Oral cavity, oropharynx, and hypopharynx.
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Carcinoma, Squamous Cell↗
Biomedical subjects
M Becker
Publications and source records attributed to M Becker.
Systemic hypertension and renal function in long-term liver transplant recipients on cyclosporine.
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Creatinine↗
Golvesin-GFP fusions as distinct markers for Golgi and post-Golgi vesicles in Dictyostelium cells.
Golvesin is a new protein associated with membranes of the Golgi apparatus and post-Golgi vesicles in Dictyostelium cells. An internal hydrophobic sequence of 24 amino-acid residues is responsible for anchoring golvesin to the membranes of these organelles. In an attempt to visualize organelle dynamics in vivo, we have used specific antibody and other labels to localize golvesin-green fluorescent protein (GFP) constructs to different cellular compartments. With a GFP tag at its N-terminus, golvesin shows the same localization as the untagged protein. It is transferred to two post-Golgi compartments, the endosomal and contractile vacuole systems. Endosomes are decorated with GFP-golvesin within less than 10 min of their internalisation, and keep the label during the acidic phase of the pathway. Blockage of the C-terminus with GFP causes entrapment of the protein in the Golgi apparatus, indicating that a free C-terminus is required for transfer of golvesin to any of the post-Golgi compartments. The C-terminally tagged golvesin proved to be a reliable Golgi marker in Dictyostelium cells revealing protrusion of Golgi tubules at peak velocities of 3 to 4 microm x s(-1). The fusion protein is retained in Golgi vesicles during mitosis, visualizing Golgi disassembly and reorganization in line with cytokinesis.
Amino Acid Sequence↗
Neoplastic invasion of laryngeal cartilage: radiologic diagnosis and therapeutic implications.
Cross-sectional imaging plays an indispensable complementary role to endoscopy in the pretherapeutic workup of laryngeal and hypopharyngeal cancer. Both computed tomography and magnetic resonance imaging are suitable for the detection of neoplastic cartilage invasion. Although MRI, due to its high negative predictive value, is now generally considered to be the most suitable imaging method for pretherapeutic evaluation of cartilage invasion CT continues to be commonly performed in many centers for practical reasons. Recent studies have shown that CT may yield acceptable sensitivity for neoplastic invasion of laryngeal cartilage if the diagnostic criteria are selected and combined appropriately. False positive results are inevitable with both CT and MRI because reactive inflammation may lead to overestimation of neoplastic cartilage invasion.
Arytenoid Cartilage↗
Differences in immunoreactivity of estrogen receptor (ER) in tamoxifen-sensitive and -resistant breast carcinomas: preclinical and first clinical investigations.
Inherited or acquired tamoxifen resistance is a major constraint in the endocrinological treatment of breast carcinomas. We developed an enzyme-immunoassay that discriminates between tamoxifen-sensitive and -resistant tumors. The procedure was established and standardized using two xenografted breast carcinomas--3366 (highly sensitive to tamoxifen) and 3366/TAM (acquired tamoxifen resistance). The latter model was developed by treatment of 3366 tumor-bearing nude mice during serial passaging over 3 years with tamoxifen. Both lines were estrogen receptor (ER) positive (101 or 82 fmol/mg protein), and revealed no differences in the nucleotide sequences of the hormone binding domain of the ER protein. However, while in the sensitive tumors an upregulation of ER levels was registered after estradiol treatment of tumor bearing nude mice, the ER expression in the resistant line remained unchanged. The tamoxifen sensitive and -resistant breast carcinoma 3366 differed, additionally, in their immunoreactivity of ER to mAB H222. While an incubation with estradiol or tamoxifen of immobilized ER prepared from cytosols of the sensitive tumors 3366 led to a significant increase in immunoreactivity, samples of resistant tumors failed in the exposition of additional immunologically reactive epitopes. These results were the basis for the development of an assay for determination of the tamoxifen response in patients. Our retrospective results with 38 breast tumors from a tumor bank indicated that patients with an increase of immunoreactivity of ER more rarely had a recurrence while under going tamoxifen therapy compared with patients expecting no increase. However, the data indicate interesting changes occurring with the ER of tam-resistant tumors that are to be explained by further mutational or protein-chemical analysis.
