PubMed Health⌕ Search

Biomedical subjects

D Ward

Publications and source records attributed to D Ward.

At least 55 records · Page 3Linked to original sources
PubMed2000

High-yield production of a human therapeutic protein in tobacco chloroplasts.

Transgenic plants have become attractive systems for production of human therapeutic proteins because of the reduced risk of mammalian viral contaminants, the ability to do large scale-up at low cost, and the low maintenance requirements. Here we report a feasibility study for production of a human therapeutic protein through transplastomic transformation technology, which has the additional advantage of increased biological containment by apparent elimination of the transmission of transgenes through pollen. We show that chloroplasts can express a secretory protein, human somatotropin, in a soluble, biologically active, disulfide-bonded form. High concentrations of recombinant protein accumulation are observed (>7% total soluble protein), more than 300-fold higher than a similar gene expressed using a nuclear transgenic approach. The plastid-expressed somatotropin is nearly devoid of complex post-translational modifications, effectively increasing the amount of usable recombinant protein. We also describe approaches to obtain a somatotropin with a non-methionine N terminus, similar to the native human protein. The results indicate that chloroplasts are a highly efficient vehicle for the potential production of pharmaceutical proteins in plants.

Blotting, Western↗
PubMed2000

Little amigo.

Explore the source record for details and available documents.

Child, Hospitalized↗
PubMed2000

A young woman with chest pain.

A case of a previously fit young woman admitted with chest pain, who was found at coronary angiography to have dissection of the left main stem which extended to the left anterior descending and circumflex coronary arteries, is presented. Emergency coronary artery bypass grafting was performed (vein grafts to the left anterior descending, the diagonal, and circumflex arteries). The patient made an uneventful recovery, and three years after initial presentation she remains free of cardiac symptoms.

Adult↗
PubMed1999

Human ligands of the Notch receptor.

During development, the Notch signaling pathway is essential for the appropriate differentiation of many cell types in organisms across the phylogenetic scale, including humans. Notch signaling is also implicated in human diseases, including a leukemia and two hereditary syndromes known as Alagille and CADASIL. To generate tools for pursuing the role of the Notch pathway in human disease and development, we have cloned and analyzed the expression of three human homologues of the Notch ligands Delta and Serrate, human Jagged1 (HJ1), human Jagged2 (HJ2), and human Delta1 (H-Delta-1), and determined their chromosomal localizations. We have also raised antibodies to HJ1, and used these antibodies in conjunction with in situ hybridization to examine the expression of these ligands in normal and cancerous cervical tissue. We find that, as reported previously for Notch, the ligands are up-regulated in certain neoplastic tissues. This observation is consistent with the notion that Notch signaling is an important element in these pathogenic conditions, raising the possibility that modulation of Notch activity could be used to influence the fate of the cells and offering a conceivable therapeutic avenue.

Amino Acid Sequence↗
PubMed1999

Coadministration of phenytoin and felbamate: evidence of additional phenytoin dose-reduction requirements based on pharmacokinetics and tolerability with increasing doses of felbamate.

PURPOSE: This open-label study investigated the pharmacokinetic interaction of phenytoin (PHT) and felbamate (FBM). METHODS: Ten subjects with epilepsy receiving PHT monotherapy were administered increasing doses of FBM (1,200, 1,800, 2,400-3,600 mg/day) at 2-week intervals. PHT doses were reduced by 20% on an individual basis when evidence of clinically significant intolerance was present. With intolerance, the PHT dose was reduced before the next incremental FBM dose. Blood samples were analyzed for FBM, PHT, and PHT metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH). RESULTS: Total PHT plasma concentrations increased with coadministered FBM. PHT Cmax increased from 15.9 microg/ml at baseline to 20.9 microg/ml after 1,200 mg/day FBM and to 26.8 microg/ml after 1,800 mg/day FBM. Four subjects required a 20% PHT dose reduction after 1,800 mg/day FBM and six after the administration of 2,400 mg/day FBM. All subjects required further 20% PHT reductions before 3,600 mg/day FBM. FBM Cmax and AUCT were reduced, and apparent clearance increased compared with data from FBM monotherapy. CONCLUSIONS: With the initiation of FBM therapy in subjects receiving PHT, the PHT dosage should be reduced by 20%. Further PHT dose reductions are likely to be necessary if the FBM dose is increased. The requirements for reductions in dose might be predicted by clinical signs of PHT intolerance.

Adult↗
PubMed1999

Country watch: USA.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1999

An open-label trial of stavudine, lamivudine and efavirenz in the treatment of HIV-positive, treatment-naive patients, and implications for clinical practice.

