In the treatment of hyperlipidemia, when to begin and end therapy is important. In recent years, potent anti-hyperlipidemia drugs have been widely used, and the results of many intervention trials have shown that combinations of diet, exercise and drug therapies are effective for the primary and secondary prevention of coronary heart disease. The present paper summarizes these trials; introduces the therapy guidelines for adult hyperlipidemia established by Japan Atherosclerosis Society in 1997; and discusses the drugs for hyperlipidemia.
(Internaml Medicine 39: 765-772, 2000)

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Hypertension is the most common complication of chronic renal insufficiency (CRI) and it accelerates the rate of progression of most forms of CRI. Several large clinical trials have clearly demonstrated the efficacy of antihypertensive treatment for prevention of progression of renal failure. Angiotensin-converting enzyme (ACE) inhibitors may have therapeutic advantages. However, large scale trials include a variety of chronic renal diseases, and the origins of renal diseases are quite diverse. Moreover, the differences in sex, age, race have not been considered. Based on these trials, it was concluded that blood pressure control is the most effective means for the prevention of deterioration of renal dysfunction. Consistent with this view, our recent preliminary data provide evidence that aggressive blood pressure control using self-reported blood pressure values measured by a home blood pressure device is promising to arrest the progression of renal failure in Japanese patients with CRI.
(Internal Medicine 39: 773-777, 2000)

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Objective This prospective pilot study was conducted to compare the usefulness of measuring fecal lactoferrin (Lf) to that of fecal occult blood (FOB) test for detection of colorectal diseases.
Patients and Methods The subjects were 351 patients who underwent colonoscopy. A fecal sample was obtained on the day before colonoscopy. Fecal Lf was measured by enzyme-linked immunosorbent assay. The FOB test was performed by combined assay (latex agglutination) of hemoglobin and transferrin.
Results The specificities of the fecal Lf and FOB tests were the same (88.7%). For patients with colorectal cancer (13), colorectal polyp (69), ulcerative colitis (18), Crohn's disease (13), non-specific colitis (8), internal hemorrhoids (60), colon diverticulum (27), and miscellaneous diseases of the colon (10), the rates of positivity for fecal Lf were 7/13, 14/69, 12/18, 7/13, 4/8, 22/60, 8/27, and 6/10, respectively. The corresponding rates for FOB were 8/13, 12/69, 11/18, 4/13, 4/8, 9/60, 2/27, and 1/10. For patients with internal hemorrhoids, the rate of positivity for fecal Lf was significantly higher than that for FOB. In other disease groups, there was no significant difference in the rate of positivity between fecal Lf and FOB.
Conclusion These findings suggest that measurement of fecal Lf is as useful as FOB in detecting colorectal diseases.
(Internal Medicine 39: 778-782, 2000)

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Objective Evaluation of metabolic states and chronic complications is essential for maintaining a high quality of care for diabetic patients. We have assessed the quality of care in routine outpatient clinics for diabetic subjects in our university hospital, and compared with those in a newly introduced standardized clinic to evaluate the new care system.
Methods The quality of care was assessed by the chart review in 1995, and compared with those from 1996-1997 in the "Diabetes Follow-up Clinic" which is systematically designed for the standardized care.
Patients The subjects were recruited among 860 patients who visited the outpatient clinic in July and August of 1995 with a diagnosis of diabetes or glucose intolerance. Six hundred seventy-two patients whose follow-up period had been more than 6 months with clinically diagnosed diabetes were used for the analysis.
Results Laboratory tests such as determination of HbA1c, and serum levels of lipids and creatinine were performed in more than 90% of the patients in the routine outpatient clinics. However, ophthalmology referral, 24-hour urine collection for the determination of creatinine clearance and albumin excretion, and electrocardiograms were not well performed and were incompletely documented (40-60% of the patients within a previous year and 70-80% in the last 2 years). In the standardized "Diabetes Follow-up Clinic", only four out of 555 diabetic patients failed to collect their 24-hour urine, and all participants had ankle blood pressure measurements, nerve conduction study, and nylon monofilament tests, etc. Furthermore, more than 95% of the patients had funduscopic examinations by ophthalmologists as well as records of electrocardiogram.
Conclusion Introduction of the standardized "Diabetes Follow-up Clinic" may be one of the choices for increasing the quality of outpatient care and for the prevention of chronic diabetic complications.
(Internal Medicine 39: 783-787, 2000)

