Cerebrospinal fluid orexin-A levels in systemic lupus erythematosus patients presenting with excessive daytime sleepiness.

Objective Involvement of the hypothalamus is rare in patients with systemic lupus erythematosus (SLE). In this study, we measured cerebrospinal fluid (CSF) orexin-A levels in SLE patients with hypothalamic lesions to investigate whether the orexin system plays a role in SLE patients with hypothalamic lesions who present with excessive daytime sleepiness (EDS). Methods Orexin-A levels were measured in CSF from four patients with SLE who presented with hypothalamic lesions detected by MRI. Three patients underwent repeated CSF testing. All patients met the updated American College of Rheumatology revised criteria for SLE. Results Tests for serum anti-aquaporin-4 antibodies, CSF myelin basic protein and CSF oligoclonal bands were negative in all patients. All patients presented with EDS. Low to intermediate CSF orexin-A levels (92-180 pg/ml) were observed in three patients in the acute stage, two of whom (patients 1 and 2) underwent repeated testing and showed increased CSF orexin-A levels, reduced abnormal hypothalamic lesion intensities detected by MRI and EDS dissipation at follow-up. In contrast, CSF orexin-A levels were normal in one patient (patient 4) while in the acute stage and at follow-up, despite improvements in EDS and MRI findings. Patient 4 showed markedly increased CSF interleukin-6 levels (1130 pg/ml) and a slightly involved hypothalamus than the other patients. Conclusions Our findings suggest that the orexinergic system has a role in EDS in SLE patients with hypothalamic lesions. Furthermore, cytokine-mediated tissue damage might cause EDS without orexinergic involvement.

Early detection of Niemann-pick disease type C with cataplexy and orexin levels: continuous observation with and without Miglustat.

STUDY OBJECTIVES: Niemann-Pick type C (NPC) is an autosomal recessive and congenital neurological disorder characterized by the accumulation of cholesterol and glycosphingolipids. Symptoms include hepatosplenomegaly, vertical supranuclear saccadic palsy, ataxia, dystonia, and dementia. Some cases frequently display narcolepsy-like symptoms, including cataplexy which was reported in 26% of all NPC patients and was more often recorded among late-infantile onset (50%) and juvenile onset (38%) patients. In this current study, we examined CSF orexin levels in the 10 patients of NPC with and without cataplexy, which supports previous findings. METHODS: Ten patients with NPC were included in the study (5 males and 5 females). NPC diagnosis was biochemically confirmed in all 10 patients, from which 8 patients with NPC1 gene were identified. We compared CSF orexin levels among NPC, narcoleptic and idiopathic hypersomnia patients. RESULTS: Six NPC patients with cataplexy had low or intermediate orexin levels. In 4 cases without cataplexy, their orexin levels were normal. In 5 cases with Miglustat treatment, their symptoms stabilized or improved. For cases without Miglustat treatment, their conditions worsened generally. The CSF orexin levels of NPC patients were significantly higher than those of patients with narcolepsy-cataplexy and lower than those of patients with idiopathic hypersomnia, which was considered as the control group with normal CSF orexin levels. DISCUSSION: Our study indicates that orexin level measurements can be an early alert of potential NPC. Low or intermediate orexin levels could further decrease due to reduction in the neuronal function in the orexin system, accelerating the patients' NPC pathophysiology. However with Miglustat treatment, the orexin levels stabilized or improved, along with other general symptoms. Although the circuitry is unclear, this supports that orexin system is indeed involved in narcolepsy-cataplexy in NPC patients. CONCLUSION: The NPC patients with cataplexy had low or intermediate orexin levels. In the cases without cataplexy, their orexin levels were normal. Our study suggests that orexin measurements can serve as an early alert for potential NPC; furthermore, they could be a marker of therapy monitoring during a treatment.

Implication of dopaminergic mechanisms in the wake-promoting effects of amphetamine: a study of D- and L-derivatives in canine narcolepsy.

Using a canine model of narcolepsy and selective DA and NE uptake inhibitors, we have recently shown that DA uptake inhibition promotes wakefulness, while NE uptake inhibition inhibits rapid eye movement sleep and cataplexy. In order to further delineate the respective roles of the dopaminergic and noradrenergic systems in the pharmacological control of symptoms of narcolepsy, we compared the potency of amphetamine isomers (D- and L-amphetamines) and a derivative (L-methamphetamine) on wakefulness and cataplexy. Their respective effects on these narcolepsy symptoms were then compared with their in vivo effects on extracellular DA levels in the caudate and NE levels in the frontal cortex during local drug perfusion in narcoleptic dogs. Polygraphic recordings demonstrated that D-amphetamine was about twice as potent as L-amphetamine, and was six times more potent than L-methamphetamine in increasing wakefulness and reducing slow-wave sleep. D-Amphetamine and L-amphetamine were equipotent in reducing rapid eye movement sleep and cataplexy, and L-methamphetamine was about half as potent as L- and D-amphetamines. D-Amphetamine was found to be more potent in increasing DA efflux than L-amphetamine, and L-methamphetamine was found to have little effect on DA efflux; there was no significant difference in the potencies of the three derivatives on NE efflux. The potencies of these amphetamines on wakefulness correlated well with DA, but not NE, efflux in the brain of narcoleptic dogs during local drug perfusion. Our current results further exemplify the importance of the DA system for the pharmacological control of electroencephalogram arousal and suggest that increased DA transmission mediates the wake-promoting effects of amphetamine-like stimulants.

