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Biomedical subjects

C C Smith

Publications and source records attributed to C C Smith.

At least 37 records · Page 2Linked to original sources
PubMed1999

Epidemiology and outcome of HIV infection in North-East Scotland (1985-1997).

OBJECTIVE: to assess the epidemiology of HIV infection in North-East Scotland. METHODS: retrospective casenote review of all HIV-infected patients who have had contact with the Infection Unit in Aberdeen. RESULTS: one hundred and forty-two HIV-infected patients were treated between April 1985 and December 1997. The risk behaviour related to the acquisition of the HIV infection was: 56 (39%) homosexually infected, 45 (32%) heterosexually-infected, 34 (24%) injecting drug users (IDUs), and seven (5%) blood products or not known. Sixteen of the 45 (36%) heterosexually-infected patients were native to Africa and 16 of the 34 (31%) IDUs were prisoners in Peterhead prison at the time of referral. Fifty-two (37%) of the cohort continue to attend the Infection Unit, 41 (29%) have relocated, 40 (28%) have died and nine (6%) have been lost to follow-up. The ratio of heterosexual:homosexual men:IDUs changed significantly between the first 7 years (12:21:25) and the second 6 years (33:35:9) of the review, with significantly more patients being infected through heterosexual contact and fewer infected by IDU in the second period-P<0.001. The median AIDS survival was 17 months. Survival was significantly longer in those patients who took anti-retroviral therapy (median = 20 months) than in the patients who opted not to take anti-retroviral therapy (median = 11 months)-P<0.01. CONCLUSIONS: Although homosexual contact represents the commonest risk group for HIV infection in this region, the number of heterosexually-infected patients has increased significantly in the last 5 years. Temporary residents account for one-third of the HIV-infected population cared for in NE Scotland. Almost half of those lost to follow-up have returned to Africa or been released from prison. The introduction of anti-retroviral therapy has resulted in a dramatic improvement in AIDS survival in our cohort as it has done elsewhere.

Africa↗
PubMed1999

Effects of acute prednisone administration on memory, attention and emotion in healthy human adults.

We conducted a double-blind study in order to examine the effects of high doses of prednisone on memory, attention and emotion in humans. A total of 24 healthy undergraduate males self-administered either 160 mg of prednisone (n = 12) or a placebo (n = 12) for 4 consecutive days. We examined group differences in mood, regional brain electrical activity (EEG), the startle eyeblink response, memory recall and performance on an attention task after 4 days of treatment. We found significant group differences on measures of mood and frontal EEG alpha activity on 4-day treatment. Subjects treated with prednisone exhibited a significantly greater increase in self-reported negative emotion and greater relative right frontal EEG alpha activity on 4-day treatment compared with adults in the placebo group. We also found that subjects treated with prednisone recalled fewer objects on the memory task following treatment. No significant group differences were found on posterior EEG activity, the startle eyeblink measure, or the attention measure. These findings suggest that administration of high doses of exogenous prednisone may facilitate the experience of negative emotion and shifts in frontal EEG activity, and impair some aspects of cognitive functioning in humans. The multiple roles of glucocorticoids in memory, attention and emotion are discussed.

Adolescent↗
PubMed1999

The generation of the F(2)-isoprostane 8-epi-PGF(2alpha) by human platelets on collagen stimulation.

F(2)-isoprostanes are prostaglandin (PG) F(2)-like compounds formed via non-enzymatic peroxidation of arachidonic acid, although some F(2)-isoprostane production may be cyclo-oxygenase (COX)-mediated. Of these substances 8-epi-prostaglandin F(2)alpha (8-epi-PGF(2alpha)) has received the most attention as it induces vasoconstriction and mitogenesis, and influences pathophysiological mechanisms relevant to arterial disease. Using improved methods for F(2)-isoprostane determination we examined collagen-stimulated platelet production of F(2)-isoprostanes in platelet-rich plasma (PRP), distinguishing between the free and esterified forms of these substances. Collagen stimulation caused marked release to the plasma (platelet-poor; PPP) of free 8-epi-PGF(2alpha) (2 +/- 2 pg/mg platelet protein vs 174 +/- 53 pg/mg protein, control (i.e. non-stimulated) vs collagen-stimulated, P < 0.05) and of free 9alpha ,11alpha-PGF (37 +/- 19 pg/mg protein vs 1948 +/- 643 pg/mg protein, control vs stimulated, P < 0.05), a COX derived product. Neither free nor esterified 9alpha, 11beta-PGF and 9beta, 11alpha-PGF(2alpha) were detectable in control or collagen stimulated samples. Sample concentrations of the esters of 8-epi-PGF(2alpha) and 9alpha, 11alpha-PGF(2alpha) were unaltered by collagen stimulation. These data confirm a previous report that activated platelets release the F2-isoprostane 8-epi-PGF(2alpha), accompanying the release of a COX-derived product, 9alpha, 11alpha-PGF(2alpha).

