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Biomedical subjects

J Timmermans

Publications and source records attributed to J Timmermans.

At least 19 recordsLinked to original sources
PubMed2005

Gaussian broad-beam excimer laser: clinical and experimental results.

PURPOSE: To evaluate the mid-term (1-3 years) results of the Gaussian broad-beam excimer laser Delivery System (DS) after single treatment for the correction of myopia. To study the corneal surface with scanning electron microscopy (SEM) after excimer laser ablation using a flying spot delivery system (Bausch & Lomb) and a Gaussian Delivery System (GDS) (InPro). METHODS: The 1035 consecutive eyes studied were split in four groups with respect to the treated myopia, expressed in spherical equivalent: low myopia up to -3.00 D (183 eyes), moderate myopia from -3.25 D to -6.00 D (540 eyes), high myopia from -6.25 D to -10.00 D (210 eyes) and very high myopia from -10.25 D to -20.00 D (102 eyes). Four post-mortem eyes of two donors were treated using the flying spot DS on one eye and the GDS on the other eye. RESULTS: We achieved postoperative spheriqual equivalent within +/- 1 D of emmetropia in respectively 99.1%, 98.9%, 83% and 21% of the eyes of group 1, 2, 3 and 4. UCVA was 10/10 or better in respectively 65%, 51% and 19% of group 1, 2 and 3. UCVA was 5/10 or better in respectively 86% and 75% of group 3 and 4. The defocus equivalent refraction was 1.0 or less in respectively 98%, 93%, 62%, and 7% of the four groups. On SEM, the corneal surface presented a smooth and polished profile for the GDS. CONCLUSIONS: The Gaussian Delivery System gives comparable results to the flying spot laser system for surface laser ablation in myopic eyes up to -10 D. Advantages of this system are: smooth ablation surface, short treatment time, low haze rate, high reliability and easy maintenance of the device due to the optical DS. It is an interesting alternative for the more complex mechanical DS.

Follow-Up Studies↗
PubMed2004

A clinical and cardiovascular survey of Ehlers-Danlos syndrome patients with complete deficiency of tenascin-X.

BACKGROUND: We recently described a new autosomal recessive type of Ehlers-Danlos syndrome (EDS) based on a deficiency of the extracellular matrix protein tenascin-X (TNX). TNX-deficient patients have hypermobile joints, hyperextensible skin and show easy bruising. Because of the reported cardiovascular abnormalities in other EDS types and the excessive haematoma formation after mild trauma in TNX-deficient individuals, we investigated whether cardiovascular or coagulation abnormalities occur in these patients. METHODS: We examined seven TNX-deficient patients. One of them had a mitral valve prolapse and died postoperatively after valve replacement, before the study was completed. RESULTS: Bleeding time and coagulation factors (INR, APTT, PT and fibrinogen) were all within the normal range. Ultrasonographic examination of the carotid and femoral arteries showed normal vessel wall compliance and distensibility. Echocardiography showed a slight billowing of the mitral valve in two patients from one family. All patients had normal diameters of aortic root and ascending aorta. CONCLUSION: Although the patient group is small, there are no indications of generalised cardiovascular abnormalities in this type of EDS. We would recommend echocardiography for all these patients at the first evaluation and when a cardiac murmur appears.

Echocardiography↗
PubMed2003

Magnetic resonance imaging of the main pulmonary artery: reliable assessment of dimensions in Marfan patients on a simple axial spin echo image.

OBJECTIVE: To investigate if a simple axial spin echo (SE) image can be used for reliable assessment of pulmonary artery dimensions in patients with Marfan syndrome. METHODS: Fifty Marfan patients (mean age 33 +/- 10 years; 34 men, 16 women) and 15 normal subjects (mean age 28 +/- 4 years; nine men, six women) underwent cardiac magnetic resonance imaging (MRI). Pulmonary artery dimensions were obtained on axial SE images at two different levels: (1) the level of the pulmonary artery root, and (2) the level of the pulmonary artery bifurcation. To evaluate the accuracy of axial plane measurements 10 Marfan patients also underwent contrast-enhanced MR angiography (CE-MRA). RESULTS: In the 10 Marfan patients who also underwent CE-MRA, the mean diameter at the pulmonary bifurcation assessed with CE-MRA (31.5 +/- 3.6 mm) was almost equal to mean diameter assessed with axial SE (30.7 +/- 3.6 mm). Agreement of methodology according to Bland and Altman analysis showed a 95% confidence interval ranging from -2.6 to + 4.4 mm for all distances of the pulmonary artery root. In Marfan patients the mean right-left diameter measured on both axial SE images and CE-MRA was approximately 2.5 mm larger than the anterior-right and anterior-left diameters (p < 0.001). CONCLUSIONS: Axial SE MRI is a reliable and easy acquisition to measure pulmonary artery dimensions in patients with Marfan syndrome, and could be used for follow-up, especially in patients with severe involvement of the cardiovascular system. Not only the pulmonary artery trunk but also the asymmetric pulmonary root should be measured, although the clinical relevance of the asymmetric root is not yet known.

