presoline
e unique DON" ntihypertensive ICATIONS: Various forms of hypertension: d essential hypertension, whether of benign alignant character; hypertension associated acute and chronic glomerulonephritis; hrosclerosis; hypertensive toxemias of gnancy, pre-eclampsia, and eclampsia. SAGE: Hypertension: Orally: In general after iating therapy gradually increase dosage, usting according to individual response. As a le agent, initially 10mg, four times daily reasing slowly to a maximum practical dosage 00mg daily. In combination with other hyposive agents, lower dosages of APRESOLINE be appropriate. enterally: When there is urgent need, therapy e hospitalized patient may be initiated intraously or intramuscularly. Usual dose is 20 to mg, repeated as necessary. Certain patients, ecially those with marked renal damage, may uire a lower dose. Pressure may begin to fall in a few minutes after injection, with an rage maximal decrease occurring in 10 to 80 utes. Most patients can be transferred to oral RESOLINE within 24 to 48 hours. emia of Pregnancy: a) Early toxemia and ertension of pregnancy: One 10-mg tablet Ily 4 times daily, slowly increasing the dosage to 400mg per day, or until a therapeutic result btained. ate toxemia and pre-eclampsia: Give 20 to mg intramuscularly, or slowly by direct avenous injection or infusion. Repeat as essary. E EFFECTS: Tachycardia, headache, palpion, dizziness, weakness, nausea, vomiting, stural hypotension, numbness and tingling of extremities, flushing, nasal congestion, lachation, conjunctival injection, dyspnea, anginal ptoms, rash, drug fever, reduction in hemobin and red cell count, giant urticaria, and a us-like syndrome (arthralgia) in some cases lowing administration for long periods. UTIONS: Use cautiously in the presence of vanced renal damage and recent coronary or rebral ischemia. APRESOLINE may potentiate narcotic effects of barbiturates and alcohol. ripheral neuritis evidenced by paresthesias, mbness and tingling has been observed. blished evidence suggests an anti-pyridoxine ect and addition of pyridoxine to the regimen if ptoms develop. ERDOSAGE: Symptoms: Hypotension and hycardia. atment: Gastric lavage or, in the absence of ma, emetics. In the presence of hypotension, utiously give norepinephrine (intravenously) or hedrine to raise the blood pressure without reasing tachycardia. Avoid epinephrine. neral supportive measures include intravenous iids, external heat, and elevation of foot of bed. JPPLIED: All forms contain hydralazine drochloride. Tablets of 10mg (yellow, scored); )ttles of 100. Tablets of 25mg (blue, coated); fltles of 100 and 500. Tablets of 50mg (pink, ated); bottles of 100 and 500. Ampoules of 1 ml .ueous solution containing 20 mg; boxes of 10.
.IBA
DRVAL, QUEBEC
0-5003
sidering whether a drug is or is not available in Canada. The role of the HPB in this regard is to administer the existing regulatory controls in a manner that will encourage innovation and the early availability of new essential drugs and will not needlessly hamper industry, provided the neces.ary requisites of safety and efficacy are respected. A.B. MORRISON, PH D
Assistant deputy minister Health protection branch Health and Welfare Canada Ottawa, Ont.
Small chromosomal inversions: are they harmless? To the editor: One group of chromosomal variants identified during the last several years consists of small inversions of centromeric heterochromatin; they have been found in chromosomes 1, 3, 9 and 10. Three papers14 describe several familial cases and two of the papers2'3 present frequency figures of these inversions. The probability of crossing-over in the pericentromeric region is small and, therefore, visible deficiencies or duplications due to the heterozygosity have never been observed. Most carriers are normal; mental or physical defects or both in some carriers are often explained as coincidence and the inversions are regarded as normal variants. Their frequency in examined populations ranges from 1 to 3%. However, propositi in all three surveys were hospital patients or persons referred to the genetics service. It is possible that the frequency figures are biased by this selection process. This possibility seems to be corroborated by results from Colorado:4 inversion in chromosome 9 was found in 4 of 68 retarded or autistic children (5.9%) but in only 5 of 600 consecutive newborns (0.84%). In our laboratory1 we have identified 8 unrelated propositi with inversion in chromosome 3 among 270 mentally defective persons from eastern Ontario, giving a frequency of 3 %. However, Dr. Lin (University of Calgary, personal communication) found the same inversion in only 3 of 585 consecutive newborns in the Hamilton area. We found no inversions in 84 mentally normal male prisoners or in 38 staff men of the Kingston Psychiatric Hospital. If these numbers are pooled the frequency becomes 0.4%. The striking difference could be biased because the normal unselected groups studied were not restricted to people originating in eastern Ontario. There is some possibility that inversion in chromosome 3 could be more common in eastern Ontario; half of the propositi have AngloSaxon names and half have French names.
