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Biomedical subjects

J H McKillop

Publications and source records attributed to J H McKillop.

At least 19 recordsLinked to original sources
PubMed2001

Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study.

BACKGROUND: We examined the development of new diabetes mellitus in men aged 45 to 64 years during the West of Scotland Coronary Prevention Study. METHODS AND RESULTS: Our definition of diabetes mellitus was based on the American Diabetic Association threshold of a blood glucose level of >/=7.0 mmol/L. Subjects who self-reported diabetes at baseline or had a baseline glucose level of >/=7.0 mmol/L were excluded from the analyses. A total of 5974 of the 6595 randomized subjects were included in the analysis, and 139 subjects became diabetic during the study. The baseline predictors of the transition from normal glucose control to diabetes were studied. In the univariate model, body mass index, log triglyceride, log white blood cell count, systolic blood pressure, total and HDL cholesterol, glucose, and randomized treatment assignment to pravastatin were significant predictors. In a multivariate model, body mass index, log triglyceride, glucose, and pravastatin therapy were retained as predictors of diabetes in this cohort. CONCLUSIONS: We concluded that the assignment to pravastatin therapy resulted in a 30% reduction (P:=0.042) in the hazard of becoming diabetic. By lowering plasma triglyceride levels, pravastatin therapy may favorably influence the development of diabetes, but other explanations, such as the anti-inflammatory properties of this drug in combination with its endothelial effects, cannot be excluded with these analyses.

Anticholesteremic Agents↗
PubMed2000

Antioxidants: their role in pregnancy and miscarriage.

The aim of this study was to examine the role of antioxidants within the normal menstrual cycle, in healthy pregnancy, and in women suffering first-trimester miscarriage. The antioxidants chosen comprised of two from peripheral blood-plasma thiol and ceruloplasmin-and two extracellular parameters-superoxide dismustase (SOD) and red cell lysate thiol. We found that antioxidant levels varied little throughout the menstrual cycle. Pregnancies that went successfully to term were associated with increased levels of ceruloplasmin and SOD early in the first trimester. These changes were thought to offer the cell protection from the damage caused by the increased oxidative stress associated with pregnancy. First-trimester miscarriage was associated with significantly reduced levels of SOD. A subgroup of patients who miscarried in their first pregnancy, but whose second pregnancies were successful, had higher levels of plasma thiol and significantly reduced levels of red cell lysate thiol in the on-going pregnancy compared to levels at the time of miscarriage. Miscarriage and pregnancy appear to be associated with increased oxidative stress. In a successful pregnancy, however, changes occurred within the peripheral blood that offered protection from oxidant attack.

Abortion, Spontaneous↗
PubMed2000

99Tcm-HMPAO leucocyte labelling in orofacial granulomatosis and gastrointestinal Crohn's disease in childhood and early adulthood.

Orofacial granulomatosis is a granulomatous inflammatory disorder, affecting the soft tissues of the face and mouth. The predominant feature is disfiguring lip swelling. Patients with this condition may be exhibiting a Type IV hypersensitivity reaction to dietary or environmental allergens, or these may be the orofacial manifestations of underlying gastrointestinal Crohn's disease. The results of 99Tcm-HMPAO leucocyte labelling of the gastrointestinal tract in 14 patients with orofacial granulomatosis and 15 patients with known gastrointestinal Crohn's disease are presented, indicating that this is a useful and non-invasive screening test for the identification of gastrointestinal Crohn's disease in paediatric and young adult patients presenting with orofacial granulomatosis.

Adolescent↗
PubMed1999

Thyroid antibody titer and avidity in patients with recurrent miscarriage.

OBJECTIVE: To determine whether the titer and avidity of the thyroid peroxidase antibody differs between pregnant women in their first trimester who have a history of recurrent miscarriage and whose pregnancies continue to term and those whose pregnancies fail again later in the first trimester. DESIGN: Controlled clinical study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Pregnant women in their first trimester who had a history of recurrent miscarriage (> or = 3 miscarriages) and who were known to be positive for the thyroid peroxidase antibody. INTERVENTION(S): None of the patients received any medication. MAIN OUTCOME MEASURE(S): Thyroid peroxidase antibody titer and avidity (i.e., the net binding strength between antibody and antigen). RESULT(S): At the time of presentation, thyroid peroxidase antibody titer and avidity was significantly higher in those women who later miscarried compared with those whose pregnancies continued. In those whose pregnancies continued to term, titer and avidity declined as the pregnancy progressed. CONCLUSION(S): Autoimmunity plays a role in recurrent miscarriage. Among a group of patients who had had recurrent miscarriages, there appeared to be differences in the humoral response to the pregnancy between those whose pregnancies continued to term and those whose pregnancies failed again.

Abortion, Habitual↗
PubMed1998

A preliminary evaluation of diagnostic odds in lung scan reporting.

