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Biomedical subjects

B E de Galan

Publications and source records attributed to B E de Galan.

12 recordsLinked to original sources
PubMed2006

[Treatment of patients with diabetes mellitus by means of inhaled insulin].

Good glycaemic control of diabetes mellitus is still hampered by the fear of insulin injections. Particularly in patients with type 2 diabetes, inhaled insulin as a novel therapeutic option for glycaemic control could be an alternative to subcutaneous insulin. Phase III clinical studies have shown glycaemic equivalence between inhaled insulin and conventional subcutaneous insulin. However, no study comparing inhaled insulin with short-acting insulin analogues has yet been published. Thus, methodological problems preclude conclusive remarks concerning quality-of-life issues. Inhaled insulin should be reserved for selected patient groups only. Lengthier studies to evaluate the long-term (pulmonary) safety of inhaled insulin and a cost-effectiveness study are needed.

Administration, Inhalation↗
PubMed2006

Sensitivity-enhanced 13C MR spectroscopy of the human brain at 3 Tesla.

A new coil design for sensitivity-enhanced 13C MR spectroscopy (MRS) of the human brain is presented. The design includes a quadrature transmit/receive head coil optimized for 13C MR sensitivity. Loss-less blocking circuits inside the coil conductors allow this coil to be used inside a homogeneous circularly polarized 1H B1 field for 1H decoupled 13C MRS. A quadrature 1H birdcage coil optimized for minimal local RF heating makes broadband 1H decoupling in the entire human brain possible at 3 Tesla while remaining well within international safety guidelines for RF absorption. Apart from a substantial increase in sensitivity compared to conventional small linear coils, the quadrature 13C coil combined with the quadrature 1H birdcage coil allows efficient cross polarization (CP) in the brain, resulting in an additional 3.5-fold sensitivity improvement compared to direct 13C measurements without nuclear Overhauser enhancement (NOE) or polarization transfer. Combined with the gain in power efficiency, this setup allows broadband 1H to 13C CP over large areas of the brain. Clear 13C resonances from glutamate (Glu), glutamine (Gln), aspartate (Asp), lactate (Lac), and gamma-aminobutyrate (GABA) carbon spins in the human brain demonstrate the quality of 13C MR spectra obtained in vivo with this coil setup.

Aspartic Acid↗
PubMed2006

Pathophysiology and management of recurrent hypoglycaemia and hypoglycaemia unawareness in diabetes.

Iatrogenic hypoglycaemia is a well-known complication of insulin therapy in patients with diabetes mellitus and a limiting factor for glycaemic control. In a setting of endogenous insulin deficiency (type 1 and advanced type 2 diabetes), one episode of hypoglycaemia reduces both counterregulatory hormone responses to and subjective awareness of subsequent hypoglycaemia, thus impairing physiological defences against hypoglycaemia. This phenomenon may lead to a vicious cycle of recurrent hypoglycaemia and glucose counterregulatory failure, of which hypoglycaemia unawareness (i.e. the inability to perceive symptoms of hypoglycaemia) is the clinical representative. The underlying mechanism of hypoglycaemia-induced counterregulatory failure has not yet been disclosed. Patients with clinical hypoglycaemia unawareness are at high risk of severe hypoglycaemia that requires third-party assistance. Management options include avoidance of hypoglycaemic events and optimisation of insulin therapy to limit deterioration of glycaemic control associated with hypoglycaemia avoidance. Several counterregulatory-stimulating agents have been found to improve hypoglycaemic awareness in small clinical trials, but none have been tested in sufficiently large randomised studies to justify their use in daily practice. More research is required to elucidate the pathogenesis of counterregulatory failure and to develop adequate treatment strategies.

Adult↗
PubMed2006

Efficacy and safety of inhaled insulin in the treatment of diabetes mellitus.

