[Intraoperative enteroscopy--personal experience from 1995 to 2002]. / Intraoperacní enteroskopie--vlastní zkusenosti z období 1995-2002.

Authors present their experience with the intraoperative enteroscopy method--an invasive technique of small bowel examination. It is performed under narcosis at an operating theatre (i.e. in co-operation with surgeon and anaesthesiologist). The endoscopy-performing physician becomes one of the members of the operating team. The advantage of the method is the possibility to examine of the whole small intestine and to solve immediately the pathological findings by endoscopic or surgical intervention. The examination is invasive and the correct indication is mandatory. Authors report their results of 18 intraoperative panendoscopies of small intestine.

[Torsion of the spleen--an unusual cause of sudden acute abdomen]. / Torze sleziny--neobvyklá prícina náhlé príhody brisní.

Torsion of a wandering spleen is rare and has been diagnosed in about 0.2%-0.3% of a large group of patients who required splenectomy. Abnormalities in the ligamentous structures that fix the spleen are thought to be responsible for its abnormal position and for its torsion. Patients may present with various symptoms ranging from mild intermittent abdominal pain to an acute abdomen. Computed tomography leads to correct diagnosis.

[15 years' clinical experience in cryodestruction of malignant disorders in the anorectum]. / 15 let kryodestrukce maligních afekcí anorektální oblasti v klinické praxi.

The authors submit a clinical rectrospective study which covers fifteen years of experience in the field of the anorectal tumours cryodestruction. During the 15 years time interval altogether 720 cryodestructions were performed in 128 patients with a malignant lesion of anorectal region. The fifteen years span includes the period of time from 1983 to 1997. Cryosurgery in malignancies belongs to the complex treatment of tumors. This work statistically shows various combinations of chemotherapy, X-ray therapy and immunotherapy.

[Treatment of keloids and hypertrophic scars with cryotherapy]. / Lécba keloidní a hypertrofické jizvy kryoterapií.

Keloid and hypertrophic scars are relatively frequent not wanted consequences of surgical treatment. 145 patients with unsatisfactory skin healing were treated in our department during last 5 years. When compared with corticotherapy and laser-therapy kryotherapy is very effective method. There were outstanding results with combination of cryotherapy and corticotherapy.

[Gastrointestinal stromal tumor--GIST--case report]. / Gastrointestinální stromální tumor--GIST--kazuistika.

Authors describe a newly introduced oncological entity that represents different views on some already well known mesenchymal and neuroectodermal tumours of gastrointestinal tract. These submucosal GIT tumours, showing only few differences in both the clinical and histological pictures, are generally called gastrointestinal stromal tumours. This paper presents a case of 37 year old patient with this disease.

Percutaneous absorption of disopyramide, lidocaine and trimecaine.

Promoting effect of cyclic monoterpenes on percutaneous absorption of antiarrythmics drugs disopyramide, lidocaine and trimecaine was investigated in the rats. Laurocapram (Azone) was used as a standard comparator of penetration enhancement. The absorption of trimecaine was significantly enhanced by addition of limonene, trans-p-menthane and Azone in 1% concentration. Lidocaine and disopyramide penetrated across the skin only when 1% of limonene was used. Other cyclic monoterpenes showed no effect on percutaneous absorption of examined drugs.

Influence of acute uraemia on percutaneous absorption of nonsteroidal anti-inflammatory drugs.

The influence of uraemia on percutaneous absorption of three model drugs (diclofenac, ibuprofen and indomethacin) which are eliminated entirely via nonrenal route was investigated in the rats. Following day after bilateral nephrectomy (BUN levels were between 30-50 mmol/l), gel ointment containing drugs under test was applied on the abdominal site of the skin. Comparing with the sham operated controls the percutaneous absorption significantly decreased in all three challenged substances. Influence on percutaneous absorption of indomethacin was investigated more in depth as this compound can serve as a model for other nonsteroid anti-inflammatory drugs. The 50 mmol/l concentration of urea (equal to uraemia) added to the gel ointment did not influence percutaneous absorption while 10% concentration of urea decreased percutaneous absorption of indomethacin approximately 5 times. Solubility of indomethacin increased in the presence of 10% urea in the gel more than two times. Elimination ratios Q0 were estimated to find if there is any effect on pharmacokinetics linked directly to the renal elimination. None of such changes were observed.

