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Biomedical subjects

R Morgan

Publications and source records attributed to R Morgan.

At least 73 records · Page 4Linked to original sources
PubMed1998

Double-stranded-RNA-activated protein kinase (PKR) regulates Ca2+ stores in Xenopus oocytes.

Expression of the double-stranded-RNA-dependent protein kinase (PKR) in Xenopus oocytes attenuated Ca2+ entry-dependent membrane currents activated by depletion of Ca2+ stores, whereas expression of a dominant-negative PKR mutant had the opposite effect. These results appeared to be due to perturbation of releasable Ca2+ stores, and not actions of PKR on protein synthesis. PKR may thus have novel protein substrates and cellular functions in Ca2+ storage and signalling.

Animals↗
PubMed1998

The Philadelphia chromosome as a secondary change in leukemia: three case reports and an overview of the literature.

Three cases of acute nonlymphocytic leukemia with a Philadelphia chromosome (Ph) as a secondary abnormality are reported. The Ph was late-appearing in one patient and appeared as an additional anomaly in the other two patients. Fluorescence in situ hybridization studies of the first patient identified the presence of a minor BCR/ABL rearrangement. The findings of these cases support the conclusion that the Ph plays a role not only in leukemogenesis, but also in disease progression. An overview of the literature dealing with similar cases is also presented.

Adolescent↗
PubMed1998

Characterization of an extremely thermostable restriction enzyme, PspGI, from a Pyrococcus strain and cloning of the PspGI restriction-modification system in Escherichia coli.

An extremely thermostable restriction endonuclease, PspGI, was purified from Pyrococcus sp. strain GI-H. PspGI is an isoschizomer of EcoRII and cleaves DNA before the first C in the sequence 5' CCWGG 3' (W is A or T). PspGI digestion can be carried out at 65 to 85 degrees C. To express PspGI at high levels, the PspGI restriction-modification genes (pspGIR and pspGIM) were cloned in Escherichia coli. M.PspGI contains the conserved sequence motifs of alpha-aminomethyltransferases; therefore, it must be an N4-cytosine methylase. M.PspGI shows 53% similarity to (44% identity with) its isoschizomer, M.MvaI from Micrococcus variabilis. In a segment of 87 amino acid residues, PspGI shows significant sequence similarity to EcoRII and to regions of SsoII and StyD4I which have a closely related recognition sequence (5' CCNGG 3'). PspGI was expressed in E. coli via a T7 expression system. Recombinant PspGI was purified to near homogeneity and had a half-life of 2 h at 95 degrees C. PspGI remained active following 30 cycles of thermocycling; thus, it can be used in DNA-based diagnostic applications.

Amino Acid Sequence↗
PubMed1998

Characteristics of patients with shingles admitted to a district general hospital.

Little is known about why some patients with shingles are admitted to hospital. We reviewed 72 case notes from a list of 80 patients admitted to hospital with shingles over a six-year period. Pain was the main complaint of the patients admitted, most of whom were elderly and lived alone. The commonest site of involvement in hospital admissions was the eye (herpes zoster ophthalmicus). Diagnosis of shingles was made after admission in 12 patients, eight of whom had originally been diagnosed as having an acute medical or surgical condition. We conclude that the prodromal phase of shingles may lead to misdiagnosis.

Aged↗
PubMed1998

Hospital doctors' assessment of baseline spirometry.

Baseline spirometry is useful in diagnosing and managing pulmonary disease. In a questionnaire survey of 100 hospital doctors in two hospitals in the Mersey region, their views and ability to interpret baseline spirometry was assessed. Of the 70 doctors who responded, 65% felt they could accurately interpret baseline spirometry. However, only 12% accurately interpreted all five vitalographs in the questionnaire. The majority (72%) felt they had not had adequate teaching in interpretation of spirometry, and 63% would prefer a report from a respiratory technician. These result suggest that improvement needs to be made in interpretation of baseline spirometry.

Clinical Competence↗
PubMed1998

Mild cognitive impairment and risk of mortality in HIV-1 infection.

HIV-1-associated cognitive impairment has only been preliminarily investigated for associations with mortality. The authors examined 119 HIV-1-positive homosexual men (asymptomatic: n = 96; early symptomatic: n = 23). At follow-up (to 3.5 years), there were 105 survivors and 14 nonsurvivors. Those at the 25th percentile in response speeds and in long-term memory retrieval accuracy were at 6.4 (P < 0.02) and 3.5 (P < 0.05) times increased mortality risk, respectively, of those at the 75th percentile--independent of baseline CDC clinical stage, CD4 cell count, hemoglobin level, antiretroviral and prophylactic medication use, and sociodemographics. Cognitive impairment should be identified early--for maximization of both functional status and survival time.