Journal Article↗
PubMed1999

Nitric oxide synthesis in patients with infective gastroenteritis.

BACKGROUND: There is evidence that endogenous nitrate synthesis is notably increased in patients with infective gastroenteritis. AIMS: To determine whether this is due to nitric oxide (NO) production via the L-arginine/NO pathway. METHODS: Seven male patients with community acquired bacterial gastroenteritis and 15 healthy male volunteers participated in this study. All patients had stool culture positive infective gastroenteritis. A bolus of 200 mg L-[(15)N](2)-arginine was administered intravenously after an overnight fast. Urine was collected for the next 36 hours. Urinary [(15)N:(14)N]nitrate ratio was assessed by dry combustion in an isotope ratio mass spectrometer. RESULTS: Mean 36 hour total urinary nitrate excretion in the gastroenteritis group was 5157 (577) micromol compared with 2594 (234) micromol in the control group (p<0.001). Thirty six hour urinary [(15)N]nitrate excretion was considerably higher in the gastroenteritis group compared with the control group (13782 (1665) versus 1698 (98) etamol; p<0.001). These values represent 1.129 (0.139)% and 0.138 (0.007)% of [(15)N]nitrogen administered (p<0.001), respectively. Corrected 36 hour urinary [(15)N]nitrate excretion for urinary creatinine was also significantly higher in the patient compared with the control group (1934 (221) versus 303 (35) etamol/mmol; p<0.001). CONCLUSION: Results show notably enhanced nitrate synthesis due to increased activity of the L-arginine/NO pathway in patients with infective gastroenteritis.

Adult↗
PubMed1999

Risk of latex allergy from medication vial closures.

A latex allergy, like all allergies, is a serious matter that requires special precautions on behalf of patients and healthcare workers. The FDA final rule on the labeling of natural rubber-containing medical devices will assist in the creation of a latex-safe environment for latex-sensitive individuals. Currently, this ruling does not apply to medication vial closures that contain latex. Until further action by the FDA, the only way to determine whether a medication vial closure contains latex is by directly contacting the pharmaceutical manufacturer. Moreover, in order to rule whether special labeling should be mandatory for latex-containing medication vials, additional evidence is needed to clarify whether exposure to trace amounts of latex from a medication vial stopper can cause allergic reactions in individuals who are sensitive to latex.

Drug Packaging↗
PubMed1999

Analysis of gene mutations and clastogenicity following short-term treatment with azathioprine in MutaMouse.

