- Email: [email protected]
Clinical and laboratory residuals in patients treated for sprue
Special Feature The
Southern
ABSTRACTS
OF PAPERS
Society PRESENTED
for Clinical
AT THE THIRD JANUARY
29,
(Read by Presentation) ON
Two
NEWER
POIETIC VITAMINS-VITAMIN
HEMO-
Biz AND ANI-
FACTOR. William J. Darby, and (by invitation) Edgar Jones, M.D.
MAI, PROTEIN
M.D. From and
The
Departments
Biochemistry,
School
of Medicine,
of
Vanderbilt Nashville,
Medicine
CLINICAL
University
1949
AND.
NEW
LABORATORY
ORL.EANS,
Tenn.
Fox, M.D. Jr., M.D.) of Medicine,
RESIDUALS
IN
Herbert 3. (Introduced by Eugene A. Stead,
PATIENTS TREATED
Patients with anemias associated with megalohlastic arrest respond hemopoietically to four types of nutritional factors or metabolic products: the pteroylglutamates, vitamin Br2, microbial animal protein factor (APF) and thymine. Three of these are available in crystalline form; the fourth (APF) is not but may be quantitated by chick growth studies. We have made observations on the responses to crystalline Brf (administered parenterally) in eleven patients with pernicious anemia, nutritional macrocytic anemia or sprue. These studies have included evaluations of the minimal effective dosage for induction of hemopoietic and clinical remissions and for maintenance of the patient. These observations to date indicate the approximate equivalence of 1 microgram of crystalline Blz to 1 USP unit of antipernicious anemia liver extract. In pernicious anemia the remissions produced by Brt therapy have been characterized by relief of glossitis, an increased sense of well being, initial hemopoietic response typical of an adequately treated anemia patient, maturation of the megaloblastic marrow, weight gain, decrease in fecal urobilinogen and, in two patients, disappearance of early neurologic symptoms. In two cases of sprue the results have been less clearly defined and our experience indicates a greater quantitative requirement in this syndrome. Nutritional macrocytic anemia has responded in a manner comparable to pernicious anemia. Evidence will be presented indicating an approximate correspondence of AUGUST,
ANNUAL MEETING,
1949
activity of APF in pernicious anemia (parenteral administration) and in the chick. Since these two factors are effective parenterally it does not appear that they correspond to Castle’s extrinsic factor although their association with animal protein would imply that they. may.
PROCEEDINGS
OBSERVATIONS
Research
From
FOR SPRUE.
Duke
Durham,
University
School
N. C.
A follow-up clinical and laboratory study was made on twenty patients previously diagnosed as having sprue who had had from five to fourteen years of nutritional rehabilitation and specific therapy. Each had had a chronic illness characterized by loss of weight, anemia, glossitis, diarrhea, meteorism and steatorrhea. This study was undertaken to determine the residual disability and laboratory evidence of absorptive defects in sprue that persisted despite prolonged therapy. Nine of the twenty patients had not achieved full rehabilitation, had remained underweight, deficient in strength and had periodic recurrences of diarrhea and glossitis. Physical activity was restricted. Dietary fat was tolerated poorly. Continued liver therapy was necessary. A five-day fat balance test showed a sub-normal absorption of dietary fat in all nine patients. Their stools, by a measured fecal output over three-day periods, were increased in bulk. Mild anemia with a tendency toward macrocytosis was present. I:nemulsified vitamin A showed flat absorption curves in contrast to normal curves with emulsified material. Roentgenologic study of the small intestine showed coarse irregularities and segmentation alternating with dilatation. The effect of folic acid on fat absorption was observed in seven of these nine patients. Although they had received maintenance doses of folic acid, 15 to 30 mg. daily for six months or longer and had 241
The Southern Society for Clinical Research bowel habit improvements not seen in liver therapy, still all seven showed steatorrhea. Eleven of the twenty had not received specific therapy for several years and were apparently fully recovered, showing none of the clinical or laboratory residuals seen in the other nine patients. The sprue syndrome apparently represents a temporary motor and absorptive abnormality of the intestines from nutritional deficiency, or a more permanent disease which persists in spite of nutritional rehabilitation and therapy. The latter may be congenital or represent a sequela of inflammatory or other damage to the gut wall. CHANGES
IN ELECTROPHORETIC
OF SERA MYELOMA
IN PATIENTS TREATED
WITH WITH
PATTERNS MULTIPLE URETHANE.
