Successful treatment with hydroxychloroquine for systemic lupus erythematosus with cutaneous involvement accompanied by a xanthomatous reaction.

Antimalarials are usually recommended for the first-line systemic treatment of cutaneous lupus erythematosus. Alopecia in patients with discoid lupus erythematosus (DLE) is sometimes a refractory condition in spite of topical therapies. We herein described a case of DLE on the scalp with a pathological change of a xanthomatous reaction, which was successfully treated with hydroxychloroquine (HCQ). A 34-year-old woman presented with hair loss to the parietal region. She had been diagnosed with systemic lupus erythematosus (SLE) four years previously. Treatment with 30 mg/day of prednisolone (PSL) had been initiated, and the dose was gradually reduced. At 10 mg/day of PSL, she had noticed her hair loss. Physical examination revealed some small erythematous lesions to the parietal region with accompanying hair loss. Pathological findings of the erythematous lesion on her head revealed thickening of the basement membrane zone, the interface dermatitis with vacuolar degeneration, and both superficial perivascular and perifollicular infiltration of inflammatory cells in the dermis. In addition, there was an infiltrate of xanthomatous cells detected in the papillary dermis, which were positive for CD68 and CD163. The patient started treatment with HCQ at a dose of 200 mg/day. The skin lesions completely resolved within five months after initiation of HCQ without increase in the dose of PSL. Xanthomatous reactions are rarely recognized in lupus erythematosus. The chronic epithelial injury in DLE could be implicated in triggering the secondary reactive process of a xanthomatous reaction. We believe that the reaction seen in our patient was a secondary change to pathological alteration due to SLE. However, as yet unrecognized factors may play a role in the development of a xanthomatous reaction in DLE.

Palisaded neutrophilic and granulomatous dermatitis associated with systemic lupus erythematosus: possible involvement of CD163+ M2 macrophages in two cases, and a review of published works.

BACKGROUND: Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a commonly occurring condition related to systemic autoimmune disease. It is characterized histopathologically by a distinct pattern of granulomatous inflammation in the presence or absence of leukocytoclastic vasculitis. The properties of granulomatous cells in PNGD are still uncertain. OBJECTIVE: We sought further investigation on the phenotype of the infiltrated cells in PNGD from two patients with systemic lupus erythematosus (SLE) and reviewed the previous published reports in order to provide a comprehensive summary on the clinical features of PNGD in SLE. METHODS: The immunohistochemical features of granulomatous cells in PNGD associated with SLE were analyzed. Immunohistochemical studies were performed on sections from our two cases using antibodies against CD68, CD163, CD15, Factor XIIIa, myeloperoxidase and neutrophil elastase. The clinical characteristics of the SLE patients who developed PNGD were also evaluated. We included all cases retrieved through a PubMed search with the key words PNGD and SLE. RESULTS: Cutaneous lesions consisted of erythematous plaques distributed on the face and upper limbs in both cases. The infiltrated cells were mainly positive for CD68 and CD163, a phenotype suggestive of M2 macrophages. Some mature neutrophils and lymphocytes were also present. A review of the literature of PNGD associated with SLE revealed a predominance in females, high prevalence of lupus nephritis and a good response to systemic steroids, with frequent skin lesions relapses during tapering of the treatment. LIMITATIONS: This study examined only two cases; the pathogenesis of the disease remains to be clarified. CONCLUSION: PNGD lesions were abundantly infiltrated by M2 macrophages, suggesting that they may have a role in this condition. SLE accompanied by PNGD might be associated with lupus nephritis and frequent relapses of skin lesions.

Advancement of the Subjective Vitality Scale: examination of alternative measurement models for Japanese and Singaporeans.

The Subjective Vitality Scale (SVS: Ryan & Frederick, 1997) is a 7-item self-report instrument to measure one's level of vitality and has been widely used in psychological studies. However, there have been discrepancies in which version of the SVS (7- or 6-item version) employed between as well as within researchers. Moreover, Item 5 seems not be a good indicator of vitality from a content validity perspective. Therefore, the present study aimed to evaluate the validity and reliability of the SVS for Japanese and Singaporeans rigorously by comparing 3 measurement models (5-, 6-, and 7-item models). To this end, the scale was first translated from English to Japanese and then the Japanese and English versions of the scale were administered to Japanese (n = 268) and Singaporean undergraduate students (n = 289), respectively. The factorial and concurrent validity of the three models were examined independently on each of the samples. Furthermore, the covariance stability of the vitality responses was assessed over a 4-week time period for another independent Japanese sample (n = 140). The findings from this study indicated that from methodological and content validity perspectives, the 5-item model is considered most preferable for both language versions of the SVS.

