Obligate aerobic,gram-positive,weak acid-fast,nonmotile bacilli,Tsukamurella tyrosinosolvens: Minireview of a rare opportunistic pathogen

Tsukamurella species are obligate aerobic, gram-positive, weak acid-fast, nonmotile bacilli. They are found in various environments, such as soil, water, sludge, and petroleum reservoir wastewater, and belong to the order Actinomycetales. In 2016, there was a reclassification of species within the genus Tsukamurella, merging the species Tsukamurella tyrosinosolvens (T. tyrosinosolvens) and Tsukamurella carboxydivorans. Tsukamurella species are clinically considered to be a rare opportunistic pathogen, because most reported cases have been related to bacteremia and intravascular prosthetic devices and immunosuppression. To date, it has been isolated only from human specimens, and has always been associated with clinical disease; human infections are very rare. Reported infections have included pneumonia, brain abscesses, catheter-related bloodstream infections, ocular infections, bacteremia, and sepsis presenting with septic pulmonary emboli in patients who are immunocompromised. To date, there is no commercially available test for identification. On the other hand, sequence-based identification, including matrix-assisted laser desorption ionization time-of-flight mass spectrometry, is an alternative method for identifying clinical isolates that are either slow growers or difficult to identify through biochemical profiling. The golden standards for diagnosis and optimal management still remain to be determined. However, newer molecular biological techniques can provide accurate identification, and contribute to the appropriate selection of definitive therapy for infections caused by this organism. Combinations of several antimicrobial agents have been proposed for treatment, though the length of treatment for infections has yet to be determined, and should be individualized according to clinical response. Immunocompromised patients often experience severe cases due to infection, and life-threatening T. tyrosinosolvens events associated with dissemination and/or failure of source control have occurred. Favorable prognoses can be achieved through earlier identification of the cause of infection, as well as successful management, including appropriate antibiotic therapy together with source control. Further analyses of similar cases are required to establish the most adequate diagnostic methods and treatment regimens for infections.     

A case of gastric cancer presenting with obstructive jaundice and responding to biweekly CPT-11 and CDDP combination administration

A 74-year-old man was suffering from Borrmann type 2 advanced gastric cancer with abdominal lymph node metastases and multiple lung metastases. He started to undergo outpatient treatment with oral administration of TS-1. But pyloric stenosis was found after 6 courses of TS-1 chemotherapy, so he underwent palliative distal gastrectomy. TS-1 chemotherapy was continued afterwards, however obstructive jaundice was found. So combination chemotherapy of CPT-11 60 mg/m(2)and CDDP 30 mg/m(2)biweekly was selected as a second-line therapy after PTCD. As no side effects were found, he could be treated on an outpatient basis by CPT-11 60 mg/body and CDDP 30 mg/body biweekly. Four months has passed since the palliative operation, and the PTCD tube was successfully removed. The abdominal lymph nodes had decreased in size and the patient has maintained good QOL. Thus, combination CPT-11 and CDDP therapy could well be a new candidate for a second-line chemotherapy in outpatients.     

Pathologic complete response of thoracic esophageal cancer developing after gastrectomy to neoadjuvant low-dose nedaplatin (CDGP), 5-fluorouracil and radiotherapy

We treated a 69-year-old man who had developed esophageal cancer following gastrectomy. Pathologic complete response (pCR) was obtained by neoadjvant chemoradiotherapy using low-dose nedaplatin (CDGP) and 5-fluorouracil. The cancer located in the middle of the thoracic esophagus, had invaded the trachea and metastasized to cervical lymph nodes according to computed tomography. Preoperative chemoradiotherapy combining a low-dose of CDGP with 5-FU was administered together with radiotherapy. Adverse effects included grade 2 stomatitis and leukocytopenia. The esophageal cancer was found by endoscopy to have diminished significantly after completion of neoadjuvant therapy, An endoscopic biopsy specimen was found to contain no malignant cells. The tumor also was smaller by CT, where cervical lymph nodes no longer showed involvement. Partial response was diagnosed based on imaging, and radical resection of the esophageal cancer was performed via right thoracotomy and laparotomy. Operative staging findings indicated Ch x R-T 3 N 0 M 0, Stage II R 0 D 2 Cur A. Pedicled jejunum was used to reconstruct the esophagus through a mediastinal route. Pathologic examination of resected specimens disclosed no viable cancer cells in the esophagus or metastasis to dissected lymph nodes. Neoadjuvant chemoradiotherapy using low-dose CDGP/5-FU is an effective treatment for esophageal cancer.     