The mutagenicity and clastogenicity of the immunosuppressive drug azathioprine (AZA), a multitissue rodent carcinogen and IARC-classified human carcinogen, was investigated using transgenic lacZ mice (MutaMouse). Male animals (n = 5 per group) were dosed with AZA (10, 50, 100 mg/kg p.o. daily for 5 days), vehicle (n = 10), or the positive control, chlorambucil (15 mg/kg i.p., n = 3), and killed 24 hr or 25 days after the last treatment. Micronucleus assays were performed with bone marrow (24-hr samples) or peripheral blood (24-hr and 25-day samples) and DNA was extracted from bone marrow and liver for gene mutation analysis at the transgenic lacZ locus. AZA induced 5.3-111.3-fold increases in %MNPCE (P < 0.01) in bone marrow compared with vehicle control, accompanied by 4.4-5. 6-fold increases in %MNRETs (P < 0.01) in peripheral blood. Chlorambucil caused a 14.5-fold increase in %MNRET and there was evidence of significant stem cell toxicity in both positive control and AZA treatment groups. By day 25, however, there was evidence of substantial recovery of the bone marrow as determined by the frequency of RET, and the %MNRET in all treatment groups was the same as the vehicle control. Analysis of lacZ MF showed 1.4-1.6-fold increases in AZA 24-hr bone marrow samples, increasing to approximately 2.0-fold above concurrent controls by day 25 (medium dose P < 0.05, high dose P < 0.01). For liver, there was a 2-fold increase in MF (P < 0.05) in the 24-hr sample at the highest dose only, and increases of 1.3-1.5-fold by day 25 in the medium (P < 0. 05) and high (P = 0.055) dose groups, respectively. The positive control, chlorambucil, induced 2-3-fold increases (P < 0.01) in mean MF in both bone marrow (25-day sample) and liver (24-hr and 25-day samples). These data confirm the clastogenicity of AZA in the mouse, and show that this compound induces gene mutations in bone marrow and liver, in vivo, at the highest dose and supports the view that AZA is a genotoxic carcinogen.

Animals↗
PubMed1998

Depletion of endogenous dopamine stores and shift in beta-adrenoceptor subtypes in cardiac tissue following five weeks of chronic denervation.

Surgical ablation of extrinsic cardiac nerve fibers results in a chronically denervated state of the left ventricle of the heart. The present study was performed to elucidate the effect of a period of 5 weeks of chronic denervation on cardiac catecholamine levels in general and dopamine in particular. Moreover, the possible effect on cardiac beta-adrenoceptor subtypes was investigated. Experiments were performed on adult dogs. In addition to adrenaline and noradrenaline the tissue levels of dopamine were found to be severely depressed. A significant shift from beta1- to beta2-adrenoceptor subtype was observed, while the total beta-adrenoceptor density remained unaffected. The present findings indicate that catecholamine synthesis in chronically denervated hearts is impaired upstream of dopamine and that a shift in beta-adrenoceptor subtype occurs already within a relatively short period of five weeks of denervation, and suggest that the lack of endogenous catecholamines influence the relative expression levels of the two subtypes of beta-adrenoceptors present in cardiac tissue.

Animals↗
PubMed1998

The PK domain of the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) is required for immediate-early gene expression and virus growth.

The large subunit of herpes simplex virus (HSV) ribonucleotide reductase (RR), RR1, contains a unique amino-terminal domain which has serine/threonine protein kinase (PK) activity. To examine the role of the PK activity in virus replication, we studied an HSV type 2 (HSV-2) mutant with a deletion in the RR1 PK domain (ICP10DeltaPK). ICP10DeltaPK expressed a 95-kDa RR1 protein (p95) which was PK negative but retained the ability to complex with the small RR subunit, RR2. Its RR activity was similar to that of HSV-2. In dividing cells, onset of virus growth was delayed, with replication initiating at 10 to 15 h postinfection, depending on the multiplicity of infection. In addition to the delayed growth onset, virus replication was significantly impaired (1,000-fold lower titers) in nondividing cells, and plaque-forming ability was severely compromised. The RR1 protein expressed by a revertant virus [HSV-2(R)] was structurally and functionally similar to the wild-type protein, and the virus had wild-type growth and plaque-forming properties. The growth of the ICP10DeltaPK virus and its plaque-forming potential were restored to wild-type levels in cells that constitutively express ICP10. Immediate-early (IE) genes for ICP4, ICP27, and ICP22 were not expressed in Vero cells infected with ICP10DeltaPK early in infection or in the presence of cycloheximide, and the levels of ICP0 and p95 were significantly (three- to sevenfold) lower than those in HSV-2- or HSV-2(R)-infected cells. IE gene expression was similar to that of the wild-type virus in cells that constitutively express ICP10. The data indicate that ICP10 PK is required for early expression of the viral regulatory IE genes and, consequently, for timely initiation of the protein cascade and HSV-2 growth in cultured cells.

Animals↗
PubMed1998

Spinal epidural abscess: the importance of early diagnosis and treatment.

