Surgical management of lacrimal punctal cauterization in chronic GVHD-related dry eye with recurrent punctal plug extrusion.

We investigated the efficacy of lacrimal punctal occlusion surgery with a cautery device in patients with chronic GVHD (cGVHD)-related dry eye, with recanalization of puncta and recurrent punctal plug extrusion. A total of 23 puncta from 14 eyes of 10 patients with chronic GVHD (cGVHD)-related dry eye underwent punctual thermal cauterization with a high-temperature disposable cautery device. All patients were refractory to conventional treatment, including artificial tear eye drops, autologous serum eye drops and vitamin A eye drops, and had a history of recanalization and recurrent punctal plug extrusion. The effect of lacrimal punctal cauterization by thermal cautery device was evaluated by changes in subjective symptom scores, corrected distance visual acuity, Schirmer's test values, fluorescein staining scores, rose bengal staining scores, and tear-film break-up time before and 3 months after the surgery. Subjective symptom scores, Schirmer's test values, fluorescein and rose bengal scores, and tear-film break-up time improved significantly 3 months after the surgery. Recanalization of puncta was not observed in all the cases (0 of 14 eyes, 0%). Lacrimal punctal cauterization was effective with no recanalization and significant improvements in subjective symptoms and the ocular surface environment in cGVHD-related dry eye patients who had been refractory to conventional treatments.

Influence of anti-HBc seropositivity on the risk of hepatocellular carcinoma in HCV-infected patients after adjusting for confounding factors.

It is controversial whether past hepatitis B virus infection constitutes an additional risk of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV). The incidence of HCC between 1994 and 2004 was analysed among 1262 patients who were only positive for HCV. The cumulative incidence of HCC was assessed by Kaplan-Meier analysis and the difference between two groups was assessed by the log-rank test. The effect of anti-HBc positivity on the risk of HCC was assessed with multivariate Cox proportional analysis. Anti-HBc was positive in 522 (41.4%) patients. The proportion of male patients (56.7 vs 46.8%, P < 0.001) and mean age (60.8 vs 56.9 years, P < 0.001) were significantly higher in the anti-HBc positive group. HCC developed in 339 patients (mean follow-up 7.0 years), with cumulative incidence rates at 3, 5 and 10 years of 12.7, 24.5 and 41.9% in the anti-HBc positive group and 10.6, 17.7 and 33.4% in the negative group, respectively (P = 0.005). However, anti-HBc seropositivity did not reach statistical significance in multivariate analysis including age and gender (hazard ratio, 1.06; 95% CI, 0.85-1.31; P = 0.63). Anti-HBc positivity and HCC incidence were confounded by male gender and older age.

Visceral fat accumulation is an independent risk factor for hepatocellular carcinoma recurrence after curative treatment in patients with suspected NASH.

BACKGROUND AND AIMS: Visceral fat accumulation reportedly increases the risk of hepatocellular carcinoma (HCC) development in patients with chronic liver disease. However, it has not been fully elucidated whether visceral fat accumulation increases the risk of HCC recurrence after curative treatment in patients with suspected non-alcoholic steatohepatitis (NASH). Therefore this was investigated in the current study. METHODS: 62 patients with naive HCC with suspected NASH were enrolled. All were curatively treated with percutaneous radiofrequency ablation between 1999 and 2006. The visceral fat area (VFA) was determined in each patient from CT images, taken at the time of HCC diagnosis. Patients were divided into two groups based on VFA: the high VFA group (>130 cm(2) in males, >90 cm(2) in females, n = 27) and the others (n = 35). The effects of VFA on HCC recurrence were analysed together with other factors including patients' background, tumour-related factors and liver function-related factors. RESULTS: The cumulative recurrence rates differed significantly between the two groups; 15.9, 56.5 and 75.1% at 1, 2 and 3 years, respectively, in the high VFA group, and 9.7, 31.1 and 43.1%, respectively, in the controls (p = 0.018). Multivariate analysis indicated visceral fat accumulation (risk ratio 1.08, per 10 cm(2), p = 0.046) and older age (risk ratio 1.06 per 1 year, p = 0.04) as independent risk factors of HCC recurrence. CONCLUSIONS: Visceral fat accumulation is an independent risk factor of HCC recurrence after curative treatment in patients with suspected NASH.

Tear function and lipid layer alterations in dry eye patients with chronic graft-vs-host disease.

