Rhinocerebral mucormycosis: Diagnosis and treatment Report
of two
Cliflord Richard
J. Berger, D.N.D.,” Fredrick C. Disque, G. Topazian, D.D.X.,**’ Augusta, Ga.
SCHOOL
OF DENTISTRY,
cases
MEDICAL
COLLEGE
D.M.D.,“*
md
OF GEORGIA
Rhinocerelxal mucormycosis (phycomycetes), a human fungal disease with oral and perioral findings, has an extremely high morbidity and mortality. The disease is most frequently seen in patients with poorly controlled diabetes. The symptoms, findings, and treatment of rhinocerebral mucormycosis are discussed, and two case histories are presented.
D
entists are frequently asked to evaluate patients presenting with periorbital cellulitis, since this finding is often associated with odontogenic infections. When careful examination, especially examination of a diabetic patient, reveals a triad of unilateral proptosis with periorbital cellulitis, ophthalmoplegia associated with blindness or some loss of visual acuity, and paranasal sinusitis with an associated necrotic area of the hard palate, the patient should be considered to have rhinocerebral mucormycosis until proven 0therwise.l Mucormycosis is a human fungal infection which occurs in four forms: rhinocerebral, pulmonary, gastrointestinal, and disseminated. The rhinocerebral form of this disease often has oral manifestations. The disease has a high mortality and morbidity, and thus prompt diagnosis and treatment are critical to the patient’s survival. Because of oral findings, it is important that dentists be aware of the presenting signs and symptoms. The classic syndrome of uncontrolled diabetes, nasal sinusitis, orbital cellulitis, *Former “*Former
Resident in Orxl Surgery; nom in private practice in Savannah, Assistant Professor of Oral Surgery; now in private praaticr
Ga. in West
ChrstW,
Pa. “*“Former Professor of Oral and Maxillofxeial Farmington, Conn.
and Chairman Surgery,
of Oral Surgery; School of Dental
now Professor and Head, Medicine, IJnivrarsity of
1)epartmrnt Connrcticut,
28
Berger,
Disque,
and Topazian
Oral July,
Surg. 1975
ophthalmoplegia, and meningoencephalitis caused by mucormycosis was first described by Gregory, Golden, and Haymake? in 1943. This fungus normally is saprophytic and commonly is found in soil, fruits, and starchy foods. It may become a human pathogen in patients with pre-existing disease, particularly diabetes mellitus, especially in the presence of acidosis. Some 70 per cent of the reported cases of this disease are associated with diabetic acidosis.” The infection is characterized by the proliferation, in tissue, of broad, branching (20 to 40 microns), rarely septate hyphae. These organisms are all of the class phycomycetes, a name sometimes used in place of mucormycosis to designate this disease process.4 Diabetic acidosis is the usually predisposing factor,“, ‘; but patients with leukemia, multiple myeloma, oliguric renal failure, severe diarrhea, or blood dyscrasias and patients undergoing intensive chemotherapy for cancer have an increased susceptibility to the disease.7-11 The nose is the most frequent portal of entry for the rhinocerebral form of mucormycosis. Then, by direct extension, the paranasal sinuses, orbit, and cranial cavity may become involved. The organisms, though of limited virulence, may be highly invasive, once infection is established. Propagation occurs in a unique manner, with invasion and proliferation of the organisms within the muscular wall of arteries, causing thrombosis and subsequent infarction. Involvement of the nasal cavity results in a dark, blood-tinged discharge and a reddish black necrotic appearance of the turbinates and septum. There is a tendency toward pansinusitis. A dull, steady pain, with tenderness over the sinus, is a common finding. When the orbit is involved, symptoms include a gradual visual deterioration which may result in complete blindness, internal and/or external ophthalmoplegia, and orbital and ocular pain.
Volume Number
Rhinocerebral
40 1
Fig.
n~t~ormycasis
29
2.