Adult↗
PubMed2001

Morphological and neurochemical differentiation of large granular layer interneurons in the adult rat cerebellum.

The granular layer of the cerebellar cortex consists of densely packed neuronal cells, classified into granule cells and large interneurons. In this study, we provide a comparative survey of large granular layer interneurons in the adult rat cerebellum based on both morphological and neurochemical criteria. To this end, double immunofluorescence histochemistry was performed by combining antibodies against the cytoplasmic antigen Rat-303, calretinin, the metabotropic glutamate receptor mGluR2 and somatostatin. Based on Rat-303/calretinin double immunohistochemistry, three distinct populations of large granular layer interneurons could be discerned: cells immunopositive for Rat-303, calretinin or both. Rat-303 or calretinin single-labeled cells represented Golgi cells and unipolar brush cells, respectively. Rat-303/calretinin double-labeled cells located just underneath the Purkinje cell layer represented Lugaro cells. Morphometrical analysis distinguished two populations of Rat-303-positive Golgi cells according to their location: vermis versus hemisphere. Immunostaining for the metabotropic glutamate receptor mGluR2 combined with Rat-303 or calretinin revealed that the majority of Golgi cells (about 90%) appeared to be mGluR2 positive. Lugaro cells were mGluR2 negative. In addition, a limited population of large polymorphous interneurons in the depth of the granular layer with morphological features resembling Golgi cells also displayed Rat-303/calretinin immunoreactivity and were mGluR2 negative. Double immunohistochemistry for Rat-303 and somatostatin revealed three populations of labeled cells in the depth of the granular layer. Besides double-labeled Golgi cells, Rat-303 or somatostatin single-labeled cells were present. Based on mGluR2/somatostatin and calretinin/somatostatin double immunostainings, Rat-303 single-labeled cells were found to correspond to Rat-303/calretinin-positive, mGluR2-negative Golgi-like cells, while the identity of somatostatin single-labeled cells remained unclear. The data presented in this article elaborate previous reports on the morphological and neurochemical differentiation of large interneurons in the rat cerebellar granular layer. In addition, they indicate that the current classification of these cells into Golgi cells, Lugaro cells and unipolar brush cells does not describe the observed neurochemical heterogeneity.

Animals↗
PubMed2001

Biophysical properties of the normal-sized aorta in patients with Marfan syndrome: evaluation with MR flow mapping.

PURPOSE: To investigate the feasibility of magnetic resonance (MR) flow mapping in the assessment of aortic biophysical properties in patients with Marfan syndrome and to detect differences in biophysical properties in the normal-sized aorta distal to the aortic root between these patients and matched control subjects. MATERIALS AND METHODS: Seventy-eight patients with Marfan syndrome with aortic root dilatation and 23 matched control subjects underwent MR flow mapping in four locations in the normal-sized aorta (1, ascending aorta; 2, thoracic descending aorta; 3, descending aorta at the level of the diaphragm; and 4, abdominal descending aorta). Distensibility at each location and flow wave velocity between locations were calculated. RESULTS: Compared with the control subjects, patients with Marfan syndrome had decreased aortic distensibility at three of the four locations (levels 1, 2, and 4; P <.05) and increased flow wave velocity between all locations (P <.05) in the aorta. In patients with Marfan syndrome, flow wave velocity was also significantly increased along the entire aortic tract beyond the aortic root (from level 1 to level 4). CONCLUSION: MR imaging reveals abnormal biophysical properties of the normal-sized aorta in patients with Marfan syndrome. Monitoring of these properties is relevant for evaluating disease progression and treatment options.

Adolescent↗
PubMed1999

Regional differences in the sympathetic innervation of the guinea pig large intestine by neuropeptide Y- and tyrosine hydroxylase-immunoreactive nerves of divergent extrinsic origin.

