A reliable diagnosis of porphyria should precede any conclusion concerning the safety of a drug in porphyria.
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Anesthetics, Intravenous↗
Biomedical subjects
N Schoenfeld
Publications and source records attributed to N Schoenfeld.
Clinical problem-solving. A leading question.
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Abdominal Pain↗
Clinical findings in 715 patients with newly detected pulmonary sarcoidosis--results of a cooperative study in former West Germany and Switzerland. WATL Study Group. Wissenschaftliche Arbeitsgemeinschaft für die Therapie von Lungenkrankheitan.
BACKGROUND AND AIM OF WORK: Clinical appearance of sarcoidosis depends on the methods of case finding and geographical factors. In a further effort to clarify clinical characteristics of pulmonary sarcoidosis, we examined a larger population of consecutive pulmonary sarcoidosis cases throughout former West Germany and Switzerland. METHODS: In a prospective multicenter study from January 1982 to December 1984, 715 patients with newly-diagnosed pulmonary sarcoidosis were studied for their clinical appearance, roentgenological and laboratory findings and pulmonary function. RESULTS: The group consisted of 366 male and 349 female patients with a median age of 33 years (range 14 to 76). 35% presented with roentgenological stage I disease, 51% with stage II and 14% with stage III. Extrapulmonary manifestations were found in 16%. Angiotensin converting enzyme was elevated in 62% of the cases. Lung function tests revealed a restrictive pattern in 19% and airway obstruction in 4%; 2% showed a combined ventilation disturbance. 66% of our patients were symptomatic in contrast to reports from former East Germany, a country with mass X-ray screening where only 18 to 35% of the patients presented with symptoms and 51 to 74% were in stage I. CONCLUSIONS: Differences between our findings and data from East Germany underline the importance of case finding methods for the patterns of clinical appearance of sarcoidosis.
Adolescent↗
Yeast, creatinine and false diagnosis of porphyria.
A distressingly common occurrence is the erroneous diagnosis of hepatic porphyria in patients with chronic abdominal pain in which either urinary porphyrins are elevated and/or Watson-Schwarz test is positive. This work investigates a characteristic case and points at possible pitfalls in establishing a diagnosis. In the patient described, spot urine analysis showed positive Watson-Schwarz test and increased porphyrins at three separate occasions, while normal values of precursors and porphyrins were recorded in 24-hrs. urinary collections during four hospitalization periods for acute abdominal pain. Various colorimetric and HPLC methods employed excluded the diagnosis of porphyria and led to resolving the discrepancy between home and hospital results. It was found that the false increase in porphyrins in the spot samples emerged from a substance present in yeast tablets which the patient was consuming. The positive Watson-Schwarz test obtained was probably the result of the fact that the urine samples were concentrated with creatinine values exceeding 400 mg%. The case reported above, as well as studies carried out in three healthy volunteers and in an AIP patient, led to the conclusion that in order to obtain reliable result, 24-hrs. urinary collections should be examined, rather than spot urine samples.
Alanine Transaminase↗
Laminin fragment P1 in the sera of patients with pulmonary sarcoidosis.
Laminin is a noncollagenous component of the extracellular matrix in the alveolar wall and may play a role in the development of fibrotic lung disease. Serum levels of laminin fragment P1 as well as procollagen III peptide were determined in 28 patients with pulmonary sarcoidosis and 10 healthy controls using specific radioimmunoassays. The patients' results were compared with the clinical appearance, lung function values (vital capacity, total lung capacity, FEV1, transfer coefficient (KCO), and alveolar-arterial oxygen difference during exercise) and serum concentrations of angiotensin converting enzyme and soluble interleukin 2 receptor. Laminin levels in patients were significantly higher than in controls but always remained within normal limits. Although there was a tendency towards higher values in patients with active disease and with radiographic involvement, no significant correlation was found between laminin concentration and clinical, functional or biochemical data. In contrast, procollagen III N-terminal peptide concentrations were elevated in 19 of 28 patients and showed a weak but significant inverse correlation with parameters of restriction with significantly higher values in patients with active disease. In conclusion, serum levels of laminin fragment P1 are not elevated in pulmonary sarcoidosis and do not correlate with other parameters of the disease. Yet serum levels of procollagen III N-terminal peptide were associated with the degree of parenchymal involvement as expressed by functional disturbance and with active disease.