Thalidomide increases both REM and stage 3-4 sleep in human adults: a preliminary study.

Polysomnography was used to assess the effect of thalidomide on human sleep. This compound significantly increased the time spent in REM and stage 3-4 sleep as compared with placebo. On the other hand, thalidomide significantly decreased the time spent in stage 1, while the time spent in stage 2 was unchanged. The effect of thalidomide on REM and stage 3-4 sleep is unique as compared with other hypnotics. Although the mode of action of this compound is unknown, further studies on thalidomide should help in our understanding of the mechanisms of sleep regulation.

Thalidomide, a hypnotic with immune modulating properties, increases cataplexy in canine narcolepsy.

Thalidomide is a sedative hypnotic that was widely used in the 1950s but was withdrawn due to its teratogenic properties. The compound has recently been reintroduced as an immune modulating agent. Thalidomide significantly aggravates canine cataplexy, a pathological manifestation of rapid eye movement (RFM) sleep atonia seen in narcolepsy. This compound also increases REM sleep and slow wave sleep in these animals. In vitro receptor binding and enzyme assays demonstrate that thalidomide does not bind to or enzymatically modulate the neurotransmitter systems reported to be involved in the regulation of cataplexy. Thalidomide may therefore affect cataplexy through its immune modulation properties. Further studies on the mechanisms of action of thalidomide should increase our understanding of the pathophysiology of this disabling disorder.

Intraoperative blood pressure control by ATP in pheochromocytoma.

Three cases of pheochromocytoma which were successfully treated with the use of adenosine triphosphate (ATP) during the operation are reported. The mechanism of the hypotensive effect of ATP has been proved due to the antagonizing action of the agent to the vasoconstriction by noradrenaline and/or sympathetic nerve stimulation. In these 3 cases, ATP has been safely and effectively applied to control blood pressure in pheochromocytoma. ATP could be used as the first-choice drug to keep the circulatory state stable during surgery for pheochromocytoma.

Systemic lupus erythematosus with pulmonary hypertension.

A 50-year-old Japanese female with a long history of Raynaud's phenomenon presented with progressive dyspnea due to pulmonary hypertension. The diagnosis of systemic lupus erythematosus was confirmed by proteinuria, lymphocytopenia, bilateral pleurisy, and a seizure of convulsion which was consistent with neurological manifestations of systemic lupus erythematosus, whereas the antinuclear antibody showed a low titer. Despite improvement in the activity of systemic lupus erythematosus, steroid treatment did not alter the progression of pulmonary hypertension, which increased in severity, eventually resulting in her death. We believe pulmonary hypertension to be an unusual but critical complication of systemic lupus erythematosus.

Ganglioneuroblastoma with disseminated bone marrow infiltration in an adult.

Ganglioneuroblastoma is an extremely rare neoplasm of adults. We present a case of adrenal ganglioneuroblastoma in a 47-year-old female with disseminated bone marrow involvement. Bone marrow involvement was the major manifestation which determined the mortality of this patient. This case suggests that the diagnosis of bone marrow involvement should be carefully considered even in adult-onset ganglioneuroblastoma.

Narcolepsy in a hypocretin/orexin-deficient chihuahua.

A two-year-old male chihuahua suffered attacks of muscle weakness and immobility, although it had no family history of paroxysmal attacks. No neurological or blood biochemical abnormalities were recorded when it was first examined. The attacks were typically elicited by stimulation, such as feeding, and a case of sporadic narcolepsy-cataplexy was therefore suspected. Treatment orally three times a day with 1 mg/kg imipramine, was effective in reducing the attacks. The concentration of hypocretin-1/orexin A in the dog's cerebrospinal fluid was less than 80 pg/ml (22.5 pmol/litre), compared with normal canine levels of 250 to 350 pg/ml (70.0 to 98.3 pmol/litre), supporting a diagnosis of hypocretin-deficient narcolepsy.

On the arterial supply in the human biceps brachii muscle.

