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Myelofibrosis and renal osteodystrophy
b
0‘
w
Renal osteodystrophy Bone and marrow disease Pancytopenia Fibrosis/Sclerosis
overdose
Hypoglycemia
Diazoxide
K cells
Cyclic
Skeletal
disease nucleotides
muscle
Carnitine Glucagon
deficiency
A patient with progressive skeletal muscle weakness had lipid-containing vacuoles in type I muscle fibers and partial carnitine deficiency of skeletal muscle. Results of certain liver function tests were abnormal, and the cyclic adenosine 3’,5’-monophosphate (cyclic AMP) response to glucagon was reduced. After the oral administration of prednisone, there was gradual but striking clinical improvement, skeletal muscle fiber vacuoles could no longer be demonstrated, and the glucagon-provoked cyclic AMP response reverted to normal, but liver abnormalities persisted and utilization by skeletal muscle of long-chain fatty acids, pyruvate and $-hydroxybutyrate was depressed. Involvement of skeletal muscles may have been due to an inability of carnitine to attach to or penetrate the sarcolemmal membrane. Some of the derangement was apparentiy COiie&d ;Y ihe Oial adiiiifiiSiaC%i of prednisone although ske!etaf musc!e metabolism remained impaired.
Whitaker JN, DiMauro S, Solomon SS, Sabesin S, Duckworth WC, Mendell JR: Corticosteroid-responsive skeletal muscle disease associated with partial carnitine deficiency. Studies of liver and metabolic alterations. Am J Med 63:805-815, 1977.
Liver abnormalities
Corticosteroids
Among the epithelial elements of the pulmonary airways are cells with features suggestive of endocrine function. Although these cells share a number of properties with the intestinal endocrine (argentaffine) cells, peptide hormones analogous to the multitude of those present in the gastrointestinal tract have yet to be identified in the lung. The oat cell carcinoma, which arises from this cell type is of importance clinically, yet investigations into the basic properties and functions of this cell have been difficult and sparse, in part due to a lack of appreciation of the problem.
Bonikos DS, Bensch KG: Endocrine cells of bronchial and bronchiolar epithelium. Am J Med 63: 765-771, 1977.
Endocrine cells Oat cell carcinoma Pulmonary airways cells of uncertain function
Continued on page A 107
A healthy adolescent boy was treated on two occasrons for an overdose of chlorpropamide (Diabinese’a). Glucose therapy alone was not sufficient to control the hypoglycemia, but the administration of glucose plus diazoxide raised the blood sugar to supranormal levels. A bolus of intravenous glucagon briefly raised the blood sugar level to within normal limits, increased the blood ketones but also augmented insulin secretion. An overdose of sulfonylurea may cause prolonged and fatal hypoglycemia. Rational therapy, both in diabetic and normal persons, is glucose plus an “insulin antagonist.” The administration of diazoxide was effective in our patient. substantially reducing ihe plasma insulin level: this agent may be the “insulin-antagonist” of choice for use in sulfonylurea-induced hypoglycemia.
Suc-
Glucose
Johnson SF, Schade DS, Peake GT: Chlorpropamide-induced hypoglycemia. cessful treatment with diazoxide. Am J Med 63: 799-804, 1977
Sulfonylurea
Chlorpropamide
Two groups of patients undergoing long-term dialysis, one with and one without pancytopenia, were compared. Marrow biopsy specimens compatible with renal osteodystrophy, but also suggesting replacement of functional marrow by fibrosis and sclerosis, were found in both groups. However, bone and marrow disease, as measured by serum parathyroid hormone and alkaline phosphatase, bone surveys and per cent fibrosis on marrow biopsy, tended to be more severe in the patients with pancytopenia than in the control group. A hypersplenic picture, defined by chromium-51 (!j’Cr) red blood cell survivals, was found only in cytopenic patients, Extramedullary hematopoiesis was present in two splenectomized patients. Of the patients without cytopenia, only those with significant marrow fibrosis and sclerosis had peripheral marrow expansion or, scan. The data suggest that myelofibrosis secondary to renal osteodystrophy is common, and that severity of marrow disease, and type and degree of response to marrow obliteration determine in part the success of hematologic compensation.
Weinberg SG. Lubin A. Wiener SN. Deoras MP, Ghose MK, Kopelman RC: Myelofibrosis and renal osteodystrophy. Am J Med 63: 755-764, 1977.
