medical progress along a broad front; other factors, such as the breakdown of proved principles of sterile tech¬ nique are avoidable. Dr McGowan, using his own work as reference, also points out that the resistance patterns that I presented reflected overall susceptibility of both community-acquired and hospital-ac¬
quired organisms and, therefore, tended to dilute the importance of re¬ sistant organisms in the hospital set¬ ting.5 However, this same paper
noted that "there were no striking or significant differences in the suscepti¬ bility of the strains" of Gram-nega¬ tive bacilli isolated at Boston City Hospital in 1972 when compared to a period of November 1965 to August 1966.
Finally, it was not my intention to condone or justify misuse or overuse of antibiotics. It was my aim to point out the extensive body of data that conflict with the premise that present patterns of antibiotic use are respon¬ sible for the increased incidence of, and mortality from, Gram-negative bacteremia. In light of these data, do we want to overemphasize the role of anti¬ biotics to the exclusion of other fac¬ tors? Is it in the patient's interest to discontinue antibiotic therapy dur¬ ing unconsciousness when bactério¬ logie and roentgenographic evidence of pneumonia is present (as did the authors of one reference" cited by Dr McGowan)?
Joseph T. Curti, MD Pfizer Pharmaceuticals New York 1. Briody BA: Chemotherapy of infectious disease, in Briody BA (ed): Microbiology and Infectious Disease. New York, McGraw-Hill Book Co Inc, 1974, pp 644-651. 2. Altemeier WA, McDonough JJ, Fullen WD: Third day surgical fever. Arch Surg 103:158-166, 1971. 3. Sanford JP: Hospital-associated respiratory infections, in Holloway WJ (ed): Infectious Disease Reviews. Mt Kisco, NY, Futura Publishing, 1973, vol 2, pp 141-153. 4. Tillotson JR, Finland M: Secondary pulmonary infections following antibiotic therapy for primary bacterial pneumonia. Antimicrob Agents Chemother 8:326-330,
1968. 5. McGowan
biotic
JE, Garner C, Wilcox C, et al: Antisusceptibility of Gram-negative bacilli isolated
from blood cultures. Am J Med 57:225-238, 1974. 6. Price DJE, Sleigh JD: Control of infection due to Klebsiella aerogenes in a neuro-surgical unit by withdrawal of all antibiotics. Lancet 2:1213-1215, 1970.
False-Positive Liver Scan
Following Colectomy To the Editor.\p=m-\Thepurpose of this letter is to report an interestingly abnormal liver scan in a normal liver. A falsely abnormal liver scan was obtained in a patient following total colectomy. True normalcy of the liver in this case was confirmed by liver function tests, liver biopsy, and, finally, laparotomy. To our knowledge, this type of observation has not previously been reported in the literature.
Technetium Tc 99m sulfur colloid liver-spleen scintiscans (anterior views). Top, Normal appearance before colectomy. Bottom, Definite but false abnormality after colectomy. Note overall decreased colloid uptake in liver and increased splenic uptake with focal defects in liver that suggest mass lesion.
