Accurate diagnosis and treatment of Vibrio vulnificus infection: a retrospective study of 12 cases

Background and aimsVibrio vulnificus causes an infectious disease that has extremely poor convalescence and leads to necrotic fasciitis. In this study, we sought to define the characteristic epidemiology of V. vulnificus infection and clarify its diagnosis at the global level.MethodsOver a period of 10 years, we investigated the appearance of symptoms, underlying conditions, treatment, and mortality in 12 patients (eight men, four women; >50 years old; average age, 66 years,) infected with V. vulnificus.ResultsThe development of symptoms occurred primarily between June and September, a period during which seawater temperature rises and the prevalence of V. vulnificus increases. All patients had underlying diseases, and seven patients reported a history of consuming fresh fish and uncooked shellfish. The patients developed sepsis and fever with sharp pain in the limbs. Limb abnormalities were observed on visual examination. All patients underwent debridement; however, in the survival group, the involved limb was amputated early in 80% patients. The mortality rate was 58.3%.ConclusionRecognition of the characteristic epidemiology and clinical features of this disease is important, and positive debridement should be performed on suspicion. When the illness reaches an advanced stage, however, amputation should be the immediate treatment of choice.     

Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients

Cryopyrin-associated periodic syndrome (CAPS) is a spectrum of systemic autoinflammatory disorders in which the majority of patients have mutations in the cold-induced autoinflammatory syndrome (CIAS)1 gene. Despite having indistinguishable clinical features, some patients lack CIAS1 mutations by conventional nucleotide sequencing. We recently reported a CAPS patient with mosaicism of mutant CIAS1, and raised the possibility that CIAS1 mutations were overlooked in "mutation-negative" patients, due to a low frequency of mosaicism. To determine whether there were latent mutant cells in "mutation-negative" patients, we sought to identify mutation-associated biologic phenotypes of patients' monocytes. We found that lipopolysaccharide selectively induced necrosis-like cell death in monocytes bearing CIAS1 mutations. Monocyte death correlated with CIAS1 up-regulation, was dependent on cathepsin B, and was independent of caspase-1. Cell death was intrinsic to CIAS1-mutated monocytes, was not mediated by the inflammatory milieu, and was independent of disease severity or anti-IL-1 therapy. By collecting dying monocytes after lipopolysaccharide treatment, we succeeded in enriching CIAS1-mutant monocytes and identifying low-level CIAS1-mosaicism in 3 of 4 "mutation-negative" CAPS patients. Our findings reveal a novel effect of CIAS1 mutations in promoting necrosis-like cell death, and demonstrate that CIAS1 mosaicism plays an important role in mutation-negative CAPS patients.     

Randomized study of the benefits of preoperative corticosteroid administration on the postoperative morbidity and cytokine response in patients undergoing surgery for esophageal cancer

OBJECTIVE: To investigate whether preoperative corticosteroid administration plays a role in attenuating postoperative morbidity. SUMMARY BACKGROUND DATA: There is as yet no consensus on the beneficial effects of steroids in alleviating surgical stress. METHODS: A total of 66 patients undergoing surgery for thoracic esophageal cancer were randomly categorized preoperatively into two groups of 33 patients each. One group was administered an intravenous infusion of methylprednisolone (10 mg/kg body weight) 30 minutes before the surgery (MP group), while the other group received a placebo infusion (control group). The primary endpoint was organ system failure during the first 7 days after surgery. Comparisons of surgery-related complications, cytokine responses, and blood counts were also made between the two groups. RESULTS: The percentage of patients in the MP group who had one or more organ system failures was 33%, significantly lower than the corresponding percentage of 61% in the control group. The surgery-related complication rate and long-term survival rate were similar in the two groups. The peak plasma levels of interleukin (IL)-1 receptor antagonist, IL-6, and IL-8 were significantly lower in the MP group than in the control group. Changes in the plasma levels of IL-10 were significantly larger in the MP group. No significant differences in the circulating lymphocyte and neutrophil counts were observed between the groups. CONCLUSIONS: The results suggest that prophylactic administration of corticosteroids is associated with a decrease in postoperative morbidity in patients undergoing invasive surgery. The laboratory data suggest that corticosteroids may attenuate surgical stress-induced inflammatory responses both directly by suppressing the release of proinflammatory cytokines and via inducing IL-10 synthesis.     

