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PubMed2003

Laser microdissection of small tissue samples--application to chronic pancreatitis tissues.

Laser microdissection is considered to be the gold standard of tissue sampling, especially if a defined small tissue area consisting of single or few cells within a heterogeneous tissue compartment is of interest. This sophisticated technique offers the opportunity of rapid and contamination-free tissue sampling for RNA- or DNA-based molecular genetic studies. We have applied laser microdissection to a molecular genetic study of pancreatic intraductal lesions (PanINs) in tissues of chronic pancreatitis, where an exact microdissection of small ducts within a dense fibrous tissue is of paramount importance for following analysis. From nine patients suffering from chronic pancreatitis, formalin-fixed, paraffin-embedded tissue specimens were laser microdissected, and a total of 202 normal ducts and PanINs of grade PanIN-1A to grade PanIN-2 were harvested. After whole genome amplification by improved primer extension and preamplification PCR (I-PEP-PCR), microsatellite-PCR based loss of heterozygosity analysis (LOH) of the tumor suppressor gene loci TP53, p16INK4, and DPC4 was performed. One of 85 informative duct lesions (1.2%) had LOH of TP53, 1 of 76 duct lesions (1.3%) had LOH of DPC4, and 2/29 duct lesions (6.9%) showed LOH of p16INK4. Microsatellite instability (MSI) was seen in 2 of 178 duct lesions (1.1%). Immunohistochemical staining of p53 protein and DPC4 protein revealed no aberrant expression. These preliminary data indicate that LOH of tumor suppressor genes, important in pancreatic cancer genesis or MSI, can be found in chronic pancreatitis tissues, but their incidence is low.

Chronic Disease↗
PubMed1998

Fucosyltransferase activities in human pancreatic tissue: comparative study between cancer tissues and established tumoral cell lines.

Human pancreatic cancer is characterized by an alteration in fucose-containing surface blood group antigens such as H antigen, Lewis b, Lewis y, and sialyl-Lewis. These carbohydrate determinants can be synthesized by sequential action of alpha(2,3) sialyltransferases or alpha(1,2) fucosyltransferases (Fuc-T) and alpha(1,3/1,4) fucosyltransferases on (poly)N-acetyllactosamine chains. Therefore, the expression and the function of seven fucosyltransferases were investigated in normal and cancer pancreatic tissues and in four pancreatic carcinoma cell lines. Transcripts of FUT1, FUT2, FUT3, FUT4, FUT5, and FUT7 were detected by RT-PCR in carcinoma cell lines as well as in normal and tumoral tissues. Interestingly, the FUT6 message was only detected in tumoral tissues. Analysis of the acceptor substrate specificity for fucosyltransferases indicated that alpha(1,2) Fuc-T, alpha(1,3) Fuc-T, and alpha(1,4) Fuc-T were expressed in microsome preparations of all tissues as demonstrated by fucose incorporation into phenyl beta-d-galactoside, 2'-fucosyllactose, N-acetyllactosamine, 3'-sialyl-N-acetyllactosamine, and lacto-N-biose. However, these fucosyltransferase activities varied between tissues. A substantial decrease of alpha(1,2) Fuc-T activity was observed in tumoral tissues and cell lines compared to normal tissues. Conversely, the activity of alpha(1,4) Fuc-T, which generates Lewis a and sialyl-Lewis a structures, and that of alpha(1,3) Fuc-T, able to generate a lactodifucotetraose structure, were very important in SOJ-6 and BxPC-3 cell lines. These increases correlated with an enhanced expression of Lewis a, sialyl-Lewis a, and Lewis y on the cell surface. The activity of alpha(1,3) Fuc-T, which participates in the synthesis of the sialyl-Lewis x structure, was not significantly modified in cell lines compared to normal tissues. However, the sialyl-Lewis x antigen was expressed preferentially on the surface of SOJ-6 and BxPC-3 cell lines but was not detected on Panc-1 and MiaPaca-2 cell lines suggesting that several alpha(1,3) Fuc-T might be involved in sialyl-Lewis x synthesis.

