Severe impairment in adenine metabolism with a partial deficiency of adenine phosphoribosyltransferase.

Among three unrelated patients with recurrent 2,8-dihydroxyadenine urolithiasis, two completely lacked adenine phosphoribosyltransferase (APRT) in both erythrocytes and proliferative T cells. The third patient possessed significant enzyme activities in both hemolysates and T-cell extracts at levels comparable to heterozygotes for complete APRT deficiency. Despite significant APRT activities in cell extracts, cultured T cells from the third patient were at least 100-fold more resistant than normal T cells to an adenine analog, 6-methylpurine, whose cytotoxicity is dependent on APRT. These data indicate that APRT activity in T cells from the third patient is positive in cell extracts, but apparently not operating in viable cells. Although the cells from the patients with complete APRT deficiency were as resistant to 6-methylpurine as the cells from the third patient, the cells from the heterozygotes for complete APRT deficiency were almost as sensitive as normal T cells. Therefore, adenine metabolism in the third patient but not in the heterozygotes seems to be as severely impaired as in the patients with complete APRT deficiency, which is quite consistent with the clinical manifestations in these individuals.

Peritoneal transport of beta-lactam antibiotics: effects of plasma protein binding and the interspecies relationship.

In order to examine quantitatively the effect of plasma protein binding on the peritoneal transport of beta-lactam antibiotics, we employed a kinetic model based on the pore theory of transcapillary exchange. This model incorporates the changes in the volume, osmolality, and antibiotic concentration in the dialysate, so that the apparent capillary membrane permeability (Pd) and the reflection coefficient (sigma d) of an antibiotic could be assessed. Six cephalosporins (cefatrizine, cefazolin, cefpiramide, ceftazidime, ceftriaxone, cephaloridine) were used as model compounds. While the unbound fractions of these antibiotics ranged widely from 0.08 to 0.57, including linear and nonlinear protein binding, the concentration-time profiles in plasma and the peritoneal dialysate after intravenous administration in rats could be interpreted well by our model, assuming that only the unbound antibiotic is available for the peritoneal transport. The estimated Pd values were almost the same among the drugs examined. Moreover, the Pd values of cefazolin in mice, rats, and rabbits exhibited a 0.83-power dependency on the animal body weight, indicating that Pd is significantly related to the peritoneal surface area. On the other hand, the sigma d values of cefazolin were found to be almost the same among the animal species examined. Finally, the concentration-time profile of cefazolin in the dialysate after intravenous administration in a patient with end-stage renal failure was successfully predicted using the Pd value extrapolated from those of the experimental animals.

Nephrotic syndrome due to focal glomerulosclerosis and undifferentiated carcinoma.

In neoplastic disorder-related nephrotic syndrome, focal glomerulosclerosis (FGS) has been reported mainly in hematological disorders like minimal change nephrotic syndrome (MCNS) in association with presumed T lymphocyte dysfunction. The association of FGS with cancer or solid tumor is rare. We report a case of nephrotic syndrome due to FGS in a patient with undifferentiated adenocarcinoma of the cystic duct. Although the underlying mechanism is unclear, the development of FGS seemed to be related to the poor histological differentiation of the cancer in the possibility of production of an active peptide.

Glomerular deposition and serum levels of complement control proteins in patients with IgA nephropathy.

We examined complement control proteins focusing on the role of modulating the complement activation in IgA nephropathy. Glomerular C4-binding protein (C4-bp) deposits were found in 60% of patients with IgA nephropathy, while C4 deposits were found in 30%. Glomerular deposits of beta 1H globulin (beta 1H) were found in 85% of patients with IgA nephropathy. The frequency of glomerular deposits of C4-bp tended to be higher in the group with deposits of various immunoglobulin types than in the group with deposits of IgA alone, and it increased parallel with the progression of glomerular histologic changes. The serum C4-bp level was higher in IgA nephropathy patients. No significant correlation was found between the serum level of C4-bp or beta 1H and the extent or distribution of tissue deposits of these complement control proteins. These results suggest that glomerular immune deposits in IgA nephropathy may be attributable to the activation not only of the alternative pathway but also of the classical pathway, the latter of which may take place locally in glomeruli with advanced histologic change or various immunoglobulin deposits in IgA nephropathy.

Electrolyte disorders following massive insulin overdose in a patient with type 2 diabetes.

We present a case of a 47-year-old man with Type 2 diabetes mellitus who attempted suicide with 2,100 U of insulin injected subcutaneously. Administration of dextrose intravenously was required to maintain the blood glucose concentration normally for 5 days. Moreover, hypokalemia, hypophosphatemia, and hypomagnesemia were also seen for 24 hours after insulin injection. The serum phosphorus and magnesium concentrations decreased to nadirs of 1.6 mg/dl and 1.6 mg/dl respectively 7 hours after insulin injection. Electrolyte disorders other than hypokalemia may be induced in hypoglycemic patients by massive insulin overdose.