The influence of detergents on skin barrier properties.

The influence of surfactants on the changes in skin barrier properties was investigated in rats. Various ionic and non-ionic surfactants were assessed using indomethacin as a model penetrant. The surfactants appeared to either increase or decrease the skin permeability, due to the properties of both compound and surfactant. Ionic surfactant sodium dodecylsulfate was the most powerful and exceeded controls by approximately 10 times measured by means of serum levels of indomethacin. Other surfactants caused concentration increase or decrease of indomethacin in serum.

Influence of limonene and laurocapram on percutaneous absorption of nonsteroidal anti-inflammatory drugs.

The promoting effect of cyclic monoterpenes, 1% limonene (CAS 5989-27-5) and 1% cineole (CAS 470-82-6), on percutaneous absorption of nonsteroidal anti-inflammatory drugs was investigated in the rats. Compared with 1% laurocapram, drug absorption from the gel ointments was significantly more enhanced by addition of 1% limonene, while without any enhancer only ibuprofen penetrated across the skin in the limited amount. When using formulation with propylene glycol or 50% propylene glycolethanol solution, instead of carboxyvinyl polymer gel, percutaneous absorption significantly decreased and neither limonene nor cineole or laurocapram were capale to promote percutaneous absorption of flufenamic acid to sufficient serum level. Cineole and limonene were also evaluated in permeation experiments in vitro. Enhancement ability of limonene in the gel oinment was approximately 5 times higher comparing with enhancement ratio of cineole, while in 100% propylene glycol enhancement ability of both cyclic monoterpenes was equal. Good correlation was observed between in vivo and in vitro experiments. Evaluation of solubility proved that in the gel ointment simulated as water-ethanol solution were relatively best condition for percutaneous absorption of flufenamic acid when comparing with propylene glycol or 50% propylene glycol-ethanol solution.

Changes of lithium elimination in acute polyuric renal failure caused by cisplatin and mercuric chloride.

Changes in lithium elimination were studied under the condition of experimentally induced polyuric acute renal failure by cisplatin (6 mg/kg body wt) or HgCl2 (3 mg/kg body wt). The histologically proven lesions of tubuli were associated with the decrease of plasma clearance of lithium (C(Li)) and polyfructosan-S (CP(FS). The decrease of these clearance values was not proportional and the ratio C(Li)/CP(FS) (indicating renal fractional excretion of Li+) increased significantly (p less than 0.01). The increase of C(Li)/CP(FS) was related to the increase of renal fractional sodium excretion (FENa) (p less than 0.01). The results suggest that the impairment of tubular cells by cisplatin or HgCl2 caused the decrease of tubular reabsorption of Li+ and Na+. From the pharmacokinetic point of view, these experiments suggest that changes in tubular transport of drugs should be taken into account in their dosing adjustment in patients with acute polyuric tubular lesion.

Evaluation of in-vitro percutaneous absorption across human skin and in animal models.

The in-vitro permeability characteristics of human skin have been examined and compared with results in laboratory animals using various types of penetration enhancers. The study was focused on evaluation of predictable validity of the data obtained in animals mostly used in permeation studies. The results in man using the same penetration enhancers were about 30% of the value in the rat. The least potent enhancer was dimethylsulphoxide and the maximum efficacy was observed with sodium laurylsulphate in the rat experiments while in man the results were approximately equal when using any of the studied enhancers. Comparison of the results of experiments performed with N-methyl-2-pyrrolidone in several laboratory animals and man showed that the skin permeability in man is approximately 4 times lower than with the rat. Man and guinea-pig were not significantly different in these experiments. There were no significant differences in laurocapram penetration enhancing effect in the concentration range 0.1 to 0.5%, but there was an optimum concentration of laurocapram of 1%. The results showed quantitative differences in percutaneous absorption in various animal species in comparison with man. These differences should be considered in selecting a suitable model for preclinical drug evaluation. The guinea-pig skin penetration seems to be most similar to that in man.

[Cryotherapy of an inoperable breast tumor]. / Kryolizace inoperabilního nádoruprsu.

