HDlive imaging of intra-amniotic umbilical vein varix with thrombosis.

We present a case of intra-amniotic umbilical vein varix with thrombosis using conventional two-dimensional (2D) sonography, power Doppler, three-dimensional (3D) HD-flow, and HDlive at 35 weeks of gestation. 2D sonography showed a large banana-like umbilical cord enlargement (100 × 43.3 × 45.9 mm) including umbilical vein varix (maximum vein diameter = 25.5 mm) with massive thrombosis. Power Doppler and 3D HD-flow revealed bidirectional turbulent blood flow inside the varix. The HDlive clearly demonstrated fragile massive thrombosis inside the varix. Elective cesarean section was performed on the same day in order to avoid additional risks of umbilical cord complications and umbilical venous embolism. A male infant weighing 2501 g was delivered with an umbilical artery pH of 7.334, and Apgar score of 8/9 at 1 and 5 min, respectively. The macroscopic and microscopic findings revealed umbilical cord vein varix with thrombosis. On the basis of the laboratory date of the neonate, the diagnosis of consumptive coagulopathy was made. However, the neonate followed a favorable course after delivery.

Aldosterone: a mediator of retinal ganglion cell death and the potential role in the pathogenesis in normal-tension glaucoma.

Glaucoma is conventionally defined as a chronic optic neuropathy characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve fibers. Although glaucoma is often associated with elevated intraocular pressure (IOP), significant IOP reduction does not prevent progression of the disease in some glaucoma patients. Thus, exploring IOP-independent mechanisms of RGC loss is important. We describe chronic systemic administration of aldosterone and evaluate its effect on RGCs in rat. Aldosterone was administered via an osmotic minipump that was implanted subcutaneously into the mid-scapular region. Although systemic administration of aldosterone caused RGC loss associated with thinning of the retinal nerve fiber layer without elevated IOP, the other cell layers appeared to be unaffected. After chronic administration of aldosterone, RGC loss was observed at 2 weeks in the peripheral retina and at 4 weeks in the central retina. However, administration of mineralocorticoid receptor blocker prevented RGC loss. These results demonstrate aldosterone is a critical mediator of RGC loss that is independent of IOP. We believe this rat normal-tension glaucoma (NTG) animal model not only offers a powerful system for investigating the mechanism of neurodegeneration in NTG, but can also be used to develop therapies directed at IOP-independent mechanisms of RGC loss.

EVI-1 interacts with histone methyltransferases SUV39H1 and G9a for transcriptional repression and bone marrow immortalization.

The ecotropic viral integration site-1 (EVI-1) is a nuclear transcription factor and has an essential function in the proliferation/maintenance of haematopoietic stem cells. Aberrant expression of EVI-1 has been frequently found in myeloid leukaemia as well as in several solid tumours, and is associated with a poor patient survival. It was recently shown that EVI-1 associates with two different histone methyltransferases (HMTs), SUV39H1 and G9a. However, the functional roles of these HMTs in EVI-1-mediated leukemogenesis remain unclear. In this study, we showed that EVI-1 physically interacts with SUV39H1 and G9a, but not with Set9. Immunofluorescence analysis revealed that EVI-1 colocalizes with these HMTs in nuclei. We also found that the catalytically inactive form of SUV39H1 abrogates the transcriptional repression mediated by EVI-1, suggesting that SUV39H1 is actively involved in EVI-1-mediated transcriptional repression. Furthermore, RNAi-based knockdown of SUV39H1 or G9a in Evi-1-expressing progenitors significantly reduced their colony-forming activity. In contrast, knockdown of these HMTs did not impair bone marrow immortalization by E2A/HLF. These results indicate that EVI-1 forms higher-order complexes with HMTs, and this association has a role in the transcription repression and bone marrow immortalization. Targeting these HMTs may be of therapeutic benefit in the treatment for EVI-1-related haematological malignancies.

AML1-Evi-1 specifically transforms hematopoietic stem cells through fusion of the entire Evi-1 sequence to AML1.