Hereditary angioedema complicated with chronic renal failure: report of sibling cases.

Hereditary angioedema (HAE) is known as a deficiency state of C1 inhibitor (C1 INH), an important protease inhibitor protein involved in the complement system. As with other components of the classical pathway of the complement system, a state of its deficiency often causes clinical immunoregulatory disorders. A 45-yr-old brother and a 63-yr-old sister with HAE both developed chronic renal failure, probably due to chronic glomerulonephritis, and required regular hemodialysis. This is, to our knowledge, the first report of sibling cases of HAE associated with chronic renal failure.

Intense and prolonged Tl-201 accumulation in a slow growing bronchioloalveolar carcinoma.

Thallium-201 SPECT was performed to evaluate a pulmonary lesion in a 73-year-old male which had been considered to be an inflammatory lesion for two years. The lesion has slowly increased in size on x-CT. Tl-201 was intensely taken up and retained in the lesion, suggesting a malignant lesion. Histological examination revealed that the lesion was bronchioloalveolar carcinoma. This case suggested that Tl-201 uptake of pulmonary carcinoma would not be necessarily related to cell growth rate.

[201Tl SPECT for suspected lung cancer in a case of a systemic arterial supply to the lung without sequestration].

201Tl SPECT showed negative result for the presence of a malignant lesion in a 54-year-old male suspected with primary lung cancer on plain x-ray CT. Thin-section contrast x-ray CT and aortography revealed anomalous left lower pulmonary artery arising from the aorta which mimicked a pulmonary mass lesion in the initial study. 201Tl SPECT gave us a clue to the correct diagnosis.

[Hemolytic anemia and acute renal failure caused by blood transfusions].

We report a case of 33 years old woman who developed hemolytic anemia after blood transfusion. In this case no abnormalities were observed by the cross-match test performed before blood transfusion. She was undergone the surgical resection of liposarcoma of her right arm in June, 1984 and 8 units of the concentrated red blood cells were transfused during the operation. During the following 2 months 13 units of the concentrated red blood cells were transfused. Immediately after blood transfusion, she developed icterus and oliguria and was diagnosed acute renal failure associated with hemolytic anemia. At this time we examined the antigen type of her red blood cells and of three donors' red blood cells which had been given to her. As the result, either C (Rh-hr), Pi (P), Lea (Lewis), Fyb (Duffy) antigens were found in some of donors' RBC, but no such antigens were detected in her RBC. The half life span of RBC measured using 51Cr labeled RBC was 6.2-14.5 hours, in respect of the antigen-positive RBC, where as it was 49.4 hours in the RBC without the antigens. It is more likely that the blood transfusion was the cause of hemolytic episode in this case, because the half life span of the donors' RBC was extremely shortened, compared with that of her own blood which was 16 days.

[A case of renal hypouricemia associated with IgA nephropathy--with special reference to changes in serum uric acid and uric acid clearance in a clinical course exceeding 15 years].

We report a case of IgA nephropathy associated with renal hypouricemia. The patient's renal function had decreased gradually during the previous 15 years, resulting in chronic renal failure. Levels of serum uric acid and uric acid clearance were 1.0 mg/dl and 39.4 ml/min, respectively. Pyrazinamide suppression test indicated that the patient had defective tubular reabsorption of uric acid at the presecretory site. The serum uric acid level elevated linearly to 5.0 mg/dl during the 15-year period, in parallel with a change in serum creatinine level, giving a significantly positive correlation coefficient of 0.9776. The ratio of uric acid and creatinine clearances showed no significant change, although both decreased during the 15 years. These results were a different from those in patients with chronic glomerulonephritis, including IgA nephropathy, where the serum uric acid level had shown no significant correlation with serum creatinine level above 2.0 mg/dl and the ratio of uric acid clearance and creatinine clearance had exponentially elevated after the latter decreased below 30-40 ml/min. The patient presented here has defective tubular transport of uric acid at the site of urate reabsorption, and appears to show a different tubular dysfunction response from patients with chronic glomerulonephritis and decreased renal function.

Urine anion gap in patients with chronic renal insufficiency.

