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Biomedical subjects

G Phillips

Publications and source records attributed to G Phillips.

At least 19 recordsLinked to original sources
PubMed1992

Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia.

Patients with sickle cell anemia were treated with daily doses of hydroxyurea, to assess pharmacokinetics, toxicity, and increase in fetal hemoglobin (Hb) production in response to the drug. Plasma hydroxyurea clearances were not a useful guide to maximum tolerated doses of the drug. The mean daily single oral dose that could be maintained for at least 16 weeks was 21 mg/kg (range, 10 to 35 mg/kg). Among 32 patients, last HbF levels were 1.9% to 26.3% (mean, 14.9%) with increases in HbF over initial values of 1.4% to 20.2% (mean, 11.2%). The most significant predictors of last HbF were last plasma hydroxyurea level, initial white blood count and initial HbF concentration. Last HbF was not related to beta globin haplotype or alpha globin gene number. No serious toxicity was encountered. Clinically significant bone marrow depression was avoided, and chromosome abnormalities after 2 years of treatment were no greater than those observed before treatment. The period of observation has been too short to evaluate the risk of carcinogenesis. Patient's red cells developed striking macrocytosis. Median red cell Hb concentrations did not change. Hb concentrations increased, on average 1.2 g/dL, but serum erythropoietin levels increased. Patients' body weights increased, and some returned to work or school, but no conclusions regarding therapeutic efficacy could be drawn from this uncontrolled open-label study.

Adult↗
PubMed1992

Prevalence and pathologic features of sickle cell nephropathy and response to inhibition of angiotensin-converting enzyme.

BACKGROUND: Nephropathy may develop in patients with sickle cell disease. We determined the prevalence of proteinuria and renal insufficiency in a group of patients with sickle cell disease and investigated the renal pathologic changes and the effects of an angiotensin-converting-enzyme inhibitor (enalapril) on protein excretion in patients found to have nephropathy. METHODS: We prospectively screened 381 patients with sickle cell disease for the presence of proteinuria and renal insufficiency. Renal biopsy and measurements of glomerular filtration rate, effective renal plasma flow, and urinary protein excretion were performed in 10 patients with mild nephropathy before and after the administration of enalapril, and again two to three weeks after its discontinuation. RESULTS: Of the 381 patients with sickle cell disease, 26 (7 percent) had serum creatinine concentrations above the normal range and 101 (26 percent) had proteinuria of at least 1+. The renal lesions in the 10 patients who had biopsies consisted of glomerular enlargement and perihilar focal segmental glomerulosclerosis. The mean (+/- SD) glomerular area in these patients was 28.7 +/- 4.1 x 10(3) micron 2, as compared with 15.8 +/- 4.3 x 10(3) micron 2 in 10 control patients without renal disease who had died of trauma (P less than 0.0001). During the administration of enalapril, the mean 24-hour urinary protein excretion decreased 57 percent (range, 23 to 79 percent) below the base-line value (P less than 0.001), and it increased to 25 percent below the base-line value after enalapril was discontinued. The glomerular filtration rate and effective renal plasma flow did not change significantly. CONCLUSIONS: Approximately 25 percent of patients with sickle cell disease have proteinuria. Treatment with enalapril reduces the degree of proteinuria in these patients, suggesting that glomerular capillary hypertension may be a pathogenic factor in sickle cell nephropathy.

Adult↗
PubMed1992

The complex CD44 transcriptional unit; alternative splicing of three internal exons generates the epithelial form of CD44.

We have utilized the polymerase chain reaction (PCR) to isolate a 3.5 kilobase pair (kb) genomic fragment that encodes the additional extracellular domain unique to the epithelial isoform of CD44 (CD44E). Nucleotide sequence was determined for this complete region and sequence comparison to our previously determined CD44R1 and CD44R2 cDNA sequences revealed the R region to be comprised of three exons of 102 bp, 90 bp, and 204 bp. Northern blot analysis of CD44 expressing cell lines confirmed the presence of CD44R1 transcripts and indicates that the epithelial domain may be inserted through alternative splicing into all CD44 transcript classes. Southern blot analysis of the CD44E genomic fragments is consistent with a single copy per human haploid genome. The data presented here further supports our model of the human CD44 transcriptional unit as a single gene complex that utilizes an invariant 5' initiation site, alternative internal and 3' end splicing, and multiple poly (A) sites to generate through RNA processing a diverse number of human CD44 isoforms.