OBJECTIVES: To remind clinicians of the dangers of delayed diagnosis and the importance of early treatment of spinal epidural abscess. METHODS: A review of the literature on spinal epidural abscess and a comparison of the published literature with local experience. RESULTS: Imaging with MRI or CT enables early diagnosis of spinal epidural abcess and optimal therapy is surgical evacuation combined with 6-12 weeks (median 8 weeks) of antimicrobial chemotherapy. Clinical features are fever, pain, and focal neurological signs and may be associated with preceding and pre-existing bone or joint disease. The commonest aetiological organism is S aureus. CONCLUSION: Early diagnosis and appropriate early antimicrobial chemotherapy with surgery is associated with an excellent prognosis.

Abscess↗
PubMed1998

Raw egg ingestion and salmonellosis in body builders.

Four patients with Salmonella enteritidis infection are reported. All were body builders who regularly consumed substantial quantities of raw eggs. They presented with a severe febrile illness and diarrhoea--presumably reflecting a large bacterial inoculum. Advice regarding the potential hazards of raw egg ingestion has been repeatedly issued by the Department of Health--but this report highlights the fact that this practice continues in spite of this. The epidemiology of S. enteritidis infection in relation to raw egg ingestion is discussed.

Adult↗
PubMed1998

Prevalence of serum antibodies to LA-1 oncoprotein, herpes simplex virus type-2 glycoprotein and human papillomavirus type 16 transactivator (E2) protein among Indian women with cervical neoplasia.

Prevalence of serum antibodies to synthetic peptide to oncoprotein of LA-1 known as oncogene of herpes simplex virus type-2, herpes simplex virus type-2 glycoprotein-D as an determinant of viral pathogenicity and human papillomavirus type 16 transactivator E2 protein was studied among 46 Indian women with cervical neoplasia using immunoblot assay for HSV-2 gD glycoprotein and LA-1 antibodies as well as peptide ELISA assay to detect HPV16 E2 antibodies. The seropositivity to LA-1 oncoprotein was found to be high (61%) among patients with invasive cervical carcinoma as compared to 35% in various grades of cervical intraepithelial neoplasia (CIN) and 36% in normal control women. In contrast to this, a uniformly high frequency of antibody to HPV 16 E2 was observed among women with CIN (68%), normal healthy controls (50%) and invasive cervical carcinoma (43%). However, a low frequency of seropositivity (13%) to recombinant vaccinia virus HSV-2 gD protein was found among 15 tested sera each from group of women with various grades of CIN as well as invasive cervical carcinoma as compared to 28% among seven normal healthy control. A negative correlation of LA-1 and HPV16 E2 seropositivity on patient by patient comparison among CIN and invasive cervical carcinoma group was observed which is statistically significant (P = 0.019 for CIN; P = 0.038 for invasive cervical carcinoma). However, a positive correlation (P = 0.144) was found among normal control women. The study has shown a desirable serological marker of cervical neoplasia. This serological marker could be employed as a screening tool in conjunction with cytopathological screening to diagnose women harbouring LA-1 oncogene associated cervical lesions.

Adult↗
PubMed1997

Stimulated release of the beta-amyloid protein of Alzheimer's disease by normal human platelets.

The circulatory system is a potential source of the beta-amyloid protein (A beta) of ageing and Alzheimer's disease (AD), platelets accounting for the bulk of A beta immunoreactivity detectable in blood. Evidence for the release of A beta by platelets, however, has not been reported. Platelets from normal donors were therefore stimulated with collagen to establish if A beta immunoreactive material is released on activation. For comparison, the release of the platelet monoamines, serotonin (5-HT) adrenaline (Adr) and noradrenaline (NA) was also measured. Like the monoamines, collagen-induced A beta release was concentration-dependent, maximal stimulated release exceeding basal efflux by 184%. Collagen EC50 values for A beta release were similar to those for Adr and NA (3.6 +/- 0.6, 3.4 +/- 0.6 and 3.3 +/- 0.2 microg/ml collagen, respectively) but not 5-HT (9.8 +/- 1.9 microg/ml). These data provide the first evidence that platelets release A beta immunoreactive material on stimulation and may indicate that A beta, Adr and NA reside in the same subcellular compartment.

Adult↗
PubMed1997

The large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) is associated with the virion tegument and has PK activity.

