Biomedical subjects
Publications and source records attributed to S E Young.
The incidence of ocular metastases is approximately 300,000 cases a year, most often from breast or lung primaries. Usually, the primary has already been diagnosed, and the appearance of ocular metastases is an ominous sign. Sometimes ocular metastases may be the first sign of a systemic primary. The authors describe what to expect on ophthalmological examination of a patient with cancer, and what the findings can tell you.
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Comparing data relating to the estimated incidence of infective endocarditis and deaths due to this condition highlights the changing age and sex patterns over the last 50 years. Using these data it is estimated that about 20 cases per million population per year can now be expected many of whom will be aged 65 years or more. About 20% of cases die. Viridans streptococci are responsible for almost half the cases of endocarditis, faecal streptococci for 11%, staphylococci for 20% and Coxiella burnetii for 2-3%. The laboratory data for 1976-85 showed that 86 of 821 (10.5%) patients with Staphylococcus aureus endocarditis had valve prostheses and 55 (6.7%) were iv-drug abusers. Of the patients with endocarditis due to coagulase-negative staphylococci 100 of 361 (27.7%) had prostheses.
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The epidemiology of meningococcal infections that arose in England and Wales during the period 1912-1983 has been reviewed. The outcome of meningococcal disease was dramatically improved when treatment with sulphonamides was introduced. With the emergence of sulphonamide-resistant strains, penicillin has become the drug of choice. Despite modern treatment, however, the mortality ratio during the last 30 years has remained about the same. Prompt diagnosis as well as immediate and effective treatment are cardinal needs. Even so, when infection is overwhelming there is little chance of saving the patient. Immunisation is probably the only effective answer but as yet there is not an effective vaccine to prevent group B infections which predominate in this country.
Thirty-five patients with malignant brain tumors (23 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation +/- chemotherapy received cisplatin, 60 to 120 mg/m2, into the internal carotid artery by a transfemoral approach. Courses of therapy were repeated every 4 weeks. Therapeutic evaluation was performed monthly using the CT scan of the brain and clinical neurologic examination. Thirty patients were evaluable for response. Of 20 evaluable patients with primary malignant brain tumors, 6 responded to therapy and 5 had stable disease. The median time to tumor progression for responding patients was 33 weeks, for stable patients 16 weeks, and 13 weeks for all patients. Five of 10 evaluable patients with brain metastases responded to intracarotid cisplatin, and 2 patients had stable disease. The estimated median time to progression for responding patients was 30+ weeks and 12+ weeks for patients with stable disease. Side effects included seizures in 5 courses, mental agitation and motor restlessness in 1, and transient hemiparesis in 7. One patient may have had a drug-related death, and one patient appeared to develop encephalopathy after treatment. Five patients had clinical deterioration in vision; in two patients it was bilateral. Intracarotid cisplatin has definite activity in patients with malignant primary brain tumors and in patients with brain metastases. The recommended starting dose for intracarotid cisplatin is 60 to 75 mg/m2. At this dose level side effects are uncommon, but includes the risk of neurologic and retinal toxicity.
A study of routine data on mumps in England and Wales suggests that its epidemiological features are changing from those of an epidemic disease in young adults and older children to a more endemic disease in younger children. Infection now occurs at an earlier age, at which complications are less frequent and symptomless infection may be more common. The incidence of clinical disease may be falling. The high proportion of registered deaths in the middle aged and elderly may be an artifact due to misclassification of causes of death and to misdiagnosis. These changes lessen the need for routine immunisation. Indeed with low acceptance rates of measles vaccination of 50% at age 15 months, mumps/measles routine vaccination at the same age is contraindicated because similarly low acceptance rates might lead to an increase in the number of cases of mumps in older children and young adults, at which ages complications are more frequent.
Of 582 episodes of infective endocarditis 75 were attributable to organisms normally resident in the bowel and 12 others were associated with alimentary tract operations, investigations, or disease. The mean age of the 87 patients in this particular group was higher (59.7 years) than that of all the patients with infective endocarditis (51.4 years). As far as could be ascertained 41% had no pre-existing cardiac abnormality, and in a little under a half no predisposing event to initiate the illness was apparent. Where the portal of entry of the organism to the blood stream was evident it was slightly more often in the genitourinary than the alimentary tract. Bowel organisms are no less important than those associated with the teeth in causing infective endocarditis. It is suggested that in all those patients with known cardiac abnormalities and possibly in those over the age of 60 with normal hearts antibiotic cover should be considered when they undergo genitourinary or alimentary tract surgery or instrumentation.
Some details of 544 episodes of infective endocarditis occurring in 541 patients during 1981 and 1982 are reported. The mean age of patients was 51.6 years and there was a greater proportion of males (2:1). Of the 544 episodes 347 (63%) were due to streptococci, 19% to staphylococci, and 14% to bowel organisms. A wide variety of other organisms were responsible for a few cases, and 10% were culture negative. In 60% the portal of entry of the infection could not be ascertained: 19% were probably of dental origin: 16% arose from the alimentary, genitourinary, or respiratory tracts or from the skin or in association with drug addiction, fractures, or pregnancy; the remaining 5% were related to cardiac or other vascular surgery, cardiac catheterisation, haemodialysis, or other procedures involving the blood stream. Seventy-four (14%) of the 541 patients (mean age 59.0 years) died; the mortality was 30% in staphylococcal cases, 14% in infections due to bowel organisms, and 6% in other streptococcal infections. One hundred and seventy-one (32%) of the patients appeared to have had normal hearts before the onset of illness and another 59 (11%) had cardiac lesions not previously recognised. The aortic valve was the most common site of infection. Ninety (17%) of the patients had prosthetic valves or had undergone other cardiac surgery while 34 (6%) had had a previous episode of infective endocarditis. Nine (1.6%) episodes were not diagnosed until necropsy or operation and 34 (6.3%) required urgent valve replacement.