Once the unchecked infection reaches the cranial cavity, involvement of the central nervous system with motor and sensory deficits and meningoencepllalitis resultsI” In a high percentage of cases, this results in death of the patient. Oral manifestations are usually limited to the hard palate, where there are sharply demarcated areas of blackish gray csehar covering the surface mucosa with some areas of bony denudation. These areas of necrotic tissues are caused by the thrombosis of blood vessels supplying the area.‘” Radiographic examination demonstrates a combination of changes consisting of nodular thickening of the soft-tissue lining of the maxillary and ethmoid sinuses, but rarely of the frontal sinuses. Radiographs show cloudy antra but noticeable absence of fluid levels in these areas..I43 I5 Tomographic stud,v is cxtremely valuable in evaluating the extent and nature of the bone destructi0n.l” The unilateral exophthalmos seen in this disease sometimes causes confusion, because it is also commonly seen in suppurative sinus infections, cavernous sinus thrombosis, neoplasms, and cellulitis.’ If possible, biopsy specimens should be obtained from involved areas. The diagnosis of mucormycosis is confirmed by microscopic examination of a biopsy specimen and positive mycotic cultures. The mortality in acute cases has been estimated to bc as high as 90 per cent. The high mortality is due, in part, to delayed diagnosis and rapid progression of the underlying disease process.x The first and most important step in treatment is rapid correction of the acidosis.8 Concomitant antibiotics, steroids, and radiation are believed to cause accelerated growth of fungal organisms in the debilitated patient. If mucormycosis is suspected, the USC of these moclalitics sl~oultl he careful1.v re-evaluated and discontinued if possible. Surgical dhbridement of necrotic and &vitalized tissue is helpful in aiding rapid resolution. In 1958, amphotericin B (Fungizone) was shown to be effective in the treatment of mucormycosis.l” Alternate-date administration is the technique of choice, since amphotericin B is nephrotoxic and serum levels of amphotcriein B 48 hours after infusion are considered adequate for most systemic mycotic ag(1nts.l BCcause of nephrotoxicity, therapy should bc temporarily withheld if the blood
30
Berger,
lhpe,
and l'opuziun
urea nitrogen level cswc~ls 50 mg.1100 ml. or the weatinine lrvcl exceeds 3.0 mg./IOO ml.3 The dose of amphotericin B is slowly increased to a final alternateclay tlosc of 1 to 1.2 mg. of alnl)llotcl~i~in B per kilogram of body weight in a time rcgimcn of 4 to 8 weeks.
Volume Number
Rhinocerebral
40 1
mucomycosis
31
right quadrant. Extraction of the maxillary right premolars and first molar did not relieve the pain. Diabetes mellitus was diagnosed 1 year prior to admission, and the patient was placed on an American Diabetic Association diet and Diabinese, 250 mg. three times a day, but follow-up was erratic because of poor cooperation from the patient. One month prior to admission a bloody nasal discharge was noted. The patient’s local physician started antibiotic and analgesic therapy. Over the next several days, the distribution of the right frontal, maxillary, and mandibular nerves exhibited numbness. During the week prior to admission, analgesics became less effective in controlling the pain and the patient was referred to the hospital for treatment. The patient had total right ophthalmoplegia, ptosis, decreased vision of the right eye, and an ulcer on the hard palate (Figs. 1 and 2). A differential diagnosis included carcinoma of the palate, carcinoma of the maxillary antrum, and mucormycosis. The patient was admitted to the hospital in mild ketoacidosis. Admission laboratory findings included hemoglobin, 13.2 Gm. per cent; hematocrit, 42 per cent; white blood count, 7,500/mm.a; and a fasting blood sugar of 420 mg. per cent. Radiographic examination revealed considerable membrane thickening and an air-fluid level in the right maxillary antrum (Fig. 3). Biopsy of the palatal ulceration was performed by the oral surgery service and a diagnosis of mucormycosis was made. The patient received 4 weeks of amphotericin B therapy. The dosage was increased until a dose of 1 mg. per kilogram of hody weight was reached. Sugical therapy included excision of the necrotic area of the hard palate and a right maxillary antrectomy. The surgical site healed well, and a prosthesis was inserted. The patient was discharged 2 months after admission and was seen as an outpatient on March 9, 1968. He was in good health and the diabetes was well controlled. The right eye ptosis mas completely resolved, but the patient had not regained function of the fourth and sixth cranial nerves of the right eye. CASE
2
In August, with the chief
1973, a 34-year-old Negro woman complaint of blindness of the left
was admitted to the hospital eye. Other findings included
medicine associated
service prop-
32
Berger,
Disque,
or:11 July,
and Topazian
Fig.
