Biomedical subjects
Publications and source records attributed to L Kramer.
A pre-term baby girl presented at birth with respiratory distress and pleural effusion on the left. A soft tissue mass was found via lateral x-ray and CT scan; the mass proved to be extralobar pulmonary sequestration.
The widespread opinion that both protein and phosphorus cause calcium loss is examined. Controlled human studies show that commonly used complex dietary proteins, which have a high phosphorus content, do not cause calcium loss in adult humans. Similarly, a phosphorus intake of up to 2000 mg/d does not have adverse effects on calcium metabolism; however, the type of phosphate contained in carbonated beverages may not behave in the same manner. In contrast, a diet low in protein and phosphorus may have adverse effects on calcium balance in the elderly. Studies with adults suggest that high protein foods do not cause calcium loss.
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Pharmacologic doses of zinc are widely used as zinc supplements. As calcium and zinc may compete for common absorption sites, a study was carried out on the effect of a pharmacologic dose of zinc on the intestinal absorption of calcium in adult males. The analyzed dietary zinc intake in the control studies was normal, averaging 14.6 mg/day. During the high zinc study, 140 mg zinc as the sulfate was added daily for time periods ranging from 17 to 71 days. The studies were carried out during both a low calcium intake averaging 230 mg/day and during a normal calcium intake of 800 mg/day. Calcium absorption studies were carried out during the normal and high zinc intake by using an oral tracer dose of Ca47 and determining plasma levels and urinary and fecal excretions of Ca47. The study has shown that, during zinc supplementation, the intestinal absorption of calcium was significantly lower during a low calcium intake than in the control study, 39.3% vs 61% respectively, p less than 0.001. However, during a normal calcium intake of 800 mg/day, the high zinc intake had no significant effect on the intestinal absorption of calcium. These studies have shown that the high zinc intake decreased the intestinal absorption of calcium during a low calcium intake but not during a normal calcium intake.
A large percentage of subjects receiving a normal calcium intake of 800 mg per day was in negative calcium balance and increasing the calcium intake to various levels up to 2200 mg per day showed a plateau of the calcium balance at the 1200 mg per day intake, indicating a threshold of calcium absorption at this intake level. Dietary factors, such as a phosphorus intake up to 2000 mg per day and complex proteins, such as red meat, do not cause calcium loss. Several commonly used drugs induce significant calcium loss, particularly aluminum-containing antacids, and, if used for prolonged periods of time, can contribute to the development of osteoporosis.
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The effect of phosphorus on the endogenous fecal calcium excretion was investigated in man by administering tracer doses of 47Ca intravenously in control studies and during phosphorus supplementation. The phosphorus intake was approximately 800 mg/day in control studies and 2000 mg during phosphorus supplementation of the constant diet. The studies were carried out during different calcium intake levels of approximately 200, 800, 1300, 2000, and 2600 mg/day. Following the dose of 47CaCl2, the values of the plasma levels, urinary, and fecal excretions of 47Ca were used to calculate the endogenous fecal calcium. None of these values differed significantly during phosphorus supplementation from those in corresponding control studies, irrespective of the calcium intake. During addition of phosphorus to the different calcium intakes, a consistent finding was a significant decrease of the urinary calcium and a slight, but not significant increase of the fecal calcium except during the 800 mg calcium intake.
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A rapid reproducible technique for measuring antihistone antibodies is described in which unfractioned nuclear histones covalently bonded to plastic discs are employed in an ELISA system. All 20 patients with drug induced lupus erythematosus had antihistone antibodies, usually at high titer. In contrast, 22% of 18 asymptomatic patients with drug induced antinuclear antibodies (ANA), 15% of 20 patients with seropositive RA and 42% of 60 patients with systemic lupus erythematosus (SLE) had detectable antihistone antibodies. High titers of antihistone antibodies were not seen in drug induced ANA or RA. This assay differentiates between patients with drug induced lupus and drug induced ANA (p less than 0.01) and drug induced lupus erythematosus and SLE (p less than 0.01). In patients with SLE antihistone antibodies had no association with disease activity.
Studies carried out under strictly controlled conditions during different calcium intakes in adult males have shown that the average calcium balance was only slightly positive (+22 mg/day) during a calcium intake of 800 mg/day, the recommended dietary calcium intake, not taking into consideration dermal losses of calcium. During this calcium intake, the calcium balances were negative in 34% of the subjects studied. Increasing the calcium intake to 1200 mg/day resulted in a significant increase of the calcium balance; further increases to different intake levels up to 2300 mg/day did not improve the calcium balance further. Increasing the phosphorus intake up to 2000 mg/day as well as increasing the protein intake from 1 g/kg body weight to 2 g/kg, given as meat, did not have an adverse effect on calcium metabolism. A variety of drugs, notably aluminum-containing antacids, induced calcium loss. Increasing the calcium intake more than 10-fold from 200 to 2500 mg/day did not lower the blood pressure in a large number of normotensive patients and in a small number of hypertensive patients studied.