Animals↗
Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis.
Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. In approximately one-third of all cases, no aetiological factor can be found, and these patients are classified as having idiopathic disease. Pathophysiologically, autodigestion and inflammation may be caused by either increased proteolytic activity or decreased protease inhibition. Several studies have demonstrated mutations in the cationic trypsinogen gene (PRSS1) in patients with hereditary or idiopathic CP. It is thought that these mutations result in increased trypsin activity within the pancreatic parenchyma. Most patients with idiopathic or hereditary CP, however, do not have mutations in PRSS1 (ref. 4). Here we analysed 96 unrelated children and adolescents with CP for mutations in the gene encoding the serine protease inhibitor, Kazal type 1 (SPINK1), a pancreatic trypsin inhibitor. We found mutations in 23% of the patients. In 18 patients, 6 of whom were homozygous, we detected a missense mutation of codon 34 (N34S). We also found four other sequence variants. Our results indicate that mutations in SPINK1 are associated with chronic pancreatitis.
Adolescent↗
The changing pattern of mortality and morbidity from radical cystectomy.
OBJECTIVES: To examine the morbidity and mortality of radical cystectomy as currently practised, and to compare the findings with historical data. PATIENTS AND METHODS: The operative mortality and early and late complications were recorded in 101 consecutive patients (median age 65 years, range 38-81; 33 aged >70 years) undergoing radical cystectomy between April 1992 and October 1997. Fifteen patients had relapsed after previous radical radiotherapy. RESULTS: The median postoperative stay was 14 days (range 8-44). There were two deaths within 60 days of surgery (of patients aged 46 and 59 years) from respiratory failure and sepsis, respectively. The mortality in the elderly was not more than in other age groups. The early morbidity included two cases of lower limb insufficiency, both in the salvage cystectomy group, where the morbidity was significantly higher than in those undergoing primary cystectomy (chi-squared, P<0.01). Three patients underwent early re-exploration. There were four clinically significant episodes of deep vein thrombosis and two pulmonary emboli that were not fatal. CONCLUSION: As currently practised, radical cystectomy is associated with a lower mortality (<2%) and morbidity than described previously. The added morbidity of salvage cystectomy and the acceptable mortality of primary cystectomy suggests that the treatment of choice for muscle-invasive disease is primary cystectomy, with external beam radiotherapy reserved for those patients unfit for major surgical intervention. Age alone should no longer be considered a contraindication to cystectomy.
Adult↗
Autoantibodies to tissue transglutaminase are sensitive serological parameters for detecting silent coeliac disease in patients with Type 1 diabetes mellitus.
AIMS: To investigate the clinical significance of the determination of IgA antibodies to tissue transglutaminase (tTG) for the detection of silent coeliac disease in patients with Type 1 diabetes mellitus. METHODS: A total of 520 patients with diabetes (median age 14.2 years, range 1-27) were tested for IgA antibodies to tTG (IgA anti-tTG, ELISA), endomysium (EmA, indirect immunofluoresence) and gliadin (IgA-AGA, enzyme immunometric assay) after ruling out IgA deficiency. RESULTS: The prevalence of IgA anti-tTG among patients with diabetes was 4.4% (23 of 520), and that of EmA and IgA-AGA 3.5% (18 of 520, respectively). The coefficient of agreement between IgA anti-tTG and EmA was high (Cohen's kappa = 0.87, P < 0.001). Thirteen of the 23 IgA anti-tTG-positive patients underwent duodenal biopsy. Coeliac disease was confirmed in nine of 13 patients. One of them was negative for EmA and AGA, but positive for IgA anti-tTG. Retrospective annual determinations up to 8 years in six IgA anti-tTG-positive patients showed both permanent and transient elevations of the serological markers. CONCLUSIONS: These data show that a positive IgA antibody test to tTG is a more sensitive parameter than EmA for silent coeliac disease in patients with diabetes. Confirmatory small bowel biopsy, however, remains necessary for diagnosis as some patients with positive antibodies may be without histological changes.
Adolescent↗
Development and characterization of a tamoxifen-resistant breast carcinoma xenograft.
