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J L Caddell

Publications and source records attributed to J L Caddell.

At least 19 recordsLinked to original sources
PubMed2001

Magnesium deficiency promotes muscle weakness, contributing to the risk of sudden infant death (SIDS) in infants sleeping prone.

A review was published (1991) of 19 retrospective case-control studies that had investigated the relationship between prone sleeping position (on the stomach) and the sudden infant death syndrome (SIDS). These studies, which had been conducted between 1965 and 1990 in New Zealand, Australia, England, France and the Netherlands, showed an overall higher rate of SIDS in infants who usually slept prone. In those countries, vigorous community intervention to change babies' sleep position away from the prone has resulted in marked declines of 50 per cent or more in the rate of SIDS. Such encouraging reports from many countries prompted the American Academy of Pediatrics to recommend that infants be placed to sleep on their backs to reduce the risk of SIDS. This was followed by a successful campaign in the United States between mid-1994 and 1998. Despite the decreased incidence, SIDS remains the leading cause of death in infants 1 month to 1 year of age of industrialized nations of the world. Studies have been conducted in human infants, mechanical models and animal models to learn the role of risk factors in prone sleeping infants. Soft bedding, thermal stress and biologic risk factors such as impaired ventilatory and arousal responsiveness are among many factors that have been investigated. Hunt states that there is not a single unifying factor that explains increased SIDS in prone sleeping infants. Two major studies conducted in the 1970s showed: (1) muscle weakness in the upper half of the body in infants who subsequently died of SIDS, and (2) shoulder hypotonia in near-miss for SIDS infants. An infant sleeping face-down in the prone position could be jeopardized if he lacked the muscle strength to shift his position or turn his head to rescue himself from a life-threatening situation. In contrast, recent studies in neonates sleeping in the prone position report that normal infants can spontaneously arouse and turn their heads. Some data support the hypothesis that magnesium deficiency contributes to SIDS. Muscle strength is seriously impaired in the young magnesium deficient subject, while magnesium rapidly reverses muscle weakness. In rats, marginal deprivation in dietary magnesium reduces exercise capacity, an early effect of magnesium deficiency which is preventable by consuming magnesium-enriched mineral water. It is concluded that magnesium deficiency is at least one major unifying factor that explains increased SIDS in prone sleeping infants.

Humans↗
PubMed2001

A triple-risk model for the sudden infant death syndrome (SIDS) and the apparent life-threatening episode (ALTE): the stressed magnesium deficient weanling rat.

A triple risk model for the sudden infant death syndrome (SIDS) as described by Filiano and Kinney involves the intersection of three risks: (1) a vulnerable infant, (2) a critical developmental period in homeostatic control, and (3) an exogenous stressor(s). The triple risk model aptly describes the dynamics of an animal model for SIDS: (1) a vulnerable animal that is young and magnesium deficient: (2) a critical developmental period revealed by hyperirritability, labile cardiovascular and respiratory control; and (3) an exogenous stressor such as soft, high-pitched noise; motion or handling; or a chill. Together these three risks may trigger a shock-like episode of apnea, unconsciousness and bradycardia. The lung is the shock organ. An animal that dies quietly or after physical activity following the episode, models SIDS. However, if the shock-like episode resolves spontaneously or after resuscitation, the survivor is a model for an apparent life-threatening episode (ALTE). If, while still in the critical developmental period the ALTE survivor is stressed again, there is a risk for a recurrent episode, with the final outcome still unpredictable but with increasing risk for SIDS with multiple recurrences. The purpose of this communication is to present an illustrated review of the magnesium deficient weanling rat as an animal model for SIDS/ALTE, showing pertinent physical, electrocardiographic and pathological features. In the weanling rat, magnesium deficiency appears to be the single common pathway upon which multiple stressors may impinge to produce sudden death during the relatively brief critical developmental period, while magnesium supplements may protect the animal. If significant magnesium deficiency is subsequently diagnosed in a properly controlled study of human SIDS tissue, it is likely that a high proportion of SIDS deaths could be prevented by simple oral magnesium supplementation to infants during the first critical weeks and months of life.

Animals↗
PubMed2001

The apparent impact of gestational magnesium (Mg) deficiency on the sudden infant death syndrome (SIDS).

