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Biomedical subjects

N Kennedy

Publications and source records attributed to N Kennedy.

At least 37 records · Page 2Linked to original sources
PubMed2000

Olanzapine for chronic, stereotypic self-injurious behaviour: a pilot study in seven adults with intellectual disability.

Dopamine one (D1) receptor supersensitvity in the corpus striatum is said to be the primary mechanism within the dopamine model proposed for chronic, refractory self-injurious behaviour (SIB), which may explain why conventional neuroleptics have proven largely ineffective. In common with other atypical antipsychotic agents, olanzapine has more affinity for the D1 receptor. The present study explored whether olanzapine could reduce rates of the stereotypic form of chronic SIB, a subtype where dopamine dysfunction is the most likely underlying mechanism. A clinical sample of seven patients with various levels of learning disability who displayed features of stereotypic SIB were assessed over a 6-week period of baseline measurement and a 15-week treatment phase during which olanzapine was added to existing medication. Both SIB and other aberrant behaviours were measured by daily nurse rating and the Self-Injury Trauma Scale (SITS). All measurements were unblind. Doses ranged from 5 to 15 mg. Out of the seven subjects, three showed a clear improvement, one showed a marginal improvement, one deteriorated, and the data was equivocal for the remaining two individuals. The means of the SITS Number and Severity Indices (NI and SI, respectively) reduced significantly from baseline during both the 5- and 10-mg treatment phases, and taking treatment as a whole, by 53% and 48%, respectively (NI: mean = 0.7 units reduction, P = 0.02; SI: mean = 0.9 units reduction, P = 0.04). The risk index also reduced, but did not reach significance. A modest reduction in mean nurse-rated SIB was not significant for either phase or for treatment as a whole. At doses above 5mg, mean scores deteriorated on balance, although two responders showed a marginal additional improvement. Olanzapine was well tolerated with one adverse event reported (somnolence) which was mild and transient. The present pilot study suggests that olanzapine can reduce stereotypic SIB. A larger trial is indicated.

Adult↗
PubMed1998

Hepatitis G virus infection in drug users in Liverpool.

OBJECTIVES: To establish the prevalence of hepatitis G (HGV) in drug users in Liverpool; to explore the risk factors for, and the effects of, HGV infection. METHODS: Serum samples from 129 drug users who had attended the Infectious Diseases Unit at Fazakerley Hospital, Liverpool, between January 1995 and June 1996 were examined for HGV RNA using PCR, HGV RNA results were collated with demographic data, information on drug-use behaviour, hepatitis B (HBV) and C (HCV) serology, and the results of serum bilirubin and aspartate amino-transferase (AST) measurements. RESULTS: Overall, 37 (29%) of patients were HGV RNA positive, 89 (69%) were negative, and equivocal results were obtained in three (2%) cases. Direct sequencing of PCR products of the 5' non-translated region for 13 patients showed that these were generally more closely related to the HGV than the GB virus C (GBV-C) sequence. HGV co-infection with HCV and HBV was common: of HGV-positive patients, 28 (76%) and 16 (44%) had antibodies to HCV (anti-HCV) and hepatitis B core protein (anti-HBc), respectively. Increasing duration of injecting drug use was associated with a decreasing seroprevalence of HGV RNA, dropping from 39% for 0-4 years of injecting to 14% for > 12 years injecting. Serum bilirubin and AST values were frequently elevated, but statistical analysis showed no differences between HGV-positive and HGV-negative patient groups. CONCLUSIONS: HGV infection is common in drug users in Liverpool, but HGV RNA prevalence falls with increasing duration of injecting drug use, probably as a result of viral clearance and the development of protective immunity. HGV infection does not appear to be a significant cause of hepatic dysfunction in Liverpool drug users.

Adult↗
PubMed1998

Hepatitis B and hepatitis C virus infections: risk factors among drug users in Northwest England.

OBJECTIVES: to identify the risk factors for hepatitis B (HBV) and hepatitis C (HCV) virus infections in drug users attending two drug treatment centres in Northwest England, and to evaluate the effect of both needle exchange and hepatitis B vaccination on the prevalence of hepatitis B and hepatitis C infections. METHODS: a retrospective, cross-sectional study performed at the Regional Infectious Disease Unit and a Primary Care Centre for drug users in Liverpool. The study population included 773 drug users who had hepatitis serology performed between January 1992 and April 1996. Information on risk factors was obtained from clinical records; hepatitis serology data were obtained from the Liverpool Public Health Laboratory database. RESULTS: the overall seroprevalences of exposure markers for HBV (anti-HBc antibody) and HCV (anti-HCV antibody) were 48% and 67%, respectively. Duration of injecting drug use was the strongest predictor of HCV infection, with a crude odds ratio of 8.9 (95% confidence interval (CI): 4.5-17) for >10 compared to <3 years of injecting, and was also a strong predictor of HBV infection, with an adjusted odds ratio (controlled for the effects of HBV vaccination) of 5.7 (95% CI: 3.2-10) for >10 compared to <3 years' injecting. Vaccination against HBV was associated with greatly reduced HBV seroprevalence (crude odds ratio 0.11, 95% CI: 0.06-0.18). Overall, HCV was acquired earlier in the injecting career than HBV, but drug users who were not vaccinated against HBV acquired markers for HBV even more rapidly than for HCV. We found no independent protective effect for either anti-HBc or anti-HCV acquisition after the introduction of a needle-exchange scheme. CONCLUSIONS: hepatitis C is highly prevalent among Merseyside drug users and is likely to prove difficult to control because of rapid acquisition early in the injecting career. Vaccination against hepatitis B is the best means of protecting drug users from hepatitis B, and should be offered before injecting is commenced.

