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Biomedical subjects

C Reid

Publications and source records attributed to C Reid.

At least 73 records · Page 4Linked to original sources
PubMed1996

Selection conditions affect the evolution of specific mutations in the reverse transcriptase gene associated with resistance to DMP 266.

OBJECTIVE: To monitor the appearance of HIV-1 variants resistant to inhibition by DMP 266, a benzoxazinone non-nucleoside reverse transcriptase inhibitor using two different protocols for applying drug selective pressure in tissue culture. To compare the phenotype and genotype of viral isolates selected by each method. METHODS: MT-2 cells and fresh donor peripheral blood mononuclear cells (PBMC) were infected with HIV-1 strain RF. The MT-2 cells were infected in the presence of a 50% inhibitory concentration (IC50) of DMP 266 and the concentration was slowly increased during the selection period. The PBMC were infected for 1 week in the absence of inhibitor and then a single concentration was maintained throughout the selection period. Both cultures were passaged for approximately 4 months. Virus and cell pellets were harvested over this in vitro selection period, the RT genes amplified by polymerase chain reaction from the cell pellets, and the proviral DNAs sequenced. Isolated virus was tested for DMP 266 susceptibility in either the AIDS Clinical Trials Group/Department of Defense consensus assay or MT-2 yield reduction assay. RESULTS: Passage in MT-2 cells resulted in accumulation of three substitutions in RT (V179D, L1001, Y181C) after 24 passages associated with 1000-fold reduced susceptibility to DMP 266. In PBMC cultures treated with 0.96 microM DMP 266, virus replication was completely suppressed after 2 weeks; no regrowth occurred in the presence of compound after 10 weeks or in the absence of compound for 3 additional weeks. The 0.096 microM treated cultures had an initial 2.5-log reduction in infectious virus titre followed by rapid regrowth. Virus obtained at week 6 displayed a 28-fold reduction in susceptibility with an L1001 substitution in RT, and by week 11 displayed a 1000-fold reduction in susceptibility with an additional V1081 substitution. CONCLUSIONS: High-level resistance to DMP 266 may develop by at least two pathways and experimental conditions influence the genotype selected. The continued absence of detectable virus in the PBMC cultures grown at 0.96 microM is supportive evidence that maintaining trough plasma levels of DMP 266 which result in sustained antiviral activity in vivo may delay emergence of highly resistant viral variants. Confirmation of this hypothesis will require clinical trials.

Alkynes↗
PubMed1996

Maxillary premolar crown morphology. A preliminary study.

There seems to be a reluctance to use the Osborn terminology for identifying crown structures in the premolars of man. This may be attributed to the lack of studies on the premolars of man in which their topography has been compared with molars. We have attempted to do this using the principles of serial homology. Our study confirms that the two major maxillary premolar cusps in man are the paracone and protocone. We suggest that the lingual cingulum and the metacone have been lost and that remnants of the metaconule have made a contribution to the distal crown margin.

Bicuspid↗
PubMed1995

Development of spontaneous seizures over extended electrical kindling. II. Persistence of dentate inhibitory suppression.

The effect of an extended program of perforant path or amygdala kindling on paired-pulse suppression in the dentate gyrus was studied in male hooded rats. Repeated kindling stimulations were delivered twice or three times daily until either 300 stimuli had been delivered or generalized convulsions had been observed to occur spontaneously. Paired-pulse suppression was monitored prior to and over the course of kindling using a standard variable interval paradigm. We also used a variable intensity paradigm in which the intensity of the conditioning pulse was varied while the test pulse intensity was fixed at 600 microA and the interpulse interval was fixed at 30 ms. Both procedures revealed progressive increases in paired-pulse suppression which persisted over the course of kindling. This increased inhibition also persisted in animals which developed spontaneous seizures. The variable intensity paired-pulse procedure also allowed us to monitor facilitation effects which were relatively uncontaminated by recurrent inhibition (when the conditioning pulse intensity was low). Kindling was found to increase paired-pulse facilitation. With the standard variable interval paradigm, these increases in facilitation masked the increases in suppression.

Amygdala↗
PubMed1995

Cell lineage and patterns of migration in the developing cortex.

