We analyzed 56 of 75 previously untreated patients with hepatocellular carcinoma who entered on a prospectively randomized trial of acivicin versus 4'deoxydoxorubicin (esorubicin). At least one ...episode of severe toxicity was documented in 23% of the patients on acivicin and 45% of those on 4'deoxydoxorubicin. Two patients responded to 4'deoxydoxorubicin. One response was partial, lasting 58 weeks, and one was complete, lasting more than 4 years. The 90% confidence interval for response is 1-20%. In view of a 45% rate of severe or worse toxicity with 4'deoxydoxorubicin, this drug cannot be recommended as treatment. There were no responses on acivicin.
EST 2287 was a Phase II clinical trial conducted by the Eastern Cooperative Oncology Group (ECOG) designed to evaluate trimetrexate in patients with advanced, measurable, inoperable squamous cell ...carcinoma of the esophagus. The drug was given at a dose of 12 mg/m2 daily for 5 days every 21 days to patients with carcinoma of the esophagus. The purpose of this study was to evaluate treatment efficacy in terms of tumor response and to assess the toxicity. According to a two-stage stopping rule, the study closed after 15 patients had entered. There were no responses to treatment, and median survival from study entry was 4.3 months. There was one treatment-related death caused by infection. One patient experienced life-threatening hematologic toxicity. Overall severe or worse toxicity occurred in more than half of the patients. It is concluded that additional trials of trimetrexate at this dose and schedule in patients with carcinoma of the esophagus are not warranted.
A woman's risk of dying due to pregnancy or childbirth is approximately one in six in the poorest parts of the world and one in 30,000 in Northern Europe (Ronsmans & Graham, 2006). In developed ...countries, substandard care has been identified as a major factor in maternal deaths. In the United Kingdom, 67% of direct and 36% of indirect maternal deaths were identified by reviewers of the Confidential Enquiry into Maternal Deaths (period 2000-2002) as having some form of substandard care (Lewis, 2004). One facet of this substandard care is the lack of interprofessional collaboration. The UK enquiry reported, for example, that relevant information was not shared between health professionals, or only through brief phone consultations, and healthcare professionals showed poor interpersonal communication skills (Lewis, 2004). Similar weaknesses in interprofessional collaboration were identified in the Report on Maternal Deaths in Australia (Sullivan & King, 2006), which found that 48% of cases of maternal mortality were associated with communication breakdown between health services, inappropriate patient management, and logistical system failures. Adapted from the source document.
Exertional muscle pain, contractures, recurrent rhabdomyolysis, and pigmenturia are common in certain muscle glycolytic disorders. However, the frequency, distribution, and long-term significance of ...these findings are poorly understood. First we performed magnetic resonance imaging (MRI) of the extremities as a screening test for the detection of muscle abnormalities incurred in activities of daily living in four patients with myophosphorylase deficiency (MPD) and three with muscle phosphofructokinase deficiency (PFKD). MRI findings of abnormal muscles detected upon screening were next compared with changes observed in a prospective study of muscle contractures involving the forearms of four of the patients (two MPD, two PFKD). Screening revealed abnormalities of proximal thigh muscles in three of seven patients, in two of whom (one MPD, one PFKD) a recent history of exertional myalgia coincided with increases in T1 and T2 estimates of isolated thigh muscles. In the third patient (PFKD), focal atrophy of the adductor magnus was present bilaterally. In prospective studies, focal areas of prolonged T1 and T2 appeared in the flexor digitorum superificalis in all four cases and in the flexor digitorum profundus in two cases. Serial imaging suggested that the onset of MRI abnormalities begins within 24 hours of contracture and persists for at least several days and possibly for much longer, with complete recovery apparently the rule. These cases suggests a high prevalence of focal muscle abnormalities in patients with glycolytic myopathies and show the potential of MRI to detect them.
Abstract only
Objective
Evaluate the invivo muscle glycogen content in patients with glycogen storage disease by performing noninvasive
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C NMR spectroscopy in ultra‐high fields with the advantages ...of improved signal‐to‐noise ratio and spectral resolution.
