- Email: [email protected]
Ingestion of antacid tablets (Rennie®) and acute confusion
The Journal of Emergency Medicine, Vol. 19, No. 2, pp. 169 –171, 2000 Copyright © 2000 Elsevier Science Inc. Printed in the USA. All rights reserved 0736-4679/00 $–see front matter
PII S0736-4679(00)00206-7
Selected Topics: Toxicology
INGESTION OF ANTACID TABLETS (RENNIE姞) AND ACUTE CONFUSION Dominique Vanpee,
MD,*
Etienne Delgrange, MD,† Jean-Bernard Gillet, and Julian Donckier, MD, PhD†
MD,*
*Department of Emergency Medicine and †Department of Internal Medicine, Universite´ Catholique de Louvain, Cliniques Universitaires de Mont-Godinne, Yvoir, Belgium Reprint Address: Dominique Vanpee, MD, Department of Emergency Medicine, Catholic University of Louvain, Mont–Godinne Hospital, B-5530 Yvoir, Belgium
e Abstract—The authors describe a case of milk-alkali syndrome in a man who consumed antacid tablets (Rennie®) for chronic epigastric pain. Simultaneous occurrence of hypercalcemia, metabolic alkalosis, and renal insufficiency, in conjunction with the appropriate history of ingestion of calcium carbonate-containing antacids, was suggestive of the syndrome. The syndrome became uncommon with the advent of modern ulcer therapy, but currently is increasing in frequency with the calcium supplementation drugs taken to prevent osteoporosis. This syndrome may produce life-threatening hypercalcemia. © 2000 Elsevier Science Inc.
mental status, becoming disoriented and so lethargic that he did not want to leave his bed. Vital signs were: blood pressure 120/80 mmHg, pulse 90 beats/min and regular, and respiratory rate 14 breaths/ min. The patient was afebrile, apathetic, and confused as to where he was and to the time of day. Cardiac examination revealed a grade 2/6 systolic murmur over the apex. The head, lungs, and abdomen were normal. The oral mucous membranes were dry. The muscle power of the extremities and the deep tendon reflexes were symmetrical but mildly diminished. Initial laboratory data revealed elevated serum creatinine (7.6 mg/dL) and serum urea nitrogen (295 mg/dL). Electrolyte results were: Na⫹ 140 mmol/L, K⫹ 3.4 mmol/L,Cl⫺ 98 mmol/L, and HCO3⫺ 27 mmol/L. The albumin, globulin, aspartate amino-transferase, alanine amino-transferase, alkaline phosphatase, and bilirubin were within the normal range. Room air arterial blood gas analysis showed: pH 7.43, PaO2 91 mmHg, PaCO2 38.6 mmHg. The admission electrocardiogram showed sinus rhythm and no QT prolongation. The chest X-ray study was normal. An abdominal X-ray series showed interstitial calcifications of the upper pole of the left kidney. Renal ultrasound showed normal-sized kidneys. The relative metabolic alkalosis despite severe renal failure prompted us to determine the serum calcium. It was elevated up to 14 mg/dL (normal range: 8.5–10.5). Phosphorus was 4.6 mg/dL (2.5– 4.6) and magnesium 2.6 mg/dL (1.5–2.6). Further pertinent laboratory data were
e Keywords— hypercalcemia; milk-alkali syndrome
CASE REPORT A 64-year-old man presented to the Emergency Department (ED) because of nausea, vomiting, and weakness of 1 week’s duration. He had also been confused for 3 days. The patient was known to have tonsil carcinoma 3 years previously as well as partial renal failure secondary to abuse of non-steroidal anti-inflammatory agents for headaches. The creatinine level was running about 1.7 mg/dL for 2 years. He also had a history of alcohol abuse that stopped 3 years before. He initially denied the use of any medication. The history given by the relatives revealed that three days earlier, the patient had a change in
RECEIVED: 1 October 1999; FINAL ACCEPTED: 3 April 2000
SUBMISSION RECEIVED:
25 February 2000; 169
170
D. Vanpee et al.
obtained including: intact parathyroid hormone 6.9 pg/mL (normal range: 10 –55), 25-hydroxyvitamin D3 18 ng/mL (10 – 40), 1–25 dihydroxyvitamin D3 2.8 pg/ml (18 – 45). The 24-h urinary excretion of calcium was 0.15 g with a clearance of creatinine of 22.4 mL/min. Urine and serum immunoelectrophoresis were normal. Skull and spine X-ray studies were normal. A bone scan showed no evidence of metastasis. The patient received intravenous (i.v.) saline and loop diuretics, resulting in a decrease in the serum calcium level and in a resolution of the confusional state. On further questioning, the patient reported that he had been taking antacid tablets (Rennie®) for chronic epigastric pain. Two weeks before admission to the ED, his consumption increased to 10 tablets a day (each of which contains 680 mg of calcium carbonate and 80 mg of magnesium carbonate). He was discharged 14 days after admission; serum creatinine level was 2.4 mg/dL and serum calcium was 8.7 mg/dL. The renal function remained stable without recurrence of hypercalcemia during follow-up (serum creatine 1.9 mg/dL, 2 years later).
DISCUSSION Alteration in serum electrolytes, principally such as hyper- or hyponatremia or hypercalcemia, can cause altered mental status or coma (1). This case illustrates the need for routine measurement of serum electrolytes in all patients with this neurologic presentation. The patient suffered from severe hypercalcemia with dehydration and renal failure. The relative alkalosis was unexpected. Differential possibilities included excessive vomiting, excessive alkali intake (milk-alkali syndrome), or diuretic therapy. Severe hypercalcemia is a life-threatening emergency requiring aggressive treatment. The clinical presentation and prognosis depend on the acuity of the development of hypercalcemia, the degree of hypercalcemia, and the underlying cause (2). Our patient had the classic features of the acute form of milk-alkali syndrome (MAS) (3–5). The simultaneous occurrence of hypercalcemia, metabolic alkalosis, and renal insufficiency, in conjunction with the history of excessive ingestion of calcium carbonate-containing antacids (Rennie®), was suggestive of the syndrome. These abnormalities reversed after appropriate treatment was administered and ingestion was stopped. More common causes of hypercalcemia, which must be excluded to confirm the diagnosis, were not found; there was no evidence of multiple myeloma, malignant tumors, or sarcoidosis. The parathyroid hormone level was suppressed, ruling out primary hyperparathyroidism. Vitamins A–D levels were normal.
The syndrome was originally reported as a triad of hypercalcemia, metabolic alkalosis, and renal insufficiency in a patient with peptic ulcer disease who ingested large amounts of calcium and absorbable alkali. It became rare with the advent of new therapeutic drugs for peptic ulcers and by 1985, milk-alkali syndrome caused less than 1% of hypercalcemia and was considered of historical interest only (6). Currently, milk-alkali syndrome is frequently found in women taking calcium carbonate for treatment or prophylaxis of osteoporosis (7). The symptoms of milk-alkali syndrome are usually related to the severity of the hypercalcemia, although some manifestations may result from renal dysfunction. The acute form of this syndrome has several biochemical alterations associated with the alkalosis, consisting usually of hypochloremia and occasionally hypokalemia (8). Hyperphosphatemia has been associated with renal dysfunction (9). Three forms of this syndrome have been described, all of which seem to be stages of the same condition (10,11). The acute syndrome is characterized clinically by irritability, weakness, myalgias, headache, nausea, and vomiting. With a continuing ingestion of calcium and alkali, other neurologic symptoms such as memory loss, lethargy, stupor, and coma become prominent and reflect the increasingly severe hypercalcemia (5). In addition to the acute syndrome described above, there is a subacute syndrome after intermittent, long-term milk-alkali treatment with additional features of conjunctivitis and occasional band keratopathy (Cope’s syndrome) (12). The chronic syndrome occurs after longterm absorption, with additional features of pruritus, and soft tissue calcifications including nephrocalcinosis. At this point, although symptoms might improve with treatment, renal function will continue to be at least partially impaired (Brunet’s syndrome) (13). The rapid reversal of hypercalcemia by the cessation of calcium intake in patients with a history of ingestion of calcium carbonate is also helpful to differentiate most cases of milk-alkali syndrome from other causes of hypercalcemia. The amount of ingested calcium carbonate necessary to develop milk-alkali syndrome has been reported to range from 4 to 60 g daily (10). Patients with pre-existing renal failure require less calcium carbonate to develop the syndrome than those with normal renal function (10). Patients and sometimes physicians are unaware of the calcium and alkali content of many nonprescription medicines. The diagnosis of MAS can be missed if a detailed history of such an intake is not realized. A detailed pharmacological history, including brand names of medicines and inspection of the ingredient lists, must be obtained in hypercalcemic patients due to the plethora of
