Acute interstitial nephritis. A clinical and pathologic study based on renal biopsies.

To define interstitial nephritis without preselection bias, 25 consecutive renal biopsy specimens from patients with tubular damage, interstitial damage and interstitial inflammation were analyzed in detail. In four patients (all with acute renal failure), tubulitis, and interstitial eosinophil and lymphocyte infiltration were found, but no glomerular abnormalities. In four others, the findings were similar but some glomerular abnormalities were noted. Two patients had probable healed interstitial nephritis. The clinical presentation varied from transient renal insufficincy to oliguric renal failure. Three of the patients with glomerular abnormalities had significant proteinuria. When the 10 patients with interstitial nephritis were compared with the other 15 serving as controls, striking features in the former group were skin rash, eosinophilia, the absence of hypertension and the frequency of administration of penicillin and its analogs. Serum immunoglobulin E (IgE) levels were elevated in three of the patients. The striking eosinophilia, interstitial eosinophil infiltration and increased IgE levels suggest that allergen-reaginic complexes may be involved in the pathogenesis of the lesion.     

Acute hepatitis C: a retrospective study of 62 cases

OBJECTIVES: Retrospective study of acute hepatitis C cases observed in general hospitals. METHODS: Questionnaire sent by mail to members of the Association Nationale des Gastroentérologues des H?pitaux Généraux (ANGH) in December, 1997. Data were updated in September, 2001. RESULTS: Sixty-two cases were reported in 40 centers. Patients were predominantly female (58%), the median age was 33 years-old. Symptoms revealed the disease in 65% of cases (jaundice in 53%) and screening in 30%. The main suspected routes of infection were intravenous drug use (32%), nosocomial exposure (29%) and professional accidents (11%). Sustained viral clearance occurred in 12 out of the 28 patients who were followed without treatment for 6 months, in 14 of 30 treated early, and 4 out of 7 treated secondarily with interferon alpha alone. No prognostic factor was identified, except for a low total dose of interferon in treated patients. CONCLUSIONS: Acute hepatitis C is a rare disease, occurring in younger and more often in female patients than chronic hepatitis C. Spontaneous cure is not infrequent, and could justify a period of simple follow-up before starting treatment. A national observatory would help for epidemiologic surveillance and therapeutic studies.     

Acute fatty liver of pregnancy. A reassessment based on observations in nine patients

Acute fatty liver of pregnancy was diagnosed in nine patients over a 10-year period. Eight patients had severe hepatic dysfunction typical for this syndrome and one had subclinical disease but typical hepatic histologic findings. All patients survived with little fetal wastage; all had preeclampsia. Histologic findings included cholestasis, hepatocellular necrosis, and inflammation, as well as microvesicular fat. Histologic findings from biopsy specimens of four of seven patients were initially misinterpreted as hepatitis. This disorder may have both a broad clinical and histologic spectrum; it is probably not rare but often misdiagnosed, perhaps as viral hepatitis. The concurrence of this disorder with toxemia of pregnancy suggests that these entities may be pathophysiologically related.     

Antipyrine clearance in chronic and neoplastic liver diseases: A study of 518 patients

Antipyrine metabolism is widely used as an index of the drug-metabolizing reserve of the liver. It is well known that metabolism of this drug is impaired in subjects with acute hepatitis or cirrhosis, but conflicting data have been reported regarding patients with chronic postinfectious hepatitis or liver cancer. We studied conventional liver-function parameters and antipyrine metabolism (antipyrine per o.s. 18mg/kg) in 518 subjects. One hundred and one patients had liver metastases (various primaries). Based on the number and size of lesions, the hepatic involvement was considered minimal in 47 and massive in 54 (groups B1 and B2, respectively). One hundred and two had chronic active hepatitis (CAH); 51 patients with histological evidence of fibrosis/early cirrhosis and 51 patients were without histological evidence of fibrosis/early cirrhosis. Ninety-two had histologically confirmed cirrhosis (group D), and the remaining 120 had cirrhosis and hepatocellular carcinoma (group E). The control group was composed of 103 subjects with healthy livers (group A). Antipyrine clearance (AP Cl) in CAH patients with fibrosis (0.246 ± 0.98 mL/min per kg) was similar to that observed in patients with cirrhosis (0.223 ± 0.148 mL/min per kg), and both values were significantly lower than that found in CAH patients without fibrosis (0.406 ± 0.159 mL/min per kg, P < 0.01). Antipyrine clearance in patients with liver metastases (0.426 ± 0.174 mL/min per kg) was similar to that of the healthy group (0.489 ± 0.210 mL/min per kg). Cirrhotics and cirrhotics with hepatocellular carcinoma (HCC) presented similar degrees of impairment. Antipyrine clearance was positively correlated with serum albumin (r²= 0.10, P= 0.01) and prothrombin time (r²= 0.129, P < 0.01) in all groups, except those with liver metastases. In patients with CAH, the presence of fibrosis/cirrhosis is associated with impaired antipyrine metabolism. The lack of impairment in groups with liver metastases suggests that the functional hepatic reserve is maintained even in the presence of massive neoplastic invasion.     

