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Biomedical subjects

T Frank

Publications and source records attributed to T Frank.

At least 37 records · Page 2Linked to original sources

Cardiodepressant mediators are released after myocardial ischaemia: modulation by catecholamines and adenosine.

The interaction of recently characterized cardiodepressant mediators with catecholamines and adenosine after myocardial ischaemia was investigated using a model of sequential perfusion of two isolated guinea-pig hearts. Sequential perfusion was initiated after 10, 20, and 30 min (group I, II, and III) of global ischaemia in the first heart. At the onset of sequential perfusion LVdP/dtmax and min of Heart II decreased by 46 and 44% in group I, by 28 and 34% in group II, and increased by 60 and 24% in group III. Infusion of the beta1-receptor antagonist metoprolol (2.8 micromol L(-1)) into Heart II did not modulate contractile changes after 10 min of ischaemia in Heart I, prevented the attenuation of the cardiodepressant effect after 20 min of ischaemia, and completely reversed the positive inotropic effect after 30 min of ischaemia. The A1- and A2-receptor antagonists DPCPX (2 micromol L(-1)) and DMPX (20 micromol L(-1)) enhanced the positive inotropic and lusitropic effects in Heart II (LVdP/dtmax +154%, LVdP/dtmin +71%) during sequential perfusion after 30 min of ischaemia in Heart I. It is concluded that the effects of cardiodepressant mediators released after myocardial ischaemia are counteracted by a time-dependent release of catecholamines. Endogenous cardiac adenosine, in turn, attenuates the modulatory effects of catecholamines.

Adenosine↗

[Preoperative clonidine comedication within the scope of balanced inhalation anesthesia with sevoflurane in oral surgery procedures].

Both clonidine and sevoflurane are interesting drugs for anaesthesia in maxillo-facial surgery. The present study was performed to discover how far it is possible to combine the benefits of sevoflurane (fast modulation of depth of anaesthesia, rapid emergence and recovery) and clonidine (reduction of perioperative stress response, prophylaxis of postoperative shivering, analgetic, antiemetic and anaesthetic-saving effect) without compromising the pharmacokinetic of sevoflurane. Twenty-eight patients were included in the present double-blinded prospective study. These patients were randomly treated with an infusion of 4 micrograms kg-1 clonidine (group 1) or a placebo (group 2) preoperatively. For anaesthesia a standardized procedure with fentanyl, propofol, rocuronium, N2O/O2/sevoflurane and an antiemetic prophylaxis with DHB was performed. The depth of anaesthesia was controlled by using spectral edge frequency (target--SEF90 = 10 Hz). Perioperative stress response was assessed by noting the effects on haemodynamic parameters (MAP, heart rate), and emergence and recovery were assessed by using established standardized tests. We confirmed the anaesthetic-saving property of clonidine only for fentanyl (-20%). On the other hand, there was no difference in MAC-sevoflurane values between the groups in keeping a steady target--SEF90 (1.62 +/- 0.26 versus 1.65 +/- 0.24 vol.%). The time until emergence and recovery was not significantly different. Even the occurrence of PONV, the VAS level or the postoperative analgesic requirement did not differ in the two groups. However, the incidence of postoperative shivering was significantly higher in the placebo group. The stress response to intubation or extubation was lower in the clonidine group. The haemodynamic parameters in the clonidine group were intraoperatively always below the baseline, in some cases by more than 20%, making therapy for hypotension or bradycardia frequently necessary. Postoperatively, the majority of the patients showed similar changes in these parameters, but did not reach the 20% mark. Preoperative clonidine comedication seems to complicate the management of anaesthesia. On the other hand, it is beneficial during the early postoperative period (e.g. stability in haemodynamics, prophylaxis of shivering) without compromising emergence and recovery. Our results show that therapy with clonidine should be better placed at the end of anaesthesia.

Adult↗

Alteration of thiamine pharmacokinetics by end-stage renal disease (ESRD).

