Assessment of the bioavailability of an antibiotic prophylactic protocol in patients undergoing third molar surgery.

The aim of this prospective study was to determine the antibiotic bioavailability of a prophylactic protocol in patients undergoing third molar surgery. Samples from 25 patients were analysed (average age 21 ± 3.89 years, range 18-33 years; 14 female). The patients received single-dose prophylaxis of 2 g amoxicillin orally 1 hour prior to third molar surgery. Venous blood (1.5 ml) and blood from the third molar socket (1.50 ml) were obtained. The amoxicillin plasma concentration was determined in both samples by high performance liquid chromatography with a diode-array detector (HPLC/DAD). Their associations with demographic variables (age, height, weight, body mass index (BMI), sex) and antibiotic exposure time were analyzed using linear regression models. The mean amoxicillin plasma level detected in the venous blood was 1.21 ± 1.17 µg/ml (range 0.49-6.34 µg/ml) and in the third molar socket was 4.14 ± 2.24 µg/ml (range 0.86-7.46 µg/ml) (P < 0.001). No relationship was observed between the bioavailability of the drug and the patient biometric indices evaluated. The prophylactic administration of 2 g amoxicillin in third molar surgery showed greater bioavailability in the molar socket than the concentrations established as necessary to inhibit the growth of microorganisms that cause oral infections. The results show the need to review the current infection control protocols in oral surgery in light of the overestimated doses observed.

Prognostic impact of lymphovascular invasion in lymph node-negative superficial esophageal squamous cell carcinoma.

The relationship between lymphovascular invasion (LVI) and prognosis in patients with superficial esophageal squamous cell carcinoma (SESCC) is unclear. The aim of this study is to evaluate prognostic factors in patients with lymph node-negative SESCC. A total of 195 patients with pathologically confirmed T1a-MM, T1b, and lymph node-negative SESCC were retrospectively reviewed in this study. Overall, the disease-free survival (DFS) rate was poorer in the lymphatic invasion-positive group than in the lymphatic invasion-negative group (p = 0.002) and a multivariate analysis suggested that lymphatic invasion was the only independent prognostic factor of DFS in patients with lymph node-negative SESCC (HR = 4.075, p = 0.005). Distant organ recurrence occurred in one patient (1/52, 1.9%) in the T1b-SM2 group and in six patients (6/61, 9.7%) in the T1b-SM3 group; all of these patients had LVI. LVI-positive patients had a poorer DFS than invasion-negative patients in the T1b-SM2 and SM3 groups (p = 0.026), and a multivariate analysis suggested that LVI was the only independent prognostic factor of DFS in patients with lymph node-negative SM2 and SM3 SESCC (HR = 5.165, p = 0.031). Lymph node-positive patients had a significantly poorer DFS rate than lymph node negative and LVI positive patients among the SM2 and SM3 SESCC patients (p = 0.018). The present results suggested that LVI was an independent prognostic factor in patients with SM2 and SM3 lymph node-negative SESCC; however their prognosis was not worse than that of patients with lymph node-positive SM2 and SM3 SESCC, for whom adjuvant therapy is indicated as a standard treatment.

Prognostic significance of sarcopenia in patients undergoing esophagectomy for superficial esophageal squamous cell carcinoma.

Nononcological prognostic factors in superficial esophageal squamous cell carcinoma (SESCC) patients remain unclear. The aim of this study is to evaluate the relationship between sarcopenia and surgical outcome in patients with SESCC who had undergone definitive surgery. A total of 194 SESCC patients who had undergone thoracic esophagectomy with three-field lymphadenectomy without neoadjuvant therapy at Tokai University Hospital between January 2006 and December 2015 were analyzed retrospectively. Manual tracing using CT imaging was used to measure the cross-sectional areas of the skeletal muscle mass. The cutoff values for the skeletal muscle index used to define sarcopenia were based on the results of a previous study. Twenty-eight patients (14.4%) had sarcopenia, while the remaining 166 patients (85.6%) did not. A multivariate analysis suggested that sarcopenia was an independent risk factor for postoperative pulmonary complications (OR = 3.232, P = 0.026). The overall survival rate and the disease-free survival rate were both significantly worse in the sarcopenia group than in the nonsarcopenia group (P < 0.001). In a multivariate analysis, sarcopenia was an independent prognostic factor affecting overall survival (HR = 7.121, P < 0.001) and disease-free survival (HR = 6.000, P < 0.001). Patients with sarcopenia and lymph node metastasis (n = 18) had a worse outcome than the other patients (P < 0.001). This study suggests that the alleviation of sarcopenia through nutritional support and rehabilitation in SESCC patients scheduled to undergo surgery might help to prevent postoperative pulmonary complications and to improve the long-term outcome.

