Starting learning in medical practice: an evaluation of a new Introductory Clerkship.

The transition from undergraduate medical education to learning in clinical clerkships can be difficult for students. Learning in clinical practice requires awareness of learning opportunities and goals, active elaboration and reflection. Staff should provide students with guidance to learn from their experiences. A new Introductory Clerkship was designed to facilitate the start of goal-oriented, active and reflective work-based learning. This four-week clerkship is a result of the cooperation of six major specialties in the university hospital. The innovations included explicitly formulated goals, a description of the student's activities in daily practice and of the staff's role, group meetings, a logbook, a halfway formative interview and a final summative interview. The aim of this study was to investigate to what extent the innovations of the new Introductory Clerkship were implemented and how students and residents valued them. Two questionnaires were constructed: one was administered to students (n = 54) and the other to residents (n = 27). Students considered participation in daily practice very instructive, although more observations of history taking and physical examination are wanted. The interviews and group meetings promote students' learning. Use of the logbook needs improvement. Residents perceived a shortage of time and would appreciate more participation of staff members, as well as a better preparation for supervising tasks. Overall, the study demonstrates that it is possible to introduce innovations in clinical clerkships to improve the learning environment of work-based learning.

[Decision support in primary care--a vertical second opinion]. / De tweede mening en het wérkelijk geneeskundig consult.

This comment concerns a specific second opinion practice in Amsterdam. In this practice a physician limits her consultations by optimally preparing patients for their subsequent encounter with the responsible clinician. It is argued that this type of practice must be discouraged, as due to its limited goal, lack of personal responsibility and subordination of 'confidence' in doctor-patient relationships, it constitutes a strongly deviant form of clinical practice.

[Comments on separate consultations for second opinions]. / Kanttekeningen bij aparte spreekuren voor een tweede mening.

Second opinion consultations are an accepted phenomenon in daily clinical practice. In well defined situations such a consultation may be welcomed as a mean to obtain proper medical counselling and advice. However, to preserve a good doctor-patient relationship it is of utmost importance for what reason and by whom such a consultation is initiated. Setting up a specific second opinion outpatient clinic, where oncological patients are welcomed without prior knowledge of the primary consultant, is medically unnecessary and may well be the wrong solution for counselling problems that may originate in busy surgeries of general hospitals.

[Thrombotic thrombocytopenic purpura in 13 Dutch centres: treatment and longterm follow-up]. / Trombotische trombocytopenische purpura in 13 Nederlandse centra: behandeling en beloop.

OBJECTIVE: Analysis of the incidence, treatment modalities and disease course of thrombotic thrombocytopenic purpura (TTP) in the Netherlands. DESIGN: Retrospective follow-up study. SETTING: 13 centres in the Netherlands. METHODS: Regarding all patients admitted between 1-1-1979 and 1-1-1992 to one of 13 Dutch haematological centres, in whom the diagnosis of TTP was made for the first time, information was gathered from the medical records and from the patients own physicians on patient characteristics at presentation and the occurrence of relapse or death. The follow-up period tended on 1-4-1995. RESULTS: A total of 65 patients with newly diagnosed TTP were identified: 0.34 per 1,000,000 persons a year (95% confidence interval (95%-CI): 0.26-0.45), increasing to 0.83 in the last year of the study. Forty-six (95%) patients were treated with fresh frozen plasma: 18 (28%) by plasma infusion and 44 (68%) by plasma exchange; 48 (74%) (additionally) received corticosteroids. All 52 patients (80%) who survived the first four weeks after admission reached complete remission. Twelve patients with relapsing TTP underwent splenectomy in remission. The 5-year survival rate was 77% (95% CI: 66-87) and the 5-year relapse-free survival rate 38% (95% CI: 25-52). Cardiac symptoms, severe thrombocytopenia and a high serum LDH were risk factors for acute mortality, but no risk factors for relapse or late-occurring death could be identified. CONCLUSION: TTP is a rare disease which is increasingly being recognized. Plasma exchange and corticosteroids are the most frequently used therapies. The disease has a high mortality rate in the acute phase of the disease.

Sporadic mutations of the p53 gene in multiple myeloma and no evidence for germline mutations in three familial multiple myeloma pedigrees.

The recent finding that eight out of 10 multiple myeloma cell lines have p53 gene mutations prompted us to examine the p53 tumour suppressor gene in 25 non-related multiple myeloma patients. None of 19 patient bone marrow samples available for Southern blot analysis showed rearrangements in the p53 gene and only one patient showed loss of the p53 locus. DNA encompassing exons 5, 7, and 8, where p53 mutations commonly cluster, was amplified by PCR. Single-strand conformation polymorphisms of the PCR-amplified exon 5 region were detected in two patients. Direct sequencing of the mutant band revealed that one patient had a C to T transition at codon 138 (Ala to Val) and one patient had a G to C transversion at codon 139 (Lys to Asn). p53 mutations in germline cells in hereditary cancer syndromes predispose the family members to the development of malignancies. We therefore searched for p53 germline mutations in exons 5, 7, and 8 in the affected individuals from three families each with two multiple myeloma patients (these patients include three individuals from the non-related group mentioned above). Using Southern blotting, polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing, no germline mutations were found. These results indicate that mutations in exons 5, 7, and 8 of the p53 gene are infrequent in multiple myeloma.

Proliferation patterns in acute myeloid leukemia: leukemic clonogenic growth and in vivo cell cycle kinetics.

