Hypertrophy of medial globus pallidus and substantia nigra reticulata in 6‐hydroxydopamine‐lesioned rats treated with L‐DOPA: Implication for L‐DOPA‐induced dyskinesia in Parkinson's disease

The medial globus pallidus plays a crucial role in generation of L‐DOPA‐induced dyskinesia in patients with Parkinson's disease. The 6‐hydroxydopamine‐lesioned rat exhibiting behavioral sensitization to L‐DOPA is one useful animal model for examining L‐DOPA‐induced dyskinesia. To determine neuropathological abnormality responsible for behavioral sensitization, the medial globus pallidus and the substantia nigra reticulata in 6‐hydroxydopamine‐lesioned rats treated with L‐DOPA were examined. Intermittent L‐DOPA treatment induced hypertrophy of the lesioned‐side of medial globus pallidus and substantia nigra reticulata of 6‐hydroxydopamine‐lesioned rats with behavioral sensitization to L‐DOPA. Additionally, coadministration of a 5‐HT_1A receptor agonist, 8‐hydroxy‐2(di‐n‐propylamino)tetralin with L‐DOPA, alleviated the hypertrophy with improvement of the behavioral sensitization. These results suggest that hypertrophy of the medial globus pallidus and substantia nigra reticulata is associated with induction of behavioral sensitization to L‐DOPA in 6‐hydroxydopamine‐lesioned rats. Therefore, neuropathological changes corresponding to hypertrophy might underlie L‐DOPA‐induced dyskinesia in patients with Parkinson's disease.     

Surgical treatment of acquired tricuspid stenosis]

There is no definitive surgical procedure for acquired lesions of the tricuspid valve (TV). From Feb, 1978, through March, 1990, the surgical treatment for the organic lesions of TV was performed in 10 patients, repair in 6 and TV replacement in 4. TV was repaired by commissurotomy, annuloplasty or valvuloplasty, or combination of them. When residual significant tricuspid regurgitation (TR) and/or stenosis (TS) was detected by intraoperative pulsed Doppler echocardiography after reparative procedures, TV was replaced. Follow-up periods ranged from 1 to 12 years (mean, 45.3 months). There was no early death, and late death was noted in one patient 32 months after operation. Preoperatively, 7 patients were in NYHA class IV and 3 in class III. Out of survivors, 7 are in class I and 2 in class II because of progression of mitral stenosis or coronary artery disease. Following surgery, the patients exhibited significant decrease in the cardiothoracic ratio (69.3 +/- 7.2 to 56.9 +/- 6.4%; p less than 0.01) and in the mean right atrial pressure (11.4 +/- 3.6 to 8.6 +/- 3.1 mmHg; p less than 0.05). The postoperative right ventriculography showed mild to moderate TR in 3 of 6 patients who underwent TV repair. In conclusion, TV repair could be a reasonable procedure for the organic TV lesions, although careful follow-up is recommended for residual TR.     

Cross-sectional study of allergic disorders associated with breastfeeding in Japan: The Ryukyus Child Health Study

Uncertainties remain as to whether breastfeeding is protective against childhood allergic disorders. Positive relationships of breastfeeding with asthma and atopic eczema were observed in two previous Japanese studies. This cross-sectional study investigated the association between the feeding pattern after birth and the prevalence of allergic disorders during the past 12 months in Japanese schoolchildren. Study subjects were 24,077 children aged 6-15 yr in Okinawa. The outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Allowance was made for age, sex, number of siblings, smoking in the household, paternal and maternal history of asthma, atopic eczema, and allergic rhinitis, and paternal and maternal educational level. Breastfeeding, regardless of exclusivity, for 13 months or longer and exclusive breastfeeding for 4-11 months were independently associated with a higher prevalence of atopic eczema, particularly among children without a parental allergic history. A clear positive dose-response relationship was observed between prolonged duration of breastfeeding, regardless of exclusivity, but not exclusive breastfeeding, and the prevalence of atopic eczema. We found a significant positive trend for atopic eczema across the three categories (formula milk, partial and exclusive breastfeeding) in the first 4 months of life although the odds ratio for exclusive breastfeeding was not statistically significant. No material association was found between the feeding pattern after birth and the prevalence of wheeze or allergic rhinoconjunctivitis. Prolonged breastfeeding may be associated with a higher prevalence of atopic eczema in Japanese children.     