[Pathogenesis of pulmonary thrombosis in Duchenne muscular dystrophy; a consideration from changes in serum CK and LDH levels].

We assessed the hypercoagulative state in patients with Duchenne muscular dystrophy (DMD) by measuring peripheral blood creatine kinase (CK) and lactate dehydrogenase (LDH) levels. In 76 patients with DMD who had no complications during examination, the CK and LDH levels were examined in a total of 173 times. Both enzyme levels were elevated and highly correlated (R = 0.93). We examined the temporal alteration of serum CK and LDH levels during episodes of pulmonary thrombosis experienced in 7 DMD patients who fulfilled the following diagnostic criteria: 1. sudden onset of dyspnea, chest pain, and hypoxia; 2. abnormal coagulation profile or abnormal chest CT findings, such as peripheral wedged shaped shadow and; 3. pneumothorax ruled out from X-ray findings. Throughout the episode of pulmonary thrombosis, CK and LDH levels changed within the range of those from DMD patients who had no complications, however, the CK level was significantly elevated from the basal level (2.12 times, p = 0.0075) on the first day of the episode. The LDH level rose for several days, and subsequently both CK and LDH returned to the basal level. In patients with compartment syndrome, CK levels were reportedly elevated due to muscle fiber necrosis which lead a hypercoagulative state. Therefore, we propose that muscle fiber necrosis is one of causal factors in pulmonary thrombosis. In addition, elevated CK may be helpful in predicting pulmonary thrombosis.

[The usefulness of tracheostomy in Duchenne muscular dystrophy ventilated by a chest respirator].

The respiratory dysfunction in Duchenne muscular dystrophy (DMD) patients increases with age. We have attempted various methods of artificial respiration for them. Recently, a non-invasive positive pressure ventilation (NIPPV) became the first choice of respiration, but the chest respirator (CR) was still one of the choices. In our hospital, DMD patients with tracheostomy wearing a CR were alive for longer period, despite of respiratory dysfunction and complications. We studied 6 DMD patients with CR to evaluate nocturnal hypoxia index (NHI) by examining nocturnal periodic hypoxia, and measured oxygen saturation after 20 mg of clomipramine hydrochloride administration before sleep. Three patients had periodic nocturnal hypoxia which was prevented by the clomipramine administration. Two patients with tracheostomy did not exhibit hypoxia. We speculated that pharyngeal hypotonia during REM sleep induces periodic nocturnal hypoxia, therefore the tracheostomy would prevent hypoxia. Next, we examined the pharyngeal MRI on one DMD patient at the same disease stage who also had night NIPPV. We found that his soft palate and tongue shifted downward, which narrowed his pharynx during REM sleep. Consequently we have concluded that noctunnal periodic hypoxia is mainly caured by obstructive sleep apnea. For DMD patients with CR, the tracheostomy may be effective to prevent hypoxia during sleep.

[Diagnosis of inflammatory myopathy; usefulness of 99mTc MDP scintigraphy and muscle MRI for determination of affected sites].

We studied the effectiveness of 99mTc-MDP (methylendiphosphate) scintigraphy in imaging inflammatory myopathy. The three subjects including 1 male and 2 female patients had high creatine kinase (CK) levels and proximal dominant muscle weakness. In whole body muscle surveillance by 99mTc-MDP scintigraphy, abnormal 99mTc-MDP accumulation was found in the extremities of all patients. The sites with high 99mTc-MDP accumulation showed high intensity on T2 weighted MR imaging, suggesting an inflammatory process. Muscle biopsy was performed on two patients from the muscles with the abnormal MRI findings, which showed the diagnostic finding of inflammatory changes. Because muscle involvement in inflammatory myopathy differs from muscle to muscle, it is sometimes difficult to choose appropriate muscle biopsy sites for diagnostic purposes. Affected muscles are more easily identified by using 99mTc-MDP muscle scintigraphy and muscle MRI, therefore, a correct diagnosis and choice of biopsy site can be made. 99mTc-PYP scintigraphy is permitted for use in myocardial infarction alone and 111In-antimyosin scintigraphy is not available in Japan. Therefore, we recommend 99mTc-MDP scintigraphy for diagnosis of inflammatory myopathy and for determination of muscle biopsy sites.

[The significance of Ulex europaeus agglutinin I lectin binding fibers in various muscular diseases].

