Intractable hiccup and nausea in neuromyelitis optica with anti-aquaporin-4 antibody: a herald of acute exacerbations.

BACKGROUND: Intractable hiccup and nausea (IHN) are unique symptoms in neuromyelitis optica (NMO). Recent studies have strongly suggested that the pathogenesis of NMO is closely associated with anti-aquaporin-4 (AQP4) antibody. However, clinical implications of IHN and the relationship with anti-AQP4 antibody remain unknown. METHODS: The past medical records of 35 patients with seropositivity for anti-AQP4 antibody were reviewed. We also followed the titres of anti-AQP4 antibody in a patient with NMO, who had newly developed IHN. RESULTS: Of the 35 patients, 15 patients (43%) had episodes of IHN. There was a total of 35 episodes of IHN in these 15 patients and, of the 35 episodes, hiccup was seen in 23 episodes (66%) and nausea was seen in 28 episodes (80%). The IHN frequently preceded (54%) or accompanied (29%) myelitis or optic neuritis. The IHN was often preceded by an episode of viral infection. The titres of anti-AQP4 antibody were remarkably increased when the intractable hiccup appeared in a case. CONCLUSIONS: IHN could be a clinical marker for the early phase of an exacerbation. Careful observation may be needed when INH is seen in patients with NMO, and the early initiation of the treatment could prevent subsequent neurological damage.

Elemental diet modulates the growth of Clostridium difficile in the gut flora.

BACKGROUND AND AIMS: Tube feeding is regarded as a risk factor for Clostridium difficile-associated diarrhoea. Recently, we reported that C. difficile toxin was frequently found in patients receiving an elemental diet. The present study was conducted to clarify whether elemental diets are associated with the growth of C. difficile in the gut flora. METHODS: C. difficile was cultured for 72 h in various concentrations of elemental diet containing 3% thioglycollate, and the growth rate or activity of C. difficile was evaluated by Gram stain or by measuring optical density at 560 nm. Faecal samples from 10 healthy adults were cultured in elemental diet + 3% thioglycollate. RNA was extracted from faeces with glass powder, which can eliminate PCR inhibitors, and mRNA of C. difficile toxin B was measured by reverse transcription PCR. RESULTS: Maximum OD560 value during culture in thioglycollate-containing elemental diet was 2.4 times higher than that in thioglycollate alone (P = 0.0163). Viability of C. difficile was decreased in thioglycollate but not in thioglycollate-containing elemental diet. Toxin B mRNA was detected in five faecal samples (50%) before culture and in all samples after culture. CONCLUSIONS: Our results suggest that an elemental diet can modulate the growth of C. difficile in the gut flora.

Attenuated nuclear shrinkage in neurones with nuclear inclusions of SCA1 brains.

BACKGROUND: Spinocerebellar ataxia type 1 (SCA1) is one of the autosomal dominant neurodegenerative disorders commonly linked to pathological expansion of the CAG repeat of the relevant gene. Nuclear inclusions and neurodegeneration are both triggered by this pathological expansion of the CAG/polyglutamine repeat on ataxin-1, but it remains to be determined whether or not nuclear inclusion formation is associated with accelerated neurodegeneration. OBJECTIVE: To examine the influence of nuclear inclusions on nuclear size and deformity in human brains from patients suffering from SCA1. MATERIAL: Pontine sections of brains obtained at necropsy from seven patients with SCA1 and five controls. METHODS: The size and deformity of each neuronal nucleus was quantified. Nuclei with and without inclusions were examined separately to assess the possible influence of nuclear inclusions on neurodegeneration. RESULTS: Nuclear shrinkage and deformity were more marked in SCA1 brains than in controls. This shrinkage was attenuated in neurones containing nuclear inclusions. CONCLUSIONS: The existence of nuclear inclusions in SCA1 is presumably linked to a mechanism that attenuates rather than accelerates nuclear shrinkage. This in vivo finding may provide a clue to constructing a rational therapeutic strategy for combating neurodegeneration associated with nuclear inclusions.

Arthroscopic diagnosis of tibiofibular syndesmosis disruption.

