Monitoring Dietary Change in a Low-Fat Diet Intervention Study: Advantages of Using 24-Hour Dietary Recalls vs Food Records

Objective The purpose of the study was to evaluate two methods of dietary assessment for monitoring change in fat intake in a low-fat diet intervention study.Design The two dietary assessment methods were a 4-day food record (4DFR) and an unannounced 24-hour dietary recall conducted by telephone interview (referred to as a telephone recall [TR]). Subjects were assigned randomly to either a low-fat diet intervention group or a control group that received no counseling about fat intake. Dietary data were collected at baseline, 6 months, and 12 months.Subjects Two hundred ninety postmenopausal women with localized breast cancer were recruited at seven clinical centers in the United States.Statistical analysis Analysis of variance was used to test for significant differences in mean fat and energy intakes.Results Three sources of error were identified: (a) an instrument effect, suggesting underreporting at baseline of approximately 8% in mean energy intake and 11% in mean fat intake in the TR group compared with the 4DFR group (P=.0001); (b) a repeated measures effect observed for the 4DFR, suggesting underreporting of approximately 7% for energy intake and 14% for fat intake in the control group at 6 and 12 months compared with baseline values (P<.001); and (c) an adherence effect (or compliance bias), suggesting greater compliance to the low-fat intervention diet when subjects were keeping food records than when estimates were based on the unannounced TR. Compared with the TR, the 4DFR overestimated the extent of fat reduction in the low-fat diet intervention group by 41% (P=.08) and 25% (P=.62) at 6 and 12 months, respectively.Application Multiple days of unannounced 24-hour recalls may be preferable to multiple-day food records for monitoring dietary change in diet intervention studies. J Am Diet Assoc. 1996; 96:574-579.     

The Inhalation Toxicology, Genetic Toxicology, and Metabolism of Difluoromethane in the Rat

Difluoromethane (HFC32) is under development as a replacementfor chlorofluorocarbons (CFCs) in some refrigeration applications.It has been evaluated by standard studies of toxicity, developmentaltoxicity, and genotoxicity. In addition, the metabolism anddisposition of HFC32 was investigated and a physiologicallybased pharmacokinetic (PB-PK) model constructed. Inhalationof HFC32 (up to 50,000 ppm) caused no organ-specific effects,but resulted in slight maternal toxicity to the pregnant ratand rabbit and some fetotoxicity to the rat. HFC32 did not sensitizethe heart to adrenaline. The pharmacokinetics of [¹⁴C]difluoromethane(10,000 to 50,000 ppm/6 hr) revealed that about 2.1% of theinhaled HFC32 was absorbed and that steady state blood levelswere achieved within 2 hr and were proportional to dose. Carbondioxide was the major metabolite of HFC32 at all exposure levels.Carbon monoxide was not detected. The in vivo data were usedto validate a PB-PK model to describe the uptake and metabolismof HFC32. Absorption and distribution are adequately describedusing rat blood:air and tissue:air partition coefficients. Metabolism,which was linear across the dose range, was described by a firstorder rate constant (K_f=8.98 hr^–1). Of the absorbed HFC32,about 63% was metabolized at all doses; however, when metabolismwas expressed as a percentage of the inhaled dose it was muchlower, being about 1.4% of the HFC32 entering the airways. Overall,the results indicate that HFC32 is of very low toxicity andshould be an acceptable alternative to CFCs.     

Acute Lymphoblastic Leukaemia in Adults in the Northern Region of England - A Study of 75 Cases

Over a ten-year period we have studied 75 cases of adult acutelymphoblastic leukaemia (ALL) Sixty of the cases were seen from1979 to 1984 and represent an unselected series of all knowncases in a region of 3 000 000 people. Study of these patientshas given further insight into the heterogeneous, clinical andcytological nature of adult ALL. Three protocols have been usedand results are presented indicating that conventional approachesto treatment in this disease are unsatisfactory. Not all patientscould be entered on protocols but these patients are includedto give the overall perspective of this disease in clinicalpractice. A new strategy is proposed which envisages abandoningtraditional maintenance chemotherapy in favour of either allogeneicmarrow transplant or autologous transplant in first remissionin the post-consolidation phase. Preliminary results of thisflexible approach are given.     

Comparison of Biphasic and Monophasic Pulses: Does the Advantage of Biphasic Shocks Depend on the Waveshape?