[The third repair for pseudoaneurysm following Bentall procedure: report of a case].

A 77-year-old male, who had undergone the Bentall procedure 27 years ago, was admitted to our hospital for the repair of postoperative pseudoaneurysm. This was the 3rd repair, and the pseudoaneurysm was close to the sternum. Total extracorporeal circulation was established with femorofemoral cannulation and sternotomy was performed under deep hypothermia. During sternotomy, we encountered massive hemorrhage due to injury of the aortic graft. We coped effectively with the situation utilizing temporary circulatory arrest. Aortic graft reimplantation was performed under continuous retrograde cerebral perfusion. Collapse of the suture line of the left coronary orifice was recognized and was reconstructed. The patient was discharged uneventfully on the 26th postoperative day.

[Clinical outcome of aortic valve replacement with 19-mm prosthetic valve in elderly patients].

From 1979 to June 2005, 90 patients aged 65 or older underwent aortic valve replacement with 19-mm prosthetic valve. They were 84 women and 6 men, with a mean age of 74. The mean body surface area was 1.35 m2. Bioprosthetic valves were implanted in 77 patients (85.6%). In-hospital mortality was 2.2% (2 of 90). There were 13 late deaths. New York Heart Association (NYHA) functional class improved to class I in most of survivors. Survival rates for 5 and 10 years were 84.9 and 71.2%, respectively. The outcome of aortic valve replacement with 19-mm prosthetic valve in elderly patients was excellent.

Autonomic heart rate regulation during mild dynamic exercise in humans: insights from respiratory sinus arrhythmia.

To better understand the neural mechanism of heart rate (HR) regulation during dynamic exercise, the responses of HR and the magnitude of respiratory R-R interval variation were examined during exercise and recovery at mild intensities in humans. Eight subjects performed 3-min constant load cycle exercises in a semi-supine position at work rates of 25, 50, and 100 W. The respiratory interval was fixed at 4 s. Peak-to-valley variation in R-R interval caused by respiration was measured breath-by-breath and standardized for tidal volume (DeltaRRst, a noninvasive index of the degree of parasympathetic cardiac control). At all work rates the HR increased significantly from 2.5 s after the beginning of exercise (p <0.05) and decreased temporarily and slightly at around 15 s, and the DeltaRRst varied almost inversely. The HR and the DeltaRRst until 12.5 s after the beginning of exercise changed independently of work rate (ANOVA, p=0.27 and p=0.08). The HR-DeltaRRst relationship at the initial phase of exercise (for 12.5 s) was almost the same at all work rates. These results suggest that the initial HR response to exercise is strongly parasympathetically regulated independently of work rate. The HR recovered slower than the DeltaRRst at 50 and 100 W. On the HR-DeltaRRst relationship, the HR during recovery was significantly higher than during exercise at 1/3, 1/2, and 2/3 levels of pre-exercise DeltaRRst at 50 and 100 W and at the 1/3 level at 25 W (p < 0.05). At 25 W, the difference in HR at the 1/3 level was 5.5 beats.min(-1), and the HR increase to exercise was 21.2 beats.min(-1). We suggest that a HR regulatory system responds slower than a cardiac parasympathetic system to exercise, a cardiac sympathetic system, is activated even during mild exercise in humans.

Epinastine inhibits eosinophil chemotaxis and adhesion molecules in atopic dermatitis.

PURPOSE: To investigate the effects of epinastine on eosinophil chemotaxis and changes in eosinophil adhesion molecules induced by epinastine and three other antiallergic agents, using eosinophils of atopic dermatitis (AD) patients. RESULTS: Epinastine reduced eosinophil chemotaxis toward eotaxin when the eosinophils had been prestimulated with interleukin (IL)-5, but given alone it did not alter eosinophil chemotaxis toward IL-5. CD11b expression was inhibited when peripheral blood was prestimulated with IL-5, but eosinophil adhesion molecule expression was not altered. CONCLUSIONS: Epinastine suppresses allergic inflammation not only through its strong antihistamine and antimediator effects, but also by inhibiting eosinophilic chemotaxis and the expression of adhesion molecules involved in chemotaxis, especially CD11b.

[Surgical treatment of Marfan syndrome; analysis of the patients required multiple surgical interventions].