The large subunit of herpes simplex virus type 2 (HSV-2) ribonucleotide reductase (ICP10) was identified in sucrose gradient-purified HSV-2 virions by immunoprecipitation/immunoblotting with antibody specific for the protein kinase (PK) domain. Immunoblotting of individual gradient fractions indicated that ICP10 cosediments with the major capsid protein and the highest virus titers. ICP10 was not labeled by iodination of purified virions, indicating that it is not located on the virion surface. After envelope glycoproteins were removed by detergent treatment, ICP10 was associated with capsid-tegument particles and became sensitive to trypsin digestion. The capsid-tegument-associated ICP10 was phosphorylated and had PK activity in vitro and on Immobilon membranes. A mutant ICP10 protein deleted in the PK domain (p95) was also associated with purified virions (ICP10deltaPK virus) but it lacked PK activity. The data indicate that ICP10 is contained within the tegument component where it retains intrinsic PK activity.

Herpesvirus 2, Human↗
PubMed1997

Behavioral and neuroendocrine responses in shy children.

Previous research has shown that infants who display a high frequency of motor activity and negative affect at 4 months of age are likely to be behaviorally inhibited toddlers. We examined social behaviors, maternal report of temperament, salivary cortisol, and baseline startle responses at age 4 in a sample of children, some of whom displayed a high frequency of motor activity and negative affect at 4 months of age. Infants who displayed this temperamental profile were reported by their mothers as more shy at age 4 compared with other children. We also found that 4-year-olds who displayed a high frequency of wary behavior during peer play exhibited relatively high morning salivary cortisol, were reported as contemporaneously shy by their mothers, and were behaviorally inhibited at 14 months of age. There were no significant relations found between baseline startle and morning salivary cortisol and measures of shyness at age 4. We speculate that high levels of cortisol in shy children may induce changes in the amygdala, exacerbating their fearfulness.

Affect↗
PubMed1997

Reduced platelet serotonin content and release in familial hypercholesterolaemia.

Plasma and platelet serotonin (5-HT) concentrations, and resting and collagen-induced 5-HT release in platelet-rich plasma were studied in normal and familial hypercholesterolaemic (FH) subjects. Platelet 5-HT concentrations were significantly reduced (-37%, P < 0.01) in FH patients whilst mean plasma concentrations, although increased, were not significantly different from those in normal subjects. Platelet 5-HT correlated negatively with plasma cholesterol when the data for normal subjects and FH, patients were combined (r = -0.48, P = 0.005). It also correlated negatively with low-density lipoprotein (LDL) (FH data, r = -0.59, P = 0.03; normal and FH data, r = -0.49, P = 0.004) but positively with high-density lipoprotein (HDL) (FH r = 0.79, P = 0.001; normal and FH, r = 0.37, P = 0.03). Collagen (5-160 micrograms/ml) stimulated platelet 5-HT release occurred in a concentration-dependent manner. In FH patients stimulated 5-HT release was reduced (10 micrograms/ml collagen, -40%, P < 0.05) and accompanied by increased collagen EC50 values (P < 0.02). Resting 5-HT release was increased substantially in FH patients but not significantly. Our data provide evidence for a relationship between circulating cholesterol and platelet serotonergic mechanisms. It is proposed that abnormalities relating to platelet-plasma 5-HT dynamics, perhaps due to enhanced platelet activity or decreased platelet uptake, may contribute to the cardiovascular complications in FH.

Adult↗
PubMed1997

In vitro adrenaline and collagen-induced mobilization of platelet calcium and its inhibition by naftopidil, doxazosin and nifedipine.