Surg. 1975
6.
tosis, ophthalmoplegia, orbital cellulitis, a dull, throbbing pain in the left eye, and a history of poorly controlled juvenile diabetes mellitus (Fig. 4). A differential diagnosis of cavernous sinus thrombosis, mucormycosis, retrobulbar tumor, and retro-orbital abscess was made. Admission laboratory findings included hemoglobin, 15.0 Gm. per cent; hematocrit, 4(i per cent ; white I)lood count 21,500; and fasting blood sugar, 310 mg. per cent. Urinalysis revealed 4+ glucose and a large amount of acetone in the urine. Radiographic examination disclosed cloudiness of both frontal sinuses, more on thr left than on the right. Tomograms revealed cloudiness in the anterior ethmoids and the left maxillary sinus, with no air-fluid level (Fig. 5). Further examination disrlosed a black lesion of the nasal septum and a 5 mm. necrotic ulceration of the hard palate. Microscopic examination of biopsy specimens obtained from these arcas by the oral surgery service led to the diagnosis of mucormycosis (Fig. 6). The patient’s diabetic acidosis man quickly corrected with the use of regular insulin. A regimen of alternate-day administration of the antifungal chemotherapeutic agent amphotericin B, involving a total dose of 2 grams divided over a Z-month period, was instituted. An antrectomy through :I Caldwell-Luc approach was performed in order to d6bride the maxillary sinus and to establish drainage. During the 3-month hospitalization, the patient’s diabetes was controlled and the drainage site closed spontaneously with healthy tissue. The necrotic areas on the hard palate and nasal septum healed, and the ocular and paranasal pain gradually disappeared. The patient was discharged when free of clinical signs of active disease, although the blindness, proptoais, and ophthalmoplegia did not resolve. The patient was given periodic re-call appointments but was lost to follow-up when she moved out of state. Attempts to locate her and refer her for follow-up have been unsuccessful.
SUMMARY Dentists need to be aware of the signs and symptoms of rhinocerebral mucormycosis, since it has oral and perioral findings, is associated with extremely high morbidity and mortality, and has clinical findings permitting early diagnosis and treatment. ton, Ga.
The patient in Case 1 was treated KY., by Dr. Topazian. The patient
at the University of Kentucky Medical Center, Lexingin Case 2 was treated at University Hospital, Augusta,
Volume Number
Rhinocerebral
40 1
nwmnzycosis
33
REFERENCES
1. Battock, D. J., et al.: Alternate-Day Amphotericin B Therapy in the Treatmrnt of Rhinocerebral Phycomycosis (Mucormycosis), Ann. Intern. Med. 68: 122, 1968. of the CNS: Report of Three 2. Gregory, J. E., Golden, A., and Haymaker, W.: Murormycosis Cases, Bull. Johns Hopkins Hosp. 73: 405, 1943. 3. Bernstrom. L.. Hemenwav. TN. G.. and Barnhart. R. A.: R,hinocerebral and Otoloaic Mueorm+&is, rinn.‘Otol. 79: id, 1970.’ -1. Lie-Kian-Joe, Eng, N.-I.T., Tjokronegoro, S., Schaafmn, S., and Emmons, C. W.: Phycomycosis of the Central Nervous System Associated With Diabetes Mellitus in Indonesia, Am. J. Clin. Pathol. 32: 62, 1959. 5. Gass. J. D. M.: Ocular Manifestations of Acute Mucormycosis, Ophthalmol. 65: 226, I Arch. 1961:
