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Biomedical subjects

A Frick

Publications and source records attributed to A Frick.

At least 37 records · Page 2Linked to original sources

Biopharmaceutical characterization of oral immediate release drug products. In vitro/in vivo comparison of phenoxymethylpenicillin potassium, glimepiride and levofloxacin.

The development of in vitro dissolution tests using the paddle and basket apparatus is described with respect to the qualification/validation of the testing procedure. Three examples of immediate release products containing phenoxymethylpenicillin potassium, glimepiride, and levofloxacin providing different solubility characteristics are evaluated. The solubility was high in the case of phenoxymethylpenicillin potassium and levofloxacin and low for glimepiride according to the biopharmaceutics classification system. The permeability is studied using the human colorectal carcinoma cell line CaCo-2. The permeability (10(-6) cm/s) of phenoxymethylpenicillin potassium, glimepiride, and levofloxacin was high. The determined permeability data are confirmed by absorption data obtained by means of numerical deconvolution of plasma concentrations. Recommendations are given for the biopharmaceutical characterization of the three immediate release drug products, taking into account in vitro and in vivo comparison as well as the biopharmaceutics drug classification system. The evaluated acceptance criteria are the following: phenoxymethylpenicillin potassium (80% in 30 min), glimepiride (80% in 15 min) and levofloxacin (80% in 30 min). Typically, for immediate release formulations, one limit is specified for the dissolution to ensure the release of the active ingredient within the present time period. Since phenoxymethylpenicillin potassium and levofloxacin belong to Case 1, no in vitro/in vivo correlation is expected, absorption may be gastric emptying dependent. Glimepiride is categorized to Case 2. Nevertheless, a correlation with the in vivo dissolution profile does not exist, because of the pH-dependent low solubility of the drug. Finally, recommendations are made for the batch control of drug products in accordance with the four Cases.

Absorption↗

Biopharmaceutical characterization of oral controlled/modified-release drug products. In vitro/in vivo correlation of roxatidine.

From the marketed drug product Roxane(R) 75 mg C/MR capsules (roxatidine controlled/modified-release capsules), an in vitro/in vivo comparison was performed to demonstrate a 1:1 correlation between in vitro and in vivo dissolution, and, furthermore, to ensure bioequivalence of the roxatidine controlled/modified-release (C/MR) capsules exhibiting dissolution profiles within the defined acceptance criteria. This 1:1 in vitro/in vivo comparison was calculated using a model independent numerical deconvolution method. The high degree of correlation is extremely rare, nevertheless it allows to omit the testing of clinical side batches for the setting of acceptance criteria for the in vitro dissolution of roxatidine controlled/modified-release (C/MR) capsules. The 1:1 in vitro/in vivo correlation can be explained by the biopharmaceutical characteristics of the drug substance as well as the drug product, that is, pH-independent high solubility of the drug substance as well as dissolution which is independent of pH and agitation. These facts lead to a controlled/modified-release formulation. Therefore, it is important to keep in mind that in most cases in which a pH-dependent solubility/dissolution as well as permeability characteristics can be found, a 1:1 in vitro/in vivo correlation could not be expected.

Administration, Oral↗

NMDA and AMPA receptors on neocortical neurons are differentially distributed.

The distribution of glutamate receptor subtypes on the surface of neurons is highly relevant for synaptic activation and signal processing in the neocortex. As a novel approach we have used infra-red videomicroscopy in combination with photostimulation or microiontophoresis in brain slices of rat neocortex to map the distribution of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on pyramidal neurons of layer V. Both modes of application revealed a spatially distinct distribution of glutamate receptor subtypes: the soma and the proximal dendrite of neurons are highly sensitive to NMDA, whereas the more distal parts of the dendrite are more sensitive to AMPA. An implication is that NMDA receptors near the soma might regulate the amplification of synaptic signals resulting from AMPA receptor activation on remote dendritic sites.

Animals↗

[Examination of the hand and wrist joints with a dedicated low-field MRI device].

Purpose of this study was to evaluate the diagnostic value of a low field dedicated MRI system in hand and wrist imaging. All 308 exams of the hand and wrist, that were performed on a low-field dedicated MRI system (Artoscan, Esaote Biomedica, Italy) in our institution in 1996, and high-field MRI exams performed in addition as part of the diagnostic work-up, were evaluated and correlated to final operative (n = 64) and histologic (n = 12) reports. 90% of all low-field MRI scans stated a diagnosis according to clinical suspicion. In 62% the clinical question was answered, and in 26% additional pathologies were identified. An MR-diagnosis completely different from the clinical suspicion was stated in 2%. High field exams contributed additional information in 6 of 36 patients. In 3 patients a tumor was not shown completely in the limited field-of-view of the dedicated low-field MRI-system. Frequency-selective fat-suppression pulse sequences and a better spatial resolution were the reasons for the additional information obtained in the other three patients. Low-field dedicated MR-imaging is a valuable method in the extensive work-up of the hand and wrist. Osseous, ligamentous and tendinous pathologies are well depicted. Large or infiltrative tumors should be referred to a high-field system.

