Consensus clinical scoring for suspected perioperative immediate hypersensitivity reactions.

BACKGROUND: Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents. METHODS: We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1-9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated. RESULTS: Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5); these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase. CONCLUSION: We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.

Management of a surgical patient with a label of penicillin allergy: narrative review and consensus recommendations.

Unsubstantiated penicillin-allergy labels are common in surgical patients, and can lead to significant harm through avoidance of best first-line prophylaxis of surgical site infections and increased infection with resistant bacterial strains. Up to 98% of penicillin-allergy labels are incorrect when tested. Because of the scarcity of trained allergists in all healthcare systems, only a minority of surgical patients have the opportunity to undergo testing and de-labelling before surgery. Testing pathways can be modified and shortened in selected patients. A variety of healthcare professionals can, with appropriate training and in collaboration with allergists, provide testing for selected patients. We review how patients might be assessed, the appropriate testing strategies that can be used, and the minimum standards of safe testing.

Effects of DSP-8658, a novel selective peroxisome proliferator-activated receptors a/γ modulator, on adipogenesis and glucose metabolism in diabetic obese mice.

AIMS/INTRODUCTION: Peroxisome proliferator-activated receptors (PPARs) play a key regulating role in homeostasis. In this study, we investigated the effects of DSP-8658, a novel selective PPARa/γ modulator, on adipogenesis and glucose metabolism in diabetic obese mice and compared these effects to those of pioglitazone, a PPARγ full agonist. MATERIALS AND METHODS: DSP-8658 functional activity was assessed by PPARγ-target genes expression in adipose 3T3-L1 cells and its anti-diabetic efficacy evaluated in db/db mice. The effects of DSP-8658 on adipogenesis were investigated diet induced obese (DIO) KK-A(y) mice. RESULTS: DSP-8658 reduced the expression of PPARγ-target gene 11 beta hydroxysteroid dehydrogenase type 1 with an EC50 value 2.1-fold that of pioglitazone and 28.4-fold that of rosiglitazone. On the other hand, DSP-8658 increased the expression of fatty acid binding protein 4 and glycerol kinase genes with EC50 values 33-fold and >15-fold those of pioglitazone and 163-fold and >38-fold those of rosiglitazone, respectively. In db/db mice, DSP-8658, like pioglitazone, decreased blood glucose, HbA1c, and plasma triglyceride levels and increased plasma insulin concentration and pancreatic insulin contents. In DIO KK-A(y) mice, DSP-8658, unlike pioglitazone, decreased subcutaneous adipose tissue weight and mean adipocyte size. However, both DSP-8658 and pioglitazone improved blood glucose and HbA1c levels with similar efficacy. Although DSP-8658 did not change the expression levels of fatty acid transport protein 1 and glycerol kinase genes in subcutaneous adipose tissue of KK-A(y) mice, pioglitazone increased these gene expression levels. CONCLUSION: Unlike PPARγ full agonists, DSP-8658 ameliorates blood glucose without increasing adipogenesis in diabetic obesity mice.

Percutaneous radio-frequency mandibular nerve rhizotomy guided by CT fluoroscopy.

We describe a new method for radio-frequency mandibular nerve rhizotomy under CT fluoroscopy. A patient with cancer had severe intractable and drug-resistant pain in his left mandibular region. Because he had an anatomic deformity due to cancer invasion and radiation therapy, we planned a mandibular nerve rhizotomy under CT fluoroscopic imaging. The needle was advanced to the mandibular nerve just caudal to the foramen ovale under real-time CT fluoroscopy, avoiding the cancer region. Pain scores of the patient were reduced after the nerve rhizotomy, without any complications.

Current perception thresholds of patients with long-term administration of maprotiline.