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A gradual loss of bone occurs with age. There are indications in the literature that not only calcium but also fluoride may play an important role in maintaining the bone mass. In view of the high incidence of osteoporosis and its complications, and in view of the fact that fluoride is beneficial for the treatment of osteoporosis, studies have been carried out in this research unit to determine the retention and excretion of fluoride both during a normal dietary intake of fluoride and during fluoride supplementation. Another problem to be examined was to delineate whether certain substances interfere with the intestinal absorption of fluoride and of calcium. One such substance is aluminum contained in commonly used antacids. The use of small amounts of aluminum-containing antacids increased fecal fluoride significantly, thereby decreasing the intestinal absorption of fluoride. In addition, the small doses of aluminum-containing antacids also affected the metabolism of calcium and phosphorus, the primary effect being complexation of phosphorus in the intestine leading to phosphorus depletion. This change in phosphorus metabolism was associated with an increase of the urinary and fecal calcium excretion resulting in a negative calcium balance. The dual effect of aluminum, namely in causing calcium loss and inhibition of the intestinal absorption of fluoride, can result in adverse effects on bone which may contribute to bone loss.
Clinical and pathologic findings in a 65-year old woman with fever of unknown origin are described in this report. Generalized aspergillosis with endocarditis was demonstrated at autopsy. The patient had no recognized risk factors for the development of fungal infection. A functional transvenous pacemaker lead, inserted 2 years previously, was completely encased in a large infected thrombus and may have been the initial site of infection. Septicemia and endocarditis are rare but well-described complications of cardiac pacing, and should be considered in the differential diagnosis of fever of unknown origin in patients with pacemakers.
The effect of calcium on phosphorus metabolism was studied in adult males by determining phosphorus and calcium balances during three calcium intakes of approximately 200, 800, and 2000 mg/day. Each of these calcium intakes were given during two intake levels of phosphorus of approximately 800 and 2000 mg/day. In all studies, the addition of different amounts of calcium led to a significant decrease of the urinary phosphorus, a significant increase of the stool phosphorus, and significant improvement of the phosphorus balance irrespective of the phosphorus intake. Only in one study in which the calcium intake was increased from 230 to 831 mg/day during the high phosphorus intake of approximately 2000 mg/day were these changes not significant. During all calcium intakes, the decrease in urinary phosphorus was greater than the increase in stool phosphorus irrespective of the phosphorus intake. The apparent absorption of phosphorus decreased on increasing the calcium intake. The calcium balance was not adversely affected by increasing the phosphorus intake to 2000 mg/day during any of the calcium intakes.
Calcium and phosphorus have been shown to inhibit the availability of zinc for absorption in animal studies, but limited information is available on this subject in man. In the present study, the effect of both calcium and phosphorus on zinc metabolism was investigated in adult men by determining metabolic balances of zinc during three intake levels of calcium of 200, 800, and 2000 mg/day, and during two intake levels of phosphorus of 800 and 2000 mg/day. The analyzed dietary zinc intake was normal and was kept constant throughout all study phases. Increasing the calcium intake from 200 mg to two higher intake levels up to 2000 mg/day did not significantly change the urinary or fecal zinc excretions or the zinc balance. Also, increasing the phosphorus intake from 800 to a high intake of 2000 mg/day did not have any effect. The simultaneous use of the high calcium and high phosphorus intake also had no effect on zinc excretions and on the zinc balance.
Presently submitted and previously available data indicate that the recommended calcium requirement of 800 mg/day is inadequate for a large segment of the population, particularly the elderly. With an intake of 800 mg of calcium/day, calcium balance was only slightly positive, without consideration of dermal losses or other risk factors that may play a role in calcium bioavailability and calcium retention. A calcium intake of 1000-1200 mg/day is preferable, as calcium balance increased significantly when calcium intake was increased from 800 to 1200 mg/day; there was no further improvement in calcium balance on higher calcium intakes, up to 2300 mg/day.
Multiple forms of treatment are used for osteoporosis, Paget's disease of the bone, and osteogenesis imperfecta. Because of the effect of fluoride (F) on bone, these bone conditions may benefit from F therapy. In the present study, the metabolic effects of two dose levels of F (20 and 45 mg, given as sodium fluoride) were studied on calcium (Ca) and F metabolism in patients with osteoporosis, whereas the effect of the 45-mg dose was studied in patients with Paget's disease. In patients with osteoporosis, the retention of F increased with increasing F intake, indicating F deposition in bone. However, only the 45-mg dose decreased urinary Ca excretion. F did not decrease fecal Ca excretion, indicating that the intestinal absorption of Ca did not improve during F therapy. This was confirmed in 47Ca absorption studies. The duration of F therapy was 3 months, utilizing the 45-mg dose. Clinically, the patients experienced relief of bone pain, and the onset of this change coincided with the decrease in urinary Ca. The 3-month course of treatment was sufficient for alleviation of clinical symptoms for many months and even years. In patients with Paget's disease, F supplements decreased urinary Ca and also resulted in relief of bone pain. F therapy for osteogenesis imperfecta resulted in decreased fracture incidence.