A Clinicopathological Study of Idiopathic Normal Pressure Hydrocephalus

Background : Since Hakim and Adams introduced the clinical entity of normal pressure hydrocephalus (NPH) in 1965, postmortem studies of idiopathic NPH have been few in number. Several autopsy cases reported with clinically probable "idiopathic NPH" were diagnosed with Alzheimer's disease (AD) or Binswanger's disease (BD) neuropathologically. Therefore, the neuropathological study of pathologically confirmed idiopathic NPH remains to be completed both quantitatively and qualitatively.
Methods : Out of 239 autopsy cases in Fukushimura Hospital, 13 patients had been diagnosed clinically as having NPH. After excluding seven cases diagnosed neuropathologically with other diseases or secondary NPH, we investigated the clinicopathological findings of six patients with idiopathic NPH.
Results : Four patients presented with the complete classic triad consisting of progressive dementia, gait disturbance, and urinary incontinence. All cases exhibited progressive ventricular enlargement with periventricular lucency by computed tomography images. We found (1) diffuse marked dilatation of the lateral ventricles of unknown etiology, and (2) the changes of ependymal cells and subependymal tissue around the callosocaudate angle. Furthermore, no complications were suspected neuropathologically in all cases, such as AD, BD, or Lewy body disease.
Conclusion : We experienced six autopsy cases with pathologically confirmed idiopathic NPH. They had two pathological features of NPH but no other pathological disorders that might cause NPH. Several "idiopathic NPH" cases reported previously have been diagnosed neuropathologically with other disorders. However, the presented cases could be clearly distinguished from such "idiopathic NPH." Therefore, our cases should be defined as idiopathic NPH neuropathologically. By accumulating more cases and investigating further we hope to elucidate the pathogenesis and further develop treatment for idiopathic NPH.     

Comparison of effects of olmesartan and telmisartan on blood pressure and metabolic parameters in Japanese early-stage type-2 diabetics with hypertension.

Angiotensin II type-1 receptor blockers (ARBs) are regarded as first-line treatments for type-2 diabetes with hypertension. Despite the availability of various types of ARBs, there are no comparative studies of their effects on patients with diabetes. In this open-label prospective crossover study, we compared the effects of olmesartan (20 mg/day) and telmisartan (40 mg/day). Twenty Japanese early-stage type-2 diabetes patients with hypertension treated with valsartan (80 mg/day) for at least 8 weeks were recruited to this study. At study entry, valsartan was changed to olmesartan (20 mg/day) or telmisartan (40 mg/day) and administered for 8 weeks. The drugs were then switched and treatment was continued for another 8 weeks. We analyzed the blood pressure lowering effects of each drug by 24-h ambulatory blood pressure monitoring at 0, 8, and 16 weeks. Simultaneously, we measured metabolic parameters and inflammation markers. Olmesartan lowered mean systolic and diastolic blood pressure more significantly than did telmisartan. While there were no differences between the groups in metabolic parameters, including HbA1c and adiponectin, the decreases in serum interleukin-6 and highly sensitive C-reactive protein were more significant by olmesartan treatment. Our results indicate that olmesartan has more potent arterial blood pressure lowering and anti-inflammatory effects than telmisartan.     

Serum Prolactin, Cortisol and Growth Hormone Concentrations after Various Epileptic Seizures

Abstract: The serial serum concentrations of prolactin (PRL), Cortisol and growth hormone (GH) were measured after clinical fits of seizures in 49 epileptic patients, aged 13-77. In generalized tonic-clonic seizures, both the serum PRL and Cortisol levels transiently rose and reached their maximum 30 min after the onset of clinical fits. Serum GHs were elevated in some of the patients. After complex partial seizures, significant rises were found only in serum Cortisol, but no demonstrable change was observed in PRL and GH. In the other minor seizure group, no remarkable change was observed in any of the hormones. These results suggest that the postictal hormonal change is different in each type of seizure, respectively.     

Short‐ and long‐term outcomes following redo valvular surgery

Aim

We reviewed our experience in redo valvular surgery to evaluate trends in short‐ and long‐term outcomes.

Methods

We reviewed 414 patients (mean age, 62.8 ± 13.6 years) who underwent redo valvular surgery in the past 25 years. A total of 301 patients (54.2%) underwent first‐time redo valvular surgeries; 178 (32.1%) were second redos, 60 (10.8%) were third redos, and 16 were fourth redos (2.9%). The mean follow‐up period was 6.8 ± 6.3 years.

Results

Hospital mortality was 5.8%. New York Heart Association (NYHA) class III/IV (P = 0.0007, odds ratio = 4.403) and hemodialysis (P = 0.0383, odds ratio = 7.196) were risk factors for hospital death. Long‐term survival rates at 15 and 20 years were 64.7% ± 4.3% and 59.1% ± 5.0%, respectively. Predictors of late death were first time redo (P = 0.0076, hazard ratio = 0.422) and age younger than 61 years (P = 0.0005, hazard ratio = 0.229). There were significant differences in long‐term survival between NYHA classes I/II and III/IV (log‐rank test, P = 0.0419) and between the time from redo surgery (log‐rank test, P = 0.0189) and age (log‐rank test, P = 0.0001).

Conclusions

The hospital mortality rate for redo valve surgery has improved. Early referral for redo surgery can contribute to improving early and late outcomes.     

