Natale G. De Santo

Phase Contrast Microscopy of the Urine Sediment for the Diagnosis of Glomerular and Nonglomerular Bleeding-Data in Children and Adults with Normal Creatinine Clearance

In a pediatric and in an adult group of patients with hematuria and normal creatinine clearance overnight urine examination was carried out on 2 nonconsecutive days by means of phase contrast microscopy by two independent observers working in two different institutions. In this way it was possible to distinguish between patients on the basis of dysmorphic (glomerular) and isomorphic (nonglomerular) red cells in urine and to correlate the findings with the final diagnosis. A clear-cut indication (more than 80% of isomorphic and/or dysmorphic red cells) was obtained in 163 patients (102 of pediatric age) and final diagnosis of hematuria correlated with red-cell microscopy findings in 96.4% of glomerular diseases and in all cases of nonglomerular origin. Mixed hematuria (50-75% of dysmorphic red cells) was found in 2 cases of renal tuberculosis, 2 cases of polycystic kidney disease and in 1 child with viral meningoencephalitis with a bladder stone. The data indicate that the method is safe and accurate but further experience must be gathered for the many etiologies of glomerular and nonglomerular diseases hitherto not studied.

A History of Salt

The medical history of salt begins in ancient times and is closely related to different aspects of human history. Salt may be extracted from sea water, mineral deposits, surface encrustations, saline lakes and brine springs. In many inland areas, wood was used as a fuel source for evaporation of brine and this practice led to major deafforestation in central Europe. Salt played a central role in the economies of many regions, and is often reflected in place names. Salt was also used as a basis for population censuses and taxation, and salt monopolies were practised in many states. Salt was sometimes implicated in the outbreak of conflict, e.g. the French Revolution and the Indian War of Independence. Salt has also been invested with many cultural and religious meanings, from the ancient Egyptians to the Middle Ages. Mans innate appetite for salt may be related to his evolution from predominantly vegetarian anthropoids, and it is noteworthy that those people who live mainly on protein and milk or who drink salty water do not generally salt their food, whereas those who live mainly on vegetables, rice and cereals use much more salt. Medicinal use tended to emphasize the positive aspects of salt, e.g. prevention of putrefaction, reduction of tissue swelling, treatment of diarrhea. Evidence was also available to ancient peoples of its relationship to fertility, particularly in domestic animals. The history of salt thus represents a unique example for studying the impact of a widely used dietary substance on different important aspects of mans life, including medical philosophy.

Beneficial Effects of Atrial Natriuretic Factor on Cisplatin-Induced Acute Renal Failure in the Rat

The organometal cisplatin has potent antitumor properties. However, its use is sometimes complicated by significant nephrotoxicity. This is characterized by tubular necrosis and impairment of the glomerular filtration rate (GFR). On the other hand, it has been demonstrated that atrial natriuretic factor (ANF) increases GFR in normal euvolemic rats. In the present study, we have therefore tested if this new potent natriuretic compound could restore some of the renal parameters affected by cisplatin. To investigate this issue, acute renal failure was induced in 9 rats by intraperitoneal injection of cisplatin 10 mg/kg body weight (b.w.). Renal function was studied 72 h later using the 3H-inulin clearance method and was compared with the renal function of 5 normal euvolemic rats. The cisplatin-treated rats showed high blood urea nitrogen levels, a 74% reduction of whole kidney GFR (0.308 +/- 0.047 vs. 1.17 +/- 0.08 ml/min/100 g b.w.) and a significant increase in the fractional excretion of urine, sodium and potassium. After 2 control clearances, synthetic ANF was administered intravenously as a prime (12 micrograms/kg b.w.) and then as a constant infusion (1 microgram/kg/min) to 6 cisplatin-treated rats. This promptly doubled the GFR (0.603 +/- 0.113 ml/min/100 g b.w.) and induced a significant increase in the excretion rate of urine, sodium and potassium. These results demonstrate that the administration of ANF has a beneficial effect on the experimental model of acute renal failure induced by cisplatin.

Actinomyces Peritonitis Associated with Dialysis

A case of actinomyces peritonitis occurring in a young girl undergoing regular dialytic treatment is reported. The peritoneal localization was the only one detectable and occurred in a patient who at the beginning of the dialytic treatment had received peritoneal dialysis on two occasions. During 4 months of treatment the patient underwent surgical drainage of the peritoneal fluid and medical treatment with various antibiotics. Super-infection with Escherichia coli and Candida, and an acute episode of bronchopneumonia, complicated the course of the treatment which was finally successful

Ethyl Alcohol Sniffing by Patients Undergoing Hemodialysis

Seven uremic patients undergoing long-term hemodialysis became addicted to vapors of denaturated ethyl alcohol. Sniffing produced relaxation, euphoria, and a sense of well-being. In all but one patient, this was the the only form of deviance. Two patients who tried stopping this practice while under psychiatric help were unsuccessful because of acute abstinence symptoms. Denaturated ethyl alcohol does not seem to be toxic per se. In these patients, results of hematological and liver function tests were within normal limits. Anemia supervened in one patient after two years of dialysis, and peripheral neuropathy developed in another.

