A 16-month-old boy vomits a double tongue: intraluminal duplication of the cervical esophagus in children.

A 16-month-old boy presented with a story of stridor, solid dysphagia and a history of spectacular protrusion underneath his tongue which was mistaken by the parents for a snake's tongue! The radiological examinations showed a filling defect of the upper and middle third esophagus which compressed the cervical trachea. This was found to be an intraluminal tubular esophageal duplication. Treatment by cervicotomy and unusual histological facts are presented.

Transcriptional inactivation of c-myc and the transferrin receptor in dibutyryl cyclic AMP-treated HL-60 cells.

Treatment of HL-60 cells with dibutyryl cyclic AMP induced rapid transcriptional inactivation of c-myc and the transferrin receptor. Transcriptional inactivation was followed by loss of c-myc and transferrin receptor mRNA and protein. Treated cells completed one round of proliferation, followed by growth arrest, G1 synchronization, and monocytic differentiation. These data suggest that cyclic AMP-mediated control of growth and differentiation may be achieved, at least in part, by transcriptional regulation of certain growth-associated proto-oncogenes and growth factor receptor genes.

Insecticidal proteins from Bacillus thuringiensis protect corn from corn rootworms.

Field tests of corn co-expressing two new delta-endotoxins from Bacillus thuringiensis (Bt) have demonstrated protection from root damage by western corn rootworm (Diabrotica virgifera virgifera LeConte). The level of protection exceeds that provided by chemical insecticides. In the bacterium, these proteins form crystals during the sporulation phase of the growth cycle, are encoded by a single operon, and have molecular masses of 14 kDa and 44 kDa. Corn rootworm larvae fed on corn roots expressing the proteins showed histopathological symptoms in the midgut epithelium.

On-line characterization of YBCO coated conductors using Raman spectroscopy methods.

The use of Raman spectroscopy for on-line monitoring of the production of superconducting YBa2Cu3O6+X (YBCO) thin films on long-length metal tapes coated with textured buffer layers is reported for the first time. A methodology is described for obtaining Raman spectra of YBCO on moving tape exiting a metal-organic-chemical-vapor-deposition (MOCVD) enclosure. After baseline correction, the spectra recorded in this way show the expected phonons of the specific YBCO crystal orientation required for high supercurrent transport, as well as phonons of non-superconducting second-phase impurities when present. It is also possible to distinguish YBCO films that are properly textured from films having domains of misoriented YBCO grains. An investigation of the need for focus control on moving tape indicated that focusing of the laser on the surface of the highly reflective YBCO films exiting the MOCVD enclosure tends to produce aberrant photon bursts that swamp the Raman spectrum. These photon bursts are very likely a consequence of optical speckle effects induced by a combination of surface roughness, crystallographic texture, and/or local strain within the small grain microstructure of the YBCO film. Maintaining a slightly out-of-focus condition provides the best signal-to-noise ratio in terms of the obtained Raman spectra. In addition to examining moving tape at the post-MOCVD stage, Raman spectra of the film surface can also be recorded after the oxygen anneal performed to bring the YBCO to the optimum superconducting state. Consideration is given to data processing methods that could be adapted to the on-line Raman spectra to allow the tagging of out-of-specification tape segments and, at a more advanced level, feedback control to the MOCVD process.

Benzoquinonoid ansamycins possess selective tumoricidal activity unrelated to src kinase inhibition.

The benzoquinonoid ansamycin antibiotics herbimycin A and geldanamycin have been shown to reverse the oncogenic phenotype of pp60v-src transformed cells as well as induce differentiation in a number of in vitro model systems, reportedly due to their inhibition of src family protein tyrosine kinases. We now report that these agents are potent cytotoxins in vitro against a panel of highly malignant human tumor cell lines possessing primitive neural features. Proliferation and/or survival of fibroblasts, primary neuronal cultures, and several leukemia cell lines are unaffected at concentrations resulting in greater than 99% cell loss in sensitive lines. The tumorigenicity in nude mice of sensitive cell lines can also be markedly reduced by either systemic or topical administration of these agents without apparent toxicity to the whole animal. The cytocidal action of these ansamycins is initiated very rapidly, is irreversible, and is clearly distinct from the delayed inhibition of src family kinases that has been reported previously. Due to their potency, relative selectivity, and novel mechanism(s) of action, these drugs could prove clinically useful in the therapy of a number of human cancers of neural derivation.