Amino Acid Sequence↗
PubMed1992

Vancomycin and teicoplanin: something old, something new.

OBJECTIVE: To compare and contrast the pharmacology, activity and clinical efficacy of two glycopeptide antibiotics, vancomycin and teicoplanin. DATA SOURCES: English language literature search using MEDLINE, Index Medicus, relevant textbooks and product information literature. STUDY SELECTION: Over 200 publications were examined extending back to the period of initial Phase I trials with vancomycin. DATA EXTRACTION AND SYNTHESIS: Many publications covered similar ground and came to the same conclusions. In these instances one or two of the best pieces were chosen as cited reference material. Conflicting results and conclusions are discussed and an attempt is made to interpret the findings. CONCLUSION: Vancomycin and teicoplanin show differences in activity both in vitro and in vivo. Vancomycin is superior against coagulase-negative staphylococci and reliable dosage regimens are available. Teicoplanin, however, needs to be given in significantly larger doses than initially thought necessary to maximise clinical efficacy. Teicoplanin has a lower incidence of side effects but in clinical practice this advantage is small. Vancomycin remains the glycopeptide of choice for the treatment of infections due to Gram-positive bacteria.

Anti-Bacterial Agents↗
PubMed1992

Relationship of plasma alpha tocopherol to index of clinical severity in individuals with sickle cell anemia.

Several parameters of micronutrition related to antioxidant activity are reduced in individuals with sickle cell anemia (SCA). The data presented here suggest that vitamin E, specifically alpha tocopherol, has a significant correlation (r = -0.38, P < 0.04) with a retrospective survey of clinical events and a significant correlation with a prospective survey of clinical events (r = -0.42, P < 0.03). The survey of clinical events score takes into account important vaso-occlusive manifestations in SCA. Differences in plasma vitamin E levels explained about 15% of the variability in the clinical manifestations of SCA in the population studied. Previously reported data from our lab suggests that the differences in alpha tocopherol levels are not related to dietary intake. Vitamin E may play an important role in modulating the ability of sickle hemoglobin containing erythrocytes to produce vaso-occlusion. Alternatively, it may simply be a marker of disease activity. Studies are ongoing at our center to determine if the relationship of alpha tocopherol to clinical events is causal.

Adult↗
PubMed1992

Adult sexual orientation in relation to memories of childhood gender conforming and gender nonconforming behaviors.

Heterosexual, bisexual, and homosexual men recalled the extent to which they had engaged in gender conforming (masculine) and gender nonconforming (feminine) behaviors as a child. Adult sexual orientation was predicted as accurately by memories of childhood gender conforming behaviors as by memories of childhood gender nonconforming behaviors. However, childhood scripts as recalled by homosexual men were considerably more diverse. Twenty-two of 61 homosexual men reported having experienced few, if any, of the gender conforming behaviors and most, if not all, of the gender nonconforming behaviors. Another 18 homosexual men had the same profile of recalled childhood experiences as heterosexual men (high probability of masculine behaviors and low probability of feminine behaviors). Such diversity has implications not only for commentaries on the basis for homosexuality but for issues to be addressed in future research.

Adolescent↗
PubMed1992

Pseudotumoral paraesophageal varices.

We report a case of paraesophageal varices presenting as a posterior mediastinal mass in a patient with long-standing portal hypertension. These collaterals were present, despite multiple previous sclerotherapies for submucosal esophageal varices and no endoscopic evidence of their recurrence.

Adult↗
PubMed1992

Behavioural tests of the dopamine depletion hypothesis of neuroleptic-induced response decrement.

