Selective trihydroxylated azepane inhibitors of NagZ, a glycosidase involved in Pseudomonas aeruginosa resistance to ß-lactam antibiotics.

The synthesis of a series of d-gluco-like configured 4,5,6-trihydroxyazepanes bearing a triazole, a sulfonamide or a fluorinated acetamide moiety at C-3 is described. These synthetic derivatives have been tested for their ability to selectively inhibit the muropeptide recycling glucosaminidase NagZ and to thereby increase sensitivity of Pseudomonas aeruginosa to ß-lactams, a pathway with substantial therapeutic potential. While introduction of triazole and sulfamide groups failed to lead to glucosaminidase inhibitors, the NHCOCF3 analog proved to be a selective inhibitor of NagZ over other glucosaminidases including human O-GlcNAcase and lysosomal hexosaminidases HexA and B.

Prevalence of avian paramyxovirus 1 and avian influenza virus in double-crested Cormorants (Phalacrocorax auritus) in eastern North America.

Although it is well established that wild birds, such as cormorants, carry virulent avian paramyxovirus serotype 1 (APMV-1; causative agent of Newcastle disease) and avian influenza virus (AIV), the prevalence of these viruses among Double-crested Cormorants (Phalacrocorax auritus) in the Great Lakes region of North America has not been rigorously studied. We determined the prevalences of APMV-1 and AIV in Double-crested Cormorants from the interior population of eastern North America. From 2009 to 2011, oropharyngeal and cloacal swabs and serum samples were collected from 1,957 individual Double-crested Cormorants, ranging from chicks to breeding adults, on breeding colony sites in Michigan, Wisconsin, and Mississippi, USA, and Ontario, Canada, as well as on the wintering grounds of migratory populations in Mississippi, USA. Prevalence of antibodies to APMV-1 in after-hatch year birds was consistently high across all three years, ranging from 86.3% to 91.6%. Antibody prevalences in chicks were much lower: 1.7, 15.3, and 16.4% in 2009, 2010, and 2011, respectively. Virulent APMV-1 was detected in six chicks sampled in 2010 in Ontario, Canada. Only one adult was positive for AIV-specific antibodies and five individuals were positive for AIV matrix protein, but the latter were negative for H5 and H7 AIV subtypes. We provide further evidence that Double-crested Cormorants play an important role in the maintenance and circulation of APMV-1 in the wild, but are unlikely to be involved in the circulation of AIV.

Stability of ondansetron hydrochloride and 12 medications in plastic syringes.

The stability and compatibility of ondansetron hydrochloride with neostigmine methylsulfate, naloxone hydrochloride, midazolam hydrochloride, fentanyl citrate, alfentanil hydrochloride, atropine sulfate, morphine sulfate, meperidine hydrochloride, propofol, droperidol, metoclopramide monohydrochloride, and glycopyrrolate were studied. Ondansetron 1.33 or 1.0 mg/mL was combined with 0.9% sodium chloride injection and each of the 12 drugs in duplicate in plastic syringes (or glass for propofol). The syringes were stored at 21.8-23.4 or 4 degrees C in the dark, except for those containing propofol, which were stored at ambient temperature. Samples were removed at 0, 4, 8, and 24 hours for analysis by high-performance liquid chromatography and pH measurement; the propofol-containing samples were removed at 0, 1, 2, and 4 hours. Syringes were visually assessed for color and clarity, and particulate content was measured with a particle counter at the end of the study period. All solutions containing ondansetron retained more than 90% of their initial ondansetron concentration. Solutions containing each of the other drugs except droperidol retained more than 90% of their initial concentration of these drugs. The solutions containing droperidol retained more than 90% of their initial droperidol concentration for up to eight hours at ambient temperature but precipitated quickly at 4 degrees C. In combinations of ondansetron 1.33 or 1.0 mg/mL and 10 of 12 drugs, all drugs were stable for 24 hours in plastic syringes at 23 and 4 degrees C; ondansetron hydrochloride 1.0 mg/mL and propofol 1.0 and 5.0 mg/mL in admixtures were stable for 4 hours, and droperidol on its own and combined with ondansetron 1.0 mg/mL was stable for no more than 8 hours at ambient temperature.

