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Biomedical subjects

D Schuller

Publications and source records attributed to D Schuller.

At least 19 recordsLinked to original sources

Relationship between protein kinase C and derepression of different enzymes.

The PKC1 gene in the yeast Saccharomyces cerevisiae encodes for protein kinase C which is known to control a MAP kinase cascade consisting of different kinases: Bck1, Mkk1 and Mkk2, and Mpk1. This cascade affects the cell wall integrity but the phenotype of pkc1Delta mutants suggests additional targets that have not yet been identified [Heinisch et al., Mol. Microbiol. 32 (1999) 671-680]. The pkc1Delta mutant, as opposed to other mutants in the MAP kinase cascade, displays defects in the control of carbon metabolism. One of them occurs in the derepression of SUC2 gene after exhaustion of glucose from the medium, suggesting an involvement of Pkc1p in the derepression process that is not shared by the downstream MAP kinase cascade. In this work, we demonstrate that Pkc1p is required for the increase of the activity of enzymatic systems during the derepression process. We observed that Pkc1p is involved in the derepression of invertase and alcohol dehydrogenase activities. On the other hand, it seems not to be necessary for the derepression of the enzymes of the GAL system. Our results suggest that Pkc1p is acting through the main glucose repression pathway, since introduction of an additional mutation in the PKC1 gene in yeast strains already presenting mutations in the HXKII or MIG1 genes does not interfere with the typical derepressed phenotype observed in these single mutants. Moreover, our data indicate that Pkc1p participates in this process through the control of the cellular localization of the Mig1 transcriptional factor.

Agar↗

Perioperative complications after living donor lobectomy.

OBJECTIVE: Clinical lung transplantation has been limited by availability of suitable cadaveric donor lungs. Living donor lobectomy provides right and left lower lobes from a pair of living donors for each recipient. We reviewed our experience with living donor lobectomy from July 1994 to February 2000. METHODS: Sixty-two donor lobectomies were performed. The hospital and outpatient records of these 62 donors were retrospectively analyzed to examine the incidence of perioperative complications. RESULTS: Twenty-four (38.7%) of 62 donors had no perioperative complications and had a median length of hospital stay of 5.0 days. Thirty-eight (61.3%) of 62 donors had postoperative complications. Twelve major complications occurred in 10 patients and included pleural effusions necessitating drainage (n = 4), bronchial stump fistulas (n = 3), bilobectomy (n = 1), hemorrhage necessitating red cell transfusion (n = 1), phrenic nerve injury (n = 1), atrial flutter ultimately necessitating electrophysiologic ablation (n = 1), and bronchial stricture necessitating dilatation (n = 1). These 38 donors had 55 minor complications including persistent air leaks (n = 9), pericarditis (n = 9), pneumonia (n = 8), arrhythmia (n = 7), transient hypotension necessitating fluid resuscitation (n = 4), atelectasis (n = 3), ileus (n = 3), subcutaneous emphysema (n = 3), urinary tract infections (n = 2), loculated pleural effusions (n = 2), transfusion (n = 2), Clostridium difficile colitis (n = 1), puncture of a saline breast implant (n = 1), and severe contact dermatitis secondary to adhesive tape (n = 1). There were no postoperative deaths and only 1 donor required surgical re-exploration. CONCLUSIONS: Living donor lobectomy can be performed with low mortality and remains an important alternative for potential recipients unable to wait for cadaveric lung allografts. However, morbidity is high and must be considered when potential living donors are being counseled.

Female↗

Pulmonary complications after coronary revascularization.

Pulmonary complications are common after coronary artery bypass grafting. Identifying those individuals with increased risk of respiratory complications allows for appropriate preoperative intervention. The most commonly seen pulmonary complications include pleural effusion, hemothorax, atelectasis, pulmonary edema, diaphragmatic dysfunction, and pneumonia. Clinical features and appropriate management of these common problems are discussed.

Humans↗

Ruptured pulmonary infarction: a rare, fatal complication of thromboembolic disease.