AIMS: The aim of the study was to obtain further information regarding the modes of action of doxazosin, naftopidil and nifedipine on platelet function. METHODS: We conducted an in vitro study of drug influences on adrenaline and collagen-induced mobilization of platelet calcium. RESULTS: In the presence of fibrinogen (300 micrograms ml-1) both collagen (5 micrograms ml-1) and adrenaline (16 microM) stimulated the aggregation of washed platelets. Collagen induced a transient rise (+4.97 +/- 0.63 microM) in platelet Ca2+ concentration, [Ca2+]i, as measured using the photoprotein aequorin, which coincided with the onset of aggregation. Adrenaline induced a smaller rise (+3.6 +/- 0.96 microM) which, however, occurred after the onset of aggregation. Naftopidil, an alpha 1-adrenoreceptor antagonist produced a concentration-dependent inhibition of collagen-induced Ca2+ mobilization, maximum inhibition (22.9 +/- 4%, P < 0.05) occurring with 40 microM naftopidil. The inhibition of Ca2+ mobilization was not reflected by a concentration-dependent inhibition of platelet aggregation, although 40 microM naftopidil produced statistically significant inhibition (23.3 +/- 11.7%, P < 0.05). The adrenaline-induced rise in [Ca2+]i was inhibited dose dependently by naftopidil (e.g. 40 microM naftopidil, 100 +/- 0%, P < 0.05), as was aggregation (40 microM naftopidil, 100 +/- 0%, P < 0.05). Doxazosin, another alpha 1-adrenoreceptor blocker, inhibited Ca2+ mobilization induced by collagen to similar extents as for naftopidil (30 microM doxazosin, 17.4 +/- 2.5%, P < 0.05), but did not inhibit platelet aggregation. It also inhibited the adrenaline-induced rise in [Ca2+]i in a concentration-dependent manner (30 microM doxazosin, 37.6 +/- 13.7%, P < 0.05), significant inhibitions of platelet aggregation also being produced (30 microM, 49.6 +/- 17.2%, P < 0.05). As expected, the calcium channel blocker nifedipine produced concentration-dependent inhibitions of both collagen-induced Ca2+ mobilization (e.g. 28 microM nifedipine, 47.8 +/- 2.7%, P < 0.05) and aggregation (28 microM, 55.1 +/- 9.2%, P < 0.05). CONCLUSIONS: These data indicate that the alpha 1-adrenoreceptor blockers, naftopidil and doxazosin, inhibit Ca2+ mobilization, this mechanism being possibly the means whereby these drugs inhibit platelet aggregation.

Adrenergic alpha-Antagonists↗
PubMed1997

An investigation into the release and mobilisation of sulphate-conjugated catecholamines by human platelets.

Collagen (5-160 microg/ml) induced release of free and sulphate conjugated noradrenaline (NA), adrenaline (Ad) and dopamine (DA) by platelets in platelet-rich plasma (PRP) was investigated in human subjects. Stimulated efflux of free NA, Ad and DA to the plasma (platelet-poor plasma; PPP) increased in a concentration-dependent manner, NA release being reflected by reduced platelet free NA contents. Collagen EC(50) values for free NA, Ad and DA release were similar, i.e. 3.8, 3.3 and 4.5 microg/ml collagen, respectively. Subtracting resting PPP free catecholamine (CA) concentrations from those obtained with 160 microg/ml collagen revealed that 52%, 31% and 33% of PPP free NA, Ad and DA, respectively, resulted from collagen stimulation. Under resting conditions sulphate conjugated NA, Ad and DA accounted for 74%, 78% and 99% of total (sum of free and sulphate conjugated) PPP concentrations. Collagen elicited concentration-dependent release of sulphate conjugated DA and, to a lesser extent, NA, but not Ad. Sulphate conjugated NA release was mirrored by decreases in platelet sulphate conjugated NA contents. Resting platelet sulphate conjugated NA and Ad represented 42% and 50% of total (free plus sulphate conjugated) NA and Ad concentrations. EC(50) values for sulphate conjugated DA and NA release were, respectively, 14.5 and 6.25 microg/ml collagen, which exceeded the values for free DA and NA release by 222% and 64%. With 160 microg/ml collagen 44% and 15% of PPP sulphate conjugated DA and NA, respectively, had resulted from platelet activation, and of the total (sum of free and sulphate conjugated) DA and NA released, 99.5% and 39.7% were sulphate conjugated. Total (sum of PPP and platelet) free and sulphate conjugated NA and Ad concentrations were unaltered by collagen stimulation indicating that platelet activation does not cause mobilisation (i.e. hydrolysis) of platelet sulphate conjugated CA. Thus, platelet activation causes the liberation of sulphate conjugated CA (particularly DA) as well as free CA. The differences with regard to the collagen EC(50) values for free and sulphate conjugated CA release indicate that these species arise from different subcellular compartments.

Journal Article↗