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Biomedical subjects

J Phillips

Publications and source records attributed to J Phillips.

At least 127 records · Page 7Linked to original sources

Anterior callosotomy for intractable epilepsy: outcome in a series of twenty patients.

This series reports 20 patients with intractable epilepsy who underwent corpus callosotomy during the period 1984-1993. The mean age of patients at the time of onset of seizures was 9 years and at the time of callosotomy 26 years. The seizure types were generalized tonic-clonic (18/20), drop attacks (13/20), absences (12/20) and complex partial seizures (8/20). The most common electroencephalographic (EEG) abnormalities were 'bilateral multiple spike and wave' (7/20), or 'generalized/multifocal spike and slow wave' (7/20). The follow-up was 5.6 (SD 0.6) years. Six patients have remained free of major generalized motor seizures and 10 additional patients experienced significant sustained reduction in the severity and frequency of the seizures. In total, 16 of 20 patients (80%) had a favourable outcome. The type of seizures associated with the most improved outcome were drop attacks, and generalized tonic-clonic seizures, in 11/13 and 14/18 of the patients, respectively. No relationship was established between seizure control and preoperative EEG patterns, computed tomography or magnetic resonance imaging findings. The most frequent complication was transient mild left hemiparesis that occurred in four patients. The mortality was nil. This study confirms the efficacy of corpus callosum division as a surgical option for selected patients with medically intractable epilepsy. In addition, results suggest that the history and clinical classification of the seizures have prognostic value as selection criteria for patients referred for this operation.

Adolescent↗

Resistant starch lowers fecal concentrations of ammonia and phenols in humans.

We investigated the effect of resistant starch (RS) on markers of colonic protein metabolism. Eleven subjects participated in a randomized crossover study in which they consumed either high-RS (39 +/- 3 g/d, -chi +/- SEM) or low-RS (5 +/- 0.4 g/d) diets for 3 wk. All other macronutrients were kept constant. During the high-RS diet daily excretion of fecal nitrogen increased from 1.84 +/- 0.15 to 2.86 +/- 0.42 g/d (P < 0.01) and excretion of fecal phenols fell from 9.2 +/- 1.4 to 5.3 +/- 0.8 mg/d (P < 0.01). Fecal concentrations of ammonia decreased from 397 +/- 33 to 278 +/- 49 microgram/g (P < 0.01) and phenols decreased from 69 +/- 8 to 39 +/- 10 microgram/g (P < 0.001). Daily output of urinary ammonia, urea, phenols, and total nitrogen did not change significantly, but pH decreased from 6.4 +/- 0.1 to 6.2 +/- 0.1 (P < 0.05) during the high-RS period. These results suggest that RS significantly attenuates the accumulation of potentially harmful byproducts of protein fermentation in the human colon.

Adult↗

Induction of apoptosis by La Crosse virus infection and role of neuronal differentiation and human bcl-2 expression in its prevention.

La Crosse virus causes a highly cytopathic infection in cultured cells and in the murine central nervous system (CNS), with widespread neuronal destruction. In some viral infections of the CNS, apoptosis, or programmed cell death, has been proposed as a mechanism for cytopathology (Y. Shen and T. E. Shenk, Curr. Opin. Genet. Dev. 5:105-111, 1995). To determine whether apoptosis plays a role in La Crosse virus-induced cell death, we performed experiments with newborn mice and two neural tissue culture models. Newborn mice infected with La Crosse virus showed evidence of apoptosis with the terminal deoxynucleotidyl transferase-mediated nicked-end labeling (TUNEL) assay and, concomitantly, histopathological suggestion of neuronal dropout. Infection of tissue culture cells also resulted in DNA fragmentation, TUNEL reactivity, and morphological changes in the nuclei characteristic of apoptotic cells. As in one other system (S. Ubol, P. C. Tucker, D. E. Griffin, and J. M. Hardwick, Proc. Natl. Acad. Sci. USA 91:5202-5206, 1994), expression of the human proto-oncogene bcl-2 was able to protect one neuronal cell line, N18-RE-105, from undergoing apoptosis after La Crosse virus infection and prolonged the survival of infected cells. Nevertheless, expression of bcl-2 did not prevent eventual cytopathicity. However, a human neuronal cell line, NT2N, was resistant to both apoptosis and other types of cytopathicity after infection with La Crosse virus, reaffirming the complexity of cell death. Our results show that apoptosis is an important consequence of La Crosse virus infection in vivo and in vitro.

Animals↗

Applications of retrovirus-mediated expression cloning.

