Biomedical subjects
Publications and source records attributed to J Smith.
This study developed a method of in-school intervention that dramatically reduced the suspension rate and violence in elementary schools. It suggests that children who were not read to by their parents often become bullies and/or victims of bullies. Other parental practices, including inconsistent discipline in the home, also may be contributing factors.
The present study (N = 122) examined whether older adults (M = 79 years) differed from younger age groups (Ms = 25 and 45 years) in their experience of 35 situations of unsolicited support selected from 7 content areas (e.g., health, cognition, finances, life management). Examined were reported occurrence, affective quality, interpretation, and strategies used when support was unwelcome. At all ages, unasked-for support was regarded as more unpleasant than pleasant, primarily because it implied incompetence. Unexpectedly, compared with the younger adults, older adults reported less occurrence overall (with some variations by content area) but the same level of unpleasant affect. Cognitive and social-relational factors that are age related (e.g., the use of active discounting strategies) played a role in reported occurrence and affective appraisal and may determine whether unsolicited support has positive or negative outcomes.
BACKGROUND: Evidence suggests that embolization precedes carotid thrombosis, a previously unpredictable event complicating 2-3 per cent of all carotid endarterectomies. It was hypothesized that dextran 40 therapy might prevent progression to complete thrombosis in high-risk patients. METHODS: Between October 1995 and July 1998, 400 consecutive patients were monitored following carotid endarterectomy using transcranial Doppler ultrasonography. Those with sustained embolization (more than 25 in 10 min) or those with emboli that distorted the middle cerebral artery waveform were commenced on an incremental dextran 40 infusion. RESULTS: Two hundred and sixteen patients (54 per cent) had one or more emboli detected (96 per cent within 2 h of flow restoration) but only 15 (4 per cent) required dextran therapy. Embolization ceased in each case although the dextran dose had to be adjusted in four. In one of the latter patients, embolization recurred on day 5 but was again controlled with high-dose dextran. Overall, the death and any stroke rate was 2 per cent and no patient suffered a stroke due to carotid thrombosis. CONCLUSION: A few patients develop sustained embolization following carotid endarterectomy which, in previous studies, has been shown to be highly predictive of carotid thrombosis. The authors' experience to date suggests that dextran can stop this phase of embolization and prevent progression to complete carotid thrombosis. However, the dose of dextran has to be adjusted in 25 per cent of patients (i.e. blind administration of dextran may not be effective) and, very rarely, embolization may recur later.
When peripheral blood stem cell (PBSC) concentrates are used for allogeneic transplants, two or more apheresis procedures must often be performed. To determine how many cells could be collected from healthy people by two back-to-back apheresis procedures and what effect these collections would have on donors, we gave 19 healthy people 5 micrograms kg-1 day-1 and 21 people 10 micrograms kg-1 day-1 of granulocyte colony stimulating factor, filgrastim, for 5 days. We then collected two PBSC concentrates, one on day 5 and one on day 6. A third group of six people was given filgrastim 10 micrograms kg-1 day-1 for 5 days but had no PBSC concentrates collected. PBSC concentrate cell counts and donor cell counts, symptoms, and blood chemistries were assessed for up to 1 year. On day 5, three times more CD34+ cells were collected from donors given 10 micrograms kg-1 day-1 than those given 5 micrograms kg-1 day-1 (P = 0.009) but on day 6 the quantity of cells collected was the same (P = 0.23). The total number of CD34+ cells collected was two times greater in donors given the higher dose of filgrastim (median = 579 x 10(6); range = 174-1639 x 10(6) compared to 237 x 10(6); 103-1670 x 10(6); P = 0.061). Platelet counts fell after each PBSC concentrate collection, but there were no differences between the two groups of donors in platelet counts measured immediately after each collection. The platelet counts also fell in people who did not donate PBSC concentrates. The lowest counts in all three groups of people also occurred on day 10. In PBSC donors given 10 micrograms kg-1 day-1 of filgrastim the absolute neutrophil count (ANC) fell below premobilization counts on day 14. In donors given 5 micrograms kg-1 day-1 the ANC fell below premobilization counts on days 21, 28 and 49, CD34+ cell counts were significantly lower than premobilization counts on days 14 and 28 in donors given 10 micrograms kg-1 day-1 of filgrastim and on day 14 in those given 5 micrograms kg-1 day-1. No decrease in neutrophil or CD34+ cell counts occurred after filgrastim was given in the people who did not donate PBSC concentrates. The incidence of symptoms was similar in both groups of PBSC concentrate donors, except that those given 10 micrograms kg-1 day-1 were more than twice as likely to experience myalgias as those receiving the lower dose (P = 0.029). Several blood chemistries changed. Levels of alkaline phosphatase, LDH, SGPT, SGOT, uric acid and sodium increased. Levels of bilirubin, total protein, potassium, calcium and chloride decreased. In conclusion, twice as many CD34+ cells were collected from donors given 10 micrograms kg-1 day-1 of filgrastim. Platelet, neutrophil and CD34+ cell counts fell after the PBSC concentrate collections. The fall in platelet counts was due to both the collection and the administration of filgrastim. The falls in neutrophil and CD34+ cell counts were due to the loss of haematopoietic progenitor cells in the PBSC concentrates. Allogeneic PBSC concentrate donors should be given 10 micrograms kg-1 day-1 of filgrastim, and if possible only one component should be collected in order to avoid thrombocytopenia.