We describe 2 men, ages 69 and 49 years, who experienced fatal rupture of pulmonary infarcts. Both patients had documented prior thromboembolic events and subsequently had abrupt deterioration in cardiorespiratory function. Autopsies showed massive unilateral hemothorax in both patients. Rupture of a pulmonary infarct may occur spontaneously or iatrogenically due to aggressive anticoagulation. This may be difficult to distinguish from secondary hemothorax with an intact pleura, but rupture typically has a considerably more rapid clinical evolution. Treatment should include immediate withdrawal of thrombolytic or anticoagulant medications and evacuation of the pleural space. Surgical intervention can be considered, although the utility of that approach must await prospective trials.

Aged↗

A differential medium for the enumeration of the spoilage yeast Zygosaccharomyces bailii in wine.

A collection of yeasts, isolated mostly from spoiled wines, was used in order to develop a differential medium for Zygosaccharomyces bailii. The 118 selected strains of 21 species differed in their origin and resistance to preservatives and belonged to the genera Pichia, Torulaspora, Dekkera, Debaryomyces, Saccharomycodes, Issatchenkia, Kluyveromyces, Kloeckera, Lodderomyces, Schizosaccharomyces, Rhodotorula, Saccharomyces, and Zygosaccharomyces. The design of the culture medium was based on the different ability of the various yeast species to grow in a mineral medium with glucose and formic acid (mixed-substrate medium) as the only carbon and energy sources and supplemented with an acid-base indicator. By manipulating the concentration of the acid and the sugar it was possible to select conditions where only Z. bailii strains gave rise to alkalinization, associated with a color change of the medium (positive response). The final composition of the mixed medium was adjusted as a compromise between the percentage of recovery and selectivity for Z. bailii. This was accomplished by the use of pure or mixed cultures of the yeast strains and applying the membrane filtration methodology. The microbiological analysis of two samples of contaminated Vinho Verde showed that the new medium can be considered as a differential medium to distinguish Z. bailii from other contaminating yeasts, having potential application in the microbiological control of wines and probably other beverages and foods.

Colony Count, Microbial↗

Joint Task Force Algorithm and Annotations for Diagnosis and Management of Rhinitis.

The algorithm and text annotations in this document are intended to assist clinical decision making about patients who present with symptoms of rhinitis. This document complements the Executive Summary of Joint Task Force Practice Parameters for Diagnosis and Management of Rhinitis (Ann Allergy, Asthma, Immunol 1998; 81:463-468) and Diagnosis and Management of Rhinitis: Complete Guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology (Ann Allergy, Asthma, Immunol 1998;81:478-578). The Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology is co-sponsored by the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology and the Joint Council of Allergy, Asthma and Immunology.

Algorithms↗

Diagnosis and management of rhinitis: complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology. American Academy of Allergy, Asthma, and Immunology.

This document contains complete guidelines for diagnosis and management of rhinitis developed by the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology, representing the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology and the Joint Council on Allergy, Asthma and Immunology. The guidelines are comprehensive and begin with statements on clinical characteristics and diagnosis of different forms of rhinitis (allergic, non-allergic, occupational rhinitis, hormonal rhinitis [pregnancy and hypothyroidism], drug-induced rhinitis, rhinitis from food ingestion), and other conditions that may be confused with rhinitis. Recommendations on patient evaluation discuss appropriate use of history, physical examination, and diagnostic testing, as well as unproven or inappropriate techniques that should not be used. Parameters on management include use of environmental control measures, pharmacologic therapy including recently introduced therapies and allergen immunotherapy. Because of the risks to patients and society from sedation and performance impairment caused by first generation antihistamines, second generation antihistamines that reduce or eliminate these side effects should usually be considered before first generation antihistamines for the treatment of allergic rhinitis. The document emphasizes the importance of rhinitis management for comorbid conditions (asthma, sinusitis, otitis media). Guidelines are also presented on special considerations in patients subsets (children, the elderly, pregnancy, athletes and patients with rhinitis medicamentosa); and when consultation with an allergist-immunologist should be considered.

Diagnosis, Differential↗

Confirmatory factor analysis of the revised Personal Style Inventory.

