Giant cell tumor of bone: Oncologic and functional results

Giant cell tumor of bone is a challenging surgical problem due to its mostly aggressive growth with tendency to recur locally, to develop in rare instances pulmonary metastases without histologic evidence of malignant changes, and due to its potential to dedifferentiate into a frankly malignant tumor in a limited number of patients. It is treated in many different ways because of the difficulties in finding a type of treatment with the best functional results without compromising oncologic results. This paper describes 19 patients with giant cell tumor of bone. Following 19 procedures (including 6 intracapsular resections [curettage]) in 17 patients in our hospital only 2 recurrences (10.5%) occurred, both after curettage. Functional results after curettage without recurrence were favorable. Marginal or wide resections did not result in any recurrence, but were functionally inferior to curettage; an exception to the latter was the resection-arthrodesis of the distal radius in one patient. © 1994 Wiley-Liss, inc.     

Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017

Objective

To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients.

Participants

A multispecialty task force of 16 international experts in Critical Care Medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine.

Design/methods

The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members.

Results

The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of <9 µg/dl) after cosyntropin (250 µg) administration and a random plasma cortisol of <10 µg/dl may be used by clinicians. We suggest against using plasma free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using intravenous (IV) hydrocortisone <400 mg/day for ≥3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO₂/FiO₂ < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence).

Conclusions

Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.

     

Decreased levels of dehydroepiandrosterone sulphate in severe critical illness: a sign of exhausted adrenal reserve?

Introduction

Dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) are pleiotropic adrenal hormones with immunostimulating and antiglucocorticoid effects. The present study was conducted to evaluate the time course of DHEAS levels in critically ill patients and to study their association with the hypothalamic–pituitary–adrenal axis.

Materials and method

This was a prospective observational clinical and laboratory study, including 30 patients with septic shock, eight patients with multiple trauma, and 40 age- and sex-matched control patients. We took serial measurements of blood concentrations of DHEAS, cortisol, tumour necrosis factor-α and IL-6, and of adrenocorticotrophic hormone immunoreactivity over 14 days or until discharge/death.

Results

On admission, DHEAS was extremely low in septic shock (1.2 ± 0.8 mol/l) in comparison with multiple trauma patients (2.4 ± 0.5 μmol/l; P < 0.05) and control patients (4.2 ± 1.8; P < 0.01). DHEAS had a significant (P < 0.01) negative correlation with age, IL-6 and Acute Physiology and Chronic Health Evaluation II scores in both patient groups. Only during the acute phase did DHEAS negatively correlate with dopamine. Nonsurvivors of septic shock (n = 11) had lower DHEAS levels (0.4 ± 0.3 μmol/l) than did survivors (1.7 ± 1.1 μmol/l; P < 0.01). The time course of DHEAS exhibited a persistent depletion during follow up, whereas cortisol levels were increased at all time points.

Conclusion

We identified extremely low DHEAS levels in septic shock and, to a lesser degree, in multiple trauma patients as compared with those of age- and sex-matched control patients. There appeared to be a dissociation between DHEAS (decreased) and cortisol (increased) levels, which changed only slightly over time. Nonsurvivors of sepsis and patients with relative adrenal insufficiency had the lowest DHEAS values, suggesting that DHEAS might be a prognostic marker and a sign of exhausted adrenal reserve in critical illness.     

Analysis of Ig and T-cell receptor genes in 40 childhood acute lymphoblastic leukemias at diagnosis and subsequent relapse: implications for the detection of minimal residual disease by polymerase chain reaction analysis

The rearrangement patterns of Ig and T-cell receptor (TcR) genes were studied by Southern blot analysis in 30 precursor B-cell acute lymphoblastic leukemias (B-ALLs) and 10 T-ALLs at diagnosis and subsequent relapse. Eight precursor B-ALLs appeared to contain biclonal/oligoclonal Ig heavy-chain (IgH) gene rearrangements at diagnosis. Differences in rearrangement patterns between diagnosis and relapse were found in 67% (20 cases) of precursor B-ALLs (including all eight biclonal/oligoclonal cases) and 50% (five cases) of T-ALLs. In precursor B-ALLs, especially changes in IgH and/or TcR-delta gene rearrangements were found (17 cases), but also changes in TcR-beta, TcR- gamma, Ig kappa, and/or Ig lambda genes (11 cases) occurred. The changes in T-ALLs concerned the TcR-beta, TcR-gamma, TcR-delta, and/or IgH genes. Two precursor B-ALLs showed completely different Ig and TcR gene rearrangement patterns at relapse, suggesting the absence of a clonal relation between the leukemic cells at diagnosis and relapse and the development of a secondary leukemia. The clonal evolution in the other 23 ALL patients was based on continuing rearrangement processes and selection of subclones. The development of changes in Ig and TcR gene rearrangement patterns was related to remission duration, suggesting an increasing chance of continuing rearrangement processes with time. These immunogenotypic changes at relapse occurred in a hierarchical order, with changes in IgH and TcR-delta genes occurring after only 6 months of remission duration, whereas changes in other Ig and TcR genes were generally detectable after 1 to 2 years of remission duration. The heterogeneity reported here in Ig and/or TcR gene rearrangement patterns at diagnosis and relapse might hamper polymerase chain reaction (PCR)-mediated detection of minimal residual disease (MRD) using junctional regions of rearranged Ig or TcR genes as PCR targets. However, our data also indicate that in 75% to 90% of ALLs, at least one major rearranged IgH, TcR-gamma, or TcR-delta band (allele) remained stable at relapse. We conclude that two or more junctional regions of different genes (IgH, TcR-gamma, and/or TcR-delta) should be monitored during follow-up of ALL patients for MRD detection by use of PCR techniques. Especially in biclonal/oligoclonal precursor B-ALL cases, the monitoring should not be restricted to rearranged IgH genes, but TcR-gamma and/or TcR-delta genes should be monitored as well, because of the extensive changes in IgH gene rearrangement patterns in this ALL subgroup.     