BACKGROUND: Activated macrophages play a central role in crescentic glomerulonephritis. Interleukin-4 (IL-4) down-regulates many macrophage proinflammatory activities. We therefore studied the effect of IL-4 on glomerular injury in a model of crescentic glomerulonephritis in the Wistar Kyoto rat. METHODS: Glomerulonephritis was induced by i.v. administration of rabbit antirat glomerular basement membrane antiserum (nephrotoxic serum, NTS). In experiment 1, IL-4 was given from two hours before NTS until day 6. In experiment 2, rats were treated from day 0 to 7 and were then monitored until killed on day 28. In experiment 3, IL-4 was given from day 4 to 7. RESULTS: Continuous IL-4 treatment (experiment 1) significantly (P = 0.001) reduced proteinuria (3 +/- 1 mg per 24 hr vs. 56 +/- 7), fibrinoid necrosis (0.06 +/- 0.04 quadrants/glomulus vs. 1.2 +/- 0.1), macrophage infiltration (6.7 +/- 2.6 cells/glom vs. 33 +/- 2.5), CD8+ cells (1.5 +/- 0.6 cells/glom vs. 6.2 +/- 1.1), inducible nitric oxide synthase positive cells (0.04 +/- 0.04 cells/glom vs. 3.7 +/- 0.6), proliferating cell nuclear antigen positive cells (3.2 +/- 1 cells/glom vs. 15 +/- 2.3), and glomerular intercellular adhesion molecule-1 expression. Follow-up after seven days of treatment (experiment 2) showed that at four weeks, creatinine clearance was higher in treated rats (1.1 +/- 0.1 ml/min vs. 0.4 +/- 01, P = 0.011), and both glomerular scarring (P = 0.006) and tubular atrophy (P = 0.006) were less. Delayed treatment (experiment 3) reduced proteinuria (41 +/- 5 mg per 24 hr vs. 97 +/- 9, P = 0.004) and fibrinoid necrosis (0.39 +/- 0.05 quadrants/glom vs. 1.6 +/- 0.1, P = 0.004). There was no difference in macrophage infiltration, but inducible nitric oxide synthase positive cells were reduced (0.6 +/- 0.1 cells/glom vs. 1.8 +/- 0.4, P = 0.01) as were ED3+ cells (0.18 +/- 0.06 cells/glom vs. 1.86 +/- 0.21, P = 0.004). CONCLUSION: In this model of crescentic glomerulonephritis, early IL-4 treatment abolished proteinuria and markedly reduced glomerular inflammation. If treatment was stopped after seven days, there was continuing benefit on glomerular and tubulointerstitial scarring and creatinine clearance at four weeks. If treatment was delayed until inflammation was established, there was still a reduction of injury, but without an alteration of macrophage numbers, suggesting that IL-4 may be acting, in part, to reduce macrophage activation.
