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Biomedical subjects

M Mack

Publications and source records attributed to M Mack.

At least 73 records · Page 4Linked to original sources

Thoracoscopy for the Diseases of the Mediastinum Including Thymectomy for Myasthenia Gravis.

The majority of mediastinal structures and diseases can be approached thoracoscopically. Diagnostic procedures for anterior mediastinal masses, mediastinal cysts, and staging of lung cancer are well accepted. Small but increasing experience has been gained with posterior neurogenic tumors. Complete thymectomy for management of myasthenia gravis has been performed, but the efficacy of the procedure for this indication awaits longer-term results.

Journal Article↗

Thoracoscopic Surgery of the Spine.

Anterior approach to the thoracic spine has been limited by the morbidity of a thoracotomy. By a thoracoscopic approach, a majority of thoracic spine procedures can now be performed from the anterior approach including diskectomy for herniation, release for correction of spinal deformity and corpectomy for tumor. Although experience is limited and results still short term, the thoracoscopic approach appears to be a promising one for the treatment of thoracic spine disease.

Journal Article↗

Minimally Invasive Cardiac Surgery.

Minimally invasive techniques have recently been introduced into cardiac surgical procedures. Opportunities to make coronary artery bypass less invasive include elimination or minimization of both incisions and cardiopulmonary bypass. The current spectrum of minimally invasive coronary bypass procedures range from the minimally invasive direct vision coronary artery bypass procedure, which eliminates both the sternotomy incision and cardiopulmonary bypass, to the port access approach, which uses femoral-femoral bypass. Current procedures are also being used to make mitral and aortic valve surgery as well as saphenous vein harvest less invasive.

Journal Article↗

[Use of MR-controlled laser-induced thermotherapy in recurrent squamous epithelial carcinoma of the head-neck area].

BACKGROUND: The management of patients with recurrent carcinomas of the head and neck that had been treated before by surgery, radiation, and/or chemotherapy presents a considerable problem. The value of the MR-controlled laser-induced thermotherapy (LITT) was analysed as a new palliative treatment modality. METHOD: LITT was used in five patients with recurrent head and neck squamous cell carcinomas, who had undergone established methods of treatment. One patient with a primary laryngeal carcinoma, who refused surgery, was treated by LITT in addition to radiation. A Nd:YAG laser was used to deliver laser light via an applicator directly into the tissue and to produce tumor necrosis. Using two special MR thermosequences (Thermo-TurboFLASH-, modified FLASH-2 D-Sequenfe) the laser process was controlled on line. The necroses were measured by a static and dynamic area calculation program based on a pixel evaluation. RESULTS: The induced tumor necroses ranged from 4 cm3 to 28 cm3. In all cases the MR thermosequences showed a loss of the signal up to 15 mm around the top of the applicator. In the post-interventional T1 sequences with intensified contrast, the coagulation necroses were represented as hypovascular areas. No side effects were seen and five of the patients felt an improvement of clinical symptoms. CONCLUSION: LITT as a minimal invasive, MR-controlled method may be a good alternative in palliative therapy of head and neck carcinomas.

Adult↗

Comparative evaluation of reactogenicity and immunogenicity of two dosages of oral tetravalent rhesus rotavirus vaccine. US Rhesus Rotavirus Vaccine Study Group.

OBJECTIVE: To compare the safety and immunogenicity of two dosages of tetravalent rhesus rotavirus vaccine (RRV-TV) and the effect of age at dosing. METHODS: A total of 195 infants were stratified by age into 2 groups, 6 to 12 weeks and 16 to 24 weeks, and randomly assigned to receive a single dose of placebo or RRV-TV containing either 4 x 10(5) or 4 x 10(6) plaque-forming units (pfu). Symptoms were recorded for 5 days after vaccination. Anti-rotavirus IgA and neutralizing antibody to human rotavirus serotypes G1 to G4 and RRV were measured in serum obtained pre- and postvaccination. RESULTS: Rates of fever > 38 degrees C (9%), diarrhea (6%) and vomiting (8%) were similar in all groups. IgA (69% vs. 49%, P = 0.02) and RRV (85% vs. 66%, P = 0.004) seroconversion rates were significantly higher in the 4 x 10(6) pfu vaccine group as were antibody titers to RRV (440.2 vs. 263.7, P = 0.04). Older infants demonstrated significantly higher seroconversion rates and antibody titers for IgA (71% vs. 52%, P = 0.03; and 110.6 vs. 54.8, P = 0.004) and RRV (92% vs. 66%, P = 0.05 and 498.3 vs. 205.6, P = 0.01) at either dose level than did the younger infants. There were no significant differences in seroconversion rates or antibody titers to human rotavirus types G1 to G4 between the two vaccination groups. CONCLUSIONS: RRV-TV at a dose of 4 x 10(6) pfu can be safely administered to infants 6 to 24 weeks of age. A single dose of 4 x 10(6) pfu of RRV-TV was significantly more immunogenic than a single dose of 4 x 10(5) pfu but did not improve responses to the human serotypes. Older vaccine recipients demonstrated significantly higher IgA and neutralizing antibody seroconversion rates and antibody titers than younger infants independent of dosage.