Expression of the interleukin 6 receptor and interleukin 6 in prostate carcinoma cells.

We have probed for the presence of interleukin 6 (IL6) receptors in prostatic carcinoma cell lines (LNCaP, DU 145, and PC3) by examining their sensitivity to the cytotoxic effects of a chimeric toxin composed of IL6 and Pseudomonas exotoxin (PE). All three cell lines were killed by IL6-PE66(4)Glu, a version of IL6-PE in which the binding domain of native PE has been mutated to debilitate PE binding to its own receptor. This cytotoxic activity confirmed the presence of IL6 receptors on prostatic carcinoma cells. We have measured the number of IL6 receptors found on these cells and have further determined that they secrete IL6. These data provide evidence that IL6 and its receptor may play an important role in human prostate cancer.

Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy.

PURPOSE: To explore the use of SD/01 (a polyethylene glycol-conjugated filgrastim shown in preclinical studies to have a prolonged half-life) in patients with chemotherapy-induced neutropenia. PATIENTS AND METHODS: Thirteen patients with non-small-cell lung cancer were randomized to receive daily filgrastim (5 microg/kg/d) or a single injection of SD/01 (30, 100, or 300 microg/kg) 2 weeks before chemotherapy and again 24 hours after administration of carboplatin and paclitaxel. Pharmacodynamic, pharmacokinetic, and safety analyses were performed. RESULTS: Peak serum concentrations of SD/01 and the duration of increased serum concentrations were dependent on the SD/01 dose. SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia. Prechemotherapy median absolute neutrophil counts (ANCs) in patients receiving SD/01 were increased in a dose-dependent fashion, with the duration of this effect also being dose dependent. After chemotherapy, median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 microg/kg, with higher nadirs seen in the cohorts receiving SD/01 100 or 300 microg/kg. Dose-limiting toxicities were not noted. CD34(+) cells were mobilized in all cohorts. CONCLUSION: A single dose of SD/01 increases the serum concentration of SD/01 for several days in a dose-dependent fashion and is not associated with significant toxicity. The effects of SD/01 on ANC and CD34(+) cell mobilization are comparable or greater than those achieved with daily filgrastim. The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical settings associated with neutropenia.

Significant weight loss after laparoscopic Nissen fundoplication.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) has evolved as a gold standard in antireflux surgery. However, the association between body weight and gastroesophageal reflux disease (GERD) is still unclear, and no data are available concerning the effect of fundoplication on body weight. We present the first report elucidating the impact of LNF on body weight in GERD patients with special emphasis on patients' quality of life. METHODS: From July 2000 to March 2003, LNF was carried out in 213 patients (85 women and 128 men) after thorough preoperative examination including clinical interview with standardized assessment of symptoms and quality of life (QoL), endosocopy, barium swallow, 24-h pH-metry, and manometry. Follow-up investigations were performed 3 and 12 months after LNF obtainable from 209 patients (98.1%) and 154 patients (72.3%), respectively. RESULTS: The mean body mass index (BMI) decreased significantly after LNF (27.6 +/- 5.6 kg/m(2) before LNF vs 26.0 +/- 3.8 kg/m(2) after LNF, p < 0.001). Twelve months after LNF, neither a tendency toward a renewed increase nor a further decrease in BMI was observable. The average body weight loss was 3.9 kg. BMI reduction was higher in women than in men (p < 0.002), and obese patients lost more weight than lean patients (p < 0.001). There was no association between BMI reduction and dysphagia. Plasma cholesterol and triglyceride levels did not change after LNF. The mean general score of the Gastrointestinal Quality of Life Index markedly improved (90.1 +/- 21.3 before LNF vs 118.0 +/- 16.2 after LNF, p < 0.01), as did the GERD-Health Related Quality of Life Index (21.9 +/- 6.4 before LNF vs 3.5 +/- 2.7 after LNF, p < 0.001). However, there was no association between changes in BMI and QoL. CONCLUSION: LNF leads to significant and persistent body weight loss.