Nurse home visitation has been an important component of public health for over 100 years. Recent reports of large clinical trials have provided a convincing body of evidence of the cost-effectiveness of home visitation. The findings from these studies have helped to renew policy interest in nurse home visitation as a means of improving health and quality of life for low-income families. Reimplementing home visitation on a large scale, however, will require using nurses with little or no home-visiting experience. Sponsoring organizations must delegate, and nurses from hospitals or clinics must accept, responsibility for both increased autonomy and discretion of home visitors. Case study analysis of observational and interview data from the implementation of a large demonstration home visitation program carried out in a health department in a mid-South city from 1989 to 1994 provides evidence that the bottom-up perspective of Hanf and Toonen (1983) best describes how such programs can be put in place. Nurses with little community experience were able to create appropriate strategies to help families achieve the broad program goals in the context of resource constraints associated with a poverty-level lifestyle and the existing health and human service system. Furthermore, nurses were able to establish an organizational culture and job structure in a city/county health department to support their work.
BACKGROUND: The use of granulocyte-colony-stimulating factor (G-CSF) to increase the granulocyte count and the yield from leukapheresis in normal donors is leading to renewed interest in granulocyte transfusion. Therefore, it is important to understand the side effects of G-CSF. STUDY DESIGN AND METHODS: We studied the effect of G-CSF on peripheral blood counts and recorded the side effects experienced 24 hours after an injection of G-CSF in normal subjects donating peripheral blood progenitor cells for research. RESULTS: Following administration of G-CSF to 261 donors, the neutrophil count increased to 20.6 to 24.5 x 10(9) per microL depending on the dose of G-CSF. This represented a 6.2 to 7.4-fold increase over the neutrophil count before G-CSF administration. Of all donors, 69 percent experienced one or more side effects. The most common effects were: muscle and bone pain, headache, fatigue, and nausea. There was a relationship between the dose of G-CSF and the likelihood of experiencing a side effect. Most side effects were mild, but about 75 percent of donors took analgesics because of them. CONCLUSIONS: In a granulocyte donation program involving G-CSF stimulation, about two-thirds of donors would experience one or more side effects, but these would usually be mild and well tolerated.
This study investigated the effect of alcohol consumption and smoking during pregnancy on the fatty acid composition of the infants. A total of 40 very-low-birth-weight (VLBW) infants, weighing between 750 and 1500 g, were enrolled in the study after being hospitalized and ventilated for respiratory distress syndrome (RDS). Maternal and infant demographic information was recorded. Questions regarding maternal smoking (none, < 10 and > or = 10 cigarettes/d) and alcohol consumption (none, occasionally, moderate and severe) were recorded. Erythrocyte membrane (EMB; n = 40) total fatty acid analyses were performed at birth (baseline) and on days 14 and 28 postnatally. During pregnancy, 42% of mothers consumed alcohol and 50% smoked. At birth, infants of mothers who smoked and consumed alcohol during pregnancy, had significantly higher blood docosahexaenoic acid (DHA; p < 0.05) than infants of mothers who abstained from both alcohol and smoking. The consequences of this finding remain unknown.
Prostate cancer clusters in some families, and an estimated 5%-10% of all cases are estimated to result from inheritance of prostate cancer-susceptibility genes. We previously reported evidence of linkage to the 1q24-25 region (HPC1) in 91 North American and Swedish families each with multiple cases of prostate cancer (Smith et al. 1996). In the present report we analyze 40 (12 original and 28 newly identified) Swedish families with hereditary prostate cancer (HPC) that, on the basis of 40 markers spanning a 25-cM interval within 1q24-25, have evidence of linkage. In the complete set of families, a maximum two-point LOD score of 1.10 was observed at D1S413 (at a recombination fraction [theta] of.1), with a maximum NPL (nonparametric linkage) Z score of 1.64 at D1S202 (P=.05). The evidence of linkage to this region originated almost exclusively from the subset of 12 early-onset (age <65 years) families, which yielded a maximum LOD score of 2.38 at D1S413 (straight theta=0) and an NPL Z score of 1.95 at D1S422 (P=.03). Estimates from heterogeneity tests suggest that, within Sweden, as many as 50% of early-onset families had evidence of linkage to the HPC1 region. These results are consistent with the hypothesis of linkage to HPC1 in a subset of families with prostate cancer, particularly those with an early age at diagnosis.
