Cephalosporin allergy

Allergic reactions to cephalosporins may occur because of sensitization to cephalosporin determinants shared with penicillin or to unique cephalosporin haptens. The exact nature of the haptenic determinants resulting from the degradation of currently available cephalosporins is incompletely understood. Cephalosporin skin testing or specific IgE immunoassays have limited clinical utility. Patients with a history of allergy to cephalosporins or penicillin may be at increased risk for a reaction to cephalosporins. Skin testing for an allergy to penicillin may be helpful in patients with a history of penicillin allergy who have a clinical indication for cephalosporin use. Most of these patients have negative tests and should not be at increased risk for a reaction to cephalosporins.     

Distinct structural and functional epitopes of the αEβ7 integrin

Intestinal intraepithelial lymphocytes (iIEL) are predominantly CD3⁺, CD8⁺ T lymphocytes located above or adjacent to the mucosal basement membrane. Although they are positioned to interact with intercellular luminal antigen or with enterocytes, the function of iIEL remains unknown. Most (> 85%) of the iIEL express the α^Eβ₇ integrin which appears to be involved in the adhesion of lymphocytes to epithelial cells. We report the characterization of three monoclonal antibodies (mAb) termed αE7-1, αE7-2, and αE7-3, that react with the α^Eβ₇ integrin recognized by the previously described mAb HML-1 as demonstrated by identical sodium dodecyl sulfate – polyacrylamide gel electrophoresis mobility and charge. Flow cytometric analysis of antibody cross-blocking indicated that these mAb recognize distinct epitopes of α^Eβ₇. While all of the mAb were capable of blocking the adhesion of cultured iIEL to a breast epithelial cell line, only HML-1 and αE7-1 (which recognize an identical or closely related epitope) were co-stimulatory with suboptimal concentrations of anti-CD3 mAb in inducing proliferation of cultured iIEL. Thus, these mAb appear to recognize functionally distinct epitopes of α^Eβ₇ and will be useful to study relationships between the structure and function of this integrin.     

Cryptococcosis in a bottlenose dolphin (Tursiops truncatus) caused by Cryptococcus neoformans var. gattii

We describe the first case of cryptococcosis caused by Cryptococcus neoformans var. gattii in a male Atlantic bottlenose dolphin (Tursiops truncatus). The dolphin showed clinical signs of tachypnea, transient dyspnea, and mild tachycardia and developed multiple hyperechoic nodules, parenchymal consolidation, and thickening of pleura. A diagnosis of bronchopneumonia with pleuritis was made. Itraconazole therapy was implemented for 120 days, and trough levels in serum were within or above the suggested therapeutic range. Titers of cryptococcal antigen in serum increased eightfold during therapy, and the case had a fatal outcome. Necropsy examination findings included enlarged pulmonary lymph nodes and extensive coalescing granulomatous lesions throughout both lungs. Histologic examination revealed numerous, spherical to ellipsoidal, mucicarmine-positive, 3- to 14-microm, encapsulated, budding cells consistent with C. neoformans. Culture of the lung tissue yielded colonies of C. neoformans. The isolate was urease positive and nitrate negative and exhibited phenoloxidase activity. It was positive on canavanine-glycine-bromothymol blue agar. When tested by the Iatron serodiagnostic reagent kit (Iatron Laboratories, Inc.), it was shown to belong to serotype B.     

Use of negative pressure wound therapy on malignant wounds – a case report and review of literature

The presence of malignancy is considered a contraindication to the use of negative pressure wound therapy (NPWT) because of concerns that it may promote tumourigenesis and expedite metastasis. This notion is extrapolated from studies evaluating NPWT in normal tissues. Despite the absence of direct evidence, the use of this technology in malignant wounds is widely considered a contraindication. We present the case of a patient with treatment‐resistant metastatic colon cancer, who developed a chronic abdominal wound with positive margins. A staged reconstruction using NPWT was performed and wound closure allowed the patient to meet eligibility criteria and enrol in a clinical trial for treatment of his oncological disease. Skin closure remained intact until the patient expired 6 months after the wound closure. This case, as well as others in the literature, demonstrated that the use of NPWT should not be considered an absolute contraindication in malignancy. Individualised approaches taking into account the patient's clinical scenario, the available evidence, as well as the risks and benefits of this technology are recommended.     