Edith S. Dillon, M.D. (by invztation), M. L. Dillon, M.D. (by invitation) and R. W. Rundles, M.D. From Duke University School
of Medicine,
Durham,
N. C.
In six patients with multiple myeloma treated with urethane, fever and bone pain at rest and during activity subsided and anemia, hyperglobulinemia and proteinuria were ameliorated or corrected. Abnormal plasma cells in the bone marrow became altered in appearance and decreased in number or disappeared from the marrow. After six to eight months there was x-ray evidence of recalcification of bone. Electrophoretic studies on sera of four of these patients showed conspicuous reduction in the amount of abnormal serum globulin after urethane therapy. In one patient globulin with gamma mobility comprised 45.7 per cent of the total serum protein before treatment. A total dosage of 240 Gm. of urethane was given orally over a period of two months. Five months after completion of therapy the gamma globulin component was 23.8 per cent and at nine months it was 22.9 per cent. In a second patient with 49 per cent gamma globulin before treatment there was a fall to 18 per cent in four months and 19.1 per cent at seven months. In a third patient “M” globulin comprised 45.2 per cent of the serum protein before treatment and 33.4 per cent three and one-half months later. The abnormal globulin rose again to 40.6 per cent accompanied by a decline in hemoglobin, red count and hematocrit and the reappearance of over 20 Gm. per day of Bence-Jones protein
in the urine. A fourth patient excreting about 25 Gm. of Bence-Jones protein daily in the urine had a normal percentage distribution of serum protein components before therapy. After two months of urethane the gamma globulin fell from 10.5 per cent to 8.5 per cent with a 75 per cent reduction in the amount of Bence-Jones protein in the urine.
OF SERUM PROTEOLYTIC ENZYME.Jessica H. Lewis, M.D. (by inoita-
ACTIVATION
tion) and John H. Ferguson, M.D. The versity
Department of North
of
Physiology,
Carolina,
Chapel
From UniHill,
N. C. Normal blood contains a powerful proteolytic enzyme system which, if fully activated, is capable of destroying all the fibrinogen and probably much of the other plasma protein in a few minutes. Serum contains enzyme precursor (proenzyme) and enzyme inhibitor (anti-enzyme). In viuo activation occurs only under certain rare pathologic conditions. We have set up systems for study of the activation of this proenzyme in vztro, using various “activators” including chloroform, streptokinase and staphylokinase. Proteolytic activity is measured by the rate of lysis of a standard fibrin clot. Proenzyme is prepared from (1) human, (2) canine (3) bovine serum by 25 per cent alcohol fractionation at 0’~. This fraction contains almost all the proenzyme and a reduced amount of anti-enzyme. Spontaneous activation of these preparations did not occur. Chloroform treatment of the proenzyme preparations causes further marked reduction of the antifibrinolytic activity of these fractions. Fibrinolytic activity appears in these preparations only slowly and rarely to maximal amounts. It is concluded that the main action of chloroform is to remove enzyme inhibitors and to allow either spontaneous activation or activation by substances already present in the serum fractions. Streptokinase readily activates human proenzyme but does not affect dog or bovine preparations. In optimal amounts its effect is immediate but in suboptimal amounts a period of preliminary incubation with proenzyme is for maximal fibrinolytic activity. necessary Staphylokinase activates both human and dog proenzyme but does not affect bovine material. The kinetics of the staphylokinase reaction also AMERICAN
JOURNAL
OF
MEDICINE
Southern
ABSTRACTS
OF PAPERS
Society PRESENTED
for Clinical
AT THE THIRD JANUARY
29,
(Read by Presentation) ON
Two
NEWER
POIETIC VITAMINS-VITAMIN
HEMO-
Biz AND ANI-
FACTOR. William J. Darby, and (by invitation) Edgar Jones, M.D.