Contamination of illicit phencyclidine with 1-piperidinocyclohexanecarbonitrile.

A retrospective study of illicit phencyclidine (PCP), which consisted of 94 different cases or 213 individual samples, has shown that one third of both the powder/tablets and green plant material contained the synthetic contaminant 1-piperidinocyclohexanecarbonitrile (PCC). The mole % PCC/PCP ranged from 1 to 68%. The method of analysis was gas chromatography (3% OV-7, 205 degrees C) and in preparation for analysis the sample was dissolved directly in chloroform or extracted from a strongly acidic solution (0.1 N HCl). Using these extraction conditions PCC was found not to undergo measurable decomposition.

Morphologic evidence of accelerated closure of the ductus arteriosus in preterm infants.

In preterm infants, closure of the ductus arteriosus (DA) is often delayed, especially in those with respiratory distress syndrome (RDS). However, it has been suggested that functional closure of the DA may occur as early as 24 hours of age in some preterm infants exposed to intrauterine stress, and this is usually associated with decreased incidence of RDS. This suggests that accelerated maturation of the DA as well as of the lungs occurs in utero. Accordingly, histologic evidence of accelerated maturation of the DA was sought in a prospective autopsy study of 55 preterm infants ranging in gestational age from 19 to 32 weeks. There were four infants with clinically closed DA which showed histologic evidence of closure. The birth weight of these four infants ranged from 750--1,100 gm, the gestational age ranged from 24--32 weeks, and age of death was 39 hours to 6 days. The immediate causes of death were intracerebral hemorrhage or intrapulmonary hemorrhage, or both. Obstetric complications included chronic second trimester vaginal bleeding, abruptio placenta, malnutrition, diabetes, pulmonic stenosis of moderate degree, and chronic hypertension. These findings support the hypothesis that in some preterm infants exposed to chronic intrauterine stress, maturation of the DA is accelerated. This may result clinically in effective postnatal closure of the DA.

Bizarre cutaneous neurofibromas.

Bizarre cutaneous neurofibroma is an uncommon benign neoplasm. Microscopically, it is usually characterized by stellate and polyhedral cells embedded in a myxoid stroma, and less commonly by solid sheets of epithelioid cells. Cellular pleomorphism and mitotic figures are regular features and have resulted in erroneous diagnosis of malignancy. The mucinous material has the staining characteristics of a sulfated mucosubstance, probably chondroitin sulfate B. Terms previously applied to this lesion include nerve sheath myxoma. Pacinian neurofibroma, myxoid neurofibroma, and neurotheceoma.

Chief cell intracytoplasmic fat used to evaluate parathyroid disease by frozen section.

The chief cells of parathyroid adenomas were found to contain less intracytoplasmic fat than normal parathyroid glands and/or the adjacent rims of nonadenomatous parathyroid tissue. The amount of sudanophilic material in the chief cells was relatively uniform for each individual adenoma, but varied between patients. In half of the patients with parathyroid adenomas, Sudan-positive granules were generally absent from the adenomatous cells, whereas in the other half the granules were easily identifiable. The chief cells of secondary hyperplasia showed a less uniform pattern in each gland. In some areas, the stain for intracellular fat was negative, while adjacent cells contained prominent Sudan-positive granules. These findings suggest that staining frozen sections for intracellular fat is a useful but limited aid in the differentiation of parathyroid adenomas from normal parathyroid gland tissue.

Syringometaplasia: mucinous and squamous variants.

