Down syndrome associated with hypothyroidism and chronic pericardial effusion: echocardiographic follow-up.

We present a 39-year-old male patient with Down syndrome who was evaluated for fatigue, palpitations and bouts of cyanosis. Physical examination showed features of trisomy-21(Down syndrome), with a slow pulse rate, distant cardiac sounds and absent apex beat. He had normal jugular venous pressure without pulsus paradoxus. The ECG showed QRS microvoltage and flattened P and T segments. The 48-hour ambulatory ECG depicted normal sinus rhythm with intermittent short PR interval without tachyarrhythmias. The chest Xray revealed cardiomegaly without pulmonary venous congestion. Although serial transthoracic echocardiographic examination demonstrated pericardial effusion with features of tamponade, there were no overt signs of clinical cardiac tamponade. Biochemically, the serum thyroxine of 3 pmol/l (normal 10 to 25) and thyroid-stimulating hormone of 160 mU/l (normal 0.20 to 4.20)) were compatible with hypothyroidism. The patient was treated with L-thyroxine sodium daily, which was gradually increased to 0.125 mg daily. Within a few months he lost weight and became more alert; furthermore, the symptoms of hypothyroidism and the pericardial effusion resolved. It can be concluded that Down syndrome may be associated with hypothyroidism and pericardial effusion. These were alleviated following hormone replacement. Regular evaluation of thyroid function tests is important in Down syndrome. (Neth Heart J 2007;15:67-70.).

Randomised Phase III study of biweekly 24-h infusion of high-dose 5FU with folinic acid and oxaliplatin versus monthly plus 5-FU/folinic acid in first-line treatment of advanced colorectal cancer.

BACKGROUND: A phase III study was started to compare oxaliplatin/5FU/LV in the first-line with bolus FU/LV in metastatic colorectal cancer. PATIENTS AND METHODS: 302 patients were randomised and received bolus 5-FU 425 mg/m(2) day 1-5, FA 20 mg/m(2) day 1-5, q 4 wk or oxaliplatin 85 mg/m(2), 2 h-infusion, FA 200 mg/m(2), 1-h infusion. 5-FU 2600 mg/m(2), 24-h infusion day 1, q 2 wk. The primary endpoint was response rate (RR). RESULTS: The median follow-up is 31.8 months, 90.4% of the patients have died. Confirmed RR, progression free survival (PFS; months) and median overall survival (OS; months) in 5FU/LV versus 5FU/LV/oxaliplatin were respectively 18.5% versus (vs) 33.8% (P = 0.004), 5.6 vs 6.7 (P = 0.016) and 13.3 vs 13.8 (P = 0.619). In the 5FU/LV/oxaliplatin arm less grade (3/4) toxicity was measured for diarrhoea, stomatitis, an increase in idiosyncratic side effects and neurosensory events compared with 5FU/LV. The quality of life (QOL) was equal in both arms. Second line treatment was given in 62% of the patients, crossover of 5FU/LV to 5FU/LV/oxaliplatin occurred in 14%. CONCLUSIONS: Oxaliplatin in the first-line resulted in an increased RR and PFS with less grade 3/4 mucositis/diarrhoea compared with 5FU/LV alone. Idiosyncratic side effects deserve attention with oxaliplatin. Despite a low treatment cross over rate, OS in both groups was comparable.

Persistence with inhaled corticosteroid therapy in daily practice.

OBJECTIVE: To quantify persistence with inhaled corticosteroids (ICS) among new users in daily practice and identify determinants of persistence. METHODS: A retrospective cohort study was performed with data from the Dutch PHARMO system. This system consists of medication and hospital admission records of 325,000 inhabitants of 12 Dutch cities. In patients who were already using other drugs with a labeled indication of obstructive lung diseases (ATC: R03), individuals with a first dispensing of ICS between January 1, 1994 and December 31, 2000 were identified. Persistence with ICS was defined as the number of days on ICS treatment in the first year of use. Determinants of persistence were identified one year before start of the first dispensing of ICS. RESULTS: Approximately 50% of the patients used inhaled corticosteroids (ICS) for less than 200 days, while 18% continued treatment for one year. One-year persistence rates increased to 40% in patients with a history of multiple respiratory disease related drugs. Persistence rates also increased with lower initial doses, if the initial prescription was instituted by a medical specialist, if a patient was previously hospitalized for obstructive lung diseases, and with increasing age. CONCLUSION: The persistence rate of ICS is poor. Preventing early treatment discontinuation may be important to ensure maximal benefit from ICS treatment.