A phase II, open-label study of stavudine, lamivudine and efavirenz resulted in significant reductions in plasma HIV-1 RNA over a 24 week period in human immunodeficiency virus (HIV)-infected individuals. The trial currently has 68 patients, and this presentation covers data on the first 42 patients enrolled for 24 weeks. The mean plasma HIV-1 RNA on entry was 75858 HIV RNA copies/ml, and the mean CD4 count was 380 cells/mm3. After 24 weeks, the CD4 count increased by 169 cells/mm3 above baseline. plasma HIV-1 RNA was markedly reduced: at 24 weeks, more than 97% of patients had <50 HIV RNA copies/ml based on observed data, and 89% of patients had <50 copies/ml based on strict intent-to-treat analysis (non-completer=failure). The favourable interactions of these agents resulted in no discontinuations owing to adverse effects. This regimen provides an important first-line treatment for antiretroviral-naive patients.

Adult↗
PubMed1998

Child mental health services. Side by side.

The appointment of a primary care mental health worker can relieve pressure on child and adolescent mental health services. In one health authority, GP practices with access to a liaison clinic run by a primary care mental health worker referred a third fewer cases to child and adolescent mental health services than practices without such access. Referrals by these practices were more likely to be assessed as appropriate and as high priority.

Adolescent↗
PubMed1998

Extracorporeal membrane oxygenation in the treatment of inhalation injuries.

Smoke inhalation is a leading cause of death in burns patients. Conventional ventilation cannot always maintain adequate tissue oxygenation. Extracorporeal membrane oxygenation (ECMO) has rarely been used in the treatment of smoke inhalation injuries. ECMO is a proven therapy in severe neonatal respiratory failure and has also been used to good effect in the treatment of children and adults. We report the cases of two children who developed severe respiratory failure refractory to maximal ventilation, one case followed smoke inhalation alone, the other followed smoke inhalation and burns. Pre-ECMO PaO2/FIO2 ratios were 6.5 and 8 kPa, respectively. The patients were treated with veno venous ECMO for 72 and 144 h, respectively. The use of ECMO for respiratory failure due to smoke inhalation and thermal injury is discussed.

Accidents, Home↗
PubMed1998

Assembly of the VirB transport complex for DNA transfer from Agrobacterium tumefaciens to plant cells.

The VirB transporter is a type IV secretion system that mediates the genetic transformation of plant cells by Agrobacterium tumefaciens. Assembly of this transporter depends on, first, formation of a VirB7/B9 complex that stabilizes many of the VirB proteins, second, formation of a virulence-specific pilus composed primarily of VirB2 and VirB5, and, third, post-translational processing of VirB1 and VirB2.

Agrobacterium tumefaciens↗
PubMed1998

Segmental hyperhidrosis as a manifestation of spinal and paraspinal disease.

BACKGROUND: Segmental hyperhidrosis is an uncommon finding which is usually associated with irritation or infiltration of pre-ganglionic sympathetic fibres or the sympathetic chain. METHODS: We report two cases of segmental hyperhidrosis with striking clinical features. RESULTS: In one case, a mesothelioma produced ipsilateral simultaneous underactivity and overactivity of sympathetic outflow and in the other case a thoracic central disc herniation was probably responsible for a band of sweating which clearly extended beyond the segmental level of injury. CONCLUSION: Segmental hyperhidrosis should trigger a search for structural disease in the spinal and paraspinal region.

Humans↗
PubMed1998

Post-infection fatigue syndrome following Q fever.

In 1989, 147 individuals in the West Midlands, UK, were infected with Q fever. Five years later, following anecdotal reports of fatigue, we used a questionnaire-based case-control study to determine the prevalence of chronic fatigue syndrome symptoms in this group. Replies from 71 patients were compared with those from 142 age- and sex-matched controls. Increased sweating (52.9% vs. 31.6%, p = 0.006), breathlessness (50.7% vs. 30.6%, p = 0.006), blurred vision (34.3% vs. 17.8%, p = 0.016) and undue tiredness (68.7% vs. 51.5%, p = 0.03) were found in controls compared to cases. These findings were similar to those in Australian abbatoir workers occupationally exposed to Q fever. CDC criteria for chronic fatigue syndrome were fulfilled by 42.3% of cases and 26% of controls. Using visual analogue scores, symptoms were more severe in cases than in controls. Our findings support the existence of a chronic fatigue state following acute Q fever, in a group of patients exposed just once to the organism, and in circumstances free of such confounding factors as lawsuits over compensation.

Acute Disease↗
PubMed1997

Genomic structure, sequence, and mapping of human FGF8 with no evidence for its role in craniosynostosis/limb defect syndromes.