Many patients with diabetes mellitus view subcutaneous injections of insulin as a daily burden. Pulmonary delivery of insulin offers an alternative route of administration and may as such improve diabetes treatment. Inhaled insulin provides a rapid absorption of insulin, but with low bioavailability. Phase III clinical trials in type 1 and type 2 diabetes have disclosed clinical equivalence between three inhaled insulin products (Exubera, AErx idMs, and hIIp) and regular human insulin, both in terms of glycaemic control and hypoglycaemic risk. Inhaled insulin cannot be used to replace basal insulin requirements. The most commonly reported adverse effects of inhaled insulin are cough and insulin antibody formation, the clinical significance of which is uncertain. No or minimal deterioration in pulmonary function parameters have been recorded, although studies were typically of short duration. Patients participating in inhaled insulin trials generally expressed satisfaction with the product and chose to remain on it. The availability of inhaled insulin may increase willingness in type 2 diabetic patients to consider insulin therapy. More studies of longer duration are required to determine (pulmonary) safety and cost-effectiveness of inhaled insulin, and to disclose which patients may benefit the most.

Administration, Inhalation↗
PubMed2004

Hypothesis: Normalisation of cytokine dysbalance explains the favourable effects of strict glucose regulation in the critically ill.

Recent trials investigating the effects of strict glucose regulation in critically ill patients have shown impressive reductions in morbidity and mortality. Although the literature focuses on the possible toxic effects of high blood glucose levels, the underlying mechanism for this improvement is unclear. We hypothesise that strict glucose regulation results in modulation of cytokine production, leading to a shift towards a more anti-inflammatory pattern. This shift in the cytokine balance accounts for the reduction in morbidity and mortality. To support our hypothesis, effects of glucose and insulin on cytokine release and effects of glucose, insulin, and cytokines on host defence, cardiac function and coagulation will be reviewed.

Blood Coagulation↗
PubMed2004

Insulin pump therapy, should we consider it more often?

Erratic blood glucose control, hypoglycaemia unawareness and optimisation of glycaemic control during pregnancy are widely recognised indications for commencing diabetic patients on continuous subcutaneous insulin infusion (CSII) using an insulin pump. In patients without such a specific condition, the benefit of CSII over other forms of intensified treatment on glycaemic control and hypoglycaemic rate is generally viewed as too modest to warrant a change of regimen. However, the impact of the treatment regimen on psychosocial parameters is often undervalued, at least in randomised trials. This is unfortunate as quality of life and treatment satisfaction probably determine the patient's preferences more than metabolic parameters. To truly appreciate all potential benefits of either strategy (CSII or injection therapy), these data are urgently required. In the meantime, doctors should keep an open eye for the specific needs of the individual patient to find the best treatment available for that person.

Blood Glucose↗
PubMed2003

Hypoglycaemia downregulates endotoxin-induced production of tumour necrosis factor-alpha, but does not affect IL-1beta, IL-6, or IL-10.

The aim of the present study was to investigate the effect of hypoglycaemia on the production capacity of the proinflammatory cytokines tumour necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) in subjects with and without diabetes. Hyperinsulinaemic (360 pmolm(-2) x min(-1)) stepped hypoglycaemic (5.0-3.5-2.5 mmoll(-1)) glucose clamps were performed in eight diabetic patients and in six non-diabetic subjects, and hyperinsulinaemic normoglycaemia (5.0 mmoll(-1)) control experiments were performed in four non-diabetic subjects. Circulating levels of cytokines and endotoxin-induced production of TNFalpha, IL-1beta, IL-6, and IL-10 were assessed. The effects of insulin and adrenaline were measured in separate in vitro experiments. In non-diabetic subjects, hypoglycaemia downregulated the production capacity of TNFalpha in a concentration-dependent fashion (P=0.007), but not of IL-1beta, IL-6, or IL-10. Compared to controls, the production capacity of TNFalpha in diabetic patients was already suppressed at normoglycaemia (P=0.02) and only fell in response to hypoglycaemic nadir (P=0.04). The downregulation of TNFalpha could not be explained by increased insulin or adrenaline levels. We conclude that hypoglycaemia specifically downregulates TNFalpha production capacity. Diabetic patients already have a suppressed TNFalpha production capacity at non-hypoglycaemic levels.