Reporting of lung scans for pulmonary embolism (PE) using a descriptive probability notation is tried and tested. Subjectivity in interpretation of this jargon can be a problem for internists. Parallel descriptive and numerical probability reporting has been recommended, but the numerical probability scale is less precise than likelihood ratios expressed as odds. We therefore assessed internists' intuitive understanding of lung scan reports in the odds format compared to the descriptive probability notation. A questionnaire was sent to Scotland's 217 internists to assess their intuitive understanding of odds reporting and to compare their management strategies when confronted by lung scan reports in both an odds and a descriptive probability notation. There was a broad understanding of numerical odds. Internists used 'normal' and '100:1 against PE' identically; similarly, 'low probability' and '10:1 against PE'. There was a statistically significant preference for the diagnosis of PE when internists were given the '1:1 evens' report compared with the 'indeterminate' report. There does appear to be a greater awareness of the risk of PE when non-diagnostic lung scans are reported in numerical odds as compared with the descriptive probability format.

Diagnosis, Differential↗
PubMed1998

Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.

PURPOSE: To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS: Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS: One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION: A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.

Adult↗
PubMed1998

Evidence for carbimazole as an antioxidant?

There is evidence in the literature to support the view that antioxidants are involved in the pathogenesis of Graves disease and that antioxidants may act as free radical scavengers. This study has compared the effects of a 12 month course of conventional Carbimazole therapy on peripheral blood antioxidant levels with those of a 12 month course of a higher dose treatment regime. Fifty seven patients were enrolled into the study. Those in Group 1 (n = 23) received a 12 month course of 60 mg/day Carbimazole. Those in Group 2 (n = 34) received 45 mg/day for the first month, 30 mg/day for the second and 20 mg/day for the remaining 10 months of treatment. T3 was added in both groups after 2-4 months to maintain patients euthyroid. Baseline samples were also obtained from 30 control subjects. Blood samples were taken for the measurement of plasma thiol (PSH), lysate thiol (LSH), superoxide dismutase (SOD) and caeruloplasmin (CP) and for routine thyroid function tests (TT4, TT3 and TSH). In untreated Graves' patients, serum levels of PSH and SOD were reduced and levels of LSH increased compared to controls. Following 2 months high dose Carbimazole therapy there was a significant increase in PSH levels and a significant reduction in CP levels compared to presentation levels. In the more conventional dose Group 2 patients PSH levels also rose significantly during the first 2 months of treatment. Levels for both groups were still significantly lower than the control group. After 12 months high dose Carbimazole therapy PSH levels had decreased so that they no longer differed from untreated levels. LSH and SOD levels still remained abnormal. CP levels continued to fall. Similar findings were obtained in those patients receiving the more conventional course of treatment. At no point was their any significant difference in antioxidant levels between the two treatment groups. The abnormal levels of antioxidants in the serum of untreated Graves' patients confirm their involvement in the pathogenesis of Graves' disease. Carbimazole therapy appeared to have only short term effects on the peripheral blood levels of the antioxidants measured. Carbimazole appeared to act only on the extra cellular markers of antioxidant activity (PSH, CP) although the disease itself had marked intracellular effects (LSH, SOD). These findings suggest that Carbimazole does not act as a free radical scavenger.

Adult↗
PubMed1997

Altered interleukin 12 and nitric oxide levels in recurrent miscarriage.

The causes of recurrent miscarriage are not fully understood. Recent studies have suggested that whilst a TH 2 type immune response may be associated with a healthy pregnancy, miscarriage may be associated with a TH 1 type response. Serum levels of nitric oxide (NO) and Interleukin 12 (IL 12) were measured in; healthy non-pregnant women; healthy pregnant women; women suffering spontaneous abortion; pregnant women with a history of recurrent miscarriage; non-pregnant women with a history of recurrent miscarriage. Normal pregnancy was associated with a significant decrease in serum levels of nitrite (13.0 vs. 22.0 P < 0.0001). In women admitted with spontaneous abortion there was a significant increase in the levels of nitrite (16.0 vs. 13.0 P < 0.05), but no change in IL 12 compared to normal pregnant women. In pregnant women with a history of recurrent miscarriage levels of nitrite (16.0 vs. 13.0 P < 0.05) and IL 12 (10.0 vs. 6.0 P < 0.0006) were significantly elevated compared to normal pregnancy. When these women were sampled prior to becoming pregnant the levels of NO were found to be significantly lower than those in the non-pregnant control group (13.1 vs. 22.0 P < 0.05) although levels of IL 12 were unchanged. No correlation was found between serum nitrite and IL 12 levels. This report further supports the idea that polarisation of the immune response during pregnancy may predispose to recurrent miscarriage.

