Two unusual cases of Guillain-Barre syndrome after snake bite: the rare immune mediated complication of Elapid venom.

In this report, we present a series of two unusual cases of elapid snakebite with acute neuroparalysis, that after initial response to standard anti-snake venom therapy, developed recurrence of disabling quadriparesis with dysautonomia, that on detailed evaluation turned out to be immune-mediated polyradiculoneuropathy (GB syndrome). Both the cases then responded to therapy with intravenous immunoglobulins. These cases bring out the rare immune-mediated late complication of snake venom, which if recognized and treated in time, can significantly reduce the morbidity and mortality.

Adaptive Enrichment of a Thermophilic Bacterial Isolate for Enhanced Enzymatic Activity.

The mimicking of evolution on a laboratory timescale to enhance biocatalyst specificity, substrate utilization activity, and/or product formation, is an effective and well-established approach that does not involve genetic engineering or regulatory details of the microorganism. The present work employed an evolutionary adaptive approach to improve the lignocellulose deconstruction capabilities of the strain by inducing the expression of laccase, a multicopper oxidase, in Geobacillus sp. strain WSUCF1. This bacterium is highly efficient in depolymerizing unprocessed lignocellulose, needing no preprocessing/pretreatment of the biomasses. However, it natively produces low levels of laccase. After 15 rounds of serially adapting this thermophilic strain in the presence of unprocessed corn stover as the selective pressure, we recorded a 20-fold increase in catalytic laccase activity, at 9.23 ± 0.6 U/mL, in an adapted yet stable strain of Geobacillus sp. WSUCF1, compared with the initial laccase production (0.46 ± 0.04 U/mL) obtained with the unadapted strain grown on unprocessed corn stover before optimization. Chemical composition analysis demonstrated that lignin removal by the adapted strain was 22 wt.% compared with 6 wt.% removal by the unadapted strain. These results signify a favorable prospect for fast, cost competitive bulk production of this thermostable enzyme. Also, this work has practical importance, as this fast adaptation of the Geobacillus sp. strain WSUCF1 suggests the possibility of growing industrial quantities of Geobacillus sp. strain WSUCF1 cells as biocatalysts on reasonably inexpensive carbon sources for commercial use. This work is the first application of the adaptive laboratory evolution approach for developing the desired phenotype of enhanced ligninolytic capability in any microbial strain.

Metastatic appendiceal cancer treated with Yttrium 90 radioembolization and systemic chemotherapy: A case report.

BACKGROUND: Primary appendiceal cancers are rare, and they generally present with liver and/or peritoneal metastases. Currently there are no guidelines to treat metastatic appendiceal cancer, and hence they are treated as metastatic colorectal cancer. Combining Yttrium 90 (Y-90) radioembolization (RE) with systemic chemotherapy early in the treatment of right sided colon cancers has been shown to improve survival. Based on this data, a combination of systemic chemotherapy and Y-90 RE was used to treat a case of metastatic appendiceal cancer. CASE SUMMARY: A 76-year-old male presented to the emergency room with progressive right lower quadrant pain. A Computed Tomography of the abdomen and pelvis was performed which showed acute appendicitis and contained perforation. Urgent laparoscopic appendectomy was then followed by histological analysis, which was significant for appendiceal adenocarcinoma. After complete workup he underwent right hemicolectomy and lymph node dissection. He received adjuvant chemotherapy as the local lymph nodes were positive. Follow-up imaging was significant for liver metastasis. Due to rapid growth of the liver lesions and new peritoneal nodules, the patient was treated with a combination of Y-90 RE and folinic acid, fluorouracil, and irinotecan with bevacizumab and not microwave ablation as previously planned. Follow up imaging demonstrated complete response of the liver lesions. At 12-mo follow-up, the patient continued to enjoy good quality of life with no recurrent disease. CONCLUSION: Utilization of Y-90 RE concomitantly with systemic chemotherapy early in the treatment of appendiceal cancer may provide improved control of this otherwise aggressive cancer.

Unusual presentation of a left testicular carcinoid.

Testicular carcinoid generally presents either with a palpable (painful or painless) or rarely a nonpalpable mass (when it is diagnosed incidentally on scrotal imaging) of the involved testis. An ipsilateral testicular carcinoid presenting exclusively with contralateral testicular symptoms has never been described in the literature to date. We report a case of nonpalpable left testicular carcinoid diagnosed incidentally on a sonogram done for right testicular pain and swelling, with conspicuous absence of left testicular symptoms. This case highlights the importance of recognizing such an atypical presentation of testicular carcinoid.

Life-threatening retro-pharyngeal bleed in a case of systemic lupus erythematosus--an uncommon but important evil of a common disease.