A
man with Crohn disand carcinoma of the colon underwent total colectomy. His preoperative liver scan (Figure, top) was within normal limits. The postoperative liver scan (Figure, bottom) was apparently abnormal, characterized by heterogeneous colloid uptake and focal defects in the liver and increased splenic uptake. This may erroneously be attributed to parenchymal liver disease with possible portal hypertension. In this patient, however, there was no disease in the liver, as evidenced by normal liver function tests, liver biopsy, and laparotomy. The most logical explanation for this pseudoabnormal liver scan is that af¬ ter intravenous administration of radiocolloid, 80% of radioactivity is transported via the portal vein and 20% via the hepatic artery. Total col¬ ectomy will cause substantial reduc¬ tion of portal blood flow because of li-
27-year-old
ease
Downloaded From: http://jama.jamanetwork.com/ by a UCSF LIBRARY User on 06/15/2015
gation of the inferior mesenteric vein and of some branches of the superior mesenteric vein. Thus, a total colec¬ tomy will greatly reduce the radiocolloid delivery to the liver and result in decreased liver uptake and com¬ pensatory increased uptake in the spleen, a picture similar to that seen in portal hypertension. Since this is a new entity of etiol¬ ogy for false-positive liver scan, nu¬ clear physicians should be cautious in interpreting liver scan in a patient who has had colectomy. Tapan K. Chaudhuri, MD Veterans Administration Center Hampton, Va
Augmenting Cryoprecipitate Factor VIII Activity To the Editor.\p=m-\Recently,there has been an outcry in the medical journals as well as in some daily newspapers regarding the astronomical
cost of
treating hemophilic patients cryoprecipitate factor VIII. This, as stated by many physicians,
with
has resulted in the chronic undertreatment of these unfortunate patients. Since most of the commercial preparations are imported from the United States, I thought you might be kind enough to include my letter in your column. The basic scientific problem is a well-known and accepted fact, namely, that the benefit derived from transfused factor VIII is far below that expected from in vitro activity. Various methods for improving the therapeutic effect of factor VIII in hemophilia have been tried. A peanut extract was claimed to diminish hemorrhagic episodes, but a controlled trial showed that this could not be substantiated and its beneficial effect, if any, was most probably due to an antifibrinolytic action. E-Aminocaproic acid was then advocated by some researchers, but was soon found to provide no consistent benefit of significant value and may cause cer¬ tain complications. The use of longterm steroids is beset with danger, and Bennett and Ingram,1 in 1967, found that daily doses of prednisolone (adults, 7.6 mg; children, 3 mg) pro¬ vided only a marginal improvement in children. In 1963, my studies2 showed a blood fraction that, by neu¬ tralizing the inhibitory effect of hé¬ mophilie plasma, improves the action of factor VIII. A preliminary clinical trial3 of this fraction gave results that appeared more promising than the peanut extract, £-aminocaproic acid, and steroids. However, the prep¬ aration of this fraction (bridge anti¬
coagulant neutralizing agent or BANA) on a large scale proved diffi¬ cult for two reasons: (1) the method
entailed two steps, activation with ether followed by adsorption or elution or precipitation with ethanol, and (2) it required a supply of blood other than that used for preparing factor VIII, which is extremely diffi¬ cult to obtain in the United Kingdom. A new, simple method overcomes these difficulties by preparing cryoprecipitate factor VIII and BANA in a continuous process from the same unit of blood. After obtain¬ ing factor VIII, the supernatant is transferred to a third satellite bag, where it is clotted by the addition of calcium. The bag containing the clot is frozen overnight and then, after thawing, aliquots of serum are trans¬ ferred to bottles kept at 0 C. Activa¬ tion and precipitation of BANA are carried out by ether fractionation. Further purification with adsorption
and elution is now in progress. I believe that the preparation of this blood fraction on a large scale for a controlled clinical trial is essential, not only to decide its merits in the treatment of these unfortunate pa¬ tients but also in the cause of medical science. In order to achieve the larg¬ est possible clinical trial, may I
appeal through your journal to our colleagues in America, whom I think could give us a lead in this sequential prospect—the present financial posi¬ tion in the United Kingdom could very well delay further progress. I would be pleased to supply further in¬ formation to those interested.
F. Nour-Eldin, PhD, MB, BCh, LMSSA, MRCPath
Shenley Hospital St Albans, Herts,
1. Bennett AE,
England
Ingram GIC: A controlled trial of long\x=req-\ haemophilia. Lancet 1:967,
term steroid treatment in
1967.
2. Nour-Eldin F: Bridge anticoagulant neutralizing agent: Properties and isolation. Acta Haematol 30:168, 1963.
3. Nour-Eldin F: Haematology: Rudimental, Practical and Clinical. London, Butterworths, 1972.
Runaway Children To the Editor.\p=m-\Iread with a great deal of interest Dr William Schmidt's article (232:651, 1975) on runaway children since it pertains to what I feel is the most critical area in preserving an important natural resource: our
juveniles.
Our rural community of Lebanon, Mo had no facility to administer to the needs of juveniles prior to an innovative program called "Project Misdemeanant." Project Misdemeanant was a community-produced and -supported volunteer program to provide an alternative to jail or release of the juvenile after an offense, such as a misdemeanor or running away. Prior to this project, the circuit judge had no recourse but to detain juveniles in a county jail, send them to a detention home, or release them without
supervision.