Knowledge of cell lineage in the cortex is important for understanding normal development as well as brain malformations. We studied cell lineage in rats by injecting a library of up to 3400 retroviruses, distinguishable by PCR analysis and encoding alkaline phosphatase, at E14-19. Histological analysis at P15 revealed normal cell morphology and allowed identification of about 80% of all labelled cells. PCR amplification of DNA tags allowed clonal analysis. Cortical cells labelled at E15 formed clustered or widespread clones with equal frequency. Clustered clones contained one to four cells within about 1 mm that had similar morphology and laminar location. However, 48% of cortical clones contained multiple cell types with widely different locations (2.1-6.7 mm; mean, 3.8 mm). Widespread clones contained two to four 'subunits' (one to five neurons each), spaced at apparent intervals of 2-3 mm, with each subunit morphologically indistinguishable from a clustered clone. Distinct subunits in the same clone usually differed in laminar location suggesting sequential formation. Clones labelled at E17 contained fewer neurons and up to two subunits. Clustered clones seem to be produced by stationary progenitors, whereas progenitors of clusters may themselves be produced by migratory, multipotential cells.

Animals↗
PubMed1995

Psychological responses to malignant melanoma. An investigation of traumatic stress reactions to life-threatening illness.

A cross-sectional study of 95 individuals with malignant melanoma was conducted to investigate posttraumatic stress responses to a diagnosis of melanoma and to validate the use of the Impact of Event Scale (IES) as a measure of the response to the trauma of life-threatening disease. The diagnosis and progression of malignant disease are likely to present a range of acute and chronic trauma to the individual and the individual's family. The findings suggest that the IES is a reliable and valid measure of this distress, with scores varying according to disease progression and prognostic status of nonmetastatic disease patients. This indicates the importance of clinical attention to the specific symptoms that may best reflect the traumatic impact of life-threatening illness and its progression, and the applicability of posttraumatic stress syndromes in understanding the psychological distress of this clinical population.

Adult↗
PubMed1995

Seromuscular colocystoplasty lined with urothelium: experience with 16 patients.

OBJECTIVES: Report of initial clinical experience with seromuscular colocystoplasty lined with urothelium (SCLU), a new operation to increase bladder capacity and compliance without incorporating intestinal mucosa into the urinary tract. We have previously reported the technique and results of this procedure in a canine model. METHODS: Sixteen patients underwent SCLU at two institutions. Their charts were reviewed retrospectively. The patients have been observed for a mean of 12 months. RESULTS: Postoperatively, the bladder capacity increased an average of 2.4-fold from a mean of 139 mL (+/- 23.7 SEM) to 335 mL (+/- 38.9 SEM) in 14 patients (P < 0.001). Two patients required reaugmentation. Preoperative and postoperative bladder end filling pressures were available in 13 patients and decreased from a mean of 51.6 cm H2O (+/- 4.2 SEM) to 27.7 cm H2O (+/- 2.4 SEM) (P < 0.001). Of the 16 patients, 13 were incontinent preoperatively; 5 had renal insufficiency. Three patients have undergone renal transplantation following SCLU. After SCLU, 13 patients were dry day and night, 1 incontinent at night only, and 2 remained incontinent. Ten patients have undergone postoperative bladder biopsy. Seven demonstrate urothelium covering the augmented portion of the bladder, 2 have regrowth of colonic mucosa, and 1 shows a mixture of colonic mucosa and urothelium. CONCLUSIONS: The results presented suggest that SCLU is a viable alternative to the more conventional forms of bladder augmentation in selected patients.

Adolescent↗
PubMed1995

Functional evaluation of the results of hypospadias surgery with uroflowmetry.

