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Biomedical subjects

A Block

Publications and source records attributed to A Block.

At least 19 recordsLinked to original sources

Revision arthroplasty with use of a total femur prosthesis.

BACKGROUND: Surgeons performing revision arthroplasties of the hip and knee are confronted with a growing number of patients with extensive loss of bone stock. Implantation of a total femur prosthesis is a possible method of treatment of such patients. The purpose of this study was to assess the functional outcomes and the complications associated with total femur replacements used in revision arthroplasty. METHODS: We evaluated the results associated with 100 total femur prostheses that had been implanted during revision arthroplasty in 100 consecutive patients without infection. The mean duration of follow-up was five years. The prosthesis was implanted because of a complication of a total hip replacement in seventy-seven patients, because of a complication of a total knee replacement in four, and because of a complication affecting the diaphysis of the femur in nineteen. Thirty-nine patients had sustained a periprosthetic fracture, usually in combination with loosening of the prosthesis, before the revision. The radiographs made at the time of the latest follow-up were evaluated for signs of loosening and material failure. The preoperative and postoperative function of the hip and knee was assessed according to the Enneking score. Five patients were lost to follow-up. RESULTS: Sixty-five patients (68%) had no complications. Deep infection was found in twelve patients (13%); dislocation, in six (6%); material failure, in three (3%); patellar problems, in two (2%); and peroneal nerve palsy, in one (1%). The mean preoperative Enneking score for hip function was 1.25 points, and it improved to 3.29 points postoperatively. The mean Enneking score for knee function was 2.09 points preoperatively and 3.29 points postoperatively. CONCLUSIONS: We believe that the total femur prosthesis is a useful implant for patients with extensive bone loss at revision arthroplasty. While the infection rate was high, the overall functional results for both the hip and the knee were rated as better than good with the Enneking classification.

Adult↗

Planetary habitability: is Earth commonplace in the Milky Way?

Is there life beyond planet Earth? This is one of the grand enigmas which humankind tries to solve through scientific research. Recent progress in astronomical measurement techniques has confirmed the existence of a multitude of extra-solar planets. On the other hand, enormous efforts are being made to assess the possibility of life on Mars. All these activities have stimulated several investigations about the habitability of cosmic bodies. The habitable zone (HZ) around a given central star is defined as the region within which an Earth-like planet might enjoy the moderate surface temperatures required for advanced life forms. At present, there are several models determining the HZ. One class of models utilises climate constraints for the existence of liquid water on a planetary surface. Another approach is based on an integrated Earth system analysis that relates the boundaries of the HZ to the limits of photosynthetic processes. Within the latter approach, the evolution of the HZ for our solar system over geological time scales is calculated straightforwardly, and a convenient filter can be constructed that picks the candidates for photosynthesis-based life from all the extra-solar planets discovered by novel observational methods. These results can then be used to determine the average number of planets per planetary system that are within the HZ. With the help of a segment of the Drake equation, the number of "Gaias" (i.e. extra-solar terrestrial planets with a globally acting biosphere) is estimated. This leads to the thoroughly educated guess that there should exist half a million Gaias in the Milky Way.

Astronomical Phenomena↗

Gene therapy of metastatic colon carcinoma: regression of multiple hepatic metastases by adenoviral expression of bacterial cytosine deaminase.