Administration, Oral↗

MR characteristics of primary extramedullary plasmacytoma in the head and neck.

PURPOSE: To define MR characteristics of primary extramedullary plasmacytoma in the head and neck using a variety of plain and contrast-enhanced MR protocols. METHODS: Six patients with primary extramedullary plasmacytoma in the head and neck were examined clinically and with MR imaging at 1.5 T. The morphologic appearance and signal intensities of the lesions were analyzed and the results of the imaging findings were compared with histopathologic findings. RESULTS: Qualitative analysis showed that five lesions were oval and sharply demarcated without signs of infiltration; the other lesion filled the parapharyngeal space bilaterally. On t2-weighted sequences, the lesions had moderate signal intensity. On plain T1-weighted sequences, the tumors were isointense or slightly hyperintense with respect to surrounding muscles; after administration of contrast medium, four lesions notable enhancement, with distinct central inhomogeneity. CONCLUSION: Although morphologic features or evidence of contrast enhancement do not assure certain diagnosis of extramedullary plasmacytoma, these MR imaging characteristics should prompt the radiologist to include this rare lesion in the differential diagnosis.

Adolescent↗

A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity.

Construction of a bispecific single-chain antibody derivative is described that consists of two different single-chain Fv fragments joined through a Gly-Ser linker. One specificity of the two Fv fragments is directed against the CD3 antigen of human T cells and the other is directed against the epithelial 17-1A antigen; the latter had been found in a clinical trial to be a suitable target for antibody therapy of minimal residual colorectal cancer. The construct could be expressed in CHO cells as a fully functional protein, while its periplasmic expression in Escherichia coli resulted in a nonfunctional protein only. The antigen-binding properties of the bispecific single-chain antibody are indistinguishable from those of the corresponding univalent single-chain Fv fragments. By redirecting human peripheral T lymphocytes against 17-1A-positive tumor cells, the bispecific antibody proved to be highly cytotoxic at nanomolar concentrations as demonstrated by 51Cr release assay on various cell lines. The described bispecific construct has a molecular mass of 60 kDa and can be easily purified by its C-terminal histidine tail on a Ni-NTA chromatography column. As bispecific antibodies have already been shown to be effective in vivo in experimental tumor systems as well as in phase-one clinical trials, the small CD3/17-1A-bispecific antibody may be more efficacious than intact antibodies against minimal residual cancer cells.

Amino Acid Sequence↗

Identification of glutamate beta 54 as the covalent-catalytic residue in the active site of glutaconate CoA-transferase from Acidaminococcus fermentans.

In the course of glutamate fermentation by Acidaminococcus fermentans glutaconate coenzyme A-transferase catalyzes the transfer of CoAS- from acetyl-CoA to (R)-2-hydroxyglutarate, forming (R)-2-hydroxyglutaryl-CoA. Glutamate (E) 54 of the beta-subunit was postulated to be directly involved in catalysis by formation of a CoASH ester intermediate [(1994) Eur. J. Biochem., in press]. In order to prove this preliminary result, the following mutations, beta E54A, beta E64A, beta E54Q and beta E54D, were introduced by mismatch oligonucleotide priming. As expected, beta E54A was inactive (0.02% of the wild-type), whereas beta E64A and beta E54D were active, 30% and > 7%, respectively. However, no CoASH intermediate was detected in the latter mutant, indicating a change in the catalytic mechanism. The activity of the beta E54Q mutant increased from 1% to almost 100% upon incubation with acetyl-CoA and glutaconate at 37 degrees C within 40 h. Hence, the substrates induced the conversion of the mutant glutamine residue into the glutamate residue of the wild-type enzyme.

Base Sequence↗

Combination gonadotropin-releasing hormone agonist and oral contraceptive therapy improves treatment of hirsute women with ovarian hyperandrogenism.