Endocarditis was recorded in 92 (11%) of 839 confirmed Q-fever infections reported for the Communicable Disease Report by laboratories between 1975 and 1981; Q-fever endocarditis accounted for approximately 3% of all cases of endocarditis reported. Two-thirds of the 92 reports were of men, and in both men and women endocarditis affected mainly young and middle-aged adults. Only one-third of Q-fever endocarditis patients were noted to have an underlying heart-valve lesion. There were also 30 reports of chronic Q-fever infection, and in 10 the primary clinical feature was liver disease. The laboratory data do not support the view that Q-fever endocarditis is a rare compilation of Coxiella burnetii infection, and the condition may be considerably underdiagnosed. Joint veterinary and medical investigations should be undertaken to establish the natural history of Coxiella burnetii infection in the U.K. in order to formulate policies for prevention of acute and chronic infection.
Two hundred fifty patients with breast carcinoma had ocular examinations between 1973 and 1980. One hundred fifty-two patients were referred because of ocular symptoms or signs, and 98 were asymptomatic. Of the symptomatic patients, 58 had choroidal metastases; nine of the asymptomatic patients with stage IV metastatic breast cancer had choroidal involvement (9.2%). For the 67 patients with metastases, the median age at ocular diagnosis was 51 years. The median interval from primary to choroidal metastases was three years. Survival after ocular diagnosis ranged from one week to four years, with a median of nine months. Among the 67 patients, choroidal tumor deposits occurred bilaterally in 27 patients (40.3%), in 18 right eyes (26.9%), and in 22 left eyes (32.8%). Irradiation led to stabilization or improvement in visual acuity in virtually all cases. Patients in whom acuity was not threatened were observed on medical therapy. Four of these patients eventually required irradiation for increasing disease. Choroidal metastases tended to follow pulmonary dissemination, and to occur with or before central nervous system disease. Choroidal metastases are a common, treatable event in breast carcinoma and may represent the smallest detectable clinical lesion.
A phase I study of intracarotid cis-diamminedichloroplatinum was performed in 11 patients with intracerebral tumors (five glioblastoma, four melanoma, one meningeal sarcoma, and one lung carcinoma) progressing after radiation +/- chemotherapy. The internal carotid artery was temporarily cannulated by a percutaneous transfemoral approach. All patients received i.v. heparin, mannitol, and fluids; seven received dexamethasone, 50 mg i.v., twice the day before and the day of treatment. Intracarotid cis-diamminedichloroplatinum, 60 to 100 mg/sq m in 175 to 250 ml 0.45% NaCl solution with 1000 units heparin, was infused over 1 hr. Six patients received two or more courses (maximum of 6) at 2- to 8-week intervals. Gastrointestinal toxicity was mild to moderate. Ototoxicity was minor. Central nervous system (CNS) toxicity was focal, severe, permanent, and possibly due to embolus in one patient at 75 mg/sq m; focal and reversible in one patient at 100 mg/sq m; and generalized but reversible in one patient at 75 mg/sq m. Possible CNS toxicity was noted in two additional patients. Two patients with CNS toxicity developed permanent ipsilateral retinal toxicity, and one patients without CNS toxicity developed bilateral decreased visual and auditory acuity 2 weeks after his sixth treatment. Renal and hematological toxicity and orbital pain were mild. Response status included: early death, one; probable responses, six (2+ 4+, 6, 6+, 8, and 8+ months); stabilization, two (3+ and 4 months); and failure, two. We recommend cis-diamminedichloroplatinum (60 mg/sq m) every 2 to 4 weeks for Phase II studies. Severe CNS and retinal toxicity are possible.
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We reviewed the records of 73 patients with primary melanoma of the choroid and ciliary body with metastasis treated at M. D. Anderson Hospital and Tumor Institute between 1973 and 1979. At time of diagnosis of primary melanoma 71 of 73 patients had tumor localized to the eye and were treated with enucleation of the affected eye. The interval from resection of primary tumor to detection of systemic metastases in the 71 patients ranged from one to 201 months (median 43.5 months). Weight loss and abdominal pain due to hepatomegaly were the most common symptoms, and hepatomegaly was the most common physical sign. The liver was the most common site of tumor recurrence, occurring in 44 of 71 patients. Among liver enzymes, serum lactic dehydrogenase was found to be the most sensitive indicator of liver metastasis and was elevated in 96% of patients with tumor in the liver. Liver involvement with tumor was associated with poor response to chemotherapy and significantly poorer survival than involvement of other extracranial sites. The survival duration from time of development of systemic metastasis ranged between one and 31 months (median seven months), with a one-year survival rate of 29%. The median survival of patients from diagnosis of ocular melanoma was 52 months, with a five-year survival rate of 43%.
Fifty incidents of scombrotoxic fish poisoning affecting nearly 200 people have been reported in Britain, the majority in 1979. Increased consumption of mackerel, inadequate storage conditions, and more general clinical recognition of the condition are considered responsible for the rise in outbreaks. Though the illness is generally not serious, it may be alarming and unpleasant and is totally preventable by proper attention to principles of hygiene at all stages of production, distribution, and storage.
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This monograph has considered the clinical features, differential diagnosis, diagnostic approaches, treatment and prognosis for primary and secondary tumors of the uveal tract. Tumors metastatic to the uvea are the most common intraocular malignant lesions, although primary uveal melanomas are recognized more frequently clinically. These tumors differ considerably with regard to clinical features and in the recommended approach to systemic evaluation and treatment. The diagnosis and management of such tumors should be a joint effort between the ophthalmologist and other physicians.
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