Combined genotypes of ACE and NADPH oxidase p22phox associated with somatic mutation of mtDNA and carotid intima-media thickness in Japanese patients with type 2 diabetes mellitus

Background: We previously reported that the carotid artery intima-media thickness (IMT) increased with age and that patients with type 2 diabetes mellitus (DM) had a significantly larger IMT than did age-matched nondiabetic subjects with normal glucose tolerance. Although the exact mechanism behind the increase in IMT in diabetic patients has not been determined, data obtained from in vivo and in vitro studies suggest that hyperglycemia-induced oxidative stress may lead to atherogenesis.Objective: The aim of this single-center study was to determine whether long-term oxidative stress and the carotid IMT are influenced by differences of the angiotensin-converting enzyme insertion/deletion (ACE I/D) and NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) oxidase p22phox C242T genotypes.Methods: Eligible subjects were Japanese patients with type 2 DM. Polymorphism of the ACE I/D and p22phox gene was investigated using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively. The rate of an acquired mutation of mitochondrial DNA—that is, A-to-G substitution at position 3243 (mtDNA A3243G)—was determined by real-time PCR. As a marker of early atherosclerosis, the carotid artery IMT was measured using high-resolution B-mode ultrasonography.Results: A total of 262 Japanese patients (173 men, 89 women; mean [SEM] age, 58 [0.6] years [range, 18-80 years]) were recruited and enrolled for study. An ACED-positive (DD or DI) and p22phox 242T-negative genotype (CC) was associated with a significantly higher mtDNA A3243G mutation rate than the other 3 possible genotypes (0.0219% [0.0028%] vs 0.0097% [0.0012%]; P < 0.05). This genotype also had higher maximum and mean IMT values than the other genotypes (1.13 [0.048] mm vs 0.99 [0.03] mm and 1.01 [0.036] mm vs 0.92 [0.023] mm; P < 0.05). These parameters were similar among the other 3 genotypes.Conclusion: In this study, the ACED-positive and p22phox 242T-negative genotype showed higher rates of somatic mtDNA mutation (mtDNA A3243G) and higher carotid mean and maximum IMT levels.     

Reactivation of hepatitis B virus in HBsAg-negative patients with multiple myeloma: two case reports

It was recently reported that hepatitis B virus (HBV) reactivation had occurred in HBsAg-negative lymphoma patients who received rituximab plus steroid combination chemotherapy. HBV reactivation in myeloma patients have not been reported extensively. We describe here two cases of HBV reactivation in HBsAg-negative myeloma patients receiving systemic chemotherapy: one from the medical records of 40 patients and another from 61 patients with prospective HBV-DNA monitoring. In the first case positive for anti-HBs, HBV reactivation was diagnosed when hepatitis developed during conventional chemotherapy such as MP and MCP regimen in a relapsed patient after autologous stem cell transplantation (APBSCT); in the second case positive for anti-HBc and anti-HBs, elevation of HBV-DNA was recognized by serial HBV-DNA monitoring performed prospectively following APBSCT. Interestingly, these two cases had the reduction of the titer of anti-HBs during the treatment, followed by HBV reactivation. These clinical data suggest that the HBV-DNA monitoring is necessary for not only HBsAg-positive but also HBsAg-negative myeloma patients with anti-HBc-positive and/or anti-HBs-positive following transplantation and after conventional chemotherapy in the salvage setting. Establishment of a standard strategy to prevent HBV reactivation is important for myeloma patients receiving systemic chemotherapy.     

Cibenzoline attenuates systolic anterior motion of the mitral valve after mitral valvoplasty

We report a patient in whom severe hemodynamic instability occurring after mitral valvoplasty (MVP) was successfully treated with cibenzoline. Left ventricular outflow tract obstruction (LVOTO) with mitral regurgitation (MR) resulting from the systolic anterior motion (SAM) of the mitral valve that occurs after MVP often leads to hemodynamic collapse. Patients who develop SAM after MVP have been managed with intravenous volume loading, reduction/discontinuation of inotropic drugs, and with increased afterload, but these strategies were often ineffective. Cibenzoline decreased myocardial contraction, attenuated SAM, and improved hemodynamics in our patient. We recommend that cibenzoline be administered before further surgical manipulation is considered for patients who develop SAM after MVP.     

Lack of Spem1 causes aberrant cytoplasm removal, sperm deformation, and male infertility

We identified a previously uncharacterized gene, spermatid maturation 1 (Spem1), encoding a protein exclusively expressed in the cytoplasm of steps 14-16 elongated spermatids in the mouse testis. This protein contains no known functional domains and is highly conserved across mammalian species. Male mice deficient in Spem1 were completely infertile because of deformed sperm characterized by a bent head wrapped around by the neck and the middle piece of the tail. We show that lack of Spem1 causes failure of the cytoplasm to become loose and detach from the head and the neck region of the developing spermatozoa. Retained cytoplasmic components mechanically obstruct the straightening of the sperm head and the stretching of the growing tail, leading to the bending of the head in the neck, followed by the wrapping of the head by the neck or the middle piece of the sperm tail. Our study reveals that proper cytoplasm removal is a genetically regulated process requiring the participation of Spem1 and that lack of Spem1 causes sperm deformation and male infertility.