OBJECTIVE: In a comparative study with 20 end-stage renal disease (ESRD) patients the pharmacokinetics of two therapeutically used thiamine (vitamin B1) preparations were assessed. SUBJECTS, MATERIAL AND METHODS: After a single oral dose of either 100 mg benfotiamin (S-benzoylthiamine-o-monophosphate, BTMP) or 100 mg thiamine mononitrate (TN), blood levels of thiamine phosphate esters were analyzed by HPLC after precolumn derivatization to thiochrome phosphate esters for a 24-hour period. RESULTS: The pharmacokinetic parameters AUC0-24h, Cmax and tmax of the benfotiamin group in whole blood and plasma exceeded significantly those in the TN group. Only 1.0 vs. 0.6% of the administered dose were excreted in urine in the BTMP group and TN group, respectively. A high cellular efficacy, as was concluded from the short-term stimulation of the thiamine-dependent transketolase activity in erythrocytes (ETKA), was assessed for BTMP as well as TN. The activation coefficient (ETK-AC) decreased significantly from 1.10 to 1.04 vs. 1.12 to 1.07 in both the BTMP as well as TN groups, respectively. In addition, a high transfer rate to thiamine diphosphate (TDP) was observed in the patients after ingestion of BTMP. The TDP concentration in whole blood increased by 2.6 and 1.4 times from baseline levels to Cmax in the BTMP and TN groups, respectively. The AUC0-24h of TDP in whole blood after BTMP ingestion exceeded those after TN ingestion by 420%. CONCLUSION: These findings justify the therapeutic application of BTMP in ESRD, because a high intracellular concentration of TDP may protect against numerous adverse effects of uremia in the long run.

Chromatography, High Pressure Liquid↗

Percutaneous endoscopic external ring hernioplasty using Dundee inguinal canal retractor.

The percutaneous endoscopic external ring (PEER) hernioplasty is a novel technique that uses a minimal access approach to the inguinal canal by the anterior route and reproduces the conventional open tension-free mesh repair. The procedure consists of two stages: an open phase through a 2.5-cm incision over the external ring followed by an endoscopic repair of the defect. During the open stage, the spermatic cord is mobilized from the external ring, blunt finger dissection of the inguinal canal is used to create a space beneath the external oblique aponeurosis, and the hernial sac is dissected down to level of the preperitoneal fascia. The second endoscopic stage is performed after insertion of a telescope-mounted retractor through the external ring. The posterior wall of the inguinal canal is visualized and the hernial defect repaired by a tension-free mesh repair (Lichtenstein onlay mesh repair or mesh plug repair). The procedure provides an anatomic approach that is familiar to general surgeons. In a pilot study, the authors have established that the PEER hernioplasty is an easily learned, safe, and cost-effective operation that offers the benefits of minimal access surgery in terms of patient recovery and early return to work, and can be performed as a day case under local or regional anesthesia.

Adult↗

[Clinical relevance of I-123/I-131-MIBG scintigraphy in intestinal carcinoid tumors].

AIM: Of this retrospective study was to determine the value of MIBG-scintigraphy in patients with intestinal carcinoids dependent on histological, clinical, and biochemical parameters. METHODS: In 15 patients uptake in carcinoid tumors and metastasis was correlated with location of the primary tumor, intra- and extrahepatic tumor masses, histology, immunhistochemistry, neuroendocrinological markers, and clinical symptoms. RESULTS: High uptake was to be seen almost only in tumor masses of primary tumors located in the terminal ileum. There also was a positive correlation with clinical symptoms for carcinoids and urinary 5-HIAA level. No correlation between MIBG uptake and tumor masses, histology, and most of the immunhistochemical and neuroendocrinological markers could be found. CONCLUSION: There is a limited indication for MIBG-scintigraphy in follow up of intestinal carcinoids. In patient with proven uptake MIBG scintigraphy is suitable for long-term follow up and therapy monitoring.

3-Iodobenzylguanidine↗

[New methods for transurethral electroresection of the prostate from the anesthesiologic viewpoint].

