Unrelated donor bone marrow transplantation for chronic myelogenous leukemia: a decision analysis

BACKGROUND: Chronic myelogenous leukemia (CML) is an indolent but ultimately fatal disease. Because the natural history of CML varies and quality of life with CML may be excellent until shortly before death, deciding whether and when to pursue unrelated donor bone marrow transplantation is often difficult. OBJECTIVE: To compare early transplantation, delayed transplantation, and no transplantation for patients with chronic-phase CML on the basis of discounted, quality-adjusted life expectancy. DESIGN: A markov model comparing different strategies was constructed. This model considers patient age, quality of life, risk aversion, and the competing risks for CML progression and transplant toxicity. SETTING: Therapeutic decision at the time of diagnosis of CML. PATIENTS: The base case is a 35-year-old patient with intermediate-prognosis CML. Younger and older patients with better and worse prognoses are also evaluated. INTERVENTION: Early transplantation, delayed transplantation, and no transplantation. MEASUREMENTS: Quality-adjusted, discounted life expectancy. RESULTS: For patients with newly diagnosed CML, transplantation within the first year provides the greatest quality-adjusted expected survival, although this benefit decreases with increasing patient age. For a 35-year-old patient with intermediate-prognosis CML, transplantation within the first year results in 53 more discounted, quality-adjusted years of life expectancy than does no transplantation. This finding is robust even with varying baseline assumptions. CONCLUSIONS: These results support the use of early unrelated donor bone marrow transplantation for most patients with CML.     

Congenital encephalocele of the medial skull base

Intensive case management for severely psychiatrically ill patients is a relatively new phenomenon in the private sector. The authors describe a comprehensive case management program designed at Blue Cross Blue Shield of Massachusetts to meet the needs of the most severely ill psychiatric patients in a private managed care environment. The case management program emphasizes involvement of patients in creating comprehensive treatment plans; development of a relationship between case managers, patients and their families, and providers; and clinical coordination between the public and private sectors to create individualized treatment plans. The program's case managers are able to flex the benefit limitations of a managed care or indemnity plan to integrate public and private services and can enlist providers outside a managed care network. The paper describes service utilization by the first 33 patients who participated in the program for one year.     

Onychomycosis. Baseline results of an observational study

The investigators present an analysis of baseline quality-of-life and patient-management approaches from an observational study of 150 patients being treated by podiatric physicians and dermatologists for onychomycosis. The majority (73%) made the initial office visit specifically because of their onychomycosis. Both men and women indicated that they had substantial physical discomfort as well as concerns related to appearance. Women reported significantly more problems than did men as a result of their onychomycosis. Physicians reported that 54% of patients suffered from toenail discomfort, 36% had pain while walking, 40% reported that their condition limited wearing of shoes, and 67% were embarrassed by the condition. The results of this study suggest that the treatment approach of podiatric physicians is more likely to address the palliative concerns of patients with onychomycosis, while the approach of dermatologists is more likely to attempt a definitive cure.     

High prevalence of adynamic bone disease diagnosed by biochemical markers in a wide sample of the European CAPD population

BACKGROUND: Adynamic bone disease (ABD) has been described in the current dialysis population to have an unexpectedly high prevalence. Moreover, it is clearly more prevalent in CAPD patients, compared to haemodialysis patients. Recently we demonstrated that both a low (< or = 27 U/1) level of bone alkaline phosphatase (BAP) as determined by an optimized agarose gel electrophoretic technique and a low (< or = 150 pg/ml ) level of iPTH are good markers of ABD with sensitivities of 78.1% and 80.6% and specificities of 86.4% and 76.2% respectively. METHODS: In this study (n = 212), the prevalence of ABD in the European CAPD population was evaluated by means of these biochemical markers. Clinical data on the patients included were recorded at the moment of blood sampling. In patients under CAPD treatment for longer than 9 months, we calculated an index of calcium exposure through PD fluid. RESULTS: In this population with a low exposure to aluminium, the prevalence of ABD as indicated by either a low level of BAP or PTH was 43%. The following risk factors could be identified: advanced age, shorter time on renal replacement therapy, male gender, and high calcium content of PD fluid. The index of calcium exposure was significantly higher in the patients with low BAP and low iPTH levels compared to those with either BAP > or = 27 U/1 or iPTH > 150 pg/ml. The latter finding gives further support to the hypothesis that a high calcium load administered to renal failure patients may lead to 'oversuppressed' parathyroids in ABD. In a subgroup of patients with a high level of BAP associated with a low iPTH level a profile previously shown to be associated in the presence of aluminium overload, significantly higher serum aluminium levels were noted. suggesting that even in patients with low exposure to aluminium, this element still can affect bone metabolism. CONCLUSION: A high prevalence of ABD--as diagnosed by biochemical markers--was observed in the European CAPD population. A number of risk factors could be put forward. The aetiology and pathogenesis of this type of renal osteodystrophy remain to be elucidated, but appear, however, to be multifactorial.     