MAI, PROTEIN
M.D. From and
The
Departments
Biochemistry,
School
of Medicine,
of
Vanderbilt Nashville,
Medicine
CLINICAL
University
1949
AND.
NEW
LABORATORY
ORL.EANS,
Tenn.
Fox, M.D. Jr., M.D.) of Medicine,
RESIDUALS
IN
Herbert 3. (Introduced by Eugene A. Stead,
PATIENTS TREATED
Patients with anemias associated with megalohlastic arrest respond hemopoietically to four types of nutritional factors or metabolic products: the pteroylglutamates, vitamin Br2, microbial animal protein factor (APF) and thymine. Three of these are available in crystalline form; the fourth (APF) is not but may be quantitated by chick growth studies. We have made observations on the responses to crystalline Brf (administered parenterally) in eleven patients with pernicious anemia, nutritional macrocytic anemia or sprue. These studies have included evaluations of the minimal effective dosage for induction of hemopoietic and clinical remissions and for maintenance of the patient. These observations to date indicate the approximate equivalence of 1 microgram of crystalline Blz to 1 USP unit of antipernicious anemia liver extract. In pernicious anemia the remissions produced by Brt therapy have been characterized by relief of glossitis, an increased sense of well being, initial hemopoietic response typical of an adequately treated anemia patient, maturation of the megaloblastic marrow, weight gain, decrease in fecal urobilinogen and, in two patients, disappearance of early neurologic symptoms. In two cases of sprue the results have been less clearly defined and our experience indicates a greater quantitative requirement in this syndrome. Nutritional macrocytic anemia has responded in a manner comparable to pernicious anemia. Evidence will be presented indicating an approximate correspondence of AUGUST,
ANNUAL MEETING,
1949
activity of APF in pernicious anemia (parenteral administration) and in the chick. Since these two factors are effective parenterally it does not appear that they correspond to Castle’s extrinsic factor although their association with animal protein would imply that they. may.
PROCEEDINGS
OBSERVATIONS
Research
From
FOR SPRUE.
Duke
Durham,
University
School
N. C.
A follow-up clinical and laboratory study was made on twenty patients previously diagnosed as having sprue who had had from five to fourteen years of nutritional rehabilitation and specific therapy. Each had had a chronic illness characterized by loss of weight, anemia, glossitis, diarrhea, meteorism and steatorrhea. This study was undertaken to determine the residual disability and laboratory evidence of absorptive defects in sprue that persisted despite prolonged therapy. Nine of the twenty patients had not achieved full rehabilitation, had remained underweight, deficient in strength and had periodic recurrences of diarrhea and glossitis. Physical activity was restricted. Dietary fat was tolerated poorly. Continued liver therapy was necessary. A five-day fat balance test showed a sub-normal absorption of dietary fat in all nine patients. Their stools, by a measured fecal output over three-day periods, were increased in bulk. Mild anemia with a tendency toward macrocytosis was present. I:nemulsified vitamin A showed flat absorption curves in contrast to normal curves with emulsified material. Roentgenologic study of the small intestine showed coarse irregularities and segmentation alternating with dilatation. The effect of folic acid on fat absorption was observed in seven of these nine patients. Although they had received maintenance doses of folic acid, 15 to 30 mg. daily for six months or longer and had 241
The Southern Society for Clinical Research bowel habit improvements not seen in liver therapy, still all seven showed steatorrhea. Eleven of the twenty had not received specific therapy for several years and were apparently fully recovered, showing none of the clinical or laboratory residuals seen in the other nine patients. The sprue syndrome apparently represents a temporary motor and absorptive abnormality of the intestines from nutritional deficiency, or a more permanent disease which persists in spite of nutritional rehabilitation and therapy. The latter may be congenital or represent a sequela of inflammatory or other damage to the gut wall. CHANGES
IN ELECTROPHORETIC
OF SERA MYELOMA
IN PATIENTS TREATED
WITH WITH
PATTERNS MULTIPLE URETHANE.