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Objective Interferon has been used as a new therapeutic agent for glomerulonephritis since a manifest relationship between membranoproliferative glomerulonephritis (MPGN) and hepatitis C virus (HCV) infection was documented. However, several side effects and rebound phenomenon have been significant problems. We retrospectively evaluated the therapeutic effect and safety of the standard treatment with steroids and/or immunosuppressive agents for MPGN patients with an HCV infection.
Methods Remission and renal survival rates as well as clinical and histological data were compared between MPGN groups with or without an HCV infection. In addition, the hepatic function was followed-up after the treatment.
Patients The subjects were 42 biopsy proven MPGN patients. Seven were positive for an HCV infection. Secondary causes of MPGN excluding an HCV infection were omitted. Most patients were treated with steroids and/or immunosuppressive agents.
Results The mean age of the MPGN patients with an HCV infection was significantly higher than that of those without an HCV infection. The renal function and the interstitial change of the former group were significantly worse than those of the latter. Nevertheless, remission and renal survival rates were not significantly different between the two groups. None in the HCV positive MPGN group showed an impairment of hepatic function during the clinical course. However, 2 subjects died from severe pneumonia during the treatment.
Conclusion The standard treatment with steroids and/or immunosuppressive agents did not reveal a statistical difference in the therapeutic efficacy between MPGN patients with or without an HCV infection. However, some in the former group showed a poor prognosis.
(Internal Medicine 39: 788-793, 2000)

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Objective To determine an appropriate duration for a short course of oral steroids in cases of asthma exacerbations.
Setting A 1, 000 bed city hospital in Kobe, Japan.
Patients Patients with asthma exacerbations who needed hospital admission.
Methods Following an initial treatment with a 3-day course of intravenous methylprednisolone, patients were allocated to either a 1-week (1W) or a 2-week (2 W) course of oral prednisolone (PSL, 0.5 mg/kg).
Outcome measures Peak expiratory flow rate (PEF) and rate of unscheduled hospital visits and readmission.
Results Twenty patients were enrolled (10 in 1 W, 10 in 2 W). Mean PEF just before starting oral PSL in 1W and 2 W were 51 and 58% of each patient's best value. PEF was significantly improved and to a similar degree over the course of time in both 1W and 2 W. The frequency of unexpected hospital visits during a 3-month period after discharge was similar (2 in 1W and 2 in 2 W). No readmission occurred during the same period.
Conclusions Because both the 1-week and the 2-week course of oral PSL were equally effective in the treatment of asthma exacerbations, 1 week may be appropriate as the maximum duration of a short rescue course of oral steroids.
(Internal Medicine 39: 794-797, 2000)

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Objective To assess the applicability of Hyland's Living with Asthma Questionnaire (LWAQ, 1991), one of the international health-related quality of life scales, for Japanese asthmatic patients with reference to its reproducibility and validity.
Subjects and Methods The LWAQ was given to randomly selected asthmatic patients on two occasions separated by a 12-week interval.
Results The mean scale score in the first study (n=304) was 1.83 (range, 1.14-2.77) and logarithmic values of the scores approached normal distribution. The scale scores in the first and second (n=158) studies were well correlated (r=0.81), however, the mean score decreased (0.08) significantly. The questions were further separated into 11 domains. The sex-domain was notable for a low response rate (68%), and scale scores in the sleep-, colds- and sex-domains in the first study varied considerably from those of the other domains. Frequency distributions of scores in the five constructs (Hyland 1996) were not normal and, with the exception of the colds construct, the relations among the remaining four constructs were similar to those previously reported (Hyland 1996).
Conclusion Analysis using the mean scale score, domain and construct in the LWAQ is applicable to Japanese asthmatic patients.
(Internal Medicine 39: 798-803, 2000)

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A 61-year-old Japanese woman with heterozygous familial hypercholesterolemia (FH), type 2 diabetes mellitus and coronary artery disease underwent coronary artery bypass grafting (CABG) utilizing a saphenous vein graft at the age of 46, in June 1984, 6 months before low density lipoprotein (LDL) apheresis was started. She had received LDL apheresis every two weeks, along with combined drug treatment since the age of 47 (December 1984). She had bilateral xanthelasma and Achilles tendon xanthomas. Her fasting baseline serum total cholesterol and triglyceride level were 464 mg/dl and 57 mg/dl, respectively at the age of 47 when she visited our hospital for the first time. Analysis of the genomic DNA from the patient revealed heterozygous amino acid substitution of Leu for Pro⁶⁶⁴ in the LDL receptor gene. She was diagnosed as type 2 diabetes mellitus at the age of 53. Combined treatment in the steady state yielded a pretreatment LDL cholesterol level of 230 ±14 mg/dl and a posttreatment level of 57±7.6. All grafts were widely patent after as long as 14 years since CABG, suggesting that LDL apheresis combined with drug therapy is highly effective in preventing the occlusion of bypass grafts in a patient with heterozygous FH and type 2 diabetes mellitus.
(Internal Medicine 39: 804-809, 2000)