6. Gass, J. D. M.: Acute Orbital Mucormycosis: Report of Two Cases, Arch. Ophthalmol. 65: 214, 1961. 7. Baum, J. L. : Rhino-orbital Mucormycosis, Am. J. Ophthalmol. 63: 335, 1967. 8. Deweese, D. D., Schleuning, A. J., and Robinson L. B.: Mwomycosis of the Nose and Paranasal Sinuses, Laryngoscope 75: 1398, 1965. 9. Pastore. P. N.: Mucormvcosis of the Maxillarv I Sinus and Diabetes Mellitus. South. Med. J. 60: il64, 196i. ” IO. Ginsberg, J., et al.: Cerebral Phycomycosis (Mucormycosis) With Ocular Involvement, Am. J. Onhthalmol. 62: 900. 1966. 11. Blodi, F.-C., et al.: Lethal Orbito-cerebral Phycomycosis in Otherwise Healthy Children, Am. J. Ophthalmol. 67: 698, 1969. 12. Reeves, D. L., et al.: Phycomycosis (Mucormycosis) of the Central Nervous System, J. Neurosurg. 23: 82, 1965. 13. Taylor, C. G., et al.: Mucormycosis (Phycomycosis) Tnvolving the Maxilla, ORAL SURO. 27:
806, 1969.
14. Baker, R. 15. Chick, E., bits With 16. Green, W. 101: 802,
D.: Editorial: Diabetes and Mucormycosis, Diabetes 9: 143, 1960. Evans, J., and Baker R. D.: Treatment of Experimental Mucormycosis in RabAmphotericin B, Antibiot. Chemother. 8: 394, 1958. H.: Mucormycosis Infection of the Craniofacial Structures, Am. J. Roentgenol. 1967.
Reprint requests to : Dr. Richard G. Topazian School of Dental Medicine Room B-7094 University of Connecticut Farmington, Conn. 06032
Health
Center
of two
Cliflord Richard
J. Berger, D.N.D.,” Fredrick C. Disque, G. Topazian, D.D.X.,**’ Augusta, Ga.
SCHOOL
OF DENTISTRY,
cases
MEDICAL
COLLEGE
D.M.D.,“*
md
OF GEORGIA
Rhinocerelxal mucormycosis (phycomycetes), a human fungal disease with oral and perioral findings, has an extremely high morbidity and mortality. The disease is most frequently seen in patients with poorly controlled diabetes. The symptoms, findings, and treatment of rhinocerebral mucormycosis are discussed, and two case histories are presented.
D
entists are frequently asked to evaluate patients presenting with periorbital cellulitis, since this finding is often associated with odontogenic infections. When careful examination, especially examination of a diabetic patient, reveals a triad of unilateral proptosis with periorbital cellulitis, ophthalmoplegia associated with blindness or some loss of visual acuity, and paranasal sinusitis with an associated necrotic area of the hard palate, the patient should be considered to have rhinocerebral mucormycosis until proven 0therwise.l Mucormycosis is a human fungal infection which occurs in four forms: rhinocerebral, pulmonary, gastrointestinal, and disseminated. The rhinocerebral form of this disease often has oral manifestations. The disease has a high mortality and morbidity, and thus prompt diagnosis and treatment are critical to the patient’s survival. Because of oral findings, it is important that dentists be aware of the presenting signs and symptoms. The classic syndrome of uncontrolled diabetes, nasal sinusitis, orbital cellulitis, *Former “*Former
Resident in Orxl Surgery; nom in private practice in Savannah, Assistant Professor of Oral Surgery; now in private praaticr
Ga. in West
ChrstW,
Pa. “*“Former Professor of Oral and Maxillofxeial Farmington, Conn.