Aged↗
PubMed2003

Tissue counter analysis of tissue components in skin biopsies: evaluation using CART (Classification and Regression Trees).

In tissue counter analysis, complex histologic sections are overlaid with regularly distributed measuring masks of equal size and shape, and the digital contents of each mask (or tissue element) are evaluated by gray level, color, and texture parameters. In this study, the feasibility of tissue counter analysis and classification and regression trees for the quantitative evaluation of skin biopsies was assessed. From 100 randomly selected skin biopsies, a learning set of tissue elements was created, differentiating between cellular elements, collagenous elements of the reticular dermis, fatty elements and other tissue components. Classification and regression trees based on the learning set were used to automatically classify tissue elements in samples of normal skin, benign common nevi, malignant melanoma, molluscum contagiosum, seborrheic keratosis, epidermoid cysts, basal cell carcinoma, and scleroderma. The procedure yielded reproducible assessments of the relative amounts of tissue components in various diagnostic groups. Furthermore, a reliable diagnostic separation of molluscum contagiosum versus normal skin and epidermal cysts, benign common nevi versus malignant melanoma, and seborrheic keratosis versus basal cell carcinoma was possible. Tissue counter analysis combined with classification and regression trees may be a suitable approach to the fully automated analysis of histologic sections of skin biopsies.

Biopsy↗
PubMed1996

Marginal zone lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type) of skin and subcutaneous tissue: a study of 15 patients.

Extranodal low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type occurs in the gastrointestinal tract, salivary gland, thyroid, orbit, lung, and breast. We report 15 patients with MALT-type lymphomas involving skin and subcutaneous tissue. All patients had tumors with histologic features of low-grade B-cell lymphoma of MALT type, including marginal zone cells (15 of 15 cases), plasmacytic differentiation (10 of 15 cases), Dutcher bodies (three of 15 cases), and reactive germinal centers (10 of 15 cases). All expressed pan B-cell antigens and monotypic immunoglobulin. Seven patients (five women, two men) aged 29 to 86 years (median, 53 years) had primary MALT-type lymphoma of skin (6) or subcutaneous tissue (1). One patient had persistent disease, and four patients had relapses involving skin, subcutaneous tissue, breast, orbit, and lymph node. At last follow-up (11-121 months; median, 36 months), one patient was alive with disease, and six patients had no evidence of disease. Three patients (two women, one man) aged 36 to 67 years (median, 57 years) had concurrent MALT-type lymphoma involving both subcutaneous tissue and extracutaneous sites at primary diagnosis, including lung, breast, orbit, lymph node, and bone marrow. One patient responded to treatment but relapsed with lymphoma of the skin and breast. The other two patients had persistent disease despite treatment. One patient died of disease at 25 months, and, at last follow-up (7 and 46 months), two patients were alive with disease. Five patients (four women and one man) aged 29 to 72 years (median, 63 years) had secondary skin or subcutaneous involvement by MALT-type lymphoma with primary tumors of ocular adnexa (3) or parotid gland (2). All five patients had relapses, which involved skin or subcutaneous tissue, parotid gland, lacrimal gland, breast, and lymph node. At last follow-up (61-137 months), two patients were alive with disease and three were alive with no evidence of disease. Low-grade B-cell lymphomas of MALT type may arise in or secondarily involve the skin and subcutaneous tissue and have a tendency to affect middle-aged to older women. These tumors are characterized by multiple extranodal relapses and are associated with long patient survival. Patients with primary MALT-type lymphoma of skin or subcutaneous tissue without extracutaneous involvement at diagnosis were more likely to experience prolonged disease-free survival than patients with extracutaneous spread at presentation (p < 0.03).

Adult↗
PubMed2001

Tissue factor pathway inhibitor response does not correlate with tissue factor-induced disseminated intravascular coagulation and multiple organ dysfunction syndrome in trauma patients.