Abortion, Habitual↗
PubMed1996

Tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in pre-eclampsia.

Pre-eclampsia is an endothelial disorder and TNF-alpha has fundamental effects on endothelial cells by several means, including altering the balance between oxidant and anti-oxidant, changing the pattern of prostaglandin production and affecting expression of several cell surface components. To determine whether TNF-alpha mRNA expression is increased in pre-eclamptic patients, leucocytes from pre-eclamptic patients, normal pregnant women and normal non-pregnant women were studied for TNF-alpha expression using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Using a model of 373A ABI Sequencer, TNF-alpha gene polymorphism was also analysed by GENESCAN and Genotyper software in order to explain the mechanism of abnormal TNF-alpha expression. Our results show that TNF-alpha mRNA expression is significantly elevated in pre-eclamptic patients compared with the other two control groups. The high expression of TNF-alpha may be associated with the TNF1 allele, whose frequency is markedly increased in pre-eclamptic patients. These observations are consistent with a major role for TNF-alpha in mediating endothelial disturbances, and suggest a key role for TNF-alpha in the development of pre-eclampsia.

Adult↗
PubMed1996

Recurrent miscarriage is associated with increased numbers of CD5/20 positive lymphocytes and an increased incidence of thyroid antibodies.

The aim of this study was to determine whether recurrent miscarriage (three or more miscarriages, no live children) was associated with an increased incidence of autoantibodies. Five groups were enrolled into the study; healthy non-pregnant women, healthy first-trimester pregnant women, women suffering spontaneous abortion, those undergoing termination of pregnancy and those with a previous history of miscarriage. The number of total B cells and the numbers of the antibody producing B cell subset CD5+/CD20+ were determined for each group. Samples were tested for anticardiolipin antibodies, antinuclear antibodies and thyroid microsomal and thyroglobulin antibodies. The results showed that compared to normal pregnancy or spontaneous abortion, recurrent miscarriage was associated with a significant increase in the number of CD5+/20+ positive cells (0.8 +/- 0.3 vs 0.5 +/- 0.1 vs 1.1 +/- 0.3 x 10(8)/l; p < 0.001). These women were also found to have a higher incidence of thyroid antibodies, with four out of the 11 patients being positive for thyroid microsomal antibodies. These results suggest that there may be an association between autoimmunity and recurrent miscarriage.

Abortion, Habitual↗
PubMed1996

An increased incidence of thyroid antibodies in patients with Turner's syndrome and their first degree relatives.

Previous studies have suggested that there may be a link between Turner's syndrome and autoimmunity. The numbers involved in these studies have tended to be small and few studies have included family members. This study has compared the incidence of thyroid antibodies in the serum of 60 patients with Turner' syndrome and 50 of their mothers with 127 controls. Total T4 and TSH levels were also measured. Of the 60 patients with Turner's syndrome 18 (30%) were positive for either thyroid peroxidase (TPO) and/or thyroglobulin antibodies. The peak incidence of thyroid antibodies occurred at 13 years of age. 11 (22%) of the mothers were also antibody positive. The incidence of thyroid antibodies was significantly higher in both the patients with Turner's Syndrome (30 vs 1.7% p < 0.001) and their mothers (22 vs 6.6% p < 0.05) than in the control groups. The increased incidence of thyroid antibodies found in these patients and their mothers confirms that there is an association between Turner's Syndrome and autoimmunity. However unlike previous studies we found more patients were positive for thyroglobulin than TPO antibodies.

Adolescent↗
PubMed1995

Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group.

BACKGROUND: Lowering the blood cholesterol level may reduce the risk of coronary heart disease. This double-blind study was designed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infarction reduced the combined incidence of nonfatal myocardial infarction and death from coronary heart disease. METHODS: We randomly assigned 6595 men, 45 to 64 years of age, with a mean (+/- SD) plasma cholesterol level of 272 +/- 23 mg per deciliter (7.0 +/- 0.6 mmol per liter) to receive pravastatin (40 mg each evening) or placebo. The average follow-up period was 4.9 years. Medical records, electrocardiographic recordings, and the national death registry were used to determine the clinical end points. RESULTS: Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent, whereas there was no change with placebo. There were 248 definite coronary events (specified as nonfatal myocardial infarction or death from coronary heart disease) in the placebo group, and 174 in the pravastatin group (relative reduction in risk with pravastatin, 31 percent; 95 percent confidence interval, 17 to 43 percent; P < 0.001). There were similar reductions in the risk of definite nonfatal myocardial infarctions (31 percent reduction, P < 0.001), death from coronary heart disease (definite cases alone: 28 percent reduction, P = 0.13; definite plus suspected cases: 33 percent reduction, P = 0.042), and death from all cardiovascular causes (32 percent reduction, P = 0.033). There was no excess of deaths from noncardiovascular causes in the pravastatin group. We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group (95 percent confidence interval, 0 to 40 percent; P = 0.051). CONCLUSIONS: Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.