Colon carcinoma accounts for 20% of deaths due to malignancies in the Western world. Once metastases occur, therapeutic options are limited, with an approximate 5-year survival of only 5%. To investigate the potential of new gene therapeutic approaches, a hepatic micrometastasis model of colon carcinoma in BALB/c mice was established. Inoculation of syngeneic MCA26 colon carcinoma cells into the spleens of 18- to 20-week-old mice resulted in the formation of multiple hepatic metastases. Selective transduction of developing hepatic metastases was demonstrated using a beta-galactosidase-expressing recombinant adenovirus. Cytosine deaminase (CD) can metabolize 5-fluorocytosine into the chemotherapeutic reagent 5-fluorouracil (5FU). The antitumoral potential of this suicide gene therapy approach was explored by systemic application of a recombinant replication-deficient adenovirus encoding for the bacterial CD gene under the control of the cytomegalovirus promoter (Ad.CMV-CD). Injection into the tail vein of tumor-bearing mice resulted in delayed tumor growth with significant reduction in hepatic metastases. The potential of this experimental approach for possible future clinical applications was evaluated by investigating adenoviral transduction efficiency, 5FU sensitivity, and 5-fluorocytosine-dependent Ad.CMV-CD toxicity in a variety of human colon cancer cell lines. Although the murine cell lines MCA26 and CC36 were highly sensitive to 5FU, the human colon cancer cell lines showed a 1-100 times higher resistance to 5FU. Specific Ad.CMV-CD toxicity correlates with 5FU toxicity. Transduction efficiency in human colon carcinoma cell lines was shown to be 10-1700 times higher compared with murine cell lines, thus compensating for 5FU resistance. In conclusion, suicide gene therapy using CD may be promising as an adjuvant treatment regimen for hepatic micrometastases of human colon carcinoma.

Adenoviridae↗

Treatment of feline leukemia virus (FeLV) infection.

FeLV infection is still considered to account for most disease-related deaths in pet cats. Different treatment attempts with various drugs were performed in the past but none resulted in healing or complete virus elimination. Therefore, it caused a sensation when Horber and Mayr [Horber, D., Mayr, B., 1991. Prax. 19, 311-314; Horber, D., Schnabl, W., Mayr, B., 1992. Tierarztl. Umschau 47, 556-560; Mayr, B., Horber, D., 1992. Kleintierprax. 37, 515-518] published that they were able to cure 80 to 100% FeLV-infected cats from viremia by using an immunomodulating compound. Articles in cat breeder and cat owner journals appeared assuming that obviously there is a rescue for FeLV-infected cats suffering from this deadly infection. The immunomodulator [Buttner, M., 1993. Comp. Immun. Microbiol. Infect. Dis. 18, 1-10] used in those studies was the so-called 'paramunity inducer' PIND-ORF (Baypamun, Bayer, Leverkusen, Germany) consisting of inactivated parapox ovis virus. Since that time, Baypamun is the most commonly used drug for treatment of FeLV infection in Germany and other European countries. Four placebo-controlled double-blind trials were performed to determine the therapeutic efficacy of Baypamun and other compounds in naturally FeLV-infected cats under controlled conditions.

Adjuvants, Immunologic↗

Effect of aspirin and ifetroban on skeletal muscle blood flow in patients with congestive heart failure treated with Enalapril. Ifetroban Study Group.

OBJECTIVES: The purpose of this study was to determine the acute and chronic effects of cyclooxygenase inhibition with aspirin and thromboxane A2 receptor blockade with ifetroban on the chronic vasodilating effects of enalapril in the skeletal muscle circulation of patients with heart failure. BACKGROUND: Angiotensin-converting enzyme inhibition and antiplatelet therapy with aspirin independently reduce the risk for subsequent nonfatal coronary events in survivors of myocardial infarction. The safety of the combined administration of angiotensin-converting enzyme inhibitors and aspirin has been questioned due to their divergent effects on the vascular synthesis of vasodilating prostaglandins. METHODS: Forearm blood flow (ml/min/100 ml) at rest and during rhythmic handgrip exercise and after transient arterial occlusion was determined by strain gauge plethysmography before and 4 h and six weeks after combined administration of enalapril with either aspirin, ifetroban or placebo in a multicenter, double-blind, randomized trial of 62 patients with mild to moderate heart failure. RESULTS: Before randomization, forearm hemodynamics were similar in the three treatment groups except for increased resting forearm blood flow and decreased resting forearm vascular resistance in the aspirin group when compared with the placebo group. After combined administration of enalapril and study drug for 4 h and six weeks, changes from prerandomization values of mean arterial pressure, forearm blood flow and forearm vascular resistance at rest, during handgrip exercise and after transient arterial occlusion did not differ among the three treatment groups. CONCLUSIONS: These findings demonstrate that the vasodilating effects of enalapril in the skeletal muscle circulation of patients with heart failure are not critically dependent on prostaglandin pathways.

Aged↗

Can patients perform volitional motor acts at the start of a seizure?