PURPOSE: To investigate the changes in the tear film lipid layer in haematopoietic stem cell transplantation (HSCT) patients with dry eye (DE) associated with chronic graft-vs-host disease (cGVHD) and compare with HSCT recipients without DE. METHODS: We performed a prospective study in 10 HSCT patients with DE associated with cGVHD and 11 HSCT recipients without DE. We performed Schirmer's test, tear film break up time examinations, ocular surface dye staining and meibum expressibility test and DR-1 tear film lipid layer interferometry. DR-1 interferometry images of the tear film surface were assigned a 'DR-1 grade' according to the Yokoi severity grading system. The DR-1 grades were analysed according to the presence or absence of DE, conjunctival fibrosis and systemic cGVHD. RESULTS: The mean DR-1 severity grade in patients with DE related to cGVHD (DE/cGVHD group; 3.9+/-0.9) was significantly higher than in patients without DE after HSCT (non-DE/non-cGVHD group; 1.3+/-0.6; P<0.05). The DR-1 grade for HSCT recipients with conjunctival fibrosis was significantly higher than in patients without conjunctival fibrosis (P<0.05). When DE severity was graded according to the recommendation of the 2007 Dry Eye Workshop Report, our results showed a correlation between the severity of DE and DR-1 grades (r=0.8812, P<0.0001). CONCLUSION: DR-1 interferometry may be applicable to diagnosing DE and evaluating its progression subsequent to HSCT.

Human bronchial intraepithelial T cells produce interferon-gamma and stimulate epithelial cells.

Intraepithelial lymphocytes (IELs) can be identified among epithelial cells in systemic mucosal tissues. Although intestinal IELs play a crucial role in mucosal immunity, their bronchial counterparts have not been well studied. The purpose of this study was to determine the immunological functions of human bronchial IELs, which interact directly with epithelial cells, unlike lamina propria lymphocytes (LPLs). We isolated successfully bronchial IELs and LPLs using a magnetic cell separation system from the T cell suspensions extracted from bronchial specimens far from the tumours of resected lungs. Human bronchial IELs showed an apparent type 1 cytokine profile and proliferated more actively in response to CD2 signalling than did bronchial LPLs. CD8(+) IELs were identified as the most significant sources of interferon (IFN)-gamma. Human bronchial epithelial cells constitutively produced the T cell growth factors interleukin (IL)-7 and IL-15, and levels of those factors increased when cells were stimulated by IFN-gamma. Bronchial epithelial cells expressed cell surface proteins CD58 and E-cadherin, possibly enabling adhesion to IELs. In summary, human bronchial IELs have immunological functions distinct from bronchial LPLs and may interact with epithelial cells to maintain mucosal homeostasis.

Alterations of the tear film and ocular surface health in chronic smokers.

OBJECTIVE: To investigate the effects of chronic smoking on ocular surface and tear functions. METHODS: Fifteen right eyes of 15 healthy chronic smokers (9 men, 6 women; age range: 36-47 years) who smoked 20 cigarettes per day for 20 years and 20 eyes of 20 control non-smokers (12 men, 8 women; age range: 38-43 years) were included in this prospective study. All subjects underwent measurements of breath and haemoglobin CO concentration, tear lipid layer interferometry, evaporimetry, tear film break-up time (TBUT), Schirmer's I test, corneal fluorescein staining, conjunctival impression, and brush cytology. RESULTS: The mean Hb CO level was significantly higher in smokers compared to non-smokers. TBUT was also significantly shorter in smokers. Tear lipid layer showed significant slowing in spread over the tear film with a concomitant significant increase in tear evaporation rate. Conjunctival impression cytology revealed significant loss of goblet cells and squamous metaplasia in smokers. Brush cytology showed significant conjunctival neutrophil infiltration in smoker subjects. CONCLUSION: Chronic smoking induced distinctive quantitative and qualitative disturbances on the ocular surface health.

Albumin as a tear supplement in the treatment of severe dry eye.