PURPOSE: We have been able to diagnose tibiofibular syndesmosis injury by ankle arthroscopy, and in the present study we compare these results with the results from plain radiographs. TYPE OF STUDY: Case series. METHODS: Thirty-eight type-B (Weber system) distal fibular fractures in 38 patients were diagnosed to determine whether tibiofibular syndesmosis disruption was present. According to the Lauge-Hansen system, 16 patients had supination-external rotation fractures and 22 had pronation-abduction fractures. Standard non-weight-bearing anteroposterior radiographs and mortise radiographs were evaluated. Furthermore, ankle arthroscopy was performed on all patients. RESULTS: Tibiofibular syndesmosis disruptions were diagnosed in 16 of the 38 patients (42%) by anteroposterior radiography, 21 of 38 patients (55%) by mortise radiography, and 33 of 38 patients (87%) by ankle arthroscopy. All of the patients who were diagnosed with tibiofibular syndesmosis disruption by anteroposterior radiography and mortise radiography were also confirmed by ankle arthroscopy to have injured their tibiofibular syndesmosis. In 12 patients, ankle arthroscopy was the only method used to diagnose the tibiofibular syndesmosis disruption. CONCLUSIONS: Ankle arthroscopy excels in term of the diagnosis ratio for tibiofibular syndesmosis disruption compared with both anteroposterior and mortise radiography. Therefore, we conclude that ankle arthroscopy is necessary for the correct diagnosis of tibiofibular syndesmosis disruption.

Staphylococcus aureus in inflammatory bowel disease.

BACKGROUND: The potential role of superantigens in inflammatory bowel disease (IBD), particularly Crohn disease, has been broached in studies of the functions of T cell receptors. Staphylococcal cells have been found in intestinal lymph follicles of IBDs. To clarify a role of staphylococcal superantigens in IBD, we attempted to determine whether Staphylococcus aureus could be detected in intestinal mucosa, including surgical specimens and lymph follicles of initial cases. METHODS: One-hundred-and-six colonic and ileal specimens were obtained from 38 Crohn disease, 25 ulcerative colitis and 36 non-IBD patients through therapeutic surgery or endoscopic biopsy. In Crohn disease, 23 surgical specimens and 11 biopsy specimens from initial cases were included. DNA was extracted with phenol-chloroform after homogenization and proteinase K treatment in 73 mucosal specimens. Using an inverted microscope, lymph follicle tissue was microdissected from the remaining 33, mostly biopsy, specimens. DNA was then extracted by freeze-thawing. A coagulase gene characteristic of S. aureus was sought. A nested polymerase chain reaction was performed utilizing primers that amplify a region of the coagulase gene. Polymerase chain reaction products were analyzed with polyacrylamide gel electrophoresis. RESULTS: Only one surgically resected colonic specimen, from a 42-year-old male ulcerative colitis patient, registered positive staphylocoagulase amplification. CONCLUSIONS: Staphylococcal superantigens are not involved in either the early lesions or the established lesions of Crohn disease. However, S. aureus infection occasionally may occur during the course of IBD.

Current concepts in tissue engineering technique for repair of cartilage defect.

Hunter's observation in 1743 that cartilage "once destroyed, is not repaired," has not essentially changed for 250 years. At present, there is no well-established procedure for the repair of cartilage defect with articular cartilage, which has the same biochemical and biomechanical properties as the surrounding normal intact cartilage. In 1994, transplantation of human autologous chondrocytes in suspension, as reported by Brittberg et al., provided a potential procedure for articular cartilage repair. We have improved their procedure and developed a new technique which creates new cartilage-like tissue by cultivating autologous chondrocytes embedded in Atelocollagen gel for 3 weeks before transplantation. These improvements maintained the chondrocyte phenotype, evenly distributed chondrocytes throughout the osteochondral defects, and decreased the risk of leakage of grafted chondrocytes into the defects. Good clinical results suggest that this technique should be a promising procedure for repairing articular cartilage defect.

A case of superficial peroneal nerve injury during ankle arthroscopy.