Feasibility of Induction Chemotherapy Using Bronchial Arterial Infusion for Locally Advanced Non-Small Cell Lung Cancer: A Pilot Study

Purpose: We examined the feasibility and effectiveness of bronchial arterial infusion (BAI) as induction chemotherapy before surgery for locally advanced non-small cell lung cancer (NSCLC). Methods: Eighteen patients with locally advanced NSCLC were given BAI consisting of cis-diamminedichloroplatinum (CDDP) (50–100 mg/m²) as induction chemotherapy before surgery (induction BAI). Six patients with clinical stage IIIA cancer had bulky N2 metastatic lymph nodes, and 12 patients with clinical stage IIIB cancer had T4 disease. Results: Of the 18 patients, 12 (67%) showed a partial response to the BAI therapy. Standard pulmonary resection was performed in 5 patients, pulmonary resection with the combined resection of adjacent organs was performed in 10 patients, and pulmonary resection with carinal resection and reconstruction was performed in 3 patients. Complete resection was possible in 14 patients (78%). There were no serious BAI therapy-related complications or postoperative deaths. The 5-year survival rate of the 18 patients was 35.7% and the median survival time (MST) was 19.4 months. Survival was better when complete resection was achieved after the induction BAI, especially in patients with stage IIIB (T4) disease. Conclusion: Based on our preliminary findings, BAI with CDDP as induction chemotherapy is feasible and may be an effective therapeutic modality for locally advanced NSCLC. Received: July 26, 2001 / Accepted: March 5, 2002     

Determinants of mortality in patients with severe blunt head injury

CONTEXT: Head injury is the leading cause of traumatic death in the United States. HYPOTHESIS: A set of clinical parameters available soon after injury can be used to accurately predict outcome in patients with severe blunt head trauma. DESIGN: Validation cohort study. SETTING: Urban level I trauma center. PATIENTS AND METHODS: Data from patients with severe blunt head injury, as defined by inability to follow commands, were prospectively entered into a neurosurgical database and analyzed. The impact on survival of 23 potentially predictive parameters was studied using univariate analysis. Logistic regression models were used to control for confounding factors and to assess interactions between variables, whose significance was determined by univariate analysis. Goodness of fit was calculated with the Hosmer-Lemeshow c statistic. The predictability of the logistic model was evaluated by measuring the area under the receiver operating characteristic curve (AUC). RESULTS: Logistic regression analysis revealed that 5 risk factors were independently associated with death. These variables included systemic hypotension in the emergency department, midline shift on computed tomographic scan, intracranial hypertension, and absence of pupillary light reflex. A low Glasgow Coma Scale score and advanced age were found to be highly correlated risk factors that, when combined, were independently associated with mortality. The model showed acceptable goodness of fit, and the AUC was 80.5%. CONCLUSIONS: Systemic hypotension and intracranial hypertension are the only independent risk factors for mortality that can be readily treated during the initial management of patients with severe head injuries. When used together, Glasgow Coma Scale score and age are significant predictors of mortality.     

Lumbar posterolateral fusion inhibits sensory nerve ingrowth into punctured lumbar intervertebral discs and upregulation of CGRP immunoreactive DRG neuron innervating punctured discs in rats

Degeneration of lumbar intervertebral discs is thought to be a cause of low back pain. Studies have found that a cause of discogenic low back pain is intervertebral disc inflammation and axonal growth of afferent fibers innervating the disc. Lumbar spine fusion for chronic discogenic low back pain is considered an effective procedure. However, no study has investigated the mechanism of pain relief. We did this by applying Fluoro-Gold (FG) to the ventral aspect of the L4–L5 intervertebral discs of 40 rats. We exposed the nucleus pulposus to the annulus fibrosus in a disc punctured model. Rats were divided into 4 groups. Group A: Punctured intervertebral disc with sham posterolateral fusion (PLF) (n = 10), Group B: Punctured intervertebral disc with PLF (n = 15), Group C: Normal intervertebral disc (no puncture) with PLF (n = 10), and Group D: Normal disc (no disc puncture) with sham PLF (n = 5). Four weeks after surgery, bilateral L1–L5 dorsal root ganglia (DRGs) were stained with growth-associated protein 43 (GAP43), a marker of axonal growth, and calcitonin gene-related peptide (CGRP), a neuropeptide marker of pain. Bone union was evaluated using X-ray imaging. Of the FG-labeled neurons, the proportions of GAP43- and CGRP-immunoreactive (IR) neurons in Group A were significantly higher than in Group D (P < 0.05). The proportions of GAP43- and CGRP-IR neurons in bone union rats in Group B were significantly lower than in nonunion rats in Group B and in the rats in Group A (P < 0.05). No significant differences in GAP43- and CGRP-IR neurons were observed between bone union and nonunion rats in Group C and the rats in Group D (P > 0.05). PLF is strongly related to the downregulation of GAP43 and CGRP expression. Therefore, PLF may suppress the increase of inflammatory neuropeptides and the process of axonal growth. Moreover, these results may explain, in part, the mechanism of pain relief following lumbar spinal fusion for chronic discogenic low back pain in humans.     