Without treatment, the life expectancy of patients with Marfan syndrome is reduced by the associated cardiovascular abnormalities. In this study, we reviewed our experience of the patients with Marfan syndrome who required multiple surgical interventions to identify the optimal treatment for these patients. Between January 1986 and December 2000, 44 patients with Marfan syndrome were operated on at Shizuoka City Hospital (SCH). Among them, 10 patients (22.7%) underwent multiple surgical interventions. There were 5 male and 5 female patients with a mean age of 40.6 +/- 16.1 years at the initial surgery. Only one patient was operated on at another hospital for his first, second, and third operations. His fourth operation was carried out at SCH. The remaining 9 patients underwent a total of 14 additional surgical procedures at SCH. Computed tomography (CT) scans were taken every 6 months postoperatively, and aortic diameter greater than 60 mm was considered as the indication for the additional surgery. There were no early death and one late death. The causes of additional surgery were enlargement of true aneurysm in 6, enlargement of residual dissection in 4, new dissection in 4, false aneurysm at the coronary anastomosis of Bentall procedure in 1. In 9 patients, both ascending and descending aorta were replaced. Among these 9 patients, only 3 patients underwent total arch replacement, and remaining 6 patients had their arch left in place with or without dissection. Our current strategy of the treatment of Marfan patients with acute type A dissection is total arch replacement with an elephant trunk at the initial emergent surgery.

[Long-term results after surgery for aortic arch nondissection aneurysm].

Between 1990 and August 2001, 109 patients were treated surgically for nondissection fusiform or saccular aortic arch aneurysm. Fifteen patients were emergent. There were 89 male and 20 female patients (mean 71.7 +/- 6, range 49 to 84). Eight patients underwent hemiarch replacement, 57 total arch replacement, 44 distal arch replacement, which were performed with the aid of hypothermic extracorporeal circulation with antegrade selective cerebral perfusion or retrograde cerebral perfusion. The early mortality was 8.5% with elective operations and 53.3% with emergent operations. The incidence of post operative permanent neurological dysfunction was 12.8% with elective operations and 46.7% with emergent operations. The 5-year and 10-year survival rate including in-hospital deaths was 52 +/- 6% and 29 +/- 9%. The 5-year event free rate was 89 +/- 5%.

Immunohistochemical detection for nuclear beta-catenin in sporadic basal cell carcinoma.

BACKGROUND: Despite the increasing incidence of basal cell carcinoma (BCC), its pathogenesis has remained largely unknown. Recently, it was reported that genes involved in tissue morphogenesis, such as sonic hedgehog or patched, were found to be mutated in BCC, suggesting the involvement of those molecules in the pathogenesis of this tumour. Furthermore, there is evidence that the Wnt-mediated signalling pathway may be one of the downstream targets of sonic hedgehog-mediated signalling, which has led us to focus on molecular events on the Wnt pathway in BCC. Among the signal transducers involved in the Wnt pathway, it is clear that beta-catenin plays a pivotal role in the promotion of morphogenesis and cell growth. In respect to this, it has been reported that, in particular circumstances, as in colorectal cancers, beta-catenin migrates to the nuclei, where it exerts an ability to activate the transcription of various genes. OBJECTIVES: To investigate the cellular distribution of beta-catenin in skin tumours, in particular, in BCC. METHODS: Twenty skin biopsy specimens derived from BCC, 10 from inflammatory skin diseases and five from squamous cell carcinomas were immunostained with an antibody directed against beta-catenin. RESULTS: Fourteen of the 20 BCC samples tested showed nuclear localization of beta-catenin, while none of the other samples gave rise to positive nuclear staining. CONCLUSIONS: Nuclear localization of beta-catenin is a characteristic feature of BCC; this suggests its tumorigenic role in this tumour. This gives us a further insight into the molecular pathogenesis of BCC.

Hypovolemic intolerance to lower body negative pressure in female runners.

PURPOSE: An attenuated baroreflex response and orthostatic intolerance have been reported in endurance-trained male athletes; however, it is still unknown whether this occurs also in females. The purpose of the present study was to examine whether endurance exercise-trained women had a predisposition to orthostatic compromise, and if so, what causative factor(s) may induce orthostatic intolerance. METHODS: We studied cardiovascular and hormonal responses to graded lower body negative pressure (LBNP) (0 to -60 mm Hg) in 26 middle-distance female runners (18.6 +/- 0.1 yr) as the exercise-trained (ET) subjects and 23 age-matched untrained (UT) control subjects. On the basis of the occurrence of syncope episodes during LBNP, ET and UT subjects were further allocated to two groups; ET with presyncope (ET+syncope) and without presyncope (ET-syncope) and UT with presyncope (UT+syncope) and without presyncope (UT-syncope). RESULTS: Occurrence of presyncope episodes during LBNP was higher in ET (65.4%, P < 0.05) than that for UT (34.8%). Leg compliance was higher (P < 0.05) in ET than in UT. LBNP reduced stroke volume (SV) more (P < 0.05), increased heart rate (HR) higher (P < 0.05), and increased forearm vascular resistance (FVR) more in ET+syncope as compared with the other groups. Response of vasoactive hormones to LBNP was higher in ET+syncope (P < 0.05) than that of the other groups except for norepinephrine (NE); high in both ET+syncope and UT+syncope. The relationship between SV and NE, an index of sympathetic neuronal response, had no training-related changes during LBNP. CONCLUSION: We conclude that exercise-trained females have a high incidence of orthostatic intolerance during LBNP, with a greater reduction of SV independent of changes in baroreflex and neurohumoral function. A lower incidence of LBNP intolerance in UT may be accounted for by a lower reduction of SV during LBNP. An increase in leg compliance in the exercise-trained females may play an important role in inducing pronounced reduction of SV and hence the intolerance to LBNP.