OBJECTIVE: To determine the precise relationship between tissue factor and tissue factor pathway inhibitor (TFPI) after trauma, as well as to test the hypothesis that low TFPI levels are not sufficient to prevent tissue factor-dependent intravascular coagulation, leading to multiple organ dysfunction syndrome (MODS). DESIGN: Prospective, observational cohort study. SETTING: Emergency room and intensive care unit in a university hospital. PATIENTS: Thirty-three trauma patients, 18 with disseminated intravascular coagulation (DIC) and 15 without DIC were studied. Ten normal, healthy volunteers served as control subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Antigen concentration of tissue factor and TFPI, and global parameters of coagulation and fibrinolysis were measured on the day of admission, and on days 1-4 after admission. The number of systemic inflammatory response syndrome (SIRS) criteria that patients met and the DIC score were determined, simultaneously. The results of these measurements, incidence of MODS, and outcome were compared between the DIC patients and those without DIC. In the DIC patients, significantly higher tissue factor levels (p =.0049) and lower platelet counts (p =.0016) were found compared with the non-DIC patients and control subjects. However, the TFPI values remained at normal levels during the study period. No correlation was found between the peak levels of tissue factor and TFPI. The mean duration of SIRS and the maximum number of the SIRS criteria being met by the patients in the DIC group were statistically longer and higher than those in the non-DIC patients. The incidence of MODS and the number of the dysfunctioning organs were higher in the DIC patients compared with those in the non-DIC patients, and the DIC patients had a poor outcome. CONCLUSIONS: We systematically elucidated the relationship between tissue factor and TFPI in post-trauma patients. Highly activated tissue factor-dependent coagulation pathway is not sufficiently prevented by the normal TFPI levels in patients with DIC. The DIC associated with thrombotic and inflammatory responses causes MODS, and leads to poor outcome in post-trauma patients.

APACHE↗
PubMed2002

Discriminating vital tumor from necrotic tissue in human glioblastoma tissue samples by Raman spectroscopy.

Vital and necrotic glioblastoma tissues were studied by Raman microspectroscopy to identify possibilities for the development of an in vivo Raman method for real-time intraoperative brain biopsy guidance. The histologic malignancy grade of gliomas depends on the presence of parameters such as endothelial proliferation and necrosis, which are often not evenly distributed within the tumor. Because tissue samples obtained by stereotactic surgery are relatively small, sampling errors may easily occur by missing these crucial features. Although necrosis is important for grading, specimens containing only necrosis are diagnostically useless. Raman microspectroscopic mapping experiments were performed on unfixed cryosections of glioblastoma, obtained from 20 patients. After spectral acquisition, a clustering analysis was performed, resulting in groups of similar spectra. Each cluster was assigned a color, and pseudo-color Raman maps of the tissue sections were constructed. After the Raman experiments, the tissue sections were stained for histopathologic analysis, enabling identification of the histologic origin of the Raman spectra and assignment of the Raman spectral clusters to either vital or necrotic tissue. A classification model for discrimination between vital and necrotic tumor tissue based on linear discriminant analysis was developed. The classification model was evaluated using independent Raman data obtained from nine other tissue sections and yielded 100% accuracy. Information about the biochemical differences between necrosis and vital tumor was obtained by the analysis of difference spectra. Necrotic tissue was found to consistently contain higher levels of cholesterol (-esters). This in vitro result indicates that Raman spectra contain the information to distinguish vital glioblastoma from necrosis and makes Raman spectroscopy a powerful candidate for guidance of stereotactic brain biopsy.

Brain↗
PubMed2006

A 1-D model to explore the effects of tissue loading and tissue concentration gradients in the revised Starling principle.