Measurement of subclavicular pressure on the subclavian artery and brachial plexus in the costoclavicular space during provocative positioning for thoracic outlet syndrome

Background  

Thoracic outlet syndrome is thought to be caused by compression of the brachial plexus or subclavian artery in the interscalene, costoclavicular, or subcoracoid space. Some provocative tests are widely used for diagnosing thoracic outlet syndrome. However, whether provocative positions actually compress the neurovascular bundle in these spaces remains unclear. The purpose of this study was to investigate the possibility of neurovascular bundle compression in the costoclavicular space by measuring the pressure applied to the brachial plexus and subclavian artery in provocative positions.     

Voriconazole-associated salt-losing nephropathy

A 74-year-old man was diagnosed with nephrotic syndrome due to focal segmental glomerulosclerosis, and steroid therapy was initiated. Subsequently, he was affected by deep mycosis, and hence, voriconazole (VRCZ) was administered. On the 16th day, he was transferred to our hospital because of somnolence and malaise. His systolic blood pressure was approximately 80 mmHg, and he showed decreased skin turgor, indicating volume depletion. Laboratory analysis revealed hyponatremia and liver dysfunction. Discontinuation of VRCZ and drip infusion of normal saline improved the consciousness disorder, hyponatremia, and liver dysfunction. The levels of antidiuretic hormone (ADH) and plasma renin activity were elevated. This patient showed high excreted urine sodium, despite volume depletion and low serum osmolality. Therefore, this patient was diagnosed with salt-losing nephropathy (SLN). SLN should be considered for treatment of VRCZ-associated hyponatremia, together with syndrome of inappropriate secretion of ADH.     

Low-level Er:YAG laser irradiation enhances osteoblast proliferation through activation of MAPK/ERK

Although the use of high-level Er:YAG laser irradiation has been increasing in periodontal and peri-implant therapy, the effects of low-level Er:YAG laser on surrounding tissues and cells remain unclear. In the present study, the effects of low-level Er:YAG laser irradiation on osteoblast proliferation were investigated. Cells of the osteoblastic cell line MC3T3-E1 were treated with low-level Er:YAG laser irradiation with various combinations of laser settings (fluence 0.7–17.2 J/cm²) and in the absence or presence of culture medium during irradiation. On day 1 and/or day 3, cell proliferation and death were determined by cell counting and by measurement of lactate dehydrogenase (LDH) levels. Further, the role of mitogen-activated protein kinase (MAPK) pathways in laser-enhanced cell proliferation was investigated by inhibiting the MAPK pathways and then measuring MAPK phosphorylation by Western blotting. Higher proliferation rates were found with various combinations of irradiation parameters on days 1 and 3. Significantly higher proliferation was also observed in laser-irradiated MC3T3-E1 cells at a fluence of approximately 1.0–15.1 J/cm², whereas no increase in LDH activity was observed. Further, low-level Er:YAG irradiation induced the phosphorylation of extracellular signal-regulated protein kinase (MAPK/ERK) 5 to 30 min after irradiation. Although MAPK/ERK 1/2 inhibitor U0126 significantly inhibited laser-enhanced cell proliferation, activation of stress-activated protein kinases/Jun N-terminal kinase (SAPK/JNK) and p38 MAPK was not clearly detected. These results suggest that low-level Er:YAG laser irradiation increases osteoblast proliferation mainly by activation of MAPK/ERK, suggesting that the Er:YAG laser may be able to promote bone healing following periodontal and peri-implant therapy.     

Remifentanil is useful for cardiovascular stability during cesarean delivery in a parturient with Marfan's syndrome

A 25-year-old parturient with Marfan's syndrome was scheduled for cesarean delivery. She suffered with severe scoliosis and asymptomatic aortic root dilatation. To establish a cardiovascular stability and prevent aortic dissection perioperatively, we selected the use of remifentanil, an ultra-short acting opioid analgesic with general anesthesia. General anesthesia was induced with remifentanil (0.2 microg x kg(-1) x min(-1)), propofol (100 mg), and vecuronium bromide (10 mg). Anesthesia was maintained with 100% O2, sevoflurane (1-1.5%), and remifentanil (0.2-0.25 microg x kg(-1) x min(-1)). She remained hemodynamically stable during surgery. A lively infant was delivered and Apgar scores were 8 and 9 at 1 and 5 min, respectively. Their post-delivery courses were uneventful. Remifentanil was useful for anesthetic management in a pregnant patient with Marfan's syndrome undergoing cesarean delivery, although attention to infant's respiratory condition should be paid because remifentanil can cross the placenta.