The t(3;21) chromosomal translocation seen in blastic crisis of chronic myeloid leukemia and secondary leukemias results in a formation of a chimeric protein AML1-Evi-1, which suppresses wild-type AML1 function. Loss of AML1 function causes expansion of hematopoietic progenitor cells, whereas it is not sufficient for the development of leukemia. To identify essential mechanisms through which AML1-Evi-1 exerts full leukemogenic potential, we introduced AML1-Evi-1 and its mutants in murine bone marrow cells, and evaluated their transforming activities by colony replating assays. The transforming activity of AML1-Evi-1 was lost when any of the known functional domains of Evi-1 was deleted from the chimeric protein, and forced expression of Evi-1 did not transform the AML1-deleted bone marrow cells. Unlike the MLL-ENL and AML1-ETO leukemia-related chimeric proteins, AML1-Evi-1 could transform only the hematopoietic stem cell fraction. Moreover, AML1-Evi-1-transformed cells show a cell-marker profile distinct from that of the cells transformed by AML1-ETO, which also suppresses AML1 function. Thus, leukemogenic activity of AML1-Evi-1 may be due to activation of molecular mechanisms distinct from those activated by MLL-ENL or AML1-ETO in the hematopoietic stem cell fractions.

A high incidence of late-onset neutropenia following rituximab-containing chemotherapy as a primary treatment of CD20-positive B-cell lymphoma: a single-institution study.

BACKGROUND: Late-onset neutropenia (LON) has been reported following rituximab-containing chemotherapy. Its incidence and risk factors, however, have not been extensively studied. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 107 patients treated with rituximab-containing chemotherapy as a primary treatment of CD20-positive B-cell lymphomas and identified cases with LON as defined by the neutrophil count of

Role of mastication and swallowing in the control of autonomic nervous activity for heart rate in different postures.

Mastication and swallowing increase the heart rate, and posture change and respiration also modulate the heart rate. To clarify the role of mastication and swallowing in the modulation of the autonomic nervous activity, we investigated how they interact with modulation of the heart rate by changing body positions and respiration in young healthy subjects. R-R intervals of electrocardiogram at rest were significantly changed with different body positions, compared with supine and standing. A net shortening by mastication of a chewing gum base was similar in various postures. Respiration induced a periodic change in the R-R intervals, depending on the body postures, but mastication did not markedly change them in each posture. Dry swallowing at rest and spontaneous swallowing during the mastication in the sitting position induced a similar transient shortening and suppressed the respiration-induced changes after the swallowing. The net transient shortening by dry swallowing at rest was similar in the different postures. These results suggest that signals from mastication and swallowing are summated with those from body positions and respiration for shortening the R-R intervals and that signals from swallowing suppress the respiration-induced periodic changes.

Evaluation of mastication-induced change in sympatho-vagal balance through spectral analysis of heart rate variability.

Mastication modulates the autonomic nervous activity of the digestive glands and the heart. The autonomic nervous balance is evaluated with spectral analysis of heart rate variability. In the present study, we investigated the effects of mastication of chewing gum base on heart rate variability to clarify the role of mastication in the sympatho-vagal balance for the regulation of the heart rate. Mastication of a chewing gum base stimulated the salivary secretion and shortened the R-R intervals in the electrocardiogram of healthy young subjects without swallowing of saliva at a fixed rate of respiration. Based on the analysis of heart rate variability, mastication increased the low-frequency band spectral power (LF), and decreased the high-frequency band spectral power (HF). The LF/HF was markedly increased by the mastication. Mastication enhances the sympathetic nervous activity and/or suppresses the parasympathetic nervous activity for the heart. Feeding behaviour with mastication might play a role in the modulation of the autonomic nervous activity.

Homozygosity and linkage disequilibrium mapping of autosomal recessive distal myopathy (Nonaka distal myopathy).

Autosomal recessive distal myopathy or Nonaka distal myopathy (NM) is characterized by its unique distribution of muscular weakness and wasting. The patients present with spared quadriceps muscles even in a late stage of the disease. The hamstring and tibialis anterior muscles are affected severely in early adulthood. We have localized the NM gene to the region between markers D9S319 and D9S276 on chromosome 9 by linkage analysis. To further refine the localization of the NM gene, we conducted homozygosity and linkage disequilibrium analysis for 14 patients from 11 NM families using 18 polymorphic markers. All of the patients from consanguineous NM families were found to be homozygous for six markers located within the region between markers D9S2178 and D9S1859. We also provided evidence for significant allelic associations between the NM region and five marker loci. Examination of the haplotype analysis identified a predominant ancestral haplotype comprising the associated alleles 199-160-154-109 (marker order: D9S2179-D9S2180-D9S2181-D9S1804), present in 60% of NM chromosomes and in 0% of parent chromosomes. On the basis of the data obtained in this study, the majority of NM chromosomes were derived from a single ancestral founder, and the NM gene is probably located within the 1.5-Mb region between markers D9S2178 and D9S1791.