Ratings of “trust” and hypnotic susceptibilty

The relationship of trust to hypnotic susceptibility has been only peripherally explored. This study tests the hypothesis that hypnotic susceptibility in females is related to traits associated with trust. A 38-adjective Trust Rating Scale for females was constructed and the relationship between ratings on this scale and a modified version of the Harvard Group Scale of Hypnotic Susceptibility, Form A (Shor & E. Orne, 1962) was examined. 4 subgroups of Ss, with a total N of 102, were used. No relationship was found between group ratings of trust and hypnotic susceptibility, but self-ratings of trust correlated .40 with hypnotic susceptibility. Relationships among variables for all subgroups were generally consistent. The split-half reliability of .79 and alpha coefficient of .82 for the Trust Rating Scale indicate an encouraging degree of internal consistency for the trait being measured.     

Plasma pharmacokinetics,tissue disposition,excretion and metabolism of vinorelbine in mice as determined by high performance liquid chromatography

Summary We have investigated the pharmacokinetics of the investigational semi-synthetic vinca alkaloid vinorelbine (navelbine, NVB). The analyses have been performed by using a sensitive and selective method based on ionexchange normal phase high-performance liquid chromatography with fluorescence detection combined with liquid-liquid extraction for sample clean-up. Pharmacokinetic studies were performed in male FVB mice receiving 12 mg/kg NVB through intravenous injection. The results have been compared to those obtained for vinblastine (VBL). The plasma pharmacokinetics of NVB can be described by a three compartment model. The elimination half-life is significantly longer and the plasma AUC values higher for NVB compared to VBL. This is reflected in tissues, where, 24 hr after drug administration, the concentration of NVB is 5 to 10-fold higher compared to VBL. Qualitatively, the tissue distribution and retention of the drugs is very similar. The drug concentrations in most tissues decline parallel with the circulating plasma levels, whereas prolonged retention is found in tissues of lymphatic and testicular origin. Deacetylation yielding deacetylnavelbine (DNVB) is the primary metabolic route for NVB. This cytotoxic metabolite accounts for a substantial part of the overall disposition of drug. Only 58% of the administered dose is excreted in the urine (17%) and faeces (41%) as NVB or DNVB. No other metabolites have been detected.     

Degradation Kinetics of Three Gonadorelin Analogues: Developing a Method for Calculating Epimerization Parameters

Purpose. To develop a method for calculating epimerisation parameters, find out if the kinetics of the independent reactions can be established, and elucidate primary structure-chemical degradation relationships in the degradation kinetics of three gonadorelin analogues. Methods. The influences of pH, temperature, and buffer concentration on the degradation of the three gonadorelin analogues buserelin, goserelin, and triptorelin were investigated using RP-HPLC. A method was developed to calculate epimerisation and hydrolysis rate constants independently. Results. Explicit structure-degradation mechanism relations were found in the degradation of all three compounds. The L-serine residue was found to be involved in both a solvent-catalysed backbone hydrolysis and a hydroxyl-catalysed epimerisation whereas, the O-tertiary butyl D-serine residue was only involved in proton-catalysed ether hydrolysis. The kinetics of identical reactions in different analogues were generally comparable. Conclusions. The degradation of the gonadorelin analogues is located at a relatively small number of chemical residues and prediction of the degradation mechanisms and kinetics of other peptides with similar structural elements appears to be possible.     

Urinary albumin excretion as a predictor of the development of hypertension in the general population

The hypothesis that high urinary albumin excretion (UAE; indicating mild renal damage) may precede development of hypertension was tested, and the relation among UAE, GFR, and development of hypertension was investigated. Data of 4635 patients of a prospective cohort study who participated in an extensive screening in 1997 to 1998 and 2001 to 2003 at our outpatient unit and were normotensive at baseline were used. Hypertension was defined according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria, UAE was measured in two consecutive 24-h urine samples, and GFR was calculated with the modified Modification of Diet in Renal Disease formula. Mean follow-up was 4.3 yr. Baseline UAE was significantly associated with the risk for developing hypertension (odds ratio 2.29; 95% confidence interval 1.77 to 2.95 per 10-fold increase of UAE). This association was independent of potential confounders. An interaction between UAE and GFR was found (P = 0.030), indicating that with elevated UAE and lowered GFR, but still within the normal range, the risk for developing hypertension was highest. In conclusion, these findings support the hypothesis that mild renal damage may precede the development of hypertension.