Evaluation of trainees' stay in general practice by the young physicians and their tutors

In 1991 a new reform for postgraduate trainees was introduced in Denmark. Since the reform all young doctors-as a compulsory part of their vocational training-have had to work for six months as general practice trainees, no matter their wishes for future specialization. The reform furthermore led to the general practice trainees being considerably younger than previously-the average length of postgraduate experience before working as a trainee declined from six to seven years to one to two years. In this light an investigation was conducted from August 1992 to July 1993. Seven hundred and fifty-eight questionnaires were sent to general practice trainees and their tutors in Denmark. Ninety-five percent of the questionnaires were returned, thus it was possible to evaluate the new compulsory training in general practice. In conclusion, the main part of the trainees had a positive assessment of the work conditions in general practice. However, a large part of the trainees indicated that their tutor doctors had set aside too short a time for supervision.     

The differential involvement of adrenoceptors in challenges of different intensities

We investigated a family with optic atrophy which occurred in childhood or early adulthood plus late-onset cerebellar ataxia. The magnetic resonance imaging in the proband revealed cerebellar atrophy. The proband and her brother were homoplasmic for the most common mitochondrial DNA (mtDNA) 11778 mutation associated with Leber's hereditary optic neuropathy (LHON). This study showed further evidence that central nervous system lesions can occur in cases of LHON mtDNA mutation.     

Human granulocytes contain an opiate alkaloid-selective receptor mediating inhibition of cytokine-induced activation and chemotaxis

Human peripheral blood granulocytes previously were found to contain opioid delta 2-receptors mediating stimulation by opioid peptides of chemotaxis. Studies presented in this work indicate that granulocytes also contain opiate alkaloid-selective, opioid peptide-insensitive receptors mediating inhibition by morphine and other opiates of cytokine-induced activation and chemotaxis. Binding studies with [3H]morphine and [3H]diprenorphine ([3H]DPN) indicated the presence of receptor sites, at considerable density with affinities and selectivity for opiates comparable with those of the mu 3-receptor of human peripheral blood monocytes (macrophages). The influence of the guanosine 5'-triphosphate (GTP) analogue GppNHp on binding indicated that the granulocyte receptor was linked to a G protein. Morphine but not opioid peptides interfered with activation and/or chemotaxis of the granulocytes induced by TNF-alpha, IL-1 alpha, IL-8, and FMLP (chemotactic peptide). These effects of morphine were blocked by the antagonist naloxone. Levorphanol inhibited TNF-alpha-induced activation, and also potentiated the inhibition by morphine. Furthermore, in binding assays, levorphanol enhanced the affinity of the receptor for morphine. Dextrorphan had no effect on activation or chemotaxis, and it also had no effect on binding, indicative of stereoselectivity for the effect of levorphanol. It is concluded that human granulocytes contain opiate alkaloid-selective mu 3-receptors that mediate inhibitory effects of morphine on cellular activation by cytokines.     

Recurrent sinopulmonary disease in a young adult

In 50 patients aged 60 +/- 4 operated for colorectal carcinoma simultaneous combined radionuclide phlebography (RNP) and pulmonary perfusion scintigraphy (PPS) using 99Tcm labeled macroaggregates of the human serum albumin (MAHSA) were performed within 20 postoperative days aiming to detect deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE). The aim of the study was to determine the incidence and segmental DVT localization as well as incidence, localization and clinical characteristics of developed pulmonary perfusion disorders. Deep vein thrombosis was detected in 33 (66%) patients with rather uniform distribution in vein segments. According to their scintigraphic characteristics the findings suggested recent thrombosis in almost all cases (only two of them had signs of chronic thrombosis). Of patients with detected DVT 17 (52%) had pulmonary perfusion disorders of which 10 (59%) were unilateral (7 right and 3 left) and 7 (42%) bilateral. Characteristics and extent of perfusion defects suggested very probable PTE in 11 (65%) patients and less probable in 6 (35%). It has been concluded that patients operated for colorectal carcinoma were highly exposed to DVT and PTE development which necessitates all measures contributing to their prevention.     

Can adrenal incidentalomas be safely observed?

We currently recommend excision of adrenal incidentalomas > or = 4 cm in size and all hormonally active tumors. The optimal management and follow-up of smaller nonfunctioning tumors are controversial. The aim of this study was to determine the clinical outcome of a well defined population of patients with incidentalomas followed without operative intervention. The study group comprised 231 patients, identified from the records of abdominal or thoracic computed tomographic (CT) scans performed between 1985 and 1989. The primary outcome variable analyzed was survival. Follow-up was obtained by office records, telephone contact, or letter. There were 101 male and 130 female patients with a mean age at diagnosis of 64 years (range 5-86 years). Most adrenal tumors were unilateral (right 113; left 98); 20 were bilateral. Mean tumor size was 2 cm (range 1-6 cm). In nine (4%) patients the tumor was > or = 4 cm. Follow-up [mean 7 years; range 1 month (patient died) to 11.7 years] was complete in 224 (97%) patients. Ninety-one (39%) patients had one or more additional CT scans performed during the follow-up period, with only four patients demonstrating a > 1 cm increase in the size of the adrenal mass. Surgical excision of these four lesions identified benign pathology. Eighty-one (35%) patients died of conditions unrelated to adrenal pathology. No patient developed subsequent adrenal hyperfunction or adrenal malignancy. Within the context of our guidelines, conservative management of adrenal incidentalomas considered benign or nonfunctioning at diagnosis is appropriate. Additional information provided by repeat CT scanning appears to confer limited benefit. This study does not support laparoscopic removal of small, nonfunctional adrenal tumors, as has been suggested.     