We report an evaluation of current laboratory and clinical practice for the diagnosis and management of von Willebrand disease (VWD) for a wide geographic area including Australia, New Zealand, and parts of Southeast Asia. This assessment has been undertaken in conjunction with the RCPA Quality Assurance Program (QAP) in Haematology. This external QAP currently comprises around 550 participating laboratories, of which some 450 perform coagulation testing, and from which 32 laboratories were identified to be actively involved in testing for VWD. These laboratories were targeted and their current laboratory and clinical practice evaluated by using various questionnaires. Our overall findings indicate a wide variation in laboratory test practice for VWD-based investigations. There was considerable variation among laboratories in the tests and test methods used, the control and calibration material used, the reported test reference intervals and units used, and the composite test panels used to diagnose VWD. However, substantial consensus in the clinical evaluation process, as undertaken by hematologists, also was identified. Despite the observed variations, most laboratory professionals seemed to understand the complexities involved in the diagnosis and subclassification of VWD, and the laboratories can provide an effective diagnostic service.
An allele of RFA1, the largest subunit of the single-stranded DNA-binding complex RP-A, was identified as a suppressor of decreased direct-repeat recombination in rad1 rad52 double mutants. In this study, we used two LEU2 direct-repeat assays to investigate the mechanism by which the rfa1-D228Y allele increases recombination. We found that both intrachromatid and sister chromatid recombination are stimulated in rfa1-D228Y strains. In a rad1 rad52 background, however, the majority of the increased recombination is caused by stimulation of deletion events by an intrachromatid recombination mechanism that is likely to be single-strand annealing. Studies in which an HO endonuclease cut was introduced between the two leu2 copies indicate that the rfa1-D228Y mutation partially suppresses the rad52 defect in recovering recombination products. Furthermore, molecular analysis of processing and product formation kinetics reveals that, in a rad52 background, the rfa1-D228Y mutation results in increased levels of recombinant products and the disappearance of large single-stranded intermediates characteristic of rad52 strains. On the basis of these results, we propose that in the absence of wild-type Rad52, the interaction of RP-A with single-stranded DNA inhibits strand annealing, and that this inhibition is overcome by the rfa1-D228Y mutation.
Cox regression models examined associations between 17 indicators of psychological functioning (intellectual abilities, personality, subjective well-being, and social relations) and mortality. The sample (N = 516, age range 70-103 years) comprised participants in the Berlin Aging Study assessed between 1990 and 1993. By 1996, 50% had died. Eleven indicators were identified as mortality risk factors at the zero-order level and six when age was controlled. Low perceptual speed and dissatisfaction with aging were uniquely significant after controls for age, SES, health, and the 16 other psychological factors. Low intellectual functioning was a greater risk for individuals aged 70-84 years than for the oldest old (over 85 years). The effects of psychological risk factors did not diminish over time. Future research should focus on the mechanisms and time frames that underlie the death-relatedness of intellectual functioning and self-evaluation.
Spontaneous self-definition was investigated in a heterogeneous sample of N = 516 participants of the Berlin Aging Study, aged between 70 and 103 years. The content of the self-definition revealed that old and very old persons view themselves as active and present-oriented. The self-definition also reflected an inward orientation, and central themes of life-review, health, and family. Participants generated more positive than negative evaluations in their self-definition, but the ratio of positive to negative evaluations was less favorable for the oldest old (> or = 85 years) than that of persons aged 70 to 84 years. Older individuals with more health-related constraints reported fewer and less rich self-defining domains (i.e., a less multifaceted self-definition). Positive emotional well-being was associated with naming more and richer self-defining domains. Multifacetness, however, did not buffer against the negative effect of low functional capacity on subjective well-being.