[A case of ipsilateral ageusia, sensorineural hearing loss and facial sensorimotor disturbance due to pontine lesion].

We report a 58-year-old woman with pontine lesion presented with subacute onset of unilateral gustatory disturbance accompanied by facial numbness, and hearing loss. Neurologic examination revealed superficial hypesthesia and paresthesia on the right side of the face, right peripheral type facial paresis, ageusia on the right half of the tongue and right sensorineural deafness. No other neurologic signs were observed, and laboratory data were all normal. Brain MRI revealed a small lesion in the right dorsolateral tegmentum of the middle pons. Electrogustometry showed marked reduction in the sense of taste on the right half of the tongue. ABR showed diminished amplitude in the IV-V wave of the right side, while SEP and VEP were normal. The clinical diagnosis was demyelinating lesion and intravenous methylprednisolone (1 g/day) was administered for 3 consecutive days, resulting in prompt improvement in the symptoms. The lesion was suspected of affecting ipsilateral side of the spinal trigeminal nerve tract and the nucleus, the intraaxial infranuclear facial nerve fiber, the lateral lemniscus adjacent to the superior olivary nucleus and the central gustatory tract. Our case suggests that the central gustatory pathway projecting from the nucleus of the solitary tract to the parabrachial nucleus, presumed to be pontine taste area, ascends ipsilaterally and is located laterally from the medial lemniscus.

[Pontine hemorrhage presenting with Foville syndrome and transient contralateral hyperhidrosis].

This report concerns a 88-year-old diabetic and hypertensive woman with pontine hemorrhage who presented with Foville syndrome and contralateral hyperhidrosis. She was admitted to our hospital for sudden onset of headaches and disturbed consciousness. Neurologic examination revealed bilateral miosis, Foville syndrome and superficial hemianesthesia on the right side of the face and body. No associated Horner syndrome and other autonomic dysfunction were observed. Laboratory data were normal except for diabetic findings. Brain CT and MRI revealed a hematoma in the left side at the lower pons. One month after the onset, hemihyperhidrosis on the face, arm and upper trunk contralateral side of the lesion appeared abruptly, and gradually disappeared a week later. Sweating on the ipsilateral side was normal and no new lesion was seen on the brain CT then. Only a few cases of contralateral hyperhidrosis due to pontine lesion have been reported. We suggest that the contralateral inhibitory sweating pathway was disrupted though the ipsilateral excitatory one was intact. Contralateral hyperhidrosis attributed to imbalance of the perspiratory control can be observed in the subacute or late phase after pontine hemorrhage.

[Diagnostic muscle MRI abnormality in a patient with inclusion body myositis].

A 64-year-old woman was admitted to our hospital because of muscle weakness and atrophy in the extremities. Four years before admission, he was noticed to have elevated creatine kinase (CK) level, but had no further evaluation. Two years later, she became difficult in standing up and needed a wheelchair. Six months before admission, she noticed muscle wasting in the buttock, thigh, bilateral forearms, and weakness in the upper limbs. On neurologic examination, she had weakness in sternocleidomastoid and all limb muscles, predominantly in the distal portion of the upper extremities. Laboratory study revealed elevated CK, LDH, and aldolase levels, and myogenic change with fibrillation on needle EMG. Muscle biopsy showed myopathic changes with infiltration of mononuclear cells and rimmed vacuoles. The clinical manifestations as well as poor response to corticosteroids therapy were supportive of the diagnosis of inclusion body myositis. However, the distribution of muscle weakness in her wrist, weaker in the extensors than in the flexors, was not characteristic to IBM. This problem was solved by the right forearm MRI which showed a high signal intensity area in flexor muscles, but not in extensors on T1 and T2 weighted images. Accordingly, the muscle MRI of forearm was a diagnostic aid of IBM in this patient.

Hemiballism-hemichorea from marked hypotension during spinal anesthesia.

Hemiballism and hemichorea following anesthesia-induced hypotension has rarely been described, but a recent case suggests an association. After experiencing marked hypotension during spinal anesthesia, a 70-year-old woman developed hemiballism and hemichorea. Involuntary ballistic movements with writhing, consisting of repetitive rotation and flexion-extension without apparent muscle weakness, affected her left limbs proximally. Low-amplitude, involuntary, choreiform movements involved the distal portions of these limbs. Magnetic resonance imaging demonstrated an area of high signal intensity in the contralateral subthalamic nucleus, suggestive of a focal ischemic lesion. Although such occurrences are rare, anesthesiologists should be aware of the risk of subthalamic nucleus ischemia following marked hypotension.