Intravascular absorption of large volumes of solution without electrolytes is a common problem in transurethral resection of the prostate. In the present study we compared two different methods of resection (TURP vs. Vaporization TURP; 20 patients in each group) regarding fluid absorption and loss of blood. In addition, we report on 60 patients who had Vapo-TURP. The operations were performed by different very experienced surgeons. In both groups, spinal anaesthesia and standard regimes of infusion were used. The amount of fluid absorbed was measured by the ethanol method (2 vol.% ethanol; Widmark-formula). Haemoglobin, haematocrit and electrolytes were determined at set times. Ten of the 20 patients in the TURP group showed blood-alcohol levels > 0.1%/1000. In the Vapo-TURP group, only five of 57 patients (three patients with perforation of the prostate capsula were excluded) showed positive levels of blood-alcohol (< 0.05%/1000; fluid absorption < 150 ml). The difference was statistically significant (p = 0.002). Sixty minutes after the beginning of the procedures, the values of haemoglobin and haematocrit were significantly lower in the TURP group (7.68 +/- 0.41 vs. 7.38 +/- 0.64 mmol/l and 0.36 +/- 0.02 vs. 0.34 +/- 0.03). Regarding absorption of fluid and bleeding, Vapo-TURP was superior. From the anaesthesiological point of view, Vapo-TURP should be the method of choice, especially for the elderly.

Aged↗

Deficient transforming growth factor-beta1 activation and excessive insulin-like growth factor II (IGFII) expression in IGFII receptor-mutant tumors.

The insulin-like growth factor II receptor (IGFIIR) gene has been identified as a coding region target of microsatellite instability in human gastrointestinal (GI) tumors. IGFIIR normally has two growth-suppressive functions: it binds and stimulates the plasmin-mediated cleavage and activation of the latent transforming growth factor-beta1 (LTGF-beta1) complex, and it mediates the internalization and degradation of IGFII ligand, a mitogen. We used an immunohistochemical approach to determine whether IGFIIR mutation affected expression of these proteins in GI tumors. Four highly specific antibodies were used: LC(1-30), which recognizes the active form of TGF-beta1; anti-LTGF-beta1, which detects the LTGF-beta1 precursor protein; anti-IGFIIR; and anti-IGFII ligand. Twenty GI tumors either with (6 of 20) or without (14 of 20) known IGFIIR mutation were examined, along with matching normal tissues. Results were statistically significant in the following categories: (a) decreased active TGF-beta1 protein expression in IGFIIR-mutant tumor tissues versus matching normal tissues or IGFIIR-wild-type tumor tissues; (b) increased LTGF-beta1 protein expression in IGFIIR-mutant tumor tissues versus matching normal tissues or IGFIIR-wild-type tumor tissues; and (c) increased IGFII ligand protein expression in IGFIIR-mutant tumor tissues versus matching normal tissues or IGFIIR-wild-type tumor tissues. These data suggest that in genetically unstable GI tumors, mutation of a microsatellite within the coding region of IGFIIR functionally inactivates this gene, causing both diminished growth suppression (via decreased activation of TGF-beta1) and augmented growth stimulation (via decreased degradation of the IGFII ligand).

Colorectal Neoplasms↗

Frequent mutation of the E2F-4 cell cycle gene in primary human gastrointestinal tumors.