AIDS Dementia Complex↗
PubMed1998

Combination therapy for HIV: the effect on inpatient activity, morbidity and mortality of a cohort of patients.

We set out to quantify the changes in HIV-related morbidity and mortality associated with the clinical use of antiretroviral therapy via prospectively collected patient-related events (admissions, bed days, deaths, WHO stage 3 and 4 events and drug costs) on all HIV patients known to the Regional Infectious Disease Unit (RIDU) from 1 January 1987 to 31 December 1996. The introduction of zidovudine monotherapy in 1987 for those with AIDS was associated with a subsequent decline of inpatient activity for 2 years: in 1989 there was a 23% reduction in bed days but only a 6% reduction in admissions. A further dramatic decline of patient-related events in those with AIDS was noted during 1996 following the introduction of combination therapy, a 39% reduction in admissions, 44% reduction in bed days, 54% reduction in stage 4 events, 33% reduction in WHO stage 3 events and 40% reduction in the death rate. Reductions were also observed for patients without AIDS including a 42% reduction in the rate of patients developing AIDS. Similar reductions were noted when the patients were classified by immunological instead of clinical status although data for 1997 suggest an increase in patient-related activity for those with CD4 counts >200 cells/microl possibly as a result of low levels of anti-HIV therapy. The introduction of combination therapy for HIV has to date led to a minimum saving of one inpatient bed per 100 patient years which helped defray the cost of combination therapy. Although we cannot imply causality from an observational study, dramatic reductions in patient-related activity were associated with the introduction of combination therapy into clinical practice. The ultimate extent and duration of this effect cannot as yet be predicted and caution is required since similar reductions were noted with zidovudine therapy which were unfortunately time limited.

Anti-HIV Agents↗
PubMed1998

A new design of the esophageal Wallstent endoprosthesis resistant to distal migration.

OBJECTIVE: Because plastic-covered metallic stents used in the palliation of patients with unresectable esophageal cancer are associated with significant rates of migration, particularly when the lower end of the stent projects into the gastric fundus, the purpose of this study was to establish whether two new prototype designs of the Wallstent esophageal endoprosthesis are prone to migration. SUBJECTS AND METHODS: A cylindrical stent and a conical stent were studied. Both designs included plastic covering inside the metallic mesh. In addition, the conical device incorporated a variation in the braiding angle between the upper and lower parts of the endoprosthesis. Ten conical stents and eight cylindrical stents were inserted in 18 patients with tumors involving the gastroesophageal junction who were followed up with esophagography and endoscopy. RESULTS: All insertions of stents were successful. Two cylindrical stents (25%) migrated distally. Two conical stents (20%) migrated proximally. One perforation occurred that was associated with distal migration of a cylindrical stent. CONCLUSION: The frequency of distal migration of cylindrical stents is unacceptably high. Conical stents are resistant to distal migration, although improvements in design are required to deal with the problem of proximal migration.

Adenocarcinoma↗
PubMed1998

Pre-clinical evaluation of probes to detect t(8;21) AML minimal residual disease by fluorescence in situ hybridization.

The 8;21 translocation in acute myeloid leukemia (AML) results in a consistent fusion transcript, AML1/ETO. Long-term clinical remission occurs in some patients despite incomplete eradication of AML1/ETO as demonstrated by RT-PCR, thus limiting the usefulness of this assay. An important future goal will be to determine if there is a level of minimal residual disease (MRD) in patients below which relapse is unlikely. For the detection of MRD, we have developed reagents for fluorescence in situ hybridization (FISH) that identify both derivative 8 and 21 chromosomes with a high analytical sensitivity. In t(8;21) AML cells, two fused signals were detected in addition to the normal 8 and 21 alleles. The sensitivity and specificity of this probe mixture were analyzed in cell lines and patient bone marrows. One and two randomly juxtaposed signals were observed in 2.4 and 0.04% of normal cells, respectively. However, these were easily differentiated from t(8;21) cells by the absence of signals from the normal alleles. Using as criteria the presence of two fused signals plus the normal alleles, we observed no false positives among 5,000 normal cells. The probe correctly identified 20/20 patients with t(8;21) AML and 10/10 non-t(8;21) patients. In cell dilution experiments, the analytical sensitivity of this reagent was equal to that of the X chromosome and Y chromosome alpha-satellite probes. These optimized probes should facilitate the quantitative assessment and study of MRD in t(8;21) AML.

Bone Marrow Cells↗
PubMed1998

Shingles: a review of diagnosis and management.