N-acetylcysteine reduces the risk of re-hospitalisation among patients with chronic obstructive pulmonary disease.

The aim of this study was to evaluate the effect of oral N-acetylcysteine in the prevention of re-hospitalisation for chronic obstructive pulmonary disease (COPD) exacerbations. Using the PHARmacoMOrbidity linkage (PHARMO) system the authors included all patients aged > or = 55 yrs who had been dispensed medication, labelled for respiratory indications (anatomical therapeutic chemical (ATC) classification system: R03), between 1986-1998 and who had also been hospitalised for COPD (International Classification of Diseases (ICD)-9: 491, 492, 496) in this time frame. These subjects were subsequently divided into two groups, those who had received N-acetylcysteine following discharge from their first admission between 1986-1998 and those who had not. All the patients were studied starting from their initial discharge, until their first readmission, death or end of data collection period. The maximum follow-up period was 1 yr. A total of 1,219 patients, who were hospitalised for COPD between 1986-1998, were included in this study. After adjustment for disease severity, it was observed that the use of N-acetylcysteine was significantly associated with a reduced risk of readmission. The readmission risk was significantly lower in patients with high average daily doses of N-acetylcysteine. In conclusion it was observed that N-acetylcysteine reduces the risk of rehospitalisation for chronic obstructive pulmonary disease by approximately 30% and that this risk reduction is dose-dependent.

Asthma exacerbations during first therapy with long acting beta 2-agonists.

Long-acting beta 2-agonists (LBA) have become an important therapeutic strategy in the treatment of asthma. There is, however, debate whether LBA increase the risk of asthma exacerbations (AE). We studied whether the risk of AE was increased in patients starting LBA therapy and whether the risk was associated with severity. Patients, aged 5-49 years, who were firstly prescribed LBA between 1992 and 1995, and who had at least two consecutive prescriptions of LBA, were selected from the PHARMO-RLS database. The exposure period was the interval between the first and last dispensing of the first exposure episode. The year before the onset was the control period. Single short courses of oral glucocorticosteroids or antibiotics were used as proxy indicators for AE. Severity indicators, assessed in the 6 months before initiation of LBA, were used to classify patients' severity. A total of 788 patients met the inclusion criteria (men: 45.1%, median age: 35). The incidence rate of AE increased significantly (p < 0.001) with severity from 1.7 to 2.4 and 1.1 to 2.7 AE per person year in index and control period, respectively. The risk was merely elevated among patients who start LBA therapy without being treated with other anti-asthma drugs before (RR 1.4, 95% CI 1.0-2.2). First starters of LBA showed no overall change in incidence of AE when compared with the year before starting treatment. A total of 6.9% of patients used LBA as step-one therapy. These patients suffer, in contrast to the whole population, a 40% increased risk of having AE. Although this could be due to confounding, we recommend being reluctant to prescribe LBA to patients who have not been treated before with other anti-asthma drugs.

A comparison of clinical pharmacodynamics of different administration schedules of oral topotecan (Hycamtin)