Adult↗
Twenty two year survival after incomplete resection of advanced adenoid cystic bronchogenic carcinoma.
In 1972, a 42 year old patient underwent thoracotomy for adenoid cystic carcinoma of the left main-stem bronchus. Pneumonectomy was performed, but the resection was not complete as the tumour had invaded the aortic and tracheal wall. The patient did not receive postoperative radiotherapy. In 1993, the patient was readmitted with severe respiratory insufficiency due to complete endobronchial tumour obstruction of the intermediate bronchus and extensive tumour growth in the mediastinum. Endobronchial laser treatment followed by stent implantation led to immediate symptomatic relief. The tumour then responded well to combined endobronchial and percutaneous radiotherapy. The patient died 7 months after readmission from ileus due to pancreatitis. We conclude that patients with advanced adenoid cystic carcinoma may profit from palliative surgery with respect not only to symptoms but also to duration of life.
Adult↗
Bullous dermatosis of end-stage renal disease: a possible association between abnormal porphyrin metabolism and aluminium.
BACKGROUND: Bullous dermatosis (BD) is becoming increasingly recognized in patients with end-stage renal disease (ESRD). It is clinically reminiscent of porphyria cutanea tarda, but its detailed pathogenesis remains unclear. Studies have shown increased porphyrin levels in dialysis patients, and this may partly explain the skin lesions and photosensitivity evident in these patients. In experimental studies, aluminum can induce various abnormalities in porphyrin and haem metabolism. This study investigated a possible involvement of porphyrin metabolism and aluminum in the development of bullous dermatosis in chronically dialysed patients. METHODS: Three groups were studied (12 healthy controls; 12 patients on chronic dialysis without BD and six patients on chronic dialysis with BD). Clinical characteristics of these patients were evaluated and the levels of plasma porphyrins, erythrocyte porphyrins and enzymes involved in the porphyrin chain were determined. RESULTS: The patients with BD were predominantly male, 50% had ADPKD, all had been on dialysis for a long period of time (7.8 +/- 2.1 years) and all were anuric. CAPD and haemodialysis were used equally in the affected patients. Aminolaevulinic dehydratase activity was significantly reduced in all ESRD patients (892 +/- 47 versus 302 +/- 36 versus 408 +/- 37 nmol/ml RBC/h). Plasma uroporphyrins as well as RBC protoporphyrin were significantly elevated in ESRD patients (1.7 +/- 0.6 versus 21.6 +/- 4.7 versus 43.4 +/- 12.0 nmol/L) and (1.43 +/- 0.14 versus 2.4 +/- 0.42 versus 4.19 +/- 2.44 mumol/l) respectively. Serum A1 levels were markedly elevated in patients with BD (28.3 +/- 10.0 micrograms/l). Both uroporphyrin and protoporphyrin were significantly more elevated in ESRD patients with BD compared to ESRD patients without BD. CONCLUSIONS: Elevated plasma porphyrin levels in ESRD patients are caused by lack of urinary excretion and the inability of haemodialysis and CAPD therapy to remove them. These elevated porphyrin levels may lead to the development of porphyria cutanea tarda symptoms. Elevations in plasma uroporphyrin, red blood cell protoporphyrin, and elevated A1 levels suggest a possible relationship between an A1 'load' and abnormal porphyrin metabolism in the development of overt skin disease in the dialysed patient.
Aged↗
Relation between uroporphyrin excretion, acute attacks of hereditary coproporphyria and successful treatment with haem arginate.