AIM: To determine the efficacy of using albumin tear supplements in the treatment of ocular surface disorders as a substitute for serum eye drops. METHODS: The effects of albumin on the viability of serum deprived conjunctival cell were observed in vitro. The ability for albumin to compensate for serum was demonstrated by measuring the activity of the apoptosis related enzyme, caspase-3. In an animal study, corneal erosions were inflicted in 40 Japanese white rabbits. Rabbits were treated with 5% or 10% solutions of human albumin, and the decrease in epithelial defect size was compared with saline control and 0.3% sodium hyaluronate. A clinical case series trial of 5% albumin drops was conducted in nine patients with Sjögren's syndrome with severe dry eye. RESULTS: The addition of albumin to serum deprived conjunctival cells inhibited caspase activity and increased cell viability, showing that albumin can compensate for some of the physiological properties of serum. Corneal erosions in rabbits healed significantly faster (p<0.05) in eyes treated with 10% albumin compared with control and sodium hyaluronate. Patients with Sjögren's syndrome used albumin drops showed statistically significant improvement in fluorescein and rose bengal scores, but not in tear break up time and subjective symptoms. No adverse effects of albumin were observed during the study. CONCLUSIONS: The use of albumin as a protein supplement in artificial tear solutions is a viable approach in the treatment of ocular surface disorders associated with tear deficiency.

Dyspnoea and hyperventilation induced by synthetic progesterone chlorpromadinone acetate for the treatment of prostatic hypertrophy.

We describe a 74-year-old patient with dyspnoea and tachypnoea induced by chlorpromadinone acetate, a synthetic progesterone used to treat prostatic hyperplasia. The dyspnoea, tachypnoea and hypocapnia improved after discontinuing the chlorpromadinone acetate. It is important to recognize that synthetic progesterones can cause dyspnoea and hyperventilation.

Methotrexate poisoning with acute hepatorenal dysfunction.

A 17-year-old girl receiving high-dose methotrexate for the treatment of osteosarcoma developed complications of acute renal failure and liver dysfunction with a coagulation disorder. The methotrexate concentrations were quickly reduced from 600 micromol/L to 50 micromol/L by treatment with plasma exchange and hemodialysis at 72 hours after discontinuation of the drug. After this reduction, continuous hemodiafiltration was initiated to further lower the methotrexate concentrations because of the persistently high and then the actual rebound in the plasma concentrations after plasma exchange and hemodialysis treatment. Continuous hemodiafiltration was able to reduce the concentrations without any rebound, despite its low column clearance. The rebound in plasma methotrexate concentrations seems to be corrected by plasma methotrexate after plasma exchange and/or hemodialysis.

Thymidine phosphorylase expression results in a decrease in apoptosis and increase in intratumoral microvessel density in human gastric carcinomas.

Thymidine phosphorylase (dThdPase)/platelet-derived endothelial cell growth factor (PD-ECGF) is expressed at higher levels in a variety of human carcinomas than in adjacent normal tissue. The higher expression is associated with an increase in intratumoral microvessel density (IMVD) and an unfavorable patient prognosis. This study examined the role of dThdPase in apoptosis, IMVD and p53 expression in human gastric carcinomas, dThdPase expression was noted in 12 (35.3%) of 34 early carcinomas, and in 20 (55.6%) of 36 advanced carcinomas. At least 10 areas consisting of carcinoma cells with diffuse dThdPase expression from the 32 dThdPase-positive tumors (category I), and 10 areas without dThdPase expression from the 38 negative tumors (category II) were selected from each case. For early gastric carcinoma, the mean IMVD was 88.8+/-19.4 in category I and 61.4+/-17.3 in category II carcinomas, while for advanced gastric carcinoma, the mean IMVD was 98.8+/-21.0 in category I and 76.0+/-27.1 in category II carcinomas. The mean IMVD was significantly higher in category I than in category II tumors (P<0.05). The mean apoptotic index (AI: percentage of apoptotic cells) was 1.95+/-1.30 in category I, and 3.76+/-1.49 in category II carcinomas for early gastric carcinoma, and 1.51+/-0.98 in category I and 2.14+/-0.66 in category II carcinomas for advanced gastric carcinoma, the value of the mean AI being significantly (P<0.05) higher in dThdPase-negative tumors (category II) than in the positive tumors (category I), regardless of tumor stage or histological type. There was a significant inverse correlation (P<0.001) between AI and IMVD. These results indicate that dThdPase expression is associated with both an increase in intratumoral microvessels and a decrease in apoptosis in human gastric carcinomas.

Human bronchial intraepithelial T lymphocytes as a distinct T-cell subset: their long-term survival in SCID-Hu chimeras.