Acute pericarditis: etiology, treatment and prognosis. A study of 115 patients

One hundred and 15 hospitalized patients with acute pericarditis were analyzed retrospectively for their etiology, management and long-term prognosis. It was found that most of the patients had either idiopathic or viral etiologies (60%), collagen disease (16.4%) or malignancy (6.9%). Most of the patients were treated with non-steroidal anti-inflammatory drugs (NSAID). Twenty-six patients (22%) required corticosteroids following NSAID treatment failure. Only one patient underwent pericardiocentesis for tuberculous pericarditis. The long-term prognosis was good, although 21.9% of the patients suffered from recurrent episodes of pericarditis. It is concluded that in hospitalized patients with pericarditis, an extensive workup may not reveal the major etiologies, and the disease may be more complicated than previously thought.     

A plausible model for reversal of neoplastic transformations in plants based on multiple steady states.

We offer a plausible interpretation of some experiments on the reversal of neoplastic transformations in plants. We suggest that normal cells and tumorous cells represent multiple stable-steady states corresponding to a reaction feedback mechanism. The (autocatalytic) feedback loop is constructed from observations on the role played by myo-inositol: it increases the permeability of ions through the membrane and the biosynthetic pathway to myo-inositol is activated by ions. Provided that the permeabilities of nutrients (sugars and salts) are a product-enhanced function of myo-inositol, then we have a (oversimplified) model that can exhibit multiple stationary stable states, one or two depending on the exogenous nutrients and myo-inositol concentrations, and reversible and irreversible transitions from one of these states to the other are possible. From this model, straightforward simple experiments are suggested. We also propose that recent models dealing with the intracellular calcium regulation by hormones, where one key step requires the hydrolysis of inositol phospholipids, take into account free myo-inositol and endogenous hormone concentrations (e.g., auxins).     

A hanging drop culture method to study terminal erythroid differentiation

OBJECTIVE: To design a culture method allowing the quantitative and qualitative analysis of terminal erythroid differentiation. METHODS: Primary erythroid progenitors derived either from mouse tissues or from human umbilical cord blood were differentiated using hanging drop cultures and compared to methylcellulose cultures. Cultured cells were analyzed by FACS to assess differentiation. RESULTS: We describe a practical culture method by adapting the previously described hanging drop culture system to conditions allowing terminal differentiation of primary erythroid progenitors. Using minimal volumes of media and small numbers of cells, we obtained quantitative terminal erythroid differentiation within two days of culture in the case of murine cells and 4 days in the case of human cells. CONCLUSIONS: The established methods for ex vivo culture of primary erythroid progenitors, such as methylcellulose-based burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) assays, allow the detection of committed erythroid progenitors but are of limited value to study terminal erythroid differentiation. We show that the application of hanging drop cultures is a practical alternative that, in combination with clonogenic assays, enables a comprehensive assessment of the behavior of primary erythroid cells ex vivo in the context of genetic and drug-induced perturbations.     

A new system for the study of erythroid cell differentiation

Highly purified erythroid progenitor cells (CFU-E), were cultured in vitro for 48 h. Cell division was monitored regularly and cells were isolated at times when maximal colony formation occurred. The cell mixture after one and two cell divisions consisted mainly of proerythroblasts and basophilic erythroblasts (early erythroid cells). After four cell divisions, predominantly polychromatic and orthochromatic cells (late erythroid) were present. After two days of culture, the majority of inoculated cells had differentiated into reticulocytes. This time course in vitro was comparable to the differentiation of CFU-E in vivo. As judged by cytochrome-c oxidase activity, there was an increase in total mitochondrial activity per culture; however, the activity per cell decreased during the differentiation process. The formation of hemoglobin started after the first cell division. This system is presented as a new tool for the study of biochemical processes accompanying erythroid cell differentiation.