Pituitary abscess: our experience with a case and a review of the literature

Pituitary abscess is a rare disease. Due to its potentially high mortality and morbidity rate, it should be considered in the differential diagnosis of sellar masses. Despite recent advances in radiological investigations, making a definitive diagnosis preoperatively remains challenging. This 45-year-old Indian gentleman presented with severe throbbing headache for six months. Magnetic resonance imaging of the brain revealed a sellar mass with peripheral enhancement that was misdiagnosed as a pituitary macroadenoma. A trans-sphenoidal excision was done, which surprisingly yielded only pus that was drained accordingly from the lesion. Fungal and bacterial cultures were negative. However this patient subsequently lost complete function of the pituitary gland, resulting in central diabetes insipidus and required permanent hormonal replacement therapy in the deficient endocrine axes. A Medline search was conducted and a review of 24 cases reported in the last 5 years discussed.     

Activation of MAP kinase-activated protein kinase 2 in human neutrophils after phorbol ester or fMLP peptide stimulation

In response to extracellular stimulation, one of the earliest events in human neutrophils is protein phosphorylation, which mediates signal transduction and leads to the regulation of cellular functions. Mitogen- activated protein (MAP) kinases are rapidly activated by a variety of mitogens, cytokines, and stresses. The activated MAP kinases in turn regulate their substrate molecules by phosphorylation. MAP kinase- activated protein (MAPKAP) kinase 2, a Ser/Thr kinase, has been shown to be phosphorylated by p38 MAP kinase both in vivo and in vitro. Phosphorylation of the Thr-334 site of MAPKAP kinase 2 results in a conformational change with subsequent activation of the enzyme. To better define the role of MAPKAP kinase 2 in the activation of human neutrophils, its enzymatic activity was measured after stimulation by either a phorbol ester (phorbol myristate acetate [PMA]), a potent protein kinase C activator, or the tripeptide fMLP, which is a chemotactic factor. The in vitro kinase assays indicate that both PMA and fMLP stimulated a transient increase in the enzymatic activity of cellular MAPKAP kinase 2. The induced kinase activation was concentration-dependent and reached a maximum at 5 minutes for PMA and 1 minute for fMLP. To identify potential substrate molecules for MAPKAP kinase 2, a highly active kinase mutant was generated by mutating the MAP kinase phosphorylation site in the C-terminal region. The replacement of threonine 334 with alanine resulted in a marked augmentation of catalytic activity. Analysis of in vitro protein phosphorylation in the presence of the active kinase indicates that a 60-kD cytosolic protein (p60) was markedly phosphorylated and served as the major substrate for MAPKAP kinase 2 in human neutrophils. Based on the MAPKAP kinase 2 phosphorylation site of Hsp27, a competitive inhibitory peptide was synthesized. This competitive inhibitory peptide specifically inhibited MAPKAP kinase 2 enzymatic activity, as well as the in vitro and in vivo kinase-induced p60 phosphorylation. To assess the contribution of MAPKAP kinase 2 in neutrophil function, the oxidative burst response after manipulation of endogenous kinase activity was measured. Intracellular delivery of the competitive inhibitory peptide into human neutrophils reduced both PMA- and fMLP- stimulated superoxide anion production. Thus, the results strongly suggest that MAPKAP kinase 2 is involved in the activation of human neutrophils.     

A preparation guide for surgical resident and student rotations to underserved regions

Interest in global health among surgical residents and medical students is growing. There are numerous opportunities worldwide for both short- and long-term experiences. In order to maximize the learning potential, the authors present a practical guide for residents and students to prepare for a surgical visit, elective, rotation, or mission to an underserved region. The following steps will be outlined:     

Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine

Introduction

Cardiac troponins are sensitive and specific biomarkers of myocardial necrosis. We evaluated troponin, CK, and ECG abnormalities in patients with septic shock and compared the effect of vasopressin (VP) versus norepinephrine (NE) on troponin, CK, and ECGs.

Methods

This was a prospective substudy of a randomized trial. Adults with septic shock randomly received, blinded, a low-dose infusion of VP (0.01 to 0.03 U/min) or NE (5 to 15 μg/min) in addition to open-label vasopressors, titrated to maintain a mean blood pressure of 65 to 75 mm Hg. Troponin I/T, CK, and CK-MB were measured, and 12-lead ECGs were recorded before study drug, and 6 hours, 2 days, and 4 days after study-drug initiation. Two physician readers, blinded to patient data and drug, independently interpreted ECGs.

