Elevation of serum KL-6 levels in patients with hematological malignancies associated with cytomegalovirus or Pneumocystis carinii pneumonia.

The level of serum KL-6 antigen has been reported to be a sensitive indicator of various interstitial pneumonitis, but in patients with hematological malignancies who were accompanied by infective interstitial pneumonitis like Pneumocystis carinii or cytomegalovirus (CMV) pneumonia, it is still unknown whether serum KL-6 level is useful as a good marker for the diagnosis or disease activity. In this study, the serum levels of KL-6 and soluble intercellular adhesion molecule 1 (sICAM-1) were evaluated in five patients with malignant lymphoma or adult T-cell leukemia. Serum KL-6 and sICAM-1 levels at the time of diagnosis of P. carinii or CMV pneumonia were 1220+/-323 U/ml (mean+/-SD) and 1246+/-485 ng/ml, respectively. These levels were apparently high, when compared with standard value of serum KL-6 (<520 U/ml) and that of sICAM-1 (115-306 ng/ml). In patients without P. carinii or CMV pneumonia, who had hematological malignancies or AIDS, serum level of KL-6 was not high (299+/-122 U/ml), but sICAM-1 was high (651+/-495 ng/ml) because of the elevation of sICAM-1 in four of five cases. These findings suggest that, in patients with hematological malignancies, serum level of KL-6 antigen rather than sICAM-1 may be useful in the evaluation of CMV or P. carinii pneumonia.

[Clinical study of infection associated hemophagocytic syndrome].

Hemophagocytic syndrome (HPS) causes pancytopenia, increased blood LDH level, liver dysfunction, DIC, etc. with macrophages appearing in the bone marrow, spleen, lymph nodes, etc. Adult HPS is mostly secondary to various infections, malignant tumors, etc. and sometimes has a serious outcome. Particularly infection associated HPS (IAHS) is triggered by viral, bacterial and fungal infections. The cases of unknown primary disease and suspected IAHS of unidentified pathogenic microorganism are often encountered in the clinical setting. The authors compared IAHS and malignant associated HPS (MAHS) and classified IAHS into viral associated HPS (VAHS), bacterial associated HPS (BAHS) and fungal types to compare the test values based on the test findings at the onset in the HPS cases treated at our Department. The patients consisted of 21 HPS cases, 11 IAHS cases (VAHS 4, BAHS 5, fungal 2) and 10 MAHS cases. Based on the test findings (WBC, Hb, Plt, LDH, ferritin, myelogram, cytokines, [IFN alpha, TNF gamma, IL-6, sIL-2R, M-CSF], adhesion molecules [sICAM-1, sVCAM-1, sELAM-1, sL-selectin]) at the onset, a comparison between IAHS and MAHS and among the IAHS cases classified by pathogenic microorganism was made. In the comparison between IAHS and MAHS, the Hb value was significantly decreased and sIL-2R tended to be increased at the onset in MAHS. When comparing the IAHS cases by pathogenic microorganism, Plt was significantly decreased and sICAM-1 and sVCAM-1 were increased at the onset in the BAHS, The BAHS cases had serious underlying diseases and poor prognosis with high incidence of DIC complications. We are going to accumulate more cases for early diagnosis and treatment of IAHS.

[Granular lymphocyte-proliferative disorder following initiation of protease inhibitor therapy in a patient with acquired immunodeficiency syndrome].

The authors experienced granular lymphocyte-proliferative disorder (GLPD) with increased lymphocyte and CD4 cell counts after HIV treatment with a protease inhibitor indinavir in a 51-year-old male AIDS patient. GLPD proved to be the chronic type, but we could not differentiate whether it was the T-cell type or the NK-cell type. EB virus was found to be activated and its chronic activity was suggested. We should note in this case that EB virus was involved in the GLPD onset and that GLPD followed the treatment with a protease inhibitor.

[Fatal lactic acidosis in a patient with acquired immunodeficiency syndrome treated with stavudine, lamivudine and indinavir].