The distribution of the arterial supply and innervation of skeletal muscle in the whole human body has been being researched in our laboratory. The results obtained on the biceps brachii from 25 bodies (50 sides) are reported here. Generally, in this muscle, A. coracobrachialis (Cb, SATO, 1980), a branch of A. axillaris (Ax), is distributed at the upper muscle bundles of the short head after running parallel to N. musculocutaneus (Nmc) and supplying M. coracobrachialis. The main artery (Ma), which is a branch of A. brachialis (Br), is distributed at the upper and middle parts of both heads, and the point where Ma enters the muscle bundles almost coincides with the point where R. brachialis (Rb) branches from Nmc. R. biceps brachii (Rbi), which is distributed only at this muscle and Om, the common trunk to other muscles, is distributed at the lower part of the muscle bundles. The arterial supply of this muscle was classified as follows according to the conditions of origin and its distribution. Type I: Ax(Cb) was distributed to the upper part of the muscle bundle. Type II: The absence of Ax(Cb) in the upper part of the muscle bundle. Type A, a and 1: Ma.Br(Om) supplying the long, short and both heads of the biceps brachii. Type B, b and 2: Ma.Br(Rbi) supplying the long, short and both heads of the biceps brachii. In the long head, Type II-A accounted for 62.0%, Type II-B for 30.0%. In the short head, Type I-a was 62.0%, Type I-b 28.0%. In both heads, Type I-1 was 62.0%, Type I-2 28.0%. There were significant differences in the distribution of the nutrient arteries between the long and short heads. A. brachialis superficialis (Bs) was recognized in 3 of these cases (2 cases of Type III and 1 case of Type VII by Adachi's classifications), which were rare cases. In these cases, arterial branches other than Cb branching from A. brachialis profunda are branches of Bs. This means, judging from ontogeny, that Bs, the blood vessels in the superficial layer, supplies this muscle, which belongs to the superficial layer of the brachium.

[Clinical evaluation of cefotaxime in complicated urinary tract infections].

Fourteen cases with complicated urinary tract infection were treated with 2 g of cefotaxime for 5 days; in total doses of 10 g. Excellent or good results were obtained in 11 cases (78.6%) and no adverse reaction was observed. A curious finding was the development of eosinophilia in some patients. The causative mechanisms and clinical meanings of the phenomenon have not been clarified.

[Basic and clinical evaluations of cefmetazole in postoperative wound infections].

The time course of the concentration of cefmetazole (CMZ) in the serum and in skin and intestinal tissues was determined after a single intravenous injection of 2 g of the drug. CMZ moved into them well. Furthermore, 41 patients with postoperative wound infection (superficial in 29 and deep in 12) were treated with CMZ 2-4 g daily. Bacteriological examination of the lesions with simultaneously carried out. As a result, 101 strains of bacteria were isolated and identified. Mixed infection was found in 27 cases (65.9%). Fifteen strains (14.9%) of E. coli, 15 (14.9%) of B. fragilis, 7 (6.9%) of Klebsiella sp. and 7 (6.9%) of Proteus sp., were the main bacteria isolated. Eight cases (19.5%) had mixed infection of E. coli and B. fragilis. The committee (3 members) evaluated CMZ to be effective in 75.6% (31 of 41 cases) and bacteria disappeared in 60.5% (23 of 38 cases). The side effects observed were pyrosis and feeling of gastric malaise in 1 case. The results suggest that CMZ is useful, which exerts an excellent effect on postoperative wound infections.

[Dialysis versus renal transplantation; a comparative study on medical cost and quality of life in patients with chronic renal failure].

We studied the medical costs of hemodialysis, CAPD and renal transplantation in our patients with chronic renal failure. The cost per patient averaged 660,000 yen for hemodialysis (760,000 yen for CAPD) in the first month when dialysis was started and 460,000 yen for routine maintenance hemodialysis (240,000 yen for CAPD). There was a difference in cost between recipients treated with conventional immunosuppressants (conventional group) and those receiving cyclosporine (Cs-group). That is, the estimated average cost for the conventional group was 3,800,000 in the first month after kidney grafting and at 60,000 yen in the subsequent months when the patient is cared for at the outpatient clinic; that of Cs-group was at 2,710,000 yen and 170,000 yen. This difference is due to the high cost of cyclosporine. The cumulative cost of maintenance hemodialysis is on a constant linear increase. Recently, clinical results of renal transplantation have improved markedly. Furthermore, our analysis of questionnaires to patients shows that renal transplantation is far superior to hemodialysis on the aspect of the quality of life. Thus, renal transplantation should be promoted further, and then the combined treatment of a low dose of cyclosporine and other immunosuppressants might be recommended to reduce the cost of cyclosporine.

[Primary plasma cell leukemia associated with hypercalcemia].