Another explanation of the difference is the possibility of higher risk of some defects in families carrying inversions of centromeric heterochromatin. Only extensive comparative studies of unselected normal and Selected defective samples of the population can answer this question. This study was assisted under grant no. 267-69 C of the Ontario Mental Health Foundation. D. SOUDEK, MD Cytogenetics laboratory Kingston Psychiatric Hospital Queen's University Kingston, Ont.
References 1. SOUDEK D, O'SHAUGHNESSY S, LARAYA P, Ct al: Pericentric inversion of "fluorescent" segment in chromosome no. 3. Humangenetik 22: 343, 1974 2. MADAN K, Boaaow M: Structural variation in chromosome no. 9. Ann Genet 17: 81, 1974 3. DE LA CHAPELLE A, SCHROEDER 3, STENsTRAIID K, et al: Pericentric inversions of human chromosomes 9 and 10. Am J Hum Genet 26: 746, 1974 4. Luas HA, Luas ML: New cytogenetics techniques applied to a series of children with mental retardation, in Chromosome identification, 23rd Nobel Symposium, Stockholm, 1972, edited by CAss'EassoN T and ZECH L, New York, Acad Pr, 1972, pp 241-250
Furuncle caused by Yersinia enterocolitica To the editor: It has recently become evident that Yersinia enterocolitica is capable of invading a multitude of sites. The organism has been isolated in a variety of conditions, including abscesses of the spleen and colon, gastroenteritis, septicemia, peritonitis, cholecystitis and mesenteric lymphadenitis. In the following patient the organism was isolated from a subcutaneous abscess. A 30-year-old airline pilot was first seen by a physician in December 1974, complaining of a small painful lump on the inner aspect of his left thigh. A very tender, nonfluctuant furuncle measuring 1 cm in diameter and discharging a small amount of serous fluid was noted. A swab of the fluid was taken for culture and sensitivity tests. Penicillin G (500 000 units qid) was prescribed and the patient was instructed to compress the furuncle several times each day. The furuncle enlarged rapidly over the next 4 days and became increasingly painful. Three days later a preliminary laboratory report suggested as the causative agent Y. enterocolitica, sensitive to gentamicin, neomycin, tetracycline and trimethoprim-sulfamethoxazole (Bactrim). At this time penicillin was discontinued and Bactrim prescribed (two tablets bid). The pain lessened considerably within the next 24 hours, and shortly thereafter a moderate amount of thin pus drained spontaneously. Bactrim was continued for 10 days, after which time drainage had ceased and the furuncle had become much smaller and painless. No history of recent contact with animals could be elicited. The culture was
CMA JOURNAL/JUNE 7, 1975/VOL. 112 1289
forwarded to the Y. enterocolitica and Y. pseudotuberculosis Reference Laboratory in Ontario for serotyping. The organism was confirmed to be Y. enterocolitica of biotype 1 and serotype 0:21, the first of its kind to be isolated in Canada. MICHAEL R. LAWRENCE, MB, ES S. KENNETH TiNe, MD, FRCP(C] SUE NEILLY, ART Metropolitan Bio-Medical LaboratGries 687 West 8th Ave. Vancouver, BC
Massive pulmonary gangrene To the editor: The article "Massive pulmonary gangrene: a severe complication of Klebsiella pneumonia", by Knight, Fraser and Robson (Can Med Assoc J 112: 196, 1975), was of particular interest to us because of our recent experience with a very similar case - by their counting, the 13th in the literature. We are presently conducting a study of the clinical, bacteriologic and radiologic features of acute lobar pneumonia in adults at the Kenyatta National Hospital in Nairobi. Of 100 cases only 2 were due to Kiebsiella species, 1 of which went on to massive pulmonary gangrene, with