Spontaneous arterial baroreflex control of the heart rate during head-down tilt in heat-stressed humans.

The purpose of this study was to elucidate the effect of raised body temperature per se during acute heat stress on the spontaneous arterial baroreflex control of heart rate (fc) in humans. To investigate whether unloading of cardiopulmonary baroreceptors during whole-body heating would alter the arterial baroreflex control of fc, we controlled loading of the cardiopulmonary baroreceptors by head-down tilt (HDT) at angles of 5 degrees, 10 degrees, 15 degrees, and 30 degrees during heat stress produced by hot-water-perfused suits. The sensitivity of the arterial baroreceptor-cardiac reflex was calculated from the spontaneous changes in beat-to-beat arterial pressure and fc. As an index of cardiopulmonary baroreceptor loading, the left atrial diameter (LAD) was measured by echocardiography. During whole-body heating, the LAD decreased with the rising body core temperature and increased with the HDT. The decreased LAD during heating almost recovered to the normothermic control level by 10 degrees HDT. In the supine position, cardiac baroreflex sensitivity remained unchanged during heating. Arterial pressure, fc and cardiac baroreflex sensitivity were not changed by HDT ranging from 5 degrees to 30 degrees during heating. These results suggest that cardiac baroreflex sensitivity remain unchanged during graded loading of the cardiopulmonary baroreceptors in heat-stressed humans. Also, we conclude that the sensitivity of the spontaneous arterial baroreflex controlling the fc is not influenced by raised body temperature per se during acute heat stress.

[Analysis of chimerism in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation].

Serial monitoring of chimerism after allogeneic hematopoietic stem cell transplantation (HSCT) can be performed easily and rapidly using PCR-based assays analyzing informative tandem repeat genetic markers. Sequential analysis of individual chimerism status was performed in 34 patients who underwent myeloablative allo-HSCT using a commercial multiplex short tandem repeat (STR) kit. Mixed chimerism (MC) was found in 14 of the patients for more than one month. The incidence of MC seemed to be dependent on the type of disease or pretransplantation regimen. There was no significant difference in relapse rates between MC and complete donor chimerism (CC) in all patients. However, the relapse rate was significantly higher in MC than in CC among patients with acute leukemia. The severity of acute graft-versus-host disease (aGVHD) was significantly reduced in the patients with MC. Most of the MC patients with hematologic malignancies had transient mixed T-lymphoid chimerism, and CC was achieved within 6 months after HSCT in such cases. Patients with MC beyond 6 months after HSCT and patients with reappearance of autologous signals (MC after CC) may have an enhanced risk of relapse.

Increased antibody levels to desmogleins 1 and 3 after administration of carbamazepine.

Desmoglein (Dsg) 1 and Dsg3 are recognized as the autoantigens in pemphigus foliaceus and pemphigus vulgaris. Pemphigus-like syndromes have been reported to occur in individuals after exposure to a variety of drugs, but pemphigus caused by carbamazepine is not common. We found that anti-Dsg1 and anti-Dsg3 antibody titres were increased in three individuals administered carbamazepine. Antibody titres against Dsgs 1 and 3 were measured by enzyme-linked immunosorbent assay (ELISA). Of 42 serum samples (25 patients administered carbamazepine, eight patients administered valproic acid and nine healthy volunteers) tested by ELISA, three patients administered carbamazepine showed positive reactivity against both Dsg1 and Dsg3. The patient with the highest titre against Dsg1 and Dsg3 (the index values of anti-Dsg1 and anti-Dsg3 were 79.3 and 86.4, respectively) was a 23-year-old woman (Case 1). The other two patients with positive reactivity were a 5-year-old boy (Case 2) and a 65-year-old man (Case 3). In addition, indirect immunofluorescence study showed intercellular antibodies to the cell surface of the whole epidermis with a titre of 1 : 64 in Case 1 and 1 : 2 in Cases 2 and 3. However, no skin or mucosal involvement was found in any of these cases. There was no difference in the serum concentrations of carbamazepine between the three positive cases and the 22 negative cases of carbamazepine administration. From these facts, the lack of skin diseases may be explained by relatively low values of anti-Dsg 1 and 3 antibodies in Cases 2 and 3. However, it cannot be excluded that undefined exogenous and/or endogenous factors are involved in an outbreak of pemphigus. Furthermore, these findings might be helpful for preventing susceptible individuals from exposure to the suspect drugs.

