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Biomedical subjects

J Phillips

Publications and source records attributed to J Phillips.

At least 19 recordsLinked to original sources
PubMed1995

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↗
PubMed1995

Hospital security.

Explore the source record for details and available documents.

Emergency Medical Services↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Detection of p24 antigen with and without immune complex dissociation for longitudinal monitoring of human immunodeficiency virus type 1 infection.

Sequential specimens obtained from 87 multicenter AIDS cohort study participants were tested by three p24 antigen tests. They included a polyclonal enzyme immunoassay (EIA), a monoclonal EIA, and a monoclonal EIA after immune complex dissociation (ICD) of specimens. Subjects were grouped into two categories defined by real-time testing with the polyclonal EIA: 39 had become positive for p24 antigen (antigen converters) during follow-up, and 48 had progressed to AIDS without detectable antigenemia. Twenty-four (61%) antigen converters were positive by ICD-monoclonal EIA about 1 year earlier than by monoclonal EIA. In contrast, only 12 (25%) patients who progressed to AIDS without detectable antigenemia became positive by ICD-p24 EIA before developing AIDS. Thus, the main benefit of ICD treatment may be to detect p24 antigenemia approximately 1 year before the regular assay rather than to identify additional antigenemic people. Quantitative plasma RNA levels were also determined in longitudinal samples from 20 antigen converters and 7 men who developed AIDS without antigenemia. Although mean human immunodeficiency virus type 1 RNA levels were higher in antigen-positive than in antigen-negative samples (P = 0.002), more than half (11 of 20) of the antigen converters had no measurable change in human immunodeficiency virus type 1 RNA associated with change to antigen positivity.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Elevated levels of lipoprotein (a) in association with cerebrovascular saccular aneurysmal disease.

The relationship between cerebrovascular aneurysmal disease and atherosclerosis remains unclear. Elevated serum levels of lipoprotein (a) (Lp[a]), are an independent risk factor for atherosclerosis. We measured serum Lp(a) levels in 50 patients who had angiographically proven saccular aneurysmal disease and who were free of clinically significant atheromatous disease (as judged by their medical histories and the results of physical examination, electrocardiography, and carotid angiography). The Lp(a) serum levels in these patients were compared with the Lp(a) serum levels in a group of 42 normal healthy controls. Serum Lp(a) levels in the patients was 20.1 +/- 0.42 mg/dl (median +/- standard error); however, median serum Lp(a) in the control subjects was 10.8 +/- 0.47 mg/dl (P < 0.01). Among females, the difference in serum Lp(a) levels was significant; the levels were 22.2 +/- 0.6 for female patients (n = 29) and 9.5 +/- 0.53 in female control subjects (n = 26) (P < 0.005). The most significant difference (P < 0.002) was seen in females < 50 years old (14 patients, 10 control subjects). No significant differences were seen in the Lp(a) serum levels between 21 male patients and 16 male control subjects. Lp(a) levels above the threshold level (30 mg/dl) were found in 20 patients and 7 control subjects (chi 2 = 5.99, P < 0.02); 12 female patients and 3 female control subjects (chi 2 = 6.16, P < 0.02; 8 male patients and 4 male control subjects (this difference was not significant). These results indicate either that cerebrovascular aneurysmal disease and subclinical atherosclerosis are related or that Lp(a) is a risk factor for vasculopathies other than atheroma.

Adult↗
PubMed1995

Comparison of laser Doppler flowmeter and radioactive microspheres in measuring blood flow in pig skin flaps.

Laser Doppler flowmetry is a noninvasive technique commonly used to monitor skin perfusion after free-tissue transfer or replantation in reconstructive surgery. Several investigators have expressed concern about the reliability of the quantitative value provided by laser Doppler flowmeters (LDF) and the extent to which they reflect nutrient blood flow. This experiment was designed to compare quantitatively the skin blood flow in the pig measured by LDF and by 15-micron radioactive microspheres (RMs). It was observed that the skin blood flow rates measured by LDF and RMs in the normal skin and in acute random-pattern and arterialized skin flaps were highly correlated (r = 0.93, P < .01). However, the skin blood flow rates measured by LDF were consistently higher (P < or = .05) than the corresponding flow rates measured by RMs, and this discrepancy increased considerably at low skin blood flow rates (< 2 mL/min/100 g). We speculated that the LDF most likely measured both nutrient and arteriovenous shunt flow in the skin and that this arteriovenous shunt flow at least in part caused the discrepancy in skin blood flow rates measured by the LDF and RMs because the 15-micron RMs are known to measure nutrient blood flow only. The inherent variations and errors in LDF technique were also discussed.