Myelofibrosis Dialysis
0‘
w
Renal osteodystrophy Bone and marrow disease Pancytopenia Fibrosis/Sclerosis
overdose
Hypoglycemia
Diazoxide
K cells
Cyclic
Skeletal
disease nucleotides
muscle
Carnitine Glucagon
deficiency
A patient with progressive skeletal muscle weakness had lipid-containing vacuoles in type I muscle fibers and partial carnitine deficiency of skeletal muscle. Results of certain liver function tests were abnormal, and the cyclic adenosine 3’,5’-monophosphate (cyclic AMP) response to glucagon was reduced. After the oral administration of prednisone, there was gradual but striking clinical improvement, skeletal muscle fiber vacuoles could no longer be demonstrated, and the glucagon-provoked cyclic AMP response reverted to normal, but liver abnormalities persisted and utilization by skeletal muscle of long-chain fatty acids, pyruvate and $-hydroxybutyrate was depressed. Involvement of skeletal muscles may have been due to an inability of carnitine to attach to or penetrate the sarcolemmal membrane. Some of the derangement was apparentiy COiie&d ;Y ihe Oial adiiiifiiSiaC%i of prednisone although ske!etaf musc!e metabolism remained impaired.
Whitaker JN, DiMauro S, Solomon SS, Sabesin S, Duckworth WC, Mendell JR: Corticosteroid-responsive skeletal muscle disease associated with partial carnitine deficiency. Studies of liver and metabolic alterations. Am J Med 63:805-815, 1977.
Liver abnormalities
Corticosteroids
Among the epithelial elements of the pulmonary airways are cells with features suggestive of endocrine function. Although these cells share a number of properties with the intestinal endocrine (argentaffine) cells, peptide hormones analogous to the multitude of those present in the gastrointestinal tract have yet to be identified in the lung. The oat cell carcinoma, which arises from this cell type is of importance clinically, yet investigations into the basic properties and functions of this cell have been difficult and sparse, in part due to a lack of appreciation of the problem.
Bonikos DS, Bensch KG: Endocrine cells of bronchial and bronchiolar epithelium. Am J Med 63: 765-771, 1977.
Endocrine cells Oat cell carcinoma Pulmonary airways cells of uncertain function
Continued on page A 107
A healthy adolescent boy was treated on two occasrons for an overdose of chlorpropamide (Diabinese’a). Glucose therapy alone was not sufficient to control the hypoglycemia, but the administration of glucose plus diazoxide raised the blood sugar to supranormal levels. A bolus of intravenous glucagon briefly raised the blood sugar level to within normal limits, increased the blood ketones but also augmented insulin secretion. An overdose of sulfonylurea may cause prolonged and fatal hypoglycemia. Rational therapy, both in diabetic and normal persons, is glucose plus an “insulin antagonist.” The administration of diazoxide was effective in our patient. substantially reducing ihe plasma insulin level: this agent may be the “insulin-antagonist” of choice for use in sulfonylurea-induced hypoglycemia.
Suc-
Glucose
Johnson SF, Schade DS, Peake GT: Chlorpropamide-induced hypoglycemia. cessful treatment with diazoxide. Am J Med 63: 799-804, 1977
Sulfonylurea
Chlorpropamide
Two groups of patients undergoing long-term dialysis, one with and one without pancytopenia, were compared. Marrow biopsy specimens compatible with renal osteodystrophy, but also suggesting replacement of functional marrow by fibrosis and sclerosis, were found in both groups. However, bone and marrow disease, as measured by serum parathyroid hormone and alkaline phosphatase, bone surveys and per cent fibrosis on marrow biopsy, tended to be more severe in the patients with pancytopenia than in the control group. A hypersplenic picture, defined by chromium-51 (!j’Cr) red blood cell survivals, was found only in cytopenic patients, Extramedullary hematopoiesis was present in two splenectomized patients. Of the patients without cytopenia, only those with significant marrow fibrosis and sclerosis had peripheral marrow expansion or, scan. The data suggest that myelofibrosis secondary to renal osteodystrophy is common, and that severity of marrow disease, and type and degree of response to marrow obliteration determine in part the success of hematologic compensation.
Weinberg SG. Lubin A. Wiener SN. Deoras MP, Ghose MK, Kopelman RC: Myelofibrosis and renal osteodystrophy. Am J Med 63: 755-764, 1977.
Myelofibrosis Dialysis