Ingestion of Antacid Tablets and Acute Confusion
over-the-counter preparations that contain calcium carbonate (14). The pathophysiologic mechanisms of MAS are complex and interrelated (3,10). Each of the ingested ionic compounds, i.e., calcium and bicarbonate, serve to limit the excretion of the other. Renal function may be worsened by acute hypercalcemia, which can cause vasoconstriction, leading to a decrease in renal blood flow and glomerular filtration rate (3,15). The renal dysfunction of the MAS results from multiple factors: hypercalcemia can directly cause a decrease in glomerular filtration rate and creatinine clearance, and dehydration contributes to renal impairment. Hypercalcemia enhances bicarbonate absorption at the level of the proximal tubule, which predisposes the patient to metabolic alkalosis. It remains to be explained why only a small number of subjects develop these metabolic complications. There seems to be an individual hypersensitivity, excess of calcium by itself being insufficient to induce hypercalcemia. The symptomatic and biochemical recovery in milkalkali syndrome is usually prompt after cessation of calcium and alkali ingestion (16). Patients with lifethreatening hypercalcemia are rare, and their management should be directed toward rapid control of the hypercalcemia, and an early diagnosis of the cause. The mainstay of treatment of milk-alkali syndrome in general is vigorous replacement of fluids to correct the dehydration and to increase renal calcium excretion (5). Patients with this syndrome need at least 6 liters of fluid per day (5). Symptomatic improvement can be hastened with the administration of i.v. saline solution, which relieves volume contraction and increases calcium and bicarbonate excretion (10). Once the extracellular volume has been restored, a dramatic increase in urinary excretion of calcium and sodium will usually occur with the administration of a loop diuretic (furosemide) (5). The follow-up and the correction of the magnesium and potassium levels are important. More intensive treatment of hypercalcemia of milk-alkali syndrome is not necessary
171
and may be dangerous, leading to hypocalcemia (16). Hemodialysis may be needed in severely hypercalcemic, azotemic patients in a first episode (10).
REFERENCES 1. Riggs JE. Neurologic manifestations of fluid and electrolytedisturbances. Neurol Clin 1989;7:509 –23. 2. Edelson GW, Kleerekoper M. Hypercalcemic crisis. Med Clin North Am 1995;79:79 –92. 3. Newmark K. Nugent. Milk-alkali syndrome. A consequence of chronic antacid abuse. Postgrad Med 1993;93:149 –51. 4. Abreo K, Adlakha A, Kilpatrick S, Flanagan R, Webb R, Shakamuri S. The milk-alkali syndrome. A reversible form of acute renal failure. Arch Intern Med 1993;153:1005–10. 5. Jenkins JK, Best TR, Nicks SA, Murphy FY, Bussell KL, Vesely DL. Milk-alkali syndrome with a serum calcium level of 22 mg/dL and J waves on the ECG. South Med J 1987;80:1444 –9. 6. Jamieson MJ. Hypercalcaemia. Br Med J 1985;290:378 – 82. 7. Beall DP, Scofield RH. Milk-alkali syndrome associated with calcium carbonate consumption. Report of 7 patients with parathyroid hormone levels and an estimate of prevalence among patients hospitalized with hypercalcemia. Medicine 1995;74:89 – 96. 8. McMillan DE, Freeman RB. The milk alkali syndrome: a study of the acute disorder with comments on the development of the chronic condition. Medicine 1965;44:485–501. 9. Pusnar S, Somer T. The milk-alkali syndrome: a report of three illustrative cases and a review of literature. Acta Med Scand 1963;173:435– 49. 10. Orwoll ES. The milk-alkali syndrome: current concepts. Ann Intern Med 1982;97:242– 8. 11. Fiorino AS. Hypercalcemia and alkalosis due to the milk-alkali syndrome: a case report and review. Yale J Biol Med 1996;69: 517–23. 12. Cope CL. Base changes in the alkalosis produced by the treatment of gastric ulcer with alkalies. Clin Sci 1935–1936;2:287–300. 13. Burnett CH, Commons RR, Albright F, et al. Hypercalcemia without hypercalciuria or hypophosphatemia, calcinosis and renal insufficiency. N Engl J Med 1949;240:787–94. 14. Canning G, Slater SD. Failure to diagnose the milk-alkali syndrome. Scott Med J 1987;32:56 –7. 15. Humes HD, Ichikawa I, Troy JL, Anderson AJ, Brenner BM. Influence of calcium on the determinants of glomerular ultrafiltration. Trans Assoc Am Physicians 1977;90:228 –38. 16. Wu KD, Chuang RB, Wu FL, et al. The milk-alkali syndrome caused by betelnuts in oyster shell paste. J Toxicol Clin Toxicol 1996;34:741–5.