In the present study, we have reported that Ulex europaeus agglutinin I (UEA I) lectin labeled muscle fibers in distal myopathy with rimmed vacuole formation (DMRV). UEA I binding to muscle fibers was also observed in a small number of biopsies with inflammatory myopathy, but not in other diseases, including neurogenic muscular atrophies and muscular dystrophies. In order to elucidate the relationship between this UEA I binding, rimmed vacuole formation and active autophagocytosis, we examined the UEA I binding fibers in other myopathies which frequently showed rimmed vacuoles, including adult onset acid maltase deficiency, oculo-pharyngo-distal type myopathy and oculopharyngeal muscular dystrophy. No UEA I lectin labeling fiber was observed in the diseases examined. We then studied UEA I binding behavior on 70 biopsies of inflammatory myopathy to characterize the clinical features of UEA I binding positive patients. UEA I binding fibers were observed in 3 of 28 patients (11%) with other collagen diseases, 11 of 36 (31%) without these disorders, and 2 of 6 (33%) with inclusion body myositis. There were no common clinical histories, complications or laboratory findings among the UEA I binding positive patients. In conclusion, a common process may exist between the muscle fiber degeneration in DMRV and subgroups of inflammatory myopathy patients, but the basic mechanism remains to be elucidated.

Occlusal stability after extraction orthodontic therapy in adult and adolescent patients.

In this study we compared the posttreatment stability of occlusion in adults and adolescents treated for crowding or maxillary protrusion with four-premolar extractions and edgewise mechanics at an average of more than 4 years out of treatment. The adolescent sample showed a significantly greater posttreatment increase in mandibular anterior crowding than the adult sample. Posttreatment overjet and overbite remained more stable in the adolescents. We noted a correlation between in-treatment expansion and posttreatment narrowing of mandibular intercanine width in the adults. Differences in postorthodontic occlusal changes were noted between the adult and adolescent samples.

[Hyponatremia in Duchenne muscular dystrophy on mechanical ventilation].

To evaluate the pathomechanism of hyponatremia occasionally seen in Duchenne muscular dystrophy (DMD) on intermittent positive pressure ventilation (IPPV), we performed a comparative study on 26 DMD patients, 7 IPPV in trachetomized intermittent positive pressure ventilation (TIPPV), 6 nasal intermittent positive pressure ventilation (NIPPV), 6 cuirass respirator (CR), and 7 spontaneous breathings (SB). We followed fluctuation of serum sodium levels for several years. Since the serum sodium level was gradually reduced with years on mechanical ventilation, we speculated positive relationship between hyponatremia and antidiuretic hormone (ADH) secretion. Serum sodium levels of 135.6 +/- 2.8 mEq/L in average on IPPV (TIPPV + NIPPV) patients was significantly lower than the levels of 137.8 mEq/L +/- 0.98 on CR patients and 138.8 +/- 0.69 mEq/L on SB patients. Plasma ADH levels in IPPV patients were not reduced when plasma osmolarity was less than 280 mOSm/L. Previous reports showed that ADH was inappropriately secreted only during IPPV with positive end expiratory pressure (PEEP). Ours is the first report of inappropriate secretion of ADH during IPPV without PEEP. It becomes clear that inappropriate ADH secretion is one of the causes of hyponatremia in DMD, though the exact mechanism is not clear. We should bear in mind the change of serum electrolyte level in ventilated DMD patients, especially patients on antidepressant known to release of ADH.

[Decreased blink frequency in myotonic dystrophy].

We counted spontaneous eye blink rate in 11 myotonic dystrophy (MD) patients. Seven healthy subjects as well as 10 Parkinson disease (PD) and 7 facio-scapulo-humeral dystrophy (FSH) patients were used as controls. Blink frequency was significantly decreased in MD and PD patients (7.6 +/- 4.9/min in average and 11.0 +/- 7.5/min, respectively), compared with healthy subjects and FSH patients (17.5 +/- 4.3/min and 17.3 +/- 9.9/min, respectively). Normal blink frequency in FSH suggests that the facial muscle weakness is not responsible for decreased blink frequency in MD. This observation is compatible with prolonged R1 latency in blink reflex in MD, suggesting a dysfunction of central mechanism of blink control system as in the case of PD, although there remains a possibility that the myotonia in levator palpebrae muscles disturbs blinking.

Specific binding of Ulex europaeus agglutinin I lectin to sarcolemma of distal myopathy with rimmed vacuole formation.

