Two cases of traumatic diaphragmatic hernia with atypical medical history

We have recently experienced two cases of traumatic diaphragmatic hernia which has been repaired by surgery. The first case was a 58-year-old man who had suffered left upper abdominal injury with a branch in his childhood. Although he had never symptoms, chest X-ray showed abnormal shadow in the left lower lung field. Radiologic studies indicated that the great omentum was escaped into the thoracic cavity. On patient request, we performed primary repair of the diaphragmatic hernia on thoracotomy. The second case was a 56-year-old woman who had undergone a left nephrectomy for the left renal abscess. Seven months after the operation, she began to feel nausea and vomiting, and the symptom aggravated with time. Chest X-ray showed air bubbles in the left lower lung field. It proved to be a projection of the stomach into the thoracic cavity through the iatrogenic diaphragmatic injury. We successfully performed a repairment of the diaphragm with a mesh.     

The effects of a point mutation of the beta2 subunit of GABA(A) receptor on direct and modulatory actions of general anesthetics

The gamma-aminobutyric acid type A receptor (GABA(A) receptor) sites involved in the direct and modulatory actions of general anesthetics remain to be elucidated. The mutation of tyrosine at position 157 in the beta2 GABA(A) receptor subunit was reported to reduce sensitivity to activation by GABA, but not pentobarbital. We examined whether this mutation of the beta2 subunit (Tyr157-->Phe) affects the direct and modulatory actions of other general anesthetics such as propofol and etomidate. Using the two-electrode voltage clamp method, we recorded Cl- current in Xenopus oocytes expressing alpha1beta2gamma2s and alpha1-mutated beta2gamma2s subunits. The mutation of the beta2 subunit reduced the apparent affinity for propofol. However, the mutation had no effect on both the direct actions of pentobarbital and etomidate or on the modulatory actions of pentobarbital, propofol and etomidate. These results suggest that unique loci may exist for the direct action of propofol and that the GABA binding site may not mediate the modulatory actions of general anesthetics at GABA(A) receptors.     

Factors associated with serum high mobility group box 1 (HMGB1) levels in a general population

High mobility group box 1 (HMGB1), a nonhistone chromatin-associated protein, is implicated as a mediator of both infectious and non-infectious inflammatory conditions. Clinical research on this protein in humans just has begun; serum HMGB1 was reported to be elevated in a small number of critically ill patients suffering from sepsis. However, the kinetics, distribution and factors associated with circulating HMGB1 are unknown in a general population. In this study, we examined these issues in a large population of healthy subjects. Fasting blood samples were obtained from 626 subjects (237 males and 389 females). HMGB1 levels showed a skewed distribution with a mean of 1.65 ± 0.04 ng/ml. Multiple stepwise regression analyses found that white blood cell (WBC) counts (P = .016) and the soluble form of receptor for advanced glycation end products (sRAGE; P < .001, inversely), which is also known to be a receptor for HMGB1, were independently associated with HMGB1 levels. We demonstrated for the first time that circulating HMGB1 levels were inversely associated with sRAGE levels in a general population. Because RAGE is involved in HMGB1 signaling, our present study suggests that sRAGE may capture and eliminate circulating HMGB1 in humans.     

Clinical significance of amphiregulin and epidermal growth factor in colostrum

Background

Colostrum contains a wide variety of crucial nutritional elements including growth factors for newborn infants to adapt to the extrauterine environment.

Objective

To investigate the clinical significance of epidermal growth factor receptor ligands in milk during the first month of lactation.

Methods

The concentrations of epidermal growth factor (EGF), amphiregulin (AR) and transforming growth factor-?? (TGF-??) in milk sampled from a total of 31 normal mothers at days 1?C3, 5, and 30 postpartum were examined using ELISA.

Results

At days 1?C3, the concentration of EGF was extremely high [131.6?±?20.4 (mean?±?SEM) ng/ml] compared to that of AR (4,197.2?±?1,055.2?pg/ml) or TGF-?? (261.7?±?33.6?pg/ml), while the concentration of AR was significantly elevated compared to that of TGF-??. At days 5 and 30, the concentration of EGF was significantly elevated compared to that of AR or TGF-??. In 16 mothers among the same 31 subjects, samples were longitudinally obtained on days 1, 2, 5, and 30 postpartum. Concentrations of AR were higher on days 1 and 2 and rapidly declined to below 1?ng/ml on day 5, and were maintained at lower levels on day 30. Concentrations of EGF were high on day 1 (greater than 10?ng/ml) but gradually declined by days 2, 5, and 30. Concentrations of TGF-?? remained at lower levels of below 1?ng/ml throughout the lactation period from days 1 to 30.

