Cancer surveillance. Who stands to benefit?

Currently, surveillance or risk-oriented follow-up of patients in the individual practice setting may be the most efficacious means of reducing the morbidity and mortality associated with selected types of cancer. Intervention into carcinogenesis or alteration of the natural history of cancer requires a clear understanding of the pathogenesis of the disease and patient acceptance of interval surveillance. Because etiologic information and patient compliance are frequently limited, careful scrutiny of recommendations for cancer screening or prevention is essential. It is through taking detailed family, occupational, and carcinogen-exposure histories and doing a thorough physical examination that the primary care physician can best utilize information regarding the risk of cancer and the benefits of available methods of prevention and treatment.

Effects of altered porphyrin synthesis on brain neurochemistry.

Lead is one of several environmentally significant substances which alter porphyrin synthesis in several organs. Biochemically, the consequences of both acute and chronic lead exposure, at relatively low dose, are increases in tissue and plasma levels of the porphyrin precursor aminolevulinic acid (ALA) and inhibition of the enzyme ALA dehydrase. These effects are considered for their possible role in the neurotoxicity associated with lead exposure. The effects of lead, on porphyrin metabolism and on neurochemistry and behavior, are compared to those associated with exposure to the "suicide" inhibitor of ALA dehydrase, succinylacetone. Similarities in both porphyrinopathy and in associated neurotoxicity suggest an etiologic role for altered porphyrin synthesis in lead neurotoxicity.

Hepatic protoporphyrin production in human protoporphyria. Effects of intravenous hematin and analysis of erythrocyte protoporphyrin distribution.

Human protoporphyria with atypical features suggesting increased hepatic protoporphyrin synthesis was investigated in 2 patients. Analysis of the distribution of protoporphyrin among circulating erythrocytes of increasing age indicated that the erythrocyte porphyrin burden derived predominantly from erythroid sources in case 1, and from hepatic sources in case 2. Intravenous hematin was administered to both patients to assess any negative feedback effect on protoporphyrin synthesis. Erythrocyte, fecal and plasma porphyrin levels were measured serially during basal, treatment, and follow-up periods. In case 1, a significant (P less than 0.001) drop in both fecal and plasma levels accompanied hematin, while erythrocyte levels remained unchanged. Hematin produced no appreciable changes in porphyrin concentrations in case 2. Allergic vasculitis followed hematin use in both cases. Based on data of this study and on previous data, a model for protoporphyrin transport and clearance was developed in which the variable clinical and biochemical manifestations of human protoporphyria are related to the relative contributions of erythroid and hepatic sources to the abnormal protoporphyrin pools.

Hematin therapy for acute porphyria.

1. A therapeutic trial of intravenous hematin is presented. Eleven cases of AIP and one of VP who did not improve with conventional treatment (high carbohydrate intake) received this new agent. 2. Urinary ALA, PBG and, when possible, uroporphyrin and coproporphyrin were used to monitor the chemical response to the treatment. Objective clinical parameters of hypertension and tachycardia were followed when present in addition to subjective estimates of acute porphyric symptomatology (abdominal pain, backache, extremity pain and paresthesias, weakness, depression, etc.). 3. At a dosage of approximately 3 mg/kg, diminution of urinary ALA and PBG excretion was achieved in every patients. Hypertension and tachycardia improved in those instances where they were observed in association with the attack. Also, subjective improvements in the clinical status of the patients were observed frequently. 4. Hematin appears to be a promising therapeutic agent for the treatment of acute attack forms of porphyria.

Hematin administration to an adult with lead intoxication.

Lead poisoning and acute intermittent porphyria (AIP) may exhibit similar neurologic manifestations, and they have in common elevated excretion of urinary aminolevulinic acid (ALA). Despite their similarities, the possible pathophysiologic connection between AIP and lead poisoning in not known. Because intravenous hematin administration has produced biochemical improvement in AIP, a hematin trial in lead intoxication was of interest with respect to some of the heme metabolism abnormalities observed in the condition. Significant diminution of urinary ALA and coproporphyrin excretion occurred in association with intravenous hematin administration.

Family evaluations in acute intermittent porphyria using red cell uroporphyrinogen I synthetase.