Adolescent↗

[Choice of procedure in therapy of distal median nerve compression syndrome].

Endoscopic carpal tunnel release is frequently recommended. This technique allows only for division of the retinaculum flexorum, but does not enable the surgeon to address concommitant synovialitis or compression of the motor branch of the median nerve. In 67 patients, we attempted to differentiate the indications for procedures by endoscopic versus open carpal tunnel release. Beside an electrophysiological investigation, sonography of the wrist was performed to evaluate the extent of accompanying tenosynovialitis of the flexor tendons. A possible participation of the thenar branch was examined by electromyography. If there were no additional pathologic findings in the preoperative diagnostic work-up, a simple carpal tunnel release was performed. In all other cases, open surgical release was performed.

Adult↗

Free flap survival improved by prostacyclin analogues.

Free flap transplantations and replantations of extremities are threatened by venous occlusion in the postoperative course. In rats, free autogenous groin flaps were transplanted to the neck using microsurgical techniques. On the first postoperative day, the draining vein of the flap was temporarily clamped. In the control group there was always a total loss of the flaps by haemorrhagic necrosis. The intraarterial flap perfusion by iloprost during the clamping was able to diminish the ischaemic effects; 80% of the flaps survived. The systemic application of iloprost by intravenous infusion reduced the ischaemic effects in a similar way. Serious complications such as intraabdominal bleeding or bleeding in the donor area were seen after intravenous administration. Cicaprost had a similar protective effect on flap ischaemia after intravenous infusion. Flap survival was comparable to iloprost. Severe complications seemed to be less. Prostacyclin analogues were able to diminish damage of secondary ischaemia caused by venous occlusion.

Animals↗

[Anus praeter--site, care and corrective possibilities].

BASIC REMARKS: The main indication for an colostomy is a carcinoma low down in the rectum. Apart from this, tumors in any part of the bowel or neighboring organs, and complications of inflammatory disease may make a diversion of feces necessary. POINTS DISCUSSED: A stoma should be sited at a distance from skin folds, and bony protuberance, and should be readily visible for self-care. Temporary "continence" can be achieved with special stool regulatory measures (in particular irrigation), while the patient can make to with a stoma cap or a mini-bag. Many complications of stoma, in particular necrosis, parastomal hernias, prolapse, too large a stoma, stenosis and stomal recurrent tumor can usually be eliminated by surgery. CONCLUSIONS: Today excellent possibilities of stomal care are available for a wide range of problems, which can be determined and applied in cooperation with the various specialists.

Animals↗

Relationship of fertility to milk yield in Swedish cattle.

Data consisted of 48,830 and 21,136 records of Swedish Red and White and Swedish Black and White cattle. Fertility in virgin heifers and in first lactation cows was measured by first service pregnancy rate and number of services per pregnancy. Production trait considered was FCM produced in first 100 d of lactation. The heritabilities for fertility traits in virgin heifers and first lactation cows were about .05 in both breeds. The genetic correlations between fertility measures within parity were close to one in both breeds, suggesting that these were measures of the same trait. The genetic correlations between fertility in virgin heifer and in first lactation were about .88 for Swedish Red and White breed and between .6 and .7 for Swedish Black and White breed. The association between fertility and production in first lactation cows was antagonistic, with genetic correlations between first service pregnancy rate and milk yield of -.13 and -.32 for Swedish Red and White and Swedish Black and White breed, respectively. The association between first service pregnancy rate in virgin heifers and milk yield in first lactation was also antagonistic, with genetic correlations of -.14 and -.41 for Swedish Red and White and Swedish Black and White breed, respectively.

Animals↗

[Myocutaneous and fasciocutaneous free flap for covering the lower leg and foot--a comparative study].

A comparison is presented of free myocutaneous flaps, e.g. latissimus dorsi flap, gracilis flap and the inferior gluteal flap, with fasciocutaneous flaps, especially the scapular/parascapular flap, for covering defects of the lower leg and the foot. Myocutaneous flaps are especially suited to cover deep defects with loss of bone and provide a good basis for free bone grafting. Fasciocutaneous flaps are better suited to cover plain defects, having a good blood supply due to the rich epifascial vascular network. They are thinner than the myocutaneous flaps and in extensive defects they do not need additional free skin transplantation in the recipient area.

Foot Injuries↗

Lack of effect of rat atrial natriuretic factor (rANF) on the renal function in frogs.

1. The aim of the present experiments was to examine the question whether the rat atrial natriuretic factor (rANF 1-28) could alter the fractional excretion of sodium (FENa) and other solutes in the frog (Rana esculenta). 2. Although experiments were performed throughout the year possible seasonal changes in the animals were considered in particular. 3. In all frogs, a hypotonic diuresis was induced. 4. Under these conditions in winter frogs, the control FENa was 8.8 +/- 5.8% (15) [means +/- SD (n)], and during rANF administration 7.7 +/- 6.6% (13) (NS). 5. In summer frogs, the control and experimental FENa was 5.2 +/- 2.8% (5) and 6.0 +/- 2.5% (5), respectively (NS). 6. These results show that there was no significant effect of this polypeptide on the fractional excretion of sodium in the frog.

