Nachman Brautbar

Interactions between Vitamin D Deficiency and Phosphorus Depletion in the Rat

To evaluate the role of vitamin D in the physiologic response to phosphorus depletion (P depleton) and the response to vitamin D administration in P depletion, we studied vitamin D-deficient (-D) rats, fed either a normal or low phosphorus diet and then injected intraperitoneally on alternate days with replacement vitamin D(3), 1.25 mug qod (D(3)); 1.25-dihydroxy-vitamin D(3)[1,25(OH)(2)D(3)] in physiologic, 54 ng qod (LD), and pharmacologic doses, 400 ng qod (HD); or vehicle alone (-D). The following results were obtained: (a) With P depletion, urinary excretion of inorganic phosphorus (Pi) fell to almost undetectable levels in -D rats, and two physiologic features of P depletion a calcemic effect and hypercalciuria, ensued. (b) With administration of vitamin D(3) or 1,25(OH)(2)D(3) in either doses to P-depleted rats, the renal retention of Pi was unaltered despite a significant elevation of serum Pi. (c) The calcemic response to P depletion was accentuated by vitamin D sterols, and the hypercalciuria of P depletion was reduced by 1,25(OH)(2)D(3), HD > LD > D(3). (d) In -D animals receiving normal Pi (+P), D(3), and 1,25(OH)(2)D(3), both LD and HD produced a significant calcemic and phosphatemic effect. (e) Urinary Pi excretion in +P animals was reduced slightly by vitamin D(3) whereas 1,25(OH)(2)D(3), both LD and HD, lowered urinary Pi markedly despite an increased serum Pi. (f) The serial values of serum Ca and Pi and urinary Ca in PD rats and the sequential values for urinary and serum Pi in +P rats indicated more rapid effects of 1,25(OH)(2)D(3), both HD and LD, compared with D(3). We conclude that: (a) The renal adaptation and physiologic response to PD does not require the presence of vitamin D. (b) 1,25(OH)(2)D(3) may directly enhance the renal tubular reabsorption of Pi even as serum Pi rises. (c) A hypocalciuric action of 1,25(OH)(2)D(3) in rats on low phosphorus diet could be direct or occur as a consequence of an increase in serum Pi produced by 1,25(OH)(2)D(3). The different sequential renal response to D(3) compared with 1,25-(OH)(2)D(3) raises the possibility that other natural forms of vitamin D(3) [i.e., 25(OH)D(3), 24,25(OH)(2)D(3), etc.] which may be present in vitamin D-fed rats but not those given only 1,25(OH)(2)D(3), could modify the actions of 1,25(OH)(2)D(3).

Phosphine toxicity: report of two cases and review of the literature.

Aluminum phosphide is a commonly used fumigant in the agricultural community. This article reviews the toxic effects of phosphine on the lungs and central nervous system in two workers and reviews the available scientific literature. Education for prevention of exposure and more frequent monitoring for exposure are recommended.

Hemodialysis Hypoxemia: Evaluation of Mechanisms Utilizing Sequential Ultrafiltration-Dialysis

We studied the role of blood-dialyzer-membrane interactions in hemodialysis-induced hypoxemia by measuring PaO2 and white blood cell counts during isolated ultrafiltration (UF). These values were compared to those obtained from the same patients during subsequent hemodialysis (HD; utilizing the same dialyzer and membrane). Patients in the UF period displayed no hypoxemia, rather a slight increase in PaO2 (from 82.5 +/- 3.0 to 88.5 +/- 2.0 mm Hg, mean +/- SE, p greater than 0.05). In contrast, these patients displayed significant hypoxemia when HD was imposed (88.5 +/- 2.0-78.0 +/- 1.5 mm Hg, mean +/- SE, p less than 0.02). We suggest that the hypoxemia characteristic of HD initiation is not solely dependent on blood-dialyzer-membrane interactions, but also requires blood-dialysate interactions.