The revised Personal Style Inventory (PSI) was developed to measure the sociotropy and autonomy personality dimensions; both of these dimensions are thought to confer specific vulnerabilities to the onset, maintenance, and reoccurrence of depression. Confirmatory factor analysis was used to test the theoretical structure that informed the construction of the PSI. Using a large sample of nonclinical participants (n = 869) and a sample of outpatients with major depression (n = 101), both the items and the subscales of the PSI decomposed into factor structures that were, overall, fair to good representations of the theoretical model. Modifications were needed at the subscale level to achieve an adequate fit for the nonclinical and clinical samples, which provide implications for both the measurement and theory of the PSI and the sociotropy and autonomy domains.

Adult↗

Protocol-guided diuretic management: comparison of furosemide by continuous infusion and intermittent bolus.

OBJECTIVE: To evaluate the safety and relative effectiveness of two diuretic protocols in the intensive care unit (ICU). DESIGN: Prospective, randomized comparative study. PATIENTS: Thirty-three cardiac and medical ICU patients with pulmonary edema or fluid overload for which aggressive diuresis was intended. INTERVENTIONS: Enrolled patients were randomized to fluid management strategies combining fluid restriction and individually adjusted diuretic therapy by either continuous or bolus infusions of furosemide, titrated to achieve negative hourly fluid balance. MEASUREMENTS AND MAIN RESULTS: Cumulative intake minus output (primary endpoint); change in serum creatinine, and length of ICU and hospital stay (secondary endpoints). Diuresis by either protocol was feasible, safe, and effective. The main outcome measures were not significantly different for either group managed with a standardized protocol. CONCLUSIONS: Protocol-guided diuretic management, with individualized titration of dosage to defined physiologic endpoints can be readily and safely implemented in the ICU. Both continuous and bolus diuretic regimens appear equally effective in achieving negative fluid balance. Larger studies with a randomized control arm are needed before these protocols can be recommended as routine practice.

APACHE↗

Evaluation of topotecan in patients with recurrent for metastatic squamous cell carcinoma of the head and neck. A phase II Southwest Oncology Group study.

Twenty-nine patients with persistent, recurrent and/or metastatic squamous cell carcinoma of the head and neck were treated daily for five days at three-week intervals with topotecan 1.5 mg/m2. Four patients received prior chemotherapy, 23 prior surgery and 29 prior radiation therapy. Of the 29 eligible patients, 8 patients were not evaluable for response and were assumed to be non-responders. Of the remaining 21 evaluable patients, there were zero responses (0%, 95% confidence interval [0,.12]). The most common toxicities were myelosuppression, dyspnea and malaise/fatigue/lethargy. Topotecan has limited activity in advanced head and neck cancer with this dose and schedule.

Adult↗

Pilot study of intraoperative high dose rate brachytherapy for head and neck cancer.

PURPOSE: To develop a new technique, intraoperative high dose rate brachytherapy (IOHDR), to deliver localized radiation therapy intraoperatively to head and neck tumors at sites inaccessible to intraoperative electron beam radiotherapy (IOEBRT) in the skull base region. METHODS: After maximal surgical resection, afterloading catheters spaced 1 cm apart embedded in custom surface applicators made of foam or silicone were placed on resected tumor beds. IOHDR was delivered in a shielded operating room using preplanned dosimetry with a nominal 10 Ci iridium-192 source in an HDR micro-Selectron afterloader. Twenty-nine patients (20 males, 9 females) ranging in age from 9 to 80 years (median = 61) were irradiated intraoperatively for advanced head and neck tumors at sites inaccessible to IOEBRT. Six patients who had previously received external beam radiation (EBRT) ranging from 50 to 75 Gy, were given 15 Gy of IOHDR only. Twenty-three patients who had no prior radiation received 7.5 to 12.5 Gy IOHDR, and 45 to 50 Gy EBRT was planned post-operatively; however, six of these patients did not complete the planned EBRT. Doses to normal tissues were reduced whenever possible by shielding with lead or by displacement with gauze or retractors. Treatment time ranged from 3.8 to 23 min (median = 6.5 min). Five patients received concurrent cis-platinum based chemotherapy. RESULTS: Twenty-nine patients treated to 30 sites had local tumor control of 67% and crade survival of 72%, with the follow-up ranging from 3 to 33 months (median = 21 months). In the group of 17 previously unirradiated patients who had completed full treatment (IOHDR and EBRT) to 18 sites, the local tumor control was 89%, and all of these patients survived. Tumor control in the six previously unirradiated patients who did not complete EBRT was 50% with a crude survival of 50%. In the group of six previously irradiated patients treated by IOHDR only, the local tumor control was 17% with a crude survival of 17%. No intraoperative complications were noted. The delayed morbidity included cerebrospinal fluid (CSF) leak with bone exposure (1), chronic subdural hematoma (1), septicemia (1), otitis media (1), and severe xerostomia (1). We cannot comment on long-term morbidity due to the relatively short follow-up period of 21 months. CONCLUSIONS: It is feasible to deliver IOHDR, with acceptable toxicity, to skull base tumors at sites inaccessible to IOEBRT. The use of IOHDR as a pre-radiotherapy boost produced excellent local control and survival in the selected group of patients who had no previous radiation therapy. The use of exclusive IOHDR in the previously irradiated group resulted in poor outcome, possibly due to the limitations on re-irradiation doses and/or volumes determined by normal tissue tolerance or because these patients have inherently radioresistant tumors. Higher IOHDR doses, additional EBRT, and/or chemotherapy should be considered for this group. The use of IOHDR as a pre-EBRT boost to maximize local control has a promising future in the treatment of carefully selected patients with advanced skull base tumor.