A seizure warning device might allow some individuals with partial seizures to protect themselves against consequences of seizures, but a prerequisite is the ability to take volitional action in response to a warning. The authors reviewed consecutive seizures in their epilepsy monitoring unit to determine whether patients could squeeze an event bulb, as instructed, at the start of their seizure. Only complex partial seizures with EEG changes and with the patient on camera were analyzed. Data were obtained from 77 patients, 42 with scalp monitoring and 35 with depth electrodes. Forty-seven percent had a left-hemisphere focus, 42% a right-hemisphere focus, and 11% multifocal seizures. The seizure focus was temporal in 68%. A magnetic resonance imaging consistent with mesial temporal sclerosis was seen in 29% of patients. Overall, 44% of the patients made at least one attempt to reach for the event bulb at the start of their seizures. Among the 72% of patients who gave a history of auras, 53% were able to press the event bulb compared to 20% with no history of auras (P = 0.016). EEG changes occurred a mean of 2.9+/-30.5 seconds after reaching for the bulb for scalp-recorded seizures (n = 20), and 16.2+/-13.7 seconds before behavior for depth-recorded seizures (n = 14, difference significant at P = 0.02). Neither seizure focus nor seizure laterality influenced the ability to press the event bulb. The authors conclude that nearly half of individuals with complex partial seizures can take volitional motor action at the start of their seizure. A method to enhance the intensity and timeliness of a seizure warning would not be wasted.

Adolescent↗

Treatment of feline leukemia virus-infected cats with paramunity inducer.

Two placebo-controlled double-blind trials were performed to determine the therapeutic efficacy of the paramunity inducer, Baypamun in feline leukemia virus (FeLV)-infected cats under controlled conditions. In the first study, 120 cats were involved; 60 cats were treated with Baypamun and 60 with a placebo preparation of virus-free cell culture medium. Dosage and administration of the drug over a 7-week period were performed according to the instructions given by the company. Remission of viremia occurred in 12% and 7% of the cats treated with Baypamun and placebo, respectively. This difference was not statistically significant. In the second study, 30 naturally infected cats were treated in a placebo-controlled double-blind trial. In total, 20 immunological, clinical, laboratory, and virological parameters were examined. No statistically significant differences could be demonstrated between Baypamun and placebo application. Therefore, FeLV infection was not influenced by Baypamun treatment.

Adjuvants, Immunologic↗

Hemisphere asymmetry in sympathetic control of the human myocardium.

Hemisphere asymmetry in sympathetic control of myocardial performance was studied in healthy human subjects using lateralized film presentation for selective sensory stimulation of the hemispheres and impedance cardiography for the evaluation of cardiac output, systolic time intervals and myocardial contractility. Results revealed a clear and consistent right hemisphere predominance in sympathetically mediated control of various components of myocardial performance. There is reason to assume that the obtained hemisphere differences in autonomic control of the heart are self-reliant processes not depending on emotion-related hemisphere asymmetry. As far as we know, this is the first study examining the distinct roles of the cerebral hemispheres in neural control of ventricular myocardial functions.

Adult↗

Hemisphere asymmetry in parasympathetic control of the heart.

Hemisphere asymmetry in the control of parasympathetic outflow to the sino-atrial node of the heart was studied in healthy human subjects using lateralized film presentation for selective sensory stimulation of the hemispheres and power spectral analysis of heart rate variability as a measure of vagal tone. There was a clear and consistent left hemisphere predominance in the control of parasympathetic modulation of cardiac activity which cannot be attributed to differences in emotional processing. Supplementing previous findings of our research group, the present study indicates that control of autonomic cardiac activity at the level of the cerebral cortex seems to be characterized by a division of responsibility between both hemispheres, sympathetic activity being mainly controlled by the right hemisphere and parasympathetic activity being under the left hemisphere's main control.

Adult↗

Ex vivo and in vivo adenovirus-mediated gene therapy strategies induce a systemic anti-tumor immune defence in the B16 melanoma model.

