We determined the vitamin B₁₂ clearance using an ultrafiltration technique and assessed whether the clearance of this vitamin B₁₂ Could be used to estimate the glomerular filtration rate (GFR). Fourteen subjects (5 had renal disease, 7 had diabetes mellitus, one had liver cirrhosis and one had cholelithiasis) divided into two groups were studied (group 1, 5 patients without vitamin B₁₂ preloading; group 2, 9 patients with vitamin B₁₂ preloading). Vitamin B₁₂ clearance was significantly correlated with inulin clearance (r = 0.81, p < 0.001) in group 1; group 2 showed an even better correlation (r = 0.94, p < 0.001) with the presaturated vitamin B₁₂ binding protein. In group 2, the mean inulin and vitamin B₁₂ clearance values did not differ significantly (40.3 ± 13.6 vs 48.2 ± 17.2 ml/min), but there was a significant difference between mean inulin and creatinine clearance (40.3 ± 13.6 vs 64.9 ± 19.9 ml/min, p < 0.05). In conclusion, vitamin B₁₂ clearance appears to be a more reliable method of estimating GFR than creatinine clearance.
(Internal Medicine 32: 194-196, 1993)

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The clinical features of four asthma types, Ia-1 (bronchospasm with 0-49ml/day of expectoration), Ia-2 (with 50- 99ml/day), Ib (over 100ml/day), and II (bronchiolar obstruction), as classified by the clinical symptoms, were compared in 119 patients with bronchial asthma. The age of onset characteristic symptoms of each asthma type was in the 20's in types Ia-1 and Ia-2, in the 30's in type Ib, and in the 40's in type II patients. A significant increase in the number of neutrophils in bronchoalveolar lavage (BAL) fluid was found in type II patients. The proportion of BAL eosinophils was significantly higher in types Ia-2 and Ib asthma patients compared with that in type Ia-1 patients. The BAL eosinophil count was significantly higher in type Ib than in type Ia-2 patients. The FEV1.0% and %₂₅ values were significantly lower in patients with type II asthma than in the patients with the other asthma types. Steroid-dependent intractable asthma (SDIA) was more often observed in patients with type Ib or type II asthma.
(Internal Medicine 32: 197-203, 1993)

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In hematological diseases such as myeloproliferative disorders (MPD) or myelodysplastic syndromes (MDS), some abnormalities in the chemiluminescence of neutrophils are observed. There are two groups; one includes chronic myelogenous leukemia (CML), essential thrombocythemia (ET) and MDS, which all have decreased chemiluminescence of neutrophils. The other group includes polycythemia vera (PV) which has increased neutrophil chemiluminescence. We studied the neutrophil function by analyzing the chemiluminescence in 35 patients with hematological diseases. In most of these cases the defects in chemiluminescence in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) were correlated with those in response to phorbol 12-myristate 13-acetate (PMA). But there were exceptional cases in which the maximal light emission of chemiluminescence (Max CL) in response to FMLP was obviously lower than controls despite the fact that the Max CL in response to PMA was the same as the controls. These facts suggest a heterogenicity of the defect site in these diseases. There was a correlation between the level of chemiluminescence and the neutrophil alkaline phosphatase (NAP) activity in these patients. In vitro culture of CML neutrophils with granulocyte colonystimulating factor (G-CSF) showed a correlation between the increase in the level of chemiluminescence and NAP activity. These results suggest that NAP may take part in the control of neutrophil function.
(Internal Medicine 32: 204-209, 1993)

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A partial cDNA clone encoding cholesterol 7α-hydroxylase (pHA 7α-3) was isolated from a hamster liver cNDA library using rat P-450 ch7 cDNA (p 7α-11) as a probe. In comparison with the complete base sequence of p 7α-11, pHA 7α-3 lacked about 500 base pairs at the 5' end. Circadian rhythms of mRNA for hamster liver 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol 7α-hydroxylase were investigated with cDNA clones encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase (pRed-227) and pHA 7α-3. Typical circadian rhythms of mRNA for both enzymes and a time lag between the two circadian rhythms were observed. The circadian rhythm of activity for each enzyme corresponded to that of each mRNA.
(Internal Medicine 32: 210-214, 1993)