A new form of Filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans.

Granulocyte colony-stimulating factor (G-CSF) has proven effective in the prophylaxis of chemotherapy-induced neutropenia and as a mobilizer of peripheral blood progenitor cells. The longevity of G-CSF action is limited by its removal from the body by two mechanisms. The first is thought to be mediated via receptors (receptor mediated clearance [RMC]) predominantly on neutrophils, the second process is likely the result of renal clearance. With the intention of developing a novel form of Filgrastim (r-met HuG-CSF) with a sustained duration of action in vivo, a new derivative named SD/01 has been made by association of Filgrastim with poly(ethylene glycol). The desired properties of this new agent would include a prolonged duration of action sufficient to cover a complete single course of chemotherapy. SD/01 is shown here to sustain significantly elevated neutrophil counts in hematopoietically normal mice for 5 days. In neutropenic mice effects were noted for at least 9 days, accompanying a significant reduction in the duration of chemotherapy induced neutropenia. Normal human volunteers showed higher than baseline ANC for around 9 to 10 days after a single injection of SD/01. Data from these normal volunteers also indicate that mobilization of CD34+ cells and progenitors may occur in a more timely manner and to around the same absolute numbers as with repeated daily injections of unmodified Filgrastim. These data indicate that SD/01 represents an efficacious novel form of Filgrastim with actions sustained for between one and two weeks from a single injection.

Sequential cycles of high-dose chemotherapy with dose escalation of carboplatin with or without paclitaxel supported by G-CSF mobilized peripheral blood progenitor cells: a phase I/II study in advanced ovarian cancer.

To assess high-dose carboplatin chemotherapy with or without paclitaxel with filgrastim mobilized peripheral blood progenitor cell (PBPC) support in a phase I/II study, a total of 21 patients with mostly chemonaive disease received four cycles of high-dose chemotherapy. Cycle 1 (cyclophosphamide, 6 g/m2) was followed by two cycles of carboplatin (1600 mg/m2 or 1800 mg/m2). Cycle 4 consisted of carboplatin (1600 mg/m2), etoposide (1600 mg/m2), and melphalan (140 mg/m2). Further chemotherapy intensification was achieved by adding paclitaxel (175 mg/m2) to all cycles with a fixed carboplatin dose (1600 mg/m2). Ototoxicity was dose-limiting for escalation of sequential cycles of carboplatin. Grade 2 and grade 3 ototoxicity, hearing loss not requiring a hearing aid, or hearing loss correctable with a hearing aid, was observed with carboplatin at 1800 mg/m2. The maximum tolerated dose (MTD) of sequential carboplatin, therefore, was identified in this study as 1600 mg/m2. After cycles 1, 2, 3 and 4 the median duration of leukopenia (<1.0x10(9)/l) was 7, 4, 4 and 6 days. Severe grade 3 and 4 infections were seen in only 7% of cycles. Of the 21 patients evaluable for disease response, 57% had complete remissions and 43% experienced partial remissions resulting in an overall response rate of 100%. The median progression-free survival is 25 (15-36) months, the median overall survival 36.5 (15-38) months. Most patients were suboptimally debulked or had bulky residual disease at the start of chemotherapy. Sequential high-dose chemotherapy to a maximum dose of 1600 mg/m2 carboplatin is effective and feasible. A randomized, prospective trial comparing sequential high-dose chemotherapy with optimal standard chemotherapy is now warranted.

Allogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with early leukaemia: first results of a randomised multicentre trial of the European Group for Blood and Marrow Transplantation.