We investigated the urinary acid excretion and urine anion gap (AG) (Na+ + K(+)-Cl-) during NH4Cl-induced metabolic acidosis in 38 normal subjects and 53 patients with chronic renal diseases in order to clarify the significance of the urine AG as a useful marker of the ammonium (NH4+) excretion even in a state of chronic renal insufficiency. The urine pH became higher, and the urinary excretions of titratable acid (TA) and NH4+ decreased significantly, in parallel with a reduction of the creatinine clearance (Ccr). The urinary electrolyte excretion, especially the chloride excretion, also decreased significantly as Ccr fell. As a result, the urine AG increased from negative to positive values, in proportion to the decrease in Ccr with statistical significance. The urine AG showed the most significant correlation with the urine NH4+ excretion (r = -0.707, p less than 0.001). We conclude that the urine AG provides a significant marker of the urine NH4+ excretion even in a state of moderate to severe renal insufficiency.

[Bucillamine-associated membranous nephropathy in a patient with rheumatoid arthritis].

A case of bucillamine-associated membranous nephropathy in a patient with rheumatoid arthritis was reported. A 34 year-old woman was admitted to our hospital because of proteinuria in September, 1988. Rheumatoid arthritis had been diagnosed in April, 1988, and had been treated with bucillamine (disease modifying anti rheumatic drug) and amfenac (nonsteroidal antiinflammatory drug). The renal biopsy specimens showed Stage I membranous nephropathy, on both electron and immunofluorescence microscopy. Proteinuria decreased after the drugs were withdrawn despite continued RA symptoms. These results were consistent with drug induced nephropathy. Since bucillamine has some resemblances in its structure and pharmacologic action to D-penicillamine, which sometimes induces membranous nephropathy, it is thought that the nephropathy in this case was caused by an adverse reaction to bucillamine.

[A case of renal cell carcinoma associated with rapidly progressive glomerulonephritis].

A 74-year-old man was admitted to our hospital because of a treatment for his right renal tumor. The abdominal CT scanning revealed a mass in the right kidney, and a right selective renal arteriography demonstrated a hypervascular tumor. On admission, urinalysis revealed proteinuria (3-4 g/day) and microscopic hematuria, and serum electrolytes were normal. Serum creatinine and urea nitrogen levels were 1.6 mg/dl and 30 mg/dl, respectively. A percutaneous right renal biopsy specimens showed crescentic glomerulonephritis. Direct immunofluorescence studies showed strong linear staining for IgG and IgA along the glomerular capillary walls. Electron microscopy showed increased mesangial matrix and swollen epithelial cells, but no dense deposits in the para-mesangial area and in the glomerular basement membrane. The patient underwent right radical nephrectomy. Histologic examination of the resected specimen revealed renal cell carcinoma. Postoperatively, he developed rapidly progressive renal failure and the renal function could not be recovered. Using the indirect immunofluorescence technique, we could not confirm the presence of a serum anti-glomerular basement membrane antibody, although the examination could not be carried out until the initiation of hemodialysis therapy. Some cases of glomerulopathies associated with renal cell carcinoma were previously reported, but the case of crescentic glomerulonephritis was very rare.

[A case of multiple myeloma associated with abnormal plasma cells and M-protein in pleural effusion].

A 77-year-old woman with hypertension was admitted to our hospital because of exertional dyspnea end peripheral edema. Chest X-ray showed cardiomegaly, pulmonary congestion and right pleural effusion. Hypertensive heart failure was diagnosed and treated, and right pleural effusion disappeared in 2 weeks. Abnormalities on laboratory data, i.e. anemia and increased ESR et al. continued after the improvement of heart failure. Serum IgG was elevated (2570 mg/dl), while IgA and IgM were decreased. Immunoelectrophoresis indicated the presence of monoclonal IgG-lambda in the serum. Bone marrow puncture revealed an increase in atypical plasma cells (38.4%). Multiple myeloma was diagnosed from these findings and treated with melphalan and prednisolone. But increases in atypical plasma cells (43.2%) and serum IgG (2573 mg/dl) continued. During treatment, right pleural effusion increased again. Thoracocentesis showed bloody effusion with numerous atypical plasma cells, and the presence of monoclonal IgG-lambda was indicated by immunoelectrophoresis. The patient died of renal and heart failure 2 months after the onset of malignant pleural effusion. Cytological examination and immunoelectrophoresis are necessary for pleural effusion in multiple myeloma.

[An 85-year-old case of Basedow's disease associated with high output heart failure and angina pectoris].