Region-specific patterns of nerves with immunoreactivity to neuropeptide Y (NPY) have been described previously in the submucous plexus of guinea pig large intestine. Because these may have functional significance, the possibility of similar, characteristic variations of NPY-like immunoreactivity (NPY-ir) in the myenteric plexus was explored. Regional differences were found in the occurrence and pattern of distribution of NPY-ir in the myenteric plexus of the guinea pig large intestine. NPY-ir was present rarely within neuron somata in any region of the large intestine, and NPY-ir nerve fibers were present only within the distal large intestine, increasing progressively in density from the distal spiral to the rectum. Lesion of the colonic nerves, but not the hypogastric, intermesenteric, or lumbar splanchnic nerves, resulted in a loss of NPY-ir in the distal spiral and transverse colon but not in the descending colon or rectum. Ring myotomies in the descending colon resulted in a loss of NPY-ir proximal to the lesion. Dual-labeling immunohistochemical studies revealed that the NPY-ir nerve fibers rarely contained immunoreactivity for tyrosine hydroxylase (TH). Extrinsic nerve lesions resulted in an unequivocal reduction in NPY-ir in intraganglionic fibers of the submucosal plexuses of the transverse colon and a partial loss in the distal spiral and descending colon: the rectum was unaffected; in only a minority of guinea pigs, however, was any decrease in the NPY-ir innervation of submucosal blood vessels detected. The principal projections of NPY-ir nerves were from and through the inferior mesenteric ganglion; however, NPY-ir was not colocalized with TH-ir. It is proposed that nonnoradrenergic, NPY-containing neurons located in the inferior mesenteric ganglion project through the colonic nerves and that these proximally directed fibers innervate the transverse colon and the distal spiral. Nonnoradrenergic, NPY-ir neurons lying in the pelvic ganglia or sacral sympathetic chain may make an important contribution to the innervation of the myenteric plexus of the rectum and the descending colon.

Animals↗
PubMed1998

Peroral sustained-release film-coated pellets as a means to overcome physicochemical and biological drug-related problems. I. In vitro development and evaluation.

In vitro preformulation testing has shown that the solubility and dissolution rate of the model drug compound ucb 11056 are highly pH dependent. Considering this, different sustained-release (SR) oral dosage forms of ucb 11056 were developed aiming to obtain the most constant and complete release of the drug during transit in the gastrointestinal (GI) tract. Classical approaches based on the use of SR formulations such as hydrophilic matrix tablets or pellets coated with one film-forming polymer (Eudragit NE30D or L30D-55) did not fulfill all expectations on the basis of their in vitro evaluation, i.e., the drug release and pattern remained highly dependent on the pH of the dissolution medium. Therefore, taking advantage of the flexibility of release adjustment obtainable from coating of pellets with different kinds of pH-sensitive film layers, a quite satisfactory pH independence of the release characteristics was obtained using formulation blends of neutral and anionic acrylic polymers. For the selected SR pellets batch 15 coated with NE30D/L30D-55 (7:3), the tridimensional topographic representation of the drug release versus time and pH showed that, notwithstanding the pH-dependent aqueous solubility of the drug, the release profiles were relatively homogeneous for any pH value ranging between 1 and 7.

Acrylic Resins↗
PubMed1998

Peroral sustained-release film-coated pellets as a means to overcome physicochemical and biological drug-related problems. II. Bioavailability and tolerance assessment in dogs.

Sustained-release (SR) dosage forms consisting of pellets coated with different pH-sensitive film layers, previously optimized in vitro with regard to pH independence of their drug release characteristics, were evaluated in vivo after single administration to Beagle dogs. In vivo performances were compared to those of a nonoptimized SR matrix tablet and a reference instant release (IR) capsule, in terms of the observed plasma pharmacokinetic profiles for the parent drug (ucb 11056) and its primary metabolite (ucb 26201), the bioavailability results, and the drug tolerance data. All SR dosage forms were seen to be effective in prolonging the relatively short biological half-life of the compound and in reducing the incidence of concentration-related side-effects, e.g., emesis, and of behavioral symptoms, e.g., restlessness, discomfort, and indisposition. The film-coated SR pellets offer a number of advantages over the monolithic SR matrix system in terms of a drug delivery pattern less dependent on pH changes in the gastrointestinal (GI) tract, a higher flexibility for adjusting and controlling the pharmacokinetic profiles, and a consequently more efficient approach for keeping all concentration-related side-effects under control.

Administration, Oral↗
PubMed1997

Lipomatous hypertrophy of the interatrial septum: indication for surgery?

A fortuitous finding during open heart surgery of lipomatous hypertrophy of the interatrial septum is described in a 65-year old man with ischaemic heart complaints due to coronary artery disease and with premature ventricular contractions. An incision biopsy confirmed the diagnosis. The choice of treatment of lipomatous hypertrophy of the interatrial septum is controversial. Indications for surgery and surgical techniques are discussed.

Aged↗
PubMed1996

The Floating-Harbor syndrome: two affected siblings in a family.

In this report we describe two siblings with pre- and postnatal growth retardation and clinical signs and symptoms most compatible with the diagnosis of Floating-Harbor syndrome. The oldest sibling, a girl, died in the first year of life from recurrent infections. The younger sibling, a male, is now 16.5 years old and mildly mentally retarded.