a course similar to that described by Knight and colleagues in their patients; 95% of our cases were apparently due to Pneumococcus species, as shown either by Gram's stain, culture or prompt response to penicillin. A 37-year-old Kikuyu woman had a 3-day history of fever, left-sided pleuritic chest pain and hemoptysis. She had never before been hospitalized, did not drink alcohol and had no previous chest coinplaints. She was in a toxic condition: her temperature was 400C, blood pressure 110/60 mm Hg, pulse rate 130 beats/mm and respiratory rate 32/mm. There was decreased left chest movement with a pleural rub and bronchial breathing over the left middle chest anteriorly. Clinically and radiologically she had a left upper lobe
pneumonia similar to that of our other patients with pneumococcal pneumonia. Gram's staining revealed gram-negative rods with thick mucoid capsules, and blood and sputum cultures subsequently grew Kiebsiella species sensitive to gentamicin. Her hemoglobin value was 12.1 g/dl and her leukocyte count 9800/mm3. Renal function was normal. Antimicrobial therapy was initiated with penicillin but was changed by the next day to gentamicin, 240 mg/ dl. She became afebrile by the 3rd hospital day but her chest findings remained the same and her sputum output did not diminish noticeably. She remained afebrile but relatively sick, and by the 14th day was still producing sputum containing Klebsiiella species sensitive to gentamicin in spite of treatment with this drug. The radiologic findings remained unchanged for a week, but on day 10 cavitations and some bulging of the fissure were noted on a lateral chest radiograph. Gentamicin was continued and penicillin G, 6 million units a day in divided doses, was added. She
D.I. CAMERON ). J.D. STEWART, B Sc, MB, 55, MR4 R.C.B. SLACK, MA, MB, CR B, D OB5T, RC( C.L.H. LEWIS, MB, ci B, FRcS, DM1
Box 3051 Kenyatta National Hospit Nairobi, Ken:
FIG 2 Hospital day 10 expanding pneumonia with several areas of cavitation
References 1. KLASTERSKY
J, GEUNING C, MOUAWAD
et al: Endotracheal gentamicn in bronchi infections in patients with tracheostom Chest 61. 117 1972
2. KLASTERSKY I: Experience with gentamic in respiratory infections caused by gran
negative rods. Acta Pathol Microbiol Scar [B] 81 (suppl 241): 137, 1973
/
FIG 1 Admission left upper lobe pneumonia with no cavitation or bulging of fissure
showed no improvement and her ch radiograph did not change. On the 34th hospital day she underw thoracotomy. A large cavity in the 1 upper lobe containing necrotic tissue w no pus was resected. Histopathologic amination showed extensive fibrosis a active chronic inflammation. Postope: tively she slowly improved and gen micin and penicillin were continued ur the 60th hospital day. Five days later s was discharged and 2 months later s was asymptomatic. One of our group (J.D.S.) present the findings from part of our seri including this case, in Oberurse Taunus, West Germany in early D cember 1974 to the Internation Working Meeting on Pneumonia, U proceedings of which will be publish soon. The discussion on the treatme of Kiebsiella pneumonia was intere. ing. There was unanimous agreeme that combination antimicrobial therai should be used. Although note increasing resistance of Kiebsiel species to gentamicin was made, mo combinations recommended includc gentamicin and one of the followin, a cephalosporin, sulfamethoxazol trimethoprim, chloramphenicol or tetr: cycline. Continuous intratracheal a ministration of gentamicin via a tr. cheostomy or repeated transtrache. punctures in order to attain higher coi centrations of gentamicin in the lun tissue, as described by Klastersky an colleagues,1'2 was also discussed.