The efficacy of adenovirus-mediated gene therapy for treatment of metastatic B16 melanomas, established in syngeneic C57BL/6 mice, was assessed via an ex vivo cytokine vaccine approach or via an in vivo strategy utilizing combination cytokine/herpes simplex virus-thymidine kinase (HSV-tk) suicide gene delivery and treatment with ganciclovir (GCV). In the ex vivo tumor vaccine approach, B16 melanoma cells, transduced in vitro by adenovirus containing either interleukin (IL)-2, granulocyte-macrophage colony stimulating factor (GM-CSF), or tumor necrosis factor-alpha cytokine genes and gamma irradiated, were subcutaneously injected into the flank and a distant subcutaneous challenge injection of unmodified B16 melanoma cells was performed 15 d later. Significant reductions in challenge tumor volume were observed in the IL-2 group (75% reduction; p = 0.02) and in the GM-CSF group (88% reduction; p = 0.0006), whereas the effect for tumor necrosis factor-alpha was not statistically significant. In the in vivo treatment of established melanomas, this cytokine approach was combined with a suicide gene therapy and subcutaneous B16 melanomas were directly injected with (i) IL-2/recombinant, replication-deficient adenovirus (adv) and thymidine kinase (tk)/adv, (ii) GM-CSF/adv, IL-2/adv, and tk/adv, or (iii) control beta-galactosidase (beta-gal)/adv and tk/adv. After intraperitoneal application of GCV (10 mg per kg) for 6 d, the residual tumor masses were excised and the animals challenged with unmodified B16 cells. Challenge tumor growth was reduced by 56% for the IL-2/tk/adv/GCV treatment (p = 0.041) and by 77% for the GM-CSF/IL-2/tk/adv/GCV treatment p (p = 0.037), in comparison with the beta-gal/tk/GCV control group. These data may hold significant promise for the development of effective ex vivo and in vivo gene therapy modalities to counter the highly metastatic nature of human melanoma.

Adenoviridae↗

Adenovirus-mediated suicide gene therapy for experimental bladder cancer.

OBJECTIVES: To determine the feasibility, safety, and efficacy of suicide gene therapy using adenoviral-mediated herpes simplex virus thymidine kinase gene (HSV-tk) and the prodrug ganciclovir (GCV) in a murine model of human transitional cell carcinoma. METHODS: We used a replication-defective adenoviral construct containing the beta-galactosidase gene (ADV/Rous sarcoma virus [RSV]-beta-gal) as a control or ADV/RSV-tk as the therapeutic vector under the transcriptional control of the RSV long-terminal repeat promoter. Transduction efficiency was assessed in vitro by infection of MBT-2 cells with ADV/RSV-beta-gal at various multiplicities of infection (MOI) utilizing 5-bromo-4-chlor-3-indolyl-beta-D-galactoside (X-gal) staining. Sensitivity of MBT-2 cells to the therapeutic vector was determined after infection with ADV/RSV-tk with or without GCV. Subcutaneous tumors were established in syngeneic C3H/He female mice with 5 x 10(5) MBT-2 cells. Optimal dosing of ADV/RSV-tk was determined by direct percutaneous tumor injection with increasing viral doses and treatment with GCV. Treatment efficacy, long-term survival, and toxicity were determined in separate, similar, controlled experiments. RESULTS: In vitro studies indicated greater than 95% transduction 96 hours after inoculation at an MOI of 3000 and a greater than 95% cell death rate with RSV-tk + GCV at an MOI of 61 or greater. In vivo experiments demonstrated an optimal viral dose of 3 x 10(8) plaque-forming units (pfu) and a greater than fourfold reduction in tumor growth for the animals treated with ADV/RSV-tk compared with control animals (P = 0.0013). Toxicity was limited to histologic evidence of hepatitis with ADV/RSV-tk doses greater than 3 x 10(8) pfu + GCV. Long-term survival of treatment animals was significantly increased over that of control animals (59%, P = 0.0001). CONCLUSIONS: ADV/RSV-tk with GCV treatment results in efficient gene transfer in vitro and provides effective therapy in experimental murine bladder cancer by significantly inhibiting tumor growth and improving host survival.

Adenoviridae↗

Adenoviral-mediated herpes simplex virus thymidine kinase gene transfer: regression of hepatic metastasis of pancreatic tumors.

