long-wavelength ultraviolet light. In addition, we found that anti¬ water to
Letters, if clearly marked "For Publication," will be published as space permits and at the discretion of the editor. They should be typewritten triple-spaced, with five or fewer references, should not exceed two pages in length, and will be subject to editing. Letters are not acknowledged. The Postmortem Examination To the Editor.\p=m-\Elsewherein this is-
(p 441), Dr. Stanley Burrows makes the point, often repeated but seldom backed by data, that most autopsies are routine and are not justifiable either for diagnostic or teaching purposes. We have just completed a review1 of all deaths in pediatric ages, whether dying in or out of hospital, that complements the findings of Dr. Burrows on autopsies in adults. We found that 61% of autopsies in children were unnecessary either because they confirmed or were less specific than the clinical diagnoses, against the 88% reported by Dr. Burrows in adults. There were, on the other hand, 16% of deaths in children without a well-defined clinical diagnosis, which a good autopsy could have supplied, had it been performed. The latter is a point often overlooked in investigations that limit themselves only to cases coming to autopsy. The difference in autopsy rates in the two studies may be in part ex¬ plained by the ages of patients as well as by the selection of criteria for sue
defining nonproductive autopsies. We list two desiderata concerning autopsy practices: (1) Since disease frequencies vary from region to re¬ gion, autopsy patterns should reflect regional mortality but not necessarily by performing autopsies for all major
of death. These patterns, if un¬ biased, serve clinical as well as other ends, such as social and health care planning at state and national levels. (2) In neonates and in young children, good quality autopsy data are very often needed to complete the clinical picture. In this age group, selectivi¬ ty in postmortem examinations takes causes
priority over other claims, especially since pathologists specializing in pé¬ diatrie and neonatal problems are in
short supply. One approach to a solution that would conserve scarce resources with¬ out sacrificing objectives would re¬ quire that autopsies be done in (1) Edited
by John
D.
Archer, MD, Senior Editor.
a
1%
systematic sample of
common
of death, (2) almost all deaths due to disease of unknown etiology or whose clinical picture is not com¬ pletely clear, and (3) if possible, deaths of special interest to patholo¬ causes
gists.
Louis Munan Anthea Kelly, MD
Sherbrooke
University Medical Center
Sherbrooke, Quebec
1 Munan L. Kelly A. C\l=o^\t\l=e'\R: Do the right children have autopsies? An analysis of selected determinants. Arch Dis Child, to be published.
New Application of Ophthalmic Ointments To the Editor.\p=m-\Somephysicians and are reluctant to use ophthalmic ointment as a drug delivery system. Physicians in the past have refrained from using ointments be-
patients
of a fear of altering corneal wound healing. It is now known that modern ophthalmic ointments do not with interfere ocular healing cause
(226:1568, 1973); however, patients
find that ophthalmic ointments containing drugs are irritating and produce tearing. Also, since ointments
sometimes difficult to administer in the conjunctival sac, the misplaced ointment may run down from the eyelids and blur vision temporarily. Our studies show that at least 0.1 ml of ointment is placed in the conjunctival sac by the physician or patient. However, the conjunctival sac can hold a maximum of only 0.05 ml of ointment; excess material is squeezed onto the lids and lashes. This excess ointment continues to flow into the conjunctival sac and thus serves as a reservoir for drug treatment of the anterior segment of the eye. We determined that by placing ointment on the fingertip and apply¬ ing it to the lids, lashes, and medial and lateral canthus the medication would reach the conjunctival sac. When tetracycline hydrochloride oint¬ ment was applied to the eyelids, drug movement into the tear film could be quantitatively observed by using the autofluorescence of tetracycline in are
Downloaded From: http://jama.jamanetwork.com/ by a Michigan State University User on 06/15/2015
bacterial concentrations in the tear film could be maintained for six hours in 1% chloramphenicol ointment, 1%
tetracycline hydrochloride ointment,
10% sulfacetamide ointment when ointments were applied to either the conjunctiva or the eyelids. By com¬ parison, the antibacterial concentra¬ tion of the drug in the tear film lasts for only minutes after the same con¬ centration of drug in aqueous vehicle was dropped into the eye. With a slit lamp and in the absence of excessive tearing, the ointment and drug can be seen to flow across the cornea and into the punctum. Af¬ ter application to the conjunctiva, the mineral oil in the ointment base and drugs suspended in the ointment can be tasted in back of the mouth. Like¬ wise, the drug and ointment were isolated from the nose and mouth following administration to the con¬ junctiva. This shows that the drug as well as the ointment are partly cleared from the eye by the nasolacrimal apparatus. In view of this, appli¬ cation of a small amount of ointment to the conjunctiva would be an excel¬ lent means of delivering drugs to the upper nasal cavities. When ointment is applied to the upper eyelid, blurring of vision and drug irritation is minimized. We be¬ lieve this is of practical importance in the treatment of ocular infections to all patients, but especially to those in pédiatrie and geriatric groups. Appli¬ cation can be made every six hours by an easy method with side effects re¬ duced to a minimum. or
Thomas Wallace, MD Calvin Hanna, PhD Fay Boozman, MD James Y. Massey, MD
University of Arkansas Medical
Center
Little Rock, Ark
1. Norn MS:
junctival
sac.