FIG 3 Hospital day 10 bulging of fissure
1290 CMA JOURNAL/JUNE 7, 1975/VOL. 112
Fee schedules and workloads To the editor: Efforts by the Ontari Medical Association and other div: sional associations to reduce disparitie in incomes between their sections hay been largely unsuccessful. It shoul have been obvious that tinkering wiU the fees for single items in the schedul could never achieve the desired resul because there are other factors that de termine the incomes of individual* phy sicians. The most important of thes is the workload carried by each physi cian. This is determined by the deman4 for the service being provided and th number of physicians available to do ii When the demand increases at a great er rate than the number of physician available to meet it, average income
e unique DON" ntihypertensive ICATIONS: Various forms of hypertension: d essential hypertension, whether of benign alignant character; hypertension associated acute and chronic glomerulonephritis; hrosclerosis; hypertensive toxemias of gnancy, pre-eclampsia, and eclampsia. SAGE: Hypertension: Orally: In general after iating therapy gradually increase dosage, usting according to individual response. As a le agent, initially 10mg, four times daily reasing slowly to a maximum practical dosage 00mg daily. In combination with other hyposive agents, lower dosages of APRESOLINE be appropriate. enterally: When there is urgent need, therapy e hospitalized patient may be initiated intraously or intramuscularly. Usual dose is 20 to mg, repeated as necessary. Certain patients, ecially those with marked renal damage, may uire a lower dose. Pressure may begin to fall in a few minutes after injection, with an rage maximal decrease occurring in 10 to 80 utes. Most patients can be transferred to oral RESOLINE within 24 to 48 hours. emia of Pregnancy: a) Early toxemia and ertension of pregnancy: One 10-mg tablet Ily 4 times daily, slowly increasing the dosage to 400mg per day, or until a therapeutic result btained. ate toxemia and pre-eclampsia: Give 20 to mg intramuscularly, or slowly by direct avenous injection or infusion. Repeat as essary. E EFFECTS: Tachycardia, headache, palpion, dizziness, weakness, nausea, vomiting, stural hypotension, numbness and tingling of extremities, flushing, nasal congestion, lachation, conjunctival injection, dyspnea, anginal ptoms, rash, drug fever, reduction in hemobin and red cell count, giant urticaria, and a us-like syndrome (arthralgia) in some cases lowing administration for long periods. UTIONS: Use cautiously in the presence of vanced renal damage and recent coronary or rebral ischemia. APRESOLINE may potentiate narcotic effects of barbiturates and alcohol. ripheral neuritis evidenced by paresthesias, mbness and tingling has been observed. blished evidence suggests an anti-pyridoxine ect and addition of pyridoxine to the regimen if ptoms develop. ERDOSAGE: Symptoms: Hypotension and hycardia. atment: Gastric lavage or, in the absence of ma, emetics. In the presence of hypotension, utiously give norepinephrine (intravenously) or hedrine to raise the blood pressure without reasing tachycardia. Avoid epinephrine. neral supportive measures include intravenous iids, external heat, and elevation of foot of bed. JPPLIED: All forms contain hydralazine drochloride. Tablets of 10mg (yellow, scored); )ttles of 100. Tablets of 25mg (blue, coated); fltles of 100 and 500. Tablets of 50mg (pink, ated); bottles of 100 and 500. Ampoules of 1 ml .ueous solution containing 20 mg; boxes of 10.
.IBA
DRVAL, QUEBEC
0-5003
sidering whether a drug is or is not available in Canada. The role of the HPB in this regard is to administer the existing regulatory controls in a manner that will encourage innovation and the early availability of new essential drugs and will not needlessly hamper industry, provided the neces.ary requisites of safety and efficacy are respected. A.B. MORRISON, PH D
Assistant deputy minister Health protection branch Health and Welfare Canada Ottawa, Ont.
Small chromosomal inversions: are they harmless? To the editor: One group of chromosomal variants identified during the last several years consists of small inversions of centromeric heterochromatin; they have been found in chromosomes 1, 3, 9 and 10. Three papers14 describe several familial cases and two of the papers2'3 present frequency figures of these inversions. The probability of crossing-over in the pericentromeric region is small and, therefore, visible deficiencies or duplications due to the heterozygosity have never been observed. Most carriers are normal; mental or physical defects or both in some carriers are often explained as coincidence and the inversions are regarded as normal variants. Their frequency in examined populations ranges from 1 to 3%. However, propositi in all three surveys were hospital patients or persons referred to the genetics service. It is possible that the frequency figures are biased by this selection process. This possibility seems to be corroborated by results from Colorado:4 inversion in chromosome 9 was found in 4 of 68 retarded or autistic children (5.9%) but in only 5 of 600 consecutive newborns (0.84%). In our laboratory1 we have identified 8 unrelated propositi with inversion in chromosome 3 among 270 mentally defective persons from eastern Ontario, giving a frequency of 3 %. However, Dr. Lin (University of Calgary, personal communication) found the same inversion in only 3 of 585 consecutive newborns in the Hamilton area. We found no inversions in 84 mentally normal male prisoners or in 38 staff men of the Kingston Psychiatric Hospital. If these numbers are pooled the frequency becomes 0.4%. The striking difference could be biased because the normal unselected groups studied were not restricted to people originating in eastern Ontario. There is some possibility that inversion in chromosome 3 could be more common in eastern Ontario; half of the propositi have AngloSaxon names and half have French names.