The use of cryocauter in inoperable tumor of breast is described. Case-reports are presented of successful approach by cryolysis prior to the final lobe plastic.

[Bone metabolism in patients after kidney transplantation]. / Kostní metabolismus u nemocných po transplantaci ledviny.

The bone metabolism was evaluated in 20 patients after successful transplantation of the kidneys. In case of a functional graft within 22 months after transplantation of the kidneys complete regression of histological signs of secondary hyperparathyroidism was found, i.e. of fibrous osteodystrophy with a decline of the osteoclastic absorption and in 50% of the patients bone histology revealed osteomalacia. On the X-ray of the skeleton in 65% signs of osteoporosis were found, incl. 10% where the results were in discrepancy with the histological finding. The normal plasma calcium level before and after transplantation of the kidney was not affected. Other basic indicators of bone metabolism--phosphates, alkaline phosphatase, the bone isoenzyme of alkaline phosphatase and parathormone attained normal levels within 22 months after transplantation. Bone fluorides remain elevated also after 22 months following successful transplantation of the kidneys, although significantly less than before.

Comparison of penetration-enhancing ability of laurocapram, N-methyl-2-pyrrolidone and dodecyl-L-pyroglutamate.

The study reports on penetration enhancers used to improve drug absorption through the skin. All experiments were carried out in permeation cells in vitro. Insulin (2.5 mg/ml) and Brilliant Blue (50.0 mg/ml) served as model drugs. They were formulated into a 40% solution of propylene glycol with increasing concentrations of N-methyl-2-pyrrolidone (NMP) (0.0 to 20.0%), dodecylazacycloheptan-2-one (laurocapram) and a new compound dodecyl-L-pyroglutamate (DLP; 0.0 to 0.5%). The maximum amount of insulin permeated within 24 h was almost 200 microU/ml in the case of 0.1% laurocapram, while in the case of 0.1% DLP it was approximately half of that. The optimum concentration of NMP was 12.0%. Experiments performed with Brilliant Blue showed no significant difference among formulations containing either 6.0, 12.0 or 20.0% of NMP. When NMP was omitted, flux, permeability as well as the maximum concentration estimated after 26 h reached 50% of the values obtained with NMP. The lag time was twice as long in this case in comparison with the formulations containing NMP.

Combination effect of penetration enhancers and propylene glycol on in vitro transdermal absorption of insulin.

In vitro transdermal absorption of insulin was improved when the penetration enhancers Azone, N-methyl-2-pyrrolidone (NMP) or dimethyl sulfoxide (DMSO) were incorporated in propylene glycol (PG) formulations of the drug. Maximum penetration efficacy depended on optimal concentrations of both the enhancer and PG. Azone and NMP showed maximum efficacy at 0.1% and 12.0% concentration, respectively. In both cases, the optimum concentration of PG was 40.0%. The enhancing ability of DMSO was much lower in comparison with the other two enhancers.

Preclinical modeling of changes in drug kinetics caused by acute renal failure in rats.

The rates of total and extrarenal elimination of amikacin, cefoperazone, ceftriaxone, gentamicin, mesocain, theophylline, tobramycin, and polyfructosane-S were determined in rats with intact kidneys and in those after bilateral nephrectomy. While the values of the elimination constants of the tested drugs were markedly higher in the rats than in man, the ratio of nonrenal and total elimination constants, expressing the fraction of drugs eliminated extrarenally, is close to the value found in man. These findings suggest that the model might be useful in preclinical drug testing and can help in the prediction of changes in the kinetics of drugs caused by renal failure.

Changes of pharmacokinetic in rats after bilateral nephrectomy--a model for prediction of pharmacokinetic changes in patients with chronic renal insufficiency.

Elimination of gentamicin, tobramycin, amikacin, cefoperazone, ceftriaxon and lithium was investigated in healthy and bilaterally nephrectomized rats. This model of renal failure was used to determine the nonrenal elimination constantsebz, diesambino calculation of the ratio of the nonrenal and total elimination constant Qo. The values of Qo of the investigated drugs in the used model were very close to those given in the literature for men. These results suggest that the described model can be helpful in predicting the percentage of drug excreted renally and nonrenally, and the delay in drug excretion in renal insufficiency.