Current therapy for BCL-2-associated tumors such as Non-Hodgkin Lymphomas (NHL) is inadequate. The DNAi PNT2258, a 24 base single-stranded phosphodiester DNA oligodeoxynucleotide (PNT100) encapsulated in a protective liposome, was precisely designed to treat cancers that over-express BCL-2. PNT2258 strongly inhibited BCL-2 promoter activity, confirming its predicted mechanism of action. BCL-2 mRNA and protein expression were significantly downregulated in a follicular small cleaved cell lymphoma (WSU-FSCCL) cell line. 2.5μM PNT2258 induced an initial S- phase arrest followed by a gradual increase in the sub-G0 (apoptosis) compartment and a reciprocal progressive decrease of the S phase. Terminal deoxynucleotidyl transferase (TdT)-positive populations and cleaved caspase-3 and PARP were also increased. The data are consistent with the idea that BCL-2 inhibition by PNT2258 activates apoptotic pathways in WSU-FSCCL cells. This is the first report to address the distinct mechanism of action underlying the anti-BCL-2 functions of PNT2258. Growth inhibition in two other cell lines, WSU-DLCL2 and WSU-WM, supports broad applicability of BCL-2 DNAi to treatment of B-cell NHL.

DNA interference is aimed at blocking BCL-2 gene transcription. Evaluations of this technology in preclinical and early clinical studies are very encouraging and strongly support further development of DNAi as cancer therapeutics. A pilot phase II clinical trial in patients with relapsed or refractory non-Hodgkin lymphoma, PNT2258 demonstrated clinical benefit in 11 of 13 patients with notable responses in diffuse large B cell lymphoma and follicular lymphoma. By targeting the DNA directly, the DNAi technology promises to be more effective compared with other gene-interference strategies that target the RNA or protein but leaves the dysregulated DNA functional.

We report a case of a 52-year-old immunocompetent Caucasian female treated for necrotizing Streptococcus intermedius pneumonia and review available literature of similar cases. Our patient presented with respiratory failure and required hospitalization and treatment in the intensive care unit. Moreover, she required surgical drainage of right lung empyema as well as decortication and resection. The review of literature revealed three cases of S. intermedius pneumonia, one of which was a mortality. Comparison of the published cases showed a highly varied prehospital course and radiological presentations, with a symptomatic phase ranging from 10 days to five months. Radiological findings varied from an isolated pleural effusion to systemic disease with the presence of brain abscesses. Immunocompetence appears to correlate well with the overall prognosis. In addition, smoking appears to be an important risk factor for S. intermedius pneumonia. In 2 (50%) of cases, pleural fluid analysis identified S. intermedius. In contrast, no organism was found in our patient, necessitating the acquisition of lung tissue sample for the diagnosis. In conclusion, both medical and surgical management are necessary for effective treatment of S. intermedius pneumonia. The outcome of treatment is good in immunocompetent individuals.

Liver abscesses are an uncommon disease that can present with vague symptoms. Fusobacterium necrophorum causing liver abscesses is a rare condition and only a few cases have been reported. An 88-year-old female presented to her primary care physician with one week of fevers, night sweats, chills, fatigue and vague right upper quadrant abdominal pain. She denied nausea, vomiting, constipation, diarrhea and unintentional weight loss. A computed tomography scan of the abdomen showed two liver abscesses in the right lobe as well as extensive diverticulosis. Percutaneous drainage was performed and draining catheters were placed in the abscesses. Culture of the abscess fluid grew Fusobacterium necrophorum. She was treated with ceftriaxone and metronidazole as per sensitivities. Rare cases of F. necrophorum hepatic abscesses have been published. The source of infection described in reported cases included hematogenous spread from dental caries/peritonsillar abscess and those involving the gastrointestinal tract resulting from inflammation of the bowel wall or from inflamed diverticuli via the portal circulation. In one study, thirteen cases of liver abscess due to F. necrophorum were studied, and two of these cases had diverticular disease without inflammation.

Angioedema is a well-known side effect of angiotensin converting enzyme inhibitors (ACEi). However, ACE inhibitors induced angioedema after cervical surgery is a rare condition. They result in increased levels of circulating bradykinins. Rare cases of angioedema following local trauma in patients using ACE inhibitors have been published. We present such a case. A 54-year-old Caucasian female with a history significant for hypertension, controlled with lisinopril, was admitted for routine cervical spine surgery. She has severe degenerative cervical disc disease and was admitted to the hospital for an elective cervical diskectomy. The patient failed weaning off the ventilator on multiple attempts postoperatively. There were no observed symptoms of an allergic reaction. A CT scan of the neck showed extensive soft tissue edema at the level of the arytenoids. Dexamethasone was given to reduce the edema without successful resolution. On review of her medications, it was found that the patient was resumed on lisinopril following the procedure. It was subsequently discontinued. By the following day the patient had a positive leak around the ET tube cuff and patient was successfully extubated.

The prolactin response to metoclopramide (MCP) was studied in 23 sexually immature males, 14 with isolated hypogonadotrophic hypogonadism (IHH) and nine with constitutional delayed puberty. Six of the 14 IHH patients had not been treated prior to our study, whereas eight had received long term therapy with testosterone or hCG for variable periods ranging from 1 to 20 years. We also measured the prolactin response to chlorpromazine (CPZ) in the untreated IHH men. In these untreated subjects, we observed a greatly diminished prolactin response after CPZ by comparison to that measured following MCP administration (peak 15 ng/ml, areas 86 units vs peak 43 ng/ml, area 416 units, respectively) (P less than 0.01). Furthermore, prolactin levels following MCP were similar in untreated (peak 43 ng/ml, area 416 units) and treated (peak 55 ng/ml, area 545 units, NS) IHH males as well as in boys with constitutional delayed puberty (peak 50 ng/ml, area 532 units, NS). In addition, responses in the three groups of patients were about half (P less than 0.01) those measured in normal men (peak 81 ng/ml, area 845 units). These data indicate that, unlike CPZ, MCP is not useful in distinguishing patients with hypogonadotrophic hypogonadism from boys with constitutional delayed puberty.

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