these behaviors in students. CONCLUSIONS: Parents are largely ignorant of the extent to which their adolescents are involved in major risk behaviors. Educating parents in this area encourages them to support comprehensive health education curricula and other preventive programs in schools and communities.
Adolescent↗
Survival in renal cell carcinoma-a randomized evaluation of tamoxifen vs interleukin 2, alpha-interferon (leucocyte) and tamoxifen.
Metastatic renal cell carcinoma (RCC) has a poor prognosis. Conventional treatment strategies, including chemotherapy and hormonal therapy, have limited value. Although encouraging results have been achieved in terms of objective response using immunological manipulations, no conclusive studies yet exist with a controlled comparative evaluation of survival. Therefore, the present study was undertaken, which compared one of the present (and presumed best) treatments, interleukin 2/interferon-alpha (IL-2/IFN-alpha) and tamoxifen, with a control arm of tamoxifen only. Tamoxifen has been shown to potentiate in vivo anti-tumour activity of IL-2, and because of its non-toxic behaviour it was included in both groups. The study was open, randomized and included seven institutions in Sweden. The patients were stratified according to the different centres involved. An interim analysis was planned when a minimum of 100 patients were evaluable. The 128 patients finally included had a histologically documented metastatic RCC, with a life expectancy of more than 3 months, a performance status WHO 0-2 and no prior chemo- or immunotherapy. Informed consent was obtained from each patient. The patients randomized to the control arm (n = 63) received only tamoxifen 40 mg p.o. daily for at least 1 year or until progression. The patients (n = 65) randomized to biotherapy received subcutaneous recombinant IL-2, leucocyte IFN-alpha in a treatment cycle of 42 days, as well as tamoxifen p.o. In the absence of undue toxicity or disease progression, these patients received one additional treatment cycle of 42 days followed by maintenance treatment, consisting of 5 days therapy every 4 weeks, for 1 year, or until proven progression. Only two patients in the tamoxifen-only group received immunotherapy when the disease progressed, but without any beneficial effect. All patients received appropriate local treatment when indicated. The interim analysis demonstrated no survival advantage for either group, and therefore further inclusion of patients was stopped. The median follow-up was 11 months (range 0.4-48 months). The final survival analysis showed no significant differences between the two treatment arms in so far as comparison from the day of diagnosis of primary disease, from the day of first evidence of metastatic spread, or from the onset of treatment. This was valid both when the evaluation was performed with regard to intention to treat and when the analysis was directed only to patients that managed at least one treatment cycle (42 days) of IL-2/IFN-alpha. The adverse effects were more pronounced in the IL-2/IFN-alpha group. Although the number of patients is limited, the results raise doubt concerning immunotherapy with IL-2 and IFN-alpha as a routine treatment in the management of advanced RCC. The difference in cost of drugs and health care (drug costs per patient: IL-2/IFN-alpha $27000 vs tamoxifen $360) as well as adverse effects caused by IL-2/IFN-alpha are also factors of importance. The study emphasizes the need for more effort to find the 'optimal schedule' of immunotherapy, as well as the need for randomized controlled studies before approval of a new treatment in the routine setting.
Adult↗
Easy method for defining intracranial target volumes on orthogonal simulation films using magnetic resonance images.
A technique is described for simulating intracranial radiation fields. The method involves the projection of images from magnetic resonance (MR) scans to orthogonal simulation radiographs. This approach often can supplement and occasionally obviate the need for computerized tomographic (CT) assisted treatment simulation for co-planar beam arrangements in brain irradiation. Because magnetic resonance imaging can be performed in virtually any plane and is routinely carried out in sagittal and coronal planes, transferring tumor volumes to orthogonal simulation films using this technique can be done simply and accurately. The method employs an inexpensive photographic enlarger to superimpose sagittal MR scans on the lateral skull simulation films. Tumor volumes along with other structures of interest are treated onto the film and appropriate fields and blocks are contoured. The technique is performed easily in conjunction with routine simulation sessions, provided that the appropriate MR images are available. It is most suitable for planning treatment of tumors located at midline (e.g., medulloblastomas, craniopharyngiomas, brainstem gliomas, germinomas, etc.). The technique has also been used to verify the accuracy of CT-assisted treatment planning. With relatively minor modifications, eccentric tumors also can be accurately planned, and although we have restricted our description to brain tumours, the technique may be extrapolated to tumors in other sites.