Pancreatic cancer is the fifth leading cause of cancer death in the United States. Most patients have obvious metastases or locally advanced disease at the time of presentation. Surgical resection does not significantly change the clinical outcome. Combination chemotherapy induces a partial response but overall survival remains low. The aim of this study was to evaluate the feasibility of adenovirus-mediated suicide gene transduction as a therapeutic approach for pancreatic cancer. A cell line was established from a murine pancreatic ductal adenocarcinoma and intrahepatic tumors were generated by inoculation of pancreatic cancer cells into the left lateral liver lobe. Transduction efficiency was characterized in vitro and in vivo. Intrahepatic tumors were treated by intratumoral adenovirus injection in combination with intraperitoneal administration of ganciclovir. Adenovirus-mediated herpes simplex virus (HSV)-thymidine kinase (tk) gene expression followed by ganciclovir treatment was highly efficient in inhibiting pancreatic cancer cell proliferation in vitro. The proliferation of nontransduced cells was significantly reduced in the presence of HSV-tk expressing cells. Intrahepatic inoculation of pancreatic cancer cells leads to successful formation of solid adenocarcinomas in syngeneic recipients. Ad.RSV-tk injection of the tumor followed by intraperitoneal ganciclovir application caused highly significant tumor volume reduction and necrosis. These results indicate that transduction of the HSV-tk gene followed by ganciclovir is highly efficient for growth inhibition of hepatic metastases of pancreatic carcinoma.

Adenocarcinoma↗

[Placebo-controlled double-blind study on the efficacy of a paramunity inducer in the treatment of naturally FeLV-infected cats].

The study involved 120 cats, of which 60 were treated with Baypamun HK and 60 cats received a preparation of virus free cell culture medium. Therapeutic efficacy was determined by monitoring the general status of health, body weight, skin, lymph nodes, oral cavity, the presence of the p27 antigen and the FeLV p27 antigen concentration in serum. No statistically significant differences between both groups could be demonstrated neither for clinical nor for virologic parameters. Remission of the viremia occurred in 11.7% of the cats treated with Baypamun HK and in 6.7% of the cats treated with placebo. The FeLV p27 antigen level decreased by an average of 7.2% with Baypamun HK and by an average of 5.1% with placebo.

Adjuvants, Immunologic↗

In vivo gene therapy of ovarian cancer by adenovirus-mediated thymidine kinase gene transduction and ganciclovir administration.

Efficacy and toxicity of adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene followed by administration of ganciclovir were studied in vivo. A human epithelial ovarian cancer animal model was established in nude mice using the serous ovarian adenocarcinoma cell line Ov-ca-2774. Intraperitoneal (ip) injection of 1 x 10(8) Ov-ca-2774 cells resulted in tumor growth and formation of malignant ascites in all 15 animals. In a prospective randomized experimental design mice were treated 1, 3, or 7 days after ip injection of 1 x 10(8) cells with ip injection of 2 x 10(8), 6.7 x 10(8), or 2 x 10(9) pfu ADV.RSV-TK followed by administration of ganciclovir (10 microgram /ml, ip, bid) for 6 consecutive days. End points were survival and toxicity. Mice treated with GCV or HSV-TK alone died from 14.4 +/- 1.7 to 19.5 +/- 3.5 days after treatment as did untreated controls. No toxicity of ADV.RSV-TK was found up to 2 x 10(9) pfu (2 x 10(11) particles). The mice with the highest tumor burden treated with the lowest viral dose lived significantly longer than controls (P < 0.05). Median survival in all other groups of mice treated with ADV.RSV-TK plus GCV was even longer (P < 0.01). Treatment benefit was dependent on ADV/RSV-TK dose and tumor burden. Adenovirus-mediated thymidine kinase gene therapy is a realistic approach to ovarian cancer treatment that warrants investigation in the clinical setting.

Adenoviridae↗

[Percutaneous cystoscopy in dogs and cats].

Cystoscopy enables a reliable diagnosis of urinary bladder diseases. The use of transurethral or perineal endoscopic technique is limited by anatomical features. Therefore it was examined, if the prepubic percutaneous access shows advantages referring to diagnosis and treatment. Using this technique three dogs and two cats were examined. The endoscopic instrumentarium and the technical procedure are described.

Animals↗