Diabetes prolongs the inflammatory response to a bacterial stimulus through cytokine dysregulation

Diabetes has been identified as an important risk factor for infection. But relatively little is known about how diabetes alters the inflammatory response to bacteria. The objective of this study was to investigate how diabetes affects host-bacteria interactions by focusing on the inflammatory response in a connective tissue setting. Diabetic (db/db) and control (db/+) mice were inoculated with Porphyromonas gingivalis, a pathogen associated with bite wounds and periodontal disease. The response was measured histologically or by the expression of inflammatory cytokines. By quantitative histologic analysis, there was little difference between the diabetic and control mice on day 1. On day 3, however, the inflammatory infiltrate had subsided in the control group, whereas it had not in the diabetic group (p<0.05). Similar results were noted at the molecular level by the persistent expression of tumor necrosis factor-alpha (TNF-alpha) and the chemokines MCP-1 and MIP-2. The importance of TNF in this process was demonstrated by reversal of the prolonged chemokine expression by specific inhibition of TNF with Enbrel. These results indicate that cytokine dysregulation associated with prolonged TNF expression represents a mechanism through which bacteria may induce a more damaging inflammatory response in diabetic individuals.     

Aneurysmal subarachnoid hemorrhage in the first year of life: case report and review of the literature

Introduction Primary subarachnoid hemorrhage is rare in infancy. A bleeding arterial aneurysm as its cause is even less frequent. A review of the literature turned up 85 cases of cerebral aneurysm that occurred in the 1st year of life, 63 of them presenting with subarachnoid hemorrhage (SAH).Case report The authors report a case of an 8-month-old boy who presented with seizures due to ruptured anterior communicating (ACom) artery aneurysm with subsequent subarachnoid and intraventricular hemorrhage. The infant was operated successfully, without complications.Discussion In this report the authors highlight certain clinical and diagnostic features, surgical considerations, and outcomes of aneurysmal subarachnoid hemorrhage in the 1st year of life.     

Malignant eccrine hidradenoma of neck causing acute heart failure

Tumours of eccrine sweat glands are uncommon, with complex classification and different terms used even for the same tumour. Therefore, for practical purposes, it may be sufficient to differentiate between benign and malignant. Malignant eccrine hidradenoma has a predilection for head and neck, with high incidence of recurrence following surgical excision and also regional and distant metastases. We describe a case, which presented as a medical emergency with symptoms of severe anaemia and acute heart failure secondary to intermittent bleeding from a huge ulcerative neck lesion, which was subsequently diagnosed as eccrine hidradenocarcinoma. The tumour was successfully treated with complete surgical excision and reconstruction followed by radiotherapy. Two years postoperatively, the patient is very well with no sign of recurrence.     

The use of gonadotropin-releasing hormone antagonist in a flexible protocol: a pilot study

OBJECTIVE: The purpose of this study was to investigate the efficacy of a flexible protocol of starting gonadotropin-releasing hormone antagonist according to the size of the leading follicle. STUDY DESIGN: This was a pilot study that included 123 couples who were undergoing in vitro fertilization/intracytoplasmic sperm injection cycles at the Egyptian IVF-ET Center. Couples were recruited into two groups: group I (n=64), gonadotropin-releasing hormone antagonist was administered when the diameter of the leading follicle reached 16 mm; group II (n=59), gonadotropin-releasing hormone antagonist was administered on day 6 of stimulation. RESULTS: The mean number of antagonist injections was significantly lower in the flexible protocol compared to the fixed protocol (3.4+/-1.1 vs 5.3+/-1.8, P<.05). There was no significant difference between the two protocols regarding the number of embryos, implantation rate, clinical pregnancy rate (odds ratio, 0.85; 95% CI, 0.45-1.59) or multiple pregnancy rate (odds ratio, 1.26; 95% CI, 0.45-3.51). CONCLUSION: Starting the gonadotropin-releasing hormone antagonist according to the size of the leading follicle is as effective as starting on a fixed day and reduces the antagonist administration.     

Dissolution of the lymphoid follicle is a feature of the HHV8+ variant of plasma cell Castleman's disease

The plasma cell variant of Castleman's disease (PCD) may occur in a variety of clinical settings. One recently delineated type of PCD is caused by human herpesvirus 8 (HHV8) infection. Lymph nodes from 25 patients with PCD, including six HHV8+ and 19 HHV8- cases, were studied. Three patients with HHV8+ PCD were also infected with human immunodeficiency virus-1. Features common to all cases were interfollicular plasmacytosis and variably hyperplastic and regressed follicle germinal centers. Features associated only with HHV8+ PCD included follicle dissolution resulting from blurring of the mantle zone boundary (p = 0.0001), presence of atypical plasma cells and immunoblasts within these areas (p = 0.0006), and more prominent interfollicular vascular proliferation than in HHV8- PCD. HHV8+ cells were predominantly immunoblasts and small lymphocytes that were highly enriched in the mantle zones of altered follicles. These areas showed a predominance of plasmacytoid forms expressing lambda light chain in four of six cases. The extrafollicular fibroblastic network surrounding altered germinal centers demonstrated marked upregulation of low-affinity nerve growth factor receptor in five of five HHV8+ cases but in only two of 10 HHV8- cases. We conclude that HHV8+ PCD is distinctive histologically because of the accumulation of infected lymphocytes in the mantle zone leading to progressive dissolution of the germinal center and altered regulation of the surrounding stroma.     