Reports of studies in humans as well as data from several animal models show the importance of maternal dietary magnesium for the growth, development and survival of offspring. Published findings in mothers of victims of sudden infant death syndrome (SIDS) and in the SIDS victims are compared with characteristics of magnesium deficiency in humans and animals. Observations concerning the level of magnesium in traditional diets of selected ethnic groups with the highest or lowest rates of SIDS appear to confirm the importance of magnesium in protecting the offspring from sudden death. Ethnic groups with low SIDS rates at or below 1.2 per 1000 live births have rich dietary sources of magnesium, while those with SIDS rates exceeding 5.0 typically have magnesium-poor diets. Factors other than dietary magnesium are considered. Rat pups born and suckled by magnesium-sufficient dams have superior growth, development and survival, while those of deficient dams are feeble with impaired growth and development and have high perinatal mortality. In conclusion, these observations show that gestational magnesium deficiency results in suboptimal growth and development, with reduced survival of the offspring. Although the experimental data are compatible with a role for magnesium deficiency in SIDS, the cause of SIDS remains unknown and must be proved by appropriate biochemical analysis of tissue from SIDS infants compared with well-matched controls.

Animals↗
PubMed2000

A review of the status of magnesium and related minerals in the sudden infant death syndrome (SIDS).

Sudden infant death syndrome (SIDS) is the sudden death of an infant under 1 year of age that remains unexplained after a thorough case investigation, including performance of a complete autopsy. Despite recent reductions in the SIDS rate attributed to placing the baby to sleep on his back, SIDS remains the most common cause of infant mortality between 1 month and 1 year of age in developed countries. This review concerns the current state of a hypothesis (1972) that magnesium deficiency, which causes sudden death in young mammals, is the major cause of SIDS. Numerous investigators have compared the concentration of magnesium, and other minerals from soft tissues and bone in SIDS with non-SIDS controls (normal infants who died suddenly of known cause such as trauma). Because of rapid shifts of minerals during early development, SIDS and control infants must be matched for gestational and postnatal age. About 95 per cent of SIDS occurs between 1-6 months of life, with peak incidence at 2-4 months, when vitreous magnesium is high. There is little change in magnesium in the relatively inert vitreous despite extremes in dietary magnesium. All values fall within a small range, with scatter. Magnesium rapidly increases in foetal cartilage with ossification of the bone. Early in magnesium deficiency, liver magnesium may be increased or unchanged, but it does not increase during magnesium excess. Lead accumulation is increased in magnesium deficiency. Among infants with high environmental exposure to lead, those who die of SIDS rather than non-SIDS infants have the greater lead burden. Soft water with low magnesium and calcium and with high concentration of sodium have been linked to higher SIDS rates, which have been attributed to low magnesium. It is concluded that the SIDS hypothesis has neither been proved nor disproved.

Animals↗
PubMed1999

The possible role of magnesium in protection of premature infants from neurological syndromes and visual impairments and a review of survival of magnesium-exposed premature infants.

The survival rate of very preterm, low birth weight infants (weighing less than 1500 g) is 85 per cent in the USA and is ever increasing, while 42 to 75 per cent of extremely premature infants (weighing 751-1000 g) survive. Of great concern is the lack of consistent decrease in neurological syndromes and associated visual impairments. Because of short gestations, these infants have not had time to accrue up to 80 per cent of magnesium normally present at term. These very preterm infants are at highest risk for cerebral hypoxia/ischemia (H/I), intracranial hemorrhage (ICH), periventricular leukomalacia (PVL) or cystic PVL (CPVL), and possible sequelae, cerebral palsy (CP) and mental retardation (MR). These syndromes are associated with damage to optic structures and the visual pathways which traverse the brain. Visual defects are common in surviving preterm infants. Increased levels of harmful neurochemical mediators that have been reported in these conditions include oxygen free radicals, excitatory amino acids, tumor necrosis factor-alpha (TNF-a), and thromboxane A2 (TXA2) which are aggravated in magnesium deficiency and may be ameliorated by magnesium. We review the published data concerning the effects of prenatal magnesium supplementation on ICH, CPVL, CP and MR and available reports concerning survival. Further considerations on the safety and efficacy of magnesium sulphate administration given prenatally to the preterm neonate await the outcome of three trials that are continuing for more than a year on three continents.