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A 69-year-old man visited our department of neurology with symptoms of paresthesia on the lower extremities and lumbago. Biochemical examination of serum samples showed hypercalcemia (serum concentration 15.6 mg/dl). The levels of intact parathyroid hormone (i-PTH) and 1, 25-dihydroxyvitamin D were suppressed, whereas parathyroid hormone-related peptide (PTHrP) was elevated up to 5.4 pM (normal range: below 0.6 pM). Additionally, bone survey revealed a punched-out lesion in radiological examinations of the skull. Bone marrow aspiration demonstrated many atypical plasma cells suggesting multiple myeloma. Nephrogenous cyclic adenosine monophosphate (cAMP), urinary deoxypyridinoline, plasma interleukin 6 (IL-6) and transforming growth factor β (β (TGF β) concentrations were elevated, whereas % of renal tubular reabsorption of phosphate (%TRP) was decreased. The immunohistochemical results demonstrated the expression of PTHrP in atypical plasma cells. These data indicated that hypercalcemia complicating multiple myeloma causes an elevation of renal calcium reabsorption and an increase of bone resorption mediated by PTHrP action.
(Internal Medicine 39: 810-813, 2000)

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A 59-year-old woman who had parathyroid adenoma, parathyroid hyperplasia, thyroid follicular adenoma, thyroid papillary carcinoma, astrocytoma of the right temporal lobe, cerebellar meningioma, capillary hemangioma of the left external auditory meatus and papilloma of the left upper gingiva is reported. Dynamic magnetic resonance imaging, computed tomography with contrast-enhancement and gastrofiberscopy revealed no remarkable findings in the pituitary, pancreas, adrenals, stomach or duodenum. Similar lesions were not found in any family members. Defect of the causative genes of multiple endocrine neoplasia types I and Ha, MENIN and RET was not detected. Further follow-up of this patient and family members is needed.
(Internal Medicine 39: 814-819, 2000)

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A malignant pheochromocytoma is described in a 71-year-old man. Osseous metastases became manifest 12 years after successful removal of the primary tumor which originated in paraganglionic tissue near the right adrenal gland. Although the patient had no symptoms of catecholamine excess initially, hypertension, tachycardia and excessive sweating appeared several months before his death, concomitantly with a sharp increase in noradrenaline secretion due to an accelerated growth of metastatic tumors. Since there is no histologic criterion of malignancy in this neoplasm, it would be prudent to consider every case of pheochromocytoma as potentially malignant and to follow-up carefully for a long time after removal of the primary tumor.
(Internal Medicine 39: 820-825, 2000)

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An 87-year-old woman, diagnosed with diabetes mellitus at age 73, exhibited abdominal distention and appetite loss in March 1998. She had received acarbose as well as 5 mg per day of glibenclamide and had habitually used about 100 g of maltitol daily from 1997. She was diagnosed as having paralytic ileus accompanied by pneumatosis cystoides intestinalis (PCI). This condition subsided quickly with discontinuation of diet or cessation of acarbose and maltitol usage. The patient's condition appears to be attributable to increased gas levels produced by fermentation of disaccharides and maltitol. Decreased intestinal motility may be a result of pre-existing diabetic autonomic neuropathy and hypothyroidism. The patient's clinical course suggests that paralytic ileus and PCI should be listed as rare side effects of alpha-glucosidase inhibitors and that the drug should be used with great caution for those who consume non-digestive sugar substitutes.
(Internal Medicine 39: 826-829, 2000)

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Two cases of acute eosinophilic pneumonia following cigarette smoking are analyzed for characteristic features. The first patient noted dyspnea 14 days after initiation of smoking. The second patient noted dyspnea 12 days after beginning to smoke. Both cases had characteristic features including occurrence at an age younger than 30 years; less than 1 month duration of cigarette smoking before onset of disease; and no identifiable cause of acute eosinophilic pneumonia apart from smoking. We believe that acute eosinophilic pneumonia following cigarette smoking, which has characteristic features as described above, should be considered as a distinct subtype of AEP.
(Internal Medicine 39: 830-833, 2000)