Brain Neoplasms↗
Increased growth factor transcription after pulmonary artery banding.
OBJECTIVE: Several mechanisms are known to produce mechanical stress during and after cardiac surgery, e.g. aortic cross-clamping and pulmonary artery banding (PAB). However, little is known about the transcription of myocardial genes which are changed during mechanical overload. This study was performed to investigate growth factor mRNA expression after PAB in porcine hearts. METHODS: The experiment was performed in 35 pigs (five groups). Each group consisted of three sham-pigs (S-pigs) and four banding-pigs (B-pigs). The mean transbanding gradient in B-pigs was 29 +/- 2.5 mm Hg. The hearts were excised after different time intervals. The probes were snap-frozen in liquid nitrogen and stored at -80 degrees C. Analysis was performed by Northern blot. RESULTS: Right ventricular weight increased significantly after 7 and 24 days (P < 0.05). There was an upregulation of transcriptional and growth factors in B-pigs: c-jun mRNA: 412 +/- 12.1% after 2 h (P < 0.001); c-fos mRNA: 303 +/- 18.5% after 2 h (P < 0.001); vascular endothelial growth factor (VEGF) mRNA: 203 +/- 18.2% after 2 h (P < 0.001); Flk-1 mRNA: 156 +/- 16% after 2 h (P < 0.05), 253 +/- 5% after 24 h (P < 0.01) and 184 +/- 12% after 3 days (P < 0.01); transforming growth factor-beta1 (TGF-beta1) mRNA: 255 +/- 21.5% after 24 h (P < 0.002). Fibroblast growth factors 1 and 2 (FGF-1 and FGF-2) were constitutively expressed in B- and S-pigs and did not change their expression. CONCLUSIONS: Pulmonary artery banding results in significant right ventricular hypertrophy and upregulation of different growth factors. However, growth factors known to induce hypertrophy in vitro, like the FGFs, showed unchanged expression. We think that myocardial growth factors may have trophic functions in the heart which may be useful for cardiac surgery in future.
Animals↗
Craniopharyngioma arising de novo in middle age. Case report.
The authors report the case of a 55-year-old woman who developed a symptomatic craniopharyngioma within 2 years of obtaining a normal magnetic resonance image of her brain. Craniopharyngiomas are histologically benign tumors. They are thought to arise from embryonic remnants of Rathke's pouch and sac and to manifest themselves clinically after a steady growth that commences in fetal life. To the authors' knowledge, this is the first report that documents a tumor arising de novo in the sixth decade of life. This report appears to challenge the concept of the origin and natural history of craniopharyngiomas.
Craniopharyngioma↗
Family structure versus parental attachment in controlling adolescent deviant behavior: a social control model.
This study examines the relationship between family characteristics and adolescent deviant behaviors such as major and minor delinquency, and alcohol, cigarette, and drug use, while controlling for gender and race/ethnicity. The intervening factor of the socialization of law-abiding belief was also examined. Data represent a subsample from Wave 1 of the South Florida Youth Development Project involving middle school students in Dade County public schools. A significant direct relationship was found between family attachment and each of the deviant behaviors; however, family structure was not significantly related to any of the deviant behaviors. No significant interactions were found between gender or race with family structure and family attachment regarding any of the deviant behaviors. Family attachment had a direct effect on law-abiding belief, which also had a significant effect on the deviant behaviors.
Adolescent↗
Postoperative surveillance imaging in children with cerebellar astrocytomas.