Acquired inhibitors of coagulation are antibodies that interfere with the coagulation system either by functional inhibition of the activity of clotting factors or by their increased clearance from the plasma. They can be idiopathic or seen in various physiologic (pregnancy and postpartum) or pathologic states (systemic lupus erythematosus (SLE), malignancies, rheumatoid arthritis) and can result in a variety of haemorrhagic sequelae. SLE can be associated with antibodies to multiple clotting factors and bleeding though rare can be an important haematologic manifestation with life-threatening consequences in these patients.

Thrombectomy reduces the systemic complications in device-related right atrial septic thrombosis.

BACKGROUND: Septic thrombosis of the right atrium is an unusual complication associated with the use of indwelling devices. The optimal management of this condition is unclear. Our experience with a patient with hemodialysis catheter-related septic thrombosis of the right atrium illustrates the difficulties associated with this condition. OBJECTIVES: To determine the effects of surgical thrombectomy compared with nonsurgical treatment with antibiotics (with or without anticoagulation) on mortality rates and complications in patients with device-related septic thrombosis of the right atrium. METHODS: A retrospective analysis of all reported cases of device-related right heart septic thrombosis in which therapy and outcome were reported was conducted using a PubMed search in the English-language literature (1985 to 2006). RESULTS: Forty cases of device-related right atrial septic thromboses were reported in the literature during the chosen time period. The treatments administered were none (12.5%), antibiotics (12.5%), antibiotics and anticoagulation (20%), and thrombectomy (55%). The mean clot size was significantly larger in patients who underwent thrombectomy. All untreated patients died. Excluding the untreated patients from the analysis, systemic complications were significantly lower in the thrombectomy group than in the groups receiving nonsurgical therapies. Using multivariate modelling with survival as the primary outcome, age, sex, clot size, clot location, microbial organism or type of treatment were not predictive of the outcome. CONCLUSION: Device-related right atrial septic thrombosis is associated with significant mortality and is uniformly fatal if untreated. Surgical thrombectomy is associated with less frequent systemic complications. A well-designed prospective, randomized trial is needed to determine the optimal treatment of this condition.

Nuclear factor-kappaB activation: a molecular therapeutic target for estrogen receptor-negative and epidermal growth factor receptor family receptor-positive human breast cancer.

Nuclear factor-kappaB (NF-kappaB), a transcription factor with pleotropic effects, is a downstream mediator of growth signaling in estrogen receptor (ER)-negative and erbB family particularly erbB2 (HER-2/neu) receptor-positive cancer. We previously reported activation of NF-kappaB in ER-negative breast cancer cells and breast tumor specimens, but the consequence of inhibiting NF-kappaB activation in this subclass of breast cancer has not been shown. In this study, we investigated the role of NF-kappaB activation by studying the tumorigenic potential of cells expressing genetically manipulated, inducible, dominant-negative inhibitory kappaB kinase (IKK) beta in xenograft tumor model. Conditional inhibition of NF-kappaB activation by the inducible expression of dominant-negative IKKbeta simultaneously blocked cell proliferation, reinstated apoptosis, and dramatically blocked xenograft tumor formation. Secondly, the humanized anti-erbB2 antibody trastuzumab (Herceptin) and the specific IKK inhibitor NF-kappaB essential modifier-binding domain peptide both blocked NF-kappaB activation and cell proliferation and reinstated apoptosis in two ER-negative and erbB2-positive human breast cancer cell lines that are used as representative model systems. Combinations of these two target-specific inhibitors synergistically blocked cell proliferation at concentrations that were singly ineffective. Inhibition of NF-kappaB activation with two other low molecular weight compounds, PS1145 and PS341, which inhibited IKK activity and proteasome-mediated phosphorylated inhibitory kappaB protein degradation, respectively, blocked erbB2-mediated cell growth and reversed antiapoptotic machinery. These results implicate NF-kappaB activation in the tumorigenesis and progression of ER-negative breast cancer. It is postulated that this transcription factor and its activation cascade offer therapeutic targets for erbB2-positive and ER-negative breast cancer.

Crossroads of estrogen receptor and NF-kappaB signaling.

Cellular homeostasis in higher organisms is maintained by balancing cell growth, differentiation, and death. Two important systems that transmit extracellular signals into the machinery of the cell nucleus are the signaling pathways that activate nuclear factor kappaB (NF-kappaB) and estrogen receptor (ER). These two transcription factors induce expression of genes that control cell fates, including proliferation and cell death (apoptosis). However, ER has anti-inflammatory effects, whereas activated NF-kappaB initiates and maintains cellular inflammatory responses. Recent investigations elucidated a nonclassical and nongenomic effect of ER: inhibition of NF-kappaB activation and the inflammatory response. In breast cancer, antiestrogen therapy might cause reactivation of NF-kappaB, potentially rerouting a proliferative signal to breast cancer cells and contributing to hormone resistance. Thus, ER ligands that selectively block NF-kappaB activation could provide specific potential therapy for hormone-resistant ER-positive breast cancers.