1. The increased urinary excretion of porphyrins as well as of their precursors was studied in a patient with hereditary coproporphyria during two acute attacks in which symptoms differed markedly in character and severity. 2. The increase in urinary coproporphyrin was similar in the 'mild' and in the 'severe' attack, indicating a lack of correlation between coproporphyrin level and clinical symptoms. 3. Aminolaevulinic acid, porphobilinogen and uroporphyrin exhibited significantly higher values during the 'severe' attack than during the 'mild' attack. During the severe attack these three compounds were increased 18-, 14- and 46-fold, respectively, compared with increases of 3-, 3- and 8-fold, respectively, during the mild attack. 4. The striking rise in the formation of uroporphyrin was reflected in the plasma porphyrin profile, which revealed predominance of uroporphyrin. In accordance with this finding, an increase in erythrocyte porphobilinogen deaminase of 130% was recorded. 5. The fluorescence emission spectra of saline-diluted plasma (excitation of 405 nm) showed a distinct peak at 618 nm during the 'severe' episode and a small peak during the 'mild' attack, pointing to the possibility of diagnosing an attack simply by following the fluorometric screen of plasma. 6. The 'severe' attack of coproporphyria was treated with daily infusions of haem arginate, 3 mg/kg, every day for 4 days, at the end of which period a dramatic clinical response was observed. The relief of symptoms was found to be clearly related to the moderate decrease in uroporphyrin excretion observed rather than to the steep decline in the precursors.
Acute Disease↗
Decreased uroporphyrinogen decarboxylase activity in patients with end-stage renal disease undergoing hemodialysis.
Raised plasma uroporphyrin levels were found in all the 14 patients with end-stage renal disease studied, 7 of whom were on continuous ambulatory peritoneal dialysis (CAPD) and 7 on hemodialysis (HD). The elevation observed in the HD group was higher than that noted in the CAPD group; 18-fold in the former and 13-fold in the latter. The difference in uroporphyrin plasma levels between the two dialysis populations might be explained, at least partially, by the reduced activity of uroporphyrinogen decarboxylase (UROD), the enzyme which converts uroporphyrinogen to coproporphyrinogen. A decrease of 48% was noted in the HD group, whereas no change was observed in the CAPD group. A significant negative correlation (r = -0.37, p < 0.01) was found between the concentration of uroporphyrin in plasma and the activity of UROD. In view of the data shown, it is suggested that erythrocyte UROD activity should be interpreted with caution in HD patients suspected of having porphyria cutanea tarda.
Chromatography, High Pressure Liquid↗
Activation of bronchoalveolar lavage T lymphocytes and clinical, functional and radiological features in sarcoidosis.
Previous studies on the relationship between activated BAL T lymphocytes and clinical features in sarcoidosis revealed controversial results. We determined lavage lymphocytes, T lymphocytes, activated T lymphocytes, helper, suppressor and natural killer cells in 50 patients with pulmonary sarcoidosis and compared the results with clinical findings, serum angiotensin converting enzyme (ACE), the radiological pattern and lung function data (vital capacity [VC], total lung capacity [TLC], FEV1, transfer coefficient KCO and arterial-alveolar oxygen difference [AaDO2] during exercise). Patients with erythema nodosum (n = 7) showed a lower proportion of activated T lymphocytes (p < 0.05) and lymphocytes (p < 0.01) than the other patients. There was a significant correlation between activated T lymphocytes and AaDO2 during exercise (r = 0.49, p < 0.001), and an inverse correlation was seen between activated T lymphocytes and VC or TLC (r = -0.35 and r = -0.36, p < 0.01). We conclude that the percentage of activated BAL T cells may be related to the degree of parenchymal involvement as expressed by functional disturbance.
Adult↗
Protoporphyrin biosynthesis in melanoma B16 cells stimulated by 5-aminolevulinic acid and chemical inducers: characterization of photodynamic inactivation.
The stimulation of protoporphyrin (PP) biosynthesis in B16 melanoma cells in order to facilitate photodynamic cell killing was studied. Biosynthesis and accumulation of PP in the melanoma cells was increased from 8 to 15 pmol/mg protein by the use of dimethyl-sulfoxide (DMSO), a differentiation-inducer. Treatment of the cells with the porphyrogenic agent allylisopropyl-acetamide (AIA) stimulated an additional PP increase. The most remarkable enhancement of intracellular PP was achieved by the supplementation of 5-aminolevulinic acid (5-ALA) to the growth medium following the addition of DMSO and AIA during the induction phase. The intracellular concentration of PP exceeded 21,950 pmol/mg protein following combined stimulation by DMSO/AIA and 5-ALA. The porphyrins produced in the incubated cells, in serum-depleted medium, consisted of 95% PP; 88% of it was recovered from the cells and only 7% was excreted into the medium. Photosensitization of the B16 melanoma cells containing high PP concentrations was effective even at low light doses. Potassium (K) efflux was the first measurable sign of cell damage determined by X-ray microanalysis (XRMA) following fast liquid-nitrogen fixation. During a 1 min interval, 70% of cellular K was lost. After 5 min illumination, complete cell destruction was detected by scanning electron microscopy (SEM) and XRMA. The photodamaged cells showed influx of Na, Cl and Ca ions accompanying the immediate K losses. Ultrastructural cell damage was manifested by disintegration of the outer membrane. Total cell death of B16 melanoma cells was achieved by chemical induction of endogenous PP and photosensitization.
