Do foreign bodies migrate through the body towards the heart?

UNLABELLED: Fixation of foreign bodies (FB), in the mucosa, can favor its migration, giving origin to the popular saying: 'FB walk to the heart'. AIM: Describe the mechanisms involved in FB migration and how to diagnose them. METHODOLOGY: From a sample of 3,000 foreign bodies, during 40 years, we analyzed four which had extra-lumen migration. We analyzed clinical, radiologic, endoscopic and ultrasound data collected at the medical documentation service. RESULTS: Three clinical histories are presented, describing two fish bones and one piece of fish cartilage. FB shifting was analyzed in all of them. Migration started in the esophagus in two, one going to the aorta and the other to the neck area. In the other two, migration started in the pharynx, and the FB moved towards the prevertebral fascia and the other externalized in the submandibular region. The mechanisms and the risks posed to the patient, by FB migration, and the way to diagnose them are hereby discussed. CONCLUSIONS: The study allows us to determine that FB can move through the body but not towards the heart. The study also serves as a warning sign: in cases of prolonged histories of FB ingestion, imaging studies are mandatory before endoscopic examination.

Corpos estranhos caminham pelo corpo em direção ao coração? / Do foreign bodies migrate through the body towards the heart?

A fixação dos CE, principalmente os pontiagudos, favorece a migração pelo corpo, gerando a expressão popular: "os CEs caminham pelo corpo em direção ao coração". OBJETIVO: Descrever os mecanismos envolvidos na migração do CE e a forma de diagnosticá-los. METODOLOGIA: Numa população de 3.000 casos de corpos estranhos, em 40 anos, foram analisados quatro que tiveram deslocamento extraluminal. Foram tomados os dados clínicos, radiológicos, endoscópicos e ultrassonográficos coletadas no serviço de documentação médica. RESULTADOS: São apresentadas três histórias clínicas em que o CE era de espinha de peixe e uma de cartilagem de peixe. Em todos se analisou o deslocamento. Em dois a migração se iniciou no esôfago, um para a aorta e outro para a região cervical e nos dois outros, o deslocamento ocorreu a partir da faringe: um para a fáscia pré-vertebral e outro se exteriorizou na região submandibular. Discutem os mecanismos pelos quais ocorre a migração dos CEs pelo corpo e os riscos que tais deslocamentos promovem para o paciente e a forma de diagnosticá-los. CONCLUSÕES: Os CE podem caminhar pelo corpo, porém não para o coração. Em casos de histórias arrastadas de ingestão de CEs, o estudo por imagens se faz obrigatório, previamente ao exame endoscópico.

Fixation of foreign bodies (FB), in the mucosa, can favor its migration, giving origin to the popular saying: "FB walk to the heart". AIM: describe the mechanisms involved in FB migration and how to diagnose them. METHODOLOGY: From a sample of 3,000 foreign bodies, during 40 years, we analyzed four which had extra-lumen migration. We analyzed clinical, radiologic, endoscopic and ultrasound data collected at the medical documentation service. RESULTS: three clinical histories are presented, describing two fish bones and one piece of fish cartilage. FB shifting was analyzed in all of them. Migration started in the esophagus in two, one going to the aorta and the other to the neck area. In the other two, migration started in the pharynx, and the FB moved towards the prevertebral fascia and the other externalized in the submandibular region. The mechanisms and the risks posed to the patient, by FB migration, and the way to diagnose them are hereby discussed. CONCLUSIONS: the study allows us to determine that FB can move through the body but not towards the heart. The study also serves as a warning sign: in cases of prolonged histories of FB ingestion, imaging studies are mandatory before endoscopic examination.

The effect of tyrosine-deficient total parenteral nutrition on the synthesis of dihydroxyphenylalanine in neural tissue and the activities of tyrosine and branched-chain aminotransferases.

