Factors affecting the functional results of open reduction and internal fixation for fracture-dislocations of the proximal interphalangeal joint.

To clarify the factors affecting functional results of fracture-dislocations of the proximal interphalangeal (PIP) joint treated by open reduction and internal fixation (ORIF), 60 patients, including 38 patients with a dorsal fracture-dislocation and 22 with a pilon fracture, were analysed. The mean ratio of articular surface involvement was 48.5% and a depressed central fragment existed in 75.3% of the cases. ORIF was performed in 47 patients through a lateral approach using Kirschner wires and in 13 through a palmar approach using a plate or screws. The mean flexion, extension and range of motion (ROM) of the PIP joint was 89.5°, 11.5° and 78.0°, respectively. Stepwise regression analysis revealed that a delayed start of active motion exercise after surgery, elderly age and ulnar ray digit were factors affecting functional outcomes. Although ORIF allows accurate restoration of the articular surfaces, an early start of motion exercise is essential for good results.

Cough and asthma diagnosis: physicians' diagnosis and treatment of patients complaining of acute, subacute and chronic cough in rural areas of Japan.

BACKGROUND: Cough is one of the most common reasons for visiting a clinic. The causes of cough differ according to the duration of cough. Infectious disease is commonly observed in acute cough while noninfectious disease is commonly observed in chronic cough. On the other hand, cough is frequently observed in patients with asthma/cough variant asthma (CVA). OBJECTIVE: In this study, we investigated the causes of cough in a rural region in Japan and the clinical examination and treatment for the patients diagnosed as asthma/CVA. METHODS: We analyzed 124 patients who complained of cough. RESULTS: The most common reason for acute cough was respiratory tract infection while asthma/CVA is the most common reason for subacute and chronic cough. The diagnostic procedure for asthma/CVA depends on clinical symptoms in asthmatic patients with acute cough. While in asthmatic patients with subacute and chronic cough, diagnosis of asthma depends on clinical examinations including chest radiogram, immunoglobulin E, white blood cells counts, sputum examination or spirometry as well as symptoms. For the treatment of asthma, the use of long-acting beta(2)-stimulant was dominant in asthmatic patients with acute cough while the use of leukotriene receptor and inhaled corticosteroid were dominant in asthmatic patients with subacute or chronic cough. CONCLUSIONS: Diagnosis and treatment for asthma differs according to the duration of cough. Simple guidelines for asthma/CVA according to the duration of cough might be necessary for diagnosis and treatment of asthma/CVA for general physicians especially in rural areas.

Environmental tobacco smoke and its effect on the symptoms and medication in children with asthma.

Environmental tobacco smoke (ETS) worsens asthmatic symptoms. We analyzed the relationship between levels of ETS and asthmatic symptoms and medication. We asked parents of 282 asthmatic children about the general condition, smoke exposure and medication. Patients were classified into three groups: no-ETS (no smoking), mild-ETS (smoking in the house but not in the same room as patient), and heavy-ETS (smoking in the same room as patient). We classified 116 children in no-ETS group, 124 children in mild-ETS group and 42 children in heavy-ETS group. The symptoms were worst and prevalence of leukotriene receptor antagonist and long-acting beta(2)-agonist use were highest in heavy-ETS group. However, there was no statistical difference between no-ETS and mild-ETS groups in prevalence of anti-asthmatic drug use and symptoms. We conclude that a smoking ban in rooms used by asthmatic children is an easy way to reduce ETS, asthmatic symptoms and the use of anti-asthmatic drugs.

Underrecognition of the severity of asthma and undertreatment of asthma in a rural area of Japan.

BACKGROUND AND AIM: Revised guidelines were released in Japan in 2003 for the assessment, treatment, and management of adult asthmatics, and similar guidelines for child asthmatics were released in 2002. We reassessed the severity and possible undertreatment of asthma according to these guidelines in stable asthmatics. METHODS: We reviewed medical records of 861 well-controlled asthmatic patients who, in April through June 2004 were cared for by 47 pulmonologists at 29 medical centers and 13 asthma clinics in a rural community in the San-in area of Japan. The physician obtained completed medical records about their symptoms and current treatment of the subjects, 726 adult and 135 children (aged 6 years or older) who were in stable condition and had had no exacerbations in the previous 3 months. The severity of asthma and current treatment for each patient were assessed according to the newly revised Japanese guidelines for the assessment, treatment, and management of adult and child asthmatics. RESULTS: In adult and child asthmatics, the percentage of predicted forced expiratory volume at 1 second (FEV1.0) was smaller and has a narrower distribution range than the percentage of predicted peak expiratory flow (PEF). When the severity of asthma was classified according to symptoms alone, 50% and 35% of those classified as mildly asthmatics patients with adults and children, respectively, had moderate to severe airflow limitation. Inhaled corticosteroids were prescribed to 90.6% of adult and 14.9% of child patients. When we compared the treatments that patients were actually receiving against the optimal treatments indexed according to a combined symptoms-FEV1.0 classification, we found that 49% of adult asthmatics were overtreated, 21% were properly treated, and 30% were undertreated. Among children, the respective percentages were 35%, 25%, and 40%. CONCLUSION: In well-controlled adult and child asthmatics, the severity of asthma is poorly judged when symptoms alone are considered. We suggest that the severity of asthma should be assessed through a combination of symptoms and the measurement of FEV1.0 during office visits. We also suggest that the proper dose of inhaled steroid needed to maintain stable conditions should be judged according to this combined symptoms-FEV1.0 classification.