Humans↗
PubMed1996

A review of evidence for a role of magnesium and possibly copper deficiency in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a neonatal disorder of unknown cause characterized by rapid necrosis of the bowel, primarily the ileum and colon. It is a worldwide problem. NEC is the most common gastrointestinal emergency in the neonatal intensive care unit, and ranks second as a cause of neonatal death. The incidence of NEC is inversely proportional to the birth weight and the degree of maturity. Infants born at or before 28 weeks gestational age have not received 80 per cent of the magnesium and 67 per cent of the copper found at term. Congenital deficiencies of these essential minerals may be compounded by high renal or gastrointestinal losses and high metabolic demand during the preterm infant's accelerated growth. Platelet thrombi appear early in the intestinal microvasculature in NEC. Platelet thrombosis and release of vasoconstrictor, platelet aggregating thromboxane A2 (TXA2) in human NEC appears to potentiate the intestinal ischaemia and necrosis in neonates who develop NEC. Magnesium and copper deficiency each enhance the synthesis of TXA2. Plasma levels of the inflammatory cytokines tumour necrosis factor (TNF) and interleukin-6 (IL-6) are increased in NEC and in magnesium deficiency; these experimentally produce shock and tissue injury, especially of the intestine. The synthesis of the potent vasoconstrictor endothelin is increased in magnesium deficiency. NEC has been regarded as a luminal insult that causes local generation of destructive oxygen free radicals. Tissues from animals deficient in magnesium are more susceptible to oxidative injury and lipid peroxidation than tissues from normal animals. Magnesium and copper deficiency impair antioxidant defence through decreased synthesis of glutathione and reduced activity of Cu/Zn superoxide dismutase, respectively. Although the aetiology of NEC is unknown, there appears to be sufficient data to implicate magnesium and possibly copper deficiencies in the pathogenesis. Consequences of deficiency of one or both minerals may include increased synthesis or activity of injurious mediators: IL-1, IL-6, TNF, TXA2, endothelin, and oxygen free radicals. A prospective trial of magnesium supplementation, but not copper supplementation, in very premature neonates can be recommended, with NEC as one of the outcome measures.

Copper↗
PubMed1996

Evidence for magnesium deficiency in the pathogenesis of bronchopulmonary dysplasia (BPD).

Bronchopulmonary dysplasia (BPD) has been defined as a requirement for oxygen for more than 28 days because of chronic pulmonary changes, usually in a premature infant. About 50 per cent of very low birth weight (VLBW) infants who weigh 1 kg at birth and who survive 28 days will develop BPD. Since 80 per cent of fetal accretion of magnesium occurs during the third trimester, this population is also at risk for magnesium deficiency. This paper reviews evidence for a role of magnesium deficiency in the pathogenesis of BPD. Pathology in BPD that may be caused or aggravated by magnesium deficiency is noted. Agents or mediators that are increased in BPD and in BPD include: oxygen free radicals; the inflammatory cytokines interleukin (IL)-1 and IL-6, and tumour necrosis factor-alpha; vaso- and bronchoconstrictors thromboxane A2 (TXA2) and serotonin: vasoconstrictor, endothelin-1 (ET-1); and bronchoconstrictor, histamine. Magnesium deficiency increases the susceptibility of cells and tissues to peroxidation, worsens the inflammatory reaction, reduces the immune response, exaggerates catecholamine release in stress, and diminishes energy metabolism. Possibly because of the danger of magnesium toxicity and the difficulty in studying the preterm VLBW neonate, little is known about magnesium supplementation in this group. Such information must be gained through controlled studies on the effect of antepartum exposure to maternally administered magnesium sulphate on the VLBW infant, through carefully monitored postnatal administration of magnesium in an intensive care setting, or through evaluations of combined pre- and postnatal supplementation.

Animals↗
PubMed1995

Hypothesis: the possible role of magnesium and copper deficiency in retinopathy of prematurity.