Ulex europaeus agglutinin I (UEA I) binding was studied in 83 patients with various neuromuscular disorders. UEA I labelled endomysial capillaries and endothelial cells of perimysial blood vessels in all the examined muscles. There was no UEA I binding to muscle fibres except for all (9) cases of distal myopathy with rimmed vacuole formation (DMRV), 1 of 5 cases of inclusion body myositis and 1 of 36 cases of inflammatory myopathies. The UEA I binding was completely eliminated by preincubation of UEA I solution with L-fucose. Using electron microscopy, the UEA I binding was localized to sarcolemma and intrasarco-plasmic membranous organelles other than mitochondria. Myosatellite cells were not labelled. These findings revealed the existence of fucosylated proteins or lipids in a subset of skeletal muscles suffering from DMRV. Biochemical identification of the fucosylated substance and further detailed study on subcellular localization of UEA I binding may yield important clues to the unknown pathogenesis of DMRV.

[Non-uremic neuropathy in hemodialysis patients].

We have reviewed 20 clinical records of hemodialysis patients with neuropathy admitted to the Department of Neurology during 1978 april through 1995 march. The clinical diagnosis was made based on clinical findings, neurophysiological examinations, and histopathological findings of sural nerve and peroneal muscle biopsies. Four out of twenty hemodialysis patients with neuropathy were non-uremic neuropathy. The diagnosis of neuropathy of four patients were chronic inflammatory demyelinating polyneuropathy, neuropathy with graft versus host disease, Guillain-Barré syndrome, and subacute combined degeneration of the spinal cord. All patients improved after the treatment. It is important to consider the possibility of association of non-uremic neuropathy in hemodialysis patients.

[Different mechanism may underlie respiratory failure of myotonic and Duchenne muscular dystrophies--a pulseoxymetric and spirometric study].

Respiratory failure is an important cause of death in many neuromuscular diseases. We studied the relationship between nocturnal hypoxemia and respiratory muscle weakness by nocturnal pulseoxymetry and spirometry in two major hereditary myopathies, myotonic and Duchenne muscular dystrophies (MD and DMD respectively). In DMD significant nocturnal periodic hypoxemia appears only in cases with vital capacity lower than 20% of its expected value, suggesting that % vital capacity is a useful index of early respiratory failure. In contrast there was no correlation between vital capacity and severity of hypoxemia in MD patients. Therefore, we conclude respiratory muscle weakness is a single important factor which determines the severity of respiratory failure in DMD, while another/other factor (s), such as disturbance of respiratory control or myotonia, may play an important role in MD.

[The effect of clomipramine to nocturnal periodic hypoxemia in Duchenne muscular dystrophy].

Respiratory insufficiency is a major cause of death in Duchenne muscular dystrophy (DMD). The earliest sign is a hypoventilation which appears in REM sleep. We administered 20 mg of clomipramine hydrochloride before sleep to two DMD patients with periodic nocturnal hypoxemia. The complaints such as morning headache, nausea and somnolence disappeared promptly. Polysomnography revealed complete suppression of REM sleep and disappearance of periodic hypoxemia in both cases. The most important untoward effect was intractable constipation observed in one patient. Although clomipramine dramatically improved the nocturnal periodic hypoventilation, the therapeutic effects lasted less than three months. Permanent REM sleep suppression is requisite for optimal drug therapy of periodic nocturnal hypoventilation in DMD.

[Nocturnal hypoxia index: a new pulse oxymetry index of nocturnal hypoventilation in neuromuscular disorders].

Respiratory insufficiency due to progressive muscle wasting is a major cause of death in various neuromuscular disorders. Morning headache and anorexia leading to slowly progressive body weight loss are frequently observed as initial symptoms of insufficient ventilation. From our experience nocturnal pulse oxymetry is a valuable study to detect early respiratory insufficiency and helpful to evaluate the effectiveness of ventilatory assistance, since ventilation is more impaired during sleep in early stage of respiratory insufficiency. Percent desaturation time (total desaturation time (SaO2 < or = 90%)/total sleep time) has been used as the most reasonable index of nocturnal hypoventilation. The criteria for introduction of nocturnal mechanical ventilation is 20% or more in Duchenne muscular dystrophy. Unfortunately, the earliest stage of hypoventilation cannot be detected by this index and it is of no use in advanced respiratory failure, because this index never exceeds 100% by definition. Here we propose a new index for nocturnal hypoventilation, which is defined as follows: nocturnal hypoxia index (NHI) = (% time of 95% > or = SaO2 > 90%) + (% time of 90% > or = SaO2 > 85%) x 2 + (% time of 85% > or = SaO2 > 80%) x 3 + (% time of 80% > or = SaO2 > 75%) x 4 + (% time of 75% > or = SaO2 > 70%) x 5.... This index is good for any stage of respiratory failure, and applicable to nocturnal hypoxia of other causes. The criteria for initiating mechanical ventilation in DMD can be substituted by "NHI is above 130."