The poor solubility of tyrosine (Tyr) limits the amount of this amino acid in total parenteral nutrition (TPN). In rats maintained on a standard pediatric TPN mixture, plasma and brain concentrations of Tyr are reduced to about 25% of the levels in chow-fed controls. To determine whether these low concentrations of Tyr affect the synthesis of catecholamines in neural tissue, the rate-limiting step (conversion of Tyr to dihydroxyphenylalanine [DOPA]) is studied by administering NSD-1015 to block the pyridoxal phosphate (PLP)-dependent decarboxylation of DOPA. However, in TPN rats, plasma concentrations of Tyr are increased by drug treatment. Because brain Tyr is also increased, these and other experiments using NSD-1015 clearly overestimate the rate of DOPA synthesis for drug-free rats on TPN. Nevertheless, in TPN rats, there is less DOPA in the brain in one experiment and less DOPA in the olfactory bulbs in another, versus control rats. Further examination of the metabolic effects of NSD-1015 reveals that the drug also elevates the concentration of branched-chain amino acids (BCAAs) in the plasma of TPN rats. These findings result from inhibition by NSD-1015 of the PLP-dependent aminotransferases that initiate catabolism of Tyr in the liver and BCAAs in the muscle. Despite the pronounced reduction in plasma Tyr, TPN rats showed a marked increase in the activity of hepatic Tyr aminotransferase compared with chow-fed controls. Conversely, although TPN elevates BCAA concentrations in plasma, the activity of branched-chain aminotransferase (BCAT) in the heart muscle of TPN rats is not different from control values. Different values but the same relationships are seen in drug-free rats.

Intravenous gamma-glutamyl-tyrosine elevates brain tyrosine but not catecholamine concentrations in normal rats.

A number of clinical situations may benefit from intravenous supplements of tyrosine (Tyr). In total parenteral nutrition (TPN), the supply of Tyr is limited by its poor solubility. In both rats and infants maintained on pediatric TPN, plasma Tyr levels are approximately 30% of normal, and in rat brains Tyr concentrations are similarly reduced. We reported previously that supplementing a TPN solution with the soluble peptide, gamma-glutamyl-Tyr [Glu(Tyr)], normalizes plasma Tyr and doubles brain Tyr in rats. To assess more fully the behavior of intravenous Glu(Tyr) in vivo, 20 mmol/L Glu(Tyr) was infused into the inferior vena cava of rats at rates increased every 2 hours over an 8-hour period (300 to 450 mumol Glu(Tyr)/kg body weight/h). The surgical procedure for catheterization is described. At the maximum rate of infusion, plasma Tyr and Glu(Tyr) concentrations reached mean plateau values of 326 and 252 mumol/L, respectively. Brain Tyr concentrations were 71 and 264 nmol/g wet weight in control rats infused with heparinized saline (SAL group) and rats infused with Glu(Tyr) (PEP group) respectively. No differences were found in concentrations of norepinephrine (NE), dopamine (DA), or homovanillic acid (HVA) in prefrontal cortex (PFC), striatum (STR), or remaining brain (RB) tissue in PEP and SAL rats. We did not detect undergraded Glu(Tyr) in the brain, and less than 0.5% of infused Glu(Tyr) appeared in the urine.

Use of the soluble peptide gamma-L-glutamyl-L-tyrosine to provide tyrosine in total parenteral nutrition in rats.

Limited solubility restricts amounts of tyrosine (Tyr) in amino acid solutions used in total parenteral nutrition (TPN). Excess phenylalanine (Phe) is included in TPN for conversion to Tyr by liver Phe hydroxylase. However, this conversion is limited, especially in infants. We have confirmed that infants receiving TPN have low Tyr concentrations and high Phe/Tyr ratios in plasma compared with published values for enterally fed neonates. Tyr is important in the synthesis of proteins and other biomolecules, including catecholamines in the brain. We tested the soluble peptide gamma-glutamyl-tyrosine (Glu(Tyr)) as a possible precursor of Tyr in TPN. Groups of five rats were given infusions of TPN containing an amino acid mixture simulating a commercial formulation (group A), TPN in which Glu(Tyr) was substituted for half the Phe in the group A solution) (group B), or saline (group C). Control animals (group C) were fed rodent chow. Blood was sampled at 0 time and daily for 4 days. Brains were collected at 96 hours, and aromatic amino acids in plasma and brains were measured by high-performance liquid chromatography. Throughout the experiment, plasma of animals in group A had significantly elevated Phe and reduced Tyr concentrations compared with control values; plasma concentrations in groups B and C were similar. In groups A and B, brain Tyr levels were 31% and 63% of control values, respectively. In group B, Glu(Tyr) was not detected in brains. These data suggest that supplementing current TPN mixtures with Glu(Tyr), which is stable in solution, can produce normal plasma Tyr concentrations and Phe/Tyr ratios and improve the supply of Tyr to the brain.

