Drug-induced hypersensitivity nephritis: lymphocyte stimulation testing and renal biopsy in 10 cases

The pathomorphological and clinical findings were investigated in 10 cases of drug-induced hypersensitivity nephritis. Hypersensitivity due to drugs was strongly suggested by the lymphocyte stimulation test in all patients. The offending drugs included penicillin, cephem derivatives, nonsteroidal anti-inflammatory drugs, and minocycline. All patients developed acute renal failure shortly after administration of regular doses of the drugs. Allergic symptoms plus a raised level of serum IgE or eosinophilia were seen in 7 patients. The remaining 3 patients receiving nonsteroidal anti-inflammatory drugs had no allergic symptoms, but developed severe proteinuria. Eight patients without severe glomerular damage recovered after withdrawal of the offending drugs and temporal dialysis and/or steroid therapy. Renal biopsies revealed tubulitis and tubular epithelial degeneration with interstitial edema as the common characteristic findings. Granulomatous lesions were occasionally observed. Multinucleated giant cells found in the granulomas were positive for LN-3 which is compatible with HLA-DR antigen. The glomeruli appeared normal, except in 2 cases in whom crescentic glomerulonephritis and thrombotic microangiopathy were seen. Our study suggests that the lymphocyte stimulation test and renal biopsy are the most useful means to confirm the diagnosis and provides further evidence for the participation of cell-mediated immunity in the pathogenesis of drug-induced hypersensitivity nephritis.     

Renal and hemodynamic effects of dopamine in infants following cardiac surgery

The renal and hemodynamic effects of dopamine were measured during the immediate postoperative period in six infants following repair of congenital cardiac defects. Dopamine was infused at rates of 5, 10, and 15 micrograms/kg/min. Cardiac index (CI) increased significantly at a dopamine infusion rate of 15 micrograms/kg/min. The glomerular filtration rate (GFR) and urine output increased at dopamine infusion rates of 5 and 10 micrograms/kg/min and returned to baseline at 15 micrograms/kg/min. No significant changes occurred in right atrial pressure (RAP), left atrial pressure (LAP), systemic artery pressure, systemic vascular resistance (SVR), or pulmonary vascular resistance (PVR). Heart rate (HR) increased slightly at a dopamine infusion rate of 15 micrograms/kg/min. Pulmonary artery pressure (PAP) increased significantly in only one patient. These data demonstrate that infants require high doses of dopamine to produce the hemodynamic effects seen in adults and that these higher doses may be used without adverse renal effects.     

Clinical study of estramustine phosphate disodium (Estracyt) on prostatic cancer--results of long-term therapy for 38 patients with prostatic cancer

Estramustine phosphate disodium (Estracyt) was used in the treatment of 38 patients with prostatic carcinoma for at least 1 year. Of these patients 37 patients were treated with Estracyt as primary treatment and 1 patient had been treated with another antiandrogenic therapy before the Estracyt treatment. Estracyt was given orally in a dose of 560 mg/day in divided oral doses. The clinical evaluation was done for the change of PAP, the relapse rate, the survival rate and the side effect. Among 22 cases which had shown abnormally high PAP values before the treatment started, the values decreased or normalized in 21 cases (95.5%) in the first year of administration of Estracyt. In 6 cases, however, the values increased again in the second year or later. Relapse was observed in 10 (26.3%) out of 38 cases. Relapse rate was 2.6%, 51.7%, and 51.7%, at the first, third, and fifth year, respectively. Survival rate was 97.4% at the first year, 88.5% at the third year, and 68.8% at the fifth year for the follow-up study. Side effects were observed in 14 (36.8%) out of 38 cases. The main side effect was gynecomastia. Gastro-intestinal disturbance and edema were also observed. However, there were only 2 cases (5.2%) in which administration of Estracyt had to be discontinued.     

Plasma and tumor gastrin in patients with primary hyperparathyroidism

It is well known that primary hyperparathyroidism is often associated with peptic ulcer. The purpose of this study is to confirm the relationship between the gastrin-levels before and after parathyroidectomy in fourteen patients with primary hyperparathyroidism, and to determine the localization of gastrin in the surgically resected parathyroid tumor. The results obtained were as follows: 1) Three patients had peptic ulcer (gastric ulcer and duodenal ulcer), the incidence being 21%. 2) The basal serum gastrin levels were 123.0% +/- 68.1 pg/ml before operation and decreased to 90.2 +/- 44.5 pg/ml after operation. In the 3 patients with slightly elevated gastrin levels, the mean level before operation was 209.1 +/- 61.2 pg/ml. The gastrin level decreased to 116.4 +/- 62.0 pg/ml after operation. 3) Gastrin immunoreactivity was detected in 10 out of 14 tumors and its localization was at the periphery of tumor cells. From these results, we conclude that extragastric gastrin secretion from parathyroid tumors may be one of the cause of peptic ulcer in patients with primary hyperparathyroidism.     