Identification and viability assessment of dermatophytes infecting nail based on quantitative PCR of dermatophyte actin (ACT) mRNA]

The diagnosis and choice of treatment for dermatophytoses are usually based on the result of microscopic observation of hyphal elements and culture. However, false negative cultures have sometimes been encountered and appropriate timing of discontinuation of treatment has not been formulated. In this study, we attempted the identification and viability assessment of dermatophytes based on the quantitative measurement of dermatophyte actin (ACT) mRNA. An internal fragment of the ACT, 725 to 762 bp, was isolated by PCR from the genomic DNA of dermatophytes and sequenced. ACT intron-based primers were dermatophyte species-specific and primer pairs crossing the intron were dermatophyte genus-specific. The LightCycler (LC) instrument, employing the two-step RT-PCR/fluorescent hybridization system, was used to quantify the actin mRNA (ACT) of dermatophytes. A 669 bp ACT cDNA fragment was used as a quantification standard. Several mg of samples were collected from skin scales or nail plates before and after the treatment using oral terbinafine. The results indicated that quantification of ACT mRNA correlated with the results of culture and KOH examination and that copy numbers of dermatophyte ACT mRNA per mg sample decreased with progression of the therapy. This method comprises a sensitive (1 fg), specific, rapid (< 4 h) and quantitative assessment of the viability and identification of dermatophytes in skin tissue.     

Penicillamine-Induced Degenerative Dermatoses: Report of a Case and Brief Review of Such Dermatoses

We describe a case of elastosis perforans serpiginosa with additional findings of degenerative skin changes. A 20-year-old man with hepatolenticular degeneration, under prolonged treatment with D-penicillamine, presented with a circular or serpiginous arrangement of nuchal papules. Histopathologically, transepidermal channels were accompanied by granulomatous reactions, with several giant cells engulfing elastic fibers. In addition to these findings of a typical elastosis perforans serpiginosa, we observed scar-like skin changes inside the circular arrangement of the papules. At the scar-like tissue, we found electron-microscopical evidence of randomly aggregated thin collagen fibers with no tendency toward systemic combined bundle formation, which is a characteristic feature of normal collagen fiber formation. Pseudoxanthoma-elasticum-like changes were observed on his neck. On his axillae and groin, slight skin thickening and wrinkling were detected. The diagnosis of elastosis perforans serpiginosa does not represent all of the manifestations or the pathological background described above. The skin manifestations described here represent not only an elastosis but also a total degenerative dermatosis with over-healed collagenosis. Thus, those dermatoses should be summarized as one entity, penicillamine-induced degenerative dermatosis. After considering the pathogenic background and clinical similarities, we further propose to simplify the penicillamine-induced skin manifestations to three categories: acute sensitivity reactions, bullous dermatoses, and degenerative dermatoses.     

Coexistence of cerebral aneurysm and angiographically occult AVM in the occipital lobe; a case report]

The authors report a case of an 8-year-old boy with coexistent aneurysm and arteriovenous malformation (AVM) at the periphery of the left middle cerebral artery. The patient was referred to our hospital because of intracerebral hematoma in the occipital lobe. Angiography revealed an aneurysm at the periphery of the left middle cerebral artery. A small AVM was found, adjacent to the aneurysm, by histological examination of the aneurysm and surrounding tissue resected by surgery. The patient was discharged uneventfully 17 days after surgery. The association of intracranial aneurysm with AVM is reported to be seen in 1.4% of patients with intracranial aneurysms, and 6.4% to 16.7% of patients with an intracranial AVM. Three hypotheses have been proposed in order to explain the association of an aneurysm with AVM: (1) Congenital multiple disorders of vascular development, (2) Hemodynamic stress resulting from the presence of an AVM, (3) Coincidence without any causal relationship between them. The coexistence of the two vascular lesions, adjacent to each other at the peripheral cerebral arteries is rare. Only 7 cases have been reported in the literature. Four of the 8 cases including ours were children, and 6 of the 8 cases were thought to have had a hemorrhage from the AVM. It is likely that the coexistence of the two lesions in our patient is of congenital origin, because the influence of hemodynamic stress from the AVM seemed little and coexistence of the lesions as found in our case is more frequently seen in childhood.     