The recent experiments in Hu et al. (Am J Physiol Heart Circ Physiol 279: H1724-H1736, 2000) and Adamson et al. (J Physiol 557: 889-907, 2004) in frog and rat mesentery microvessels have provided strong evidence supporting the Michel-Weinbaum hypothesis for a revised asymmetric Starling principle in which the Starling force balance is applied locally across the endothelial glycocalyx layer rather than between lumen and tissue. These experiments were interpreted by a three-dimensional (3-D) mathematical model (Hu et al.; Microvasc Res 58: 281-304, 1999) to describe the coupled water and albumin fluxes in the glycocalyx layer, the cleft with its tight junction strand, and the surrounding tissue. This numerical 3-D model converges if the tissue is at uniform concentration or has significant tissue gradients due to tissue loading. However, for most physiological conditions, tissue gradients are two to three orders of magnitude smaller than the albumin gradients in the cleft, and the numerical model does not converge. A simpler multilayer one-dimensional (1-D) analytical model has been developed to describe these conditions. This model is used to extend Michel and Phillips's original 1-D analysis of the matrix layer (J Physiol 388: 421-435, 1987) to include a cleft with a tight junction strand, to explain the observation of Levick (Exp Physiol 76: 825-857, 1991) that most tissues have an equilibrium tissue concentration that is close to 0.4 lumen concentration, and to explore the role of vesicular transport in achieving this equilibrium. The model predicts the surprising finding that one can have steady-state reabsorption at low pressures, in contrast to the experiments in Michel and Phillips, if a backward-standing gradient is established in the cleft that prevents the concentration from rising behind the glycocalyx.

Albumins↗
PubMed1988

Excised human neoplastic tissues are more sensitive to heat than the adjacent normal tissues.

In tissues from patients subjected to gastrectomy or colectomy, the heat sensitivity was determined in the case of 23 neoplastic, 15 gastric, 8 colorectal, and the adjacent normal tissues, using the in vitro succinate dehydrogenase inhibition test. The succinate dehydrogenase (SD) activity of tissue fragments was assayed, following exposure to heat at 43 degrees C (heat treatment) or 37 degrees C (control) for 5, 10, 15 or 20 h. The sensitivity to heat treatment was estimated by the percentage of SD activity of the heat-treated cells, compared to that of control cells. The decrease in SD activity varied in the tumor tissue, following exposure to heat. The SD activity decreased to a greater extent in the tumor tissue than in the adjacent normal tissue, in each case. The mean +/- standard deviation of SD activity, following exposure to heat treatment for 20 h, was 32.1 +/- 14.0% for the tumour tissues and 52.4 +/- 10.4% for the adjacent normal tissues, with a statistically significant difference (p less than 0.01). These results show that the assay of heat sensitivity is meaningful for prediciting the effectiveness of hyperthermia and that hyperthermia has a selectivity for treating a malignant lesion.

Adult↗
PubMed2000

Tissue engineering of pulmonary heart valves on allogenic acellular matrix conduits: in vivo restoration of valve tissue.

BACKGROUND: Tissue engineering using in vitro-cultivated autologous vascular wall cells is a new approach to biological heart valve replacement. In the present study, we analyzed a new concept to process allogenic acellular matrix scaffolds of pulmonary heart valves after in vitro seeding with the use of autologous cells in a sheep model. METHODS AND RESULTS: Allogenic heart valve conduits were acellularized by a 48-hour trypsin/EDTA incubation to extract endothelial cells and myofibroblasts. The acellularization procedure resulted in an almost complete removal of cells. After that procedure, a static reseeding of the upper surface of the valve was performed sequentially with autologous myofibroblasts for 6 days and endothelial cells for 2 days, resulting in a patchy cellular restitution on the valve surface. The in vivo function was tested in a sheep model of orthotopic pulmonary valve conduit transplantation. Three of 4 unseeded control valves and 5 of 6 tissue-engineered valves showed normal function up to 3 months. Unseeded allogenic acellular control valves showed partial degeneration (2 of 4 valves) and no interstitial valve tissue reconstitution. Tissue-engineered valves showed complete histological restitution of valve tissue and confluent endothelial surface coverage in all cases. Immunohistological analysis revealed cellular reconstitution of endothelial cells (von Willebrand factor), myofibroblasts (alpha-actin), and matrix synthesis (procollagen I). There were histological signs of inflammatory reactions to subvalvar muscle leading to calcifications, but these were not found in valve and pulmonary artery tissue. CONCLUSIONS: The in vitro tissue-engineering approach using acellular matrix conduits leads to the in vivo reconstitution of viable heart valve tissue.