Methods
Muscle glycogen content was measured in 3 patients with McArdle disease (MD), 1 phosphofructokinase deficient (PFKD) patient, and 4 healthy controls (C).
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C spectra were acquired on a whole‐body 7T scanner (Philips Medical) using a partial volume human calf coil operating in quadrature for
1
H and
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C. The coil had a small vial of acetate fixed inside, to serve as an external reference for quantification. For absolute quantification, a 1L cylindrical phantom was prepared with 100 mM glycogen, and 40 mM creatine.
Results
Muscle glycogen concentration was increased in MD (184.7±14.9 mM) and PFKD (196.0 mM) compared with C (73.1±13.0 mM). Creatine concentration and glycogen/creatine ratio respectively were 82.2±21.9 mM and 2.3±0.6 in MD, 120.5 mM and 1.6 in PFKD, 74.5±8.3 mM and 1.0±0.3 in C. T1 values, the strongly field dependent relaxation times, were established at 7T for glycogen 3.1±1.4 s and creatine 8.8±5.7 s in MD, 0.8±0.4 s and 2.0±1.4 s in C, respectively.
Conclusions
Muscle glycogen concentration was 2.5‐fold increased in patients with glycogen storage disease. Noninvasive ultra‐high filed
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C NMR spectroscopy may provide a valuable tool to study glycogen storage in progression of the pathology and efficacy of treatment.
Study supported by Muscular Dystrophy Association and Giant Tiger Foundation.
An internally consistent thermodynamic dataset has been derived for 148 endmember phases (145 solids and 3 fluids) comprising the elements Li, Na, K, Be, Mg, Ca, Ti, Cr, Mn, Fe, Zn, Al, Si, C, H, and ...O. This has been achieved by simultaneous treatment of phase property (like standard enthalpy of formation, standard entropy, molar heat capacity, molar volume, thermal expansivity, bulk modulus etc.) and reaction reversal data by the Bayesian method. The theory underlying the approach, and the computational methods involved, are briefly outlined. (For the benefit of readers unfamiliar with inference statistics, the basic concepts of the Bayes method are also presented in such a way that they can be grasped intuitively.) Although not yet addressed, this method can be extended to refine the thermodynamic mixing properties of crystalline solutions. The sources of the input data, culled from the literature, are summarized in the Appendix. The resulting database is succinctly documented in this paper. It includes the enthalpies of formation and entropies, their uncertainties, and the correlation among them. The database allows calculation of P-T, T-X sub(CO2), P-X sub(CO2), and T-f sub(O2) sections, with error propagation into the computed phase diagrams on a routine basis. A user-friendly computer program has been written to generate such phase diagrams. It is public domain software. The software and the thermodynamic database (which includes a complete documentation of the thermodynamic data above and beyond those listed (Table 2, here) may be downloaded from the web site http://homepage.ruhr-uni-bochum.de/niranjan.chatterjee/Index.htm. Examples of computed phase diagrams are given to illustrate the quality of the data and the capabilities of the software.
Clinical indicators are increasingly used to assess safety of patient care. In obstetrics, only a few indicators have been validated to date and none is used across specialties. The purpose of this ...study was to identify and assess for face and content validity a group of safety indicators that could be used by anaesthetists, obstetricians and neonatologists involved in labour and delivery units.
We first conducted a systematic review of the literature to identify potential measures. Indicators were then validated by a panel of 30 experts representing all specialties working in labour and delivery units. We used the Delphi method, an iterative questionnaire-based consensus seeking technique. Experts determined on a 7-point Likert scale (1=most representative/7=less representative) the soundness of each indicator as a measure of safety and their possible association with errors and complications caused by medical management.
We identified 44 potential clinical indicators from the literature. Following the Delphi process, 13 indicators were considered as highly representative of safety during obstetrical care (mean score</=2.3). Experts ranked 6 of these indicators as being strongly associated to potential errors and complications.
We identified and validated for face and content, a group of six clinical indicators to measure potentially preventable iatrogenic complications in labour and delivery units.
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