Recently, several class-related adverse events have been recognized with antiretroviral drugs. For nucleoside analogue reverse transcriptase inhibitors. (NRTI), lactic acidosis with hepatomegaly and hepatic steatosis have been reported. These appear to occur at a low frequency, but with a high fatality rate. We report a case of fatal lactic acidosis in a patient with acquired immunodeficiency syndrome (AIDS) treated with stavudine (d4T), lamivudine (3TC) and indinavir (IDV). A 48-year-old male AIDS patient was admitted with complaints of general fatigue and dyspnea. His medications at presentation included d4T, 3TC and IDV. Physical examination demonstrated icteric sclerae and abdominal tenderness with hepatomegaly. Laboratory data demonstrated a severe metabolic acidosis with an anion gap due to lactate accumulation. Despite intensive treatment, cardiorespiratory arrest occurred and this could not be resuscitated.

Role of the parathyroid gland on bone mass and metabolism in immobilized stroke patients.

The significant bone-mass reduction that occurs on the hemiplegic side of stroke patients due to disuse and vitamin D deficiency may explain the increased post-stroke incidence of hip fractures. To further evaluate this osteopenia, the Z-score of bone mineral density (BMD) in both second metacarpals was assessed in 54 stroke patients and 27 control subjects. Serum concentrations of intact parathyroid hormone (PTH), osteocalcin (OC), tartrate-resistant acid phosphatase (TRAP) and 25-hydroxyvitamin D (25-OHD) were also determined. The patients' Z-scores were lower on the hemiplegic side than on the nonhemiplegic side. Serum concentrations of PTH, OC and TRAP exceeded those in control subjects. Serum 25-OHD was reduced in patients and correlated negatively with the Z-score on the hemiplegic side. Serum PTH was elevated markedly in 17% of the patients and correlated positively with the levels of OC, but not with TRAP, 25-OHD or the Z-scores on both sides. The results indicate that skeletal remodeling is accelerated in patients with hemiplegia and suggest that vitamin D deficiency and insufficient compensatory hyperparathyroidism stimulating skeletal turnover is an important cause of osteopenia in immobilized stroke patients.

Influence of immobilization on bone mass and bone metabolism in hemiplegic elderly patients with a long-standing stroke.

Significant bone mass reduction occurs in stroke patients on the hemiplegic side compared with the intact side, correlating with the degree of paralysis and vitamin D deficiency. To evaluate the influence of long-standing immobilization on this osteopenia, we measured various serum markers of bone metabolism in 93 hemiplegic elderly patients with a long-standing stroke and in 37 controls. The bone mineral density (BMD) of the second metacarpal was determined bilaterally. The scoring of the stroke patients activity was based on the Barthel Index (BI). The serum ionized calcium was higher in the patients than in the controls, correlating negatively with the BI in the patients. The concentrations of parathyroid hormone (PTH), pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen and bone Gla protein were normal or low. The serum 25-hydroxyvitamin D level was low in the patients, correlating positively with the BMD on both sides. The serum 1,25-dihydroxyvitamin D (1,25-[OH]2D) level was markedly reduced in the patients. Hemiplegia from a stroke can result in immobilization hypercalcemia which inhibits PTH secretion and 1,25-[OH]2D production. Bone remodelling may have almost reached an equilibrium, resulting in a steady rate of bone loss. This and the hypovitaminosis D appear to be the dominant causes of immobilization-induced osteopenia in elderly, long-standing hemiplegic stroke patients.

Accelerated bone remodeling in patients with poststroke hemiplegia.

A significant bone-mass reduction occurs on the hemiplegic side of stroke patients because of disuse and vitamin D deficiency. This may explain why hip fractures in poststroke patients occur almost exclusively on the hemiplegic side. To further evaluate this osteopenia, bone mineral density (BMD) in both second metacarpals was assessed in 61 patients and 28 control subjects. Serum concentrations of intact parathyroid hormone (PTH), osteocalcin (OC), tartrate-resistant acid phosphatase (TRAP), 25-hydroxyvitamin D (25-OHD), and calcium also were determined. The patients' BMD values were higher on the hemiplegic side than on the nonhemiplegic side. BMD on the hemiplegic side correlated positively with serum concentrations of PTH, OC and TRAP, which exceeded those in control subjects. Serum 25-OHD was low in patients, correlating negatively with BMD on the hemiplegic side. Serum PTH correlate positively with the levels of OC and TRAP and negatively with 25-OHD concentrations. The results indicate that skeletal remodeling is accelerated in patients with hemiplegia, with resorption predominating. We concluded that vitamin D deficiency and compensatory secondary hyperparathyroidism stimulating skeletal turnover is an important cause of osteopenia in the hemiplegic limbs of stroke patients. This osteopenia might be corrected by administration of etidronate to inhibit osteoclastic bone resorption together with a vitamin D supplement.