In a multicentre trial involving 20 transplant centres from 10 countries haematopoietic stem cells were obtained either from the bone marrow of 33 sibling donors or from the peripheral blood of 33 such donors after administration of filgrastim (10 microg/kg/day). The haematopoietic stem cells were infused into their HLA-identical recipients suffering from acute leukaemias in remission or chronic myeloid leukaemia in chronic phase. PBPC donors tolerated filgrastim administration and leukapheresis well with the most frequent side-effects being musculoskeletal pain, headache, and mild increases of LDH, AP, Gamma-GT or SGPT. Pain and haematoma at the harvest site and mild anaemia were the most frequent complaints of BM donors. Severe or life-threatening complications were not seen with any type of harvest procedure. Time to platelet recovery greater than 20 x 10(9)/l was 15 days (95% confidence interval (CI) 13-16 days) in the PBPCT group and 19 days (CI 16-25) in the BMT group. Time to neutrophil recovery greater than 0.5 x 10(9)/l was 14 days (CI 12-15 days) in the PBPCT group as compared to 15 days (CI 15-16 days) in the BMT group. The numbers of platelet transfusions administered to PBPCT and BMT patients were 12 (range: 1-28) and 10 (range: 3-39), respectively. Sixteen patients (48%) transplanted with bone marrow and 18 patients (54%) transplanted with PBPC developed acute GVHD of grades II-IV; acute GVHD of grades III or IV developed in six (18%) and seven (21%) patients, respectively. Kaplan-Meier plots for transplant-related mortality until day 100 and leukaemia-free survival at a median of 400 days after BMT or PBPCT showed no significant differences. Administration of filgrastim and leukapheresis in normal donors were feasible and well tolerated. The number of days with restricted activity and of nights spent in hospital was lower in donors of PBPC. Transplantation of PBPC to HLA-identical siblings with early leukaemia resulted in earlier platelet engraftment. The incidence of moderate to severe acute GVHD, transplant-related mortality, and leukaemia-free survival did not show striking differences. Further investigation of allogeneic PBPCT as a substitute for allogeneic BMT is warranted.

Traumatic bilhemia.

BACKGROUND: Retrospective analysis was done of three cases with severe liver trauma and excessive serum bilirubin levels caused by a traumatic biliovenous fistula. The literature is reviewed. METHODS: Diagnostic measures included laboratory findings, computed tomography, ultrasonography, and endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: The biliovenous fistula was detected by ERCP in two cases. In one case a left hemihepatectomy was carried out, and the patient was cured. The other patient received drainage of a huge necrotic cavity in the center of the liver. Ten months later the patient underwent reoperation, and left hepatic resection was performed. The patient died of liver function failure on postoperative day 7. In the third case the fistula subsided spontaneously. CONCLUSIONS: An excessively high serum level of direct bilirubin and only moderately elevated liver enzymes indicate bilhemia in trauma patients. ERCP is most reliable in localizing the fistula; computed tomography/ultrasonography are valuable in detecting the extension and localization of the parenchymal destruction. Conservative therapy is justified if the patient is in good condition or if the localization of the fistula is unclear. Spontaneous closure of the fistula may occur. Surgical treatment options are partial liver resection and suture of the fistula and T-tube drainage of the common bile duct and drainage of the rupture site.

Respiratory symptoms in patients with gastroesophageal reflux disease following medical therapy and following antireflux surgery.

BACKGROUND: It is not known whether antireflux surgery is more effective than medical therapy to control respiratory symptoms (RS) in gastroesophageal reflux disease (GERD). METHODS: In 21 GERD patients with RS, reflux was assessed by endoscopy, manometry, and pH monitoring. Patients had proton pump inhibitor therapy and cisapride for 6 months. After GERD relapsed following withdrawal of medical therapy, 7 patients with normal esophageal peristalsis had a laparoscopic Nissen fundoplication and 14 with impaired peristalsis a Toupet fundoplication. Respiratory symptoms were scored prior to treatment, at 6 months following medical therapy, and at 6 months after surgery. RESULTS: Heartburn and esophagitis were effectively treated by medical and surgical therapy. Only surgery improved regurgitation. Respiratory symptoms improved in 18 patients (85.7%) following surgery and in only 3 patients (14.3%) following medical therapy (P <0.05). Esophageal peristalsis improved following the Toupet fundoplication. CONCLUSION: Medical therapy fails to control reflux since it does not inhibit regurgitation. Surgery controls reflux and improves esophageal peristalsis, which contributes to its superiority over medical therapy in the treatment of RS associated with GERD.