Daily profiles of plasma phenylalanine and tyrosine in patients with osteogenic sarcoma during treatment with high-dose methotrexate-citrovorum rescue.

Three adolescents and one child with osteosarcoma were studied during multiple courses of high-dose methotrexate, citrovorum factor rescue (HDMTX-CFR), with one adolescent treated intermittently over a period of 6 years. Plasma phenylalanine (Phe) and tyrosine (Tyr) were measured immediately before the infusion of MTX and then daily until serum MTX fell below 10(-7) M. At 24 hours, all showed marked increases in Phe and in the Phe/Tyr ratio. This suggests inhibition of dihydropteridine reductase (DHPR) which, in association with hepatic Phe hydroxylase, controls plasma concentrations of Phe. Inhibition of this enzyme system is not relieved by CFR. In the adolescent patients, although MTX levels in plasma declined steadily, Phe concentrations, which fell between 24 and 48 hours, rose to a new peak at 4-7 days. Possible reasons for this secondary increase are discussed. The patient with the longest exposure to HDMTX showed an increase in pretreatment Phe/Tyr ratios with time, suggesting damage to liver parenchymal cells not indicated by standard tests of liver function. Evaluation of plasma Phe during the course of HDMTX-CFR may permit assessment of intracellular concentrations of MTX or its metabolites in the liver without interference by CFR.

A simple method for detection of heterozygous carriers of the gene for classic phenylketonuria.

Plasma phenylalanine (Phe) and tyrosine (Tyr) concentrations were measured by high-performance liquid chromatography in arteriolar blood obtained by finger prick from 78 normal volunteers and 36 heterozygote carriers of phenylketonuria (PKU). Subjects were tested at midday, 3 to 4 hours after their breakfast. Values for the micromolar ratio of Phe/Tyr and Phe2/Tyr for control subjects fell below 1.2 and 80, respectively; values for all carriers of PKU were higher for one or both ratios. This method should be applicable to widespread screening of the general population for carriers of the gene for PKU.

Effect of hypoxic hypoxia on taurine concentrations in ventricles of mouse hearts.

The effects of hypoxic hypoxia on the concentration of taurine in right ventricles was studied in the hearts of male CF1 mice caged individually and maintained for 16 hr per day in a hypobaric chamber evacuated to an air pressure of 307 mm Hg. After 23 days hearts were excised and right and left ventricles were separated and lyophilized. Hematocrits in chamber animals were 77-82%, compared to 45-49% for control mice. Mean weights of right ventricles of animals from the chamber were 11.2 +/- 0.9, compared to control values of 7.0 +/- 0.4, mg dry weight. The mean dry weights of left ventricles in both groups of animals were the same. There were no significant differences in the nmoles taurine per mg day tissue in either heart chamber, with mean values +/- S.E.M. of 124.0 +/- 4.6 and 135.0 +/- 4.5 in right ventricles and 128.0 +/- 4.3 and 110.9 +/- 15.3 in left ventricles of experimental and control animals respectively. Thus, hypertrophy which results from hypoxia is not accompanied by increased concentrations of taurine in right ventricles.

Taurine in hearts and bodies of embryonic through early postpartum CF1 mice.

The hearts and remaining bodies of embryonic and fetal mice of known gestational age and of neonatal mice up to the age of 8.5 days were freeze-dried, weighed, and analyzed for the amino acid, taurine, by high performance liquid chromatography. Although cardiac taurine is only a small fraction of the taurine in the rest of the body in all animals studied, the concentration of taurine in the heart is similar to that in the rest of the body (40-45 nmole/mg freeze-dried wt) in embryos through Day 14.5 of gestation. Cardiac taurine concentration then begins to exceed that of the remainder of the body which gradually declines throughout the period studied. A doubling of cardiac taurine concentration is seen at birth (Day 19.5) when the cardiac to body taurine ratio rises markedly and is maintained at 2-4 throughout the period of observation. A maximum concentration of cardiac taurine (110 nmole/mg freeze-dried wt) is recorded 2.5 days after birth. The dramatic increase in cardiac taurine concentration at the time of birth follows the reported appearance in neonatal mouse hearts of adult levels of beta-adrenergic receptors and the increased work load of the heart.

Effect of methotrexate with 5-methyltetrahydrofolate rescue and dietary homocystine on survival of leukemic mice and on concentrations of liver adenosylamino acids.