Effects of alpha-1-blocking agent in the treatment of detrusor sphincter dyssynergia

Effects of adrenergic alpha-1-blocking agent, prazosin, in the treatment of detrusor external-sphincter dyssynergia (DSD) were evaluated in both experimental and clinical aspects. Experimentally, in the urethral pressure profile in dogs, the maximum urethral closing pressure was depressed after intravenous injection of 1 mg prazosin. When experimental DSD was obtained in dogs by stimulating electrically the unilateral 2nd sacral root, intra-venous injection of 1 mg prazosin inhibited contraction of the external urethral sphincter. Clinically, 74 patients with DSD based on neurogenic bladder from cerebral vascular attack (CVA) (13 cases) and spinal cord injury (61 cases) were retrospectively surveyed in terms of therapeutical effects of prazosin for DSD. Spinal cord injury was subdivided to 4 groups for clinical evaluation; cervical cord injury (C) with complete paralysis, thoracic cord injury (Th) with complete paralysis, lumbar cord injury (L) with complete paralysis and spinal cord injury with incomplete paralysis. Patients with CVA and spinal cord injury with incomplete paralysis showed good response rates in subjective improvement, 69% and 60% respectively. However, those with spinal cord injury with complete paralysis showed a poor response (28% for C, 23% for Th and 14% for L). The amount of residual urine significantly decreased after treatment, in all the groups except that of lumbar cord injury with complete paralysis. In all the groups, however, even after the drug treatment the amount of residual urine ranged from 80 to 170 ml and the rates of needing clean intermittent catheterization unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrine and hemodynamic responses to total body hyperthermia in humans

We investigated effects of total body hyperthermia (TBH) on endocrine and hemodynamic responses. A total of five treatments were performed in five patients with gastric cancer under neuroleptanesthesia with morphine followed by 0.2 to 0.4% enflurane. TBH was extracorporeally induced with veno-venous shunt incorporating with heat exchanger to keep their temperature between 41.5 degrees C and 42.0 degrees C for three hours. The patients were administered angiotensin to maintain tumor blood flow. Lactated Ringer's solution was administered at the rate of 10 to 15 ml.kg-1.hr-1 for five hours. Plasma cortisol levels decreased significantly to about one third of the control value after heating and the levels recovered to the control value after cooling. Plasma norepinephrine level increased significantly to about 7 to 9 times the control value following TBH, but this hormonal response was insufficient to reveal marked direct hemodynamic effects. The magnitude of fall in SVR was more significant in spite of the administration of angiotensin. Cardiac index increased significantly to about 2.0 to 2.6 fold of control value, but mean arterial blood pressure (MAP) decreased significantly to about two thirds to four fifths of the control value. Morphine relieved the hormonal response in ACTH and cortisol strongly, but morphine suppressed hemodynamics by decreasing SVR. Neither norepinephrine released from sympathetic nerve endings nor even 50 to 200 ng.kg-1.min-1 of angiotensin administered failed to restore SVR or MAP during hyperthermia.     

Rapid release of gentamicin from collagen sponge. In vitro comparison with plastic beads

The gentamicin-containing collagen sponge is a new product intended for local application in bone and soft-tissue infections. The release of gentamicin from the collagen sponges was compared in vitro to that from polymethyl-methacrylate (PMMA) beads. A static and kinetic experimental design was used. In the static model, pieces of collagen sponge or PMMA beads were added to 20 mL of distilled water, and during the following hours the gentamicin concentrations in the water were repeatedly measured. This simple model was extended to the kinetic model as the released gentamicin was removed from the water exponentially by means of an infusion-withdrawal pump. The gentamicin was released from the carrier substances with increasing half lives. During the first 4 hours, the half life increased from 0.2 to 1.5 hours for the collagen sponge and from 3 to 78 hours for the PMMA beads. After 1.5 hours, 95 percent of the gentamicin was released from the sponges, whereas only 8 percent was released from the beads.     

Diagnosis of deep vein thrombosis by high resolution ultrasonography

Using high resolution ultrasonography (US), diagnostic accuracy of thrombi in each venous segment of lower limbs and qualitative evaluation of thrombi in deep vein thrombosis (DVT) were investigated. The subjects were 106 lower limbs in 81 patients. The thrombi in common femoral vein (CFV), were diagnosed by compression technique and, were qualitatively analysed by echogenicity and consistency. Venography was performed in 18 limbs and histologic tests of thrombi were made in 6 limbs. The total accuracy of US was 100% for diagnosis of DVT, but was 83% for diagnosis of its extent. The total accuracy of US in each segment was greater than 90%, but the sensitivity of iliac veins was less than 90%. The thrombi in CFV were divided into 3 types and 8 sub-types. Type A was homogenous, type B was heterogenous, and type C was contracted echo. The types of us were consistent with results of histologic tests. We concluded that high resolution US is available for screening test for diagnosis of DVT and that qualitative evaluation of thrombi by US is a useful clinical test for selection of more adequate treatments.     

Effects of sevoflurane anesthesia and baroreceptor function on renal sympathetic nerve activity in rats

Effects of sevoflurane at various anesthetic levels on renal sympathetic nerve activity (RSNA), blood pressure and heart rate were studied in rats. Changes of these parameters produced reflexly by noxious cutaneous stimulation and effects of baroreceptor on them were also studied. Under the resting condition by increasing inspired sevoflurane concentration decreased blood pressure and heart rate dose-dependently, whereas, RSNA was unchanged. But, without the baroreceptor function, RSNA decreased and the change paralleled with changes of blood pressure and heart rate. When noxious stimulation was applied on a hindpaw by pinching, blood pressure, heart rate and RSNA all increased at sevoflurane 2.1%. The responses of these parameters were attenuated at 3.1% and almost disappeared at 4.2% of sevoflurane. However, without the baroreceptor function, RSNA increased even at 3.2 and 4.2% as at 2.1% of sevoflurane. It is suggested that under sevoflurane anesthesia, baroreceptor system has strong influences on RSNA even under sevoflurane 4.2% (2MAC).     

Nonocclusive mesenteric ischemia in renal patients: recognition and prevention of intestinal gangrene

Nonocclusive mesenteric ischemia (NOMI) is a disorder with an extremely high mortality. Salvage of affected patients requires early recognition and aggressive intervention to prevent intestinal gangrene. Dialysis patients represent a group at particularly high risk for this condition. Clinicians should develop a high index of suspicion for NOMI in dialysis patients to lessen the risk of death. A high interventional posture must be maintained due to the notoriously unreliable signs and symptoms of this disorder.