Determining an individual's ideal body weight from skeletal measurements: a new method

Determining an individual's "ideal" body weight is fundamental in nutritional therapy. A simulation of the human body to a cylindrical volumetric model permits the calculation of the ideal body weight from the measured height, interacromioclavicular distance, and humeral length. A group of 189 healthy normal volunteers were assessed. The calculated "Pitt" ideal body weight correlated closely (r = 0.88 for males, r = 0.72 for women) with values obtained from the Metropolitan tables. The technique provides an estimate of ideal body weight based upon reproducible, easily obtained measurements of fixed bony landmarks.     

Angiography in poor-risk patients with massive nonvariceal upper gastrointestinal bleeding

The purpose of this retrospective study was to determine the diagnostic and therapeutic usefulness of gut angiography in patients with massive upper gastrointestinal bleeding from a nonvariceal source. All patients (n = 64) in this category who underwent a gut angiogram between 1980 and 1986 were studied. Pre-angiogram endoscopy was attempted in all patients and was nondiagnostic in 14 (22%). Contrast extravasation at angiography was seen in 25 of 64 patients (39%), and in over half of these patients endoscopy was nondiagnostic (n = 11) or wrong (n = 3). Attempts to control bleeding in this group by selective arterial embolization (n = 14) or intra-arterial vasopressin (n = 11) successfully averted operation in 13 of 25 patients (52%) and was associated with a 50% reduction in mortality (83% versus 38%). Selective embolization of vessels thought to be bleeding on clinical grounds without evidence of contrast extravasation (i.e., "blind" embolization) was not helpful in controlling hemorrhage. Urgent gut angiography in patients with massive upper gastrointestinal bleeding of arteriocapillary source is a useful diagnostic and therapeutic maneuver and warrants continued application in this group of poor-risk patients.     

Childhood leukaemia: a model of pre-obesity.

The prevalence of obesity in children, as in adults, is increasing dramatically. The extent to which this is due to reduced energy expenditure, increased energy intake, or both, is unclear at present. This in part reflects the limitations of existing models of the pre-obese state. In childhood acute lymphoblastic leukaemia (ALL), patients typically gain weight excessively during and after 2 years of therapy, and are at high risk of becoming obese. Previous studies have failed to identify the cause of obesity in these patients. We have tested the hypothesis that excess weight gain in ALL is due to reduced total energy expenditure (TEE), measured using the doubly-labelled water method, and have identified risk factors for excess weight gain in ALL. Pre-obese children with ALL in the dynamic phase of weight gain are less physically active than their peers, with a reduced TEE of approximately 1.2 (95% CI 0.2, 2.2) MJ/d. While other factors might contribute to excess weight gain, lifestyle (i.e. reduced habitual physical activity) plays a central role in ALL. Several considerations suggest that ALL might be a useful model of the pre-obese state: lifestyle is critical to development of obesity in ALL; ALL is relatively common; approximately 70% of patients survive; patients are readily accessible during the 2 years of therapy and beyond.     

Human endothelin-1 clearance kinetics revealed by a radiotracer technique

Levels of endothelin-1 (ET-1) are elevated in many disease states, although its total body kinetics of elimination are poorly understood. Therefore, it remains uncertain whether the presence of elevated levels of ET-1 in the setting of disease are secondary to changes in production or clearance or some combination thereof. Using a 125I-labeled ET-1 infusion technique, the volume of distribution and kinetics of clearance of endothelin were described in five normal volunteers. Heart rate, blood pressure, right atrial pressure, and arterial blood samples for the counting of 125I and the measurement of ET-1 were obtained at multiple time points before and up to 45 h after the start of the infusion. The radiotracer infusion had no effect on heart rate, blood pressure, right atrial pressure, or endogenous ET-1 levels. ET-1 clearance was best described by a three-compartment model, which revealed that ET-1 has a much longer terminal half-life and volume of distribution than was previously reported. This suggests extensive uptake of ET-1 in various organ systems and slow clearance. These new findings have important implications for the understanding of the pathophysiology of ET-1 in disease states as well as for the understanding and development of ET-1 receptor blockers and endothelin-converting enzyme inhibitors.     

Oral-motor dysfunction in children who fail to thrive: organic or non-organic?

Forty-seven children with non-organic failure to thrive (NOFT) were identified from a whole-population survey of children's growth and development. A significant proportion (N=17) of these 47 children were found to have oral-motor dysfunction (OMD) identified using a previously validated assessment tool. NOFT children with OMD and those with normal oral-motor function (N=30) were compared in order to ascertain whether there were any neurodevelopmental differences which might explain this finding. We hypothesized that children with OMD might have a subtle neurodevelopmental disorder. Few psychosocial variables discriminated the two groups. However, cognitive stimulation within the home and cognitive-growth fostering during mealtimes was much poorer for children with OMD. Some evidence has suggested that NOFT children with OMD may be 'biologically' more vulnerable from birth. We suggest that the continued use of the term 'non-organic' to describe failure to thrive in such children is questionable and requires redefining.     