Prolonged exposure to topotecan in in vitro and in vivo experiments has yielded the highest antitumor efficacy. An oral formulation of topotecan with a bioavailability of 32-44% in humans enables convenient prolonged administration. Pharmacokinetic/pharmacodynamic relationships from four Phase I studies with different schedules of administration of oral topotecan in 99 adult patients with malignant solid tumors refractory to standard forms of chemotherapy were compared. Topotecan was administered as follows: (a) once daily (o.d.) for 5 days every 21 days (29 patients); (b) o.d. for 10 days every 21 days (19 patients); (c) twice daily (b.i.d.) for 10 days every 21 days (20 patients); and (d) b.i.d. for 21 days every 28 days (31 patients). Pharmacokinetic analysis was performed in 55 patients using a validated high-performance liquid chromatographic assay and noncompartmental pharmacokinetic methods. Totals of 109, 48, 64, and 59 courses were given, respectively. Dose-limiting toxicity consisted of granulocytopenia for the o.d. x 5-day dosage, a combination of myelosuppression and diarrhea in both of the 10-day schedules, and only diarrhea in the 21-day schedule. Pharmacokinetics revealed a substantial variation of the area under curve (AUC) of topotecan lactone in all of the dose schedules with a mean intrapatient variation of 25.4 +/- 31.0% (o.d. x 5), 34.5 +/- 25.0% (o.d. x 10), 96.5 +/- 70.1% (b.i.d. x 10), and 59.5 +/- 51.0% (b.i.d. x 21). Significant correlations were observed between myelotoxicity parameters and AUC(t) day 1 and AUC(t) per course of topotecan lactone. In all of the studies, similar sigmoidal relationships could be established between AUC(t) per course and the percentage decrease of WBCs. At maximum-tolerated dose level, no significant difference in AUC(t) per course was found [AUC(t) per course was 107.4 +/- 33.7 ng x h/ml (o.d. x 5), 145.3 +/- 23.8 ng x h/ml (o.d. x 10), 100.0 +/- 41.5 ng x h/ml (b.i.d. x 10), and 164.9 +/- 92.2 ng x h/ml (b.i.d. x 21), respectively.] For oral topotecan, the schedule rather than the AUC(t)-per-course seemed to be related to the type of toxicity. Prolonged oral administration resulted in intestinal side effects as a dose-limiting toxicity, and short-term administration resulted in granulocytopenia. On the basis of this pharmacokinetic study, no schedule preference could be expressed, but based on patient convenience, administration once daily for 5 days could be favored.

Five days of oral topotecan (Hycamtin), a phase I and pharmacological study in adult patients with solid tumours.

Topotecan is a specific inhibitor to topoisomerase I. An oral formulation of topotecan is available with a bioavailability of 32-44% in humans. A phase I and pharmacological study of the oral formulation of topotecan administered daily for 5 days every 21 days was performed in adult patients with solid tumours to determine the maximum tolerated dose (MTD). Adult patients with a WHO performance status < or = 2 adequate haematological, hepatic and renal functions, with malignant solid tumours refractory to standard forms were entered into the study. Pharmacokinetics were performed on days 1 and 4 of the first course using a validated high performance liquid chromatographic assay. 29 patients entered the study, all patients were evaluable for toxicity and response. The doses studied in the 29 patients were 1.2, 1.8, 2.3, 2.7 mg/m2/day and a fixed dose of 4 mg/day without surface area adjustment. A total of 109 courses were given. Dose limiting toxicity (DLT) was reached at a dose of 2.7 mg/m2/day and consisted of CTC (NCI-Common Toxicity Criteria) grade IV granulocytopenia. The regimen was well tolerated. Non-haematological toxicities were mild, including fatigue, anorexia, nausea, vomiting and diarrhoea. A significant correlation was observed between the percentage decrease in white blood cells versus the area under the curve (AUC(t)) of topotecan lactone (R = 0.76 P < 0.01) which was modelled by a sigmoidal Emax function. The correlation coefficient between the absolute topotecan dose administered and the AUC(t) was R = 0.52 (P = 0.04). Pharmacokinetics of the fixed dose of 4 mg/day were comparable to the 2.3 mg/m2/day dose. DLT in this phase I study of five daily doses of oral topotecan every 21 days was granulocytopenia. The recommended dose for phase II studies is 2.3 mg/m2/day or alternatively, a fixed dose of 4 mg/day.

Oral topotecan given once or twice daily for ten days: a phase I pharmacology study in adult patients with solid tumors.