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Between April 1981 and December 1987, 148 patients with newly diagnosed small cell lung cancer (SCLC) were treated using combination chemotherapy with or without thoracic irradiation and prophylactic cranial irradiation (PCI) in a series of cooperative therapeutic trials. With a minimum follow-up of 4.7 years, 13 (9%) patients survived and were free of SCLC. These included 11 (15%) of 76 patients with limited disease and two (3%) of 72 patients with extensive disease. Three died without any evidence of SCLC (one each from second leukemia, non-small cell lung cancer, and unrelated disease). The remaining 10 (7%) patients are currently alive and free of SCLC beyond 4.7 years. Since late relapse beyond 5 years is a very rare event, these patients may have been cured. However, late toxicity of PCI must be kept in mind. Three among the 10 patients have suffered from neuropsychologic symptoms of varying degrees in severity. Although the long-term survival rate is a benchmark in the treatment of SCLC, modifications of therapy that may potentially avoid such toxicities should be considered hereafter.
(Internal Medicine 32: 215-220, 1993)

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The frequency of streptococcal infections has been reported to be increasing. To determine the significance of such infections complicating treatment of leukemia, we studied the incidence and clinical features of Streptococcus mitis septicemia among51 leukemia patients in our department.During 166 consecutive treatment courses for leukemia, eight episodes of Streptococcus mitis septicemia were observed in 35 septicemic patients. In seven out of eight episodes (88%), severe mucositis developed after aggressive chemotherapy, suggesting that oral mucosamight be the site of entry for Streptococcus mitis. The isolates were sensitive to imipenam/cilastatin and cefuzonam, and were relatively resistant to amikacin. Although none of the patients died of Streptococcus mitis septicemia, life-threatening adult respiratory distress syndrome (ARDS) developed in two independent treatment courses. We should thus be aware of the risk of ARDS in patients with Streptococcus mitis septicemia.
(Internal Medicine 32: 221-224, 1993)

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A 67-year-old patient with Shy-Drager syndrome (SDS), exhibited nocturnal polyuria associated with abnormal circadian rhythm of antidiuretic hormone (ADH)secretion and nocturnal polyuria. The patient excreted a larger volume of urine during the nighttime compared to that in the daytime. The specific gravity of urine at night was lower than that during the day. In contrast to normal circadian rhythm of ADH, the patient's plasma concentration of ADH was increased in the daytime. The present study raised the possibility that an altered circadian rhythm of plasma ADH secretion might be considered a result of the neurodegenerative changes involving the hypothalamus.
(Internal Medicine 32: 225-227, 1993)

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A 36-year-old woman with positional headache was found to have primary low cerebrospinal fluid (CSF) pressure syndrome and galactorrhea. The CSF pressure at lumbar puncture was not measurable. Magnetic resonance imaging demonstrated that the ventricle and cerebral sulcus were narrowed and the pituitary stalk was oppressed by the brain. Hyperresponsiveness of prolactin was noted after stimulation with thyrotropin-releasing hormone. These abnormalities disappeared with normalization of CSF pressure with the treatment. Galactorrhea was apparently due to oppression of the pituitary stalk by downward movement of the brain.
(Internal Medicine 32: 228-231, 1993)

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A 58-year-old woman suddenly developed right exophthalmos. A CT scan of her orbit revealed an increase in volume and density of extraocular muscles and intraorbital soft tissues that resembled exophthalmos in Graves' disease. The exophthalmos gradually improved without treatment. Two months later she developed mononeuritis multiplex in her limbs, and then showed a sudden onset of swelling of her right calf. Sural nerve biopsy was performed and the diagnosis of polyarteritis nodosa (PN) was established from the histological findings. A rare case of PN with exophthalmos is herein reported with a review of the literature.
(Internal Medicine 32: 232-236, 1993)

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A78-year-old female was found to have angiotropic lymphoma, a rare fatal disease, with initial symptoms of oculomotor nerve palsy. A biopsy of the paranasal sinus mucosa showed that the small vessels were occupied by large mononuclear cells which upon immunohistochemical examination tested positive for pre B-cell markers. She felt a gradually increasing pain in her left thigh. Magnetic resonance imaging suggested the involvement of neoplastic cells in the left femoral bone marrow. Following chemotherapy treatment remission was achieved. Early diagnosis of angiotropic lymphomaappears very significant, as this disorder could be well controlled by systemic chemotherapy.
(Internal Medicine 32: 237-242, 1993)

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A 72-year-old patient with von Recklinghausen's disease showed akinetic mutism within 6 months of the onset of dementia. The findings of diffuse cerebral atrophy on CT and periodic synchronous discharges (PSDs) in EEG suggested Creutzfeldt-Jakob disease. However, autopsy findings of diffuse softening of the subcortical white matter and marked arteriosclerotic changes of the subcortical arterioles with sparing of the cortex in the cerebrum confirmed a diagnosis of Binswanger's disease. Binswanger's disease should be included in the differential diagnosis of dementia showing PSDs in EEG.
(Internal Medicine 32: 243-246, 1993)