This study was carried out to test the hypothesis that neuroleptic-induced within-session response decrements reflect a fatigue process, resulting from dopamine depletion, that is present before the session begins but is masked briefly by activational cues present at the start of the session. Response decrementing effects of pimozide were examined in rats lever pressing on random interval schedules of food reinforcement. An initial experiment was carried out to rule out a pharmacokinetic explanation of the response decrement. In a second experiment, the response decrement was not exacerbated by an immediately preceding period of intense forced motor activity (wheel running). Experiments 3 and 4 tested two further predictions: that the pimozide-induced response decrement should be overcome by removing the animal to its home cage and then replacing it in the apparatus (thereby reinstating the activational cues present at the start of the session); and that response impairments should be present from the outset if the animal is confined in the apparatus prior to the start of the session (thereby allowing activational cues to dissipate). Neither prediction was confirmed. Overall, the results provide no support for the dopamine depletion hypothesis.

Animals↗
PubMed1992

Hypothyroidism in adults with sickle cell anemia.

Persons with sickle cell anemia have several indications for transfusion of red blood cells. One of the complications of transfusion of red blood cells is iron overload. Iron overload has been associated with multiple endocrine abnormalities. We report herein three cases of hypothyroidism in adult individuals with sickle cell disease. All three patients were over the age of 45 years at the time of the diagnosis and had received multiple units of transfused red blood cells and had serum ferritin levels of greater than 6,000 ng/mL. All patients were diagnosed during times when they were critically ill. Replacement therapy was instituted in all cases; however, all three patients died shortly after the diagnosis of hypothyroidism was made. Congestive heart failure appeared to be a primary cause of death in all three patients. In the one patient in whom a postmortem examination was done, there was evident extensive fibrosis of the thyroid gland as well as extensive deposition of iron in the cells lining the thyroid follicles. We believe that this represents the first report of clinical hypothyroidism in patients with sickle cell anemia who have received multiple transfusions. Awareness of this condition is especially important given that congestive heart failure is common in sickle cell disease.

Anemia, Sickle Cell↗
PubMed1992

Microbial growth and blockage of sub-floor drains in a renal dialysis centre: a problem highlighted.

The accumulation of microorganisms embedded in biofilm within the drainage pipework leading from individual dialysis monitors in a renal dialysis centre, represents a significant threat to the safe operation of the whole centre due to blockage of the pipes and overflow of waste water. Attempts to disperse the growth with chemicals and disinfectants have been unsuccessful. Only mechanical rodding has removed the deposit, and regrowth has occurred. Those planning new dialysis centres should ensure that effluent pipework is readily accessible with multiple rodding eyes and is made of material able to withstand rodding and chemicals.

Bacteria↗
PubMed1992

Decreased reactivity to sweetness following chronic exposure to mild unpredictable stress or acute administration of pimozide.

Consumption of a palatable wet mash was examined in rats subjected chronically (4-10 weeks) to unpredictable mild stress. Intake of mash containing 0, 10%, or 20% additional sucrose was normal in stressed animals. In control animals, the addition of 30% or 40% sucrose caused a decrease in the quantity of mash consumed, but increased the rate of eating. Both the increase in eating rate and the decrease in intake, at high sucrose concentration, were markedly attenuated in stressed animals (which therefore had higher intakes of very sweet mash and lower rates of eating, relative to control animals). Like chronic mild stress, the dopamine receptor antagonist pimozide (0.2 mg/kg) also increased the intake of a wet mash with 30% added sucrose, while decreasing the rate of consumption. Stressed animals were relatively insensitive to pimozide, though there were significant additive effects on duration of eating (increased) and on postprandial resting (suppressed). The failure of stressed animals to adapt their intake to increases in sweetness, and the similarities between the effects of chronic mild stress and acute pimozide, are compatible with the hypothesis that animals exposed to chronic mild stress are anhedonic.

Animals↗
PubMed1992

Sickle cell disease pain: 2. Predicting health care use and activity level at 9-month follow-up.