Eyelid ointment penetration into the conOphthalmol 50:206-209, 1972.
Acta
Drug Lag
in the United States
To the Editor.\p=m-\ATRENDS IN THERAPY article (231:635, 1975) implied that
trimethoprim-sulfamethoxazole (Bactrim, Septra) is a new introduction to the US medical profession. It was
launched here in Britain in 1968, and years of usage have confirmed its invaluable and by-and-large danger-free contribution to medicine. I am reminded that only a year or so ago it was possible to read American papers on the treatment of asthma without any mention of cromolyn sodium (Aarane, Intal), which seven
revolutionized asthma treatment here from its introduction in 1968. Seven years seems too long for the benefit of these drugs to be withheld from US patients. Whatever the reason, should not efforts be made to improve the situation? Ernest L. Lonbay, MB, BS New Romney, Kent England
Clindamycin-Associated Colitis
With Toxic Megacolon To the Editor.\p=m-\Lincomycinand clin-
damycin have been reported as causing a spectrum of diarrheal diseases ranging from mild nonspecific colitis to severe pseudomembranous colitis,
which may be lethal.1-6 We wish to report a patient presently in our care for clindamycin-induced pseudomembranous colitis complicated by toxic
megacolon.
Report of a Case.\p=m-\A30-year-old, previously healthy man was admitted on Jan 7, 1975, with a two-week history of diarrhea, at times bloody. Prior to admission, he had
been treated in the emergency rooms of hospitals and given a mixture of kaolin, pectin, atropine, scopolamine, and hyoscyamine (Donnagel) and a mixture of two
Figure
1.
atropine sulfate and diphenoxylate hydrochloride (Lomotil), without relief. Because of worsening diarrhea, upper abdominal pain, and dehydration, he was admitted to our hospital with the diagnosis of enterocolitis. On admission, he
de110 beats per minute; temperature was 37.8 C (100 F). Upper abdomen was slightly distended but soft. White blood cell count was 33,100, with 89% polymorphonuclear leukocytes. The patient was treated with intravenous fluids, a liquid diet, and the atropine-diphenoxylate mixture (Lomotil). Increasing upper abdominal distention occurred, not relieved by nasogastric suction. A flat film of the abdomen on Jan 11 and Jan 13 showed dilatation of the transverse colon compatible with toxic megacolon (Fig 1). Therapy was started with hydrocortisone, 300 mg, intravenously and cephalothin so¬ dium (Keflin) intravenously. Therapy with the atropine-diphenoxylate mixture was discontinued.7 Proctosigmoidoscopy per¬ formed the following day showed typical pseudomembranous colitis. At this time, the patient was questioned regarding recent drug ingestion, and it was determined that he had visited an oph¬ thalmologist in another state on Dec 10 for an "infection of the eye lid." He had been given a prescription for 20 capsules of clindamycin (Cleocin) phosphate, 150 mg, and
hydrated.
acutely ill and
was was
Pulse rate
'
Figure
2.
Downloaded From: http://jama.jamanetwork.com/ by a Michigan State University User on 06/15/2015
advised to take one capsule four times a day. Because of nausea, he took one three times a day, using 16 of the capsules. Diarrhea started about ten days after the last dose. Despite all therapy, including increase of hydrocortisone dose to 600 mg daily intravenously, the abdomen showed in¬ creasing megacolon, and clinical deteri¬ oration was evident (Fig 2). At surgery on Jan 17, there was enormous dilatation of the transverse colon with areas of gan¬ grene. The remainder of the colon was congested and edematous. A subtotal colectomy with ileostomy was done. The rectum and lower sigmoid were retained and a colostomy performed. Path¬ ological findings showed pseudomembranous colitis involving the entire colon, with gangrenous areas in the transverse colon (Fig 3). The postoperative course has been complicated by small-bowel ileus, but the patient is doing well. An ileocolostomy is planned for several months from now.
