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Biomedical subjects

M Levin

Publications and source records attributed to M Levin.

At least 19 recordsLinked to original sources
PubMed2006

Randomised controlled trial of the efficacy of a metered dose inhaler with bottle spacer for bronchodilator treatment in acute lower airway obstruction.

BACKGROUND: Inhaled bronchodilator treatment given via a metered dose inhaler (MDI) and spacer is optimal for relief of bronchoconstriction. Conventional spacers are expensive or unavailable in developing countries, but there is little information on the efficacy of low-cost spacers in young children. OBJECTIVE: To compare the response to bronchodilator treatment given via a conventional or a low-cost bottle spacer METHODS: A randomised controlled trial of the efficacy of a conventional spacer compared with a bottle spacer for bronchodilator treatment in young children with acute lower airway obstruction. Bronchodilator treatment was given from an MDI via an Aerochamber or a bottle spacer. Clinical score and oximetry recording were carried out before and after 15 min of treatment. MDI-spacer treatment was repeated up to three times, depending on clinical response, after which nebulisation was used. The primary outcome was hospitalisation. RESULTS: 400 children, aged (median (25th-75th centile)) 12 (6-25) months, were enrolled. The number of children hospitalised (n = 60, 15%) was identical in the conventional and bottle spacer groups (n = 30, 15% in each). Secondary outcomes including change in clinical score (-2 (-3 to -1)), oxygen saturation (0 (-1 to 1)) and number of bronchodilator treatments (2 (1 to 3)) were similar in both groups. Oral corticosteroids, prescribed for 78 (19.5%) children, were given to a similar number in the conventional (37 (18.5%)) and bottle spacer groups (41 (20.5%)). CONCLUSION: A low-cost bottle spacer is as effective as a conventional spacer for bronchodilator treatment in young children with acute obstruction of the lower airways.

Asthma↗
PubMed2006

Composition of coronary plaques obtained by directional atherectomy in stable angina: its relation to serum lipids and statin treatment.

OBJECTIVES: The stability and inflammatory activity in atherosclerotic plaques may be modulated by lipids and lipoproteins as well as the pleiotropic effects of statins. The aim of this study was to analyse the effect of statin treatment as well as the relation of plasma lipids and lipoproteins to tissue composition in atherosclerotic plaques. DESIGN: Patients with stable angina and coronary plaques suitable for directional coronary atherectomy (DCA) were randomized to atorvastatin (80 mg once daily) or placebo (29 randomized, 22 underwent DCA, 11/group). After an average treatment of 10 weeks, patients underwent DCA, tissue specimens were obtained, and the tissue composition was determined by immunohistochemistry. RESULTS: Atorvastatin reduced the T-cell content, but did not change lipid, collagen, smooth muscle cell, or macrophage content. Plasma levels of apolipoprotein AI (apoAI) correlated positively with tissue collagen and inversely with metalloproteinase-9 and macrophage content. About half the specimens contained neutrophil granulocytes. CONCLUSIONS: Short-term atorvastatin treatment tended to reduce the T-cell content of atherosclerotic plaques, indicating modulation of cell-mediated immunity. High plasma levels of apoAI correlated with increased collagen content and reduced inflammation, supporting the notion that plasma apoAI stabilizes atherosclerotic plaques. The significance of neutrophils in the lesions merits further study.

Adult↗
PubMed2006

Interferon-gamma therapy in two patients with progressive chronic pulmonary aspergillosis.

Infection by Aspergillus species causes a wide spectrum of pulmonary disease in humans. In two patients with semi-invasive Aspergillus-induced lung disease, significantly reduced levels of interferon-gamma secretion by peripheral blood mononuclear cells were found after in vitro stimulation with the T-cell mitogen phytohaemagglutinin. Despite anti-fungal therapy, both patients exhibited progressive disease, and adjunctive interferon-gamma therapy was associated with significant clinical improvement. The data suggest that impaired production of interferon-gamma can be seen in patients with chronic pulmonary aspergillosis. Adjunctive cytokine therapy with interferon-gamma may be useful in patients with progressive disease despite adequate anti-fungal therapy.

Adult↗
PubMed2005

Headache in giant cell arteritis and other arteritides.