Conclusion

These results suggested that EGF and amphiregulin in colostrum might contribute to the early stage of development of neonatal gastrointestinal function.     

Choroidal metastasis in a patient with small cell lung cancer discovered during treatment with chemotherapy

A 56-year-old male patient complaining of productive cough, hoarseness, and fatigue was found to have extensive disease of small cell lung cancer (ED-SCLC), with staging of cT4N3M1(PUL). He was treated with chemotherapy. While undergoing treatment with chemotherapy, he complained of a right visual disturbance, and choroidal metastasis was diagnosed. Because the primary site responded well to chemotherapy alone and the visual disturbance did not worsen, the patient refused radiotherapy to the choroidal metastasis. Two months after the first diagnosis of the choroidal metastasis, while he was receiving the first treatment regimen for SCLC, the visual disturbance suddenly worsened; emergent radiotherapy was started, with a total dose of 40 Gy, given as 2.0 Gy/fraction per day. The visual disturbance never improved, and the patient lost 80% of his right visual field. Within 6 months of diagnosis, the patient became blind in his right eye. The patient died of septic shock related to treatment received during his third chemotherapy regimen. Choroidal metastasis is very rare with extraocular malignant tumors, though it is common with intraocular malignant tumors. Choroidal metastasis secondary to SCLC has a poor prognosis, but in order to maintain quality of life during the patients’ remaining lifespan, aggressive treatment would appear appropriate for these patients, because SCLC is a chemo-sensitive cancer.     

Intraocular lens roll-up technique: foldable IOL implantation using forceps through incisions smaller than 3.2 mm

We describe the intraocular lens (IOL) roll-up technique, which uses lens forceps to insert 3 types of foldable polyacrylic IOLs with optic diameters of 6.0 mm through small sclerocorneal incisions comparable to those used by injector systems.     

Comprehensive evaluation of variability in nicotine metabolism and CYP2A6 polymorphic alleles in four ethnic populations

Human cytochrome P450 (CYP) 2A6 metabolizes nicotine to cotinine and is a possible modulator of nicotine addiction. Quantitative and qualitative differences in nicotine addiction have been observed between ethnic groups. However, there are few data on the ethnic influences of the CYP2A6-nicotine metabolism relationship, particularly with regard to black subjects. We determined the nicotine metabolism and CYP2A6 genotype in 176 white subjects and 160 black subjects, comparing them with our previous data from 209 Korean subjects and 92 Japanese subjects. Large interindividual differences were observed in the cotinine/nicotine ratios in plasma calculated as an index of nicotine metabolism in white subjects (range, 0.6-36.5) and in black subjects (range, 0.9-30.4). No ethnic difference in the metabolic ratio was observed among white subjects (mean, 7.2 +/- 5.0), black subjects (mean, 7.1 +/- 4.7), and Korean subjects (mean, 8.7 +/- 11.9), whereas Japanese subjects showed a significantly (P < .005) lower metabolic ratio (mean, 3.8 +/- 3.1) compared with the other populations. Women showed significantly (P < .05) higher metabolic ratios than men in the black population (8.0 +/- 5.3 versus 6.0 +/- 3.7). Obvious ethnic differences in the CYP2A6 alleles were observed among these 4 populations. The combined frequencies of the alleles lacking or showing reduced enzymatic activity (CYP2A6*2, CYP2A6*4, CYP2A6*5, CYP2A6*7, CYP2A6*9, CYP2A6*10, CYP2A6*11, CYP2A6*17, CYP2A6*19, and CYP2A6*20) were 9.1%, 21.9%, 42.9%, and 50.5% in white, black, Korean, and Japanese subjects, respectively. These CYP2A6 alleles were associated with reduced nicotine metabolism. Among the homozygotes of CYP2A6*1, interindividual and ethnic differences in the metabolic ratio were still observed. Thus some factors other than genetic ones might also contribute to the interindividual and ethnic differences. This comprehensive study of 4 populations extends our understanding of nicotine metabolism and the impact of genetic polymorphisms of the CYP2A6 gene.