Role of growth hormone in experimental phosphorus deprivation in the rat

SummaryThe demands of growth are known to exacerbate the effect of phosphorus deprivation (PD). We examined whether changes associated with PD could be prevented in young rats in which growth and growth hormone (GH) were eliminated by hypophysectomy (HPX) and whether PD in normal intact rats (INT) was associated with increased secretion of GH. INT or thyroxine- and ACTH-replaced HPX rats were fed one of the three diets: 0.31% P (NP); 0.027% P (LP), and 0.31% P, pair-fed with LP-mates (NP-PF). The results indicate that HPX did not qualitatively alter several physiologic responses to PD: (a) serum and urinary phosphorus (P) decreased and urinary calcium (Ca) increased; (b) net intestinal Ca retention fell and duodenal sac uptake of45Ca rose; and (c) external P balance was restored and duodenal sac uptake of32P-phosphate increased. Only the hypercalcemia seen in INT, LP rats was prevented by HPX. In INT rats serum immunoassayable GH levels, measured in single samples, were not different between different dietary groups while pituitary bioassayable GH was reduced in both LP and NP-PF rats when compared to the NP rats. Thus, except for hypercalcemia, the physiologic responses associated with PD are not prevented by the elimination of growth and GH, and the development of these responses in INT rats was not associated with a consistent or specific alteration in GH secretion.

AMMONIA EXPOSURE : A COMMON CAUSE FOR SINUSITIS A CASE REPORT AND REVIEW OF THE LITERATURE

Sinuses are a part of the upper respiratory system and sinusitis has been well-defined as an inflammation of the mucous membrane. Sinusitis occurs commonly as a result of allergies, polyps, common cold and environmental pollution. Reports of sinusitis secondary to ammonia exposure, while common clinically from a reporting point of view, have not been described extensively in the literature. We describe here a patient who was exposed to ammonia gas and developed chronic relapsing sinusitis. The mechanism of injury and review of the world literature indicate that although common clinically, chronic sinusitis as a result of ammonia exposure has not been described extensively.

Hydroquinone, a benzene metabolite, and leukemia: A case report and review of the literature

Hydroquinone is a phenolic metabolite of benzene, a known human carcinogen. Hydroquinone is widely used in the industry. We report a case of a 43-year-old male diagnosed with antecedent myelodysplastic syndrome and acute myeloid leukemia following 16 years of occupational exposure to hydroquinone in radiographic developer solution. Cytogenetic studies revealed aberrations in chromosome 5 and chromosome 7. We review the literature on hydroquinone as a potential cause of hematolymphatic cancers and discuss the role of hydroquinone as a genotoxic and leukemogenic agent.

How Can the Care of Elderly Dialysis Patients Be Improved

Thus, there is ethical support for the use of the scientific method: testing the hypothesis of benefit to be derived from dialysis for a specific patient, while reserving the right to discontinue the experiment or treatment if it proves not to be beneficial or if, in the value judgment of the patient or those speaking for the patient, the burdens of the treatment outweigh the benefits. To the extent that there is open communication from the beginning of treatment between the dialysis team and the patient (and/ or family or representative) and that the team is prepared to respect the wishes of the patient or representative (and understands that the most authentic and accurate judge of the patient’s “quality of life” is the patient himself or herself), the level of care for, and the satisfaction of, elderly ESRD patients can be enhanced. It can be psychologically stressful for dialysis team members (as well as for patients and patients’ families and significant others) to stop dialysis and allow the elderly patient to die, which is why all three groups must be supported if such a decision is reached. This approach, endorsed by Rubin (l), has also found support in the medical (7, 8) and nursing (9) literature, and suggests the wisdom of marrying the existing concept of a liberal policy of accepting elderly or diabetic patients for dialysis with an equally liberal policy of discontinuing treatment at the request of a patient or the family or representative of a patient who lacks decision-making capacity

REACTIVE AIRWAY DISEASE IN PATIENTS WITH PROLONGED EXPOSURE TO INDUSTRIAL SOLVENTS

This study examines the effects of volatile organic compounds (VOCs) at the workplace on pulmonary function tests. Forty-two patients with a history of industrial exposure to organic solvents and pulmonary symptomatology were studied. Lung function tests were determined utilizing screening spirometry lung volumes, diffusion capacity and methacholine stimulation test. While only 10-15% of the symptomatic patients had abnormal screening spirometry, 42% of the patients had significantly abnormal methacholine stimulation tests. These data show that exposure to volatile organic solvents is associated with bronchial hyperreactivity not commonly detected by screening spirometry and requires methacholine stimulation testing in individuals with unexplained symptomatology and history of exposure to industrial solvents. These findings indicate that the incidence of bronchial hyperreactivity is underestimated in patients with (1) verifiable exposure history to volatile organic compounds known to be pulmonary irritants, (2) pulmonary symptomatology with normal screening spirometry.