BACKGROUND: The aim of this study was to develop and characterize a rat model of crescentic glomerulonephritis which progresses to glomerulosclerosis and renal failure. METHODS: Glomerulonephritis was induced in Wistar Kyoto rats by a single injection of rabbit anti-glomerular basement membrane antiserum. Albuminuria and serum creatinine were monitored. Kidneys were examined, from 2.5 h to 44 days, using light-microscopy and immunohistochemistry. To characterize the glomerular inflammatory infiltrate, glomeruli were digested to single cells and analysed by fluorescence-activated cell sorter (FACS) and by immunohistochemistry on cytospins. RESULTS: Rats developed albuminuria by 4 days and increased serum creatinine by day 18. Histology showed glomerular fibrinoid necrosis by day 4 and cellular crescents in a mean of 63% of glomeruli by day 11. By 6 weeks, rats had developed renal failure (mean creatinine >300 micromol/l) with 94% of the glomeruli showing glomerulosclerosis. The kidneys were also affected by severe interstitial nephritis and tubular loss. The glomeruli were infiltrated by monocytes/ macrophages (ED1+) and CD8+ (OX8+) cells. FACS analysis showed that CD8+ cells did not express T-cell markers (CD3, TCRalphabeta or TCRgammadelta) or the NK-cell marker (NKR-P1). FACS analysis of peripheral blood mononuclear cells demonstrated a population of monocytes reactive with OX8, and double-labelling of cytospin preparations of glomerular digests showed that a proportion of the CD8+ cells were a subset of ED1+ monocyte/macrophages. CONCLUSIONS: We have characterized a reproducible model of crescentic glomerulonephritis which rapidly progresses to chronic renal failure with glomerulosclerosis and tubulo-interstitial scarring. This model will be useful for testing new therapeutic approaches in crescentic glomerulonephritis.
Thirty-five patients with inoperable recurrent head and neck cancer previously treated with definitive irradiation were treated with reirradiation and concomitant chemotherapy. Patient records were retrospectively reviewed to assess toxicity, response, and survival. Patients received one of three regimens: 1) 40 Gy total (2 Gy daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 2 g hydroxyurea orally daily for 5 days; 2) 48 Gy total (1.2 Gy twice daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 1.5 g hydroxyurea orally daily for 5 days; 3) 60 Gy total (1.5 Gy twice daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 1.5 g hydroxyurea orally daily for 5 days. For all regimens, treatment was given only on weeks 1, 3, 5, and 7. Acute toxicity was mainly hematologic and was less severe with the lower hydroxyurea dose. Acute mucosal and skin toxicity was acceptable for all regimens. Late toxicity was noted in 4 of 17 patients who survived 12 months or more. Late effects were Radiation Therapy Oncology Group grade 3 or less. Fifteen of 35 patients achieved a complete response, and 11 of 35 patients achieved a partial response. The median survival rate was 10.5 months. There was no significant difference in responses or median survival between the groups. Reirradiation of head and neck cancer with 5-fluorouracil and hydroxyurea offers acceptable acute toxicity and minimal late effects. The clinical response rates and median survival are encouraging. Further investigation is warranted.
In this article, we present our experience of group lightning injury. Individual injuries are most common after single strikes. The largest group previously reported was 10 patients. In our series, 17 victims were hit by a single strike; 11 were admitted to the hospital and 6 were discharged from the accident and emergency department. Although injured under the same circumstances, these patients presented with a wide range of symptoms and signs. We also describe a characteristic burn pattern, the "tip-toe sign."
OBJECTIVES/HYPOTHESIS: Abnormalities of the fourth branchial arch are much less common than those of the second arch and present in a different manner. The authors report their experience with five cases of fourth arch sinuses. METHODS: Retrospective chart review of patients at a tertiary care center. RESULTS: All patients presented in the first or second decade of life, and all but one had left-sided neck involvement. Four patients presented with recurrent low neck inflammatory episodes, and one with respiratory compromise. Diagnostic studies performed included ultrasound, computed tomography (CT) scan, barium swallow, magnetic resonance imaging, and fine-needle aspiration. Barium contrast studies and CT scan were the most useful in demonstrating a fourth arch sinus tract preoperatively. Surgical treatment with an emphasis on complete exposure of the recurrent laryngeal nerve and exposure of the lateral piriform sinus to facilitate complete sinus tract excision was successful in all patients. CONCLUSION: The clinical history of recurrent low neck inflammatory episodes in young patients, especially on the left side, should raise the suspicion of this entity. Investigation using barium swallow in combination with CT scanning is useful. Excision of the sinus tract taking care not to injure the recurrent laryngeal nerve is curative.