Another explanation of the difference is the possibility of higher risk of some defects in families carrying inversions of centromeric heterochromatin. Only extensive comparative studies of unselected normal and Selected defective samples of the population can answer this question. This study was assisted under grant no. 267-69 C of the Ontario Mental Health Foundation. D. SOUDEK, MD Cytogenetics laboratory Kingston Psychiatric Hospital Queen's University Kingston, Ont.
References 1. SOUDEK D, O'SHAUGHNESSY S, LARAYA P, Ct al: Pericentric inversion of "fluorescent" segment in chromosome no. 3. Humangenetik 22: 343, 1974 2. MADAN K, Boaaow M: Structural variation in chromosome no. 9. Ann Genet 17: 81, 1974 3. DE LA CHAPELLE A, SCHROEDER 3, STENsTRAIID K, et al: Pericentric inversions of human chromosomes 9 and 10. Am J Hum Genet 26: 746, 1974 4. Luas HA, Luas ML: New cytogenetics techniques applied to a series of children with mental retardation, in Chromosome identification, 23rd Nobel Symposium, Stockholm, 1972, edited by CAss'EassoN T and ZECH L, New York, Acad Pr, 1972, pp 241-250
Furuncle caused by Yersinia enterocolitica To the editor: It has recently become evident that Yersinia enterocolitica is capable of invading a multitude of sites. The organism has been isolated in a variety of conditions, including abscesses of the spleen and colon, gastroenteritis, septicemia, peritonitis, cholecystitis and mesenteric lymphadenitis. In the following patient the organism was isolated from a subcutaneous abscess. A 30-year-old airline pilot was first seen by a physician in December 1974, complaining of a small painful lump on the inner aspect of his left thigh. A very tender, nonfluctuant furuncle measuring 1 cm in diameter and discharging a small amount of serous fluid was noted. A swab of the fluid was taken for culture and sensitivity tests. Penicillin G (500 000 units qid) was prescribed and the patient was instructed to compress the furuncle several times each day. The furuncle enlarged rapidly over the next 4 days and became increasingly painful. Three days later a preliminary laboratory report suggested as the causative agent Y. enterocolitica, sensitive to gentamicin, neomycin, tetracycline and trimethoprim-sulfamethoxazole (Bactrim). At this time penicillin was discontinued and Bactrim prescribed (two tablets bid). The pain lessened considerably within the next 24 hours, and shortly thereafter a moderate amount of thin pus drained spontaneously. Bactrim was continued for 10 days, after which time drainage had ceased and the furuncle had become much smaller and painless. No history of recent contact with animals could be elicited. The culture was
CMA JOURNAL/JUNE 7, 1975/VOL. 112 1289
forwarded to the Y. enterocolitica and Y. pseudotuberculosis Reference Laboratory in Ontario for serotyping. The organism was confirmed to be Y. enterocolitica of biotype 1 and serotype 0:21, the first of its kind to be isolated in Canada. MICHAEL R. LAWRENCE, MB, ES S. KENNETH TiNe, MD, FRCP(C] SUE NEILLY, ART Metropolitan Bio-Medical LaboratGries 687 West 8th Ave. Vancouver, BC
Massive pulmonary gangrene To the editor: The article "Massive pulmonary gangrene: a severe complication of Klebsiella pneumonia", by Knight, Fraser and Robson (Can Med Assoc J 112: 196, 1975), was of particular interest to us because of our recent experience with a very similar case - by their counting, the 13th in the literature. We are presently conducting a study of the clinical, bacteriologic and radiologic features of acute lobar pneumonia in adults at the Kenyatta National Hospital in Nairobi. Of 100 cases only 2 were due to Kiebsiella species, 1 of which went on to massive pulmonary gangrene, with a course similar to that described by Knight and colleagues in their patients; 95% of our cases were apparently due to Pneumococcus species, as shown either by Gram's stain, culture or prompt response to penicillin. A 37-year-old Kikuyu woman had a 3-day history of fever, left-sided pleuritic chest pain and hemoptysis. She had never before been hospitalized, did not drink alcohol and had no previous chest coinplaints. She was in a toxic condition: her temperature was 400C, blood pressure 110/60 mm Hg, pulse rate 130 beats/mm and respiratory rate 32/mm. There was decreased left chest movement with a pleural rub and bronchial breathing over the left middle chest anteriorly. Clinically and radiologically she had a left upper lobe