Adult↗
PubMed2001

Glucose counterregulation in Type 2 diabetes mellitus.

Glucose counterregulatory failure and hypoglycaemia unawareness frequently complicate treatment of Type 1 diabetes mellitus, especially when aiming for intensive metabolic control. Since tight metabolic control reduces microvascular long-term complications in Type 2 diabetes mellitus, the integrity of glucose counterregulation in Type 2 diabetic patients is important. Using a Medline search, we identified 12 studies in which counterregulatory responses to insulin-induced hypoglycaemia were compared between Type 2 diabetic patients and appropriate controls. A review of these studies showed that some patients with Type 2 diabetes mellitus develop mild counterregulatory dysfunction and reduced awareness of insulin-induced hypoglycaemia. Some studies suggested an association between counterregulatory impairment and intensity of metabolic control. We speculate that the relatively low frequency of (severe) hypoglycaemic events in Type 2 diabetes may explain why glucose counterregulation remains unaffected in most patients. We hypothesize that residual beta-cell reserve and insulin resistance provide protection against severe hypoglycaemia and limit impaired counterregulation. Diabet. Med. 18, 519-527 (2001)

Awareness↗
PubMed1999

Hospital-related outbreak of infection with multidrug-resistant Streptococcus pneumoniae in the Netherlands.

Multidrug-resistant strains of Streptococcus pneumoniae were isolated over a two-year period (July 1995 until August 1997) from the sputum of 36 patients who were hospitalized in a Dutch medical centre. Nosocomial transmission was confirmed by typing of the bacterial isolates: all 36 multidrug-resistant isolates shared the same genotype, serotype, and displayed overlapping drug resistance profiles. Thirty-two of the 36 (89%) patients had chronic obstructive pulmonary disease (COPD). The outbreak was initiated by a 76-year old patient, who had been colonized with the same strain since 1993. Because staff screening of the hospital and pulmonary function department was negative, patient-to-patient spread was the most likely cause of this outbreak. The epidemic ceased following the commencement of barrier nursing, a treatment course of ceftriaxone, and a five-day rifampicin eradication therapy for the positive patients. The outbreak resulted from failure to recognize quickly the rapid transmission of this multidrug-resistant pneumococcal clone. We conclude that patients with COPD are at high risk of acquiring multidrug resistant pneumococci, and suggest that COPD patients who are colonized or infected with multidrug-resistant pneumococci should be isolated to prevent future transmission.

Aged↗
PubMed1995

Extremely elevated body temperature: case report and review of classical heat stroke.

Classical heat stroke is a rare disease in moderate climates. We report a patient who demonstrated the classical triad of elevated body temperature, neurological disturbances, and anhidrosis. He developed rhabdomyolysis and acute renal failure. Eventually he died. Since manifestations of classical heat stroke appear to mimic an acute phase response, cytokines are thought to play an important role in its pathogenesis.

Acute Kidney Injury↗
PubMed1991

Expression of herpes simplex virus type 2 latency-associated transcript in neurons and nonneurons.

The presence of herpes simplex virus type 2 (HSV-2) transcription during in vivo latent infection was investigated by in situ hybridization. Latent infection of mouse dorsal root ganglion was investigated with the BamHI p fragment of HSV-2, which resulted in evidence of ganglion hybridization, and other fragments representing approximately 40% of the genome, which did not result in hybridization. Strand specificity of hybridization was investigated in studies with synthetic oligonucleotides, which supported the conclusion that a latency-associated transcript(s) had been detected. Hybridization was detected with oligonucleotides complementary to the infected-cell polypeptide 0 (ICP0) template strand but not with oligonucleotides synthesized from the ICP0 template strand. Although most hybridization occurred over neurons, in some instances hybridization appeared to occur over nonneuronal ganglion cells, and this was more evident when tissue sections were examined by phase contrast microscopy. Although these results supported the usual neuronal site of HSV-2 latency, latency in nonneuronal cells may be important in considering the pathobiology of HSV-2 infections.

Animals↗