We have recently established a novel expression cloning system using retroviral vectors. The system is based on a high-efficiency packaging cell line, BOSC23, and a simplified retroviral vector, pBabeX, carrying no selection marker. cDNA libraries, constructed in the pBabeX vector, are transiently transfected into BOSC23 cells. The supernatant contains more than 3X10(6)/mL, which would cover large complexities of cDNA libraries. The retrovirus stock gave 100% infection efficiency in NIH3T3 cells and 5-40% infection efficiency in various hematopoietic cell lines. In contrast to the conventional expression cloning system, in which it is necessary to transfect cDNA libraries transiently into particular cell types such as COS cells, retrovirus-mediated expression cloning allows us to transduce cDNAs into a wide variety of cell types. This method therefore makes it possible to select cells expressing a cDNA of interest by various functional assays. When combined with polymerase chain reaction (PCR)-driven random mutagenesis, this system is also useful in searching for mutations of various molecules that will result in alterations of their functions.

3T3 Cells↗

Assessment tools: functional health status and patient satisfaction.

This article addresses an aspect of outcomes assessment that includes outcomes from the perspective of the patient; namely, functional health status and patient satisfaction. For rehabilitation care they are the only outcomes that can be measured. Measurement tools exist and are being used to quantify the qualitative perspectives of patient care to produce valuable information about the quality and the efficiency of rehab services. The biggest challenge is lack of standardization to allow comparability of data. Different users bring different perspectives to the issue. The researcher, the software developer, the health care facility, and the payer all have an interest in using functional status and patient satisfaction to evaluate outcomes.

Activities of Daily Living↗

Caring for head and neck oncology patients. Does social support lead to better quality of life?

OBJECTIVE: To determine whether social support contributes to better quality of life and psychological state of head and neck oncology patients. DESIGN: A structured questionnaire, administered orally to patients face-to-face, with specific questions about demographic and medical information and social support and two standardized scales; a cancer-specific quality of life scale and a depression scale. SETTING: Head and Neck Oncology Clinic, an institutional referral centre providing ambulatory care at the Camp Hill Medical Centre in Halifax, NS. PARTICIPANTS: Forty-five head and neck oncology patients (33 men, 12 women) who came for follow-up appointments at the clinic. One person did not complete the interview. Fifty patients were approached, but five were not included: one died before the interview, and four agreed to participate but were prevented by transportation or timing problems. MAIN OUTCOME MEASURES: Scores on the Functional Living Index-Cancer Scale and the Center for Epidemiologic Studies Depression scale. RESULTS: Four main factors predicted quality of life: satisfaction with family physician support, severity of cancer, sex of patient, and type of cancer. Three important predictors of psychological state were loss of appetite, family physician support, and sex of patient. CONCLUSION: Social support, particularly from family physicians, contributes greatly to better quality of life and psychological state for head and neck oncology patients.

Adult↗

Treatment with letrazuril of refractory cryptosporidial diarrhea complicating AIDS.

Thirty-five AIDS patients (mean CD4 count 44 x 10(6)/L) with chronic cryptosporidiosis were treated with letrazuril at an initial oral daily dose of 50 mg in an open-label Phase I prospective trial. Treatment was continued for > or = 10 days and for as long as there was a response. The majority of subjects (91%), had previously failed paromomycin treatment. At baseline, 74% of patients had moderate (five to nine bowel movements per day) to severe (> 10 bowel movements per day) diarrhea. Twenty-three subjects (66%) had a clinical response within a mean of 1.7 weeks of treatment initiation. Twenty-two patients had a partial response (> 50% reduction in bowel movements per day for > or = 1 week), one patient had a complete response (two or fewer bowel movements per day). Of the responders, 15 (65%) had a clinical relapse with worsening diarrhea at an average of 1.2 months following initiation of letrazuril. The other eight (35%) had had symptom control for an average of 2.9 months from initiation of letrazuril to the latest follow-up. Microbiologic eradication was demonstrated in 10 (40%) of 25 patients with follow-up stool examinations. Seven patients (20%) experienced a rash, all within 1 week of starting the drug, and resolved in all patients when the drug was discontinued. In conclusion, severely immunocompromised AIDS patients with refractory cryptosporidiosis may show a modest, short-lived response to letrazuril. Microbiologic response is variable and relapse high. Rash is a major limiting side effect of the drug.

Acetonitriles↗

Hospital security.

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Emergency Medical Services↗

Virologic and immunologic characterization of symptomatic and asymptomatic primary HIV-1 infection.