Brachytherapy↗

Desmoplastic malignant melanoma presenting as a lung mass.

A case of metastatic desmoplastic malignant melanoma is reported. The patient presented initially with a lung mass and subsequently developed facial swelling and numbness secondary to tumor involvement of the maxillary division of the trigeminal nerve. The pleomorphism, histochemistry, and schwannoid differentiation of these tumors is discussed.

Cranial Nerve Neoplasms↗

Evaluation of 96-hour infusion fluorouracil plus cisplatin in combination with alpha interferon for patients with advanced squamous cell carcinoma of the head and neck: a Southwest Oncology Group study.

BACKGROUND: Recurrent cancer of the head and neck after primary therapy is almost always fatal. The combination of 5-fluorouracil (5-FU) and cisplatin is considered the best available therapy but complete response rates remain too low to affect survival. This study was designed to evaluate the complete response rate and toxicity of 5-FU, cisplatin, and alpha-interferon (alpha-IFN) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). METHODS: Fifty eligible patients with recurrent or metastatic SCCHN and no prior chemotherapy (40 men, 10 women; age range, 26-77 years; median, 59 years; 82% white; 88% had prior surgery and 92% had prior radiation therapy) were treated every 21 days with 96-hour infusion of 5-FU 1000 mg/m2/day; cisplatin 100 mg/m2, day 1; and alpha-IFN 5 x 10(6) units/day, days 1-4. RESULTS: One hundred fifty-seven courses of chemotherapy were administered, with a median of three courses. Thirty-seven patients experienced Grade 3 or 4 toxicity. Of the 17 patients with Grade 4 toxicity; 12 had hematologic toxicity, 3 stomatitis, and 2 vomiting. Two additional patients died of myelosuppression-related sepsis. Of the 50 patients, 3 (6%) achieved a complete response, five (10%) had a partial response, 3 (6%) had unconfirmed response (1 complete and 2 partial), 10 (20%) had stable disease, 17 (34%) progressed, and 12 (24%) were considered nonresponders owing to early death (6) or inadequate assessment (6). The median survival was 5 months. CONCLUSION: The complete response rate of patients with recurrent or metastatic SCCHN treated with 5-FU, cisplatin, and alpha-IFN does not appear to be superior to that observed for 5-FU and cisplatin. Alpha-interferon appears to augment hematologic and gastrointestinal toxicities associated with this combination.

Adult↗

Surgical reporting instrument designed to improve outcome data in head and neck cancer trials.

Precise reporting of surgical staging and operative data in multi-institutional protocol studies could provide a number of benefits: 1) fewer cases would be discarded because of inadequate data, 2) staff review time would be reduced, 3) there would be assurance that participating surgeons were performing similar operations on similar tumors, 4) the resulting precision in stratification should improve the likelihood of achieving accurate comparison of the treatment options under study, and 5) by comparing the surgical parameters with local-regional control of disease, the specific factors that have a statistically significant correlation with outcome could be identified. This paper presents a computer-based, anatomically oriented reporting instrument that should improve the reliability of surgical data available to multi-institutional protocols.

Clinical Trials as Topic↗