Intestinal intraepithelial T lymphocytes (i-IELs) show features different from those of conventional T cells and play specific roles in the mucosal immunity. To investigate whether human bronchial intraepithelial T lymphocytes (IELs) are a distinct entity, we examined T cells in human bronchial xenografts transplanted on mice with severe combined immune deficiency (SCID). We transplanted human bronchi subcutaneously into mice with SCID, resected the xenografts after various incubation periods (7-174 d), and examined them for CD3(+), CD4(+), CD8(+), and CD45(+) cells by immunohistochemistry. The number of CD3(+) cells in the lamina propria decreased significantly in the first month (from 308.7 +/- 60.2 to 70.9 +/- 49. 4/mm(2); P < 0.05), and xenografts more than 5 mo of age had scant T cells in the lamina propria (5.2 +/- 2.0/mm(2)). However, there was no significant difference between the number of CD3(+) IELs in freshly isolated bronchi and in xenografts maintained for more than 5 mo. In freshly isolated bronchi, the number of CD4(+) IELs was significantly lower than that of CD8(+) cells (2.35 +/- 0.62 versus 4.56 +/- 1.32/mm basement membrane; P < 0.01). After transplantation, the mean CD4-to-CD8 ratio of all xenografts was significantly higher than that of freshly isolated bronchi (5.2 +/- 0.9 versus 0.6 +/- 0.2; P < 0.005). The IELs were positive for CD45, which is specific for human leukocytes, and they were eliminated by irradiation before the transplantation. Almost all IELs (99.5%) in the xenografts expressed alphabeta T-cell receptor, and 35.8% of IELs expressed alpha(e)beta7 integrin. Bronchial epithelial cells in the xenografts expressed interleukin (IL)-7, stem cell factor, intercellular adhesion molecule (ICAM)-1, and human leukocyte antigen-DR (HLA-DR). We conclude that in the SCID-Hu chimera model, human bronchial IELs survive for more than 5 mo, unlike the T cells in the lamina propria, and we suggest that human bronchial IELs may be stimulated by bronchial epithelial cells expressing IL-7, stem cell factor, ICAM-1, and HLA-DR.

Efficacy and safety of infrared warming of the eyelids.

PURPOSE: To evaluate our newly developed infrared heater (IRH) and compare it to a broad-spectrum heater (BSH) for warming the eyelids. MATERIALS AND METHODS: Ten normal subjects were enrolled in this study. All measurements were recorded in a room with temperature 23 degrees C, 40% humidity, and no wind. The IRH is composed of two hard eye patches that have light-emitting diodes (LEDs) emitting near-infrared radiation. We first compared the temperature rises in the cornea, lacrimal gland, and eyelids after warming through closed eyelids with the IRH for 5 and 10 min. Next, we compared warming with the IRH or BSH for 30 min. We then used the IRH for 5 min with the eyes open to confirm its safety. Finally, we determined subjective feeling after warming the eyes. RESULTS: Direct comparison of 5 versus 10 min of warming with the IRH showed no significant differences in temperature rises in the upper eyelid (p = 0.09). The IRH caused significantly more heating (p < 0.05) than did the BSH everywhere except the cornea. The temperatures never rose above 37.7 degrees C for either heater during 30 min or with the IRH with the eyes open for 5 min. The subjects' comfort level rose significantly (p < 0.05) after treatment with the IRH. CONCLUSIONS: Our study showed the efficacy and safety of warming the eyelids with a newly developed IRH. Only 5 min is necessary to increase ocular temperature and enhance comfort.

Possible involvement of central C-type natriuretic polypeptide receptor on water intake in spontaneously hypertensive rats, but not in normotensive Wistar-Kyoto rats.

The present study was designed to examine the possible role of brain C-type natriuretic polypeptide receptor (GC-B) in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). The level of GC-B mRNA in various regions of the brain in both SHR and WKY was examined in the present study. The GC-B mRNA was unevenly distributed in rat brain, the transcript being expressed predominantly in the hypothalamus and cerebellum but comparatively at low level in the striatum and septum. However, the level in the septum was 3-fold higher in SHR than than in age-matched WKY, while no differences were observed in other regions of the brain. Intracerebroventricular administration of antisense oligonucleotide to GC-B mRNA inhibits the night-time water intake in SHR, but not in WKY. However, the daily food intake was not significantly altered by the injection of antisense oligonucleotide in both strains. These results demonstrate that the brain GC-B mRNA, particularly in septum, is increased in SHR and this increase may be closely related to the regulation of water-drinking behaviour in SHR.

Allergen exposure induces the expression of endothelial adhesion molecules in passively sensitized human bronchus: time course and the role of cytokines.