This hypothesis states that magnesium and copper (Cu) deficiency as well as high arterial oxygen pressure may contribute to the pathogenesis of retinopathy of prematurity (ROP), a major cause of blindness in very low birthweight preterm infants. Infants at highest risk have severe respiratory distress with hypoxia and require prolonged oxygen supplements. The retina is a multilayer sheet of neural tissue very rich in polyunsaturated fatty acids (PUFAs), oxygen, and mitochondria, with the highest oxygen consumption of all body tissues. Oxygen free radicals which are generated during metabolism cause lipid peroxidation of the PUFA-rich membranes, impairing retinal function. Magnesium and copper deficiencies provide less protection from oxidative injury which damages neurosensory tissue critical for photodetection. Protective antioxidant enzyme activity is reduced in magnesium and copper deficiency. There is some evidence for a raised level of vasoconstrictor thromboxane A2 (TXA2) in respect to vasodilator prostacyclin (PGI2), which would promote vasoconstriction. Deficiency of magnesium and of copper increase synthesis of TXA2 and decreases synthesis of PGI2. Sustained vasoconstriction leads to vascular occlusion, retinal ischaemia, reactive proliferation of retinal vasculature, and the final stages of ROP. Abundant magnesium and copper may protect the retina from developing ROP.

Copper↗
PubMed1993

Hypothesis: possible links between the respiratory distress syndrome of the premature neonate, the sudden infant death syndrome, and magnesium deficiency shock.

This hypothesis notes the similarities in the respiratory distress syndrome (RDS) of premature neonates, sudden infant death syndrome (SIDS) of postneonates, and the seizure-shock syndrome of acute magnesium (Mg) deficiency in stressed weanling animals, and suggests a common pathogenic link between the three. In each of these syndromes the lung is the major target organ, with haemorrhage, oedema, and microvascular congestion. It is suggested that platelet aggregation, leading to the transient release of mediators of shock, causes an acute, self-limited arachidonic acid cascade. The result of the shock is early death or spontaneous recovery with a propensity for recurrence; premature neonates who have had RDS are at particularly high risk for SIDS. Cases linking RDS and SIDS are cited.

Animals↗
PubMed1992

Hypothesis: new concepts concerning the pathophysiology of the sudden infant death syndrome due to magnesium deficiency shock.

There appear to be many contributing factors to sudden infant death syndrome (SIDS). One final common pathway that may explain some cases of SIDS is presented as a hypothesis: SIDS occurs as a shock-like event in a stressed infant with congenital or acquired magnesium deficiency with respect to calcium, or with genetically determined high magnesium requirements. Increased calcium and stress-related catecholamines favour platelet aggregation and release of mediators, chief of which appears to be thromboxane A2 (TXA2). TXA2, a major vasoconstrictor, bronchoconstrictor, and platelet aggregator is relatively unopposed during shock by prostacyclin, a vasodilator, bronchodilator, and platelet disaggregator which normally counterbalances its effects. The shock episode is self-limited. Infants who recover have suffered an apparent life threatening event (ALTE); those who die have insufficient pathology to explain the cause of death; the diagnosis is SIDS.

Humans↗
PubMed1989

Unreliability of plasma magnesium values in asphyxiated neonates.

The severely asphyxiated neonate usually shows a decreased blood pH and, if measured, a normal plasma Mg value. This is a retrospective review of the changes in these two parameters measured 2 or 3 times in 16 asphyxiated neonates as homeostasis was reestablished. The group was comprised of all asphyxiated neonates with 2 or 3 blood pH determinations, each with a plasma Mg determination within 6 h. Repeating these two tests had been prompted by poor clinical courses that suggested acid-base imbalance and Mg deficiency. The blood pH found on first sampling (day 0.42, with 0 the first day of life) was 7.24 +/- 0.02 (normal 7.35-7.45). This increased to 7.40 +/- 0.02 a mean of 2 days later (p less than 0.001 compared to first value by t test) and was still normal 4 days later (NS, compared to second value). The plasma Mg showed an opposing trend, with the first value 1.76 +/- 0.1 mEq/l (hospital normal 1.6-2.2 mEq/l); the second value 1.38 +/- 0.06 (p less than 0.004, compared to the first value), and the third, 1.30 +/- 0.11 (NS compared with the second value). It is concluded that plasma Mg determined during acidosis may give a falsely elevated value and may mask a true Mg deficiency which can be diagnosed only after homeostasis is reestablished, as when the blood pH is normal. While some asphyxiated infants were found to be hypomagnesemic, this study does not implicate Mg deficiency in meconium aspiration or any other cause of asphyxia.