We report a rare case of Basedow's disease associated with high output heart failure and angina pectoris over the age of 80 years. An 85-year-old woman was admitted with palpitation, finger tremor, hyperidrosis and weight loss. Basedow's disease was diagnosed by physical (diffuse goiter) and laboratory (free T3 19.4 pg/ml, free T4 > 8.0 ng/dl, TSH < 0.1 microU/ml, TRAb positive, 123I uptake high) findings and was treated with methimazole. Chest oppression and dyspnea on exertion with negative T wave, cardiomegaly and pulmonary congestion appeared after methimazole. Cardiac catheterization showed a high cardiac output (CI 5.01/min/m2, PCW 26 mmHg, PA 57/26 mmHg, RA 15 mmHg) and a significant coronary stenosis (LAD [symbol: see text] 99%). High output heart failure and angina pectoris responded to treatment. They subsequently worsened, because she stopped taking methimazole for a month and serum levels of thyroid hormones increased again. After retreatment with methimazole, serum levels of thyroid hormones decreased to within normal limits, and high output heart failure and angina pectoris also improved.

[An elderly case of idiopathic thrombocytopenic purpura associated with acute myocardial infarction].

We report a rare case of idiopathic thrombocytopenic purpura (ITP) associated with acute myocardial infarction (AMI). A 72-year-old woman with hypertension and hemorrhoids was admitted because of chest pain, severe anemia (RBC 340 x 10(4)/microliter, Hb 5.4 g/dl, Ht 21.7%) and thrombocytopenia (0.2 x 10(4)/microliter). AMI was diagnosed by electrocardiogram (ST elevation and negative T in V2-5), echocardiogram (hypokinesis in anteroseptal wall) and laboratory (CPK 470 U/l) findings and was treated with only blood transfusion. Chest pain disappeared the day after admission, and neither heart failure nor arrhythmia occurred. Based on bone marrow findings (hyperplasia of erythroblast and megakaryocyte), endoscopic (internal hemorrhoids) and laboratory (antiplatelet antibody positive, platelet associated IgG 257.8 ng/10(7) cells) findings, iron deficiency anemia and ITP were diagnosed. Anemia improved after blood transfusion, but thrombocytopenia (< 1.0 x 10(4)/microliter) without active bleeding continued after steroid and gamma-globulin therapy. At discharge, electrocardiogram showed a negative T in I, aVL and V2-5, and T1 and BMIPP myocardial scintigram showed defects in the anteroseptal and apical wall.

[Gastroesophageal reflux and respiratory tract infection in tube-fed elderly patients--a comparison between scintigraphy and 24-h pH monitoring].

Aspiration pneumonia in patients who received enteral feeding via a nasogastric tube may result from retrograde colonization from the stomach, and this may be more likely when the gastroesophageal reflux is severe and the gastric pH is relative high. We investigated 11 elderly patients fed via nasogastric tube with suspected recurrent aspiration pneumonia by means of esophageal scintigraphy, 24-h pH monitoring, gastric pH and concentrations of gram-negative bacilli in gastric aspirates. The grade of respiratory tract infection (RTI) was evaluated by the frequency of episodes of fever with respiratory symptoms. The correlation between the grade of RTI and reflux index by scintigraphy was statistically significant (p < 0.05), but the correlation between the grade of RTI and reflux rate by 24-h pH monitoring was not statistically significant. Although the correlation between gastric pH and log (base 10) concentration of gram-negative bacilli/ml of gastric aspirates was statistically significant (p < 0.001), the correlation between the grade of RTI and gastric pH was not statistically significant. Scintigraphy was superior for evaluation of gastroesophageal reflux resulting in aspiration pneumonia in the tube-fed elderly patients.

[Guanidino compounds in the elderly].

To examine the metabolism of guanidino compounds in the elderly, we measured the serum concentrations of urea nitrogen, creatinine (Cr), guanidinoacetic acid (GAA) and creatine (CR) in middle-aged and elderly subjects. We also measured muscle mass in the elderly. The elderly subjects tended to have lower serum GAA concentrations than middle-aged subjects. On the contrary, CR concentrations of elderly subjects were higher than those of middle-aged subjects. Bedridden elderly subjects tended to have lower serum GAA concentrations and lighter muscle mass than ambulatory elderly subjects. On the contrary, serum CR concentrations of bedridden subjects were higher than those of ambulatory subjects. CR is an essential substance for muscle energy metabolism. These results indicate that high serum CR concentrations due to low CR metabolism in skeletal muscle might suppress glycine amidinotransferase (GAT) activity, resulting in decreased GAA production in the elderly.

[Renal diseases in disturbance of urate metabolism].

Although serum concentrations of uric acid could be frequently measured in various diseases, most clinicians are less interesting in the significance of serum urate levels. Since uric acid is produced in the body and eliminated through the kidney into the urine, the kidney plays a main role in controlling serum urate level. On the other hand higher concentrations of uric acid in blood and urine could involve renal damage because uric acid is less soluble in acidic solutions like a tubular fluids, resulting in tubulointerstitial nephropathy. In this paper I described that the mechanism of urate metabolism in the human kidney and then how disorders of urate metabolism involve the kidney.