To study the mechanisms contributing to the recruitment of a selective leukocyte subset in allergic inflammation involving the airways as may occur in asthma, we examined whether allergic exposure induces the expression of cell adhesion molecules (CAMs) on the bronchial endothelium of passively sensitized human bronchi. Human bronchial tissue obtained from patients undergoing lung cancer surgery was passively sensitized with serum from patients with atopic asthma who were sensitive to house dust mite. We incubated the tissues for 30, 120, 240, and 480 min in the presence or absence of the dust mite allergen. The tissues were stained immunohistochemically for intercellular adhesion molecule 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule 1 (VCAM-1). ICAM-1 was constitutively expressed in both the epithelium and endothelium in all tissues but after allergen stimulation significantly increased at 240 and 480 min. E-selectin expression also existed constitutively and increased significantly at 120 and 240 min with allergen exposure. The constitutive expression of VCAM-1 was less than that of ICAM-1 and E-selectin. Following allergen exposure, VCAM-1 expression increased significantly at 30, 120, 240, and 480 min, and at 480 min reached an almost 3.5-fold increase from baseline expression. The TNF-alpha level in the supernatants significantly increased at 120 min after allergen stimulation, and the interleukin (IL)-1beta level increased in 4 of 15 samples. We also examined the induction of CAMs by TNF-alpha, IL-1beta, and IL-4 on human bronchial tissue. TNF-alpha and IL-1beta increased the expression of ICAM-1, E-selectin, and VCAM-1, whereas IL-4 induced only that of VCAM-1. In addition, neutralizing antibody against TNF-alpha and IL-1beta partially blocked the upregulation of CAMs on passively sensitized bronchial tissue after allergen exposure. Thus, both an IgE-dependent allergic response and selected cytokines are able to upregulate endothelial CAMs in human bronchial tissue. These observations provide further evidence that leukocyte infiltration into the site of allergic inflammation as occurs in atopic asthma is in part regulated by the expression of ICAM-1, VCAM-1, and E-selectin.

Lecithin-bound superoxide dismutase in the prevention of neutrophil-induced damage of corneal tissue.

PURPOSE: To evaluate the effects of a lipophilic analog of superoxide dismutase (SOD) in the prevention of polymorphonuclear leukocyte (PMN)-induced damage to corneal epithelial cells in vitro and in bacterial corneal ulcers in vivo. METHODS: Immortalized human corneal epithelial cells (T-HCEC) were cocultured with human PMNs activated with N-formyl-methionyl-leucyl-phenylalanine for 18 hours, after which lactate dehydrogenase (LDH) activity of the supernatant was measured as a marker of cellular damage. The inhibitory effects of lecithin-bound SOD (PC-SOD) and unmodified SOD, as well as PMNs pretreated with anti-CD 18 monoclonal antibody, were compared with untreated control. The retention of each drug on the ocular surface of healthy volunteers was measured by flow cytometry using brush cytology samples. The protective effects of a 0.1% solution of PC-SOD on Pseudomonas aeruginosa corneal infection in guinea pigs were assessed by inflammatory grading scores and histology. RESULTS: Both PC-SOD and SOD effectively suppressed PMN-induced LDH release in T-HCEC in a dose-dependent manner. LDH release was also attenuated when PMNs were pretreated with anti-CD 18 antibodies, suggesting that adhesion molecules were involved in the process. Brush cytology of conjunctival samples showed that PC-SOD was retained longer on the ocular surface compared with unmodified SOD. PC-SOD significantly prevented excessive tissue damage by infiltrating PMNs in P. aeruginosa corneal infection, whereas in control eyes, perforation of the cornea occurred by 6 days. CONCLUSIONS: PC-SOD was effective in attenuating PMN-related tissue damage to corneal tissue both in vitro and in P. aeruginosa infection in guinea pigs.

Novel phosphodiesterase 4 inhibitor T-440 reverses and prevents human bronchial contraction induced by allergen.