Giant cell arteritis remains the most common systemic vasculitis in patients over the age of 50. Headache is the most common symptom, but is not invariably present. The headache may take almost any form, and may resemble any of the primary headaches, even cluster. Prompt diagnosis is important to prevent the well known serious complications. Accurate diagnosis allows appropriate therapy. Other forms of vasculitis may also cause headaches so correct diagnosis is essential as therapies may differ.

Aged↗
PubMed2004

The relationship between serum cobalamin concentration and mean red cell volume at varying concentrations of serum folate.

There is concern that exposure of patients to folic acid may prevent the development of the macrocytosis of cobalamin deficiency and thus delay the detection of the neurological complications. We examined the relationship between low cobalamin levels and mean cell volume (MCV) at different serum folate concentrations in 63,472 blood samples tested in a community pathology laboratory over 2 years. We found no evidence that high serum folate levels masked the macrocytosis of cobalamin deficiency in this population with similar increases in MCV regardless of whether the serum folate was low, normal or high. Macrocytosis appears to retain its value as a marker of cobalamin deficiency in people with serum folate concentrations above the population average.

Anemia, Macrocytic↗
PubMed2004

Evolution of an adenovirus outbreak in a multidisciplinary children's hospital.

OBJECTIVE: To describe the course of an evolving adenovirus outbreak in a multidisciplinary children's hospital with a high-risk patient population. METHODS: Observational study in a 280-bed university hospital during June 2002. Active case finding identified children with adenovirus infection. Data are median (interquartile range) or n (%). Adenovirus infection was diagnosed in 49 children, median age 12 months (4-33). RESULTS: New cases were diagnosed over 26 days and peaked on day 17 (n = 15). Total infected inpatients peaked on days 17-21 (n = 36). Twenty-three infections (47%) were community-acquired and 26 (53%) hospital-acquired. Thirty-three children (67%) had a coexistent high-risk condition. Median hospital stay before and after diagnosis was 9 days (3-18) and 9 days (4-29), respectively. Twenty-two children (45%) were admitted to PICU. Overall hospital mortality was 22% (n = 11) and mortality attributed to adenoviral disease 12% (n = 6). Hospital mortality was similar between community- and hospital-acquired infections (22% compared to 23%) (P = 1.0). Twenty children (41%) received intravenous immunoglobulin (IVIG). Children treated with IVIG had a longer hospital stay (median 40 days vs 14 days) than those who did not receive IVIG (P = 0.01). Neither PICU mortality (29% vs 12%), nor hospital mortality (35% vs 14%), differed significantly between IVIG treated and untreated children (P = 0.76 and P = 0.16, respectively). CONCLUSION: The rapid spread of hospital-acquired adenovirus underlines the importance of effective infection control measures. Despite nosocomial infection amongst high-risk patients, mortality was similar to that of community-acquired infection. Administration of immunoglobulin was not associated with demonstrable benefit. A prospective randomized trial would be required to resolve this issue.

Adenoviridae↗
PubMed2004

Circulating aldosterone levels are unexpectedly low in children with acute meningococcal disease.

The incidence of meningococcal disease in childhood has risen over the past decade. Mortality remains high for those who develop septic shock and purpura fulminans. Poor perfusion, hypotension, and loss of intravascular circulating volume may be expected to influence both mineralocorticoid and glucocorticoid secretion. The aim of the study was to define adrenocortical hormone status at presentation. Sixty children admitted to the pediatric intensive care unit were studied. Children were divided into two groups: group A (n = 31), with meningococcal sepsis, mean age 4.4 yr (range 0.5-14.4), predicted risk of mortality mean 32.3% (range 0.5-99.3%); and group B (n = 29), with other diagnoses (post major surgery and with severe respiratory infections), mean age 4.1 yr (range 0.3-16.3), predicted risk of mortality mean 9.4% (range 0.2-83%). The groups were not significantly different for age. Plasma levels of aldosterone and cortisol were determined by RIA. The mean plasma aldosterone concentration on admission in group A was 427.5 +/- 88.1 pg/ml, with 96.7% of values within the normal range for age for healthy children and were significantly lower than group B mean, 1489.2 +/- 244.2 pg/ml (P < 0.0001), with 59.3% of values above the normal range. In group A there was no correlation with plasma concentrations of sodium, potassium, or volume of colloid infused in the previous 8 h. In group A mean serum cortisol mean values were 799.5 +/- 75.9 nmol/liter and in group B cortisol levels were 703.4 +/- 78.6 nmol/liter (P = n.s.). We conclude that children with meningococcal disease present with lower plasma aldosterone concentrations than other patients in the pediatric intensive care unit, for which there is no clear explanation. Further work is needed to elucidate the mechanisms underlying this finding and to examine its clinical implications.