Prolonged exposure to topotecan (TPT) in in vitro experiments and in vivo studies in animals yielded the highest antitumor efficacy. An oral bioavailability of TPT of 32-44% enables convenient prolonged administration. Because of unpredictable diarrhea in the third week of the twice daily (b.i.d.) 21-day schedule of p.o. administered TPT and the finding of optimal down-regulation of topoisomerase I level after 10-14 days in mononuclear peripheral blood cells, a shorter period of administration (10 days) was chosen for Phase I and pharmacological studies of oral administration of TPT. Adult patients with malignant solid tumors that were refractory to standard forms of chemotherapy were entered. Two dose schedules were studied: once daily (o.d.) and b.i.d. administration for 10 days every 3 weeks. TPT o.d. for 10 days was studied at dose levels 1.0, 1.4, and 1.6 mg/m2/day, and dose levels were 0.5, 0.6, 0.7, and 0.8 mg/m2 with the 10-day b.i.d. schedule. Pharmacokinetics were performed on days 1 and 8 of the first course using a validated high-performance liquid chromatographic assay and noncompartmental pharmacokinetic methods. Nineteen patients were entered in the 10-day o.d. schedule, with a total of 48 courses given. Dose-limiting toxicity (DLT) was reached at 1.6 mg/m2/day and consisted of common toxicity criteria (CTC) grade IV thrombocytopenia and CTC grade III diarrhea. The maximum tolerated dose was 1.4 mg/m2/day. In the 10-day b.i.d. administration of TPT, a total of 64 courses were studied in 20 patients. DLT was reached at a dose of 0.8 mg/m2 b.i.d. and consisted of CTC grade IV myelosuppression and CTC grade IV diarrhea. The maximum tolerated dose was 0.7 mg/m2 b.i.d. Nonhematological toxicities with both schedules included mild nausea and vomiting, fatigue, and anorexia. Pharmacokinetics revealed a substantial variation of the area under the plasma concentration-time curve of TPT lactone in both schedules. Significant correlations were observed between the myelotoxicity parameters and the area under the plasma concentration-time curve at day 1 of TPT lactone o.d. and b.i.d. The DLT of 10 daily administrations of oral topotecan every 3 weeks consisted of a combination of myelosuppression and diarrhea for both schedules studied. The recommended doses for Phase II studies are 1.4 mg/m2/day for 10 days for the o.d. administration and 0.7 mg/m2 for the b.i.d. schedule.

Phase I and pharmacologic study of oral topotecan administered twice daily for 21 days to adult patients with solid tumors.

PURPOSE: Topotecan is a specific inhibitor of topoisomerase I. Recently bioavailability of an oral formulation of approximately 30% with limited variability was reported. We conducted a phase I and pharmacokinetic study of the oral formulation of topotecan to characterize the maximum-tolerated dose (MTD), toxicities, pharmacokinetics, and antitumor effects in patients with refractory malignancies. PATIENTS AND METHODS: Patients were treated with oral topotecan given twice daily for 21 days, with cycles repeated every 28 days. In subsequent cohorts, the dose was escalated from 0.15 to 0.6 mg/m2 twice daily. Pharmacokinetics were performed on day 1 and 8 of the first course using a validated high-performance liquid chromatographic assay and noncompartmental pharmacokinetic methods. RESULTS: Thirty-one patients entered the study; one patient was not assessable for toxicity and response as therapy was prematurely interrupted on request of the patient who had not experienced toxicity. Thirty patients received a total of 59 courses. The dose-limiting toxicity (DLT) was reached at a dose of 0.6 mg/m2 twice daily and consisted of diarrhea, which started subacutely at a median onset on day 15 (range, 12 to 20) and resolved after a median of 8 days (range, 7 to 16). Other toxicities were mild, including leukocytopenia, thrombocytopenia, nausea, and vomiting. The MTD was 0.5 mg/m2 twice daily. No responses were observed. Pharmacokinetics showed a substantial variation of the area under the plasma concentration-time curve at time point "t" [AUC(t)] of topotecan and ring-opened product hydroxyacid. A significant correlation was observed between the percentage of decrease in WBC count versus the AUC(t) of topotecan (r = .75), which was modeled by a sigmoidal maximal effect concentration (Emax) function. CONCLUSION: The DLT in this phase I study for chronic oral topotecan for 21 days was diarrhea. The recommended dose for phase II studies is 0.5 mg/m2 twice daily.