We have increased significantly the survival time of DBA/2 mice bearing methionine-dependent L1210 or L5178Y leukemia cells by i.p. administration of lethal doses of methotrexate (five daily doses of 25 mg/kg body weight) followed by rescue with 5-methyl tetrahydrofolate (five daily doses of 20 mg/kg body weight). The mice were maintained on a semipurified choline- and cyst(e)ine-free diet containing 0.32% L-methionine. We further increased significantly the survival time of the treated animals bearing L5178Y cells, but not those bearing L1210 cells, by substitution of 0.86% DL-homocystine for the methionine in the diet. We have examined the effects of both diets in mice treated with methotrexate and 5-methyl tetrahydrofolate, singly and in combination, on the concentrations of S-adenosylmethionine and S-adenosylhomocysteine in the liver, a tissue highly active in the metabolism of these amino acids. The substitution of homocystine for methionine in the diet of untreated animals led to a significant increase in S-adenosylhomocysteine and decrease in S-adenosylmethionine in the liver, with a resultant profound decrease in the ratio of S-adenosylmethionine to S-adenosylhomocysteine which was not further altered significantly by administration of methotrexate.

Liquid-chromatographic direct determination of phenylalanine and tyrosine in serum or plasma, with application to patients with phenylketonuria.

With this method, picomole amounts of phenylalanine and tyrosine can be rapidly separated and directly measured by absorbance at 206 nm. As little as 25 microliters of serum or plasma suffices. Plasma is deproteinized and 20 microliters of the supernate, representing 1.8 microliters of plasma, is applied to a reversed-phase column and eluted isocratically with a solution containing methanol and H3PO4, pH 2.4. The tyrosine and phenylalanine peaks appear at 6 and 10 min, respectively. We used the method to measure phenylalanine in plasma from six children with phenylketonuria.

Plasma phenylalanine: tyrosine ratios during high-dose methotrexate-citrovorum "rescue".

We have measured phenylalanine and tyrosine in the plasma of patients with osteogenic sarcoma undergoing chemotherapy with high-dose methotrexate (HDMTX) citrovorum factor rescue (CFR). During 14 treatments in six different patients, the phenylalanine to tyrosine ratio (PHE/TYR) at 21 to 38 hours was elevated over pretreatment levels. The observed increase in plasma phenylalanine is attributed to inhibition by MTX of the phenylalanine hydroxylase system of the liver, which is not folate-dependent and thus is not corrected by administration of CV. A post-infusion increase in PHE/TYR of 571% after 22 hours in one patient and of 410% after 30 hours in another were associated with marked MTX toxicity. The greatest increase in PHE/TYR seen in a patient who did not experience toxicity was was 249% in 21 hours. Thus, in this group of patients, there appears to be a correlation between evidence of clinical MTX toxicity and the magnitude of the percentage increase in PHE/TYR in the plasma, which indicates inhibition of a liver enzyme and thus reflects the intracellular concentration of MTX.

Changes in concentrations of taurine in murine Harderian glands and retinas during postnatal development.

Quantitative measurements of taurine in the Harderian glands of male and female CF-1 mice were made by standard methods of amino acid analysis. Values, in nmoles per mg dry weight of gland, were 60 to 70 in the first 4 postnatal days with a gradual decrease to 31.1 +/- 3.5 at 12 days, just prior to eye opening. This was similar to the value of 27 +/- 1 observed in sexually mature males, 53 days old. Two to 11 animals were used to establish each value. Other free amino acids in the glands are present in much lower concentrations, difficult to quantitate. Comparisons of the nmolar concentrations of taurine in dry retinas and Harderian glands from the same animals revealed two to three fold higher concentrations in the retina until the time of eye opening, after which concentrations increased markedly to greater than 160 nmoles per mg dry retina at 16 days and older.

An amino acid diet supporting superior growth in mice.

A diet containing, as a source of nitrogen, a mixture of purified L-amino acids simulating the amino acid composition of a successful diet containing vegetable and milk proteins was fed to mice in a 3% agar gel. This diet, at 17% amino acids, supported better growth of young male animals during a 21-day period than did the same assortment of amino acids at 23% of the diet, a commercial mouse food or the same basic diet containing a different assortment of amino acids from a published diet developed for rats. Cystine was removed from the diet, which contained 0.317% methionine and no choline, and this diet, fed for 52 days, continued to support growth and produced no microscopic evidence of fatty liver.