We report a case of superficial peroneal nerve (SPN) injury caused by ankle arthroscopy. A 20-year-old woman underwent arthroscopy on her right ankle because of chronic ankle pain after a sprain. After arthroscopy, the patient complained of pain on the dorsum of her right foot and felt a radiating pain from the anterolateral portal to the dorsomedial aspect of her foot. Eight months after arthroscopy, we found that a neuroma had developed on the intermediate dorsal cutaneous nerve, and performed neurolysis of the SPN. Her symptoms gradually decreased after surgery, and had disappeared by 45 months. To avoid such an injury of the SPN, the safest placement of the anterolateral portal is necessary and is, according to our previous anatomic study, 2 mm lateral to the peroneus tertius tendon.

Proprioceptive improvement in knees with anterior cruciate ligament reconstruction.

The correlation between the prospective course of proprioceptive improvement and knee stability after anterior cruciate ligament reconstruction was investigated in 38 patients. Proprioception, on the basis of the patient's capacity to reposition the limb accurately, was evaluated at 3-month intervals for 24 months after hamstring graft anterior cruciate ligament surgery. Knee stability was evaluated concurrently with a KT-2000 knee arthrometer. Thirty patients experienced improvement in postoperative position sense in at least one of the examinations, although eight patients had no improvement at any time. Of the 30 patients who had improvement, 28 maintained improved position sense from 18 months to the final followup. Thirty patients maintained significantly better knee stability for a postoperative period of at least 24 months. These results indicated that a minimum of 18 months after anterior cruciate ligament reconstruction may be needed for complete restoration of the proprioceptive function in knees, although the mean position sense in all patients gradually improved from 9 months. Improvement in postoperative knee stability may have facilitated recovery of proprioception.

DNA single-strand breaks are increased in muscle diseases with rimmed vacuoles.

Some pathological similarities between Alzheimer's disease and muscle diseases with rimmed vacuoles (RV) have been pointed out. For example, several pathological hallmark proteins have been reported to be immunopositive in the lesions of both diseases. Since apoptotic processes or primary DNA damage are suggested to play a role in the pathomechanism of Alzheimer's disease, we examined DNA double-strand breaks (DSB) and single-strand breaks (SSB) in the muscle biopsy specimens of several diseases, including muscle diseases with RV. Although no DSB-positive myonuclei were detected in any muscles examined, the number of SSB-positive myonuclei markedly increased in the muscles from cases with polymyositis and muscle diseases with RV. In polymyositis, SSB-positive myonuclei were observed in regenerating fibers and muscle fibers in the vicinity of inflammatory infiltrates, suggesting that the increase of SSB is due to muscle fiber regeneration following necrosis and inflammation. In muscle diseases with RV, however, SSB-positive myonuclei were observed in small angulated fibers and in morphologically normal fibers, regardless of necrosis, regeneration or inflammation. These findings suggest that muscle diseases with RV may share a common pathological process involving DNA damage.

Repair of articular cartilage defects with cultured chondrocytes in Atelocollagen gel. Comparison with cultured chondrocytes in suspension.

We attempted to repair full-thickness articular cartilage defects in rabbit knee joints with allogeneic cultured chondrocytes embedded in Atelocollagen gel. An articular cartilage defect was created on the patellar groove of the femur. The defect was filled with chondrocytes cultured in the collagen gel and covered with periosteal flap (G group). In three other experimental groups, the same defects were transplanted with chondrocytes in monolayer culture with periosteal flap (M group), periosteal graft only (P group), or left empty (E group). At 4, 12, and 24 weeks after operation, the reparative tissue was analyzed macroscopically and histologically. At 4 weeks after operation, the surfaces of the reparative tissue were smooth, and the defects were filled with reparative tissues that resembled hyaline cartilage in all four groups. However, the reparative tissues degenerated gradually with time in the M, P, and E groups. In contrast, in the G group, the reparative tissue retained its thickness, and there was a steady integration of the grafted tissue into the adjacent normal cartilage at 24 weeks after operation. The results suggest that transplantation of allogeneic chondrocytes cultured in Atelocollagen gel is effective in repairing an articular cartilage defect.