This study examined 9-month follow-up data obtained from adults with sickle cell disease (SCD) participating in a longitudinal study of pain-coping strategies. Of 99 subjects completing the baseline assessment of pain-coping strategies, 89 (90%) completed a structured pain interview assessing health care use and activity reduction during painful episodes over the follow-up period. Regression analyses controlling for demographics and disease severity revealed that baseline Negative Thinking and Passive Adherence was associated with greater activity reduction and more frequent health care contacts during the subsequent 9 months. Additional correlational analyses revealed that if levels of Negative Thinking and Passive Adherence increased from baseline to follow-up, this increase was associated with even further reductions in activity level during painful episodes. Changes in disease severity were not associated with any of the follow-up measures. Comparing pain-coping strategies assessed at baseline to pain-coping strategies measured at follow-up revealed that, without intervention, pain-coping strategies were relatively stable over time.

Activities of Daily Living↗
PubMed1992

Stress, coping, and psychological adjustment of adults with sickle cell disease.

A transactional model of psychological adjustment to chronic illness was examined with 109 African-American adults with sickle cell disease (SCD). Good psychological adjustment was associated with lower levels of perceived daily stress and stress regarding SCD illness tasks, higher efficacy expectations, less use of palliative coping methods, less use of negative thinking/passive adherence pain-coping strategies, and family functioning characterized by high levels of support and low levels of conflict and control. Overall the underlying stress and coping conceptual model accounted for 44-50% of the variance in psychological adjustment.

Adaptation, Psychological↗
PubMed1992

Attributions and relapse in opiate addicts.

This study investigated whether attributions of opiate addicts would predict both their ability to abstain from future use and their reactions to abstinence violations. Measures of generalized beliefs about responsibility for positive and negative outcomes and specific attributions about relapse episodes were elicited from 80 addicts at the time of admission for inpatient detoxification and treatment. Addicts who at admission attributed to themselves greater responsibility for negative outcomes and who attributed relapse episodes to more personally controllable factors were subsequently (at 6-month follow-up) more likely either to be completely abstinent or to contain the effects of temporary lapses into opiate use.

Adaptation, Psychological↗
PubMed1992

Urine transparency as an index of absence of infection.

A visual assessment of the clarity of urine was used as an exclusion test to indicate the absence of infection; verified by dipslide culture, it was applied to 363 urine samples collected from patients attending 2 adult nephrology clinics over a period of 6 months. The crimped aluminium bowl used for collection of samples assisted the assessment of clarity. The sensitivity of the method compared with dipslide culture was 73%, with specificity and efficiecy both 58%. The predictive value of a negative test (clarity) was 97% with a false negative rate of 3%, enabling this simple examination to be used as an exclusion test for further testing. In simple terms, a clear urine is unlikely to be infected. It is also an advantage to have an immediate indicator of the absence of infection available at the clinic. Analysis of only those urines assessed as cloudy could result in financial savings and, from the clinics, a 56% reduction in workload.

Adolescent↗
PubMed1992

Use of telephone enquiries to a microbiology laboratory as a proxy measure of reporting efficiency.

AIMS: To assess the efficacy of a bacteriology service in respect of the time interval between collection of specimen and receipt of final report using the number and type of incoming telephone enquiries as a proxy measure. METHODS: For three months, all incoming telephone enquiries regarding the results of bacteriology specimens were monitored. Specimen type, date of sampling, the sender's location and the reason for making the telephone enquiry were recorded. RESULTS: The number of telephone enquiries made during the study was 1170, about 5% of the total number of samples received. Most enquiries related to results of urine cultures. These accounted for 33.9% of the calls, but only 5% of the total number of urines cultured. Enquiries relating to blood cultures were the next largest group accounting for 14.9% of calls, but 11% of the blood cultures received resulted in a telephone enquiry. The most frequent reason for making the telephone call was that the sender had not received the final report. CONCLUSIONS: Clinicians may have unrealistic expectations of the time taken to examine a specimen. A requirement for reporting sterile blood cultures after a shorter incubation period was found, and the value to patient management of earlier reporting of negative urine samples was identified.

Bacteriology↗