Animals↗

Reabsorption of inorganic sulfate in the frog kidney: saturation of transport mechanism.

1. Clearance experiments were performed to study reabsorption of inorganic sulfate (SO4) in the frog kidney. 2. During stepwise elevation of the SO4 concentration in plasma by i.v. sulfate administration (SO4 titration), the absolute reabsorption of SO4 did not increase but kept constant during mild SO4 loading. 3. The maximal reabsorptive capacity for SO4 (TmSO4) was about 0.37 mumol/30 min in this species. 4. The present results do not indicate renal net secretion of SO4 in the frog.

Absorption↗

[Microvascular architecture of the all-layer free inferior abdominal wall flap].

The authors dissected all layers of the inferior abdominal wall to study the possibility of free transplantation to close combined skin and mucosal defects. They perfused these flaps with a special solution of lead oxide and gelatin (Rees and Taylor 1986). After fixation in formalin the flaps were dissected in their layers and radiographs of these were taken. Networks of small vessels, which originate in the inferior epigastric artery, were found preperitoneally in the deepest compartment, in the muscular compartment and, nourished by perforators via the ventral rectus fascia, epifascially and subdermally in the subcutaneous tissue. On this basis free microvascular transplantation of a full-thickness abdominal wall flap seems to be possible to close combined mucosal and cutaneous defects. To thin this flap the subcutaneous middle third could be removed taking care to protect the epifascial and subdermal plexus of vessels. An isolated pre- and peritoneal microvascular flap also seems to be possible.

Abdominal Muscles↗

[A masked paraganglioma--a rare cause of pain in lymphedema of the arm].

The history is reported of a 66 year-old patient who suffered from postmastectomy edema and continuous pain on the ulnar side of the wrist. After microsurgical lymphatic grafting the edema diminished. At the site of pain there was a resistance palpable with reduced resonance on ultrasonography. At operation the authors excised a tumor which on histological and immunohistochemical investigation was compatible with a paraganglioma.

Aged↗

[Vascular ultrastructure of the scapular flap].

The authors dissected fourteen cadaveric scapular flaps to study isolated free fascial and subcutaneous tissue transfer. They perfused these flaps with a special solution of lead oxide and gelatin (Rees and Taylor 1986). After fixation in formaldehyde, the flaps were dissected in three layers and radiographs were made of these compartments. In the basal layer, which comprises 40% of the flap thickness, an epifascial network of small vessels was found. In the most superficial, subdermal compartment which makes up 30% of the flap, a similar network was found. Therefore, it should be possible to dissect isolated fasciocutaneous or deep subcutaneous microvascular flaps. To thin a scapular flap, the subcutaneous middle third should be removed to protect these plexus of vessels.

Arteries↗

Effect of saline infusion on net reabsorption of endogenous sulfate relative to that of phosphate in intact and thyroparathyroidectomized rats.

Clearance experiments have been performed to study the effects of saline infusion on the reabsorption of inorganic sulfate (SO4) at endogenous levels. Adult female Sprague-Dawley rats on a standard diet were used. Both intact and thyroparathyroidectomized (TPTX) animals were infused with a 130 mmol/l sodium chloride solution at a low (0.15 ml/min) and a high (0.375 ml/min) rate. This increase of the infusion rate decreased the reabsorption of SO4 in both groups of animals significantly. The fractional excretion of SO4 in the intact rats increased from 9.9 +/- 5.6 to 18.4 +/- 3.6% (mean values +/- SD, p less than 0.001) and in the TPTX rats from 5.3 +/- 2.5 to 22.4 +/- 6.3% (p less than 0.001). It is concluded that endogenous parathyroid hormone has no major effect on the saline-induced inhibition of reabsorption of SO4.

Absorption↗

Regulation of the renal transport of inorganic sulfate: effects of metabolic changes in arterial blood pH.

The present experiments were designed to examine the effects of mild metabolic changes of blood pH on the reabsorption of inorganic sulfate (SO4) in the rat. Female adult Sprague Dawley rats (which were kept on a standard diet) were used. In order to produce either a metabolic alkalosis (Alk) or a metabolic acidosis (Ac), 130 mmol/l NaHCO3 or a mixture of 130 mmol/l NH4Cl and 130 mmol/l NaCl was infused. The blood pH values were 7.49 +/- 0.02 and 7.29 +/- 0.02, respectively. The fractional excretion (FE) of SO4 was 28.6 +/- 5.7 (Alk) and 9.5 +/- 2.7 (Ac), respectively. These changes were significant (P less than 0.001). It is concluded, that physiological metabolic changes of blood pH may be important in the renal regulation of the transport of SO4.

Acid-Base Equilibrium↗