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A 63-year-old man developed pulmonary aspergilloma and was given antifungal agents systemically. However adverse reactions, including renal dysfunction and gastric ulcer necessi-tated discontinuation of the treatment. Transbronchial infusion of miconazole was also unsuc-cessful because of an asthmatic attack during the procedure. Inhalation of miconazole was started once a week, resulting in remarkable improvement after 6 months of treatment both symptomatically and radiologically without any adverse reactions. We believe that long-term intermittent inhalation therapy with miconazole is well tolerated and useful in patients with aspergilloma, particularly when systemic treatment is difficult because of other underlying diseases or adverse reactions.
(Internal Medicine 32: 247-250, 1993)

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A 56-year-old female had pure regurgitation in all cardiac valves. Color Doppler echocardiography showed a regurgitant jet in all cardiac valves. The severity of regurgitation due to the prolapse in all valves was moderate. The patient had no history of rheumatic fever, ischemic heart disease, endocarditis or hypertension. Physical characteristics of the patient were neither of Marfan's nor Ehlers-Danlos' syndrome. The etiology of regurgitation in all cardiac valves of this patient may be due to multiple valve prolapse.
(Internal Medicine 32: 251-254, 1993)

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A clonal analysis of hematopoiesis in a hypoplastic MDS patient was performed. Monoclonal utilization of PGK gene on her two X chromosomes was detected by Southern blot analysis of the bone marrow cells using a PGK probe after methylation-sensitive restriction enzyme treatment. This is compatible with monoclonal construction of her hematopoiesis, confirming MDS nature with a progression of her morphological dysplasia in bone marrow cells. RFLP of PGK gene on X chromosome is thus useful to detect a monoclonality in hematopoietic diseases.
(Internal Medicine 32: 255-256, 1993)

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A case of malignant thymoma presenting as the superior vena cava syndrome is reported. A 56-year old male was admitted with superior vena cava syndrome. CT and NMR-CT scan showed a solid homogenous superior mediastinal mass; which filled the lumen of the superior vena cava and the right atrium. A biopsy of the right atrial mass showed myxoma, and operation was performed. Histopathologically the tumor was diagnosed as thymoma. Intracaval and intracardiac extension of a thymoma is very rare.
(Internal Medicine 32: 257-260, 1993)

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A 48-year-old Japanese woman with mixed connective tissue disease (MCTD) and Sjögren's syndrome (SjS) was a carrier of HTLV-I and had anti-HTLV-I antibodies in her serum. Moreover, her peripheral blood lymphocytes contained proviral DNA for the pX region of HTLV-I as detected by the polymerase chain reaction. An immunohistological study was performed on her minor salivary gland to detect gene products of HTLV-I (P19 and P28 proteins); specific staining was demonstrated only in the epithelium of the salivary ducts. HTLV-I and its associated immune dysfuction may be responsible for MCTD and SjS in this patient.
(Internal Medicine 32: 261-264, 1993)

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A 39-year-old woman with Graves' disease associated with follicular thyroid carcinoma underwent subtotal thyroidectomy. TSH-binding inhibitor immunoglobulins (TBII) were positive, whereas thyroid-stimulating antibodies (TSAb) and thyroid-stimulation-blocking antibodies (TSBAb) were both negative before the operation. After the operation, TBII markedly increased above the pretreatment value. TSBAb became positive 3 months after the operation and then their activity increased, while TSA bremained negative after the operation. Subtotal thyroidectomy may have influenced the development of TSBAb in this patient. Irrespective of these findings, the patient became hyperthyroid again several months after the operation.
(Internal Medicine: 32: 265-268, 1993)

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A 61-year-old woman developed rhabdomyolysis and acute renal failure after strenuous walking. She had been treated for seven years with levothyroxine (T4) for hypothyroidism. On admission, her thyroid function test revealed marked hypothyroidism, suggesting poor drug compliance. Electromyographic and muscle biopsy findings were compatible with hypothyroid myopathy. Other diseases that could cause rhabdomyolysis were excluded. Her renal function completely recovered with peritoneal dialysis, and thyroid function normalized with 100μg/day of T4. The present case suggests that rhabdomyolysis could occur in patients with hypothyroidism, especially those with poor drug compliance, in combination with other aggravating factors such as exercise.
(Internal Medicine 32: 269-271, 1993)

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