The parabrachial nucleus and conditioned taste aversion

The parabrachial nucleus (PBN) surrounds the brachium conjunctivum in the dorsolateral pons. Although composed of numerous subnuclei, the PBN is typically organized into medial and lateral subdivisions according to their location relative to the brachium. In rodents, the medial PBN is part of the central gustatory system, whereas the lateral PBN is a component of the visceral sensory system. Lesions of the PBN disrupt conditioned taste aversion, a critically important learning mechanism that prevents the repeated ingestion of toxic food. Relevant neurobehavioral literature is reviewed to elucidate the role of the PBN in taste aversion learning.     

Prothrombin activation in rabbits

The suitability of rabbit prothrombin activation fragment F 1.2 as a marker for the activation of the coagulation system was tested. Monoclonal antibodies to rabbit F 1.2 were raised, and a competitive F 1.2 ELISA was developed. Within the detection limit of the ELISA, no increase in rabbit F 1.2 was detected upon recalcification of plasma, whereas human F 1.2 increased 1500-fold. The apparent lack of F 1.2 formation in rabbit serum was confirmed by immunoblotting analysis of endogenous and biotin-labeled prothrombin. Meizothrombin and the B-chain of thrombin were the only prothrombin fragments detectable. In contrast, labeled human prothrombin formed, in addition, prethrombin 2 and F 1.2 in both human and rabbit serum. In contrast, rabbit F 1.2 formation could be demonstrated using purified rabbit prothrombin and factor Xa. These observations raise the possibility that rabbit prothrombin is less susceptible than the human counterpart to factor Xa cleavage at the 271/272 peptide bond. Thus, the primary structure of rabbit prothrombin was deduced by cDNA sequencing. While the 320/321 Xa cleavage site giving rise to meizothrombin was identical in rabbit and human prothrombin, the flanking region of the 271/272 Xa sensitive site contained a six amino acid deletion in the rabbit sequence. Taken together, these observations suggest that the observed differences between human and rabbit prothrombin activation may be due to different susceptibilities of the two Xa cleavage sites rather than plasma or serum cofactor(s).     

Anti-inflammatory activity of c(ILDV-NH(CH2)5CO), a novel, selective, cyclic peptide inhibitor of VLA-4-mediated cell adhesion.

1. Small, N- to C-terminal cyclized peptides containing the leucyl-aspartyl-valine (LDV) motif from fibronectin connecting segment-1 (CS-1) have been investigated for their effects on the adhesion of human T-lymphoblastic leukaemia cells (MOLT-4) to human plasma fibronectin in vitro mediated by the integrin Very Late Antigen (VLA)-4 (alpha4beta1, CD49d/CD29). 2. Cyclo(-isoleucyl-leucyl-aspartyl-valyl-aminohexanoyl-) (c(ILDV-NH(CH2)5CO)) was approximately 5 fold more potent (IC50 3.6+/-0.44 microM) than the 25-amino acid linear CS-1 peptide. Cyclic peptides containing two more or one less methylene groups had similar potency to c(ILDV-NH(CH2)5CO) while a compound containing three less methylene groups, c(ILDV-NH(CH2)2CO), was inactive at 100 microM. 3. c(ILDV-NH(CH2)5CO) had little effect on cell adhesion mediated by two other integrins, VLA-5 (alpha5,beta1, CD49e/CD29) (K562 cell adhesion to fibronectin) or Leukocyte Function Associated molecule-1 (LFA-1, alphabeta2, CD11a/CD18) (U937 cell adhesion to Chinese hamster ovary cells transfected with intercellular adhesion molecule-1) at concentrations up to 300 microM. 4. c(ILDV-NH(CH2)5CO) inhibited ovalbumin delayed-type hypersensitivity or oxazolone contact hypersensitivity in Balb/c mice when dosed continuously from subcutaneous osmotic mini-pumps (0.1-10 mg kg(-1) day(-1)). Maximum inhibition (approximately 40%) was similar to that caused by the monoclonal antibody PS/2 (7.5 mg kg(-1) i.v.) directed against the alpha4 integrin subunit. 5. c(ILDV-NH(CH2)5CO) also inhibited oxazolone contact hypersensitivity when dosed intravenously 20 h after oxazolone challenge (1-10 mg kg(-1)). Ear swelling was reduced at 3 h and 4 h but not at 1 h and 2 h post-dose (10 mg kg(-1)). 6. Small molecule VLA-4 inhibitors derived from c(ILDV-NH(CH2)5CO) may be useful as anti-inflammatory agents.     

Electroencephalographic analysis of malignant melanoma patients.

EEGs carried out in 202 patients with melanoma were abnormal in 33%. In the absence of systemic or brain metastasis 14% of the patients had abnormal records. If systemic metastases without brain metastasis were present 45% of the patients had abnormal records and with brain metastasis 88% had abnormal EEGs. Only a third of the patients with abnormal records had brain metastasis but metastatic spread to some organ system was present in 76% of those with EEG abnormalities. The diffuse abnormality was less likely to be a "false positive." Ninety-seven percent of the patients with diffuse EEG abnormality had systemic metastasis but 43% of the patients with focal EEG changes had no detected metastasis.