Animals↗
PubMed1995

An audit of medical paediatric out-patient appointments and letters.

All medical out-patient appointments of a firm of three consultants at the Royal Hospital for Sick Children were reviewed over a four week period. Of 758 appointments initially offered, 490 (64%) patients attended; 19% of patients cancelled and 17% did not attend without cancelling. Delay from referral to attendance ranged from 0 to 9 weeks. The characteristics of those patients experiencing prolonged registrar-only follow-up are described. The content of subsequent letters to family practitioners was usually adequate compared to accepted standards. Delays in dictation of letters were usually short in comparison to delays in typing. Such delays and the intervals between consultant review of out-patients may prove costly to providers. Potential improvement strategies are discussed.

Appointments and Schedules↗
PubMed1995

Deoxyspergualin: phase I clinical, immunologic and pharmacokinetic study.

Deoxyspergualin (DSG) is an analog of the polyamine spergualin with preclinical evidence of activity in murine and human tumor models. This phase I study examined a 120 h continuous infusion schedule in 56 patients with refractory solid tumors at doses ranging from 80 to 2792 mg/m2/day. Dose-limiting toxicity was reversible hypotension and appeared to be associated with plasma levels of DSG > 4 micrograms/ml. Other dose-dependent effects noted were pruritus and circumoral paresthesias. Myelosuppression and gastrointestinal toxicities were mild and sporadic. Two patients with refractory head and neck cancer had minor responses. The recommended phase II dose on this schedule is 1800 mg/m2. Additional monitoring to identify immunologic properties included immunophenotyping of peripheral lymphocytes and cytotoxic activity by means of standard 51Cr-release assays. These studies revealed a non-dose-dependent increase in the number of cells expressing T cell antigens predominantly the T suppressor (CD8) phenotype posttreatment. In three patients, a mild increase in LAK activity was noted post-treatment without a consistent relationship to dose or change in cell surface antigens. Pharmacokinetic studies were completed on 26 patients ranging from doses of 80 to 2792 mg/m2. The average plasma concentration ranged from 0.07 to 7 micrograms/ml. DSG was rapidly cleared from the plasma with a mean terminal half-life of 1.9 h. Mean total body clearance was 25.24 l/h/m2. Further in vivo immunologic studies should be pursued while the agent is studied in fixed dosage phase II clinical trials.

Adult↗
PubMed1994

Two contiguous residues in human interleukin-3, Asp21 and Glu22, selectively interact with the alpha- and beta-chains of its receptor and participate in function.

We have previously reported that the predicted first helix of human interleukin (IL)-3 contains a hydrophilic region encompassing residues Asp21, Glu22, and Thr25 that is crucial for biological activity and IL-3 receptor binding. Using single amino acid substitution mutagenesis, we have now determined that Asp21 and Glu22, but not Thr25, were crucial for full IL-3 activity. Mutant D21R was 30-fold less potent than wild type IL-3 in the stimulation of biological activity. It also exhibited a similar reduction in its ability to bind to the cloned high affinity IL-3 receptor complex (alpha- and beta-chains) or to the receptor alpha-chain alone, indicating that residue 21 is involved in contacts with the alpha-chain. Mutant E22R was approximately 20,000-fold less potent than wild type IL-3 in the stimulation of biological activity and in binding to the IL-3 receptor high affinity complex. However, the binding of E22R to the IL-3 receptor alpha-chain alone was similar to that of wild type IL-3, suggesting that this mutant was defective in interactions with the receptor beta-chain. These results show that two contiguous residues in the N-terminal region of IL-3 mediate binding to the two different chains of the IL-3 receptor and emphasize the functional significance of the conserved Glu in the first helix of the IL-3, granulocyte-macrophage colony-stimulating factor, and IL-5 cytokine subfamily.

Amino Acid Sequence↗