To define virologic and immunologic differences in patients with acute symptomatic and asymptomatic primary human immunodeficiency virus type 1 (HIV-1) infection, sequential plasma specimens were obtained longitudinally for 1-2 years postseroconversion from subjects with well-documented time of seroconversion. Thirteen of them had an acute symptomatic primary infection, eight subjects had asymptomatic primary infection and long-term follow-up, and 27 had asymptomatic seroconversion and short-term follow-up. Quantitative plasma HIV-1 RNA levels, CD4+ lymphocyte counts, and levels of antibodies to gp120, p66, p41, p31, p24, and p17 were measured. At the time of seroconversion, there was no significant difference in HIV-1 RNA levels and CD4+ counts between symptomatic (n = 13) and asymptomatic (n = 27) subjects. Subsequently, however, establishment of low levels of plasma HIV-1 RNA was seen significantly more frequently in asymptomatic (n = 8) than in symptomatic (n = 13) primary infection; this correlated with higher levels of some (anti-gp120 and anti-p31) anti-HIV-1 antibodies and a slower decline in CD4+ lymphocyte counts. These results indicate that immunologic control of viremia early after infection may be a critical determinant to subsequent clinical course of HIV-1 infection. They also suggest that persons with acute symptomatic primary infection may generally progress to having acquired immune deficiency syndrome (AIDS) more rapidly than people with low-grade symptoms or asymptomatic primary infection.

Acquired Immunodeficiency Syndrome↗

The first elective free flap in a cardiac transplant patient.

A case of free fibula transfer for mandibular reconstruction in a cardiac transplant patient is described. The reconstructive microsurgeon should be aware of the special requirements of these immunosuppressed patients and flap transfer should be performed in specialized centers with the interaction of different specialties to make the procedure safe and successful.

Bone Transplantation↗

CD8 T cell activation after intravenous administration of CD3 x CD19 bispecific antibody in patients with non-Hodgkin lymphoma.

A bispecific antibody directed to T and B cells (CD3 x CD19 bsAb) was daily infused intravenously in escalating doses from 10 micrograms up to 5 mg in three patients with chemotherapy-resistant non-Hodgkin lymphoma; in this way we aimed to activate T cells to kill the malignant B cells. Only limited toxicity was observed, consisting of moderate fever preceded by chills or shivers and mild thrombocytopenia. No human anti-(mouse Ig) antibodies were found. Pharmacokinetics showed a t1/2 of 10.5 h with peak levels of 200-300 ng/ml after infusion of 2.5 mg bsAb. bsAb in serum was functionally active in vitro. After bsAb infusion a rise in serum tumour necrosis factor alpha was observed, accompanied by an increase in soluble CD8 and to some extent in soluble interleukin-2 receptor (IL-2R), but not in interferon gamma. IL-4 or soluble CD4. No evidence was found for monocyte activation (no increases in IL-6, IL-8 or IL-1 beta in serum). No gross changes in histology or number of IL-2R+, CD4+ or CD8+ cells were found in the lymph nodes after therapy, but one patient showed activated CD8+ T cells within the tumour nodules. In conclusion, after intravenously administered CD3 x CD19 bsAb only moderate toxicity was found, probably due to CD8+ T cell activation and cytokine release, without CD4+ T cell activation.

Adult↗

Pemoline-associated fulminant liver failure: testing the evidence for causation.

BACKGROUND: Pemoline is a central nervous system stimulant used in treating children with attention deficit-hyperactivity disorder. Hepatotoxicity has been commonly reported in association with pemoline; however, only two reports of cases of fatal liver failure have been published. OBJECTIVES: We report on a 14-year-old boy who received concomitant pemoline and methylphenidate in whom fulminant liver failure occurred and for whom liver transplantation failed. Other causes of fulminant liver failure were ruled out, and the liver biopsy was suggestive of drug toxicity. We estimated the probability that these three cases represent an increased risk of fulminant liver failure associated with pemoline. RESULTS: Based on the three known cases of fatal liver failure associated with pemoline use, we calculated that a child receiving pemoline has a relative risk of development of fulminant liver failure of 45.3 (95% confidence interval, 4.1 to 510). This highly significant association (p < 0.001) suggests causation. CONCLUSIONS: Because pemoline has been widely used in recent years, further studies are needed to better quantify this risk in children with attention deficit-hyperactivity disorder.

Adolescent↗

Prevention of biliary cirrhosis following hepatic arterial thrombosis after liver transplantation in children by using ursodeoxycholic acid.