Adolescent↗
PubMed1998

Fluoroquinolones: a new treatment for tuberculosis?

The fluoroquinolones have secured an important place in the management of bacterial infection, they are well absorbed orally, are found in respiratory secretions in higher concentrations than in serum and are concentrated inside macrophages. The agents are well tolerated and have an excellent safety record in long-term therapy. No new antituberculosis agents have been developed since the introduction of rifampicin into clinical use, so fluoroquinolones have been investigated for potential efficacy in tuberculosis. In vitro studies have shown that they are active against Mycobacterium tuberculosis at achievable concentrations. Treatment studies in mice have demonstrated efficacy. Few clinical studies have been performed in humans, but ciprofloxacin has demonstrated significant early bactericidal activity. Regimens including a fluoroquinolone have been comparable to other standard regimens, although the outcome in human immunodeficiency virus (HIV) seropositive patients was significantly poorer. There is still insufficient clinical data to use fluoroquinolones in first-line treatment of tuberculosis, but they may find a role in the management of multidrug-resistant infections or in patients with adverse reactions to other agents.

AIDS-Related Opportunistic Infections↗
PubMed1997

A study of dementia in adults with Down's syndrome using 99Tc(m)-HMPAO SPET.

Twenty-six people with Down's syndrome (DS) were investigated using 99Tc(m)-hexamethylpropylene amine oxime (99Tc(m)-HMPAO) and single photon emission tomography (SPET). Dementia was diagnosed using a structured carer interview giving a deterioration score and by studying the case notes. Five subjects were clinically demented, 7 showed mild deterioration and 14 no deterioration. Increased deterioration correlated with advancing age (correlation coefficient 0.5425; P<0.02), but there was no significant difference between older (>40 years) and younger (<40 years) patients. Only one of the subjects with dementia had a regional cerebral blood flow (rCBF) abnormality that was of the dementia of Alzheimer type. Three subjects with mild deterioration and three with no deterioration had abnormal SPET scans. There was no association between the SPET abnormality and clinical dementia or with evidence of deterioration.

Adult↗
PubMed1997

Faulty sausage production causing methaemoglobinaemia.

A family outbreak of methaemoglobinaemia following ingestion of sausages made using 'saltpetre' is reported. Saltpetre is a generic term for several potassium and sodium based compounds. On this occasion imprecise ordering led to the use of sodium nitrite rather than the usual potassium nitrate, with extremely serious consequences.

Adolescent↗
PubMed1996

Evaluation of the safety and efficacy of micronized halofantrine in the treatment of semi-immune patients with acute, Plasmodium falciparum malaria.

The efficacy of the standard formulation of halofantrine hydrochloride has been compromised by the formulation's irregular bio-availability. A micronized preparation of the drug has now been evaluated in the treatment of malaria in northern Tanzania. Overall, 100 patients with mild to moderate Plasmodium falciparum malaria were recruited and treated with the preparation over 18 h. Those weighing > 40 kg were each given three, 500-mg doses and those weighing less were given roughly equivalent doses/kg. The 95 evaluable patients were all successfully treated, with a mean fever-clearance time of 22.5 h (range 4-76 h) and a mean parasite-clearance time of 35.6 h (range 15-66 h). There were no relapses. Abdominal pain was the commonest adverse event reported (22 cases). A single patient died suddenly in the recovery phase; the cause of this event was not determined. Further studies are required to evaluate the pharmacokinetics of the halofantrine formulation under field conditions.

Adolescent↗
PubMed1996

Randomized controlled trial of a drug regimen that includes ciprofloxacin for the treatment of pulmonary tuberculosis.