Comment.—Clindamycin is an ana¬ logue of lincomycin and has a similar potential for causing severe and even fatal colonie complications. In a pro¬ spective study,1 the incidence of diarrhea was 20%, and of membranous colitis 10%. The earlier literature on clindamycin-associated colitis de¬ scribed a reversible condition.' ''
Letters, if clearly marked "For Publication," will be published as space permits and at the discretion of the editor. They should be typewritten triple-spaced, with five or fewer references, should not exceed two pages in length, and will be subject to editing. Letters are not acknowledged. The Postmortem Examination To the Editor.\p=m-\Elsewherein this is-
(p 441), Dr. Stanley Burrows makes the point, often repeated but seldom backed by data, that most autopsies are routine and are not justifiable either for diagnostic or teaching purposes. We have just completed a review1 of all deaths in pediatric ages, whether dying in or out of hospital, that complements the findings of Dr. Burrows on autopsies in adults. We found that 61% of autopsies in children were unnecessary either because they confirmed or were less specific than the clinical diagnoses, against the 88% reported by Dr. Burrows in adults. There were, on the other hand, 16% of deaths in children without a well-defined clinical diagnosis, which a good autopsy could have supplied, had it been performed. The latter is a point often overlooked in investigations that limit themselves only to cases coming to autopsy. The difference in autopsy rates in the two studies may be in part ex¬ plained by the ages of patients as well as by the selection of criteria for sue
defining nonproductive autopsies. We list two desiderata concerning autopsy practices: (1) Since disease frequencies vary from region to re¬ gion, autopsy patterns should reflect regional mortality but not necessarily by performing autopsies for all major
of death. These patterns, if un¬ biased, serve clinical as well as other ends, such as social and health care planning at state and national levels. (2) In neonates and in young children, good quality autopsy data are very often needed to complete the clinical picture. In this age group, selectivi¬ ty in postmortem examinations takes causes
priority over other claims, especially since pathologists specializing in pé¬ diatrie and neonatal problems are in
short supply. One approach to a solution that would conserve scarce resources with¬ out sacrificing objectives would re¬ quire that autopsies be done in (1) Edited
by John
D.
Archer, MD, Senior Editor.
a
1%
systematic sample of
common
of death, (2) almost all deaths due to disease of unknown etiology or whose clinical picture is not com¬ pletely clear, and (3) if possible, deaths of special interest to patholo¬ causes
gists.
Louis Munan Anthea Kelly, MD
Sherbrooke
University Medical Center
Sherbrooke, Quebec
1 Munan L. Kelly A. C\l=o^\t\l=e'\R: Do the right children have autopsies? An analysis of selected determinants. Arch Dis Child, to be published.
New Application of Ophthalmic Ointments To the Editor.\p=m-\Somephysicians and are reluctant to use ophthalmic ointment as a drug delivery system. Physicians in the past have refrained from using ointments be-
patients
of a fear of altering corneal wound healing. It is now known that modern ophthalmic ointments do not with interfere ocular healing cause
(226:1568, 1973); however, patients
find that ophthalmic ointments containing drugs are irritating and produce tearing. Also, since ointments
sometimes difficult to administer in the conjunctival sac, the misplaced ointment may run down from the eyelids and blur vision temporarily. Our studies show that at least 0.1 ml of ointment is placed in the conjunctival sac by the physician or patient. However, the conjunctival sac can hold a maximum of only 0.05 ml of ointment; excess material is squeezed onto the lids and lashes. This excess ointment continues to flow into the conjunctival sac and thus serves as a reservoir for drug treatment of the anterior segment of the eye. We determined that by placing ointment on the fingertip and apply¬ ing it to the lids, lashes, and medial and lateral canthus the medication would reach the conjunctival sac. When tetracycline hydrochloride oint¬ ment was applied to the eyelids, drug movement into the tear film could be quantitatively observed by using the autofluorescence of tetracycline in are
Downloaded From: http://jama.jamanetwork.com/ by a Michigan State University User on 06/15/2015
bacterial concentrations in the tear film could be maintained for six hours in 1% chloramphenicol ointment, 1%
tetracycline hydrochloride ointment,
10% sulfacetamide ointment when ointments were applied to either the conjunctiva or the eyelids. By com¬ parison, the antibacterial concentra¬ tion of the drug in the tear film lasts for only minutes after the same con¬ centration of drug in aqueous vehicle was dropped into the eye. With a slit lamp and in the absence of excessive tearing, the ointment and drug can be seen to flow across the cornea and into the punctum. Af¬ ter application to the conjunctiva, the mineral oil in the ointment base and drugs suspended in the ointment can be tasted in back of the mouth. Like¬ wise, the drug and ointment were isolated from the nose and mouth following administration to the con¬ junctiva. This shows that the drug as well as the ointment are partly cleared from the eye by the nasolacrimal apparatus. In view of this, appli¬ cation of a small amount of ointment to the conjunctiva would be an excel¬ lent means of delivering drugs to the upper nasal cavities. When ointment is applied to the upper eyelid, blurring of vision and drug irritation is minimized. We be¬ lieve this is of practical importance in the treatment of ocular infections to all patients, but especially to those in pédiatrie and geriatric groups. Appli¬ cation can be made every six hours by an easy method with side effects re¬ duced to a minimum. or
Thomas Wallace, MD Calvin Hanna, PhD Fay Boozman, MD James Y. Massey, MD
University of Arkansas Medical
Center
Little Rock, Ark
1. Norn MS:
junctival
sac.