The purpose of this study was to evaluate sensory nerve function using current perception thresholds (CPTs) in patients who were administrated maprotiline. Twelve patients with post-herpetic neuralgia and 20 control subjects were studied. The patients with post-herpetic neuralgia were given a daily dose of 60 mg of maprotiline and were maintained at the same dose for 6 months. Twenty control subjects were randomly selected from healthy volunteers. ACPT test was used for quantitative assessment of A beta, A sigma, and C fiber transmission, which are associated with pain, by three (2000, 250, and 5 Hz) different frequencies of electric stimulation. CPTs of 5, 250, and 2000 Hz in patients with post-herpetic neuralgia 2 months after administration of maprotiline were 141.7 +/- 17.3 for 5 Hz, 120.8 +/- 12.9 for 250 Hz, and 256.4 +/- 18.0 for 2000 Hz, which were significantly (P < 0.01) higher than those (67.0 +/- 9.1 for 5 Hz, 73.4 +/- 7.0 for 250 Hz, and 191.3 +/- 20.2 for 2000 Hz) before treatment and than those (35.3 +/- 15.8, 62.0 +/- 18.9, and 198.9 +/- 15.8) of control subjects. An increase in CPT for 5 Hz at 2 months after administration of maprotiline correlated (r = 0.71, p = 0.01) with a decrease in pain score. There were no correlations between an increase in CPT and changes in Hamilton Depression Scale (HAMD) values until 3 months after maprotiline treatment. However, we found that an increase in CPT for 5 Hz at 6 months after maprotiline treatment correlated (r = 0.68, p = 0.015) with a decrease in HAMD values. In conclusion, administration of 60 mg maprotiline significantly increased current perception thresholds at 2 months after the administration.

Plasma proinflammatory cytokine response to surgical stress in elderly patients.

We investigated the change of plasma cytokines concentrations in elderly patients during lower abdominal surgery. Plasma interleukin (IL-)6 concentrations (68.0+/-15.4 and 36.1+/-20.7 pg/ml) in elderly patients at 24 h and at 3 days after surgery were significantly higher than those (35.1+/-21.5 and 18.6+/-10.6 pg/ml) of young adults. Plasma IL-6 concentrations (92.3+/- 31.9 pg/ml) in elderly patients anesthetized with propofol and fentanyl were significantly higher at the end of the operation than that (57.9+/-36.7 pg/ml) of elderly patients anesthetized with sevoflurane and fentanyl. In conclusion, elderly patients have an increased and delayed IL-6 response to surgical trauma compared with young adults. Plasma IL-6 production after surgical trauma in elderly patients with total intravenous anesthesia with propofol was significantly higher than that in elderly patients with sevoflurane anesthesia.

Effect of epidural analgesia on postoperative paralytic ileus in chronic schizophrenia.

BACKGROUND AND OBJECTIVES: Postoperative paralytic ileus is frequently encountered in chronic schizophrenic patients who undergo abdominal surgery. We investigated whether epidural analgesia with local anesthetics minimizes postoperative ileus in schizophrenic patients who are treated long term with antipsychotic drugs. METHODS: We measured the VAS pain after surgery and the time that elapsed before the first passage of flatus and/or feces after the end of surgery in schizophrenic patients provided analgesia with systemic buprenorphine (group A) and schizophrenic patients receiving epidural analgesia with local anesthetics (group B). RESULTS: The frequency of patients who did not pass flatus and/or feces for more than 120 hours postoperatively was significantly higher in group A. Postoperative pain scores of group A at 8 and 24 hours after the end of anesthesia were 36.0 +/- 12.8 and 31.7 +/- 10.7 (0 to 100 mm scale), which were significantly higher than 25.4 +/- 13.2 and 20.5 +/- 9.4 scores in group B. CONCLUSIONS: Epidural analgesia with local anesthetics in chronic schizophrenic patients undergoing abdominal surgery minimizes postoperative ileus compared to patients receiving systemic buprenorphine.

Effects of the aminopeptidase P inhibitor apstatin on bradykinin-induced inositol 1,4,5-triphosphate in neonatal rat cardiomyocytes.