Lymphatic drainage of the gallbladder

Based upon detailed dissections of the lymphatic system in adult cadavers, the lymphatic drainage of the gallbladder was divided into three pathways: (1) The cholecystoretropancreatic pathway, which had two routes, one running spirally from the anterior surface of the common bile duct to the right rear, and the other running almost straight down from the posterior surface of the common bile duct. These routes converged at the principal retroportal node at the posterior surface of the head of the pancreas. (2) The cholecysto-celiac pathway; this was the route running to the left through the hepatoduodenal ligament to reach the celiac nodes. (3) The cholecysto-mesenteric pathway; this was the route running to the left in front of the portal vein to connect with the nodes at the superior mesenteric root. The cholecysto-retropancreatic pathway can be regarded as the main pathway, and the principal retroportal node appeared to be critical as the main terminal node in the visceral lymphatic system of the gallbladder. These three pathways converged with the abdomino-aortic lymph nodes near the left renal vein, and the nodes in the interaortico-caval space were considered to be of particular importance. Offprint requests to: M. Ito     

A case of mixed connective tissue disease successfully treated for hemophagocytic syndrome with intermittent intravenous injection of cyclophosphamide]

A 52 year-old woman noticed general fatigue, polyarthralgia, and muscle weakness of lower extremities in October 2001. In December, she felt difficulty in walking due to muscle weakness. In January 2002, she admitted another hospital because of dyspnea on exertion and edema of lower extremities. Laboratory test revealed leukocytopenia, the elevation of creatine kinase and positive anti-U1-RNP antibodies. Her chest computed tomography (CT) showed severe interstitial pneumonia. Cardiac echogram revealed that she had pericardial effusion and pulmonary hypertension. Then she was transferred to Keio University Hospital and she was diagnosed as having mixed connective tissue disease (MCTD) manifestating myositis, interstitial pneumonia, pulmonary hypertension and pericarditis. Prednisolone (PSL) 60mg daily following to methylprednisolone (mPSL) pulse therapy was begun and her symptoms were gradually improved. In middle of February, she complained of high fever over 39.0 degrees C. Bacterial culture tests were negative and laboratory data indicated pancytopenia and a high level of serum ferritin. Bone marrow aspiration revealed hemophagocytosis in bone marrow specimens and she was diagnosed as having hemophagocytic syndrome associated with MCTD. mPSL pulse therapy was not effective and intermittent cyclophosphamide pulse therapy (IV-CY) was performed resulting in improvement of the symptoms. This case suggested the effectiveness of IV-CY therapy in patients with corticosteroid-resistant HPS associated with connective tissue diseases.     

Angiotensin I-converting enzyme inhibitor improves reactive hyperemia in elderly hypertensives with arteriosclerosis obliterans.

Endothelial function in elderly hypertensive patients with arteriosclerosis obliterans has not been evaluated. We examined whether antihypertensive drugs improve vasodilatory response to reactive hyperemia of the limbs in elderly hypertensive patients (83 +/- 8 [SD] years) without (n=46, 0.9 < or = ankle-brachial pressure index < or = 1.4) and with (n=24) arteriosclerosis obliterans (ankle-brachial pressure index < 0.2). Patients were randomized for treatment with monotherapy of either temocapril (14 with and 26 without arteriosclerosis obliterans) or amlodipine (10 with and 20 without arteriosclerosis obliterans) for 6 months. Blood flows of the forearms and legs were measured by strain-gauge plethysmography. The vasodilatory response to the release of compression of the forearms and thighs at 200 mmHg or 20 mmHg more than systolic blood pressure for 5 min and to sublingual administration of nitroglycerin (0.3 mg) was assessed. The maximum reactive hyperemic flow in 35 legs with arteriosclerosis obliterans was significantly (p < 0.001) decreased compared to the value in legs in the control hypertensive subjects. Moreover, maximum reactive hyperemic flow in the forearms of patients with arteriosclerosis obliterans was significantly (p = 0.002) decreased compared to that in the control subjects. Blood pressure was similarly decreased by treatment with temocapril or amlodipine. Response to nitroglycerin (0.3 mg) was not changed by either drug. Treatment with temocapril significantly improved maximum reactive hyperemic flow of not only the legs and forearms in control hypertensives but also the legs and forearms in patients with arteriosclerosis obliterans, and attenuated the worsening of activity of daily living in these patients, although treatment with amlodipine did not. These results suggest that the angiotensin-converting enzyme inhibitor temocapril has a beneficial effect on endothelial function in elderly patients with arteriosclerosis obliterans.