In a prospective study of 33 newly diagnosed patients with acute myeloid leukemia (AML), we analyzed the relationship of proliferation parameters with clinical parameters, response to induction therapy, and survival. The median follow-up was 26 months. The proliferative capacity of the leukemic progenitor cells was studied using colony-forming assays (number of colony-forming units, growth pattern, and spontaneous clonogenic growth capacity). The cell kinetic parameters of the bone marrow blasts were determined by in vivo labeling with iododeoxyuridine and subsequent flow cytometry: labeling index (LI), DNA synthesis time (Ts), potential doubling time. No or only weak relationships were observed between the experimental and clinical parameters such as age, sex, % blasts, white blood cell count, FAB subtype, cytogenetics, and % CD 34+ cells. This suggests that clonogenic growth and cell cycle kinetics of bone marrow blasts are independent cell biologic properties of AML. No association between the proliferation parameters and induction response rate was noticed. Analysis of the overall survival and event-free survival revealed trends to longer survival rates in patients with a below-median LI (< or = 7.6%) and below-median Ts value (< or = 14.3 h). These trends were more pronounced in the group of de novo AML (n = 23), where the prolonged event-free survival in patients with below-median Ts reached statistical significance (p = 0.02). None of the other parameters appeared significantly correlated with survival, although there was a trend to longer survival rates in patients who had no spontaneous clonogenic growth capacity (p = 0.13). In conclusion, proliferation parameters in leukemic cells provide additional information on the cell biologic characteristics of AML, and these parameters may have prognostic value for response and duration of survival in AML.

[The diagnosis of a possibly malignant neck lymph node]. / Diagnostiek van een mogelijk maligne halslymfeklier.

With reference to the case histories of four patients with a possibly malignant lymph node whose diagnoses and therapies were seriously delayed, a critical discussion is presented of the recent recommendation on this problem issued by a team from the Central Peer Review Advisory Board. It appears that the observed loss of time can be attributed in part to insufficient insight into the role and technique of lymph-node puncture in patients with a presumably malignant cervical lymph node. We propose a changed diagnostic strategy in such patients, which takes into account the patient's age and the localization of the affected lymph node.

[Deposition of light chains in various organs; light chain deposition disease]. / Neerslag van lichte ketens in verscheidene organen; 'light chain deposition disease'.

The case is reported of a patient with renal insufficiency, proteinuria and heart failure caused by 'light chain deposition disease' (LCDD). A renal biopsy showed nodular glomerulosclerosis, IF examination revealed linear deposits of monoclonal lambda light chains along the glomerular and tubular basement membranes. Similar deposits could be shown in a skin biopsy. No light chains could be detected in urine and serum. The patient had a good response to treatment with melphalan and prednisone.

Plasma and cellular adriamycin concentrations in patients with myeloma treated with ninety-six-hour continuous infusion.

Adriamycin (ADM) concentrations in neoplastic plasma cells, nucleated blood cells, bone marrow cells, and plasma were measured in seven patients with advanced multiple myeloma. ADM was administered as a 96-hour infusion of 9 mg/m2/24 hr. Maximum plasma ADM concentrations were 15.8 +/- 4.4 ng/ml. ADM concentrations in nucleated blood cells, bone marrow cells, and plasma cells increased continuously throughout the 96-hour infusion. Maximum cellular levels were up to 200-fold higher than the maximum plasma concentration and were similar to levels observed shortly after administration of the total dose in one rapid injection. The cellular AUC for 96-hour infusion and bolus injection were comparable. Thus continuous infusion is the equivalent of bolus injection in delivering ADM to the target cells in bone marrow, although plasma ADM concentrations remained very low. These results provide support for administering ADM as a continuous infusion with less toxicity and better patient tolerance.

Prognostic factors in adult patients with acute leukemia at first relapse.

The case histories of 252 adolescent and adult patients with acute leukemia diagnosed and treated between 1975 and 1985 are analyzed with special attention to prognostic factors determining the second complete remission (CR) rate. A first CR was achieved in 65% of cases, 60% for acute myelogenous leukemia (AML), and 75% for lymphoblastic leukemia (ALL). In 86 patients a relapse occurred (50 AML, 36 ALL), and 50% of them entered a second CR after reinduction therapy. Median survival after first relapse of these reinduction-responders was significantly prolonged in comparison to the reinduction-nonresponders for both AML (15 versus 2 months) and ALL (11 versus 3 months). Median duration of the first CR of the reinduction-responders was significantly longer than that of the second CR (13 versus 6 months). The major determinant for the probability to obtain a second CR after reinduction therapy was the duration of the first CR. The latter was significantly longer in the reinduction-responders than in the nonresponding group (13 versus 5 months). Furthermore patients younger than 40 years, and those who relapsed after ending the maintenance therapy, tended to have better chances to achieve a second CR. Rapid achievement of the first CR, and sex of the patients seemed not to be of predictive value. The authors conclude that aiming for a second CR is worthwhile in young patients who relapse after a long first CR.

Ceftazidime does not enhance cyclosporin-A nephrotoxicity in febrile bone marrow transplantation patients.

Ceftazidime was used as monotherapy for 30 febrile episodes in 28 patients, who underwent allogeneic bone marrow transplantation and who were treated concomitantly with the immunosuppressive agent cyclosporin-A. Ceftazidime did not enhance the well established nephrotoxicity of cyclosporin-A as measured by serum creatinine levels or creatinine clearance. Although an increasing number of Gram-positive infections in these patients warrants vigilance, ceftazidime as initial empirical monotherapy proved to be successful in 95% of all febrile post-transplantation patients. All Gram-negative and 69% of the Gram-positive infections were cured with ceftazidime alone. The overall clinical cure rate was 72%, with microbiological clearance in 63%. This compares favourably with aminoglycoside containing schedules and avoids the aminoglycoside associated nephrotoxicity.