Age Determination by Skeleton↗
PubMed1994

Factors controlling the buoyancy and gastric retention capabilities of floating matrix capsules: new data for reconsidering the controversy.

Optimized floating (F) and non-floating (NF) hydrophilic matrix capsules have been characterized in vitro with regard to their buoyancy or non-buoyancy capabilities and their diametral size evolution with time. The gastric residence times (GRTs) and transit behaviors of these F and NF forms prepared in small, medium, and large sizes were then comparatively examined in fed volunteers remaining either upright or supine. The results show that all the optimized F forms do lastingly float upon the gastric contents, whereas the NF forms sink rapidly after ingestion. In upright subjects, the F forms are consequently protected against postprandial emptying. The GRTs of the NF forms are much more variable and highly dependent on their size (mean GRT small < medium < large units, p < 0.05). The GRT prolongation obtained with the F forms when compared with the NF ones is hence significantly marked for the small and medium size dosage forms (p < 0.05) but not for the large ones (p > or = 0.05). In supine subjects, a size effect influences the GRT of both the F and NF forms (p < 0.05). The F forms are more often emptied before the NF ones but, size for size, the mean GRTs do not differ in the aggregate. These findings, together with literature data, are used to explain why a number of former investigations have come to contradictory conclusions about the effect of density of an undigestible form on GRT. Uncontrolled factors are hiding from disclosure the GRT enhancement that should be observed when optimized F forms are used within defined conditions.

Adult↗
PubMed1992

The bilayer floating capsule: a stomach-directed drug delivery system for misoprostol.

A bilayer floating dosage unit is proposed to achieve local delivery of misoprostol, a prostaglandin E1 analogue, at the gastric mucosa level. The system is a capsule consisting of a floating layer maintaining the dosage unit buoyant upon the gastric content and a drug layer formulated to act as a sustained-delivery system. The differential design of the two layers allows the optimization of both floating capability and drug release profile. The layers are both composed of a hydrophilic matrix based upon hydroxypropylmethyl cellulose (HPMC). Parameters influencing the release profiles are described. The use of a large capsule increases the gastric residence time (GRT), as it impedes passage through the pylorus opening. gamma-Scintigraphic studies were performed to visualize cohesion of the two layers in vivo and to determine GRT as a function of meal regimen. The average GRTs were 199 +/- 69 min after a single meal (breakfast) and 618 +/- 208 min after a succession of meals.

Adult↗
PubMed1991

Intragastric positioning of two concurrently ingested pharmaceutical matrix dosage forms.

A triple nuclide scintigraphic technique is presented for the precise and lasting intragastric monitoring in man of two concurrently ingested hydrophilic matrix pharmaceutical forms. After in vitro testing of various labels, ion exchange resin-coupled 201T1- and 111In-oxinate were selected for their release characteristics. 99mTc-pertechnetate oral solution was used to selectively delineate the stomach. This technique was validated on healthy volunteers. It allowed measurement of the effects on gastric residence time of galenic parameters (size, density of matrices), as well as of physiological parameters such as subject posture.

Adult↗
PubMed1991

Active Ca2+ transport in primary cultures of rabbit kidney CCD: stimulation by 1,25-dihydroxyvitamin D3 and PTH.

Rabbit connecting tubules and cortical collecting ducts, which represent 79 +/- 5% of the calbindin-D28k-containing kidney cells, were isolated by immunodissection from the rabbit kidney superficial cortex and seeded on permeable filters. After 6 days in culture the monolayers developed a potential difference (PD) of -24 +/- 3 mV (lumen negative) and a transepithelial resistance (R) of 284 +/- 19 omega.cm2. Addition of 10(-6) M amiloride to or removal of Na+ from the mucosal side reversed the PD to +6 +/- 4 mV and concomitantly increased R to 660 +/- 122 omega.cm2. The cells developed functional parathyroid hormone (PTH) and arginine vasopressin receptors, but calcitonin receptors were absent. The monolayer actively absorbed Ca2+ against an electrochemical gradient with a rate of 121 +/- 13 nmol.h-1.cm-2. Removal of serosal Na+ inhibited Ca2+ absorption by 63 +/- 8%. Exposure to 10(-7) M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] for 48 h or 10(-7) M bovine PTH (bPTH)-(1-34) for 1 h, increased transcellular Ca2+ absorption by 53 +/- 13% or 24 +/- 8%, respectively. The effects of 1,25(OH)2D3 and PTH in combination were neither additive nor potentiating. In addition, the cultured cells expressed calbindin-D28k, and, after exposure to 10(-7) M 1,25(OH)2D3 for 48 h, the calbindin-D28k content increased fourfold.

Adrenocorticotropic Hormone↗