Spontaneous apoptosis and the expression of p53 and Bcl-2 family proteins in locally advanced head and neck cancer.

BACKGROUND: Apoptotic cell death plays a key role in the pathogenesis, aggressiveness, and therapy responsiveness of cancer. The suicidal machinery of apoptosis is genetically controlled. Proteins of the Bcl-2 family as well as p53 are important regulators of apoptosis. OBJECTIVE: To assess the rate of spontaneous apoptosis and the expression of p53 and Bcl-2 family proteins in locally advanced squamous cell carcinomas of the head and neck. DESIGN: Twenty-six patients with locally advanced squamous cell carcinoma of the head and neck were included in the study. The expression of p53, Bcl-2, Mcl-1, Bax, and Bak was assessed by immunohistochemical analysis. The terminal deoxytransferase-mediated deoxyuridine nick end-labeling assay was used to quantify apoptosis by flow cytometry. RESULTS: Tumor cells containing immunostaining for the antiapoptotic proteins Bcl-2 and Mcl-1 were present in 4 (15%) and 24 (92%) of the cases evaluated, respectively, whereas immunopositivity for the proapoptotic proteins Bax and Bak was found in 9 (35%) and 24 (92%) of the samples. Immunoreactivity to p53 was detected in 20 (77%) of the samples. There was a positive correlation between the expression of Bcl-2 and Bax and between Mcl-1 and Bak. A low fraction of apoptotic cells (<2.5%) in the pretreatment tumor samples was significantly correlated with increased 2-year survival in these patients. CONCLUSIONS: Our results establish the frequent expression of the Bcl-2 family proteins Bcl-2, Mcl-1, Bax, and Bak in locally advanced head and neck cancer. In addition, this study suggests that the apoptotic fraction in pretreatment tumor samples might be of prognostic importance for the outcome in these patients.

Methodological aspects of DNA image cytometry in formalin-fixed paraffin-embedded material from pancreatic adenocarcinoma.

Deparaffinized and disintegrated material from conventionally formalin-fixed and paraffin-embedded surgical specimens of 100 cases of ductal adenocarcinoma of the pancreas was Feulgen-stained, and the cytochemical DNA distribution patterns of at least 100 single tumour cells and 50 "control" cells (fibrocytes) were assessed by means of image cytometry (ICM). In 77 cases a sufficient number of neoplastic cells could be obtained for these DNA assessments. The fairly high number (23) of cases that had to be excluded due to too small amounts of disintegrated cells or cell nuclei may be explained by the high content of connective tissue stroma in these pancreatic adenocarcinomas. The tumour cell nuclei in 76 of these 77 cases showed cytochemically a clear-cut "non-diploid" DNA distribution pattern. This observation reflects the well-known highly malignant growth potential of this carcinoma. Despite the fact that about 1/4 of the tumours had to be excluded, the main result of our methodological study is, after all that conventionally formalin-fixed paraffin-embedded specimens of most pancreatic adenocarcinomas can be successfully used for the deparaffinization-disintegration procedure preceding the nuclear DNA assessments by means of ICM. Additional studies are, however, required to obtain the diagnostic and prognostic impact of the results of such cytochemical analyses of the DNA distribution pattern in adenocarcinomas of the pancreas.

Performance of an athlete with straight posterior knee instability.