Recurrence of spontaneous intracranial hypotension with subdural hematomas.

A 59-year-old man developed postural headache associated with a low CSF pressure. A CT scan revealed no abnormal findings and the orthostatic symptoms resolved without treatment 6 weeks after onset. He was diagnosed as having spontaneous intracranial hypotension (SIH) and remained symptom-free until he experienced recurrence of postural headache 9 months later. A lumbar puncture demonstrated low CSF pressure, and a CT scan revealed slit-like ventricles with narrowing of the sulci, Sylvian fissures, and infratentorial cisterns, in addition to bilateral subdural masses. After draining the hematomas, his symptoms resolved completely, and a follow-up CT scan was normal. We hypothesize that recurrent SIH in this case was due to small recurrent tears of a root sleeve. This case emphasizes the importance of follow-up of SIH for at least 9 months after resolution of symptoms.

Morphologic and histochemical evaluation of muscle in patients with chronic pulmonary emphysema manifesting generalized emaciation.

Twelve severely emaciated patients with emphysema and 4 control patients with mild emaciation were studied. Arterial blood gas analysis, pulmonary function tests, and muscle biopsy were performed. According to the percentage of ideal body weight (%IBW), patients were divided into two groups of 6 patients each; one with %IBW values greater than 70.0 (group 1) and the other with %IBW values less than 70.0 (group 2), and 4 control patients with emphysema whose %IBW values were greater than 85.5. %FEV1.0, PaO2 and Hugh-Jones scores in group 2 patients were consistent with significantly greater deterioration as compared with those in group 1 patients and controls. In the muscle fibers of 11 patients and 4 controls, nicotinamide and adenosine dinucleotide tetrazolium reductase activity was studded with spots. Nemalin rods were detected in 3 specimens in group 2 and in 1 specimen each in both group 1 and controls. These changes probably result from chronic hypoxemia. Fiber type grouping accompanied by type II dominant fiber atrophy was demonstrated in 5 patients of group 2, whereas type II fiber atrophy was shown in 2 specimens from patients of group 1. Diameters of both types I and II fibers in group 2 were smaller than those in group 1 and controls. Significant correlations were observed between fiber diameters and %IBW, %FEV1.0 and %IBW, and PaO2 and %IBW. Neurogenic and disuse muscular atrophy due to both hypoxic axonal disorder and disuse is likely to be the cause of the emaciation, and a 'vicious circle' between muscular atrophy, respiratory function and hypoxemia probably exists in group 2. Since mild or moderate emaciation was observed in controls and group 1 in spite of the lack of fiber atrophy, involvement of fat and connective tissue should also be taken into consideration to determine the cause of emaciation.

Development of osteopenia in the hemiplegic finger in patients with stroke.

Previous studies have demonstrated that hip fractures in stroke patients occurred almost exclusively on the hemiplegic side. We examined the bone changes in the second metacarpal of the hemiplegic side in terms of microdensitometric indices in 93 stroke patients with hemiplegia. All six indices indicated a significant decrease in bone mass on the hemiplegic side compared with the contralateral side. Differences in the indices between the hemiplegic and contralateral sides were correlated well with the duration of the illness and Brunstrom's stage for finger, arm, and leg. The same degree of osteopenia occurred in both small capsular and large hemispheric lesions. The same osteopenia was demonstrated in paralyzed and immobilized patients with myopathy. Thus a combination of weakness and immobilization is thought to be responsible for the osteopenia in the hemiplegic metacarpal bone. The osteopenia noted in the second metacarpal in the affected limb may account for the fact that hip fractures in stroke patients occur almost exclusively on the hemiplegic side.