In vivo formation of 8-Epi-prostaglandin F2 alpha is increased in hypercholesterolemia

F2-isoprostanes are bioactive prostaglandin (PG)-like compounds that are produced from arachidonic acid through a nonenzymatic process of lipid peroxidation catalyzed by oxygen free-radicals. 8-Epi-PGF2 alpha may amplify the platelet response to agonists, circulates in plasma, and is excreted in urine. We examined the hypothesis that the formation of 8-epi-PGF2 alpha is altered in patients with hypercholesterolemia and contributes to platelet activation in this setting. Urine samples were obtained from 40 hypercholesterolemic patients and 40 age- and sex-matched control subjects for measurement of immunoreactive 8-epi-PGF2 alpha. Urinary excretion of 11-dehydro-thromboxane (TX) B2, a major metabolite of TXA2, was measured as an in vivo index of platelet activation. Low-dose aspirin, indobufen, and vitamin E were used to investigate the mechanism of formation and effects of 8-epi-PGF2 alpha on platelet activation. Urinary 8-epi-PGF2 alpha was significantly (P = .0001) higher in hypercholesterolemic patients than in control subjects: 473 +/- 305 versus 205 +/- 95 pg/mg creatinine. Its rate of excretion was inversely related to the vitamin E content of LDL and showed a positive correlation with urinary 11-dehydro-TXB2. Urinary 8-epi-PGF2 alpha was unchanged after 2-week dosing with aspirin and indobufen despite complete suppression of TX metabolite excretion. Vitamin E supplementation was associated with dose-dependent reductions in both urinary 8-epi-PGF2 alpha and 11-dehydro-TXB2 by 34% to 36% and 47% to 58% at 100 and 600 mg daily, respectively. We conclude that the in vivo formation of the F2-isoprostane 8-epi-PGF2 alpha is enhanced in the vast majority of patients with hypercholesterolemia. This provides an aspirin-insensitive mechanism possibly linking lipid peroxidation to amplification of platelet activation in the setting of hypercholesterolemia. Dose-dependent suppression of enhanced 8-epi-PGF2 alpha formation by vitamin E supplementation may contribute to the beneficial effects of antioxidant treatment.     

Identification of beta-L-gulose as the sugar moiety of the main polar lipid Thermoplasma acidophilum

We studied the antibody binding capacity (ABC) of various cell-surface antigens in normal human fetuses and term neonates on lymphocyte, monocyte, and polymorphonuclear (PMN) cells by quantitative flow cytometry also designated by quantimetry. Analysis of changes of expression level on these leukocytes during the developmental process was also investigated. The results indicated that the ABC values of most studied markers change during the maturational process. The ABC of lymphocyte-associated antigens studied such as CD5 and CD7 showed only a decrease from fetus to adult, whereas according to the type of molecule on monocyte and PMN there was either an increase or a decrease of ABC values dependent on the stage of the developmental process, from fetus to neonate or from neonate to adult. However, the ABC values of leukocyte membrane antigens such as CD16, CD46, and CD55 on all leukocytes and CD11b, CD11c, and CD35 on myeloid cells did not change. Their expression level was already mature in fetuses compared with adult cells. In addition, in this quantimetric approach, the analysis of the results for CD11a and CD8 suggested that the changes of CD11a expression level on lymphocyte subsets can depend on one mechanism, whereas there are probably at least two for CD8. Furthermore, the expression patterns of CD5, CD7, and CD11a change during maturation. We concluded that, even if the neonate response pattern to immunological challenge differs from an adult and this is based primarily on the relative numbers and functional activity of lymphocyte T subsets (especially TH1/TH2) and their cytokine profiles, these quantitative and qualitative phenotypical differences might also contribute to explain the functional peculiarities of leukocyte fetal and cord blood cells. All these findings support the notion of immaturity and maturity of ABC expression.     

Reporting risks and benefits of therapy by use of the concepts of unqualified success and unmitigated failure: applications to highly cited trials in cardiovascular medicine

BACKGROUND: The NNT (number needed to treat) and NNH (number needed to harm) are useful in conveying the results of clinical trials because they emphasize the effort that must be expended to accomplish a single, tangible outcome. But NNT conveys the effort required to achieve a positive outcome without distinguishing between the presence or absence of treatment-related adverse events. Similarly, NNH conveys harm without accounting for the achievement or lack of achievement of the benefit of therapy. Consequently, a mathematical model was developed to extend the NNT and NNH to represent the effort required to achieve "unqualified success" (NNTUS, treatment success without treatment-induced side effects) and "unmitigated failure" (NNHUF, lack of treatment success with treatment-induced side effects). METHODS AND RESULTS: NNTUS was calculated by adjusting the absolute risk reduction to allow for the probability of not incurring a treatment-related adverse event. NNHUF was similarly calculated by adjusting the absolute risk of incurring a treatment-related adverse event by the probability of not incurring any treatment-related benefit. The impact of conveying clinical trial data by the use of NNT, NNTUS, NNH, and NNHUF is illustrated by means of 11 highly cited trials identified systematically from the cardiovascular literature. The treatment effort measured by the NNTUS and the NNHUF was consistently higher than that given by the traditional NNT and NNH. These increments ranged from 1% to several hundred percent. CONCLUSIONS: The NNTUS and the NNHUF represent the treatment effort required on average to achieve 1 unqualified success and 1 unmitigated failure. NNTUS and NNHUF balance benefit and harm in an objective way and are relevant for making service delivery decisions.