To study the roles of phosphodiesterase (PDE) 4 in the human airways, we examined the effect of the novel PDE4 inhibitor T-440 in the isolated human bronchus. T-440 inhibited PDE4 extracted from human bronchial smooth muscle. IC50 values for the effect of T-440, rolipram (a PDE4 inhibitor) and theophylline on PDE4 activity of the bronchial tissues were 0.08 microM, 2 microM and > 100 microM, respectively. T-440 (10(-6) M to 10(-5) M) and aminophylline (3.3 x 10(-5) M) significantly reversed the 10(-5) M histamine-induced contraction, the efficacy of 10(-6) M T-440 being almost the same as that of 3.3 x 10(-5) M aminophylline. T-440 (10(-6) M to 10(-5) M) and aminophylline (3.3 x 10(-5) M) significantly reversed the 10(-4) M ACh-induced contraction. But their reversal effects on the ACh-induced contraction were weaker than those on the histamine-induced contraction. T-440 (10(-5) M) significantly reversed the contraction induced by allergen in passively sensitized bronchi. The efficacy of the reversal effect of T-440 (10(-5) M) was significantly higher than that of aminophylline (10(-5) M). T-440 and aminophylline significantly relaxed the basal tension, but pretreatment with T-440 or aminophylline did not significantly prevent histamine- or ACh-induced contraction. In contrast, both T-440 (10(-5) M) and aminophylline (3.3 x 10(-5) M) prevented the contraction induced by allergen, which suggests that PDE4 inhibitor inhibits the release of chemical mediators probably from bronchial mast cells in the allergic response. T-440 (10(-6) M to 10(-5) M) caused the accumulation of cAMP at the concentration that relaxed histamine-induced contraction. Thus selective PDE4 inhibitor is a candidate for the treatment of asthma.

The clinical characteristics at the onset of a severe asthma attack and the effects of high frequency jet ventilation for severe asthmatic patients.

To clarify the relationship between the clinical characteristics and the effects of high frequency jet ventilation based on the differences in the speed of deterioration in severe asthmatic patients who required intubation and mechanical ventilation, we classified 37 severe asthmatics into two groups (acute onset group: n = 20, intubated within 24 hours; slow onset group: n = 17, intubated over 3 days) and measured the arterial blood gas values, the duration of mechanical ventilation, and the peak inspiratory pressure during synchronized intermittent mechanical ventilation with or without high frequency jet ventilation. The acute onset group showed a significantly higher incidence of cyanosis (75% vs. 41%, p < 0.05), an acute loss of consciousness (90% vs. 53%, p < 0.05), severe mixed acidosis with extreme hypercapnoea (pH 7.11 +/- 0.19, PaCO2 94.1 +/- 10.7 mmHg, BE -8.3 +/- 1.7 mEq/l), and a more elevated peak inspiratory pressure (59.7 +/- 1.8 mmHg vs. 41.1 +/- 1.8 mmHg, p < 0.05) during synchronized intermittent mechanical ventilation at admission, compared with the slow onset group (p < 0.05). The slow onset group required a more prolonged mechanical ventilation than the acute onset group (5.4 +/- 4.0 vs. 3.0 +/- 2.4 days, p < 0.05), in spite of a lower peak inspiratory pressure than that observed in the acute onset group, because of either a large amount of secretion or an infection in the airway. Both the high peak inspiratory pressure and the severe mixed acidosis with markedly elevated hypercapnoea were significantly reduced by the application of high frequency jet ventilation between the intra- and the inter-groups. These findings thus indicated the existence of significant differences in the clinical features and pathogenesis of airway hyperreactivity between these two groups, and the application of high frequency jet ventilation to the status asthmaticus was thus found to be effective.

Potentiation of dipsogenic actions by centrally administered type-C natriuretic peptide in spontaneously hypertensive but not Wistar-Kyoto rats.

1. The effects of type-C natriuretic polypeptides (CNP) on the central dipsogenic and pressor responses to angiotensin II (AngII) were studied by the administration of agents into the lateral cerebral ventricle under conscious and unrestrained conditions in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. The fluid intake induced by AngII (25 ng) and water deprivation were potentiated after pretreatment with CNP in SHR but not in WKY rats. However, carbachol-induced water intake was not altered by pretreatment with CNP (2.5 micrograms) in either WKY rats or SHR. 3. In contrast, CNP did not influence the pressor responses to AngII in either WKY rats or SHR.

Life-threatening cardiac involvement throughout life in a case of Costello syndrome.

Costello syndrome is characterized by poor postnatal growth, mental retardation, curly hair, coarse face, loose skin of the hands and feet, and nasal papillomata. Patients with Costello syndrome have a high incidence of cardiac involvement, such as arrhythmias, hypertrophic cardiomyopathy, or congenital anomalies. The importance of cardiac involvement in Costello syndrome has not been strongly emphasized thus far, although arrhythmia and hypertrophic cardiomyopathy are both serious forms of cardiac involvement. We report the case of a Japanese girl with Costello syndrome, who experienced life-threatening cardiac involvement throughout her life.