Rapid Hypertensinogenic Effect of Lead: Studies in the Spontaneously Hypertensive Rat

Chronic lead exposure may cause hypertension in normotensive rats. This hypertensinogenic effect has been attributed to perturbations in the renin-angiotensin axis, the contractile resporase of the vascular smooth muscle, or the intracellular Ca2+ homeostasis as a consequence of the inhibition of Na+-K+-ATPase activity. In this study we examined the short-term effect of lead exposure on blood pressure, plasma renin activity, vascular contractility, and renal Na+-K+-ATPase activity and abundance in the spontaneously hypertensive rat. Our data indicate that modest lead exposure caused blood pressure elevation within two weeks in this rat strain that is genetically susceptible to the development of hypertension. This rapid blood pressure-elevating effect did not appear to depend on the mechanisms described in hypertension associated with more chronic lead exposure listed above. This acute model provides an additional approach to the study of lead-induced hypertension.

Comments on: Brautbar, N. and Howard, J. 2002: Phosphine toxicity: report of two cases and review of the literature. Toxicology and Industrial Health 18, 71-75.

Sir ¡/ A paper authored by Brautbar and Howard (2002) involving two case study reports on adverse human health effects they attribute to phosphine exposure was recently brought to our attention. We wish to point out that the adverse effects attributed to phosphine are not consistent with the available literature on the toxicity of phosphine. The paper contains a number of mis-statements regarding the hazards of phosphine, some resulting from reliance on a NIOSH Alert (1999) which contains errors, and others resulting from an incomplete review of the literature which led to some erroneous conclusions by the authors. With respect to the NIOSH Alert, more detailed and accurate summaries of the hazards of phosphine are presented in US Environmental Protection Agency documents (US EPA, 1998; 1999). The literature review of the authors inexplicably missed previously published papers resulting from EPA reregistrations of phosphinegenerating products (Newton et al ., 1993; 1999; Schaefer et al., 1998). EPA required these studies due to the high acute inhalation toxicity of phosphine. These products are carefully regulated by EPA’s Office of Pesticide Programs. The first case report describes both short term and long lasting symptoms following an exposure of about 30 minutes to an estimated maximum phosphine concentration of 242 ppm. The patient reported an itching, burning sensation over exposed areas of her skin along with other short term symptoms lasting for only about four days. Neurological signs and symptoms lasting at least six months were also reported. Fumigators frequently receive dermal exposures to high concentrations of phosphine while wearing respiratory protection. Itching or burning of the skin has not been reported. Also, phosphine and aluminium phosphide have very low dermal toxicity (Pharmatox GmbH, 1997). Schaefer and coworkers (1998) reported no long lasting neurotoxic effects in rats exposed to phosphine by inhalation for four hours at levels up to 40 ppm. While rats are not humans, both are mammals and the toxic effects from phosphine inhalation exposures have been shown to be remarkably similar across several species of animals (Sciences International, Inc. 2000; Pepelko et al., 2003), suggesting that rats should have exhibited neurotoxic effects if they occur in humans. Also, 242 ppm is higher than 40 ppm; however, it has been demonstrated that the product of concentration (C) and time (T) for phosphine exposure to produce lethality is a constant (Newton et al., 1993; 1999; Schaefer et al., 1998; Sciences International, Inc. 2000; Pepelko et al ., 2003). Therefore, 40 ppm over four hours equates to a CxT of 160 ppm-hours and 242 ppm over 12 hour equates to a CxT of 121 ppm-hours, both being very similar exposures. It is interesting to note that the literature suggests that a CxT of 180¡/190 ppm-hours produces lethality in animal models (Newton et al., 1993; Schaefer et al., 1998). Again, the claimed long lasting neurotoxic effects in humans in this paper should have been observed in rats for the stated human neurotoxic effects to be more credible. The second case report involved exposure to a gas having an odour described as a fruity, sweet smell. The victim subsequently experienced itching and throat and nasal irritation, had trouble sleeping the night of the exposure and later experienced severe difficulty in breathing and pressure in the chest. About one and a half months later, he complained of shortness of breath, headaches, Toxicology and Industrial Health 2002; 18: 361¡/364