The bioavailability of oral GI147211 (GG211), a new topoisomerase I inhibitor.

Topoisomerase I inhibitors are new compounds of interest for cancer chemotherapy. We performed a study with GI147211, a new semisynthetic camptothecin analogue, to determine the absolute bioavailability of the drug given orally. Patients with a histologically confirmed diagnosis of a solid tumour refractory to standard forms of therapy were eligible for the study. GI147211 was given orally on day 1 and as a 30-min infusion daily on days 2-5. The treatment course was repeated every 3 weeks. In subsequent patient cohorts, the dose of the oral formulation was escalated from 1.5 mg m(-2) to 6.0 mg m(-2); the dose for i.v. administration was fixed at 1.2 mg m(-2). Plasma pharmacokinetics was performed on day 1 and 2 of the first course and on day 1 of the second course using a validated high-performance liquid chromatographic assay. Nineteen patients were entered into the study; one patient was not evaluable because the treatment course was stopped prematurely. Eighteen patients received a total of 47 treatment courses. The absolute bioavailability of GI147211 averaged 1.3 +/- 5.2%. Drug appeared quickly in plasma with a median Tmax at 0.5 h. Fasting or fed state had no significant influence on the bioavailability of GI147211. The terminal half-life after administration of oral GI147211 was 6.85 +/- 3.13 h, similar to the half-life after intravenous administration. The major toxicities were neutropenia and thrombocytopenia. Nadirs for neutropenia and thrombocytopenia occurred on day 8 and day 15 respectively. Other toxicities predominantly consisted of mild and infrequent nausea and vomiting, and fatigue. The oral administration of the drug is well tolerated. Oral administration of topoisomerase I inhibitor GI147211 results in a low bioavailability with relatively wide interpatient variation. The intravenous route of administration is advised for further development of this promising topoisomerase I inhibitor.

Topoisomerase I inhibitors: the relevance of prolonged exposure for present clinical development.

Topoisomerase I inhibitors constitute a new class of anti-cancer agents. Recently, topotecan and irinotecan were registered for clinical use in ovarian cancer and colorectal cancer respectively. Cytotoxicity of topoisomerase I inhibitors is S-phase specific, and in vitro and in vivo studies have suggested that, for efficacy, prolonged exposure might be more important than short-term exposure to high concentration. Clinical development of those topoisomerase I inhibitors that have reached this stage is also focused on schedules aiming to achieve prolonged exposure. In this review, we summarize all published preclinical studies on this topic for topoisomerase I inhibitors in clinical development, namely 20-S-camptothecin, 9-nitro-camptothecin, 9-amino-camptothecin, topotecan, irinotecan and GI147211. In addition, preliminary data on clinical studies concerning this topic are also reviewed. The data suggest that prolonged exposure may indeed be relevant for anti-tumour activity. However, the optimal schedule is yet to be determined. Finally, clinical data are yet too immature to draw definitive conclusions.

Phase II and pharmacologic study of topotecan administered as a 21-day continuous infusion to patients with colorectal cancer.

PURPOSE: Topotecan is a specific inhibitor of topoisomerase I. Preclinical data have indicated that topoisomerase I inhibitors demonstrate more efficacy and have a greater therapeutic index with prolonged continuous exposure. The feasibility of this concept in humans using a 21-day continuous infusion of topotecan has been reported. We conducted a phase II study of this 21-day continuous topotecan administration schedule in patients with locally advanced, unresectable or metastatic colorectal cancer. PATIENTS AND METHODS: Topotecan, initially applied at a dose of 0.6 mg/m2/d, was administered as a continuous infusion via an ambulatory pump for 21 days repeated every 4 weeks. The starting dose was reduced to 0.5 mg/m2/d, because in five of the first 11 patients, the second course had to be delayed due to prolonged myelosuppression. Forty-two patients entered the study; one patient was ineligible and was excluded from further analyses. RESULTS: The overall response rate was 10%, with one complete and three partial responses. The median response duration was 7 months (range, 4 to 11). With this schedule, the major toxicity was prolonged cumulative myelosuppression, including a marked inhibition of erythropoiesis. A total transfusion of 250 U of erythrocytes was needed to maintain a hemoglobin level greater than 6.0 mmol/L. Other side effects were mild, and included alopecia (47%), periodic nausea (40%)/vomiting (22%), and fatigue (16%). Pharmacokinetic evaluation showed a mean steady-state plasma concentration (Css) of topotecan of 0.62 ng/mL (range, 0.33 to 1.1), with a significant relationship between the Css of topotecan and common cytotoxicity criteria (CTC) grade of leukocytopenia. CONCLUSION: Topotecan administered as a 21-day continuous infusion exerts minor activity as single-agent therapy in patients with metastatic colorectal cancer.