A human tamoxifen-resistant mammary carcinoma, MaCa 3366/TAM, originating from a sensitive parental xenograft 3366 was successfully established by treatment of tumour-bearing nude mice with 1-50 mg kg(-1) tamoxifen for 3 years during routine passaging. Both tumours did not differ significantly in OR- and PR-positivity, however, when compared with the sensitive tumour line, the mean OR content of the TAM-resistant subline is slightly lower. An OR-upregulation following withdrawal of oestradiol treatment was observed in the parental tumours but not in the resistant xenografts. Following long-term treatment with tamoxifen, the histological pattern of the breast carcinoma changed. The more differentiated structures being apparent after treatment with 17beta-oestradiol in the original 3366 tumour were not induced in the resistant line. Tamoxifen failed to induce a tumour growth inhibition in comparison to the tamoxifen-sensitive line. The pure anti-oestrogen, ICI 182 780, revealed cross-resistance. Sequence analysis of the hormone-binding domain of the OR of both lines showed no differences, suggesting that either mutations in other regions of the OR are involved in the TAM-resistance phenotype or that mechanisms outside of this protein induced this phenotype. Oestrogen and anti-oestrogen regulate pS2 and cathepsin D expression in 3366 tumours as in the human breast cancer cell line MCF-7. The resistant 3366/TAM tumours have lost this regulation. The established breast cancer xenografts 3366 and 3366/TAM offer the possibility of investigating mechanisms of anti-oestrogen resistance in an in vivo situation. They can be used to test novel approaches to prevent, or to overcome, this resistance in a clinically related manner.
Animals↗
Von Langenbeck or Wardill procedures for primary palatal repair in patients with isolated cleft palate--speech results.
Sixty-six patients operated on for isolated cleft palate were evaluated as adults, and their speech was assessed clinically. Forty-four had undergone a von Langenbeck repair at the age of 7 months and 22 a Wardill repair at the age of 18 months. Speech was judged subjectively by the patients themselves, and perceptual assessment was made by three speech pathologists. The remaining speech problems, mainly hypernasality, were moderate or severe in 7 (16%) of the patients in the von Langenbeck group, and in 7 (32%) in the Wardill group. On the other hand, the patients in the Wardill group had fewer fistulas closed, and fewer velopharyngoplasties. There were no significant differences between the two methods regarding speech in adulthood. The Wardill method produced significantly more scar tissue clinically, which carries the potential risk of inhibition of facial growth. The present speech results will therefore be weighed against the outcome of maxillofacial growth for these patients.
Cleft Palate↗
Interventional sialendoscopy.
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Endoscopy↗
Pharmacokinetics of orally administered omeprazole in children. International Pediatric Omeprazole Pharmacokinetic Group.
OBJECTIVES: The aim of this study was to examine the pharmacokinetics of orally administered omeprazole in children. METHODS: Plasma concentrations of omeprazole were measured at steady state over a 6-h period after administration of the drug. Patients were a subset of those in a multicenter study to determine the dose, safety, efficacy, and tolerability of omeprazole in the treatment of erosive reflux esophagitis in children. Children were 1-16 yr of age, with erosive esophagitis and pathological acid reflux on 24 h-intraesophageal pH study. The "healing dose" of omeprazole was that at which subsequent intraesophageal pH study normalized. Children remained on this dose for 3 months, and during this period the pharmacokinetics were measured. RESULTS: A total of 57 children were enrolled in the overall healing phase of the study. Pharmacokinetic study was optional for subjects and was performed in 25 of the 57 enrolled. The doses of omeprazole required were substantially higher doses per kilogram of body weight than in adults. Values of the pharmacokinetic parameters of omeprazole were generally within the ranges previously reported in adults. However, the plasma levels, area under the plasma concentration versus time curve (AUC), plasma half-life (t(1/2)), and maximal plasma concentration (Cmax), were lower in the younger age group, when the AUC and Cmax were normalized to a dose of 1 mg/kg. Furthermore, within the group as a whole, these values showed a gradation from lowest in the children 1-6 yr of age to higher in the older age groups. CONCLUSIONS: The pharmacokinetics of omeprazole in children showed a trend toward higher metabolic capacity with decreasing age, being highest at 1-6 yr of age. This may explain the need for higher doses of omeprazole on a per kilogram basis, not only in children overall compared with adults but, in many cases, particularly in younger children.