[Late-onset adrenomyeloneuropathy perplexed with spondylosis. A case report].

We reported a 60-year-old man with late-onset adrenomyeloneuropathy (AMN). He had been well until 10 years before entry, when he noticed numbness in the legs with gait difficulty; symptoms worsened gradually with additional urinary disturbance. Transient improvement occurred after cervical and lumbar spinal operation under the diagnosis of spinal spondylosis, while his spastic gait got worse. Neurological examination on admission disclosed bilateral horizontal nystagmus, ataxic and spastic gait, increased patellar tendon reflexes, Chaddock sign, and impaired deep sense in the lower limbs with positive Romberg sign. Abnormal laboratory data included hypofunction of the adrenal cortex and elevated saturated very long chain fatty acids (VLCFAs). Serum cholestanol level was normal and anti-HTLV-1 antibody was negative. T2-weighted MRI showed a high signal intensity lesion in the occipital white matter along the optic radiation. Electrophysiological tests suggested a brainstem lesion on auditory brainstem response, thoracic or lumbar lesion on somatosensory evoked potential, and peripheral neuropathy on nerve conduction study. In the present case, it should be emphasized that the determination of serum VLCFAs unveiled the diagnosis of AMN in old patients with spinal spondylosis or without apparent clinical symptoms of adrenocortical insufficiency.

Tuberculous tenosynovitis in the elbow joint.

A 74-year-old woman was noted to have a mass lesion near the right elbow joint during medication for pulmonary tuberculosis. After discontinuation of medication, the mass gradually became enlarged with swelling and tenderness of the joint. Radiological evaluation disclosed tenosynovitis with an encapsulated abscess. Microscopic examination and culture of an aspiration biopsy specimen from the abscess showed no microorganisms. However, DNA extracted from the specimen contained mycobacterium tuberculosis DNA, permitting a diagnosis of tuberculous tenosynovitis. Mycobacterium is not always detected in biopsy specimens of tuberculous arthritis and tenosynovitis. In such cases, genetic diagnosis may be of great use.

Germanium intoxication with sensory ataxia.

Sensory ataxia in inorganic germanium intoxication is rare. A 63-year-old housewife had taken inorganic germanium preparations at a dosage of 36 mg a day for about 6 years (total dose about 80 g). She subsequently developed difficulty in writing and gait disturbance with peripheral neuropathy and renal involvement. Germanium, which is not usually detected in the non-germanium user, was accumulated in her hair and nails, permitting a diagnosis of inorganic germanium intoxication. The peripheral neuropathy and renal injury were not reversible after discontinuing the preparation. Pneumonia and sepsis then supervened and the patient died. Autopsy findings showed degeneration and loss of the dorsal root ganglion cells and degeneration of the dorsal column of the spinal cord. Two previously reported cases presented with ataxia. These patients took germanium for long periods and/or large quantities like our case. It was supposed that sensory ataxia was induced by chronic and dose dependent toxicity of inorganic germanium.

[Auditory disturbance induced by carbamazepine administration in a patient with secondary generalized seizure].

We report on an 18-year-old woman with secondary generalized seizure, who developed an auditory disturbance (flat a tone) after carbamazepine (CBZ) administration. She used to have brief episodes of conjugate deviation of the eyes to the right, head heaviness, teleopsia, and visual hallucination since 16 years of age. At the age of 18 years, she developed a tonic-clonic seizures during sleep, and was placed on CBZ 400 mg/day. Immediately after taking the medication, she developed auditory disturbance while she played the musical instruments: she felt as if she played the musical note almost a half tone lower. On admission, neurological examinations and magnetic resonance images of the brain were normal. Electroencephalogram at rest was normal. However, intravenous diphenhydramine injection induced spikes in the left temporo-occipital region, followed by diffuse spike and wave complex. Although the serum CBZ level was reduced to the therapeutic level by lowering CBZ administration from 200 to 150 mg/day, she continued to have the same auditory disturbance. When CBZ administration was discontinued, the symptoms also disappeared. It remains unknown whether such a subtle side effect of CBZ is a common thing, or it can be recognized only by persons who are well trained in music.