Bilirubin as a tracer for detecting gastroesophageal reflux

PURPOSE: The usefulness of intraesophageal monitoring of bilirubin, in diagnosing gastroesophageal reflux, was studied. PATIENTS AND METHODS: Bilirubin concentration and pH at 5 cm oral and anal to the esophagogastric junction were monitored for 24 hours in 19 patients with reflux esophagitis. The duration of bilirubin presented and pH less than 4.0 were obtained as the holding time (HT) of bilirubin and acid, respectively. RESULTS: There was no difference between HT of bilirubin and acid in the stomach and esophagus. In the stomach, HT of bilirubin did not correlate with acid. Whereas, in both of bilirubin and acid, HT in the esophagus correlated significantly with that in the stomach. The correlation was more definite for bilirubin than acid. CONCLUSIONS: Bilirubin and acid presented in the upper stomach for sufficient period independently. Bilirubin monitoring was useful to evaluate the etiology of damaging the esophageal mucosa and causes of symptoms by estimating duodenogastro-esophageal reflux, which has synergistic effect with acid.     

Clinicopathologic and immunohistochemical features of surgically resected small cell carcinoma of the esophagus

Esophageal small cell carcinoma (SmC) is considered an aggressive cancer carrying a poor prognosis, although the rarity of this tumor has impeded statistical evaluation. We reviewed records of 457 esophageal cancer patients treated in our department from 1986 to 2000, comparing clinicopathologic factors and post-treatment outcomes, for 9 patients with SmC, most undergoing esophagectomy including lymphadenectomy, with data from 128 patients with esophageal squamous cell carcinoma (SqC) invading to the muscular layer or beyond. Immunohistochemical features were compared between the SmC and 12 consecutive SqC. All patients studied had localized disease according to preoperative staging. SmC showed more ulcerative and infiltrative growth, and more aggressive lymphatic spread, than SqC. All SmC patients had lymph node metastasis (thoracic nodes, 9 patients: abdominal 6; cervical 1). All SmC specimens but no SqC were immunoreactive for neuron-specific enolase. Two and three SmC specimens were reactive for epithelial membrane antigen and keratin, respectively. Survival of SmC patients after esophagectomy (median, 11 months) was worse than for SqC patients (p=0.013). However, 1 SmC patient remains alive at 76 months. Survival was not related to any clinicopathologic or immunohistochemical features. While SmC shows aggressive behavior and worse outcomes than SqC, combining esophagectomy with chemotherapy or radiotherapy may prolong survival.     

Different genetic alterations in rat forestomach tumors induced by genotoxic and non-genotoxic carcinogens