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We describe two cases of atypical carcinoid of the thymus. One was an 82-year-old woman with complaints of nonproductive cough and back pain, and the other a 64-year-old woman with no symptoms. Computed tomography scans of the chest in both cases revealed a large mass in the anterior mediastinum. Multiple metastases to bone and liver were also noted in the former case. Histological examination of their tumors revealed that the tumor cells were arranged in a nested, trabecular, or pseudorosette pattern, with increased numbers of mitoses, nuclear pleomorphism, and presence of necrosis. In addition, immunohistochemically, the cells stained for neuron-specific enolase, synaptophysin and chromogranin A. Combination chemotherapy consisting of carboplatin and etoposide was performed as initial chemotherapy in the former case and as adjuvant therapy in the latter. The former patient achieved a short-term partial response. It is important to differentiate atypical carcinoid from other thymic tumors, since such tumors including thymoma have a much better prognosis than does atypical carcinoid.
(Internal Medicine 39: 834-838, 2000)

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A 71-year-old Japanese female Nagasaki-atomic-bomb survivor was admitted for evaluation of a mediastinal mass. She was infected with human T-cell leukemia virus type I. Histological examination of the biopsy specimen, obtained thoracoscopically from the mass, revealed amyloid lymphadenopathy confirmed by Congo-red staining and electron-microscopic examination. Amyloid deposits and the serum monoclonal peak consisted of immunoglobulin λ light chains. No atypical cells were detected in bone marrow. The case was diagnosed as an unusual amyloidosis affecting the mediastinal lymph node. No other sites were found to be affected by amyloidosis, although systemic involvement could not be conclusively ruled out.
(Internal Medicine 39: 839-842, 2000)

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Flow cytometric, immunochemical and molecular studies were performed on leukemic blasts from a patient with minimally differentiated erythroleukemia (AML-M6v). The blasts expressed CD36 and CD71 but not lymphoid antigens, myeloid antigens, CD41 or glycophorin A. Analysis of carbohydrate antigens showed that the blasts expressed the sialyl-Tn antigen. Immunochemistry revealed that the blasts had neuron-specific enolase (NSE). Serum sialyl-Tn and NSE levels were markedly increased. Finally, an erythroid lineage was confirmed in the presence of alpha-globin messages in the blasts. Sialyl-Tn and NSE expression in leukemic blasts may be useful to identify AML-M6v.
(Internal Medicine 39: 843-846, 2000)

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A 68-year-old man with sensory ataxic dominant neuropathy associated with polyarteritis nodosa (PAN) had deep sensory disturbance with unsteady gait and absence of the Achilles tendon reflex. Examination revealed weight loss, elevated CRP level, negative antineutrophil cytoplasm antibodies, decreased M-wave amplitude in the peroneal motor nerve and absence of action potentials in the sural sensory nerve. Sural nerve biopsy revealed a marked loss of myelinated fibers, myelin ovoid formation and necrotizing angiitis of large epineurial artrioles. Renal biopsy revealed global and/or segmental necrotizing angiitis in glomeruli, but not in the arcuate artery. These pathological findings were distinct from those of PAN, particularly microscopic polyangiitis (MPA). Treatment with a steroid improved the deep sensory disturbance, unsteady gait, and CRP level. This case is similar to ataxic neuropathy which can arise from various disorders. This is the first report of a case of sensory ataxic dominant neuropathy associated with MPA in PAN.
(Internal Medicine 39: 847-851, 2000)

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A case of basilar migraine (BM) with alternate numbness as the initial symptom is described. The patient's chief complaint was alternate numbness in the right and left upper extremities. After angiography the patient fell into a drowsy state, followed by excitation, and finally confusion. The EEG power topography showed slow alpha, theta and delta power in the right occipital area, and alternatively in the right and left parietal area. These findings suggest that the cause of BM is not only based on a vasoconstriction mechanism, but also cortical spreading depression. BM should be suspected as a cause of sensory symptoms.
(Internal Medicine 39: 852-855, 2000)

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Catastrophic antiphospholipid syndrome (CAPS) is a severe variant of antiphospholipid syndrome (APS) characterized by disseminated microangiopathy that results in multiorgan failure. CAPS mainly occurs in association with systemic lupus erythematosus (SLE). Clinically, CAPS mimics disseminated SLE vasculitis, intravascular coagulation (DIC), and particularly thrombotic thrombocytopenic purpura (TTP). We describe an autopsy case of young woman with CAPS in SLE, which is difficult to differentiate from TTP secondary to SLE.
(Internal Medicine 39: 856-859, 2000)

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