The project originated solely with volunteers and monies from our community and initially had no response from federal, state, or even local law enforcement agencies. We now have a
completely cooperative
program
that involves five counties, two cir¬ cuit judges, three juvenile officers, ap¬ proximately 50 volunteers, and the entire school system of Camdenton and Laclede counties. All of this has taken place over a period of three years. It has been considered a huge success and involves many segments of our community. The project recently won the Missouri Law Day Liberty Bell Award (the Valley Forge Foundation National award) and was awarded June 7, 1975.
Downloaded From: http://jama.jamanetwork.com/ by a UCSF LIBRARY User on 06/15/2015
I personally believe that physicians should become involved in their com¬ munity for the same reason that Dr Schmidt discusses in his article—that the physician has the opportunity to administer to the physical and emo¬ tional needs of adolescents and their families. If you would be interested in further comment on this very success¬ ful program, I would be happy to pro¬ vide you with articles, documentation, or any other information that you may find of interest. Dennis Hite, MD
Lebanon, Mo
Adjuvant Chemotherapy
"Works" for Breast Cancer With Involved Nodes To the Editor.\p=m-\Iwas distressed to read the following statement in a recent article (232:995, 1975): "the difference was not actually statistically significant, but the trend was similar." This kind of overoptimistic conclusion, based on a small group of patients objectively observed for a short time, is the principal cause for the muddle about therapy of breast cancer, as well as many other clinical
problems. While adjuvant chemotherapy may prove highly effective in increasing
the disease-free interval after mastectomy, it has not yet stood the test of time. Who can forget the enthusiasm over glomectomy for asthma, gastric cooling for ulcer disease, and internal mammary ligation for coronary
artery disease?
base
our
with statistics if we conclusions on "trends" that cannot be separated by statistical methods from random or chance occurrence?
Why bother
John D. Burrington, MD
University of Chicago
of Tonometers To the Editor.\p=m-\Ina recent QUESTION AND ANSWER (232:849, 1975), the comments by Dr Samuel B. Harper of Madison, Wis, have been noted. We would like to mention that our company's Schiotz tonometers, bearing serial numbers 70-2400 and up, may be autoclaved. Dr Harper's contention that the tonometer is a delicate instrument is quite correct, but if reasonable care is exercised when placing the instrument in an autoclave, the instrument will not be damaged in any way and is capable of being completely autoclaved.
Autoclaving
Alan L. Sklar J. Sklar Mfg Co Inc Long Island City, NY
quired organisms and, therefore, tended to dilute the importance of re¬ sistant organisms in the hospital set¬ ting.5 However, this same paper
noted that "there were no striking or significant differences in the suscepti¬ bility of the strains" of Gram-nega¬ tive bacilli isolated at Boston City Hospital in 1972 when compared to a period of November 1965 to August 1966.
Finally, it was not my intention to condone or justify misuse or overuse of antibiotics. It was my aim to point out the extensive body of data that conflict with the premise that present patterns of antibiotic use are respon¬ sible for the increased incidence of, and mortality from, Gram-negative bacteremia. In light of these data, do we want to overemphasize the role of anti¬ biotics to the exclusion of other fac¬ tors? Is it in the patient's interest to discontinue antibiotic therapy dur¬ ing unconsciousness when bactério¬ logie and roentgenographic evidence of pneumonia is present (as did the authors of one reference" cited by Dr McGowan)?
Joseph T. Curti, MD Pfizer Pharmaceuticals New York 1. Briody BA: Chemotherapy of infectious disease, in Briody BA (ed): Microbiology and Infectious Disease. New York, McGraw-Hill Book Co Inc, 1974, pp 644-651. 2. Altemeier WA, McDonough JJ, Fullen WD: Third day surgical fever. Arch Surg 103:158-166, 1971. 3. Sanford JP: Hospital-associated respiratory infections, in Holloway WJ (ed): Infectious Disease Reviews. Mt Kisco, NY, Futura Publishing, 1973, vol 2, pp 141-153. 4. Tillotson JR, Finland M: Secondary pulmonary infections following antibiotic therapy for primary bacterial pneumonia. Antimicrob Agents Chemother 8:326-330,
1968. 5. McGowan
biotic
JE, Garner C, Wilcox C, et al: Antisusceptibility of Gram-negative bacilli isolated
from blood cultures. Am J Med 57:225-238, 1974. 6. Price DJE, Sleigh JD: Control of infection due to Klebsiella aerogenes in a neuro-surgical unit by withdrawal of all antibiotics. Lancet 2:1213-1215, 1970.