PII S0736-4679(00)00206-7
Selected Topics: Toxicology
INGESTION OF ANTACID TABLETS (RENNIE姞) AND ACUTE CONFUSION Dominique Vanpee,
MD,*
Etienne Delgrange, MD,† Jean-Bernard Gillet, and Julian Donckier, MD, PhD†
MD,*
*Department of Emergency Medicine and †Department of Internal Medicine, Universite´ Catholique de Louvain, Cliniques Universitaires de Mont-Godinne, Yvoir, Belgium Reprint Address: Dominique Vanpee, MD, Department of Emergency Medicine, Catholic University of Louvain, Mont–Godinne Hospital, B-5530 Yvoir, Belgium
e Abstract—The authors describe a case of milk-alkali syndrome in a man who consumed antacid tablets (Rennie®) for chronic epigastric pain. Simultaneous occurrence of hypercalcemia, metabolic alkalosis, and renal insufficiency, in conjunction with the appropriate history of ingestion of calcium carbonate-containing antacids, was suggestive of the syndrome. The syndrome became uncommon with the advent of modern ulcer therapy, but currently is increasing in frequency with the calcium supplementation drugs taken to prevent osteoporosis. This syndrome may produce life-threatening hypercalcemia. © 2000 Elsevier Science Inc.
mental status, becoming disoriented and so lethargic that he did not want to leave his bed. Vital signs were: blood pressure 120/80 mmHg, pulse 90 beats/min and regular, and respiratory rate 14 breaths/ min. The patient was afebrile, apathetic, and confused as to where he was and to the time of day. Cardiac examination revealed a grade 2/6 systolic murmur over the apex. The head, lungs, and abdomen were normal. The oral mucous membranes were dry. The muscle power of the extremities and the deep tendon reflexes were symmetrical but mildly diminished. Initial laboratory data revealed elevated serum creatinine (7.6 mg/dL) and serum urea nitrogen (295 mg/dL). Electrolyte results were: Na⫹ 140 mmol/L, K⫹ 3.4 mmol/L,Cl⫺ 98 mmol/L, and HCO3⫺ 27 mmol/L. The albumin, globulin, aspartate amino-transferase, alanine amino-transferase, alkaline phosphatase, and bilirubin were within the normal range. Room air arterial blood gas analysis showed: pH 7.43, PaO2 91 mmHg, PaCO2 38.6 mmHg. The admission electrocardiogram showed sinus rhythm and no QT prolongation. The chest X-ray study was normal. An abdominal X-ray series showed interstitial calcifications of the upper pole of the left kidney. Renal ultrasound showed normal-sized kidneys. The relative metabolic alkalosis despite severe renal failure prompted us to determine the serum calcium. It was elevated up to 14 mg/dL (normal range: 8.5–10.5). Phosphorus was 4.6 mg/dL (2.5– 4.6) and magnesium 2.6 mg/dL (1.5–2.6). Further pertinent laboratory data were
e Keywords— hypercalcemia; milk-alkali syndrome
CASE REPORT A 64-year-old man presented to the Emergency Department (ED) because of nausea, vomiting, and weakness of 1 week’s duration. He had also been confused for 3 days. The patient was known to have tonsil carcinoma 3 years previously as well as partial renal failure secondary to abuse of non-steroidal anti-inflammatory agents for headaches. The creatinine level was running about 1.7 mg/dL for 2 years. He also had a history of alcohol abuse that stopped 3 years before. He initially denied the use of any medication. The history given by the relatives revealed that three days earlier, the patient had a change in
RECEIVED: 1 October 1999; FINAL ACCEPTED: 3 April 2000
SUBMISSION RECEIVED:
25 February 2000; 169
170
D. Vanpee et al.
obtained including: intact parathyroid hormone 6.9 pg/mL (normal range: 10 –55), 25-hydroxyvitamin D3 18 ng/mL (10 – 40), 1–25 dihydroxyvitamin D3 2.8 pg/ml (18 – 45). The 24-h urinary excretion of calcium was 0.15 g with a clearance of creatinine of 22.4 mL/min. Urine and serum immunoelectrophoresis were normal. Skull and spine X-ray studies were normal. A bone scan showed no evidence of metastasis. The patient received intravenous (i.v.) saline and loop diuretics, resulting in a decrease in the serum calcium level and in a resolution of the confusional state. On further questioning, the patient reported that he had been taking antacid tablets (Rennie®) for chronic epigastric pain. Two weeks before admission to the ED, his consumption increased to 10 tablets a day (each of which contains 680 mg of calcium carbonate and 80 mg of magnesium carbonate). He was discharged 14 days after admission; serum creatinine level was 2.4 mg/dL and serum calcium was 8.7 mg/dL. The renal function remained stable without recurrence of hypercalcemia during follow-up (serum creatine 1.9 mg/dL, 2 years later).