Design and synthesis of some substituted 1H-pyrazolyl-thiazolo[4,5-d]pyrimidines as anti-inflammatory-antimicrobial Agents

The synthesis of two novel series of structurally related 1H-pyrazolyl derivatives of thiazolo[4,5-d]pyrimidines is described. All the newly synthesised compounds were examined for their in vivo anti-inflammatory activity in two different bioassays namely; cotton pellet-induced granuloma and carrageenan-induced paw edema in rats. The in vitro inhibitory activity of the most active compounds towards human COX-1 and COX-2 enzymes was also estimated. In addition, the ulcerogenic effects and acute toxicity (LD(50)) values of these compounds were determined. The same compounds were evaluated for their in vitro antimicrobial activity against Escherichia coli, as an example of Gram negative bacteria, Staphylococcus aureus as an example of Gram positive bacteria, and Candida albicans as a representative of fungi. The results revealed that compounds 5a, 9a, 9b, 10b and 12a exhibited anti-inflammatory activity comparable to that of indomethacin in both local and systemic in vivo animal models with no or minimal ulcerogenic effects (0-10%) and high safety margin (LD(50) > 500 mg kg(-1)). In addition, most of them displayed appreciable antibacterial activities when compared with ampicillin, especially against S. aureus. Compounds 9a and 12a are the most distinctive derivatives identified in the present study because of their remarkable in vivo and in vitro anti-inflammatory activity in addition to their pronounced antibacterial activities comparable to ampicillin against Gram positive and -negative bacteria. Therefore, they are considered as successful dual anti-inflammatory-antimicrobial candidates.     

Design and synthesis of some substituted 1H-pyrazolyl-oxazolidines or 1H-pyrazolyl-thiazolidines as anti-inflammatory-antimicrobial agents

Four series of 1 H-pyrazole derivatives have been synthesized. The first series was synthesized starting with the reaction of 3-(5-bromo-2-thienyl)-1-phenyl-1 H-pyrazole-4-carboxaldehyde 1 with L-serine, L-cysteine, or L-penicillamine, followed by N-protection using (Boc)(2)O to provide compounds 2. The latter compounds could be N-deprotected by 4N HCl/dioxane to afford the second series 3 or reacted with NH(4)OH in the presence of DCC/HOBt to give the corresponding amides 4 followed by N-deprotection giving rise to compounds 5. The newly synthesized compounds were evaluated for their anti-inflammatory-antimicrobial activities. In addition, the ulcerogenic and acute toxicity profiles were determined. Compound 5b (2RS, 4R)-2-[3-(5-bromo-2-thienyl)-1-phenyl-1H-pyrazol-4-yl]-5-methylthiazolidine-4-carboxamide, proved to be the most active anti-inflammatory-antimicrobial agent in the present study with a good safety margin and no ulcerogenic effect.     

Torsade de pointes associated with the administration of intravenous haloperidol:a review of the literature and practical guidelines for use

Haloperidol is the most commonly used medication for the treatment of delirium and psychosis in the critically ill patient. Whilst generally considered to be safe, haloperidol has been associated with a number of important cardiovascular side effects. The major toxicities include hypotension, cardiac arrhythmias and prolongation of the corrected QT (QTc) interval. In particular, torsade de pointes, a polymorphic ventricular tachyarrhythmia, has been associated with both intravenous and oral haloperidol administration. The management of torsade de pointes consists of discontinuation of the possible offending agent(s), correction of electrolyte abnormalities, administration of magnesium sulfate and, if necessary, overdrive pacing. Although clinicians should be aware of this potentially lethal complication of intravenous haloperidol therapy, it should not deter clinicians from using intravenous haloperidol to treat acute agitation in the critically ill patient with a normal QTc.     

The management and treatment of cervical spine injuries

The cervical spine is a relatively fragile structure traversed by the spinal cord. Injuries to the cervical spine (c-spine) are therefore associated with potentially catastrophic neurological complications. This article illustrates the importance of routine c-spine immobilization in all trauma patients and highlights how early diagnosis of injuries can optimize outcome.