Acidosis↗
PubMed1989

Validity of the parenteral magnesium load test for mature mammals.

Because of the difficulty in accurately assessing the Mg status of a hospitalized patient, the parenteral Mg retention test may be a valuable diagnostic tool. In former studies in animal models, this test has reliably identified adult rats fed two extremes of dietary Mg, but we found no tests of intermediate levels of Mg in adult animals. As a means of assessing the validity of the parenteral Mg retention tests in adult rats, the present study was conducted to learn (1) the relationship between Mg in plasma and bone in adult mammals that had optimal nutrition at the onset of the experiment, and (2) the relationship between Mg retention and Mg in plasma and bone in those animals. Animals were fed five levels of dietary Mg from 0 to 150 mg/100 g purified diet. Parenteral Mg retention tests were conducted after 2 weeks of dietary treatment, and 18 h after the completion of the tests, plasma and bone were analyzed for Mg. We found that plasma and femur levels of Mg varied linearly under conditions of Mg deficit, indicated by a high retention of the Mg load. As the deficit diminished, both plasma and femur levels approached a limit and the slope of the curve tends to zero. Mg retention and plasma or femur Mg level was approximated by a negative exponential curve. Stated another way, the logarithmic values of Mg retention decreased approximately linearly with increase in bone or plasma Mg. It was concluded that the parenteral Mg retention test is a valid test to evaluate Mg deficiency and to identify Mg sufficiency in adult mammals.

Animals↗
PubMed1988

Magnesium therapy in premature neonates with apnea neonatorum.

Apnea, bradycardia, and neuromuscular hyperirritability have been associated with magnesium (Mg) deficiency in young human infants and weanling animals. This is a retrospective review of a clinical experience of Mg therapy among 200 premature neonates who showed physical and clinical chemical changes compatible with Mg deficiency. The 200 infants all had idiopathic apnea neonatorum, and 93% also had the respiratory distress syndrome (RDS). This review was conducted to learn whether Mg therapy was associated with a significant reduction in apnea. The author suggested that the dose of Mg be 0.4 mEq/kg body weight/day, as 50% MgSO4.7H2O intramuscularly (IM) for 5 days; or as 1.0 mEq/kg/day, as 10% MgCl2.6H2O by mouth for 2 or more weeks, with appropriate monitoring of plasma Mg values in all infants. Sixty-one infants received a minimum of 5 days of Mg by either route (mean, 11.4 +/- 0.9, Group A); five received 3-4 doses IM (mean, 3.6 +/- 0.2, Group B); and 134 received 0-2 doses IM (0.5 +/- 0.1, Group C). Group A infants Mg-treated before Day 20 showed earlier cessation of apnea and bradycardia than those treated after Day 20. In Group A patients, 7 dose-days [corrected] of Mg therapy was associated with continuation of apnea; 14 dose-days [corrected], with cessation of apnea. Compared with Group A, Group C continued to develop apnea (P less than .003) and bradycardia (P less than 0.03) over longer periods of time. Group A infants showed no record of death or of hospital readmission for recurrent apnea, while 32 of 134 Group C infants had one or both of those unfavorable outcomes (P less than 0.001), with four of the five deaths in Group C (NS) as the sudden infant death syndrome (SIDS). In conclusion, Mg was associated with a reduction of apnea in this population. Emphasis was placed on the need to closely observe infants receiving supplementary Mg, with monitoring of plasma Mg levels.

Apnea↗
PubMed1988

Structural changes in lungs of magnesium-deficient weanling rats dying spontaneously or after spontaneous recovery from the seizure-shock episode. Possible methods for sudden infant death syndromes.