Apraxia of single tool Use.

We report a 72-year-old right-handed man who showed an 'apraxia of tool use' after a cerebral infarct in the territory of the left middle cerebral artery. His apraxia of tool use was characterized by a clear dissociation between the inability to use a single tool and the ability to use plural tools. Most of the errors occurred in selecting an appropriate target where a tool is expected to be applied. Detailed examinations confirmed that his conceptual knowledge of tool use was well preserved. Furthermore, when a target of a tool was provided as a cue, he used a single tool correctly. These results suggest that his inability to use a single tool originated from his inability to evoke a target image from an actual tool.

[Two cases of fluent aphasia with selective difficulty of syllable identification].

We report two aphasic patients who could discriminate Japanese syllables but could not identify them. Case 1 was a 51-year-old right handed woman with 12-year education. Case 2 was a 50-year-old right handed man with 9-year education. They developed fluent aphasia after a cerebral infarction. Brain MRI of case 1 revealed widely distributed lesions including inferior frontal, superior temporal, angular and supramarginal gyri. Lesions revealed by Brain CT in case 2 included the left superior and middle temporal, angular and supramarginal gyri. Both showed severe impairment of repetition and confrontation naming. No difference of performance was present between repetition of single syllables and polysyllabic words. On the contrary, oral reading of Kana characters were preserved. We examined their ability to perceive syllables in detail. In the discrimination task, they judged whether a pair of heard syllables was same or different. Case 1 was correct in 85% of the tasks and case 2 in 98%. In an identification task, they heard a syllable and chose a corresponding Kana, Kanji, or picture out of 10 respective candidates. Case 1 was correct only in 30% and case 2 in 50% of these tasks. On the other hand, selection of a correct target in response to a polysyllabic word was much better, i.e. 70% in case 1 and 90% in case 2. Based on these data we concluded that (1) syllabic identification is a different process from syllabic discrimination, and (2) comprehension of a polysyllabic word can be achieved even when the precise phonological analysis of continuent syllables are impaired.

Bandage distraction technique for ankle arthroscopy.

In ankle arthroscopy, the joint space of the talocrural joint is often too narrow for insertion of the scope and instruments. Various distraction devices for this procedure have been used to widen the joint space. Bandage distraction is effective and noninvasive, but it is difficult to extend the posterior joint space sufficiently for insertion of the scope. Here we describe a new bandage distraction method that can extend the posterior joint space adequately. Using our method, the anterior and posterior joint spaces on direct lateral radiographs were measured after adding the distraction force in nine healthy volunteers (18 ankles; three men and 6 women). This was compared to a previously reported method. The posterior joint space was widened a greater amount when our new bandage distraction technique was used.

Saccadic ping-pong gaze.

Ping-pong gaze (PPG), or short-cycle periodic alternating gaze, consists of horizontal conjugate ocular deviations alternating every few seconds. This alternating gaze has been described as appearing to be smooth. However, our electrooculographic study of four consecutive unconscious patients with PPG showed smooth waveforms in one patient but saccadic cog-wheeling in three patients. In one of the three patients with saccadic PPG, a transition from smooth to saccadic waveforms was noted with clinical improvement. Whereas the patient with smooth PPG died immediately, the patients with saccadic PPG survived in a persistent vegetative state. These findings suggest that saccadic PPG is a clinical variant of PPG in patients in a lighter state of consciousness, possibly related to less extensive brain damage.

Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma.