The eccrine sweat ducts are normally lined by cuboidal epithelial cells which may rarely undergo metaplasia, i.e. syringometaplasia. Two lesions were observed in which eccrine sweat ducts displayed the mucinous and squamous variants of syringometaplasia. The first lesion clinically and histologically appeared to be a plantar wart. Microscopically, it consisted of a central invagination surrounded by marked epidermal acanthosis and hyperkeratosis. The invagination was lined by keratinocytes admixed with mucin-filled goblet cells. The mucin was positive by the Alcian blue (pH 2.5) and mucicarmine stains. Numerous eccrine sweat ducts led into the invagination and were focally lined by the mucin-laden cells. Recognition of mucinous syringometaplasia is important since it may be confused with primary or metastatic adenocarcinoma of the skin. The second lesion occurred on the outer ear and was clinically believed to be chondrodermatitis nodularis helicis. Microscopically, there were many islands of atypical squamous cells within the papillary and reticular dermis. These epithelial islands represented squamous syringometaplasia since many contained central lumina with eosinophilic cuticles and blended with normal ductal structures. It is important not to confuse this metaplastic change with invasive squamous cell carcinoma. Squamous syringometaplasia may be analogous to necrotizing sialometaplasia, a recently described phenomenon which occurs in minor salivary glands.

Lymphangiosarcoma arising from lymphangioma circumscriptum.

A lymphangiosarcoma arose at the site of a preexisting lymphangioma circumscriptum on the skin of the anterior part of the abdominal wall. To our knowledge, this is only the second such case to be reported, and in both patients, the preexisting lymphangioma circumscriptum had been exposed to substantial x-ray therapy. Since it is possible that x-irradiation may play a role in the development of this unusual malignant neoplasm, it seems advisable that lymphangioma circumscriptum not be exposed to substantial amounts of such radiation, if feasible.

Sebaceous carcinoma of the skin with visceral metastases.

Sebaceous carcinoma is an uncommon cutaneous malignant neoplasm that rarely metastasizes. We report a case in which a moderately well-differentiated sebaceous carcinoma arising on the anterior aspect of the chest produced widespread visceral metastases. This unexpected clinical behavior underscores the fact that sebaceous carcinoma of the skin can sometimes be very biologically aggressive.

Idiopathic calcinosis of scrotum.

A forty-three-year-old man complained of painless, firm scrotal nodules which had first appeared at age sixteen. These were diagnosed clinically as multiple epidermoid inclusion cysts and were excised. Histologically they were composed of calcified, amorphous, granular material, characteristic of idiopathic calcinosis of the scrotum. This is a rare, benign condition without any recognized underlying metabolic abnormalities. The cause of idiopathic calcinosis of the scrotum is unknown, but we believe it is due to dystrophic calcification of dartoic muscles.

Apocrine cystadenoma of the skin of the chest.

A black patient with an enlarging apocrine cystadenoma on the chest is presented herein. This location is very infrequent for this benign lesion. This is the second report of an apocrine cystadenoma in a black person.

The use of cytology to evaluate pericardial effusions.

Pericardial effusions from 27 patients were examined cytologically during the five-year period of 1973-1977. Malignant cells were found in eight cases (30 percent). In three of these patients malignancy was unsuspected clinically, and this was the first time the cancer was diagnosed. In addition, cytology often suggested the specific histological types and possible primary sites to be determined. Special stains were also found helpful. There were no false positive reports. Although the pericardial effusions from the remaining 19 patients were negative for tumor cells, metastatic carcinoma to the pericardium was discovered at autopsy in two of these cases. Thus, cytologic examination of pericardial fluid is an important tool in the diagnosis of malignancy, but false negative results may occur.

Malignant neoplasms of the paranasal sinuses involving the skin.

Malignant neoplasms of the mucosa and minor salivary glands of the paranasal sinuses may involve the skin by direct extension. When a tumor appears on the overlying skin, these sinuses should be considered as a possible site of origin. Adenoid cystic carcinoma of the paranasal sinuses arise from minor salivary glands. They can infiltrate overlying skin and easily be confused with a primary cutaneous adenoid cystic carcinoma. Malignant melanomas of the paranasal sinuses are clinically very aggressive. They are often amelanotic, and this may lead to an incorrect histopathologic diagnosis. Hence, physical and radiological examination of the nose, mouth, and paranasal sinuses should be performed whenever a tumor appears in the overlying skin that does not have a clear cutaneous origin or whenever the primary site of a metastatic malignant melanoma is unknown.