DISCUSSION Alteration in serum electrolytes, principally such as hyper- or hyponatremia or hypercalcemia, can cause altered mental status or coma (1). This case illustrates the need for routine measurement of serum electrolytes in all patients with this neurologic presentation. The patient suffered from severe hypercalcemia with dehydration and renal failure. The relative alkalosis was unexpected. Differential possibilities included excessive vomiting, excessive alkali intake (milk-alkali syndrome), or diuretic therapy. Severe hypercalcemia is a life-threatening emergency requiring aggressive treatment. The clinical presentation and prognosis depend on the acuity of the development of hypercalcemia, the degree of hypercalcemia, and the underlying cause (2). Our patient had the classic features of the acute form of milk-alkali syndrome (MAS) (3–5). The simultaneous occurrence of hypercalcemia, metabolic alkalosis, and renal insufficiency, in conjunction with the history of excessive ingestion of calcium carbonate-containing antacids (Rennie®), was suggestive of the syndrome. These abnormalities reversed after appropriate treatment was administered and ingestion was stopped. More common causes of hypercalcemia, which must be excluded to confirm the diagnosis, were not found; there was no evidence of multiple myeloma, malignant tumors, or sarcoidosis. The parathyroid hormone level was suppressed, ruling out primary hyperparathyroidism. Vitamins A–D levels were normal.
The syndrome was originally reported as a triad of hypercalcemia, metabolic alkalosis, and renal insufficiency in a patient with peptic ulcer disease who ingested large amounts of calcium and absorbable alkali. It became rare with the advent of new therapeutic drugs for peptic ulcers and by 1985, milk-alkali syndrome caused less than 1% of hypercalcemia and was considered of historical interest only (6). Currently, milk-alkali syndrome is frequently found in women taking calcium carbonate for treatment or prophylaxis of osteoporosis (7). The symptoms of milk-alkali syndrome are usually related to the severity of the hypercalcemia, although some manifestations may result from renal dysfunction. The acute form of this syndrome has several biochemical alterations associated with the alkalosis, consisting usually of hypochloremia and occasionally hypokalemia (8). Hyperphosphatemia has been associated with renal dysfunction (9). Three forms of this syndrome have been described, all of which seem to be stages of the same condition (10,11). The acute syndrome is characterized clinically by irritability, weakness, myalgias, headache, nausea, and vomiting. With a continuing ingestion of calcium and alkali, other neurologic symptoms such as memory loss, lethargy, stupor, and coma become prominent and reflect the increasingly severe hypercalcemia (5). In addition to the acute syndrome described above, there is a subacute syndrome after intermittent, long-term milk-alkali treatment with additional features of conjunctivitis and occasional band keratopathy (Cope’s syndrome) (12). The chronic syndrome occurs after longterm absorption, with additional features of pruritus, and soft tissue calcifications including nephrocalcinosis. At this point, although symptoms might improve with treatment, renal function will continue to be at least partially impaired (Brunet’s syndrome) (13). The rapid reversal of hypercalcemia by the cessation of calcium intake in patients with a history of ingestion of calcium carbonate is also helpful to differentiate most cases of milk-alkali syndrome from other causes of hypercalcemia. The amount of ingested calcium carbonate necessary to develop milk-alkali syndrome has been reported to range from 4 to 60 g daily (10). Patients with pre-existing renal failure require less calcium carbonate to develop the syndrome than those with normal renal function (10). Patients and sometimes physicians are unaware of the calcium and alkali content of many nonprescription medicines. The diagnosis of MAS can be missed if a detailed history of such an intake is not realized. A detailed pharmacological history, including brand names of medicines and inspection of the ingredient lists, must be obtained in hypercalcemic patients due to the plethora of
Ingestion of Antacid Tablets and Acute Confusion
