Neurofibromatosis type 1: A neuro-psycho-cutaneous syndrome?

Neurofibromatosis type 1 (NF1) is an inherited disorder often associated with optic nerve gliomas, low-grade brain tumors, and readily visible signs. Though these features are frequently emphasized, the psychosocial and emotional morbidities are often overlooked. We present a patient with depressive disorder resulting in suicide in a patient with NF1.

Synthesis and antibacterial activity of the C-7 side chain of 3-aminoquinazolinediones.

A novel series of bacterial topoisomerase (3-aminoquinazolinediones) inhibitors are described. The side-chain SAR against Gram-positive and Gram-negative organisms as well as DNA gyrase activity is reported.

Death due to a rare complication of colonoscopy and the potential medicolegal implications.

A 64-year-old woman was found dead at home after undergoing a screening colonoscopy. At autopsy, 1.9 L of blood was discovered within her abdominal cavity. The only major abnormality was nontraumatic avulsion of the splenic capsule. This was the only identifiable abnormality capable of causing the severe hemoperitoneum and demise of the patient. Although rare, splenic capsule avulsion is a recognized complication of colonoscopy. Many have theorized that it results from excessive traction on the splenocolic ligament resulting in a tear of the splenic capsule. Most patients present within the first 24 hours after the procedure with nonspecific symptoms, and many patients may not seek medical attention. The paucity of the literature in the area of splenic capsular avulsion after colonoscopy reinforces the importance of reporting known cases, and by doing so raise awareness of this rare but devastating complication of an otherwise beneficial screening procedure.

3-aminoquinazolinediones as a new class of antibacterial agents demonstrating excellent antibacterial activity against wild-type and multidrug resistant organisms.

The 3-aminoquinzolinediones represent a new series of antibacterial agents structurally related to the fluoroquinolones. They are inhibitors of bacterial gyrase and topoisomerase IV and demonstrate clinically useful antibacterial activity against fastidious Gram-negative and Gram-positive organisms, including multidrug- and fluoroquinolone-resistant organisms. These agents also demonstrate in vivo efficacy in murine systemic infection models.

Eosinophilic Endomyocarditis: A Rare Case of Neonatal Mortality.

Background Eosinophilic endomyocarditis (EEM) is a rare diagnosis that is extremely uncommon in newborns. This case report aimed to present a case of neonatal mortality from acute cardiac failure due to EEM. Case Our report presents a term male neonate with minor complications in the immediate postnatal course, who was discharged at 48 hours of life, but who developed unexpected respiratory distress, followed by cardiac arrest and death at 3 days of life. One day after discharge, the infant developed respiratory distress and cool skin, and then developed cardiac arrest at the pediatrician's office, undergoing resuscitation with intravenous fluid, cardiopulmonary resuscitation, epinephrine, atropine, and failed intubation. Autopsy revealed EEM, an inflammatory infiltrative process involving the endomyocardium. Pathology Pathogenesis involves three stages: (1) myocarditis with an acute eosinophilic inflammatory infiltrate followed by (2) myocyte necrosis and eventually (3) fibrosis in the final stage of the disease. Discussion The cause of death was acute cardiac failure due to intense eosinophilic infiltration and degranulation with early subendocardial myocyte necrosis but before development of extensive myocyte necrosis. This case appears to be the youngest patient reported with EEM.

Shaken adult syndrome: report of 2 cases.

IMPORTANCE: To establish that the intracranial and ophthalmologic findings present in victims of abusive head trauma can also be seen in shaken adults. OBSERVATIONS: We report 2 cases of shaken adults with intracranial and ophthalmologic findings that resulted from repetitive acceleration-deceleration injury. These findings included intracranial hemorrhages, hemorrhages involving the optic nerve sheath, intraretinal and subretinal hemorrhages, and macular folds. CONCLUSIONS AND RELEVANCE: The intracranial and ophthalmologic findings that are characteristic of abusive head trauma--subdural hemorrhages, optic nerve sheath hemorrhages, and retinal hemorrhages--are generally thought to be limited to young children and infants. Adults may also be victims of shaking abuse, and an ophthalmic examination may be beneficial when shaking is suspected.

In vitro and in vivo activities of PD 0305970 and PD 0326448, new bacterial gyrase/topoisomerase inhibitors with potent antibacterial activities versus multidrug-resistant gram-positive and fastidious organism groups.

PD 0305970 and PD 0326448 are new bacterial gyrase and topoisomerase inhibitors (quinazoline-2,4-diones) that possess outstanding in vitro and in vivo activities against a wide spectrum of bacterial species including quinolone- and multidrug-resistant gram-positive and fastidious organism groups. The respective MICs (microg/ml) for PD 0305970 capable of inhibiting>or=90% of bacterial strains tested ranged from 0.125 to 0.5 versus staphylococci, 0.03 to 0.06 versus streptococci, 0.25 to 2 versus enterococci, and 0.25 to 0.5 versus Moraxella catarrhalis, Haemophilus influenzae, Listeria monocytogenes, Legionella pneumophila, and Neisseria spp. PD 0326448 MIC90s were generally twofold higher versus these same organism groups. Comparative quinolone MIC90 values were 4- to 512-fold higher than those of PD 0305970. In testing for frequency of resistance, PD 0305970 and levofloxacin showed low levels of development of spontaneous resistant mutants versus both Staphylococcus aureus and Streptococcus pneumoniae. Unlike quinolones, which target primarily gyrA and parC, analysis of resistant mutants in S. pneumoniae indicates that the likely targets of PD 0305970 are gyrB and parE. PD 0305970 demonstrated rapid bactericidal activity by in vitro time-kill testing versus streptococci. This bactericidal activity carried over to in vivo testing, where PD 0305970 and PD 0326448 displayed outstanding Streptococcus pyogenes 50% protective doses (PD50s) (oral dosing) of 0.7 and 3.6 mg/kg, respectively (ciprofloxacin and levofloxacin PD50s were>100 and 17.7 mg/kg, respectively). PD 0305970 was also potent in a pneumococcal pneumonia mouse infection model (PD50=3.2 mg/kg) and was 22-fold more potent than levofloxacin.

Structure-activity relationships of 3-aminoquinazolinediones, a new class of bacterial type-2 topoisomerase (DNA gyrase and topo IV) inhibitors.

A series of 3-aminoquinazolinediones was synthesized and evaluated for its antibacterial and DNA gyrase activity. The SAR around the quinazolinedione core was explored and the optimal substitutions were combined to give two compounds, 2r and 2s, with exceptional enzyme potency (IC50 = 0.2 microM) and activity against gram-positive organisms (MIC's = 0.015-0.06 microg/mL).

Synthesis and structural-activity relationships of 3-hydroxyquinazoline-2,4-dione antibacterial agents.

A series of 3-hydroxyquinazoline-2,4-diones was synthesized and evaluated for antibacterial activity. This series represents a novel addition to the DNA gyrase inhibitor class of antibacterials. Appropriate substitutions onto the core template yielded compounds with excellent potency against E. coli gyrase and significant in vitro Gram-negative and Gram-positive antibacterial activity.