Free oxygen radicals—Predictors of neonatal outcome following perinatal asphyxia

The study was undertaken to evaluate the role of free oxygen radicals in asphyxiated neonates. Thirty term neonates appropriate for gestational age and with severe birth asphyxia (Apgar score of 3 or less at 1 minute of life) formed the study subjects. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), creatine phosphokinase (CPK) and lipid peroxidase (LPO) in the CSF of these neonates were estimated between 12 and 48 hrs of life. Enzyme estimation was performed by standard methods and the results were analysed statistically using Multivariate Logistic Regression analysis and non parametric tests namely Kruskal Wallis test and Wilcoxon’s rank sum test. Out of the thirty babies, 14 were observed to be neurologically normal, 9 had significant morbidity and 7 died. The SOD levels ranged from 12.4 to 140 units/ml, GPx from 128 to 1933 nmol/min/dl, CPK from 2 to 2098 IU/dl and LPO from 5.4 to 30.8 umol/hr/dl. The SOD and GPx levels had an inverse relationship whereas rise in LPO and CPK levels were directly proportional to the extent of neurological damage and ultimate clinical outcome. CPK levels higher than 140 IU/ml were lethal and associated with 100% mortality whereas, all normal neonates had CPK below 37 IU/ml. The levels of antioxidant enzymes can reliably and significantly predict mortality and morbidity whereas level of an enzyme cannot confidently confer normalcy. Hence antioxidant enzyme levels with a cut off value can be a useful marker and serve as a prognostic indicator in times to come.     

Phaeohyphomycosis Caused by Phaeoacremonium inflatipes

Phaeoacremonium inflatipes, one of three species previously classified as strains of Phialophora parasitica, was identified as the causal agent of a subcutaneous infection of the left foot of an 83-year-old woman from South Carolina. The patient had a granulomatous growth over the anteromedial aspect of her left foot. It was surgically excised, which led to complete healing without complications. Tissue sections of the excised mass stained with hematoxylin and eosin and Gomori’s methenamine silver strains showed many septate hyphal elements of various lengths, some exhibiting brownish pigment in the cell walls of the hyphae. Portions of the tissue, when cultured, yielded many colonies which were initially glabrous, off white becoming velvety, greyish brown on aging. Microscopically, their hyphae were septate, branched, and phaeoid and bore lateral and terminal, erect, septate conidiophores. The conidiogenous cells (phialides) were terminal or lateral, mostly monophialidic, subcylindrical to spinelike in shape, and constricted at their bases and bore funnel-shaped, inconspicuous collarettes at their tips. The conidia were subhyaline, oblong, and ellipsoid to allantoid.In 1996, Crous et al. (3) proposed the new hyphomycete genus Phaeoacremonium with Phaeoacremonium parasiticum (= Phialophora parasitica) as its type species. Morphologically, the genus Phaeoacremonium is intermediate between the genera Acremonium and Phialophora. It is distinguished from Acremonium by its phaeoid vegetative hyphae and conidiophores and from Phialophora by its narrow, spinelike (aculeate) conidiogenous cells and inconspicuous collarettes. A detailed study by Crous et al. (3) of a large number of isolates originally identified as P. parasitica made it obvious that it represented a cluster of related and morphologically well-defined species producing subcylindric to aculeate phialides with inconspicuous collarettes not at all resembling those of other Phialophora species. An earlier analysis of restriction fragment length polymorphism and rRNA gene sequence data from isolates of Phialophora americana, P. verrucosa, P. richardsiae, and nine isolates of P. parasitica by Yan et al. (11) revealed that six of the nine P. parasitica isolates belonged to one distinct group. The other three isolates each exhibited a unique restriction map. However, they were closer to P. parasitica than to any other species of Phialophora studied. Crous et al. (3) proposed to accommodate the isolates that caused human infections, previously grouped under Phialophora parasitica, in three species including Phaeoacremonium parasiticum and two new species, P. inflatipes and P. rubrigenum. They also described three additional species (Phaeoacremonium aleophilum, P. angustius, and P. chlamydosporum) that are not known to cause human infections. We report a subcutaneous, granulomatous infection of the left foot of a woman from South Carolina and describe salient features of the causal agent, P. inflatipes.