Human beings are exposed to a multitude of carcinogens in their environment, and most cancers are considered to be chemically induced. Here we examined differences in genetic alterations in rat forestomach tumors induced by repeated exposure to a genotoxic carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or N-methylnitrosourethane (MNUR), and chronic treatment with a non-genotoxic carcinogen, butylated hydroxyanisole (BHA) or caffeic acid (CA). A total of 132, 6-week-old male F344 rats were employed. Forty rats were treated with MNNG by intragastric administration at a dose of 20 mg/kg body wt once a week for 32 weeks, and 20 rats received 20 p.p.m. MNUR in their drinking water for 48 weeks. Further groups of 20 animals were administered 2% BHA or 2% CA in the diet for 104 weeks. The remaining rats were maintained without any supplement as controls. Multiple forestomach tumors were observed in all rats of the MNNG-, MNUR-, BHA- and CA-treated groups. Histopathologically, MNUR- and CA-treated groups showed almost the same pattern. On polymerase chain reaction-single strand conformation polymorphism analysis, H-ras and p53 gene mutations were observed at high and relatively low frequencies, respectively, in forestomach tumors induced by MNNG and MNUR. Most H-ras gene mutations were G-->A transitions in codons 7 and 12 of exon 1. On the other hand, forestomach tumors due to the non-genotoxic carcinogens, BHA and CA, had almost no mutations of the H-ras and p53 genes. Moreover, relative overexpression of cyclin D1 and p53 was detected in forestomach tumors induced by the genotoxic carcinogens, while their non-genotoxic counterparts had a tendency to show low expression of those molecules. Mutations of the beta-catenin gene were not detected in any group. The present study demonstrates that rat forestomach tumors induced by genotoxic and non-genotoxic carcinogens have different underlying genetic alterations, even if their pathological features are similar.     

Effects of guanine nucleotide and sulfhydryl reagent on subpopulations of muscarinic acetylcholine receptors in mammalian hearts: possible evidence for interconversion of super-high and low affinity agonist binding sites

Multiple site models of muscarinic acetylcholine receptors (mAChR) for agonist binding were applied to curves for the inhibition of QNB binding by carbachol by using nonlinear least square regression analysis. The effects of a guanine nucleotide guanyl-5′-yl imidodiphosphate (Gpp(NH)p) and a sulfhydryl reagent 5,5′-dithiobis(2-nitrobenzoic acid (DTNB) on the curves were also analyzed. The results suggested that mAChR of dog and guinea pig heart had three types of sites with different affinities for carbachol (super-high (SH), high (H) and low (L)). In the presence of Gpp(NH)p, SH sites were eliminated and L sites increased, indicating conversion of SH sites to L sites. On the contrary, in the presence of DTNB, L sites were converted to SH sites. These results were obtained at both 37°C and 0°C incubation although the affinity of each site was high at 0°C than at 37°C. These data suggest the interconversion of SH and L sites. The possible existence of two subtypes (GTP-regulated mAChR(SH-L type) and GTP-independent mAChR (H type)) is discussed.     

Effects of age and gender on neuroanatomical volumes

Purpose:

To investigate age‐related differences, gender differences, and age‐by‐gender interactions on the volumes of 18 neuroanatomical structures, with a large sample at a single institution.

Materials and Methods:

A total of 861 normal subjects (mean age = 56.1 ± 9.8 years, age range = 24.0–84.8 years) were included in this study. All subjects were scanned at 3.0 T. Measurement of the 18 neuroanatomical volumes was performed with FreeSurfer v. 4.5. Differences in volumes of neuroanatomical structures were tested using analysis of covariance with intracranial volume‐normalized volume as the dependent variable, and independent variables of age, sex, age × sex, age × age, age × age × sex, and scanner. Nonsignificant higher‐order terms were removed sequentially from the model. A P value of < 0.0028 (=0.5/18) was considered to indicate a statistically significant difference.

Results:

All neuroanatomical volumes, except for the caudate nucleus, pallidum, and 4th ventricle, were significantly related to age (linearly or quadratically). Significant gender differences were found in all neuroanatomical volumes, except for cerebral white matter, cerebellar cortex, caudate nucleus, and amygdala. No neuroanatomical volume showed a significant interaction between age (age × age) and gender.

Conclusion:

Our results showed age and gender effects on neuroanatomical volumes, and indicate no gender difference in the aging process of neuroanatomical volumes. J. Magn. Reson. Imaging 2013;37:1072–1076. © 2012 Wiley Periodicals, Inc.