The E2F group of transcription factors transactivates genes that promote progression through the G1-S transition of the cell cycle. Members of the retinoblastoma (Rb) family of proteins bind to E2Fs and inhibit this function. E2F-4, one example of the E2F group, functions as an oncogene when transfected into nontransformed cells in vitro. On the other hand, mice that are homozygously lacking a normal E2F-1 gene develop cancers, consistent with a tumor-suppressive role for this gene. The exact function of E2Fs has thus been unclear; moreover, direct involvement of this gene in primary human tumorigenesis has not been shown. We, therefore, investigated mutation within the E2F-4 coding region in 16 primary gastric adenocarcinomas, 12 ulcerative colitis-associated neoplasms, 46 sporadic colorectal carcinomas, 9 endometrial cancers, and 3 prostatic carcinomas. We limited our investigation to the serine repeat within E2F-4, reasoning that this tract might be altered in genetically unstable tumors (replication error-positive, or RER+). All tumors were RER+, with the exception of a control group of 15 RER- sporadic colorectal carcinomas. PCR with incorporation of [32P]dCTP was performed using primers flanking the serine trinucleotide (AGC) repeat. Twenty-two of 59 gastrointestinal tumors (37%) contained E2F-4 mutations; these comprised 5 of 16 gastric tumors (31%), 4 of 12 ulcerative colitis-associated neoplasms (33%, including 1 dysplastic lesion), and 13 of 31 sporadic colorectal cancers (42%). No mutation was present in any of the endometrial, prostate, or RER- colorectal tumors. Of note, homozygous mutations occurred in three cases, and two of seven informative patients showed loss of one E2F-4 allele in their tumors. Furthermore, the RER+ sporadic colorectal tumors were evaluated at trinucleotide repeats within the genes for N-cadherin and B-catenin; no tumors demonstrated mutation of these genes. These data suggest that E2F-4 is a target of defective DNA repair in these tumors.

Adenocarcinoma↗

Subclinical rubella reinfection during pregnancy followed by transmission of virus to the fetus.

We report a documented case of rubella reinfection during pregnancy in a previously vaccinated woman with residual antibody titre to rubella of 15 IU/ml. The reinfection occurred following an exposure to rubella virus (contact with 6-year-old daughter with clinical rubella) between the 7th and 10th week of pregnancy which resulted in transmission of the virus to the fetus. Umbilical cord blood drawn by cordocentesis was found to be strongly positive for rubella IgM antibody. After termination of the pregnancy rubella virus was isolated in cell culture from fetal tissues.

Adult↗

Hearing thresholds, threshold repeatability, and attenuation values for passive noise-reducing earphone enclosures.

Passive noise-reducing earphone enclosures contain a supra-aural earphone mounted in a plastic dome. These enclosures are used to prevent the elevation of hearing thresholds due to masking from high levels of ambient noise. This research determined normal hearing threshold levels, threshold repeatability, and attenuation values for an Audiocup, Auraldome II, AudioMate, and Madsen ME-70 enclosure. In Study I hearing thresholds were obtained for 30 normally hearing adults from 500 to 6000 Hz in four test sessions for each enclosure and a supra-aural earphone attached to a headband. The hearing thresholds and repeatability for the Audiocup and Auraldome were similar but the thresholds were higher and repeatability was poorer for the AudioMate and Madsen ME-70 compared with the supra-aural earphone. In Study II real-ear attenuation values were obtained for each enclosure using 24 normally hearing subjects. The Audiocup and Auraldome II provided less low-frequency attenuation compared with the AudioMate and Madsen ME-70. The findings were related to the coupling of the supra-aural earphone in each enclosure to the ear and the coupling of each enclosure to the head. If an enclosure is used as an alternative to a supra-aural earphone for hearing testing in high ambient noise environments, hearing thresholds and threshold repeatability should be similar to a supra-aural earphone, and the enclosures should provide adequate attenuation of ambient noise. Since none of the enclosures met all of these requirements their use is not recommended for hearing testing.

Adult↗

Genetic susceptibility to breast and ovarian cancer.

5-10% of women with breast cancer carry an inherited mutation in either the BRCA1 or BRCA2 genes. These genes confer a very high lifetime risk of breast cancer, ovarian cancer (especially BRCA1) and male breast cancer (especially BRCA2). These genes are large, of essentially unknown function, and surprisingly, play a very small role in the development of tumors in non-predisposed individuals. These genes have now been cloned, a highly automated genetic test developed and high risk populations have been screened to establish the utility of the test. The value to women and preliminary clinically recommendations are discussed.