Eyelid ointment penetration into the conOphthalmol 50:206-209, 1972.
Acta
Drug Lag
in the United States
To the Editor.\p=m-\ATRENDS IN THERAPY article (231:635, 1975) implied that
trimethoprim-sulfamethoxazole (Bactrim, Septra) is a new introduction to the US medical profession. It was
launched here in Britain in 1968, and years of usage have confirmed its invaluable and by-and-large danger-free contribution to medicine. I am reminded that only a year or so ago it was possible to read American papers on the treatment of asthma without any mention of cromolyn sodium (Aarane, Intal), which seven
revolutionized asthma treatment here from its introduction in 1968. Seven years seems too long for the benefit of these drugs to be withheld from US patients. Whatever the reason, should not efforts be made to improve the situation? Ernest L. Lonbay, MB, BS New Romney, Kent England
Clindamycin-Associated Colitis
With Toxic Megacolon To the Editor.\p=m-\Lincomycinand clin-
damycin have been reported as causing a spectrum of diarrheal diseases ranging from mild nonspecific colitis to severe pseudomembranous colitis,
which may be lethal.1-6 We wish to report a patient presently in our care for clindamycin-induced pseudomembranous colitis complicated by toxic
megacolon.
Report of a Case.\p=m-\A30-year-old, previously healthy man was admitted on Jan 7, 1975, with a two-week history of diarrhea, at times bloody. Prior to admission, he had
been treated in the emergency rooms of hospitals and given a mixture of kaolin, pectin, atropine, scopolamine, and hyoscyamine (Donnagel) and a mixture of two
Figure
1.
atropine sulfate and diphenoxylate hydrochloride (Lomotil), without relief. Because of worsening diarrhea, upper abdominal pain, and dehydration, he was admitted to our hospital with the diagnosis of enterocolitis. On admission, he
de110 beats per minute; temperature was 37.8 C (100 F). Upper abdomen was slightly distended but soft. White blood cell count was 33,100, with 89% polymorphonuclear leukocytes. The patient was treated with intravenous fluids, a liquid diet, and the atropine-diphenoxylate mixture (Lomotil). Increasing upper abdominal distention occurred, not relieved by nasogastric suction. A flat film of the abdomen on Jan 11 and Jan 13 showed dilatation of the transverse colon compatible with toxic megacolon (Fig 1). Therapy was started with hydrocortisone, 300 mg, intravenously and cephalothin so¬ dium (Keflin) intravenously. Therapy with the atropine-diphenoxylate mixture was discontinued.7 Proctosigmoidoscopy per¬ formed the following day showed typical pseudomembranous colitis. At this time, the patient was questioned regarding recent drug ingestion, and it was determined that he had visited an oph¬ thalmologist in another state on Dec 10 for an "infection of the eye lid." He had been given a prescription for 20 capsules of clindamycin (Cleocin) phosphate, 150 mg, and
hydrated.
acutely ill and
was was
Pulse rate
'
Figure
2.
Downloaded From: http://jama.jamanetwork.com/ by a Michigan State University User on 06/15/2015
advised to take one capsule four times a day. Because of nausea, he took one three times a day, using 16 of the capsules. Diarrhea started about ten days after the last dose. Despite all therapy, including increase of hydrocortisone dose to 600 mg daily intravenously, the abdomen showed in¬ creasing megacolon, and clinical deteri¬ oration was evident (Fig 2). At surgery on Jan 17, there was enormous dilatation of the transverse colon with areas of gan¬ grene. The remainder of the colon was congested and edematous. A subtotal colectomy with ileostomy was done. The rectum and lower sigmoid were retained and a colostomy performed. Path¬ ological findings showed pseudomembranous colitis involving the entire colon, with gangrenous areas in the transverse colon (Fig 3). The postoperative course has been complicated by small-bowel ileus, but the patient is doing well. An ileocolostomy is planned for several months from now.
Comment.—Clindamycin is an ana¬ logue of lincomycin and has a similar potential for causing severe and even fatal colonie complications. In a pro¬ spective study,1 the incidence of diarrhea was 20%, and of membranous colitis 10%. The earlier literature on clindamycin-associated colitis de¬ scribed a reversible condition.' ''