and Chairman Surgery,
of Oral Surgery; School of Dental
now Professor and Head, Medicine, IJnivrarsity of
1)epartmrnt Connrcticut,
28
Berger,
Disque,
and Topazian
Oral July,
Surg. 1975
ophthalmoplegia, and meningoencephalitis caused by mucormycosis was first described by Gregory, Golden, and Haymake? in 1943. This fungus normally is saprophytic and commonly is found in soil, fruits, and starchy foods. It may become a human pathogen in patients with pre-existing disease, particularly diabetes mellitus, especially in the presence of acidosis. Some 70 per cent of the reported cases of this disease are associated with diabetic acidosis.” The infection is characterized by the proliferation, in tissue, of broad, branching (20 to 40 microns), rarely septate hyphae. These organisms are all of the class phycomycetes, a name sometimes used in place of mucormycosis to designate this disease process.4 Diabetic acidosis is the usually predisposing factor,“, ‘; but patients with leukemia, multiple myeloma, oliguric renal failure, severe diarrhea, or blood dyscrasias and patients undergoing intensive chemotherapy for cancer have an increased susceptibility to the disease.7-11 The nose is the most frequent portal of entry for the rhinocerebral form of mucormycosis. Then, by direct extension, the paranasal sinuses, orbit, and cranial cavity may become involved. The organisms, though of limited virulence, may be highly invasive, once infection is established. Propagation occurs in a unique manner, with invasion and proliferation of the organisms within the muscular wall of arteries, causing thrombosis and subsequent infarction. Involvement of the nasal cavity results in a dark, blood-tinged discharge and a reddish black necrotic appearance of the turbinates and septum. There is a tendency toward pansinusitis. A dull, steady pain, with tenderness over the sinus, is a common finding. When the orbit is involved, symptoms include a gradual visual deterioration which may result in complete blindness, internal and/or external ophthalmoplegia, and orbital and ocular pain.
Volume Number
Rhinocerebral
40 1
Fig.
n~t~ormycasis
29
2.
Once the unchecked infection reaches the cranial cavity, involvement of the central nervous system with motor and sensory deficits and meningoencepllalitis resultsI” In a high percentage of cases, this results in death of the patient. Oral manifestations are usually limited to the hard palate, where there are sharply demarcated areas of blackish gray csehar covering the surface mucosa with some areas of bony denudation. These areas of necrotic tissues are caused by the thrombosis of blood vessels supplying the area.‘” Radiographic examination demonstrates a combination of changes consisting of nodular thickening of the soft-tissue lining of the maxillary and ethmoid sinuses, but rarely of the frontal sinuses. Radiographs show cloudy antra but noticeable absence of fluid levels in these areas..I43 I5 Tomographic stud,v is cxtremely valuable in evaluating the extent and nature of the bone destructi0n.l” The unilateral exophthalmos seen in this disease sometimes causes confusion, because it is also commonly seen in suppurative sinus infections, cavernous sinus thrombosis, neoplasms, and cellulitis.’ If possible, biopsy specimens should be obtained from involved areas. The diagnosis of mucormycosis is confirmed by microscopic examination of a biopsy specimen and positive mycotic cultures. The mortality in acute cases has been estimated to bc as high as 90 per cent. The high mortality is due, in part, to delayed diagnosis and rapid progression of the underlying disease process.x The first and most important step in treatment is rapid correction of the acidosis.8 Concomitant antibiotics, steroids, and radiation are believed to cause accelerated growth of fungal organisms in the debilitated patient. If mucormycosis is suspected, the USC of these moclalitics sl~oultl he careful1.v re-evaluated and discontinued if possible. Surgical dhbridement of necrotic and &vitalized tissue is helpful in aiding rapid resolution. In 1958, amphotericin B (Fungizone) was shown to be effective in the treatment of mucormycosis.l” Alternate-date administration is the technique of choice, since amphotericin B is nephrotoxic and serum levels of amphotcriein B 48 hours after infusion are considered adequate for most systemic mycotic ag(1nts.l BCcause of nephrotoxicity, therapy should bc temporarily withheld if the blood
30
Berger,
lhpe,
and l'opuziun
urea nitrogen level cswc~ls 50 mg.1100 ml. or the weatinine lrvcl exceeds 3.0 mg./IOO ml.3 The dose of amphotericin B is slowly increased to a final alternateclay tlosc of 1 to 1.2 mg. of alnl)llotcl~i~in B per kilogram of body weight in a time rcgimcn of 4 to 8 weeks.