Acute Disease↗
PubMed2003

Mapping of ATP, glucose, glycogen, and lactate concentrations within the arterial wall.

OBJECTIVE: In large- and medium-sized arteries, the diffusion distances for oxygen and nutrients are long. This has been suggested to make these vessels prone to develop local energy metabolic deficiencies that could contribute to atherogenesis. To validate this hypothesis, we introduced a new method to measure energy metabolites within the arterial wall at high spatial resolution. METHODS AND RESULTS: Bioluminescence imaging was used to quantify local metabolite concentrations in cryosections of snap frozen (in vivo) and incubated pig carotid artery rings. Incubation at hypoxia resulted in increased lactate concentrations, whereas ATP, glucose, and glycogen concentrations were decreased, especially in the mid media, where concentrations of these metabolites were close to zero. In snap frozen arteries, glycogen concentrations were markedly higher in deep layers of the media than toward the lumen. ATP, glucose, and lactate were more homogenously distributed. CONCLUSIONS: Bioluminescence imaging is a new and powerful tool to assess arterial wall energy metabolism at high spatial resolution. Our experiments demonstrate heterogeneous distributions of energy metabolites under hypoxic in vitro conditions. Furthermore, we show that glycogen concentrations are higher in deep medial layers in vivo. This might represent a local adaptation to a low-oxygen microenvironment.

Adenosine Triphosphate↗
PubMed2003

Severe P. falciparum malaria in Kenyan children: evidence for hypovolaemia.

BACKGROUND: The role of volume resuscitation in severe Plasmodium falciparum malaria is controversial. AIM: To examine the role of hypovolaemia in severe childhood malaria. STUDY DESIGN: Retrospective review. METHODS: We studied 515 children admitted with severe malaria to a high-dependency unit (HDU) in Kilifi, Kenya. On admission to the HDU, children underwent a further assessment of vital signs and a standard clinical examination. RESULTS: Factors associated with a fatal outcome included deep breathing or acidosis (base excess below -8), hypotension (systolic blood pressure <80 mmHg), raised plasma creatinine (>80 micro mol/l), low oxygen saturation (<90%), dehydration and hypoglycaemia (<2.5 mmol/l). Shock was present in 212/372 (57%) children, of whom 37 (17.5%) died, and was absent in 160, of who only 7 (4.4%) died (chi(2) = 14.9; p = 0.001). DISCUSSION: Impaired tissue perfusion may play a role in the mortality of severe malaria. Moreover, volume resuscitation, an important life-saving intervention in children with hypovolaemia, should be considered in severe malaria with evidence of impaired tissue perfusion.

Acidosis↗
PubMed2003

Pathophysiology of meningococcal meningitis and septicaemia.

Neisseria meningitidis is remarkable for the diversity of interactions that the bacterium has with the human host, ranging from asymptomatic nasopharyngeal colonisation affecting virtually all members of the population; through focal infections of the meninges, joints, or eye; to the devastating and often fatal syndrome of meningococcal septic shock and purpura fulminans.

Bacteremia↗
PubMed2003

Sibling familial risk ratio of meningococcal disease in UK Caucasians.

To quantify the host genetic component of meningococcal disease (MD) susceptibility, the sibling risk ratio (lambdaS) was calculated as the ratio of observed MD cases among 845 siblings of 443 UK Caucasian cases to that expected, calculated from age-calendar year specific rates for England and Wales. Twenty-seven siblings contracted MD compared with an expected 0.89, generating a lambdaS value of 30.3. Overestimation of lambdaS due to Neisseria meningitidis exposure was minimized by excluding siblings with MD onset within set time points of the index case. Irrespective of whether siblings contracted MD more than 1, 3, 6, 9 or 12 months after the index case, the lambdaS varied slightly (lambdaS range: 8.2-11.9), suggesting that host genetic factors may contribute approximately one third of the total lambdaS. Social class distribution did not differ between MD cases and the general population of England and Wales. This study is the first to calculate lambdaS for MD and establishes that susceptibility to MD has a significant host genetic component.