We investigated the effect of apstatin (an aminopeptidase P inhibitor) on bradykinin-induced inositol 1,4,5-triphosphate (IP3) formation and glucose uptake in isolated neonatal rat cardiomyocytes. Apstatin enhanced bradykinin-induced IP3 formation in a dose-dependent manner. We found that 1 microM Hoe 140 (a bradykinin B2-receptor antagonist) significantly decreased the potentiation of bradykinin-induced IP3 production by 5 microM apstatin from 781.8+/-67.2 to 127.4+/-33.0 pmol/mg protein; 5 microM apstatin increased bradykinin-induced glucose uptake from 197.0+/-25.5 to 297.3+/-64.0 pmol/h per milligram of protein. The stimulation of glucose uptake with apstatin was blocked to 132.5+/-26.2 pmol/h per milligram of protein by 1 microM Hoe 140. We conclude that apstatin stimulates bradykinin-induced IP3 formation and glucose uptake by preventing the degradation of bradykinin.

Endocrine response to surgical stress in three patients over 100 yr.

PURPOSE: To report the change of plasma epinephrine, norepinephrine, cortisol, plasma renin activity, plasma aldosterone and plasma atrial natriuretic peptide during general anesthesia in three centenarian patients. CLINICAL FEATURES: Three patients aged 101, 101 and 102-yr, underwent a screw fixation of femoral fracture under general anesthesia. Plasma concentrations of epinephrine, norepinephrine, cortisol, renin activity, aldosterone and atrial natriuretic peptide were measured before the induction of anesthesia, 15 min after incision and 60 min after the end of surgery. Plasma epinephrine concentrations in the three patients increased from 419, 344 and 377 pg x ml(-1) before anesthesia to 688, 534 and 478 pg x ml(-1) 15 min after skin incision. Plasma norepinephrine concentrations increased markedly from 408, 513 and 606 pg x ml(-1) before anesthesia to 2950, 1864 and 1574 pg x ml(-1) 15 min after skin incision. The cortisol response to surgery was similar to that of young adults. Plasma aldosterone and renin activity was low throughout anesthesia. Plasma atrial natriuretic peptide increased from 353, 367 and 109 pg x ml(-1) before induction to 479, 487 and 168 pg x ml(-1) 15 min after skin incision. CONCLUSION: Plasma norepinephrine concentration in patients over 100 yr increased markedly during anesthesia, while plasma renin activity and aldosterone were lower.

Plasma inflammatory cytokine response to surgical trauma in chronic depressed patients.

We investigated inflammatory cytokine response in chronic depressed patients during abdominal surgery. Twenty-five major depressed patients (Group D) and twenty-five patients (Group C) as the control were studied. Plasma interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) concentrations were measured before and at 15 min after induction of anesthesia, the end of surgery, 24 h and 3 days after the operation. Plasma IL-6 concentrations in Group D at the end of the operation and 24 h after surgery were significantly lower than those of Group C. The plasma IL-6 concentration (87.1+/-55.3 pg/ml) of patients scoring more than 18 points in the Hamilton depression-rating score at the end of the operation was significantly higher than 57.5+/-76.7 pg/ml of patients scoring less than 18 points. Plasma IL-8 concentration (6.1+/-3.2 pg/ml) in Group D at the end of the operation was significantly lower than 8.7+/-4.2 pg/ml of Group C. We conclude that plasma IL-6 and IL-8 response to surgical trauma is inhibited in chronic depressed patients. The IL-6 response to surgical trauma is depending on the clinical state of depression.

Production of functional human selenocysteine-containing KDRF/thioredoxin reductase in E. coli.

In a previous study, we reported the isolation of a cDNA encoding KDRF (KM-102-derived reductase like factor) from the human bone marrow-derived stromal cell line KM-102. Analysis of the sequence of this cDNA revealed it to be the previously reported human thioredoxin reductase cDNA. Human thioredoxin reductase, which was recently isolated from human lung adenocarcinoma NCI-H441 cells as a selenocysteine-containing selenoprotein, and its substrate thioredoxin are thought to be essential for protecting cells from the damage caused by reactive oxygen species. To obtain the selenocysteine-containing recombinant KDRF/thioredoxin reductase, we introduced a secondary structure, which is identical to the selenocysteine insertion signal of Escherichia coli formate dehydrogenase H mRNA, downstream of the TGA in the KDRF/thioredoxin reductase cDNA and expressed it in E. coli. As a result, a significant amount of selenocysteine was incorporated into the C-terminus of the KDRF/thioredoxin reductase protein. The selenocysteine-containing KDRF/thioredoxin reductase showed reducing activities toward human and E. coli thioredoxin, whereas non-selenocysteine-containing KDRF/thioredoxin reductase showed no enzyme activity. Our results suggest that this strategy will be applicable to the production of other mammalian selenocysteine-containing selenoproteins in E. coli.