Inhibitory, facilitatory, and excitatory effects of ATP and purinergic receptor agonists on the activity of rat cutaneous nociceptors in vitro.

Pathological pain is often associated with changed sympathetic nerve activities. It is known that sympathetic nerve endings release ATP as a co-transmitter of norepinephrine, but the effect of this ATP on the nociceptive system has not been properly studied in that the concentration range used in the previous studies was much higher than is expected in the surroundings of nociceptor terminals. We examined the effects of ATP, especially at low concentration (10(-5) M or less), on C-fiber polymodal receptor (CPR) activity using a rat skin-nerve preparation in vitro. We found for the first time that ATP inhibited the heat response of CPRs at low concentration (10(-5) M), but facilitated it at high concentration (10(-3) M). The former effect was mimicked by a P2X3 agonist, alpha,beta-methylene ATP, at 10(-5) M, while the latter was mimicked by 2-methylthio ADP (a P2Y1 agonist) or UTP (a P2Y2 agonist) at 10(-3) M, suggesting that the former is mediated by P2X receptors and the latter by P2Y receptors. After repetitive heat stimuli, ATP-induced CPR excitation was increased (10(-5) to 10(-3) M), but none of the purinergic agonists induced CPR excitation in a magnitude comparable to that by ATP. Possible mechanisms for these effects were discussed.

Norepinephrine reduces heat responses of cutaneous C-fiber nociceptors in Sprague-Dawley rats in vitro.

Nociceptors are excited or sensitized by many inflammatory mediators as well as by elevation of tissue temperature. We have shown that there is a facilitatory synergistic interaction between norepinephrine (NE) and bradykinin (BK) on cutaneous C-fiber nociceptors in normal Lewis rats. These interactions may play an important role in the mechanism of sympathetically maintained pain. In the present experiment, using skin-saphenous nerve in vitro preparations, we tested the effect of NE on the activity of nociceptive fibers and their response to heat in normal Sprague-Dawley rats. For comparison with the previous data on Lewis rats, we also examined the effect of NE on BK response. NE (10(-5) or 10(-6) M) did not excite nociceptive fibers before repeated heat stimuli or BK superfusion (10(-5) or 10(-6) M) to the receptive field. In contrast, after a few applications of heat or BK, NE excited 20-43% of nociceptive fibers to similar magnitudes. We also found that NE sensitized subsequent BK responses, but somewhat unexpectedly that it suppressed subsequent heat responses. This occurred regardless of the presence or absence of NE-induced excitation. These results suggest different mechanisms of NE modification to the BK and heat responses of cutaneous C-fiber nociceptors.

The immunosuppressant FK506 activates capsaicin- and bradykinin-sensitive DRG neurons and cutaneous C-fibers.

Immunosuppressant drug FK506, which is widely used for the treatment of atopic dermatitis, has multiple actions on the nervous system. In order to elucidate the mechanisms underlying transient burning sensation elicited by topical application of FK506 to the skin of atopic patients, we investigated if FK506 directly activates sensory neurons and fibers, or not. Ca(2+) imaging study on cultured DRG neurons of rats revealed that application of FK506 raised intracellular Ca(2+) levels in a subpopulation of small DRG neurons (3.1% of DRG neurons responsive to high K(+) solution). When DRGs from inflamed rats were used, the incidence increased to 7.4%. FK506 sensitive neurons also responded to a subsequent application of capsaicin (89.5% in normal, and 100% in inflamed rats) and bradykinin (31.6% in normal, and 80.9% in inflamed rats). Single fiber recordings in the skin-nerve preparation confirmed the results of cell culture study, showing that application of FK506 enhanced neuronal discharges of single C-fibers that are responsive to heat and bradykinin. These findings, taken together, indicate that FK506 application on inflamed skin may activate nociceptive C-fibers, which bear bradykinin receptors and capsaicin-sensitive heat transducer of TRP family, TRPV1.