Results

We enrolled 121 patients (median age, 63.9 years (interquartile range (IQR), 51.1 to 75.3), mean APACHE II 28.6 (SD 7.7)): 65 in the VP group and 56 in the NE group. At the four time points, 26%, 36%, 32%, and 21% of patients had troponin elevations, respectively. Baseline characteristics and outcomes were similar between patients with positive versus negative troponin levels. Troponin and CK levels and rates of ischemic ECG changes were similar in the VP and the NE groups. In multivariable analysis, only APACHE II was associated with 28-day mortality (OR, 1.07; 95% CI, 1.01 to 1.14; P = 0.033).

Conclusions

Troponin elevation is common in adults with septic shock. We observed no significant differences in troponin, CK, and ECGs in patients treated with vasopressin and norepinephrine. Troponin elevation was not an independent predictor of mortality.

Trial registration

Controlled-trials.com ISRCTN94845869     

Targeting Gonadotropin-releasing Hormone Receptor Inhibits the Early Step of Ovarian Cancer Metastasis by Modulating Tumor-mesothelial Adhesion

Ovarian cancer has a clear predilection to metastasize to the peritoneum, which represents one of the most important prognostic factors of poor clinical outcome. Gonadotropin-releasing hormone (GnRH) receptor is significantly overexpressed during the malignant progression of human ovarian cancer. Here, using lentiviral-based small interfering RNA (siRNA) technology to downregulate GnRH receptor in metastatic ovarian cancer cells, we show that GnRH receptor is an important mediator of ovarian cancer peritoneal metastasis. GnRH receptor downregulation dramatically attenuated their adhesion to the peritoneal mesothelium. By inhibiting the expression of GnRH receptor, we showed decreased expression of α2β1 and α5β1 integrin and adhesion to specific extracellular matrix (ECM) proteins. This was also associated with a reduction of P-cadherin. Furthermore, adhesion of ovarian cancer cells to different ECMs and the mesothelium were abrogated in response to β1 integrin and P-cadherin reduction, confirming that the effects were β1 integrin- and P-cadherin–specific. Using a mouse model of human ovarian cancer metastasis, we found that the inhibition of GnRH receptor, β1 integrin, and P-cadherin significantly attenuated tumor growth, ascites formation, and the number of metastatic implants. These results define a new role for GnRH receptor in early metastasis and offer the possibility of novel therapeutic targets.     

Evaluation of a rapid stoolantigen test for the diagnosis of Helicobacter pylori infection in Chinese patients

OBJECTIVE: To evaluate the accuracy of a rapid assay that wasdeveloped to detect Helicobacter pylori antigen in the stool,using the principle of immunochromatography, in the Chinese population. METHODS: Eligible patients without prior treatment of H.pylori were recruited. An in‐house rapid urease test (RUT) andhistology were used as the gold standard. The results of the rapidstool antigen test were compared with the gold standard. RESULTS: Valid rapid stool antigen test results for interpretationwere obtained from 94 consecutive patients (mean age: 52.5, range:22?82 years). Sensitivity, specificity, positive predictivevalue, negative predictive value and accuracy were, respectively, 77.5%,87.0%, 81.6%, 83.9% and 83.0%.The test was easy to perform and results were available within 15 min. CONCLUSION: The rapid stool antigen test using immunochromatography accuratelydiagnoses H. pylori infection in Chinese patients.     

Mucocutaneous manifestations in 22 consecutive cases of primary HIV-1 infection

Summary Twenty-two consecutive patients presenting with symptomatic human immunodeficiency virus 1 (HTV-1) seroconversion were studied. Most of the patients had a glandular fever-like illness.
All patients had fever and pharyngitis, and eight of them also suffered from ulcers of the oral, genital or anal mucosa. Uniform skin eruptions were observed in 17 of the 22 patients. The exanthem consisted of varying numbers of macular or maculopapular lesions that were oval or rounded in shape, ranging from a few millimetres to 1 cm in diameter. The lesions were distributed on the upper thorax in all cases, and were particularly profuse in the collar region. The face forehead and scalp were involved in most cases, but the eruption was sparse or absent at the periphery of the extremities. In the majority of patients, the exanthem appeared after 2 or 3 days of fever. The exanthem developed during the first day, persisted for 5-8 days, and then cleared concurrently with the general recovery of the patients.
Histopathological studies of skin punch biopsy specimens from four patients showed a sparse lymphocytic cell infiltrate distributed around vessels of the dermal superficial plexus. The infiltrates predominantly consisted of equally represented T-helper/inducer and T-suppressor/cytotoxic cells. A vacuolar aberration of basal layer cells was found in two of the four eases studied histologically. The microscopic findings correspond to the histopathological patterns seen in toxieodermia and in the interface dermatitis of morbilliform viral exanthems. The exanthem is a frequent and characteristic sign of primary HTV infection, which is further indicated if mucosal ulcers are present.