OBJECTIVE: To determine if combination GnRH agonist (GnRH-a) and oral contraceptive (OC) therapy was more effective than GnRH-a or OC alone in the treatment of hirsute women with ovarian hyperandrogenism. DESIGN: Thirty-three hirsute women (ages 15 to 39 years) were randomized into three groups: 3.75 mg IM leuprolide acetate (LA) depot every 28 days for 6 months, combination monophasic oral contraceptive for 6 months (OC), or GnRH-a plus OC for 6 months (LA + OC). MAIN OUTCOME MEASURES: Comparative studies of changes in hormonal and hair parameters were performed at baseline, 3, and 6 months after starting therapy. RESULTS: After 6 months, serum T and LH levels were decreased significantly in all groups although reduction was greater in GnRH-a groups than OC alone. The reduction of free T was significantly greater with LA + OC compared with LA or OC alone. This could be a consequence of the significant rise in sex hormone-binding globulin (SHBG) in LA + OC and OC groups compared with LA in which there was no change in SHBG. Reduced facila hair density and decrease in hirsutism score was observed in both GnRH-a groups after 6 months. CONCLUSION: "Add-back" OC therapy used in combination with a GnRH-a increases SHBG and more effectively lowers free T levels in women with ovarian hyperandrogenism. Enhanced suppression of "bioavailable" androgens with combined GnRH-a and OC therapy failed to improve significantly the therapeutic effect of GnRH-a treatment alone on hirsutism.

Adolescent↗

Location of the two genes encoding glutaconate coenzyme A-transferase at the beginning of the hydroxyglutarate operon in Acidaminococcus fermentans.

Glutaconate coenzyme A-transferase (Gct) from Acidaminococcus fermentans consists of two subunits (GctA, 35725 Da and GctB, 29168 Da). The N-termini sequences of both subunits were determined. DNA sequencing of a subgenomic fragment of A. fermentans revealed that the genes encoding glutaconate CoA-transferase (gctAB) are located upstream of a gene cluster formed by gcdA, hgdC, hgdA and hgdB in this order. Further upstream of gctA, a DNA sequence was detected showing significant similarities to sigma 70-type promoters from Escherichia coli. Primer-extension analysis revealed that this specific DNA sequence was indeed the location of transcription initiation in A. fermentans. The entire gene cluster, 7.3 kb in length, comprising gctAB, gcdA and hgdCAB, has tentatively been named the hydroxyglutarate operon, since the enzymes encoded by these genes are involved in the conversion of (R)-2-hydroxyglutarate to crotonyl-CoA in the pathway of glutamate fermentation by A. fermentans. The genes gctAB were expressed together in E. coli. Cell-free extracts of a transformant E. coli strain contained glutaconate CoA-transferase at a specific activity of up to 30 U/mg protein. The recombinant enzyme was purified to homogeneity with a specific activity of 130 U/mg protein by ammonium sulfate fractionation and crystallisation. The amino acid residue directly involved in catalysis was tentatively identified as E54 of the small subunit of the enzyme (GctB).

Amino Acid Sequence↗

Video-assisted thoracoscopic wedge resection of T1 lung cancer in high-risk patients.

OBJECTIVE: This study assessed the reliability and safety of VATR for treatment of peripheral T1 lung cancer in high-risk patients. SUMMARY BACKGROUND DATA: Surgical resection is the best therapy for stage I lung cancer. Patients with poor cardiopulmonary status or those who are elderly (> 75 years of age) are considered to be at high risk from thoracotomy and are frequently referred for radiation therapy or expectant palliative management. Data from previous studies suggest that survival with wedge resection is similar to that with lobectomy. The authors propose VATR, which is minimally invasive, as a therapeutic option in patients considered to be at high risk for resection by thoracotomy. METHODS: Between November 1990 and November 1992, more than 400 thoracoscopic lung resections were performed. Thirty patients with poor pulmonary function (forced expiratory volume FEV1] < 1 L or < 35% predicted; arterial oxygen tension [PaO2] < 60 mmHg on room air; diffusion capacity [DCO] < 40%) underwent 31 VATRs (1 patient had a staged procedure for bilateral synchronous lung cancers). All patients had T1 peripheral lesions with no bronchoscopically visible lesions. Computed tomography of the chest revealed no evidence of mediastinal disease in all patients. RESULTS: Patients had a mean FEV1 value of 0.9 L (38% predicted) and a mean age of 71 years. Tumors were located in left upper lobe (LUL) in 13 patients, in right lower lobe (RLL) in 7 patients, in right upper lobe (RUL) in 6 patients, in left lower lobe (LLL) in 4 patients, and in right middle lobe (RML) in 1 patient. Computed tomography-guided wire localization, methylene blue surface injection, and intraoperative ultrasonography were used to assist in defining difficult lesions. All lesions were successfully resected without converting to thoracotomy. One patient died on the 34th postoperative day of myocardial infarction (operative mortality rate of 3%). Five patients had prolonged air leaks (< 5 days), with a median chest tube time of 3 days. Two patients experienced pneumonia. CONCLUSION: The authors concluded that VATR is a safe and reliable procedure for treatment of peripheral T1 lung cancer in high-risk patients. Long-term follow-up will be required to determine the efficacy of this procedure regarding survival and locoregional recurrence.