Experimental use of a transportable hyperbaric chamber durable for 15 psi at 3700 meters above sea level.

A transportable hyperbaric chamber durable for 15 psi of pressure was used to treat a patient suffering from moderate acute mountain sickness at 3700 m above sea level. The symptoms were ameliorated a few minutes after pressurization in the chamber. After a 20-minute stay in the chamber, the patient was completely free of symptoms. Since the chamber can be inflated by using compressed air from a cylinder, no strenuous work was required of the operators. This transportable chamber seems to be useful for the treatment of high-altitude disorders at around 3000 m above sea level.

Identification and C-terminal characterization of proteins from two-dimensional polyacrylamide gels by a combination of isotopic labeling and nanoelectrospray Fourier transform ion cyclotron resonance mass spectrometry.

We propose a novel method for the identification and C-terminal characterization of proteins separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Proteins were digested in a gel in a buffer solution containing 50% 18O-labeled water, and mixtures of 18O/16O-labeled peptides were analyzed by nanoelectrospray Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). This method was evaluated using horse skeletal muscle myoglobin as the model protein in SDS gel. The high resolution of FT-ICR MS minimized the overlapping of peptide peaks and facilitated identification of the C-terminal peptide, which was done by observing the undisrupted isotope peak pattern. As well, with its low ppm-level high mass accuracy, it can rapidly and reliably identify the in-gel-separated protein and determine its C-terminal by peptide mass fingerprinting alone. Therefore, this method should be applicable to routine and high-throughput proteome studies. Here, the method was applied to the analysis of rat liver proteins separated by 2D-PAGE. The C-termini of eight proteins were successfully identified out of 10 randomly picked Coomassie brilliant blue-stained spots. The feasibility and limitations of this approach are reported in this paper.

Exercise-induced cerebral deoxygenation among untrained trekkers at moderate altitudes.

The pathophysiology of altitude-related disorders in untrained trekkers has not been clarified. In the present study, the effects of workload on cardiovascular parameters and regional cerebral oxygenation were studied in untrained trekkers at altitudes of 2700 m and 3700 m above sea level. We studied 6 males and 4 females at each altitude, and their average ages were 31.3+/-7.1 y at 2700 m and 31.2+/-6.8 y at 3700 m, respectively. The resting values of heart rate and mean blood pressure were not significantly different at 2700 m and 3700 m than at sea level. However, increases in these values after exercise were more prominent at high altitudes (heart rate increase = 51.6% at 2700 m and 70.4% at 3700 m; mean blood pressure increase: 19.0% at 2700 m and 17.2% at 3700 m). In addition, post-exercise blood lactate concentration was significantly higher at 3700 m than at sea level or at 2700 m (i.e., 7.6 mM at 3700 m, 3.8 mM at 2700 m, and 4.17 mM at 0 m, respectively). Exercise induced an acute reduction in the arterial oxygen saturation value (SpO2) at 2700 m and 3700 m (i.e., 11.2% reduction at 2700 m and 9.4% at 3700 m), whereas no changes were observed at sea level. The resting values of regional oxygen saturation (rSO2)--measured by a near infra-red spectrophotometer at sea level, 2700 m, and 3700 m-were nearly identical. Exercise at sea level did not reduce this value. In contrast, we observed a decrease in rSO2 after subjects exercised at 2700 m and 3700 m (i.e., 26.9% at 2700 m and 48.1% at 3700 m, respectively). The rSO2 measured 2 min and 3 min after exercise at 3700 m was significantly higher than the preexercise value. From these observations, we concluded that alterations in cardiovascular parameters were apparent only after an exercise load occurred at approximately 3000 m altitude. Acute reduction in cerebral regional oxygen saturation might be a primary cause of headache and acute mountain sickness among unacclimatized trekkers.