Case report.

An 83-year-old Caucasian woman reported pain in her left knee, difficulty in walking and weight bearing, and the need to sit down for long periods of time. She also had pain in her left foot with a large lump on its medial side; this lump had been enlarging. On examination, she was found to have fusiform swellings over both knees and had marked patellofemoral crepitation on both sides. However, it was more pronounced on the left than on the right side. There was no ligamentous instability, and she had good neurovascular status in both lower extremities. Examination of the left foot revealed a soft mass over the anteromedial aspect of her foot. It was minimally tender on deep palpation. When surgically excised, the mass looked like a foreign body surrounded by a granuloma. Sections of the excised tissue stained with hematoxylin and eosin, periodic acid-Schiff, and Gomori’s methenamine silver (GMS) stains revealed dense, proliferated, fibrous connective tissue showing an inflammatory reaction composed of proliferated capillary cells. Multinucleated foreign body-type giant cells were present. Epithelioid cells were prominently seen in the reactive process. Sections stained by periodic acid-Schiff and GMS stains demonstrated numerous septate, hyphal fragments of various lengths measuring 2.0 to 3.0 μm in diameter (Fig. ​(Fig.1).1). Sections stained by hematoxylin and eosin showed a few phaeoid hyphal elements, consistent with the diagnosis of phaeohyphomycosis. As has been the case with many other localized phaeohyphomycotic lesions, in this case, total excision of the granulomatous mass led to complete healing of the lesion without complications or relapse. Open in a separate windowFIG. 1Short, septate hyphal elements of P. inflatipes in biopsied tissue stained by GMS. Original magnification, ×875.Portions of the excised tissue were cultured on Sabouraud glucose agar with chloramphenicol (Sab+c) and Sab+c containing cycloheximide. Morphology was studied on potato dextrose agar (PDA). Cultures were incubated at 25 and 37°C in the dark. Initially, colonies on Sab+c and PDA were glabrous, creamy to off white, and raised, becoming greyish brown after 8 days at both temperatures of incubation. Colonies on Sab+c and PDA at 25°C after 2 weeks were velvety, flat, olivaceous brown to grey, and 26 to 28 mm in diameter. Hyphae were septate, branched, and smooth walled to warty, becoming light brown, and measured 2.0 to 3.0 μm in diameter. Conidiophores were erect, simple or branched, subcylindrical, phaeoid in the lower portions, and lighter brown toward the tips. They were smooth, zero- to four-septate, and variable in length. Conidiogenous cells were terminal or lateral, mostly monophialidic, also polyphialidic, smooth walled, hyaline to pale brown, elongated, and subcylindric and were constricted at their bases. Occasionally, percurrent growth of phialides was also observed. At the tips, they bore narrow, cylindric to funnel-shaped, inconspicuous collarettes. Conidia aggregated into slimy heads at the tips of the phialides or slid down along their sides. The conidia were subhyaline and oblong-ellipsoid to allantoid (sausage shaped) and measured 3.0 to 5.0 by 1.5 to 2.5 μm (Fig. ​(Fig.22 and ​and3).3). The isolate grew well at 25 and 37°C (8 to 11 mm in 2 weeks) but failed to grow at 40°C. It hydrolyzed gelatin. Based on the inflated phialides with basal constrictions (near the basal septum), the isolate (96-034129 = CDC B-5747) was identified as P. inflatipes. It was sent to G. S. de Hoog, Centraalbureau voor Schimmelcultures (CBS), Baarn, The Netherlands, who confirmed our identification. It was deposited in the CBS collection as CBS 729.97. Open in a separate windowFIG. 2Slide culture on PDA of P. inflatipes showing subcylindric phialides that are constricted at their bases and have inconspicuous collarettes and ellipsoid to allantoid conidia. Original magnification, ×1,000.Open in a separate windowFIG. 3Slide culture on PDA showing polyphialidic and percurrent (arrow) conidiogenous cells of P. inflatipes and conidia. Original magnification, ×1,000.Three species of Phaeoacremonium that cause human infections, namely, P. parasiticum, P. inflatipes, and P. rubrigenum, were formerly recognized under the genus Phialophora as strains of P. parasitica. The majority of human infections caused by these species that have been described in the literature were in the nature of subcutaneous abscesses, cysts, or chronic or acute arthritis in immunocompromised and immunocompetent hosts (1, 4, 6–9, 12) and were acquired through traumatic inoculation. Systemic infections, fungemia or endocarditis, have been rare (5, 10). In the present case, the host was apparently immunocompetent but did not remember having sustained any obvious trauma to her left foot.P. inflatipes can be distinguished from P. parasiticum by its slightly larger conidia and, more importantly, by its inflated phialides, which are constricted at their bases. Those of P. parasiticum are more spinelike and not constricted at their bases. P. inflatipes has a wide geographic distribution, and it has been isolated from plants such as Nectandra sp. in Finland, stems of oak trees (Quercus virginiana), Vitis vinifera in Costa Rica and the United States, stems and roots of Sorbus intermedia in Germany, and soil in Tahiti. It has been isolated from a Pyracantha thorn (8) and from synovial fluid from a patient in the United States (3), toenails of a patient from Finland (3), and white granules from a eumycotic mycetoma in a patient from Venezuela (2).When subcutaneous lesions caused by P. parasiticum or P. inflatipes were localized and diagnosed early, total surgical excision often led to uncomplicated healing. However, therapy for infections caused by P. parasiticum, P. inflatipes, and P. rubrigenum in immunocompromised hosts is not satisfactory. Antifungal agents such as amphotericin B, 5-fluorocytosine, ketoconazole, and terbinafine have been used in the past with variable success (5, 8, 9). In the present case, surgical excision led to uncomplicated cure of the infection.     