Herpes zoster or shingles results from reactivation of varicella zoster virus previously dormant in cells of the dorsal root ganglion. The incidence of shingles increases with age and immunosuppression. Guidelines for managing shingles are now available and implementation, with the emphasis on early treatment, may reduce the severity of a shingles attack and reduce the incidence of complications.

AIDS-Related Opportunistic Infections↗
PubMed1997

Some observations on fluorescence in situ hybridization evaluation of chronic myelocytic leukemia.

Cosmid probes specific for the major BCR/ABL rearrangement (commercially available probes) were employed by us to evaluate 134 patients with the clinical diagnosis of chronic myelocytic leukemia (CML). The following represent our main observations: 1) No significant statistical difference regarding a false positive fusion signal was seen in the distribution pattern between the Ph negative (-) cases (110) and the normal controls (3.23 +/- 1.97 vs 2.8 +/- 1.92, respectively). 2) The mean percentage of cells with a positive fusion signal in the Ph positive (+) CML cases at presentation was 70 +/- 12.3 in bone marrow samples (12 cases) and 45 +/- 12.4 in blood samples (3 cases). 3) A significant discrepancy was seen between the interphase FISH and cytogenetics data in the monitoring of four out of eight patients post-therapy. The clinical significance of this observation needs to be clarified. 4) Three Ph(-) patients with significant leukocytosis had closely adjacent but not fused signals (20%, 16%, and 20% of cells, respectively, vs. the control: 4%). This may indicate a temporal and spatial association between chromosomes 9 and 22 prior to the BCR/ABL rearrangement (Ph chromosome formation).

Aged↗
PubMed1997

Effect of CD34+ selection and various schedules of stem cell reinfusion and granulocyte colony-stimulating factor priming on hematopoietic recovery after high-dose chemotherapy for breast cancer.

We evaluated the effects of various schedules of peripheral blood stem cell (PBSC) reinfusion, granulocyte colony-stimulating factor (G-CSF) priming, and CD34+ enrichment on hematopoietic recovery in 88 patients with advanced breast cancer treated with high-dose chemotherapy, consisting of cisplatin 250 mg/m2, etoposide 60 mg/kg, and cyclophosphamide 100 mg/kg. PBSC (> or = 7.5 x 10(8) nucleated cells/kg) were collected following priming with G-CSF and were either immediately cryopreserved (48 patients; cohorts A and B) or were first processed for CD34+ enrichment (40 patients; cohorts C and D). Patients in cohorts A and C received PBSC on day 0; patients in cohorts B and D received 25% of their nucleated cells on day -2 and 75% on day 0 (split reinfusion). Patients in cohorts A, B, and C were primed with G-CSF 10 micrograms/kg, subcutaneously (SC), once a day; patients in cohort D were primed with 5 micrograms/kg G-CSF, SC, twice daily (bid). Bid administration of G-CSF yielded 2.3 to 4.7 x higher numbers of CD34+ cells in the PBSC product than the same total dose given once a day (P = .002). Reinfusion of 25% of unselected PBSC on day -2 (median, 2.26 x 10(8)/kg nucleated cells [range, 1.7 to 3.3 x 10(8)/kg]) with the remaining cells reinfused on day 0 resulted in earlier granulocyte recovery to > or = 500/microL when compared with reinfusion of all stem cells on day 0 (group B, median of 8 days [range, 7 to 11] v group A, 10 days [range, 8 to 11], P = .0003); no schedule-dependent difference was noted in reaching platelet independence (group B, 11.5 days [range, 5 to 21]; group A, 12 days [range, 8 to 24], P = not significant). Split schedule reinfusion of CD34(+)-selected PBSC did not accelerate granulocyte recovery. In groups D and C, the median number of days to granulocyte recovery was 12 (range, 8 to 22) and 11.5 (range, 9 to 13); patients became platelet independent by day 15 (range, 6 to 22) and 14 (range, 12 to 23), respectively. CD34(+)-selected PBSC rescue decreased the incidence of postreinfusion nausea, emesis, and oxygen desaturation in comparison to unselected PBSC reinfusion (P < or = .005 for each). Hematopoietic recovery may be accelerated by earlier reinfusion of approximately 2.26 x 10(8)/kg unselected nucleated cells. Earlier recovery may be triggered by components other than the progenitors included in the CD34+ cell population. Sustained hematopoietic recovery can also be achieved with CD34(+)-selected PBSC alone. Dosing of G-CSF on a bid schedule generates higher CD34+ cell yield in the leukapheresis product. Whether even earlier "sacrificial" reinfusion of approximately 2 x 10(8)/kg unselected nucleated cells concomitant with the administration of high-dose chemotherapy would reduce the duration of absolute granulocytopenia further while initiating sustained long-term hematopoietic recovery will require further investigation.

Adult↗