To determine the role of uroflowmetry in the evaluation of the functional results of hypospadias repair we retrospectively reviewed the records of 32 patients who underwent hypospadias repair with urethral reconstruction (mean age 2.4 years and mean followup 3.6 years). Patients with a plateau pattern and a maximum flow rate 2 standard deviations below the mean for age, body surface and voided volume on more than 1 determination were considered to have urethral obstruction. Urethroplasty had been performed with a meatal based flap in 11 cases, an onlay preputial flap in 5 and a tubularized preputial island flap in 16. Two of 11 patients with a meatal based flap, 5 of 16 with a tubularized preputial island flap and none with an onlay preputial flap had uroflow evidence of urethral stenosis. The 2 patients in the meatal based flap group responded to dilation with a normal flow. Of the tubularized preputial island flap group 3 patients required urethroplasty to correct a stricture and 2 had improvement with dilation alone. Three patients in the tubularized preputial island flap group had normal flow after treatment and 2 had improvement. Only 2 of the 7 patients with strictures were symptomatic. We conclude that uroflow examination is an important noninvasive tool to evaluate the functional results of urethroplasty in children and detect asymptomatic strictures.

Child↗
PubMed1995

Immunological factors and risk of infection in plateau phase myeloma.

AIMS: A series of patients with myeloma were investigated to assess whether immunological risk factors predisposing to serious infection could be identified. METHODS: Patients (n = 102) with predominantly plateau phase myeloma were monitored prospectively for infections. Immunological parameters including total non-paraprotein immunoglobulins and specific antibody titres were measured in all patients and compared with a control population of healthy individuals of a similar age; response to immunisation with Pneumovax II, tetanus and diphtheria toxoids and IgG subclasses were measured in a subgroup of 41 patients. Other characteristics investigated for any association with infection included age, sex, paraprotein type, disease stage, and chemotherapy. RESULTS: Specific antibody titres to pneumococcal capsular polysaccharides and tetanus and diphtheria toxoids were significantly reduced compared with the control population. Low antipneumococcal and anti Escherichia coli titres correlated with risk of serious infection and low anti-pneumococcal titres with severity of non-paraprotein immunosuppression. In 41 immunised patients responses to Pneumovax II, tetanus and diphtheria toxoids were poor; IgG subclass levels were significantly reduced and a poor IgG response to Pneumovax II immunisation was associated with an increased risk of septicaemia and low IgG2 levels. The overall serious infection rate was 0.92 infections per patient year and was four times higher during periods of active disease (1.90) compared with plateau phase myeloma (0.49). The predominant site of infection was the respiratory tract. Clinical and laboratory parameters showed only male sex and reduced non-paraprotein IgG and IgA levels to be significantly associated with at least one serious infection. CONCLUSIONS: A subgroup of patients with myeloma with poor IgG responses to exogenous antigens, who are at increased risk of serious infection, can be identified and may benefit from replacement immunoglobulin therapy to reduce the risk of infection.

Aged↗
PubMed1995

Cardiovascular risk reduction: a randomized trial of two health promotion strategies for lowering risk in a community with low socioeconomic status.

AIM: To compare the effects of information pamphlets with those of group counselling on cardiovascular risk among individuals from a community with low socioeconomic status. METHODS: Risk factors for coronary heart disease were assessed in 1131 men and women from a community with low socioeconomic status in suburban Melbourne. Individuals deemed to be at moderate risk, on the basis of an integrated risk score greater than 65, were asked to participate in a randomized trial comparing two simple interventions designed to reduce cardiovascular risk. One hundred and sixty-four individuals were randomly assigned to group A (n = 85) and participated in a single group counselling session lasting between 1.5 and 2.0 h. Group B (n = 79) received a specially prepared pamphlet that provided brief written information concerning risk-factor modification. Both groups were asked to attend a follow-up assessment of risk factors 3 and 6 months after entry. RESULTS: There were no significant difference in the change in risk-factor levels between those receiving information pamphlets and those attending the group counselling session after 3 or 6 months of follow-up. Small but significant decreases (P<0.05) were seen in systolic and diastolic blood pressures (-5/4 mmHg for group A, -5/3 mmHg for group B), total plasma cholesterol level (-0.30 mmol/l for groups A and B) and overall coronary risk score (-14.4 and -13.9 for groups A and B, respectively). Body weight remained unchanged during the study period in both groups. CONCLUSION: Screening together with 1.5-2h group counselling had no more influence on cardiovascular risk factors than screening together with provision of information pamphlets in a population with low socioeconomic status.

Adolescent↗
PubMed1995

Assessment of effects of two anti-hypertensive regimens on overall cardiovascular risk.