Atrial Natriuretic Factor Increases Glomerular Filtration Rate in the Experimental Acute Renal Failure Induced by Cisplatin

Cis-diamminodicloroplatinum (CP) is a recently developed antineoplaxadstic agent that has a remarkably broad spectrum of clinical activity in the treatment of solid tumors (1). Use of this drug has significantly improved the response rate in patients treated for metastatic testicular and ovarian carcinomas. Additionaly,cisplatin is an important component of many treatment programs for the management of bladder carcinoma,squaxadmous cell carcinoma of the head and neck,bronchogenic carcinoma of the lung,cervical and endometrial cancer.However the clinical use of the drug is largely hampered by its nephrotoxicity. In fact the degree of renal toxicity rather than the therapeutic response often determines the dosage of this therapeutic agent. A chronic,repetitive low dosage of cisplatin in rats also leads to kidney failure creating a situation similar to kidney insufficiency clinically observed during the prolonged chemotherapeutic regimens used for various malignancies (2). An acute single dose of CP induces in rats a non oligurie acute renal failure (ARF) that is charactexadrized by a reduction of whole animal glomerular filtration rate (GFR),with increase in serum creatinine concentration,diminished urine osmolality, decreased U/P creatinine concentration ratios,and a significant increase in the fractional excretion of sodium (3). Development of cisplatin to its present level of clinical usefulness was greatly facilitated by studies in which hydration-diuresis maneuvers were used in dogs (4) and subsequently in humans (5). Another promising approach to limit CP nephrotoxicity is pharmacologic inhibition of cisplatin tubular secretion. Administration of drugs such as probenecid may be effective in decreasing the intracellular concentration of drug by inhibiting its uptake by the contraluminal cell membrane (6).

The Use of Micropuncture, Isolated Tubule, and Vesicle Technique in the Study of the Action of Thyroid Hormones on the Proximal Tubule Function

In hypothyroid rats (TX), the isotonic fluid reabsorption (Jv), that is closely linked to the transepithelial sodium transport (JNa), is impaired. The administration of physiological doses (10 micrograms/kg body weight per day) of tri-iodothyronine (T3) doubles Jv in three days (TX+T3). This phenomenon could be explained by several mechanisms: a direct stimulation of Na-K-ATPase, an increase in the Na+ entry step, changes in the permeability properties of the luminal and/or basal lateral membranes. Using a kinetic microassay, Na-K-ATPase activity was measured in early (S1) and late (S2) proximal tubules segments isolated from control, TX, and TX+3T3 animals. In TX rats the enzyme activity was lower (70%) in both segments versus control rats, it remained unchanged after 3 days, and it increased after 7 days of T3 substitution. The Na+ permeability of brush border membrane (BBM) vesicles isolated from TX and TX+T3 rats was identical. However the valuation of the K+ membrane permeability by in vivo perfusion of the lumen and peritubular space of proximal tubules of TX rats, with perfusate containing the K+ ionophore valinomycin (1 microgram/ml), induced a significant increase in Jv that accounted for 40% of that elicited by T3. Taken together, the in vivo and in vitro experiments suggest that the early effect on Jv of physiological doses of T3 cannot be explained by a direct action of T3 either on the Na+ entry step across the BBM or on the Na+ exit step (i.e., the Na-K-ATPase), but rather by an increase in K+ permeability of proximal tubular cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Parathyroid Hormone on Cisplatin Nephrotoxicity

The clinical use of cisplatin as an antineoplastic agent is limited by its nephrotoxicity that, in many cases, includes acute tubular necrosis and renal wasting of various electrolytes (1–4). Several studies have been performed to account for the various disorders of renal function induced by cisplatin. The decrease in GFR, for example, has been found to be related to a reduction in renal blood flow and to a lowered effective filtration pressure (5). The reported concentrating defect and the observed impaired sodium reabsorption have been associated to a defect in papillary hypertonicity found in cisplatin treated rats (6), while the potassium wasting effect is in part due to a negative potential difference induced by cisplatin in late distal segments (6). Finally the pathogenesis of cisplatin induced hypomagnesemia has been attributed to pathological changes confined to the straight portion (S3 segment) of superficial nephrons (7). On the other hand many therapeutic strategies have been tested to reduce its nephrotoxic action: the fall in GFR, for example, can be modified by hydration, mannitol diuresis (8) and by the administration of atrial natriuretic peptide (9); moreover compounds that provide SH groups have been reported to reduce the cisplatin associated renal injury (10).