BRCA1 Protein↗

Percutaneous endoscopic external ring (PEER) hernioplasty.

This pilot study was conducted to determine if percutaneous endoscopic external ring (PEER) hernioplasty would be a viable alternative to the conventional and laparoscopic methods of tension-free repair. The procedure consists of (1) a 2.0-2.5-cm incision over the external inguinal ring to reach the emerging spermatic cord structures, and ligation and excision of the hernia sac and (2) insertion of an endoscope-attached retractor through the external ring, into the inguinal canal for visualization, dissection of posterior inguinal wall, and placement of mesh to complete tension-free repair. PEER hernioplasty was used to treat 48 patients with 60 primary hernias (bilateral in 12 patients) between January 1993 and December 1994. Median follow-up was 12 months and ranged from 5 to 22 months. All patients were discharged within 24 h after surgery except for one. All patients resumed their normal activity within 2-3 weeks. Only three complications were encountered (two scrotal hematomas and one inguinal seroma). To date, there has been recurrence of two hernias in one patient. We conclude that PEER hernioplasty is an effective method of repair of primary hernias that is less invasive than the conventional approach and both less invasive and more cost-effective than laparoscopic approaches.

Adult↗

Effects of triiodothyronine on morphology, growth behavior, and the actin cytoskeleton in mouse osteoblastic cells (MC3T3-E1).

We investigated the effects of thyroid hormone treatment on morphology, growth behaviour, and cytoskeletal structures of long-term cultured MC3T3-E1 cells. Morphological investigations were carried out on native cells by phase contrast microscopy and on epon-embedded semithin sections. The area covered by the cell and matrix layers (tissue-like area), percent extracellular matrix, average height of tissue-like area, and length and height of single cells were measured histomorphometrically on the cross sections. F-actin was analyzed histochemically and quantitated after fluorochrome-labeled phalloidin staining using confocal microscopy and fluorometry. Significant differences between control and T3-treated cells were found after confluency, but not in subconfluent cultures. Control cells continued to proliferate forming multilayers, and produced increasing amounts of extracellular matrix. In contrast, T3-treated cells stopped to proliferate forming two cell layers at the maximum. These cells were flattened, distinctly enlarged, and polygonal in shape. Histochemical staining for F-actin revealed three different staining patterns, depending on the position of the cell within the multilayer of control cultures. Basal cells contained a large number of thick stress fibers in parallel arrangement. Intermediate cells exhibited only a few thick actin filament bundles located at the outermost periphery. The superficial cells were characterized by a large number of thin, parallel-oriented microfilament bundles extending across the entire cytoplasm. The actin pattern of T3-treated cells resembled that of the basal cell layer of the control cells. The amount of F-actin increased with the prolonged T3 treatment. We conclude from these data that the known specific cellular responses to T3 treatment are accompanied by significant morphological alterations indicating pivotal effects of thyroid hormones on osteoblastic differentiation.

3T3 Cells↗

Frequency importance functions for words, sentences, and continuous discourse.

This research determined frequency importance functions (FIFs) for words, sentences, and continuous discourse under comparable conditions so that contextual effects of speech could be isolated. A male talker recorded 616 monosyllabic words, 176 meaningful sentences, and 44 continuous discourse (CD) passages. Twenty-four participants with normal hearing made intelligibility estimates of the CD passages and sentences and identified words in each of 44 low- and high-pass filtering and signal-to-noise ratio conditions. Plots of frequency versus percent of contributed intelligibility, or the FIFs, revealed that the frequency band that contributes the most to intelligibility is centered near 2000 Hz for all three types of speech. The results show a single peak in the importance function and a statistical analysis of the shape of the FIF (with kurtosis the pertinent measure) shows that there is a significant difference in the shape of the FIF based upon speech type. The data were also calculated into near-octave bands with similar results. The statistical analysis presented provides the basis for a test of the hypothesis: The degree of context or message redundancy is related to the relative importance of the frequency bands. The findings potentially have clinical as well as predictive implications.