Anti-hypertensive drugs differ in their effects on other cardiovascular risk factors. To date there have been few attempts to quantitate the impact of such differences. Twenty five unmedicated patients with primary hypertension were randomised to initial therapy with either the calcium antagonist, felodipine, or a diuretic and doses titrated to achieve similar levels of blood pressure (BP). Second drugs were added if needed (metoprolol and prazosin, respectively). The aim was to determine over 1 year whether similar anti-hypertensive effects were associated with differences in a multivariate index of overall cardiovascular risk. The target supine diastolic blood pressure (DBP) (85 mm Hg) required the second agent in four of 13 evaluable patients in the felodipine group and six of 10 in the diuretic group. There was a significant rise in serum cholesterol and a fall in serum potassium in the diuretic group, but not in the felodipine group. Cardiovascular risk scores were ranked in percentiles in relation to the age-matched general population. This score fell to a greater degree in felodipine patients particularly over the first 6 months, but remaining lower at 12 months. Left ventricular hypertrophy assessed by echocardiography, another measure of cardiovascular risk, was generally unchanged by either regimen. At equivalent blood pressure levels, the calcium antagonist-based regimen had a greater benefit on cardiovascular risk, particularly in the first 6 months of therapy. This method may be widely applicable in the assessment of anti-hypertensive therapy.

Adolescent↗
PubMed1994

Adolescent running away behavior: active or passive avoidance?

One hundred seventeen boys and 149 girls participated in a study investigating whether adolescent running away behavior is an expression of passive (internalization) or active (externalization) avoidance. Results of principal component analyses indicate that boys' running away behavior is associated with passive avoidance and internalization, whereas for girls the behavior reflects a mixed pattern simultaneously expressing withdrawal and overt deviancy.

Adolescent↗
PubMed1994

Molecular cloning and analysis of genes for sialic acid synthesis in Neisseria meningitidis group B and purification of the meningococcal CMP-NeuNAc synthetase enzyme.

The gene encoding for the CMP-NeuNAc synthetase enzyme of Neisseria meningitidis group B was cloned by complementation of a mutant of Escherichia coli defective for this enzyme. The gene (neuA) was isolated on a 4.1-kb fragment of meningococcal chromosomal DNA. Determination of the nucleotide sequence of this fragment revealed the presence of three genes, termed neuA, neuB, and neuC, organized in a single operon. The presence of a truncated ctrA gene at one end of the cloned DNA and a truncated gene encoding for the meningococcal sialyltransferase at the other confirmed that the cloned DNA corresponded to region A and part of region C of the meningococcal capsule gene cluster. The predicted amino acid sequence of the meningococcal NeuA protein was 57% homologous to that of NeuA, the CMP-NeuNAc synthetase encoded by E. coli K1. The predicted molecular mass of meningococcal NeuA protein was 24.8 kDa, which was 6 kDa larger than that formerly predicted (U. Edwards and M. Frosch, FEMS Microbiol. Lett. 96:161-166, 1992). Purification of the recombinant meningococcal NeuA protein together with determination of the N-terminal amino acid sequence confirmed that this 24.8-kDa protein was indeed the meningococcal CMP-NeuNAc synthetase. The predicted amino acid sequences of the two other encoded proteins were homologous to those of the NeuC and NeuB proteins of E. coli K1, two proteins involved in the synthesis of NeuNAc. These results indicate that common steps exist in the biosynthesis of NeuNAc in these two microorganisms.

Amino Acid Sequence↗
PubMed1993

Splenic macrophage activation and functions in amyloid enhancing factor-induced secondary amyloidosis. Study of phagocytosis, killing, respiratory burst, and MHC class II surface expression.