Animals↗
PubMed2000

Physiological and cell biological aspects of perfusion culture technique employed to generate differentiated tissues for long term biomaterial testing and tissue engineering.

Optimal results in biomaterial testing and tissue engineering under in vitro conditions can only be expected when the tissue generated resembles the original tissue as closely as possible. However, most of the presently used stagnant cell culture models do not produce the necessary degree of cellular differentiation, since important morphological, physiological, and biochemical characteristics disappear, while atypical features arise. To reach a high degree of cellular differentiation and to optimize the cellular environment, an advanced culture technology allowing the regulation of differentiation on different cellular levels was developed. By the use of tissue carriers, a variety of biomaterials or individually selected scaffolds could be tested for optimal tissue development. The tissue carriers are to be placed in perfusion culture containers, which are constantly supplied with fresh medium to avoid an accumulation of harmful metabolic products. The perfusion of medium creates a constant microenvironment with serum-containing or serum-free media. By this technique, tissues could be used for biomaterial or scaffold testing either in a proliferative or in a postmitotic phase, as is observed during natural development. The present paper summarizes technical developments, physiological parameters, cell biological reactions, and theoretical considerations for an optimal tissue development in the field of perfusion culture.

Animals↗
PubMed1994

A possible link between molecular evolution and tissue evolution demonstrated by tissue specific genes.

In this paper, we reviewed our recent works on a possible link between molecular evolution and tissue evolution. The evolutionary rates of genes that are expressed tissue specifically were shown to differ widely to one another, depending on tissues: Brain specific genes evolve with significantly slower rate than immune specific genes. The tissue dependence of molecular evolutionary rate strongly suggests the presence of functional constraints against molecular changes from tissue level. A molecular phylogenetic analysis of tissue specific isoforms that are identical to one another in function, but differ only in tissue distribution revealed frequent gene duplications and rapid accumulations of amino acid substitutions during the early evolution of chordates, where rapid evolution at the tissue or organ levels is thought to have occurred. On the basis of functional constraints, a possible explanation for the correlation between evolution at the two levels was presented.

Animals↗
PubMed1999

Increased inspired oxygen concentration as a factor in improved brain tissue oxygenation and tissue lactate levels after severe human head injury.

OBJECT: Early impairment of cerebral blood flow in patients with severe head injury correlates with poor brain tissue O2 delivery and may be an important cause of ischemic brain damage. The purpose of this study was to measure cerebral tissue PO2, lactate, and glucose in patients after severe head injury to determine the effect of increased tissue O2 achieved by increasing the fraction of inspired oxygen (FiO2). METHODS: In addition to standard monitoring of intracranial pressure and cerebral perfusion pressure, the authors continuously measured brain tissue PO2, PCO2, pH, and temperature in 22 patients with severe head injury. Microdialysis was performed to analyze lactate and glucose levels. In one cohort of 12 patients, the PaO2 was increased to 441+/-88 mm Hg over a period of 6 hours by raising the FiO2 from 35+/-5% to 100% in two stages. The results were analyzed and compared with the findings in a control cohort of 12 patients who received standard respiratory therapy (mean PaO2 136.4+/-22.1 mm Hg). The mean brain PO2 levels increased in the O2-treated patients up to 359+/-39% of the baseline level during the 6-hour FiO2 enhancement period, whereas the mean dialysate lactate levels decreased by 40% (p < 0.05). During this O2 enhancement period, glucose levels in brain tissue demonstrated a heterogeneous course. None of the monitored parameters in the control cohort showed significant variations during the entire observation period. CONCLUSIONS: Markedly elevated lactate levels in brain tissue are common after severe head injury. Increasing PaO2 to higher levels than necessary to saturate hemoglobin, as performed in the O2-treated cohort, appears to improve the O2 supply in brain tissue. During the early period after severe head injury, increased lactate levels in brain tissue were reduced by increasing FiO2. This may imply a shift to aerobic metabolism.