Acute intermittent porphyria (AIP) is a primary disorder of haem biosynthesis that is chemically characterised by raised urinary porphobilinogen (PBG). A defect in the biochemical pathway at the step of PBG conversion to uroporphyrinogen has been shown to be a result of a partial deficiency of the enzyme uroporphyrinogen I synthetase (uro I syn). The ascertainment rate of latent AIP (that is, chemically manifest but clinically asymptomatic) was examined in 185 individuals from 12 AIP kindreds using three parameters: red cell uro I syn, quantitative urinary PBG, and pedigree analysis with respect to uro I syn. Approximately 80% of individuals could be assigned as normal or latent AIP on the basis of the uro I syn assay alone. The remaining 20% could not be assigned because of an intermediate range of activity for the red cell assay in which the diagnosis cannot be certain. When the pedigree was used in the evaluation of the uro I syn data, the number of uncertain individuals, with respect to AIP, decreased to 10%. The enzyme method detected latent AIP in 37.5% of blood relatives, whereas quantitative urinary PBG alone detected only 15.2%. The pattern of inheritance for the uro I syn deficiency is consistent with Mendelian dominant inheritance, and it is likely that it is the basic inherited defect in AIP.

Idiopathic hemochromatosis in a young female. A case study and review of the syndrome in young people.

Idiopathic hemochromatosis (iH) is typically a disease of older males. The case presented here describes a 26-yr-old woman with problems presenting heart failure, insulin-dependent diabetes, hepatomegaly, and secondary amenorrhea. The diagnosis was established by serum iron and transferrin saturation measurements, liver biopsy, and bone marrow examination for iron. Twenty grams of iron were removed by phlebotomy over 30 mo, and the patient's symptoms improved. A review of the literature pertinent to people with symptomatic onset of IH before age 30 yr revealed 52 young people in addition to this case. In contrast to IH patients older than 30, there was an almost equal ratio between the sexes, a greater frequency of cardiomyopathy and hypogonadism, and a lower frequency of diabetes mellitus and hepatic involvement. An autosomal recessive mode of inheritance appears to be most likely in this young group.

Danazol administration to females with menses-associated exacerbations of acute intermittent porphyria.

Acute intermittent porphyria (AIP) is a disorder of porphyrin metabolism in which the basic defect is a partial deficiency of uroporphyrinogen I synthase. The clinical disorder is more common in women, and some experience acute attacks before menstrual periods. Oral contraceptives have prevented menstrual-associated attacks in some cases, but exogenous estrogens and progestins are otherwise contraindicated in this disease. Danazol, a new synthetic steroid with weak androgenic activity, was thought to be of potential therapeutic benefit in AIP because of its effect of decreasing gonadotropin secretion without exposure to estrogen or progesterone. The drug was administered at a dosage of 200 mg t.i.d. to two adult females with AIP who were experiencing frequent exacerbations of their disease in association with their menstrual periods. Symptomatic and chemical evidence for exacerbation of porphyria occurred within 10 days of commencing danazol treatment in both patients.

Prevention of acute porphyric attacks by intravenous haematin.

A thirty-three-year-old female with acute intermittent porphyria (A.I.P.) was having regular attacks of the disease with her menstrual periods. During several of these attacks she received intravenous haematin, which was followed by chemical and clinical remissions. Hormones failed to prevent the regular attacks, which were completely prevented by 200 mg of haematin, given approximately once a week for six months. There were no changes in menstruation. The monthly attacks recurred on withdrawal of haematin.

Screening tests in acute porphyria.

Two recognized screening procedures for rapid evaluation of urinary porphobilinogen (PBG) concentrations are compared with quantitative PBG determinations (expressed as mg/24 hours and as a concentration in urine, mg/liter). One hundred ninety-one 24-hour urine specimens from 74 patients with suspected or documented acute type porphyria are included in this investigation. The two screening tests are compared with regard to sensitivity and method of performance. In this study, the Watson-Schwartz and Hoesch tests are positive at PBG concentrations in urine greater than 9 mg/liter. Both methods produced the characteristic pink color only once at a concentration below 3 mg/liter. Both methods are useful in detecting the abnormal concentration of urinary PBG observed during an acute porphyric attack. The Hoesch procedure provides a simple and rapid evaluation of urinary PBG. Positive results from either screening test demand quantitative urinary PBG determinations to confirm the suspected abnormality.

Haemophilia, hepatitis and porphyria.

A patient with haemophilia A developed hepatitis B, seemingly as a consequence of treatment with blood products. Six years later, bullae, photosensitivity, and the biochemical findings of porphyria cutanea tarda developed.