Administration, Oral↗
Sialolithiasis and salivary ductal stenosis: diagnostic accuracy of MR sialography with a three-dimensional extended-phase conjugate-symmetry rapid spin-echo sequence.
PURPOSE: To evaluate the accuracy of magnetic resonance (MR) sialography in detecting salivary glandular calculi and ductal stenoses. MATERIALS AND METHODS: In a prospective study, 64 salivary glands in 61 consecutive patients with acute or recurrent parotid or submandibular glandular swelling were examined by using three-dimensional (3D) extended-phase conjugate-symmetry rapid spin-echo (EXPRESS) MR imaging. Transverse and sagittal-oblique source images and maximum intensity projection images were obtained. All MR images were analyzed independently by two radiologists, without knowledge of the final diagnosis. The reference standard was conventional sialography, ultrasonography (US), and sialendoscopy with or without surgery in 31 glands and was conventional sialography and US in 33 glands. RESULTS: Final diagnoses included sialolithiasis (n = 23), sialolithiasis and stenosis (n = 9), stenosis without lithiasis (n = 11), early Sjögren syndrome without ductal stenosis (n = 2), ductal displacement (n = 3), and normal salivary glands (n = 16). The sensitivity, specificity, and positive and negative predictive values of MR sialography to detect calculi were 91%, 94%-97%, 93%-97%, and 91%, respectively. False-negative readings occurred due to calculi with a diameter of 2-3 mm in nondilated salivary ducts. Ductal stenosis was assessed, with a sensitivity of 100%, specificity of 93%-98%, positive predictive value of 87%-95%, and negative predictive value of 100%. Interobserver agreement was very good (kappa = 0.85-0.97). CONCLUSION: MR sialography with 3D EXPRESS imaging enables reliable prediction of salivary gland calculi and stenoses.
Adolescent↗
[The correspondence of Gottfried Brugger (1857-1891) or the tragic fate of a young veterinarian].
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Correspondence as Topic↗
[Value of positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) in early detection of residual tumor in oro-pharyngeal-laryngeal carcinoma].
OBJECTIVE: To evaluate and compare the performances of FDG-PET imaging, MRI and clinical examination in the detection of residual tumour 3 months after treatment of patients with head and neck squamous cell carcinoma. PATIENTS: A consecutive sample of 50 patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, or a cervical lymph node metastasis from an unknown primary site excluding T1 lip and T1 vocal cord tumours. METHODS: Treatment outcome was assessed after 3 months by clinical examination, MRI, and FDG-PET scan. Sensitivity, specificity and accuracy were calculated relative to proven biopsy of residual tumour or a clinical follow-up of 4 months. RESULTS: Residual cancer was confirmed in 8 patients (16%), while the clinical follow-up was unsuspicious in the remaining 42 patients. PET-FDG had a sensitivity of 100% as compared to MRI (88%) and clinical examination (63%). Specificity was higher for clinical examination (90%), intermediate for MRI (83%) and lowest for PET-FDG (74%). CONCLUSIONS: This study finds very high sensitivity for PET-FDG in the detection of residual tumour. However, its lower specificity, lack of anatomical resolution, and high cost, require further studies to determine its role in routine screening.
Biopsy↗
A phase II study of biochemotherapy for the treatment of metastatic malignant melanoma.