pneumonia similar to that of our other patients with pneumococcal pneumonia. Gram's staining revealed gram-negative rods with thick mucoid capsules, and blood and sputum cultures subsequently grew Kiebsiella species sensitive to gentamicin. Her hemoglobin value was 12.1 g/dl and her leukocyte count 9800/mm3. Renal function was normal. Antimicrobial therapy was initiated with penicillin but was changed by the next day to gentamicin, 240 mg/ dl. She became afebrile by the 3rd hospital day but her chest findings remained the same and her sputum output did not diminish noticeably. She remained afebrile but relatively sick, and by the 14th day was still producing sputum containing Klebsiiella species sensitive to gentamicin in spite of treatment with this drug. The radiologic findings remained unchanged for a week, but on day 10 cavitations and some bulging of the fissure were noted on a lateral chest radiograph. Gentamicin was continued and penicillin G, 6 million units a day in divided doses, was added. She
D.I. CAMERON ). J.D. STEWART, B Sc, MB, 55, MR4 R.C.B. SLACK, MA, MB, CR B, D OB5T, RC( C.L.H. LEWIS, MB, ci B, FRcS, DM1
Box 3051 Kenyatta National Hospit Nairobi, Ken:
FIG 2 Hospital day 10 expanding pneumonia with several areas of cavitation
References 1. KLASTERSKY
J, GEUNING C, MOUAWAD
et al: Endotracheal gentamicn in bronchi infections in patients with tracheostom Chest 61. 117 1972
2. KLASTERSKY I: Experience with gentamic in respiratory infections caused by gran
negative rods. Acta Pathol Microbiol Scar [B] 81 (suppl 241): 137, 1973
/
FIG 1 Admission left upper lobe pneumonia with no cavitation or bulging of fissure
showed no improvement and her ch radiograph did not change. On the 34th hospital day she underw thoracotomy. A large cavity in the 1 upper lobe containing necrotic tissue w no pus was resected. Histopathologic amination showed extensive fibrosis a active chronic inflammation. Postope: tively she slowly improved and gen micin and penicillin were continued ur the 60th hospital day. Five days later s was discharged and 2 months later s was asymptomatic. One of our group (J.D.S.) present the findings from part of our seri including this case, in Oberurse Taunus, West Germany in early D cember 1974 to the Internation Working Meeting on Pneumonia, U proceedings of which will be publish soon. The discussion on the treatme of Kiebsiella pneumonia was intere. ing. There was unanimous agreeme that combination antimicrobial therai should be used. Although note increasing resistance of Kiebsiel species to gentamicin was made, mo combinations recommended includc gentamicin and one of the followin, a cephalosporin, sulfamethoxazol trimethoprim, chloramphenicol or tetr: cycline. Continuous intratracheal a ministration of gentamicin via a tr. cheostomy or repeated transtrache. punctures in order to attain higher coi centrations of gentamicin in the lun tissue, as described by Klastersky an colleagues,1'2 was also discussed.
FIG 3 Hospital day 10 bulging of fissure
1290 CMA JOURNAL/JUNE 7, 1975/VOL. 112
Fee schedules and workloads To the editor: Efforts by the Ontari Medical Association and other div: sional associations to reduce disparitie in incomes between their sections hay been largely unsuccessful. It shoul have been obvious that tinkering wiU the fees for single items in the schedul could never achieve the desired resul because there are other factors that de termine the incomes of individual* phy sicians. The most important of thes is the workload carried by each physi cian. This is determined by the deman4 for the service being provided and th number of physicians available to do ii When the demand increases at a great er rate than the number of physician available to meet it, average income