Interactions of bradykinin and norepinephrine on rat cutaneous nociceptors in both normal and inflamed conditions in vitro.

Many inflammatory chemical mediators excite or sensitize nociceptors, which had led some researchers to believe that they may interact with each other to maintain a persistent painful state. We examined how the excitatory mediators norepinephrine (NE) and bradykinin (BK) interact, using single fiber recordings from cutaneous nociceptors. We observed that NE augmented the BK-induced response in both control and adjuvant-inflamed rats in a way different from NE-induced excitation in inflamed animals only. BK also tended to augment the NE-induced response (examined only in inflamed rats). Our results provide the first evidence that BK and NE synergistically interact on nociceptors.

Surgical outcome of radial osteotomy for Kienböck's disease-minimum 10 years of follow-up.

PURPOSE: Long-term results of radial osteotomy for Kienböck's disease seldom are seen in the literature. The purpose of this study was to report the minimum 10-year results and to compare them with the 5-year results to determine whether the favorable intermediate-term results were maintained. METHODS: Twenty-five patients who underwent radial osteotomy were followed-up for a mean period of 14.5 years. They were examined for pain, grip strength, and wrist range of motion (ROM). Through a review of clinical records, 5-year postoperative results were collected. The carpal height ratio and Ståhl's index were measured and the x-rays were inspected for osteoarthritic changes. We devised an original lunate grade to evaluate radiologic improvement of the ischemic lunate. Overall results were evaluated using Cooney's wrist function score and Nakamura's scoring system for Kienböck's disease. The long-term results were compared with both the preoperative status and the 5-year results. RESULTS: Pain, ROM, and grip strength were improved significantly after surgery, and the results were maintained for a long period. Carpal height ratio and Ståhl's index did not show significant improvements but ischemic lunate showed certain radiologic improvements with time by the lunate grade system. Osteoarthritic changes were observed in 54% of patients at 5 years and in 73% of patients at the final follow-up evaluation, but the arthrosis generally was mild and did not affect the clinical results. Cooney's wrist function score was excellent or good in 96% of the patients, and the results with Nakamura's scoring system for Kienböck's disease were excellent or good in 68% of the patients at the final follow-up evaluation. The percentages were the same 5 years after surgery. CONCLUSIONS: Radial osteotomy for Kienböck's disease is a reasonable treatment option and clinical improvement lasts for a long period of time. Although radiologic improvement was not drastic, the inner structure such as sclerotic change or bone cysts of the lunate improved with time, indicating healing of the ischemic lunate. Severe osteoarthritic change or proximal migration of the capitate can be avoided.

Loose body in the wrist: diagnosis and treatment.

PURPOSE: The purpose of this study was to report on 10 cases of symptomatic loose bodies in the wrist joints diagnosed using arthroscopy. TYPE OF STUDY: Retrospective review. METHODS: From 1986 to 2000, we performed wrist arthroscopy for 707 patients, 10 of whom had loose bodies in the wrist joints. The clinical records were reviewed retrospectively. The patients included 8 men and 2 women, and the average age was 28 years (range, 16 to 67 years). The chief complaint was wrist pain in all patients, but locking was uncommon. Preoperative diagnosis was difficult in all but 3 cases; in those cases, an osseous component was found within the loose bodies. The remaining cases were diagnosed by wrist arthroscopy. RESULTS: The loose bodies existed in the radiocarpal joint in 5 cases, and all could be removed arthroscopically. In the other 5 cases, the loose bodies were in the distal radioulnar joint, and arthrotomy was needed to remove them. After removal of the loose bodies, the pain was relieved in all cases without any surgical complications. CONCLUSIONS: Loose bodies in the wrist joint should be included in the differential diagnosis for chronic wrist pain. Wrist arthroscopy is of value because the preoperative diagnosis is usually difficult.

[A case of M. avium lung disease complicated with adenocarcinoma].

A 56-year-old man was admitted to our hospital for examination of an abnormal shadow found in a chest radiograph. Chest CT demonstrated a thick-walled cavity surrounded by small centrilobular nodules in the upper lobe of the left lung. Chemotherapy with rifampin, isoniazid, ethambutol and pyrazinamide was started, because acid-fast bacilli were observed in the bronchial brushing smear. Since PCR examination of the bronchial lavage was positive for M. avium, the rifampin and ethambutol were retained, while the other drugs were replaced with streptomycin and clarithromycin. However, in this case the radiographic findings did not point to non-tuberculous mycobacterial (NTM) infection, since the thickness of the cavity was irregular in the caudal portion. In addition, the patient did not accept long-term NTM therapy. Therefore, we chose surgical therapy. In a portion of the surgical specimen, adenocarcinoma was detected. The possibility of lung cancer should be remembered in cases with a thick-walled lung cavity.