Adolescent↗

[Postoperative vomiting after pars plana vitrectomy].

In the present investigation we compared two different techniques of anaesthesia--total intravenous anaesthesia (TIVA) versus balanced anaesthesia--with and without antiemetic prophylaxis, with regard to postoperative nausea, strangling irritation and vomiting and their influence upon postoperative complications (intraocular bleedings) and postoperative intraocular pressure after pars plana vitrectomia. For this investigation four groups were formed. The anaesthesias were carried out as orotracheal intubational anaesthesia following two standard techniques, which only differ in the choice of the narcotics. Half the patients in each group were treated with an antiemetic prophylaxis of 2.5 mg DHBP. With regard to the occurrence of postoperative nausea and vomiting, the TIVA-groups proved to be better than those with balanced anaesthesia (16% to 43.5%; p < 0.05): DHBP in both methods led to a reduction of postoperative vomiting and nausea, but the differences showed not to be significant (p > 0.05). Best results were achieved with a combination of TIVA (propofol, alfentanil, atracurium, air/O2) and DHBP (4.7%). The total rate of postoperative complications in form of intraocular bleedings amounted to 8.6%. The appearance of complications increased when postoperative nausea and vomiting or increased intraocular pressure were observed (16.6% to 6.3%; 21.2% to 6.1%). Intraocular pressure, measured for four hours postoperatively, was significantly lower in the TIVA-groups than in the balanced anaesthesia-groups (15.5 +/- 7.7 mmHg to 18.3 +/- 8.2 mmHg). Therefore, we conclude that TIVA with propofol appears to be especially suitable for intraocular surgery.

Adult↗

Atraumatic retractor for endoscopic surgery.

A novel retractor has been designed to achieve atraumatic retraction of the liver and displacement of hollow viscera during endoscopic surgery. The functional section of the instrument, when locked, forms a silicon-covered uniplanar hook which can be deployed for horizontal lift of solid organs such as the liver or be used to engage bowel for displacement from the operative field. Following laboratory testing, the instrument has been evaluated clinically and its ease of deployment and atraumatic nature have been confirmed. It has been found to be particularly effective for elevation of the thick fatty left lobe of the liver during antireflux surgery.

Endoscopes↗

Clamping the small intestine during surgery: predicted and measured sealing forces.

During bowel surgery it is often necessary to occlude the bowel using clamps. Occlusion occurs in two stages: approximation of bowel internal surfaces followed by sealing which is necessary to prevent seepage. The occlusive force at both stages depends on the luminal pressure, the latter stage requiring greater force than the former. The difference in luminal pressure across the sealing line results in a slipping force which is resisted by friction between the bowel and the clamp jaw surfaces. A theoretical model was developed to describe these forces and the predicted values obtained from this model were compared with direct measurements carried out on porcine bowel samples in a test rig. It was found that the measured approximation force was between 25 and 50 per cent of the maximum theoretical values and that sealing without seepage requires a clamp force of about ten times the approximation force. Using these results and known intraluminal pressures in the human gastrointestinal tract, a bowel clamp must apply around 7 N to prevent seepage and the coefficient of friction between clamp and bowel should be between 0.6 and 0.9.

Animals↗

Detachable clamps for minimal access surgery.

A detachable clamp and applicator have been developed for use in minimal access surgical operations involving hollow visceral transection and anastomosis. The clamp has parallel jaws which ensure uniform distribution of the occlusive force. Following application on the bowel, the clamp is released from the applicator, thus freeing the access port. On completion of the anastomosis, the clamp is docked to the applicator, its jaws opened for release from the bowel and then closed prior to removal. The jaws of the clamp are kept closed by a pseudoelastic nickel-titanium (NiTi) alloy spring which imparts advantageous force characteristics when compared to stainless steel. The excellent holding and atraumatic characteristics of the detachable clamp have been confirmed by use in laparoscopic and thoracoscopic surgery on the gastrointestinal tract.

Colectomy↗