False-Positive Liver Scan
Following Colectomy To the Editor.\p=m-\Thepurpose of this letter is to report an interestingly abnormal liver scan in a normal liver. A falsely abnormal liver scan was obtained in a patient following total colectomy. True normalcy of the liver in this case was confirmed by liver function tests, liver biopsy, and, finally, laparotomy. To our knowledge, this type of observation has not previously been reported in the literature.
Technetium Tc 99m sulfur colloid liver-spleen scintiscans (anterior views). Top, Normal appearance before colectomy. Bottom, Definite but false abnormality after colectomy. Note overall decreased colloid uptake in liver and increased splenic uptake with focal defects in liver that suggest mass lesion.
A
man with Crohn disand carcinoma of the colon underwent total colectomy. His preoperative liver scan (Figure, top) was within normal limits. The postoperative liver scan (Figure, bottom) was apparently abnormal, characterized by heterogeneous colloid uptake and focal defects in the liver and increased splenic uptake. This may erroneously be attributed to parenchymal liver disease with possible portal hypertension. In this patient, however, there was no disease in the liver, as evidenced by normal liver function tests, liver biopsy, and laparotomy. The most logical explanation for this pseudoabnormal liver scan is that af¬ ter intravenous administration of radiocolloid, 80% of radioactivity is transported via the portal vein and 20% via the hepatic artery. Total col¬ ectomy will cause substantial reduc¬ tion of portal blood flow because of li-
27-year-old
ease
Downloaded From: http://jama.jamanetwork.com/ by a UCSF LIBRARY User on 06/15/2015
gation of the inferior mesenteric vein and of some branches of the superior mesenteric vein. Thus, a total colec¬ tomy will greatly reduce the radiocolloid delivery to the liver and result in decreased liver uptake and com¬ pensatory increased uptake in the spleen, a picture similar to that seen in portal hypertension. Since this is a new entity of etiol¬ ogy for false-positive liver scan, nu¬ clear physicians should be cautious in interpreting liver scan in a patient who has had colectomy. Tapan K. Chaudhuri, MD Veterans Administration Center Hampton, Va
Augmenting Cryoprecipitate Factor VIII Activity To the Editor.\p=m-\Recently,there has been an outcry in the medical journals as well as in some daily newspapers regarding the astronomical
cost of
treating hemophilic patients cryoprecipitate factor VIII. This, as stated by many physicians,
with
has resulted in the chronic undertreatment of these unfortunate patients. Since most of the commercial preparations are imported from the United States, I thought you might be kind enough to include my letter in your column. The basic scientific problem is a well-known and accepted fact, namely, that the benefit derived from transfused factor VIII is far below that expected from in vitro activity. Various methods for improving the therapeutic effect of factor VIII in hemophilia have been tried. A peanut extract was claimed to diminish hemorrhagic episodes, but a controlled trial showed that this could not be substantiated and its beneficial effect, if any, was most probably due to an antifibrinolytic action. E-Aminocaproic acid was then advocated by some researchers, but was soon found to provide no consistent benefit of significant value and may cause cer¬ tain complications. The use of longterm steroids is beset with danger, and Bennett and Ingram,1 in 1967, found that daily doses of prednisolone (adults, 7.6 mg; children, 3 mg) pro¬ vided only a marginal improvement in children. In 1963, my studies2 showed a blood fraction that, by neu¬ tralizing the inhibitory effect of hé¬ mophilie plasma, improves the action of factor VIII. A preliminary clinical trial3 of this fraction gave results that appeared more promising than the peanut extract, £-aminocaproic acid, and steroids. However, the prep¬ aration of this fraction (bridge anti¬
coagulant neutralizing agent or BANA) on a large scale proved diffi¬ cult for two reasons: (1) the method
entailed two steps, activation with ether followed by adsorption or elution or precipitation with ethanol, and (2) it required a supply of blood other than that used for preparing factor VIII, which is extremely diffi¬ cult to obtain in the United Kingdom. A new, simple method overcomes these difficulties by preparing cryoprecipitate factor VIII and BANA in a continuous process from the same unit of blood. After obtain¬ ing factor VIII, the supernatant is transferred to a third satellite bag, where it is clotted by the addition of calcium. The bag containing the clot is frozen overnight and then, after thawing, aliquots of serum are trans¬ ferred to bottles kept at 0 C. Activa¬ tion and precipitation of BANA are carried out by ether fractionation. Further purification with adsorption
and elution is now in progress. I believe that the preparation of this blood fraction on a large scale for a controlled clinical trial is essential, not only to decide its merits in the treatment of these unfortunate pa¬ tients but also in the cause of medical science. In order to achieve the larg¬ est possible clinical trial, may I
appeal through your journal to our colleagues in America, whom I think could give us a lead in this sequential prospect—the present financial posi¬ tion in the United Kingdom could very well delay further progress. I would be pleased to supply further in¬ formation to those interested.