Adult↗
PubMed2001

Human cells, tissues, and cellular and tissue-based products; establishment registration and listing. Food and Drug Administration, HHS. Final rule.

The Food and Drug Administration (FDA) is issuing a final rule to require human cells, tissue, and cellular and tissue-based product establishments to register with the agency and list their human cells, tissues, and cellular and tissue-based products. FDA is also amending the registration and listing regulations that currently apply to human cells, tissues, and cellular and tissue-based products regulated as drugs, devices, and/or biological products. These actions are being taken to establish a unified registration and listing program for human cells, tissues, and cellular and tissue-based products.

Biological Factors↗
PubMed2003

Combination of nucleic acid and protein isolation with tissue array construction: using defined histologic regions in single frozen tissue blocks for multiple research purposes.

Precise dissection of defined histological regions for nucleic acid and protein isolation is a precedent step in finding out cancer-related alterations, and high quality tissue microarrays are demanded in the validation of screened genetic alterations by multiple in situ approaches. In this study, a combined technique was developed by which sample isolation and tissue array construction could be performed on the defined morphological region(s) in single tissue block. The RNA and protein samples generated from the selected portions were of good quality and sufficient for multiple experimental purposes. The frozen tissue arrays constructed on a novel recipient are suitable for multiple in situ evaluations including immunohistochemical staining and mRNA hybridisation. In most cases, the data obtained from in situ assays coincided well with the ones revealed by RT-PCR and Western blot hybridisation. The potential experimental bias caused by cell contamination can be amended by tissue array-based retrospective examination. The combination of tissue-selective sample preparations with tissue array construction thus provide a tool by which comprehensive cancer research can be performed on defined histological regions in a series of single frozen tissue blocks.

Animals↗
PubMedDate not supplied

Potential error in the measurement of tissue to blood distribution coefficients in physiological pharmacokinetic modeling. Residual tissue blood. II. Distribution of phencyclidine in the rat.

A model for predicting the magnitude of error (% Err) in measuring tissue concentrations of a compound that have not been corrected for residual blood in the tissue was previously developed. The model was tested using data for phencyclidine tissue distribution in the rat. It is shown that % Err may be expressed as a function of volume fraction of blood in tissue (VF)B and tissue-to-blood distribution coefficient. Correction for residual blood is important when the volume fraction of the blood in the tissue is large and when the compound is not taken up substantially by the tissue. On the other hand, a correction may not be necessary when (VF)B is small and uptake of the compound into the tissue is substantial.

Animals↗
PubMed1990

[Glycosaminoglycans in human normal lung tissues and lung cancer tissues].

The quantitative changes of glycosaminoglycans in tumor tissue of human lung cancers (6 squamous cell carcinomas, 7 small cell carcinomas and 10 adenocarcinomas) were studied. Normal lung tissues contained of 3.38 mumol uronic acid/g dry weight glycosaminoglycans which consisted of hyaluronic acid, chondroitin sulfates, dermatan sulfate and heparan sulfate. The total amount of glycosaminoglycans in human lung cancer tissues increased 1.7 to 3.5 times in comparison with that in normal lung tissues. The increase in tissue content of glycosaminoglycans was accompanied by an increase in the chondroitin sulfate level in every histologic type of lung cancer, as well as marked increase in hyaluronic acid level in squamous cell carcinomas, and a moderate increase in small cell carcinomas. The concentrations of dermatan sulfate and heparan sulfate in lung cancer tissues did not show any significant changes compared with those in normal lung tissues. The increase in total amount and changes in the composition of glycosaminoglycans in human lung cancer tissue were closely related to the histologic type of the tumor. In adenocarcinomas, some acid glycoprotein with sialic acid was simultaneously detected during the separating course of glycosaminoglycans, which was considered to be derived from mucinous substances related to adenocarcinoma cells.