Allylisopropylacetamide↗
Transformation, growth rate, and the heme biosynthetic pathway in V-abl-transfected fibroblasts.
The relationship between growth rate and various parameters of the heme biosynthetic pathway was studied in two cell lines of rat fibroblasts (REabl-1 and REabl-3) transfected with v-abl oncogene, coded by the Abelson murine leukemia virus, and subjected to glucocorticoid dependent transformation. In the REabl-1 cell line, whose growth rate was only slightly affected by dexamethasone (DX), almost no change was noticed either in heme content or in the enzymatic activities of aminolevulinate synthase (ALAS), porphobilinogen deaminase (PBGD), and ferrochelatase (FC) in the presence of various concentrations of DX. In the REabl-3 cell line, exhibiting a growth rate highly sensitive to DX, a significant reduction in intracellular heme concomitantly with decreases in ALAS and FC activities and a threefold increase in PBGD were noted. The fact that incubation with 10(-5)M hemin did not result in a decrease in ALAS activity raised the possibility that REabl cells lack a negative feedback control mechanism. The relationships between transformation, growth rate, and heme biosynthetic pathway are discussed.
5-Aminolevulinate Synthetase↗
Evidence for the interference of aluminum with bacterial porphyrin biosynthesis.
Aluminum (0.74 mM) was found to retard bacterial growth, and enhance porphyrin formation and excretion in Arthrobacter aurescens RS-2. Coproporphyrin III was shown to be the main porphyrin excreted by aluminum-exposed A. aurescens RS-2 cultures and by RS-2 cultures grown under anoxic conditions. Synthesis and excretion of porphyrins in A. aurescens RS-2 increased in a dose-dependent manner when the bacteria were exposed to increasing aluminum concentrations. Incubation of A. aurescens RS-2 with delta-aminolevulinic acid (delta-ALA, 1.2 mM) brought about the intense formation and excretion of porphyrins by the cells, in the presence or absence of aluminum. delta-ALA slightly enhanced the toxicity of aluminum towards RS-2 bacteria. Furthermore, the intracellular concentration of heme was reduced by 63.9 +/- 8.67% in aluminum-exposed RS-2 bacteria when compared with control cultures. The results are discussed in light of the recent finding concerning aluminum toxicity and porphyrin biosynthesis in microorganisms.
Aluminum↗
Specification and quantitation of circulating immune complexes in the serum of patients with active pulmonary sarcoidosis.
BACKGROUND: Circulating immune complexes can be elevated in serum samples of patients with sarcoidosis and are associated with disease activity, but their diagnostic significance is not understood. METHODS: The different classes of circulating immune complexes containing immunoglobulin A, G, or M, and the content of complement in circulating immune complexes (polyethylene glycol precipitation) as well as levels of complement binding circulating immune complexes (complement binding assay) were determined in 19 patients with active, untreated pulmonary sarcoidosis. The results were compared with other parameters in the serum (soluble interleukin 2 receptor, angiotensin converting enzyme, immunoglobulin A, G, and M) and the bronchoalveolar lavage fluid (lymphocytes, helper cells, suppressor cells, activated T cells), and with radiological stage and functional parameters (FEV1, vital capacity, total lung capacity, transfer coefficient (KCO), and the alveolar-arterial oxygen difference during exercise). RESULTS: In all patients circulating immune complexes could be detected by polyethylene glycol precipitation and were similar to control subjects. The content of C1q in circulating immune complexes was higher than in controls, yet in all but one of the cases was still within normal limits. In contrast, elevated levels of complement binding circulating immune complexes were found in 67% of the patients. No correlation was seen between circulating immune complexes and any of the other parameters in the serum, bronchoalveolar lavage fluid, or lung function values. No differences were found between radiological type I and II presentations of sarcoidosis. CONCLUSIONS: The complement binding assay showed a much higher sensitivity for the detection of circulating immune complexes in active pulmonary sarcoidosis than the polyethylene glycol precipitation method. As there was no correlation between levels of circulating immune complexes and other parameters of the disease they are probably not useful for the assessment of disease activity.