Aged↗

Thoracoscopic stapled resection for spontaneous pneumothorax.

Video-assisted thoracoscopy has recently evolved as an alternative to thoracotomy for several thoracic disorders. Spontaneous pneumothorax may be ideally suited for thoracoscopic management. Stapling of apical blebs and pleurodesis or pleurectomy can now be performed thoracoscopically in a fashion identical to the standard operation done through a lateral or axillary thoracotomy. We compared our results with thoracoscopic management of spontaneous pneumothorax in 26 patients (group I) with a group of 20 patients previously subjected to axillary thoracotomy (group II). Indications for operation, sex distribution, and average age (group I, 32.3 years; group II, 33.7 years) were comparable. Hospital stay was less in group I (2.88 +/- 0.99 days versus 4.47 +/- 1.07 days; p = 0.07), as was the use of parenteral narcotics after 48 hours (2/26 = 7.7% versus 14/20 = 70%; p = 0.01). There have been no recurrences to date (mean follow-up, 8 months) in the thoracoscopic group. Video-assisted thoracoscopic management of spontaneous pneumothorax allows performance of the standard surgical procedure while avoiding the thoracotomy incision. Video-assisted thoracoscopic management is safe and offers the potential benefits of shorter hospital stays and less pain.

Adult↗

Etiology of sarcoplasmic reticulum calcium release channel lesions in doxorubicin-induced cardiomyopathy.

Alterations in the native function of the ryanodine-sensitive Ca2+ release channel complex of sarcoplasmic reticulum (SR) isolated from rat cardiac ventricles during acute and chronic exposure to doxorubicin are examined. Compared to control SR, actively loaded SR from animals exposed to a single intravenous dose of doxorubicin exhibit faster rates of doxorubicin-induced Ca2+ release and the occupancy of [3H]ryanodine is significantly enhanced with subsequent exposure of SR membranes to doxorubicin in vitro. One week after acute exposure to doxorubicin in vitro, the EC50 for activation of the binding of [3H]ryanodine by Ca2+ is not significantly different from control SR. However, the persistence of doxorubicin-sensitized SR channels appears to be latent since repeated exposure to doxorubicin in vitro significantly enhances receptor occupancy in SR obtained from the treated rats compared to control SR. Ryanodine receptors from rats chronically exposed to doxorubicin consistently exhibit a higher sensitivity to activation Ca2+ which persists at least 4 weeks following the last injection of drug. Chronic exposure produces a concomitant reduction in the capacity of [3H]ryanodine binding sites. The marked decrease in receptor density observed with SR from doxorubicin-treated rats coincides with significant reduction in body weight, suggesting a possible influence of nutrition. However, sodium dodecyl sulfate polyacrylamide electrophoresis indicates no significant loss of the high molecular weight subunit of the ryanodine receptor, suggesting that loss of [3H]ryanodine-binding capacity may be the result of progressive and permanent channel desensitization. Consistent with desensitized receptors, membrane vesicles prepared from rats chronically exposed to doxorubicin take up significantly more Ca2+ and exhibit significantly reduced rates of doxorubicin or Ca2+/ryanodine induced Ca2+ release. The data demonstrates (i) doxorubicin inflicts cumulative SR channel lesions in vivo, (ii) a persistent sensitization of the SR channel to activation by Ca2+ and (iii) a significant and apparently irreversible reduction in the number of functional channel complexes.

Animals↗

Pituitary sarcoidosis.

A 66-year-old woman presenting with pituitary insufficiency was operated on for an intrasellar tumor. Surprisingly, this tumor, at first suspected to be a hormone-inactive pituitary adenoma, consisted in fact of sarcoid granulomatous tissue in the pituitary gland as found histologically. The morphological picture as seen in the cranial computed tomography was identical with that of an adenoma. This possibility had not previously been considered, although there had been an extracerebral manifestation of the sarcoidosis in the left ovary.

Adenoma↗