Adenocarcinoma↗
PubMed1984

Critical evaluation of the existence of so-called tissue-bound lithocholate in human liver tissue by selected ion monitoring.

Monohydroxy bile acids in liver tissue may be of importance because of their hepatotoxicity and strong cholestatic effects. Recently, the existence of lithocholate in liver tissue in two forms was suggested by Nair et al. (Lipids. 1977. 12: 922-929) i.e., either in free form or as so-called tissue-bound lithocholate released exclusively by cholylglycine hydrolase treatment. The presence of the latter aroused much interest in relation to its hepatotoxicity and possible role in tumor induction. In the present investigation lithocholyl-epsilon-L-lysine, proposed as the predominant tissue-bound bile acid, was synthesized and its metabolic behavior was tested. Lithocholyl-epsilon-lysine was not deconjugated by cholylglycine hydrolase treatment but only by alkaline hydrolysis. Bile acids in seven cirrhotic and three noncirrhotic liver samples were extracted with 95% ethanol-0.1% ammonium hydroxide. The bile acids in the extract and residue were quantified by glass capillary gas-liquid chromatography using selected ion monitoring. The presence of so-called tissue-bound lithocholate could not be substantiated in either cirrhotic or noncirrhotic liver tissues. Nearly complete extraction of lithocholate was achieved by the use of organic solvent alone. Therefore, tissue-bound lithocholate, if it exists at all, may be attached to tissue by a physical linkage which can be disrupted by the use of conventional organic solvent.

Adult↗
PubMed1981

Penetration into human urogenital tissues, muscle tissues, rib and cerebrospinal fluid of thiamphenicol.

The penetration of D(+)-threo-2-dichloroacetamido-1-(p-methylsulfonylphenyl)-1,3-propanediol (thiamphenicol, TAP, Urfamycine) into human renal, ureter, prostatic, testicular and muscle tissue, perirenal fat, rib as well as cerebrospinal fluid (CSF) after a single i.v. injection of 1.0 g of thiamphenicol glycinate ester was investigated. 2 h after TAP administration to 17 patients with severely diseased kidneys, the antibiotic concentration in renal tissue ranged from 9.8 to 138.7 microgram/g (mean value 40.4 +/- 29.9 microgram/g), in ureter tissue from 6.3 to 62.0 microgram/g (mean value 20.8 +/- 17.0 microgram/g), in muscle tissue from 1.7 to 13.7 microgram/g (mean value 8.2 +/- 3.6 microgram/g), in rib from 0.8 to 3.4 microgram/g (mean value 2.4 +/- 1.5 microgram/g) and in perirenal fat from 0.6 to 5.7 microgram/g (mean value 2.1 +/- 1.5 microgram/g). At the same time the TAP serum level varied from 4.6 to 15.2 microgram/ml (mean value 9.4 +/- 3.1 microgram/ml). Prostatic tissue concentration, measured in 16 patients with prostate adenomas, varied at 2 h after dosing, from 2.1 to 15.1 microgram/g (mean value 5.7 +/- 3.8 microgram/g). The simultaneous serum level was between 4.6 and 14.5 microgram/ml (mean value 8.9 +/- 3.4 microgram/ml). In 6 of these patients additionally CSF level was measured at 1.5 h post inj. and ranged from 0.11 to 0.65 microgram/ml (mean value 0.32 +/- 0.19 microgram/ml). Testicular tissue concentration assessed in 7 patients with prostate carcinomas varied at 2 h after i.v. injection from 3.4 to 8.4 microgram/g (mean value 6.1 +/- 1.9 microgram/g). The respective serum level in these patients was between 5.2 and 10.4 microgram/ml (mean value 8.5 +/- 1.7 microgram/ml). Several factors affecting the diffusion of TAP into the reported tissues and CSF are discussed. TAP should be regarded as an antibiotic with good penetration into urogenital tissues.

Adult↗