The fluoroquinolones are promising new antituberculous agents. A randomized controlled trial of 200 adult patients with sputum smear-positive pulmonary tuberculosis was conducted in Tanzania. Patients received either a trial regimen (HRC) consisting of isoniazid (300 mg), rifampin (600 mg), and ciprofloxacin (750 mg) or a control regimen (HRZE) consisting of isoniazid (300 mg), rifampin (600 mg), pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg). The 168 evaluable patients all had negative smears and cultures by month 6, but the time to conversion to negativity was longer for the HRC group than for the HRZE group because of the poor response of patients infected with human immunodeficiency virus (HIV) to the HRC regimen. Relapse was more frequent in the HRC group. The sterilizing activity of ciprofloxacin does not appear to be equal to that of the combination of pyrazinamide and ethambutol, but the difference in outcome was significant only among HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1995

Effects of adding spironolactone to an angiotensin-converting enzyme inhibitor in chronic congestive heart failure secondary to coronary artery disease.

In chronic heart failure, a diuretic plus an angiotensin-converting enzyme (ACE) inhibitor only partially suppresses aldosterone despite the fact that aldosterone has many harmful effects independent of angiotensin II. These possible harmful effects of aldosterone are magnesium loss, increased cardiac sympathetic activity, and increased ventricular arrhythmias. We have therefore assessed whether adding the aldosterone antagonist, spironolactone, to a loop diuretic and ACE inhibitor reverses any of these potentially harmful effects of residual aldosterone. In a preliminary animal study, we found that exogenous aldosterone reduced myocardial norepinephrine uptake by 24% in anesthetized rats in vivo. In our main study, 42 patients with New York Heart Association II to III congestive heart failure were randomized to spironolactone (50 to 100 mg/day, titrated to blood pressure and plasma potassium) or placebo in a double-blind fashion. Our principal finding is that cardiac norepinephrine uptake as assessed by 123I-metaiodobenzylguanidine scintigraphy increased with spironolactone (p < 0.01). Spironolactone also elevated plasma magnesium (p < 0.05), reduced urinary magnesium excretion (p < 0.05), and caused a reduction in ventricular arrhythmias on 24-hour ambulatory electrocardiography (p < 0.05). Spironolactone increased plasma renin activity, plasma aldosterone (p < 0.01), 24-hour urinary sodium excretion (p < 0.05), and urinary sodium/potassium ratio (p < 0.01). Echocardiographic-determined measurements of left ventricular systolic and diastolic function were unaltered by spironolactone.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Effects of lisinopril on congestive heart failure in normotensive patients with diastolic dysfunction but intact systolic function.

This study examined the effects of lisinopril on diastolic function in 12 normotensive patients (mean age 72 years) with symptomatic congestive heart failure, intact left ventricular systolic function and abnormal diastolic function secondary to ischaemic heart disease in a placebo-controlled double blind crossover study, with each treatment dosed orally for 5 continuous weeks. Compared to placebo, lisinopril significantly decreased blood pressure, increased plasma renin activity without altering heart rate or plasma norepinephrine. There was no statistically significant improvement with lisinopril in radionuclide derived peak filling rate and time to peak filling rate, in Doppler echocardiographic measurements of the ratio of peak flow velocity in early diastole to the peak flow velocity of atrial contraction (E:A ratio) and in visual analogue scales of symptoms. Thus, although angiotension converting enzyme inhibitors may have an established role in the treatment of heart failure secondary to left ventricular systolic dysfunction, its use in patients with isolated diastolic dysfunction remains unclear.

Aged↗
PubMed1995

Polysialylated neural cell adhesion molecule expression by neurons and astroglial processes in the rat dentate gyrus declines dramatically with increasing age.

The expression of polysialylated neurons in the dentate gyrus of the hippocampal formation of young (postnatal day 40), mature (postnatal day 80) and aged (postnatal day 540) male Wistar rats has been investigated by immunohistochemical techniques employing a monoclonal antibody specific for neural cell adhesion molecule-linked alpha 2,8 polysialic acid. A strong immunoreactivity was found on the cell bodies, dendrites and axons of granule-like neuronal cells at the border between the hilar region and the granule cell layer of the young rat. In the mature animal the number of immunoreactive neurons declined dramatically and were virtually absent in the aged group. Using an alternative fixation procedure, glial fibrillary acidic protein-positive and polysialylated astroglia processes were found in close proximity to the dendrites of the polysialylated granule-like cells. The number of astroglial processes traversing the granule cell layer showed a similar age-dependent decline to that observed with the polysialylated neurons. Glial fibrillary acidic protein-positive and polysialylated stellate astroglia were present throughout the hippocampal formation, but did not show the marked age-dependent decline observed with the astroglial processes in the granule cell layer. The neuronal dendrites and astroglial processes exhibited a strict numerical ratio in the young and mature animal and, in double immunofluorescence studies with anti-polysialic acid and anti-glial fibrillary acidic protein, the astroglial processes exhibited apparent points of cell and/or dendritic contact. These findings suggest that loss of polysialylated astroglial processes precedes the decline in polysialylated dentate neurons.

Aging↗