Helicobacter pylori (HP) infection, a cause of multifocal atrophic gastritis, is considered an important factor related to the evolution of the human gastric mucosa from normal to intestinal-type adenocarcinoma. We examined cell proliferation and both double and single strand DNA damage in situ in 35 patients undergoing gastrectomy for adenocarcinoma with HP-infected gastric mucosa by immunolocalization of Ki-67, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, and in situ nick translation. We also studied the distribution of intraepithelial neutrophils by elastase immunolocalization. HP infection was confirmed in all cases by serum anti-HP antibodies, ureas testing, and histopathological examination. HP-infected gastric mucosa was classified according to the degree of inflammation and intestinal metaplasia. Ki-67, terminal deoxynucleotidyl transferase-mediated labeling, in situ nick translation, and intraepithelial neutrophil indices all increased with the progression of gastritis and were highest in glands with incomplete intestinal metaplasia. All indices were lowest in gastric glands with complete intestinal metaplasia. Significant positive correlations were observed among these markers. Increased proliferative activity in HP-associated chronic gastritis in response to cell damage or injury was clearly demonstrated, suggesting that both HP-associated toxins and intraepithelial neutrophils are important in HP-related gastric epithelial injury. Increased cell turnover associated with incomplete intestinal metaplasia may result in DNA instability and subsequent development of intestinal-type gastric adenocarcinoma in HP-infected mucosa.

A case of Marchiafava-Bignami disease with complete recovery: sequential imaging documenting improvement of callosal lesions.

Serial CT and MR imaging findings in a 44-year-old woman with Marchiafava-Bignami disease (MBD) are reported. In the acute stage, CT studies disclosed subtle hypodensity in the splenium, and T2-weighted MR images revealed apparent high signal intensity of the splenium and the central portion of the corpus callosum. Treatment with vitamin B complex resulted in complete recovery. T2-weighted MR images obtained three weeks after admission revealed dramatic resolution of imaging abnormalities, with only faint high signal intensity remaining in the splenium. The sequential changes observed on CT and MR images provided early diagnosis of MBD and the resolution of the lesion considered as brain edema, which suggested that edema might, in addition to demyelination or necrosis, be involved in the acute progression of MBD.

[Molecular epidemiological analysis of Pseudomonas aeruginosa by pulsed-field gel electrophoresis].

In order to see the nosocomial infection by Pseudomonas aeruginosa (P. aeruginosa) in the Akita University Hospital, we analyzed the serotype and genotype for 150 strains isolated from various clinical specimens from 1994 to 1996. One hundred strains chosen at random were divided into 11 serotypes by serotyping and into 50 genotypes by pulsed-field gel electrophoresis of Spe I-digested P. aeruginosa genomic DNAs. Serotype E strains, most common, gave 17 genome patterns. Fifty strains separated periodically in certain wards had further 7 genome patterns. The strains isolated from one patient with different times or with different serotypes showed the same stable genotype. Genome patterns were inconsistent with susceptibility to antimicrobial agents. Both drug-susceptible and -resistant strains were found in strains with the same genome pattern. The genome pattern was identical, even though the susceptibility was different due to isolation time or storage. This suggested that the multidrug-resistant strains of P. aeruginosa expanded in the hospital were not derived from one original strain.

Reduction of CAG expansions in cerebellar cortex and spinal cord of DRPLA.

Recent studies have identified an unstable expansion of a CAG repeat in a gene located on chromosome 12 as a cause of dentatorubropallidoluysian atrophy (DRPLA). To investigate whether the somatic heterogeneity may relate to the selective neuronal damage caused by the disease, genomic DNA from various tissues of an autopsied patient with DRPLA was examined to compare possible variations of expanded CAG repeats for the disease. Although the size of the expanded CAG repeat from many organs was almost the same as that from peripheral lymphocytes, those from cerebellar cortex and spinal cord were unexpectedly reduced and numbers of peaks within an expanded allele were relatively strict. These results suggest that the CAG repeat is not simply expanded in the genome of the tissues that are most involved in DRPLA, but that another mechanism might be responsible for the specific neuronal death.

MR imaging of multiple sclerosis simulating brain tumor.

Multiple sclerosis may sometimes present as a mass lesion that is indistinguishable from brain tumor both clinically and radiologically. We describe two cases of multiple sclerosis simulating brain tumor on computed tomography (CT) scans and magnetic resonance (MR) images, one of which was proved and another was suggestive to be demyelinating disease by biopsy. Steroid therapy produced regression of the lesions of MR images and CT scans. Our cases and others in the literature suggest strategies for detecting multiple sclerosis presenting as a mass lesion.