Stimulation of insulin secretion by denatonium, one of the most bitter-tasting substances known.

Denatonium, one of the most bitter-tasting substances known, stimulated insulin secretion in clonal HIT-T15 beta-cells and rat pancreatic islets. Stimulation of release began promptly after exposure of the beta-cells to denatonium, reached peak rates after 4-5 min, and then declined to near basal values after 20-30 min. In islets, no effect was observed at 2.8 mmol/;l glucose, whereas a marked stimulation was observed at 8.3 mmol/;l glucose. No stimulation occurred in the absence of extracellular Ca(2+) or in the presence of the Ca(2+)-channel blocker nitrendipine. Stimulated release was inhibited by alpha(2)-adrenergic agonists. Denatonium had no direct effect on voltage-gated calcium channels or on cyclic AMP levels. There was no evidence for the activation of gustducin or transducin in the beta-cell. The results indicate that denatonium stimulates insulin secretion by decreasing KATP channel activity, depolarizing the beta-cell, and increasing Ca(2+) influx. Denatonium did not displace glybenclamide from its binding sites on the sulfonylurea receptor (SUR). Strikingly, it increased glybenclamide binding by decreasing the K(d). It is concluded that denatonium, which interacts with K(+) channels in taste cells, most likely binds to and blocks Kir6.2. A consequence of this is a conformational change in SUR to increase the SUR/glybenclamide binding affinity.

Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion.

The insulin secretory response by pancreatic beta-cells to an acute "square wave" stimulation by glucose is characterized by a first phase that occurs promptly after exposure to glucose, followed by a decrease to a nadir, and a prolonged second phase. The first phase of release is due to the ATP-sensitive K(+) (K(ATP)) channel-dependent (triggering) pathway that increases [Ca(2+)](i) and has been thought to discharge the granules from a "readily releasable pool." It follows that the second phase entails the preparation of granules for release, perhaps including translocation and priming for fusion competency before exocytosis. The pathways responsible for the second phase include the K(ATP) channel-dependent pathway because of the need for elevated [Ca(2+)](i) and additional signals from K(ATP) channel-independent pathways. The mechanisms underlying these additional signals are unknown. Current hypotheses include increased cytosolic long-chain acyl-CoA, the pyruvate-malate shuttle, glutamate export from mitochondria, and an increased ATP/ADP ratio. In mouse islets, the beta-cell contains some 13,000 granules, of which approximately 100 are in a "readily releasable" pool. Rates of granule release are slow, e.g., one every 3 s, even at the peak of the first phase of glucose-stimulated release. As both phases of glucose-stimulated insulin secretion can be enhanced by agents such as glucagon-like peptide 1, which increases cyclic AMP levels and protein kinase A activity, or acetylcholine, which increases diacylglycerol levels and protein kinase C activity, a single "readily releasable pool" hypothesis is an inadequate explanation for insulin secretion. Multiple pools available for rapid release or rapid conversion of granules to a rapidly releasable state are required.

The effects of cerulenin, an inhibitor of protein acylation, on the two phases of glucose-stimulated insulin secretion.

The potential role of protein acylation in the control of biphasic insulin secretion has been studied in isolated rat pancreatic islets. The protein acylation inhibitor cerulenin inhibited both phases of glucose-stimulated insulin secretion. However, it did not affect the secretory response to a depolarizing concentration of KCl in either the absence or presence of diazoxide. Therefore, cerulenin has no deleterious effect on the L-type Ca(2+) channels or subsequent events in Ca(2+) stimulus-secretion coupling. Advantage was taken of this to study the effect of cerulenin on the K(ATP) channel-independent pathway of glucose signaling. In the presence of KCl and diazoxide, cerulenin powerfully inhibited the augmentation of insulin release by glucose and palmitate. Similar inhibition of the augmentation of release by glucose and palmitate was seen under Ca(2+)-free conditions in the presence of 12-O-tetradecanoylphorbol-13-acetate and forskolin. As neither glucose oxidation nor the effect of glucose to inhibit fatty acid oxidation is affected by cerulenin, these data suggest that protein acylation is involved in the K(ATP) channel-independent pathway of glucose signaling.