Water drinking causes a biphasic change in blood composition in humans.

To investigate precisely the fluid shifts associated with water drinking in humans, we measured continuously blood density and plasma electrolyte concentrations using the mechanical oscillator technique and ion-selective electrodes, respectively, in healthy young volunteers before (10 min) and after (48 min) water drinking for a period of 2 min. Beat-by-beat blood pressure was also monitored throughout the experiment. Drinking 1 l tap water caused a transient increase in blood density immediately after the drinking episode (from 1051.1+/-0.5 g/l before drinking to 1051.8+/-0.5 g/l 4 min after the start of drinking, P<0.05), followed by a gradual reduction (1050.1+/-0.5 g/l at 31 min). This drinking-induced change paralleled those of haematocrit, plasma density and plasma volume. Plasma [Na+] and [Cl-] and osmolality decreased after drinking without transient increases and reached minima at about 30 min. A transient increase in mean arterial blood pressure was observed prior to the increase in blood density. These findings suggest that water drinking causes a biphasic change in plasma volume: initial haemoconcentration, probably due to sympathetic acceleration, followed by haemodilution due to the post-absorptive effect, and further suggest that the fluid shift associated with the initial haemoconcentration is isosmotic.

Thermal stress modulates arterial pressure variability and arterial baroreflex response of heart rate during head-up tilt in humans.

To examine the effects of thermal stress on the blood pressure variability and the arterial baroreceptor-cardiac reflex during orthostatic stress, 11 male volunteers underwent whole body thermal stress using a cool or hot water-perfused suit during 5 min of 70 degrees head-up tilt (HUT). The spontaneous variability in arterial pressure was quantified by power spectrum analysis. The sensitivity of the arterial baroreceptor-cardiac reflex was calculated from the spontaneous changes in beat-to-beat arterial pressure and heart rate (fc). During supine rest the variability of arterial pressure decreased during cooling, while it remained unchanged during heating. The variability increased with HUT; it was greater (P < 0.05) with heating than with cooling. In the supine condition, the arterial baroreflex sensitivity of fc increased during cooling, while it did not change during heating. The sensitivities decreased (P < 0.05) with HUT during both thermal stresses; the decreased rate of sensitivity from the pre-tilt value was greater during heating [mean 63 (SEM 4)%] and smaller during cooling [mean 11 (SEM 24)%] than during normothermia [mean 47 (SEM 4)%] (both, P < 0.05). There were significant negative correlations between the sensitivities and the amplitude of the arterial pressure variability during normothermia and heating (P < 0.0001). The results suggest that the spontaneous baroreflex response of fc is a modulatory factor for the changes of arterial pressure variability brought about by thermal stress during orthostatic stress.

Pemphigus of the eyelids.

We report the case of a 56-year-old woman who presented with a 2-month history of widespread oral erosion and a 3-day history of small papules on the lower eyelids. No other skin involvement was found. Histopathological examination revealed suprabasal cleft and acantholysis in the lower epidermis of the papule on the lower eyelid and in the lower mucous membrane of the oral mucosa. Intercellular deposits of IgG and C3 were seen in the whole epidermis of the specimen from the papule on the right lower eyelid by direct immunofluorescence study. These deposits were also observed in the biopsy specimen from erosion on the left buccal membrane. Indirect immunofluorescence study using normal human skin as a substrate showed intercellular antibodies directed to the cell surface of the whole epidermis with a titer of 1:40. The titers of antibodies to desmoglein 3 and 1 were 118 and 25.9, respectively, by enzyme-linked immunosorbent assay. The patient was treated with an oral administration of prednisolone (0.75 mg/kg/day) for 9 days, which improved the skin eruptions and oral erosion. The dose of prednisolone was gradually tapered and it took 10 weeks to cease this treatment. These findings suggest that this patient is an unusual case of pemphigus vulgaris (mucosal dominant type) diagnosed from the clinical and histopathological findings, with positive antibodies to desmoglein 3 and 1.