The use of interleukin-2 (IL-2) and interferon-alpha (IFNalpha) in combination with chemotherapy for the treatment of advanced malignant melanoma has generated considerable interest. In particular, the relatively high number of durable complete responses has suggested this may be a significant advance in the treatment of malignant melanoma. We report our experience at the University of Colorado in 43 patients, including many with poor prognostic factors. Patients received cisplatin 20 mg/m2 on days 1-4, vinblastine 1.6 mg/m2 on days 1-4, dacarbazine 800 mg/m2 on day 1, IL-2 9 x 10(6) IU/m2 per day intravenously over 24h on days 1-4 and IFNalpha 5 x 10(6) IU/m2 per day subcutaneously on days 1-5 every 3 weeks. The median follow-up for all patients was 34 months. Responses were seen in 20 patients (47%, 95% confidence interval 31-62%) and comprised five complete responses (CRs) (12%) and 15 partial responses (PRs) (35%). Two patients achieving a CR remain disease free at 45 and 47 months follow-up. In addition three patients who obtained a surgical CR and another with only minor residual changes on computed tomography scan have not progressed at 27, 30, 40 and 27 months, respectively. Toxicity was manageable, but all patients had at least one grade 3 or 4 toxicity, predominantly hypotension and neutropenia. There were no treatment-related deaths. In conclusion, the response rate and duration is within the range previously reported for biochemotherapy. The results of ongoing randomized studies are awaited to better define the value of biochemotherapy in the treatment of advanced melanoma.
Abdominal Neoplasms↗
Direct comparison of F-18-FDG PET and ultrasound in the follow-up of patients with squamous cell cancer of the head and neck.
AIM: The objective of this study was to compare screening ultrasound (US) obtained in patients with squamous cell carcinoma of the head and neck with F-18-FDG PET and to evaluate if US obtained before F-18-FDG PET has the potential to enhance patient management by the detection of additional lesions. METHOD: 28 patients were prospectively included in the study (7 females and 21 males; range: 28-82 years). All had one follow-up examination after surgical treatment and/or radiotherapy using a combination of US and F-18-FDG PET on the same day (6-35 months after the end of treatment). Outcome was determined by either biopsyproven cancer recurrence or negative clinical follow-up for additional 6 months after this examination. RESULTS: Regarding only the regions of the neck evaluated with both methods, US detected 25 suspect lesions vs. 9 lesions detected by F-18-FDG PET. Descriptive statistical analysis showed better sensitivity, specificity and accuracy of F-18-FDG PET. Only in 3 patients a lesion was detected in the same anatomical region using both methods. One patient was false positive with both methods. In another patient US detected a calcified right carotid artery plaque that lead to surgical therapy. CONCLUSION: F-18-FDG PET is better for the detection of clinically relevant lesions in the follow-up of patients with squamous cell carcinoma of the head and neck. In this study, the additional value of morphological information obtained by screening US performed before the PET scan is limited. US may not be a suitable test to improve interpretation of PET examinations.
Adult↗
Combination therapy with efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors in children infected with human immunodeficiency virus type 1. Pediatric AIDS Clinical Trials Group 382 Team.
BACKGROUND: Consistent long-term viral suppression has been difficult to achieve in children with human immunodeficiency virus type 1 (HIV-1) infection. We tested the safety and antiviral efficacy of a novel combination consisting of efavirenz, nelfinavir, and one or more nucleoside reverse-transcriptase inhibitors in 57 children previously treated with only nucleoside reverse-transcriptase inhibitors. METHODS: The children were monitored for 48 weeks after the initiation of therapy. We assessed plasma concentrations of efavirenz and nelfinavir, plasma HIV-1 RNA levels, and lymphocyte subpopulations. RESULTS: At base line, the 57 HIV-1-infected children (age range, 3.8 to 16.8 years) had a median of 699 CD4 cells per cubic millimeter and 10,000 copies of HIV-1 RNA per milliliter of plasma. The most common treatment-related effects of at least moderate severity were rash (in 30 percent of children), diarrhea (in 18 percent), neutropenia (in 12 percent), and biochemical abnormalities (in 12 percent). Serious side effects were uncommon. The mean values for the area under the curve for efavirenz and nelfinavir corresponded to expected values. In an intention-to-treat analysis, 76 percent of children had plasma HIV-1 RNA levels of less than 400 copies per milliliter after 48 weeks of therapy and 63 percent had levels of less than 50 copies per milliliter. A high plasma HIV-1 RNA level at base line significantly decreased the likelihood that plasma levels of HIV-1 RNA would become undetectable during treatment. CONCLUSIONS: In HIV-1-infected children who were previously treated with nucleoside reverse-transcriptase inhibitors, the combination of efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors was generally well tolerated and had a potent and sustained antiviral effect.
Adolescent↗