A light and electron microscopic study of Mg-deficient weanling rats showed structural changes of the lungs associated with the audiogenic seizure-shock episode, and with sudden, spontaneous death or spontaneous recovery after the shock episode. Pathogen-free weanling males were fed a Mg-deficient (Mg-0) or Mg-sufficient (Mg-100) diet and were raised in a gnotobiotic environment. Mg-100 rats (n = 16), unstressed or stressed with noise or strychnine, showed normal lungs. Mg-0 rats (n = 20) experienced audiogenic seizure-shock, followed by hyperventilation with tonic-clonic hyperextension of the back and extremities. The lungs of Mg-0 rats sacrificed during shock showed marked hemorrhage, including petechiae; edema; and atelectasis. Eight that died after a post-shock period of hyperventilation and hyperextension of the spine showed partial recovery of the pulmonary lesion; they showed well-expanded lungs, pleural petechiae, persistent congestion, with mild to moderate pathology. Mg-0 rats killed for study 2 days after the seizure-shock episode showed few small areas of residual lung pathology. Ultrastructural changes after Mg-O shock included aggregated platelets, leukocytes, and occasional reticulocytes in congested capillaries. Surfactant was disrupted during Mg-0 seizure-shock, but a layer closely applied to the surface of the epithelium was evident 2 days after shock. Mg-0 rats dying spontaneously showed nonspecific structural changes of the lung similar to changes reported in the sudden infant death syndrome (SIDS).

Acoustic Stimulation↗
PubMed1988

Magnesium therapy in infants with postneonatal apnea.

Idiopathic postneonatal apnea is defined here as a sudden, unexpected attack of apnea that first occurs after the infant has been discharged from the neonatal nursery to his home. Little has been published concerning the patient's physical and clinical laboratory findings during the acute episode. The present report of 20 infants with postneonatal apnea retrospectively addressed these parameters, including all investigations conducted for magnesium deficiency. The first episode of apnea occurred at 48 +/- 12.5 days of age and was unpredicted, transient, and self-limited. In the sickest infants, the apneic attack was a form of shock, with apnea, bradycardia, and often with acute respiratory distress, and/or neuromuscular hyperirritability. Laboratory findings in such infants were compatible with shock, including: acidosis, hemoconcentration, and hyperkalemia. Some infants showed high retention of parenteral Mg loads and received Mg therapy. Those receiving 5 or more days of Mg supplements were called 'Mg-treated'. Seven such patients were treated for 20.4 +/- 3.7 days. They were compared with 13 'Mg-untreated' patients who received less than 5 days of Mg therapy, 0.9 +/- 0.2 days. There was no known recurrence of apnea requiring resuscitation, or any rehospitalization for an apneic attack among the Mg-treated infants. Of the 13 Mg-untreated infants, 6 were readmitted for apnea at 90 +/- 37 days of age; 2 of these had a third admission for apnea. In conclusion, in its most severe form, postneonatal apnea is a shock-like episode that is self-limited, with a propensity to recur. Mg therapy appears to be associated with a reduction in recurrent apnea. This conclusion is corroborated by the significant reduction in recurrent apnea in the follow-up of a parallel study of 61 Mg-treated versus 139 Mg-untreated premature infants with idiopathic postneonatal apnea (p less than 0.001). Further study can be recommended.

Apnea↗
PubMed1987

Pulmonary lesion induced by stress in magnesium-deficient rats. A light- and electron-microscopic study.

A light- and electron-microscopic study was made of the lungs of magnesium (Mg)-sufficient and Mg-deficient pathogen-free weanling rats raised in a gnotobiotic environment. Mg-sufficient rats were studied unstressed, after mild auditory stress, or after strychnine seizures and showed essentially no pulmonary pathology. Mg-deficient rats were studied with no known seizures or immediately after audiogenic seizure-shock. Light microscopy of lung from Mg-deficient rats with audiogenic seizure-shock revealed atelectasis, generalized edema and hemorrhage, and pleural petechiae. Ultrastructural changes in lung alveoli of Mg-deficient rats with seizure-shock included gaps in capillary endothelium, swelling and separation of endothelial cells from the underlying basement membranes; Type I cell necrosis and separation from basement membranes; and intraalveolar red blood cells, fibrin, and precipitated plasma. The seizure-shock episode of acute Mg deficiency produces structural changes in the lung similar to changes produced by several forms of shock, early acute oxygen toxicity, and the respiratory distress syndrome (RDS) in human neonates.

Animals↗