over-the-counter preparations that contain calcium carbonate (14). The pathophysiologic mechanisms of MAS are complex and interrelated (3,10). Each of the ingested ionic compounds, i.e., calcium and bicarbonate, serve to limit the excretion of the other. Renal function may be worsened by acute hypercalcemia, which can cause vasoconstriction, leading to a decrease in renal blood flow and glomerular filtration rate (3,15). The renal dysfunction of the MAS results from multiple factors: hypercalcemia can directly cause a decrease in glomerular filtration rate and creatinine clearance, and dehydration contributes to renal impairment. Hypercalcemia enhances bicarbonate absorption at the level of the proximal tubule, which predisposes the patient to metabolic alkalosis. It remains to be explained why only a small number of subjects develop these metabolic complications. There seems to be an individual hypersensitivity, excess of calcium by itself being insufficient to induce hypercalcemia. The symptomatic and biochemical recovery in milkalkali syndrome is usually prompt after cessation of calcium and alkali ingestion (16). Patients with lifethreatening hypercalcemia are rare, and their management should be directed toward rapid control of the hypercalcemia, and an early diagnosis of the cause. The mainstay of treatment of milk-alkali syndrome in general is vigorous replacement of fluids to correct the dehydration and to increase renal calcium excretion (5). Patients with this syndrome need at least 6 liters of fluid per day (5). Symptomatic improvement can be hastened with the administration of i.v. saline solution, which relieves volume contraction and increases calcium and bicarbonate excretion (10). Once the extracellular volume has been restored, a dramatic increase in urinary excretion of calcium and sodium will usually occur with the administration of a loop diuretic (furosemide) (5). The follow-up and the correction of the magnesium and potassium levels are important. More intensive treatment of hypercalcemia of milk-alkali syndrome is not necessary
171
and may be dangerous, leading to hypocalcemia (16). Hemodialysis may be needed in severely hypercalcemic, azotemic patients in a first episode (10).
REFERENCES 1. Riggs JE. Neurologic manifestations of fluid and electrolytedisturbances. Neurol Clin 1989;7:509 –23. 2. Edelson GW, Kleerekoper M. Hypercalcemic crisis. Med Clin North Am 1995;79:79 –92. 3. Newmark K. Nugent. Milk-alkali syndrome. A consequence of chronic antacid abuse. Postgrad Med 1993;93:149 –51. 4. Abreo K, Adlakha A, Kilpatrick S, Flanagan R, Webb R, Shakamuri S. The milk-alkali syndrome. A reversible form of acute renal failure. Arch Intern Med 1993;153:1005–10. 5. Jenkins JK, Best TR, Nicks SA, Murphy FY, Bussell KL, Vesely DL. Milk-alkali syndrome with a serum calcium level of 22 mg/dL and J waves on the ECG. South Med J 1987;80:1444 –9. 6. Jamieson MJ. Hypercalcaemia. Br Med J 1985;290:378 – 82. 7. Beall DP, Scofield RH. Milk-alkali syndrome associated with calcium carbonate consumption. Report of 7 patients with parathyroid hormone levels and an estimate of prevalence among patients hospitalized with hypercalcemia. Medicine 1995;74:89 – 96. 8. McMillan DE, Freeman RB. The milk alkali syndrome: a study of the acute disorder with comments on the development of the chronic condition. Medicine 1965;44:485–501. 9. Pusnar S, Somer T. The milk-alkali syndrome: a report of three illustrative cases and a review of literature. Acta Med Scand 1963;173:435– 49. 10. Orwoll ES. The milk-alkali syndrome: current concepts. Ann Intern Med 1982;97:242– 8. 11. Fiorino AS. Hypercalcemia and alkalosis due to the milk-alkali syndrome: a case report and review. Yale J Biol Med 1996;69: 517–23. 12. Cope CL. Base changes in the alkalosis produced by the treatment of gastric ulcer with alkalies. Clin Sci 1935–1936;2:287–300. 13. Burnett CH, Commons RR, Albright F, et al. Hypercalcemia without hypercalciuria or hypophosphatemia, calcinosis and renal insufficiency. N Engl J Med 1949;240:787–94. 14. Canning G, Slater SD. Failure to diagnose the milk-alkali syndrome. Scott Med J 1987;32:56 –7. 15. Humes HD, Ichikawa I, Troy JL, Anderson AJ, Brenner BM. Influence of calcium on the determinants of glomerular ultrafiltration. Trans Assoc Am Physicians 1977;90:228 –38. 16. Wu KD, Chuang RB, Wu FL, et al. The milk-alkali syndrome caused by betelnuts in oyster shell paste. J Toxicol Clin Toxicol 1996;34:741–5.