Adult↗
Role of endoscopy in the preoperative assessment of bronchial carcinoma.
The decision for surgical measures in bronchial carcinoma is mainly based on the preoperative assessment of the presumed tumour extent and cell type, as well as cardiopulmonary function. Bronchoscopy, as an obligatory procedure, allows a definite diagnosis in most of the cases, definition of the most proximal tumour extension and exclusion of bilateral endobronchial disease. Transbronchial needle aspiration can provide important information on lymph node involvement, although mediastinoscopy has the highest diagnostic yield and remains the standard procedure for lymph node staging. Thoracoscopy, providing a much higher sensitivity than thoracentesis, enables differentiation between malignant or para-malignant pleural effusion in almost all of the cases. Thus, endoscopy alone often demonstrates unresectability.
Algorithms↗
Nonproductive cough, weight loss and bilateral pulmonary infiltrates.
A 50 year old male smoker was admitted with nonproductive cough, weight loss and bilateral infiltrates predominantly in the upper lung zones on chest X-ray. Before admission he had been treated for suspected tuberculosis without improvement. The definite diagnosis of pulmonary histiocytosis X was made by open lung biopsy. High resolution computed tomography revealed the typical "ring fixtures" distributed in the parenchyma. Diffusing capacity for carbon monoxide was markedly reduced, besides mild obstruction. After six months of observation, there was seen a radiological improvement with unchanged lung function parameters.
Biopsy↗
Interference of ofloxacin with determination of urinary porphyrins.
The second-generation quinolone ofloxacin interferes with the screening test of porphyrins. We observed a 20-fold increase in the porphyrin concentration measured in urine of an ofloxacin-treated patient, compared with drug-free normal urine. Two other fluorinated 4-quinolones tested, norfloxacin and ciprofloxacin, had a less marked effect (a twofold increase), whereas the first-generation quinolone, nalidixic acid, did not affect the measured porphyrin concentration at all. The interference is probably due to the overlap in the emission fluorescence spectra of ofloxacin and urinary porphyrins at approximately 600 nm. To avoid a false-positive diagnosis of porphyria, we suggest using HPLC to separate ofloxacin (10-min retention time) from urinary porphyrins (which only start to elute at 12 min). Nonetheless, given a threefold increase in urinary porphyrins observed in the urine of an ofloxacin-treated patient, we also discuss a possible interference of the drug with the metabolism of porphyrins.
Chromatography, High Pressure Liquid↗
[Porphyria and porphyrinuria].
In latent hepatic porphyria normal porphyrins are frequently excreted, but porphyrinuria accompanies many clinical conditions not associated with porphyria. Therefore, the diagnosis of latent porphyria cannot be made by examining for urinary porphyrins alone. We use 16 laboratory methods, some of which which we developed, including sensitive HPLC separation procedures, for determining relevant enzymes, and porphyrins and their precursors in urine, feces and blood. These methods enable use to distinguish between changes in porphyrin metabolism observed in many cases of latent porphyria, as opposed to similar changes which may occur during therapy with certain drugs and in common clinical conditions. During the past 4 years we investigated 406 patients suspected of porphyria. 160 had increased excretion of porphobilinogen, and/or aminolevulinic acid, and/or porphyrins. 87 of them had porphyrinuria only. Without our clinical and laboratory experience, all would have been diagnosed as porphyria. Further examinations revealed that only 14 had porphyria, 8 of whom had porphyrinuria and 6 had normal urinary porphyrins. Overall, there have been 44 families with porphyria diagnosed in our laboratory since 1969, 1 with erythropoietic protoporphyria and the others with hepatic porphyria. In the past decade, the number of patients diagnosed during the latent phase has increased markedly. This points both to increased awareness of porphyria by physicians and to the increased skills of the laboratory staff.
Aminolevulinic Acid↗