With present implantable defibrillators, the ability to vary the defibrillation technique has been shown to increase the number of patients suitable for transvenous system. As newer waveforms become available, the need for a flexible device may change. In addition, although it has been shown that the option of biphasic waveform may increase the defibrillation efficacy, this may depend upon the shape of the biphasic waveform used. Thirty patients undergoing transvenous defibrillator implant were included in the study. In 20 patients (group I), defibrillation efficacy of simultaneous monophasic, sequential monophasic, and biphasic waveform with 50% tilt was determined randomly. Similarly, in ten patients (group II) testing of simultaneous monophasic shocks and biphasic waveforms with 65% and 80% tilt was performed in random order. The electrode system used consisted of two transvenous leads and a subcutaneous patch in all 30 patients. In group I, 50% tilt biphasic waveform consistently provided similar or better defibrillation efficacy compared to monophasic waveforms (biphasic 7.5 ±5.1 joules vs simultaneous 17 ± 7.8 joules, P < 0.01; and vs sequential 17 ± 8.4 joules, P <0.01). In group II, 65% tilt biphasic pulse required less energy for defibrillation as compared with simultaneous monophasic shocks (9.6 ± 4.5 joulesvs 15.6 ± 5.1 joules, P = 0.04). No significant difference was observed in terms of defibrillation threshold between 80% tilt biphasic shocks and simultaneous monophasic pulses (11.8 ± 6 joules vs 15.6 ±5.1 joules, P = NS). Biphasic shocks with smaller tilt delivered using a triple lead system more uniformly improved defibrillation threshold over standard monophasic waveforms.     

Clinical Efficacy and Safety of the New Cardioverter Defibrillator Systems

Clinical efficacy and safety of two new third-generation implantable cardioverter defibrillators (ICD) were studied in 38 patients with ventricular tachycardia (VT) or fibrillation (VF). There were 31 patients with coronary disease, three patients with right ventricular dysplasia, one patient with dilated cardiomyopathy, and three patients with valvular disease. Twenty-four patients (group I) received an ICD with monophasic (Ventak PRx 1700, CPI) and 14 patients (group II) with biphasic shocks (Cadence V 100, Ventritex). Intraoperatively, the mean defibrillation threshold was significantly lower in group II than in group I, both in patients with induced VT (group I 11.0 ± 6.3 joules: group N 5.8 ± 1.3 joules) (P < O.01) and induced VF (group I 17.5 ± 4.6 joules; group II 9.6 ± 5.2 joules) (P < O.O1). During the mean follow-up of 12 ± 7 months four patients (11%) died. 865 arrhythmia events (AE) occurred and were terminated by ATP (671 VTs, 78%). Acceleration of VTs was observed in 28 AE (3%) and ATP was unable to interrupt 58 AE (7%). ICD shocks were delivered as a first therapy in 108 AE (13%).     

Ventriculoatrial Conduction Time During Bundle Branch Reentrant Beat Initiating Orthodromic Tachycardia: A Simple and Reliable Method for Localization of Accessory Pathways

VA Interval Via Accessory Pathway During Bundle Branch Reentry. Bundle branch reentrant (BBR) complex is commonly induced during programmed ventricular stimulation with single ex-trastimulus. In patients with atrioventricular accessory pathway, BBR beat frequently triggers orthodromic tachycardia. This study was designed to determine whether evaluation of the ventriculoatrial conduction time during BBR (VA_BBR) induced with right ventricular extrastimulation (i.e., left bundle branch block morphology) can separate left free-wall (LFW) accessory pathways from left posteroseptal (LPS) or right-sided pathways. Thirty-eight patients with single atrioventricular accessory pathways were included. There were 28 men and 10 women with a mean age of 26 years. The accessory pathway was localized in LFW in 23 patients (group I) and LPS in seven (group ID. Eight patients (group III) had pathways located in the right side. In each patient, VA_BBR was determined and compared with the following: (1) V₂A₂ interval exclusively via accessory pathway; and (2) ventriculoatrial conduction time during orthodromic tachycardia with narrow QRS complex (VA_NQ), left bundle branch block plus normal axis (VA_LB-NA) or left axis (VA_LB-LA). In group I, VA_BBR values (170–245 msec, mean 196.1 ± 20.5 msec) were 0–25 msec longer than V₂A₂ (170–245 msec, mean 191.3 ± 19.1 msec) and 45–125 msec greater than VA_NQ (100–155 msec, mean 125.6 ± 14.1 msec). VA_BBR was identical to VA_LB-LA but 25–55 msec greater than VA,_LB-NA (140–205 msec, mean 160.9 ± 20.8 msec). In group II, VA_BBR values (100–140 msec, mean 118.6 ± 14.3 msec) were 15–30 msec shorter than V₂A₂ (125–165 msec, mean 140.7 ± 14.3 msec) and 15–25 msec longer than VA_NQ (85–120 msec, mean 100.7 ± 12.0 msec). Comparing VA_BBR with VA_LB-NA or VA_LB-LA did not show any statistically significant difference. In group III, VA_BBR values were consistently shorter than V₂A₂ and identical to VA_NQ. Thus, assessment of VA_BBR is a simple and useful method that can be reliably utilized to differentiate LFW pathways from LPS or right-sided pathways. Furthermore, these data provide new insights into the electrophysiological characteristics of bundle branch reentry. (J Cardiovasc Electrophysiol, Vol. 1, pp. 121–131, April 1990)     