Fibroblast growth factor-8 (Fgf8) is a recently identified growth factor that stimulates the androgen-dependent growth of mouse mammary carcinoma cells. Evidence from mouse development also shows that Fgf8 may play an important role in growth and patterning of limbs, face, and the central nervous system. We describe here the human FGF8 genomic sequence and demonstrate conservation between the human and mouse sequences, including alternatively spliced exons in the mouse. Mapping of FGF8 by FISH using an FGF8-containing bacterial artificial chromosome and by genetic linkage using a SSCP variant identified in this study is also reported and refines the FGF8 map location to 10q24. Since FGF8 maps to the same chromosomal region as FGFR2, has indeed been shown to be a ligand for FGFR2, and has an expression pattern consistent with limb and craniofacial anomalies, we have screened two kindreds with Pfeiffer syndrome that were previously linked to markers from 10q24-25 and a large number of individuals with craniosynostosis and limb anomalies for mutations in the coding sequence of FGF8. While no such mutations were identified, a rare polymorphic variant, consisting of an 18-base-pair (six-amino-acid) duplication in exon 1c, is reported that apparently has no clinical effect. Our exclusionary data suggest that mutations in FGF8 would be, at best, an infrequent cause of such disorders.

Amino Acid Sequence↗
PubMed1997

RheothRx (poloxamer 188) injection for the acute painful episode of sickle cell disease: a pilot study.

RheothRx (Glaxo Wellcome Inc, Research Triangle Park, NC; poloxamer 188) Injection is a nonionic surfactant with hemorrheologic properties that suggest it may be useful in treating acute painful episodes (vasoocclusive crises) of sickle cell disease (SCD). We conducted a randomized, double-blind, placebo-controlled pilot study to evaluate the safety and efficacy of poloxamer, formulated as RheothRx Injection, in 50 patients with SCD. Patients with moderate to severe painful episodes requiring parenteral analgesics were randomized to receive a 48-hour infusion of either RheothRx or placebo. Pain was assessed every 4 hours. Efficacy endpoints included: (1) painful episode duration, (2) days of hospitalization, (3) quantity of analgesics used, and (4) pain intensity scores. Three subgroups of patients were considered for efficacy analyses based on the actual duration of the study drug infusion and the completeness of pain score data collection. Compared with placebo and depending on the subgroup, RheothRx-treated patients showed a 16% to 45% decrease in duration of painful episodes, a 1- to 2-day reduction in hospital stay, a threefold to fivefold reduction in analgesic requirements, and a 1-point reduction (using a 5-point scale) in average pain intensity scores at 72 hours. RheothRx was well tolerated; no clinically significant differences were observed between treatments with respect to adverse experiences or other safety measures. In addition, there were no differences between treatment groups in the incidence of recurrent painful episodes. In this study, RheothRx significantly reduced total analgesic use and pain intensity and showed trends to shorter duration of painful episodes and total days of hospitalization. In patients with moderate to severe vasoocclusive pain, RheothRx was safe and may offer a therapeutic benefit.

Adolescent↗
PubMed1997

Outcome of patients with total colonic ischemia.

PURPOSE: In this study, we sought to determine the outcome of patients with ischemic colitis, comparing patients with segmental disease with those with total colonic ischemia. METHODS: Patients with the diagnosis of ischemic colitis over the past six years were selected and reviewed for demographics, presenting symptoms, diagnosis, and treatment. RESULTS: Forty-three consecutive patients with ischemic colitis were identified and were grouped into those with segmental ischemic colitis and total colonic ischemia. Mean age was 68.8 years; 28 of 43 patients (65 percent) were males. Diagnosis was established by colonoscopy in 31 of 43 patients (72 percent), whereas in the remainder, diagnosis was made in the operating room. Ischemic colitis developed in the hospital in 17 of 43 patients (40 percent) during admission for an unrelated illness. In 6 of 43 (14 percent) of these patients, ischemic colitis developed following surgery. Thirty-one of 43 patients (72 percent) were found to have segmental colitis; 11 of 31 patients (35 percent) were successfully managed nonoperatively. Segmental colitis was present in 31 of 43 patients (72 percent), and 12 of 31 (35 percent) of these patients were successfully managed nonoperatively. In the patients with segmental colitis who required surgery, the 30-day mortality rate was 22 percent. Among 12 of 17 patients (71 percent) with segmental ischemia treated by resection and stoma, 9 of 12 (75 percent) underwent eventual stoma closure. All 12 patients with total colonic ischemia required surgery, and 9 of 12 patients (75 percent) died. CONCLUSION: Ischemic colitis occurs commonly during an unrelated hospital admission and following previous surgery. Most patients treated by resection and stoma undergo stoma closure. Total colonic ischemia carries a worse prognosis than segmental colonic ischemia.

Adult↗