Edith S. Dillon, M.D. (by invztation), M. L. Dillon, M.D. (by invitation) and R. W. Rundles, M.D. From Duke University School
of Medicine,
Durham,
N. C.
In six patients with multiple myeloma treated with urethane, fever and bone pain at rest and during activity subsided and anemia, hyperglobulinemia and proteinuria were ameliorated or corrected. Abnormal plasma cells in the bone marrow became altered in appearance and decreased in number or disappeared from the marrow. After six to eight months there was x-ray evidence of recalcification of bone. Electrophoretic studies on sera of four of these patients showed conspicuous reduction in the amount of abnormal serum globulin after urethane therapy. In one patient globulin with gamma mobility comprised 45.7 per cent of the total serum protein before treatment. A total dosage of 240 Gm. of urethane was given orally over a period of two months. Five months after completion of therapy the gamma globulin component was 23.8 per cent and at nine months it was 22.9 per cent. In a second patient with 49 per cent gamma globulin before treatment there was a fall to 18 per cent in four months and 19.1 per cent at seven months. In a third patient “M” globulin comprised 45.2 per cent of the serum protein before treatment and 33.4 per cent three and one-half months later. The abnormal globulin rose again to 40.6 per cent accompanied by a decline in hemoglobin, red count and hematocrit and the reappearance of over 20 Gm. per day of Bence-Jones protein
in the urine. A fourth patient excreting about 25 Gm. of Bence-Jones protein daily in the urine had a normal percentage distribution of serum protein components before therapy. After two months of urethane the gamma globulin fell from 10.5 per cent to 8.5 per cent with a 75 per cent reduction in the amount of Bence-Jones protein in the urine.
OF SERUM PROTEOLYTIC ENZYME.Jessica H. Lewis, M.D. (by inoita-
ACTIVATION
tion) and John H. Ferguson, M.D. The versity
Department of North
of
Physiology,
Carolina,
Chapel
From UniHill,
N. C. Normal blood contains a powerful proteolytic enzyme system which, if fully activated, is capable of destroying all the fibrinogen and probably much of the other plasma protein in a few minutes. Serum contains enzyme precursor (proenzyme) and enzyme inhibitor (anti-enzyme). In viuo activation occurs only under certain rare pathologic conditions. We have set up systems for study of the activation of this proenzyme in vztro, using various “activators” including chloroform, streptokinase and staphylokinase. Proteolytic activity is measured by the rate of lysis of a standard fibrin clot. Proenzyme is prepared from (1) human, (2) canine (3) bovine serum by 25 per cent alcohol fractionation at 0’~. This fraction contains almost all the proenzyme and a reduced amount of anti-enzyme. Spontaneous activation of these preparations did not occur. Chloroform treatment of the proenzyme preparations causes further marked reduction of the antifibrinolytic activity of these fractions. Fibrinolytic activity appears in these preparations only slowly and rarely to maximal amounts. It is concluded that the main action of chloroform is to remove enzyme inhibitors and to allow either spontaneous activation or activation by substances already present in the serum fractions. Streptokinase readily activates human proenzyme but does not affect dog or bovine preparations. In optimal amounts its effect is immediate but in suboptimal amounts a period of preliminary incubation with proenzyme is for maximal fibrinolytic activity. necessary Staphylokinase activates both human and dog proenzyme but does not affect bovine material. The kinetics of the staphylokinase reaction also AMERICAN
JOURNAL
OF
MEDICINE