Identifying the End of Ventricular Activation:

Late Potentials: Epicardial and Body Surface. Introduction: Identification of the end of the QRS is perhaps the single most important feature obtained from the high resolution signal-averaged electrocardiogram (SAECG). This point relies on computer algorithms to select a point ahove the noise levels. Prior studies to suhstantiate this approach using eleetrograms for comparison have demonstrated many examples of the hody surface recordings failing to detect the full extent of the late potentials.
Methods and Results: An animal model that generates late potentials was used in conjunction with epicardial cardiac mapping system to systematically examine the rea.sons for these failures. In I I of 13 dogs we found a concordance hetween the signal-averaged recordings and Ihe epicardial recordings within 5 msec. The two discordant studies were attrihuted to a failure of epicardial mapping to record all late potential sources. Also, a means of accurately comparing measurements from the two recording technologies was required in this study as well as a new definition for identifying the end of activation currents in epicardial eleetrograms.
Conclusion: To achieve these results required approaches different from those used in the clinical setting to record the SAECG. These include: (1) the analysis of individual XYZ leads as opposed to the vector magnitude derived from these leads; (2) visual identification of very low level signals, as automatic algorithms often fail to detect low level signals: and (3) the use of finite impulse response digital filters instead of the bidirectional Butterworth filter.     

Unrelated donor bone marrow transplantation for children and adolescents with aplastic anaemia or myelodysplasia

Allogeneic transplantation from an HLA-matched family member has been shown to be effective in reconstituting normal haemopoiesis in young people with severe cytopenias, classified as myelodysplastic syndrome (MDS) or severe aplastic anaemia (SAA). Unrelated donor transplant is a therapeutic choice for patients without a suitable family member donor. We report the outcome of seven patients < 20 years old with SAA and 10 with MDS treated with BMT from an HLA A,B DRB1 matched ( n  =8) or A or B locus mismatched ( n  =9) unrelated donor at the University of Minnesota between March 1988 and August 1995. Primary graft failure occurred in two patients and secondary graft failure in one, who was subsequently successfully engrafted with a second donor marrow infusion. Grades II–IV GVHD occurred in 10/16 (63%), and grades III–IV in 6/16 (37%) evaluable patients. Nine of the 17 patients (six with MDS and three with SAA) survive with full donor chimaerism, a median of 1.2 years post-BMT (range 3 months to 7 years). We recommend early referral for consideration of unrelated donor BMT for young patients with MDS, and patients with SAA without response to immunosuppression.     

Variable expression of the murine natural resistance gene Lsh in different macrophage populations infected in vitro with Leishmania donovani

Various macrophage populations isolated from mice (including congenic C57BL/10ScSn and B10.LLshr) bearing resistant or susceptible alleles for the natural resistance gene (Lsh) were infected with Leishmania donovani amastigotes in vitro and examined (a) for their ability to support growth of the amastigote population over 7 days of culture in vitro, and (b) for their ability to express Lsh gene controlled resistance and susceptibility in vitro. Resident macrophages from liver (Kupffer cells), spleen and lung, as well as 7-day bone marrow-derived macrophages and bone marrow macrophages obtained after 6 weeks of continuous culture in vitro, all supported growth of the amastigote population. Of these, significant differences in amastigote numbers in macrophages from Lshs and Lshr mice were observed after 48 h of infection in vitro for liver, lung and 7-day bone marrow macrophage populations only. Resident peritoneal macrophages grown in adherent or suspension cultures neither supported growth of the amastigote population nor showed any evidence of Lsh gene expression in vitro. Hence, multiplication of the parasite appeared to be a necessary but not sufficient condition for observation of Lsh gene activity against L. donovani in vitro. Use of tritiated thymidine incorporation and autoradiography to label dividing amastigotes showed equivalent multiplication of the parasite in liver macrophages from Lshs and Lshr mice between 24 h and 48 h after infection in vitro, with a dramatic difference observed thereafter. This was consistent with earlier observations of a 2-3 day delay in expression of Lsh gene controlled resistance in vivo. Comparison with studies using Salmonella typhimurium and Mycobacterium bovis suggests that the gene may be restricted in its action to a particular point in the parasite cell cycle, perhaps at the level of regulating DNA replication.