A Case of Sclerosing Lymphocytic Lobulitis of the Breast Associated with Diabetes Mellitus.

BACKGROUND: The benign breast disease sclerosing lymphocytic lobulitis is thought to result from autoimmune diseases causing insulin-dependent diabetes mellitus (IDDM) due to insulinitis. In cases of sclerosing lymphocytic lobulitis accompanied by IDDM, the clinical term gdiabetic fibrous breast disease hhas been proposed. METHODS: A case of sclerosing lymphocytic lobulitis of the breast is described RESULTS: The patient was a 43-year-old woman diagnosed with non insulin-dependent diabetes mellitus (NIDDM) 8 years previously. Insulin therapy was thought to be necessary because treatment with glibenclamide was not effective. She visited our facility complaining of a lump in her right breast that was 5 cm in diameter, painless, rock-hard, discrete, and irregularly outlined. Biopsy was performed because breast cancer was strongly suggested by its hardness and its irregular internal echo on ultrasonography. Histopathological findings demonstrated marked stromal sclerosis and lymphocyte infiltration in the perivascular and perilobular areas. Sclerosing lymphocytic lobulitis was diagnosed. CONCLUSION: Referring physicians should avoid performing unnecessary repeated biopsies by recognizing this disease entity, which often occurs bilaterally.

A clinicopathological study on combined hepatocellular and cholangiocarcinoma.

We clinicopathologically studied 23 surgically resected cases of combined hepatocellular and cholangiocarcinoma (HCC-CC). The frequency of this cancer in our subjects, who had primary liver cancer and who underwent hepatectomy, was 6.3%. The mean age of patients was 64.0 years old and the male: female ratio was 1.9:1. Serum alpha-fetoprotein was positive in 70% of cases and its levels were relatively low (< or = 1000 ng/mL) in most cases. The positive rate of serum carcinoembryonic antigen was 18% and its levels were also low. In regard to hepatitis virus markers, 17% of the 20 combined HCC-CC cases were positive to HBs antigen and 70% were positive to the HCV antibody. Of the 23 combined HCC-CC cases, 9 cases (39%) were associated with liver cirrhosis. Tumours were classified macroscopically into a separated type (HCC and CC are clearly separated 17%), a HCC-predominant type (resembles HCC 49%), and a CC-predominant type (resembles CC 34%). The separated and HCC-predominant types were associated with liver cirrhosis in 50 and 55% of cases, respectively. These cases with liver cirrhosis presented the features of HCC more apparently, while those without liver cirrhosis presented the features of CC. Histologically, all cases were classified into either Type I (HCC and CC were clearly distinguished; 17%), Type II (HCC and CC were contiguous and shared transitional features; 66%), and Type III (cancer cells were able to be evaluated as either HCC or CC and were considered to be an intermediate type; 17%). Immunohistological stains for cytokeratin were useful to distinguish HCC and CC. Specifically, CC was positive to cytokeratin 7 and 19. The tumour, in which HCC and CC were almost indistinguishable, such as Type III), indicates the presence of intermediate tumour cells that can differentiate either to HCC or CC.

Biliary hamartomas simulating multiple hepatic metastasis on imaging findings.

We encountered a 62-year-old female with advanced gastric cancer, in whom multiple nodular lesions in the liver, which were depicted as small low density areas, less than 5 mm in diameter, on computed tomography and demonstrated as a heterogenic pattern on ultrasonograms. This patient was suspected to have multiple liver metastases of gastric cancer. She deteriorated gradually and died of respiratory failure due to lung metastasis. At autopsy these hepatic nodular lesions were biliary hamartomas. Biliary hamartoma is a lesion usually identified microscopically, and there have been only 8 cases including ours, which were depicted on images. Along with a remarkable advance in imagings, it should become more important to differentiate biliary hamartoma from malignant hepatic neoplasms on images.