A 34-year-old male was admitted to our hospital because of anorexia and nausea in September, 1987. On admission, anemia, thrombocytopenia and hypercalcemia were observed, and the peripheral blood showed leukocytosis with atypical plasma cells (50%). Bone marrow aspiration showed hypercellularity, with a presence of atypical plasma cells (82%). The M-type protein in the serum and urine was identified as lambda Bence Jones protein by immunoelectrophoresis. On systemic skeletal X-rays, osteolytic lesions were not detected. Thus, a diagnosis of plasma cell leukemia associated with hypercalcemia was made. Hypercalcemia was treated successfully with overhydration. However the disease was refractory to combination chemotherapy, and at 10 months after diagnosis, he died of septic candidiasis. Hypercalcemia associated with plasma cell leukemia in its initial stage is rare.

[Rhabdomyolysis following water intoxication in two schizophrenic patients].

We report two cases of self-induced water intoxication with rhabdomyolysis. They had been diagnosed as chronic schizophrenia, and admitted to mental hospitals. The patients were transferred to our emergency room because of sudden loss of consciousness and generalized convulsions. Laboratory findings revealed marked hyponatremia (case 1; 109 mEq/L and case 2; 104 mEq/L). CT scans showed the effacement of interhemispheric and bilateral sylvian fissures and sulci of the cerebral hemisphere due to diffuse brain edema. 10% glycerol and saline were intravenously injected to the patients. They recovered from hyponatremia after excreting a large amount of urine. Their disturbed consciousness recovered to the normal level in parallel with the normalization of their serum sodium concentration. Soon after the normalization of their consciousness level, their serum creatine kinase (CK) was markedly elevated (case 1; 13086 IU/L and case 2; 41832 IU/L), and their serum myoglobin level was also significantly elevated (case 1; 2670 ng/ml and case 2; 1420 ng/ml). A sufficient amount of transfusion was performed for avoiding the acute renal failure. The two patients recovered from rhabdomyolysis without any severe complication. We conclude that brain CT is useful for the diagnosis of brain edema, and monitoring of CK is also important to anticipate renal damage secondary to rhabdomyolysis.

[Treatment of 46 cases of renal pelvic and ureteral tumors].

During about 10 years from November, 1977 to March, 1987, 46 patients with renal pelvic and ureteral tumors were treated at the Department of Urology, Hamamatsu University School of Medicine and the affiliated hospitals. There were 34 males and 12 females with the highest age incidence in the seventies. Histologically, 44 transitional cell carcinomas and 2 squamous cell carcinomas were found. Of the 44 transitional cell carcinomas, 1 was Tis; 13 T1, 2 T2, 8 T3, 15 M+ (with metastatic lesion), and 5 TX. As to grading, 1 was G1; 24 G2, 15 G3, and 4 GX. Staging was correlated with grading. The 5-year survival rates (Kaplan-Meier's method) were 37% in patients with transitional cell carcinoma. Among patients with transitional cell carcinoma, the 5-year survival rate was 43% for G2 and 42% for G3. As to staging, the 5-year survival rates were 71% and 46% in patients with stage of T1 and T3, respectively. No patient with M+ survived longer than 4 years. The 5-year survival rates were 38% and 34% in renal pelvic tumors (24 cases) and ureteral tumors (20 cases), respectively. As to the treatments, the 5-year survival rates after curable treatment (24 cases) and non-curable treatment (20 cases) were 63% and 7%, respectively.

[Treatment of 255 patients with bladder tumors].

During about 10 years from November, 1977 to March, 1987, two hundreds and fifty-five patients with bladder tumors were treated at the Department of Urology, Hamamatsu University School of Medicine and the affiliated hospitals. There were 198 males and 57 females with the highest age incidence in the seventies. Histologically, 242, 11 and 2 tumors were of transitional cell, squamous cell and adenocarcinoma, respectively. Of the 242 transitional cell carcinomas, 7 were Tis; 43 Ta, 111 T1, 33 T2, 19 T3, 5 T4, 14 M+ (with metastatic lesion), and 10 TX. As to grading, 6 was G0; 66 G1, 100 G2, 64 G3, and 6 GX. Staging was correlated with grading. The 5-year survival rates (Kaplan-Meier's method) were 64% in patients with transitional cell carcinoma; 58% in those with squamous cell carcinoma. In patients with transitional cell carcinoma, the 5-year survival rates were 100% for G0, 73% for G1, 73% for G2 and 40% for G3. As to staging, the 5-year survival rates were 67%, 81%, 81%, 35%, 41%, 40% and 12% in patients with stage of Tis, Ta, T1, T2, T3, T4 and M+, respectively. As to the initial treatment, the 5-year survival rates after TUR (137 cases), partial cystectomy (4 cases) and total cystectomy (56 cases) were 81%, 36% and 61%, respectively. The rate of intravesical recurrence after TUR was evaluated with the cumulative non-recurrence rate calculated by Kaplan-Meier's method.(ABSTRACT TRUNCATED AT 250 WORDS)