Isolated posterior ligamentous insufficiency of the knee frequently terminates an athlete's career and may even adversely affect the performance of tasks of daily living. Return to competitive athletics following surgical reconstruction for posterior instability is unusual. The pathophysiology of the lesion and a biomechanical analysis are discussed. A case report of an athlete with a ruptured posterior cruciate ligament who is presently successfully competing in professional football is also presented. Rigorous quantitative techniques were employed to document the compensatory mechanisms involved. These consisted of extremely strong quadriceps muscles contracting much earlier than normal in the gait cycle. Earlier quadriceps contraction to increase dynamic stability in the knee is able to overcome the instability resulting from the incompetent posterior cruciate ligament.

Factors influencing elbow instability.

Stability or instability of the elbow is contingent upon three distinct but interrelated conditions: radiocapitellar articular continuity, coronoid process integrity and medial collateral ligament competency through an intact anterior oblique ligament. The latter, the anterior oblique ligament of the medial collateral ligament both in anatomic experimentation and clinical cases appears to be the most critical factor in elbow stability. The reconstruction of the unstable elbow must focus on this medial supporting ligament for a predictable result.

Grazing methods and stocking rates for direct-seeded alfalfa pastures: I. Plant productivity and animal performance.

A 4-yr study was conducted to determine the effects of two grazing methods (GM) at two stocking rates (SR) on alfalfa pasture plant productivity and animal performance and to ascertain the effect of grazing systems on subsequent performance of steers fed a high-concentrate diet. Eight pasture plots (.76 ha) were seeded in 1988 with alfalfa (Medicago sativa L. var. WL225) and divided into two blocks of four pastures each. Grazing methods consisted of a traditional four-paddock or an intensive 13-paddock system. Pastures were managed to allow a 36-d rest period with an average grazing season of 110 d. The low and high SR were 5.9 vs 11.7, 5.3 vs 10.5, 5.3 vs 7.9, and 5.3 vs 7.9 steers/ha for years 1989 to 1992, respectively. Following the grazing season, steers were placed in a feedlot and fed a high-concentrate diet (81% high-moisture corn, 14% corn silage, 5% protein-mineral supplement) for an average of 211 d. There was no effect of GM on herbage mass, pasture phase ADG, or live weight gain/hectare. Increasing the number of paddocks was beneficial when herbage mass was limited and stocking rate was above 7.9 steers/ha. Increasing SR above 7.9 steers/ha decreased herbage mass and pasture-phase ADG. As forage allowance increased, pasture-phase ADG increased quadratically (R2 = .82, P < .001), reached a plateau, and then decreased. Previous grazing system did not influence the performance of steers in the feedlot or their carcass characteristics. Optimum SR is dependent on herbage mass produced.

[Tumor markers in the upper intestinal tract--stomach and pancreas]. / Tumormarker im oberen Intestinaltrakt--Magen und Pankreas.

Expectations of early diagnosis of carcinoma of the stomach and pancreas by using the tumour markers CEA and CA 19-9 have been disappointed. Although the sensitivity of CA 19-9 for pancreatic cancer is high, its field of application for screening is not efficient due to poor specificity of the marker. CEA and CA 19-9 are of great importance in the follow-up of pancreatic cancer. Results of tests of CEA and CA 19-9 in 100 patients with gastric cancer and 50 patients suffering from pancreatic cancer are reported.

[Peptic ulcer with a visible non-bleeding vascular wall--early elective surgery or endoscopic therapy?]. / Das peptische Ulkus mit nicht-blutendem sichtbarem Gefässbürzel--Frühelektive Operation oder endoskopische Therapie?

The records of 71 patients with the endoscopic finding of a peptic ulcer with a non-bleeding visible vessel, treated between 1982 and 1987 were retrospectively analysed. 16 patients underwent early surgical treatment (group I), 15 patients were treated conservatively (group II) and 40 patients by endoscopic haemostasis (group III). Recurrent bleeding was observed in 6.25% patients in group I, in 53.3% in group II and in 25% in group III, in which case endoscopy was performed again. The patients with arterial bleeding underwent early elective operation after endoscopic haemostasis. Deaths occurred only in the postoperative period: group I 6.25%, group II 13%, and group III 5%. These findings indicate that primary endoscopic treatment in selected patients leads to results equal to those achieved with early surgery. Conservative therapy cannot, however, be recommended.