The standard follow-up care for children with cerebellar astrocytomas includes regular surveillance imaging of the brain with computerized tomography or magnetic resonance. The purpose of surveillance imaging is to detect asymptomatic tumor recurrence at an early stage and permit safer reoperation. The authors evaluated the effectiveness of an intensive surveillance program for cerebellar astrocytoma and tested different models of surveillance frequency and duration to arrive at a specific recommended program. Review of the records of 93 children with typical cerebellar astrocytomas who received follow-up care between 1975 and 1993 was performed. Immediate postoperative and surveillance images were classified as showing definite equivocal, or no tumor based on the radiology report at the time the image was obtained. Various surveillance models were then tested for their predictive value for detecting tumor recurrence. Seventeen (18%) of the 93 children had tumor recurrence or progression. Eleven of these tumors were asymptomatic and detected only by surveillance image. Tumor recurred in only one patient with a total resection, whereas tumor progression occurred in five of 21 patients with equivocal postoperative images and in 11 of 14 patients with residual tumor. A model in which patients with possible or definite residual tumor after surgery undergo surveillance at 12, 18, 30, 42, and 66 months, and later have one additional image, yielded optimum predictive value for recurrence and/or progression with the fewest images. Patients with tumor recurrence were satisfactorily treated, and only one patient died. Children with totally resected cerebellar astrocytomas do not appear to benefit from routine surveillance, because the likelihood of recurrence is small. Surveillance is of benefit in those who may have subtotal resection based on the immediate postoperative imaging.
Astrocytoma↗
Cognitive functioning and brain magnetic resonance imaging in children with sickle Cell disease. Neuropsychology Committee of the Cooperative Study of Sickle Cell Disease.
OBJECTIVE: Brain magnetic resonance imaging (MRI) and neuropsychological evaluations were conducted to determine whether neuroradiographic evidence of infarct in children with sickle cell disease between ages 6 and 12 years would result in impairment in cognitive and academic functioning. METHOD AND DESIGN: Children enrolled in the Cooperative Study of Sickle Cell Disease were evaluated with brain MRI and neuropsychological evaluation. Completed studies were obtained for 194 children, 135 with HbSS. MRIs were categorized according to the presence of T2-weighted, high-intensity images suggestive of infarct and were further categorized on the basis of a clinical history of cerebrovascular accident (CVA). An abnormal MRI but no clinical history of CVA was classified as a silent infarct. Neuropsychological evaluations included assessment of both global intellectual functioning and specific academic and neuropsychological functions. RESULTS: Central nervous system (CNS) abnormalities were identified on MRI in 17.9% of the children (22.2% of children homozygous for HbS), and a clinical history of CVA (N = 9, 4.6%) was identified in only children with HbSS disease. Subsequent analyses examined only children with HbSS. Children with a history of CVA performed significantly poorer than children with silent infarcts or no MRI abnormality on most neuropsychological evaluation measures. Children with silent infarcts on MRI performed significantly poorer than children with no MRI abnormality on tests of arithmetic, vocabulary, and visual motor speed and coordination. CONCLUSIONS: These results substantiate the importance of careful evaluation, educational planning, and medical intervention for CNS-related complications in children with sickle cell disease.
Anemia, Sickle Cell↗
[Ultrasound experience and apparatus of Swiss gynecologists. Results of a written survey].
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Female↗
MRI, MRA, and neurodevelopmental outcome following neonatal ECMO.
Cranial magnetic resonance imaging (MRI) of 31 newborn infants treated with venoarterial cardiopulmonary bypass for severe but reversible respiratory failure, revealed major focal parenchymal lesions in 7 of 31 infants (23%) and demonstrated abnormal enlargement of extra-axial and ventricular cerebrospinal fluid spaces in 16 of 31 (51%). No preferential left versus right lateralization of focal injury was observed in conjunction with right common carotid artery and jugular vein ligation. No statistically significant relationships were found between major brain lesions on MRI scans and the clinical characteristics of the pre-extracorporeal membrane oxygenation (ECMO), ECMO, and post-ECMO course. Major focal brain lesions were significantly associated with an asymmetric cerebrovascular response to carotid ligation of the right versus left middle cerebral arteries as detected by magnetic resonance angiography (P < .05). Enlarged cerebrospinal fluid spaces were not significantly related to the presence of parenchymal MRI lesions, but were associated with lower Bayley neurodevelopmental scores for mental (MDI) and psychomotor evaluations (PDI) at 6 and 12 months (P < .05). It is concluded that asymmetries of cerebral vascular adaptation detected by magnetic resonance angiography after ECMO may be associated with major brain lesions revealed by MRI. Thereafter, the presence of enlarged cerebrospinal fluid spaces on MRI is associated with a poor shortterm developmental outcome.
Brain↗