Somatostatin receptor scintigraphy in the initial staging of Hodgkin's disease.

Somatostatin receptor (SS-R) scintigraphy has been successfully used in the visualization of a variety of neuroendocrine tumours. In vitro studies have shown that SS-Rs are present in human malignant lymphomas. We conducted a prospective study in 56 consecutive untreated patients with histologically proven Hodgkin's disease (HD) and compared the results of SS-R scintigraphy with physical and radiological examinations as initial evaluation. SS-R scintigraphy was positive in 55/56 (98%) patients at sites of documented disease. In 20 patients SS-R scintigraphy disclosed lymphoma localizations not revealed following procedures of conventional staging. As a result in 12 patients (21%) SS-R scintigraphy produced a change of stage and in seven patients (13%) the additional information obtained from SS-R scintigraphy led to a change of treatment. SS-R scintigraphy failed to visualize sites of HD in four patients, mainly in the abdominal area. In three patients a false-positive result was obtained. These data show that SS-R scintigraphy provides an imaging technique that appears to visualize tumours in most patients with HD and may be clinically useful in the management of these patients.

The relationship between sigmoidal intramucosal pH and intestinal arterial occlusion during aortic reconstructive surgery.

OBJECTIVES: To investigate the effects of perioperative occlusion of intestinal arteries on clinical outcome and changes in sigmoidal intramuscular pH (pHi). To determine the value of sigmoidal pHi measurement in predicting ischaemic colitis after aortic reconstructive surgery. DESIGN: Prospective, non-selective, open study. MATERIALS: Forty patients undergoing elective aortic infrarenal surgery were monitored with pHi. Pre- and postoperative digital venous subtraction angiography was combined with operative data to evaluate perioperative occlusion of intestinal arteries. RESULTS: All patients had a significant (p< 0.05) drop in pHi after aortic clamping which returned to baseline 2-4 h after declamping. None of the patients had clinical signs of ischaemic colitis postoperatively. All patients had angiographically proven, patent superior mesenteric arteries pre- and postoperatively. Patients were divided into three groups: patients with no changes in intestinal arteries (n=13), patients with perioperative occlusion of the inferior mesenteric artery (n=22) and patients with perioperative occlusion of the inferior mesenteric and one or both iliac arteries (n = 5); there were no significant differences in pHi values between the groups. CONCLUSIONS: Return of the sigmoidal pHi to baseline values within 6-12 h after declamping probably predicts a postoperative course without ischaemic colitis. Perioperative occlusion of the inferior mesenteric artery alone, or in combination with occlusion of one or both internal iliac arteries, does not cause ischaemic colitis in patients whose sigmoidal pHi rises after declamping.

Phase I and pharmacological study of the new topoisomerase I inhibitor GI147211, using a daily x 5 intravenous administration.