Secondary amyloidosis is a systemic disease characterized by the extracellular tissue deposition of insoluble fibrillar amyloid A protein. Aberrant metabolism of serum amyloid A protein by reticuloendothelial cells is thought to result in the accumulation of fibrils within the tissue. Treatment of mice with amyloid-enhancing factor (AEF) in conjunction with an inflammatory stimulus (i.e., AgNO3) induced amyloid deposition within 48-72 h. The activation state of a macrophage largely defines its enzymatic capabilities. In the studies reported here, we examined the effect of AEF on spleen macrophage activation using both functional and phenotypic assays. We found that while AEF in the presence or absence of AgNO3 has no apparent effect on the ability of spleen and liver macrophages to phagocytose or kill Listeria monocytogenes, it appears to block enhanced respiratory burst function (as measured by O2- production) observed with AgNO3 alone. AEF therefore seems capable of inhibiting certain macrophage activation-associated functions while not affecting others. Our activation phenotype studies, using surface Ia expression, reveal that AEF blocks the increase in number of splenic macrophages expressing Ia seen with AgNO3 alone. Treatment with interferon-gamma was found to restore decreased Ia expression in animals given AEF+AgNO3 but did not prevent amyloid A fibril deposition.

Amyloid↗
PubMed1993

Ectopic salivary gland tissue in the palatine and lingual tonsil.

A case is reported of a child born with a developmental field defect of the first branchial arch in whom there was partial obstruction of the oropharynx by a horseshoe-shaped mass of what was thought to be tonsillar tissue. 'Tonsillectomy' was performed but histopathological examination of the excised specimens showed them to be almost entirely made up of salivary gland tissue.

Child, Preschool↗
PubMed1992

Isolated systolic hypertension and subclinical cardiovascular disease in the elderly. Initial findings from the Cardiovascular Health Study.

OBJECTIVE: To assess the association between isolated systolic hypertension (ISH) and subclinical disease in adults aged 65 years and above. DESIGN: Medicare eligibility lists were used to obtain a representative sample of 5201 community-dwelling elderly persons for the Cardiovascular Health Study, a National Heart, Lung, and Blood Institute--sponsored cohort study of risk factors for coronary heart disease and stroke. In this cross-sectional analysis of baseline data, we excluded 3012 participants who were receiving antihypertensive medications, had clinical cardiovascular disease, or had a diastolic blood pressure of at least 90 mm Hg. MAIN OUTCOME MEASURES: For electrocardiogram: myocardial infarction, left ventricular hypertrophy, and left ventricular mass as measures of myocardial damage and strain; for echocardiography: left ventricular mass, fractional shortening, and Doppler flow velocities as measures of cardiac systolic and diastolic function; and for carotid sonography: carotid arterial intima-media thickness as a measure of atherosclerosis. RESULTS: Among the 2189 men and women in this analysis, 195 (9%) had ISH (systolic blood pressure, greater than or equal to 160 mm Hg) and 596 (23%) had borderline ISH (systolic blood pressure, 140 to 159 mm Hg). Systolic blood pressure was associated with myocardial infarction by electrocardiogram (P = .02). Borderline and definite ISH were strongly associated with left ventricular mass (P less than .001). While there was little association with cardiac systolic function, borderline and definite ISH were associated with cardiac diastolic function (P less than .001). Isolated systolic hypertension was also strongly associated with increased intima-media thickness of the carotid artery (P less than .001). CONCLUSIONS: While cohort analyses of future repeated measures will provide a better assessment of risk, both borderline and definite ISH were strongly related to a variety of measures of subclinical disease in elderly men and women.

Aged↗
PubMed1992

Cutaneous cryptococcosis: recurrence following oral fluconazole treatment.

A case of recurrent cutaneous cryptococcosis in an immunocompromised patient is described. The patient presented with a non-healing cutaneous ulcer due to infection with Cryptococcus neoformans. Extensive investigation failed to reveal any evidence of associated systemic cryptococcosis. Treatment with oral fluconazole resulted in complete resolution of the ulcer but after several months a second cutaneous cryptococcal lesion appeared, strongly suggesting dissemination from an underlying systemic focus. This case illustrates the hazards associated with making a diagnosis of isolated cutaneous cryptococcosis and the necessity for prolonged follow-up of patients who present in this way.

Administration, Oral↗
PubMed1992

Selective embolisation of intrahepatic aneurysms.

The radiological techniques that can be used to selectively embolise small arteries have improved markedly in the past few years. This article discusses the use of transcatheter embolisation in the management of three patients with aneurysms involving the intrahepatic arterial tree.

Adult↗