Hepatic artery thrombosis (HAT) after liver transplantation is a severe complication that often requires retransplantation. The authors have adopted a different approach, aimed at treating the perioperative HAT complications aggressively and early, with ursodeoxycholic acid (UDCA), to try to preserve the original graft. Eighty-six liver transplants were performed in 73 children (age range, 4.5 months to 17.5 years; median, 2.6 years). HAT occurred eight times, in seven patients (9.3%). Patients with HAT were significantly younger and smaller (mean age, 0.8 +/- 0.4 v 4.8 +/- 5.3 years; P < .02; mean weight, 7.4 +/- 0.8 v 18.7 +/- 16.2 kg; P < .05). The incidence of HAT varied significantly according to the method of arterial reconstruction used: 4 of 16 (25%) when a donor iliac artery interposition graft to the aorta was used, 4 of 61 (6.6%) when the native hepatic artery was used, and 0 of 9 when the donor celiac axis was anastomosed directly to the aorta (P < .05). The incidence of HAT was not significantly different when reduced-size grafts were used. Early retransplantation was performed in three of the eight patients; two survived. All other patients were treated for 4 to 6 weeks with broad-spectrum antibiotics and amphotericin. Five patients were treated with UDCA, three immediately after the acute event and two after 4 and 6 months (respectively) post-HAT. The patients who had UDCA immediately post-HAT had histologically normal liver biopsy specimens. Results of liver function tests have been normal. One of these patients required transhepatic stenting of a common bile duct stricture for several months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of PCBs (Aroclor 1254) on reproduction and growth rate in Mongolian gerbils (Meriones unguiculatus).

Groups of female Mongolian gerbils were subcutaneously administered 2mg or 4mg PCBs (Aroclor 1254) in 0.1ml oil or vehicle only after pairing for two days with untreated males. No effects were found on the number of pairs breeding, birth intervals, number of pups per litter or percentage of male offspring. The preweaning growth rates of the PCBs exposed first litter offspring was retarded, but second litters showed no differences compared to controls. No other differences in growth were observed.

Animals↗

Clinical experience with CD3 x CD19 bispecific antibodies in patients with B cell malignancies.

In extensive preclinical testing, a CD3 x CD19 bispecific antibody (BsAb) induced killing of malignant B cells by resting T cells even in an autologous situation. In a 14 day clonogenic assay using a CD19+ pre-B cell line (REH), BsAb required repeated administration together with IL-2 to achieve a 5 log kill by resting peripheral blood T cells. Intravenously administered BsAb in an intrapatient dose escalation study of 3 patients with B cell non-Hodgkin's lymphoma showed limited toxicity (WHO grade II fever and chills) due to tumor necrosis factor-alpha (TNF-alpha) release by T cells. Pharmacokinetics with 2.5 mg BsAb showed peak levels of 200-300 micrograms/ml and a t1/2 of 10.5 h. The next patient, with chronic lymphocytic leukemia (CLL), received 0.6 mg BsAb/m2 as an i.v. infusion preceded by 1 MU IL-2/m2 s.c. Improved T cell activation was noted, as indicated by an increase in IFN-gamma, IL-6, IL-8, and IL-10, in addition to high TNF-alpha increases. TNF-alpha increases were highest on the first day. Toxicity remained restricted to grade II fever and chills, observed every day after the infusion of BsAb. No clear clinical effects were seen in this chemotherapy-resistant CLL patient with a high tumor burden. If subsequent patients also show limited toxicity, treatment of patients with a lower tumor load seems to be warranted to evaluate the efficacy of CD3 x CD19 BsAb therapy.

Animals↗

Effect of resistant starch on fecal bulk and fermentation-dependent events in humans.

This study investigated the effect of two diets, which differed in resistant starch (RS) concentration, on fecal bulk and fermentation-dependent events in 11 humans. Amounts of RS consumed were 5.0 +/- 0.4 and 39.0 +/- 3.0 g/d (mean +/- SEM) for the low- and high-RS diets, respectively. The two diets were fed for 3 wk each in a randomized crossover design. Fecal collections were made in the third week of each study period. The high-RS diet produced an increase (P < 0.01) in total fecal output (from 138 +/- 22 to 197 +/- 37 g/d) and lowered fecal pH (6.9 +/- 0.1 to 6.3 +/- 0.1). There were significant increases (P < 0.05) in the fecal concentrations and daily excretion of butyrate (+38% and +100%, respectively) and acetate (+26% and +72%, respectively) during the high-RS period. The fecal excretion (g/d) of nonstarch polysaccharides (NSP) also rose by 50% during the high-RS diet, suggesting that the presence of starch in the colon may affect the fermentation of NSP. Subjects reported an increase in flatulence and easier defecation. These results demonstrate that RS has a significant impact on putative markers of colonic health in humans.

Acetates↗