Volume Number
Rhinocerebral
40 1
mucomycosis
31
right quadrant. Extraction of the maxillary right premolars and first molar did not relieve the pain. Diabetes mellitus was diagnosed 1 year prior to admission, and the patient was placed on an American Diabetic Association diet and Diabinese, 250 mg. three times a day, but follow-up was erratic because of poor cooperation from the patient. One month prior to admission a bloody nasal discharge was noted. The patient’s local physician started antibiotic and analgesic therapy. Over the next several days, the distribution of the right frontal, maxillary, and mandibular nerves exhibited numbness. During the week prior to admission, analgesics became less effective in controlling the pain and the patient was referred to the hospital for treatment. The patient had total right ophthalmoplegia, ptosis, decreased vision of the right eye, and an ulcer on the hard palate (Figs. 1 and 2). A differential diagnosis included carcinoma of the palate, carcinoma of the maxillary antrum, and mucormycosis. The patient was admitted to the hospital in mild ketoacidosis. Admission laboratory findings included hemoglobin, 13.2 Gm. per cent; hematocrit, 42 per cent; white blood count, 7,500/mm.a; and a fasting blood sugar of 420 mg. per cent. Radiographic examination revealed considerable membrane thickening and an air-fluid level in the right maxillary antrum (Fig. 3). Biopsy of the palatal ulceration was performed by the oral surgery service and a diagnosis of mucormycosis was made. The patient received 4 weeks of amphotericin B therapy. The dosage was increased until a dose of 1 mg. per kilogram of hody weight was reached. Sugical therapy included excision of the necrotic area of the hard palate and a right maxillary antrectomy. The surgical site healed well, and a prosthesis was inserted. The patient was discharged 2 months after admission and was seen as an outpatient on March 9, 1968. He was in good health and the diabetes was well controlled. The right eye ptosis mas completely resolved, but the patient had not regained function of the fourth and sixth cranial nerves of the right eye. CASE
2
In August, with the chief
1973, a 34-year-old Negro woman complaint of blindness of the left
was admitted to the hospital eye. Other findings included
medicine associated
service prop-
32
Berger,
Disque,
or:11 July,
and Topazian
Fig.
Surg. 1975
6.
tosis, ophthalmoplegia, orbital cellulitis, a dull, throbbing pain in the left eye, and a history of poorly controlled juvenile diabetes mellitus (Fig. 4). A differential diagnosis of cavernous sinus thrombosis, mucormycosis, retrobulbar tumor, and retro-orbital abscess was made. Admission laboratory findings included hemoglobin, 15.0 Gm. per cent; hematocrit, 4(i per cent ; white I)lood count 21,500; and fasting blood sugar, 310 mg. per cent. Urinalysis revealed 4+ glucose and a large amount of acetone in the urine. Radiographic examination disclosed cloudiness of both frontal sinuses, more on thr left than on the right. Tomograms revealed cloudiness in the anterior ethmoids and the left maxillary sinus, with no air-fluid level (Fig. 5). Further examination disrlosed a black lesion of the nasal septum and a 5 mm. necrotic ulceration of the hard palate. Microscopic examination of biopsy specimens obtained from these arcas by the oral surgery service led to the diagnosis of mucormycosis (Fig. 6). The patient’s diabetic acidosis man quickly corrected with the use of regular insulin. A regimen of alternate-day administration of the antifungal chemotherapeutic agent amphotericin B, involving a total dose of 2 grams divided over a Z-month period, was instituted. An antrectomy through :I Caldwell-Luc approach was performed in order to d6bride the maxillary sinus and to establish drainage. During the 3-month hospitalization, the patient’s diabetes was controlled and the drainage site closed spontaneously with healthy tissue. The necrotic areas on the hard palate and nasal septum healed, and the ocular and paranasal pain gradually disappeared. The patient was discharged when free of clinical signs of active disease, although the blindness, proptoais, and ophthalmoplegia did not resolve. The patient was given periodic re-call appointments but was lost to follow-up when she moved out of state. Attempts to locate her and refer her for follow-up have been unsuccessful.