Postoperative mortality in infective endocarditis: determinant factors

OBJECTIVE: It has been shown recently that 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) is expressed as at least 2 isozymes. In the liver, 11 beta-HSD1 converts cortisone to cortisol; in the kidney, 11 beta-HSD2 converts cortisol to cortisone. Conventional assessment of 11 beta-HSD activity in vivo has relied on gas chromatographic measurement of the ratios of conjugated cortisol and cortisone metabolites. However, these do not permit distinction between the tissue-specific activities of the enzymes and do not reflect all forms of 11 beta-HSD deficiency. In this report, we have assessed the usefulness of measuring unconjugated cortisol metabolites and free cortisol and cortisone in urine as indices of renal 11 beta-HSD activity in man. DESIGN: Six healthy male subjects established in sodium balance were given either glycyrrhetinic acid (170 mg t.d.s., to inhibit 11 beta-HSD2), carbenoxolone (100 mg t.d.s., to inhibit both 11 beta-HSD1 and 11 beta- HSD2) or both inhibitors in combination. MEASUREMENTS: Urinary electrolytes were measured and the concentrations of total and unconjugated urinary cortisol and its metabolites were determined by gas chromatography mass spectrometry. RESULTS: Glycyrrhetinic acid and carbenoxolone inhibited renal 11 beta-HSD2 to a similar degree, as judged by similar sodium retention. As previously reported, conventional measurement of ratios of total cortisol to cortisone metabolites were influenced to a greater extent by glycyrrhetinic acid (100-200% increase in ratio from baseline) than by carbenoxolone (< 30% increase). However, the effect of carbenoxolone was readily detected by measurement of urinary unconjugated cortisol/cortisone (130-480% increase of ratio from baseline) and also by measurement of ratios of unconjugated cortisol metabolites (60-130% increase). CONCLUSIONS: Measurement of free cortisol and cortisone in urine provides the most sensitive index of renal 11 beta-HSD activity. Measurement of total and conjugated urinary steroids is insensitive in circumstances where 11 beta-HSD activity in liver or elsewhere may be abnormal.     

Hunterian peptic ulcers and Helicobacter pylori

Gastric spiral organisms were first described in man in 1939 and identified as Helicobacter pylori causing peptic ulcers in the early 1980s. Surgical specimens of gastric resections from 1939 showed H. pylori to be present. Full-thickness sections of gastric mucosa from gastric specimens from the eighteenth-century Hunterian Collection at The Royal College of Surgeons of England were examined by histology for the presence of H. pylori. Four gastric ulcers and a section from an oesophageal varix showed remarkable preservation of the overall architecture, but surface autolysis did not allow identification of the bacteria. However, the presence of lymphoid aggregates in the Hunterian specimens suggests that H. pylori may have been present before autolysis.     

Transformation of delithiated LiVO2 to the spinel structure

Heat-treatment of Li_0.5VO₂ obtained by chemical extraction of lithium from the layered LiVO₂ structure results in the spinel Li[V₂]O₄. Similar treatment of Li_0.45VO₂ results in a cation-deficient spinel Li_0.9V_0.1[V_1.9?_0.1]O₄ with vacancies on the octahedral B-sites of the spinel structure. Differential scanning calorimetric and powder X-ray diffraction data show that Li_0.45VO₂ transforms irreversibly to spinel at ～ 300 °C and that this phase is stable to ～ 420 °C.     

Disruption of syntaxin-mediated protein interactions blocks neurotransmitter secretion

The membrane protein syntaxin participates in several protein-protein interactions that have been implicated in neurotransmitter release. To probe the physiological importance of these interactions, we microinjected into the squid giant presynaptic terminal botulinum toxin C1, which cleaves syntaxin, and the H3 domain of syntaxin, which mediates binding to other proteins. Both reagents inhibited synaptic transmission yet did not affect the number or distribution of synaptic vesicles at the presynaptic active zone. Recombinant H3 domain inhibited the interactions between syntaxin and SNAP-25 that underlie the formation of stable SNARE complexes in vitro. These data support the notion that syntaxin-mediated SNARE complexes are necessary for docked synaptic vesicles to fuse.