Topoisomerase I inhibitors are interesting anti-cancer agents with a novel mechanism of action. We performed a phase I study with intravenous GI147211, a new semisynthetic camptothecin analogue, using a daily x 5 schedule administered every 3 weeks, to evaluate the side-effects and pharmacokinetics of the agent. Patients with a histologically confirmed diagnosis of a solid tumour refractory to standard froms of therapy were eligible for the study. GI147211 was given as a 30 min intravenous infusion daily for 5 consecutive days, repeated every 3 weeks. In subsequent patient cohorts the dose was escalated from 0.3 to 1.5 mg m-2 day-1. Pharmacokinetics analysis was performed on days 1 and 4 of the first course using a validated high-performance liquid chromatographic assay and non-compartmental methods. A total of 19 patients were entered into the study, one patient was not evaluable for toxicity because only one drug administration was given. Eighteen patients received a total of 67 courses through four dose levels. The dose-limiting toxicities were neutropenia and thrombocytopenia at the dose of 1.5 mg m-2 day-1. Nadirs occurred on day 15 and day 15 respectively. Other toxicities were mild and infrequent and included nausea/vomiting, headache and alopecia. The maximal tolerated dose was 1.2 mg m-2 day-1. One partial response was observed in a patient with colorectal cancer. The total plasma clearance was 999+/-184 ml min-1 (range 640-1329). The volume of distribution was 190+/-461 m-2 and the terminal half-life was 3.7+/-1.2 h. The AUC increased linearly with the administered dose. A steep and significant sigmoid relationship was established between the AUC and the percent decrease of ANC. GI147211 is a new topoisomerase I inhibitor that induced dose-limiting neutropenia and thrombocytopenia in this phase I study. The recommended dose for phase II studies with this schedule is 1.2 mg m-2 x 5 every 3 weeks.

Ultrasound examination of pathological cervical lymph nodes in patients with non-Hodgkin's lymphoma and Hodgkin's disease.

The choice of treatment of malignant lymphoma may vary considerably and is mainly determined by the pathology and clinical stage. Ultrasonography is currently one of the most sensitive techniques for evaluation of the cervical area. We set out to assess the value of ultrasound imaging when added to conventional staging (physical examination, laryngoscopy, computer tomography of thorax and abdomen, bone marrow cytology and histology) of malignant lymphoma in 47 patients with untreated lymphoma. Hodgkin's disease was present in 14 patients and non-Hodgkin's lymphoma in 33 individuals. The ultrasound results were independently compared with physical examination of the neck. Ultrasonography revealed additional pathological lymph nodes in 6/47 cases (13%). Furthermore, the diagnosis non-Hodgkin's lymphoma could be established in one patient merely as a result of ultrasonography. Ultrasonography of the neck may reveal more pathological lymph nodes in a significant number of patients and may be of value in the initial staging of patients with malignant lymphoma.

[Evaluation of the roentgenological and endoscopic diagnosis in malignities of the proximal digestive tract]. / Evaluatie van de röntgenologische en de endoscopische diagnostiek bij maligniteiten van de proximale tractus digestivus.

During 1968-1988 one endoscopist performed 3154 endoscopic examinations of the upper gastrointestinal tract and detected 400 (13%) malignancies. Endoscopy was indicated in persisting dyspepsia or abnormal findings on X-ray examination of the stomach. In 242 patients earlier subjected to partial gastrectomy 7% stomach cancers were found. No difference existed in the incidence of stomach cancer between patients with either BI and BII gastrectomy. Initially no malignancy was detected in 9 (2.3%) patients. The maximum diagnostic delay was 5 months in these patients. This finding underlines the necessity of a strict follow-up scheme when studying malignancies.

Omeprazole (20 mg o.m.) versus ranitidine (150 mg b.d.) in duodenal ulcer healing and pain relief.

The object of this double-blind, multicentre study was to compare duodenal ulcer healing rates after 2 to 4 weeks of treatment with either 20 mg omeprazole o.m. or 150 mg ranitidine b.d. One hundred and eighty-one patients were randomized: 91 received omeprazole and 90 received ranitidine. In a per protocol analysis at 2 weeks, 63% of the patients were healed on omeprazole and 65% of the patients were healed on ranitidine (N.S.); at 4 weeks 91% were healed in the omeprazole group and 96% were healed in the ranitidine group. There were no differences in ulcer symptom relief between the two groups. There were no significant changes in laboratory values in either of the groups. Adverse events were few and mainly mild and transient. We conclude that both omeprazole (20 mg o.m.) and ranitidine (150 mg b.d.) result in rapid, ulcer healing rates.