Correlationship of Drug-Polymer Miscibility,Molecular Relaxation and Phase Behavior of Dipyridamole Amorphous Solid Dispersions

In present work, a correlationship among quantitative drug-polymer miscibility, molecular relaxation and phase behavior of the dipyridamole (DPD) amorphous solid dispersions (ASDs), prepared with co-povidone (CP), hydroxypropyl methylcellulose phthalate (HPMC P) and hydroxypropyl methylcellulose acetate succinate (HPMC AS) has been investigated. Miscibility predicted using melting point depression approach for DPD with CP, HPMC P and HPMC AS at 25 °C was 0.93% w/w, 0.55% w/w and 0.40% w/w, respectively. Stretched relaxation time (τ^β) for DPD ASDs, measured using modulated differential scanning calorimetry (MDSC) at common degree of undercooling, was in the order of DPD- CP > DPD-HPMC P > DPD-HPMC AS ASDs. Phase behavior of 12 months aged (25 ± 5 °C and 0% RH) spray dried 60% w/w ASDs was tracked using MDSC. Initial ASD samples had homogeneous phase revealed by single glass transition temperature (T_g) in the MDSC. MDSC study of aged ASDs revealed single-phase DPD-CP ASD, amorphous-amorphous and amorphous-crystalline phase separated DPD-HPMC P and DPD-HPMC AS ASDs, respectively. The results were supported by X-ray micro computed tomography and confocal laser scanning microscopy studies. This study demonstrated a profound influence of drug-polymer miscibility on molecular mobility and phase behavior of ASDs. This knowledge can help in designing “physical stable” ASDs.