Anticholesteremic Agents↗
PubMed1995

Dynamic hepatic scintigraphy in colorectal cancer.

The clinical usefulness of the hepatic perfusion index (HPI) at the time of presentation has been evaluated in patients with colorectal cancer. In 83 consecutive patients, the HPI was abnormally elevated in 34 of 37 (93%) patients with overt metastases. This study confirms that the HPI is elevated in most patients with overt hepatic metastases. Long-term follow-up of patients with abnormal HPI and no obvious liver metastases is continuing.

Carcinoma↗
PubMed1995

Indium-111 leucocyte scintigraphy and ultrasound scanning in the detection of intra-abdominal abscesses in patients without localizing signs.

The clinical records of 45 patients with suspected intra-abdominal sepsis but without localizing abdominal signs were retrospectively reviewed. All had undergone both indium-111 leucocyte scintigraphy and real time ultrasound. Twenty-two of the 45 patients were subsequently shown to have intra-abdominal abscesses. Twenty-one patients were identified correctly by indium-111 scintigraphy (sensitivity 95%) and 10 by ultrasound (US: sensitivity 45%). There were two false positive scintiscans (specificity 91%) but no false positive US scans (specificity 100%). There was no correlation between the peripheral white cell count and the presence of absence of an abscess or the likelihood of obtaining a positive scintiscan result. Because of the excellent specificity ultrasound scanning should remain the initial investigations in this group of critically ill patients with indium-111 scintigraphy being used to clarify the US findings or in US negative patients.

Abdominal Abscess↗
PubMed1994

Immunological changes in pregnancy-induced hypertension.

Aspects of T and B cell function were studied in women with pregnancy-induced hypertension (PIH) and normotensive pregnant women by determining the proliferation of peripheral blood mononuclear cells (PBMC) with or without stimulation by mitogens (PHA, ConA and PWM) and by determining IgG and IgM levels in the culture supernatant. The results showed that the proliferation of PBMC without mitogens was significantly increased in PIH women without proteinuria compared with normotensive pregnant women. In the presence of PHA, [3H]thymidine uptake in PBMC was statistically higher in PIH women both with and without proteinuria than that in normotensive pregnant women. ConA and PWM mitogen activities were not significantly different between PIH women and normotensive pregnant women. Compared with normotensive pregnant women, IgG production was significantly increased in PIH women with proteinuria but not in those without proteinuria. IgM production was not changed in PIH women. We concluded that immunologic responses in PIH women were increased rather than decreased. This increased immunologic activity is in accordance with some important changes seen in PIH, such as an increase in intracellular calcium, the presence of blood-borne mitogenic factor and a decrease in prostaglandin E series. These findings also support the hypothesis that PIH might result from the imbalance between fetal antigenic load and maternal production of immunologic blockade.

Adult↗
PubMed1994

The role of nuclear cardiology in hypertension.

In view of the increased risk of cardiac events in systemic hypertension, particularly in patients with left ventricular hypertrophy, it is important to have reliable methods of assessing cardiac structure and function and myocardial perfusion in these patients. While echocardiography is the noninvasive method of choice for measuring the severity of left ventricular hypertrophy there is no alternative at present to invasive coronary angiography to define accurately coronary artery anatomy. Nuclear cardiological investigations are extremely useful in the assessment of systolic and diastolic function at rest and during exercise. Furthermore, myocardial perfusion imaging is of value in identifying myocardial ischaemia and assessing the functional importance of coronary artery lesions. Recent studies have also suggested that nuclear cardiology investigations may be the best way to identify nonfunctioning but viable areas of the myocardium which may benefit from revascularization.

Coronary Disease↗
PubMed1994

The role of cytokines in the production of prostacyclin and thromboxane in human mononuclear cells.

The aim of the present work was to study the regulatory effects of cytokines (TNF alpha, IL-1 beta and IL-2) on the production of the prostglandins (PGI2 and TXA2) from human mononuclear cells. Our major findings were: (1) TNF alpha, IL-1 beta and IL-2 were all able to induce PGI2 and TXA2 syntheses in mononuclear cells. (2) TNF alpha exerted a biphasic effect on prostaglandin production. The lower concentrations of TNF alpha enhanced prostaglandin synthesis while the higher concentrations did not. (3) TNF alpha had a positive effect after only a 30-minute incubation, whereas IL-1 beta and IL-2 required a 8-hour incubation to produce a significant effect. This suggests that the different mechanisms are involved in their actions. (4) The effects of cytokines on the production of PGI2 were greater than that on the production of TXA2. It is concluded that cytokines can not only regulate the production of prostaglandins but also change the pattern of their formation.

Cells, Cultured↗