Adolescent↗
PubMed2002

Isolation and community: a review of the role of gap-junctional communication in embryonic patterning.

Gap junctions are specialized channels formed between the membranes of two adjacent cells. They permit the direct passage of small molecules from the cytosol of one cell to that of its neighbor, and thus form a system of cell-cell communication that exists alongside familiar secretion/receptor signaling. Gap junction states can be regulated at many levels by factors such as membrane voltage, pH, phosphorylation state, and biochemical signals. Because of the rich potential for regulation of junctional conductance, and directional and molecular gating (specificity), gap junctional communication (GJC) plays a crucial role in many aspects of normal tissue physiology, as well as in tumor progression. However, arguably the most exciting role for GJC is in the regulation of information flow that takes place during embryonic development. This review summarizes the current knowledge of how GJC controls various aspects of embryonic morphogenesis in both vertebrate and invertebrate systems. Modern molecular embryology approaches have complemented biophysical and ultrastructural data, and we are beginning to unravel the patterning roles of GJC in embryonic events such as the patterning of the embryonic left-right axis, as well as the morphogenesis of the heart and limb. Proteins from the Connexin (Cx) gene family, as well as innexins and ductin, are now beginning to be understood as the basis for GJC underlying important embryonic patterning events.

Animals↗
PubMed2002

Analysis of pathogen-host cell interactions in purpura fulminans: expression of capsule, type IV pili, and PorA by Neisseria meningitidis in vivo.

The pattern of meningococcal surface structure expression in different microenvironments following bloodstream invasion in vivo is not known. We used immunohistochemistry to determine the expression of capsule, type IV pili, and PorA by meningococci residing in the skin lesions of children with purpura fulminans. All the skin biopsy samples showed evidence of thrombosis and, frequently, a perivascular inflammatory cell infiltrate consisting of neutrophils (elastase positive) and monocytes/macrophages (CD68 positive). Modified Gram staining revealed 20 to over 100 gram-negative diplococci in each 4-microm-thick section, usually grouped into microcolonies. Immunoperoxidase staining demonstrated that the invading meningococci expressed PorA, capsule, and type IV pilin. Expression of these antigens was not restricted to any particular environment and was found in association with meningococci located in leukocytes, small blood vessels, and the dermal interstitium. Confocal laser scanning microscopy demonstrated coexpression of pilin and capsule by numerous microcolonies. However, there was some discordance in capsule and pilin expression within the microcolonies, suggesting phase variation. The strategy employed in this study will be helpful in investigating invasive bacterial diseases where antigenic and phase variation has a significant impact on virulence and on vaccine design.

Adolescent↗
PubMed2002

Kawasaki disease: an evidence based approach to diagnosis, treatment, and proposals for future research.

This article proposes a clinical guideline for the diagnosis and treatment of Kawasaki disease in the UK based on the best available evidence to date, and highlights areas of practice where evidence is anecdotal or based on retrospective data. Future research as proposed by the London Kawasaki Disease Research Group is outlined, and clinicians are invited to prospectively enroll their suspected cases into this collaborative research project.

Adrenal Cortex Hormones↗
PubMed2002

A comparative biomechanical study of the strength of the bony patella following dome cut or uniplanar cut in total knee arthroplasty.

This study was designed to investigate whether there is a difference in the strength of the bony patella following preparation either with a dome configuration or with a regular uniplanar cut in total knee arthroplasty. For each test 4 cadaveric patellae were used. Two of the 4 patellae were prepared with a regular uniplanar cut and 2 were prepared into a dome shape with a circumferential wall, using a concave reamer. The thickness of each patella after preparation was [figure 1 & 2: see text] 15 mm. The tests were performed using an impact drop weight apparatus. In the first two tests, which tested the resistance of the patella to tensile force and evaluated the strength of the patella by impact load while under tension, the soft tissues were torn, with no harm to the bony patella. In the third test, which evaluated the resistance of the patella without tension against impact load, the force required to fracture the dome-shaped patella was greater than for the traditional uniplanar cut (500 Kg vs 350 Kg). Dome shape with circumferential wall preparations of the bony patella in total knee arthroplasty were stronger in resisting external impact than the conventional uniplanar cut patella. This established the rationale for our use of the dome-shaped patella implant with a concave undersurface.

Arthroplasty, Replacement, Knee↗