SUMMARY Dentists need to be aware of the signs and symptoms of rhinocerebral mucormycosis, since it has oral and perioral findings, is associated with extremely high morbidity and mortality, and has clinical findings permitting early diagnosis and treatment. ton, Ga.
The patient in Case 1 was treated KY., by Dr. Topazian. The patient
at the University of Kentucky Medical Center, Lexingin Case 2 was treated at University Hospital, Augusta,
Volume Number
Rhinocerebral
40 1
nwmnzycosis
33
REFERENCES
1. Battock, D. J., et al.: Alternate-Day Amphotericin B Therapy in the Treatmrnt of Rhinocerebral Phycomycosis (Mucormycosis), Ann. Intern. Med. 68: 122, 1968. of the CNS: Report of Three 2. Gregory, J. E., Golden, A., and Haymaker, W.: Murormycosis Cases, Bull. Johns Hopkins Hosp. 73: 405, 1943. 3. Bernstrom. L.. Hemenwav. TN. G.. and Barnhart. R. A.: R,hinocerebral and Otoloaic Mueorm+&is, rinn.‘Otol. 79: id, 1970.’ -1. Lie-Kian-Joe, Eng, N.-I.T., Tjokronegoro, S., Schaafmn, S., and Emmons, C. W.: Phycomycosis of the Central Nervous System Associated With Diabetes Mellitus in Indonesia, Am. J. Clin. Pathol. 32: 62, 1959. 5. Gass. J. D. M.: Ocular Manifestations of Acute Mucormycosis, Ophthalmol. 65: 226, I Arch. 1961:
6. Gass, J. D. M.: Acute Orbital Mucormycosis: Report of Two Cases, Arch. Ophthalmol. 65: 214, 1961. 7. Baum, J. L. : Rhino-orbital Mucormycosis, Am. J. Ophthalmol. 63: 335, 1967. 8. Deweese, D. D., Schleuning, A. J., and Robinson L. B.: Mwomycosis of the Nose and Paranasal Sinuses, Laryngoscope 75: 1398, 1965. 9. Pastore. P. N.: Mucormvcosis of the Maxillarv I Sinus and Diabetes Mellitus. South. Med. J. 60: il64, 196i. ” IO. Ginsberg, J., et al.: Cerebral Phycomycosis (Mucormycosis) With Ocular Involvement, Am. J. Onhthalmol. 62: 900. 1966. 11. Blodi, F.-C., et al.: Lethal Orbito-cerebral Phycomycosis in Otherwise Healthy Children, Am. J. Ophthalmol. 67: 698, 1969. 12. Reeves, D. L., et al.: Phycomycosis (Mucormycosis) of the Central Nervous System, J. Neurosurg. 23: 82, 1965. 13. Taylor, C. G., et al.: Mucormycosis (Phycomycosis) Tnvolving the Maxilla, ORAL SURO. 27:
806, 1969.
14. Baker, R. 15. Chick, E., bits With 16. Green, W. 101: 802,
D.: Editorial: Diabetes and Mucormycosis, Diabetes 9: 143, 1960. Evans, J., and Baker R. D.: Treatment of Experimental Mucormycosis in RabAmphotericin B, Antibiot. Chemother. 8: 394, 1958. H.: Mucormycosis Infection of the Craniofacial Structures, Am. J. Roentgenol. 1967.
Reprint requests to : Dr. Richard G. Topazian School of Dental Medicine Room B-7094 University of Connecticut Farmington, Conn. 06032
Health
Center