F. Nour-Eldin, PhD, MB, BCh, LMSSA, MRCPath
Shenley Hospital St Albans, Herts,
1. Bennett AE,
England
Ingram GIC: A controlled trial of long\x=req-\ haemophilia. Lancet 1:967,
term steroid treatment in
1967.
2. Nour-Eldin F: Bridge anticoagulant neutralizing agent: Properties and isolation. Acta Haematol 30:168, 1963.
3. Nour-Eldin F: Haematology: Rudimental, Practical and Clinical. London, Butterworths, 1972.
Runaway Children To the Editor.\p=m-\Iread with a great deal of interest Dr William Schmidt's article (232:651, 1975) on runaway children since it pertains to what I feel is the most critical area in preserving an important natural resource: our
juveniles.
Our rural community of Lebanon, Mo had no facility to administer to the needs of juveniles prior to an innovative program called "Project Misdemeanant." Project Misdemeanant was a community-produced and -supported volunteer program to provide an alternative to jail or release of the juvenile after an offense, such as a misdemeanor or running away. Prior to this project, the circuit judge had no recourse but to detain juveniles in a county jail, send them to a detention home, or release them without
supervision.
The project originated solely with volunteers and monies from our community and initially had no response from federal, state, or even local law enforcement agencies. We now have a
completely cooperative
program
that involves five counties, two cir¬ cuit judges, three juvenile officers, ap¬ proximately 50 volunteers, and the entire school system of Camdenton and Laclede counties. All of this has taken place over a period of three years. It has been considered a huge success and involves many segments of our community. The project recently won the Missouri Law Day Liberty Bell Award (the Valley Forge Foundation National award) and was awarded June 7, 1975.
Downloaded From: http://jama.jamanetwork.com/ by a UCSF LIBRARY User on 06/15/2015
I personally believe that physicians should become involved in their com¬ munity for the same reason that Dr Schmidt discusses in his article—that the physician has the opportunity to administer to the physical and emo¬ tional needs of adolescents and their families. If you would be interested in further comment on this very success¬ ful program, I would be happy to pro¬ vide you with articles, documentation, or any other information that you may find of interest. Dennis Hite, MD
Lebanon, Mo
Adjuvant Chemotherapy
"Works" for Breast Cancer With Involved Nodes To the Editor.\p=m-\Iwas distressed to read the following statement in a recent article (232:995, 1975): "the difference was not actually statistically significant, but the trend was similar." This kind of overoptimistic conclusion, based on a small group of patients objectively observed for a short time, is the principal cause for the muddle about therapy of breast cancer, as well as many other clinical
problems. While adjuvant chemotherapy may prove highly effective in increasing
the disease-free interval after mastectomy, it has not yet stood the test of time. Who can forget the enthusiasm over glomectomy for asthma, gastric cooling for ulcer disease, and internal mammary ligation for coronary
artery disease?
base
our
with statistics if we conclusions on "trends" that cannot be separated by statistical methods from random or chance occurrence?
Why bother
John D. Burrington, MD
University of Chicago
of Tonometers To the Editor.\p=m-\Ina recent QUESTION AND ANSWER (232:849, 1975), the comments by Dr Samuel B. Harper of Madison, Wis, have been noted. We would like to mention that our company's Schiotz tonometers, bearing serial numbers 70-2400 and up, may be autoclaved. Dr Harper's contention that the tonometer is a delicate instrument is quite correct, but if reasonable care is exercised when placing the instrument in an autoclave, the instrument will not be damaged in any way and is capable of being completely autoclaved.
Autoclaving
Alan L. Sklar J. Sklar Mfg Co Inc Long Island City, NY
