Highly Probable Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome Associated With Lenalidomide.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening hypersensitivity reaction to medications. We report a case of a 75-year-old African American female who presented with generalized rash with desquamation and malodorous secretions. She was febrile and hypotensive, and required vasopressors for hemodynamic instability. Sepsis secondary to skin or soft tissue infection was considered initially. However, she recently was started on lenalidomide for treatment of her multiple myeloma, and her white blood cell count of 17 K/µL with 55% eosinophils along with peripheral smear showing eosinophilia suggested lenalidomide-induced rash. Lenalidomide was discontinued, and methylprednisolone was initiated. Four days after lenalidomide discontinuation, vasopressors were discontinued. Blood cultures did not exhibit any growth. The Niranjo Adverse Drug Reaction Probability Scale score of 9 suggests lenalidomide was a highly probable cause of DRESS syndrome. The temporal relation of lenalidomide administration and development of symptoms plus improvement of rash with the discontinuation of lenalidomide and reappearance on restarting lenalidomide in the follow-up clinic strengthens our suspicion of lenalidomide-induced DRESS syndrome. Cases of lenalidomide-induced DRESS syndrome are sparse; however, DRESS syndrome is fatal in approximately 10% of patients. Providers should be aware and keep a vigilant eye out for this adverse reaction with lenalidomide.

Gemcitabine and Carboplatin (renally dosed) regimen for bladder cancer.

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

A case of disseminated cryptococcosis with abdominal involvement due to Cryptococcus neoformans species complex in a Ragdoll cat and false-negative cryptococcal antigen lateral flow tests due to the postzone phenomenon.

Although cryptococcosis is the most common systemic fungal disease of cats, abdominal involvement is rarely reported. The pathogenesis of cryptococcosis usually involves sinonasal colonisation, followed by tissue invasion and sinonasal infection, with possible subsequent spread to the lungs and/or direct extension into the central nervous system (CNS), for example, via the cribriform plate. Further haematogenous spread can occur to any tissue, including skin and the CNS. This report describes a case of disseminated cryptococcosis due to Cryptococcus neoformans species complex in a 13-year-old cat, the fourth documented Australian feline case with abdominal involvement. The cat presented with a chronic history of upper respiratory disease that progressed to severe lethargy and anorexia. An autopsy revealed striking peritonitis with multifocal abdominal involvement affecting the liver, spleen, adrenal glands, kidneys, pancreas and mesentery. Cryptococcal organisms were also observed in organs within the thoracic cavity, sinonasal tissues and the CNS. Testing of abdominal fluid and serum for cryptococcal antigen using a commercially available lateral flow assay using neat fluid specimen initially tested false-negative. However, after dilution of the sample to 1:64, a positive result was obtained, confirming a postzone phenomenon. Taken together, the collective findings were indicative of widely disseminated cryptococcosis due to Cryptococcus neoformans with atypical involvement of the abdominal cavity.

An exploration of parents' and young people's perspectives of hospice support.

BACKGROUND: Hospices are an important component of children's palliative care provision and increasing numbers of children/young people with life-limiting conditions mean that the demand placed on them for support is likely to increase. However, there has been a lack of published research examining how families experience the support provided by children's hospices. METHODS: The aim of the study was to investigate parents' and young people's perceptions of hospice support and identify how support could be improved. A mixed-method approach was used involving a postal survey of families and in-depth qualitative interviews with a purposively sampled subsample of parents and young people. RESULTS: A total of 108 (49.8% response rate) questionnaires were returned and interviews were conducted with 12 parents and seven young people. Families were highly satisfied with the support provided in terms of quality of care; interpersonal qualities of the staff; the individualized, family-focused approach; accessibility of support and involvement in decision making. Young people valued the opportunity to meet with other young people and take part in different activities. For parents the provision of a break from caring was the main way in which they were supported although they felt they wanted more of this form of support. A consistent theme in relation to support for young people and siblings was the need to develop facilities, activities and bereavement support specifically for teenagers/young people. CONCLUSIONS: Parents value a model of care that provides holistic, family-focused support that is responsive to individual needs and which promotes control and active involvement in decision making. The key challenge now is to respond to increasing need and a changing population of users.

Role of cyclic GMP in submandibular gland secretion.

Cholinergic stimulation of rat submandibular gland slices resulted in a rapid increase in the level of cyclic GMP. This increase was dependent upon the presence of Ca2+ and a phosphodiesterase inhibitor. Adrenergic agonists did not produce a significant elevation of cyclic GMP. The addition of Ca2+ to slices preincubated with the divalent ionophore A23187 caused a rapid rise in cyclic GMP levels which were unaffected by cholinergic stimulation. While these results could support a function for cyclic GMP in cholinergic-mediated K+-release from these glands, they do not support a role for this nucleotide in alpha-adrenergic agonist-induced K+-release or protease secretion.

Potassium release from submandibular salivary gland in vitro.

Rat submandibular gland slices, incubated in continuously-gassed Krebs-Ringer bicarbonate buffer, were shown to release K+ in response to alpha-adrenergic and muscarinic cholinergic stimulation. The system employed the specific alpha-, beta-adrenergic and cholinergic receptor-blocking agents phentolamine, propranolol and atropine, respectively, in combination with the agonists L-epinephrine and carbamylcholine both of which required the presence of Ca2+ for their effect. The introduction of Ca2+ into the cell via the ionophore A23187, with all neurotransmitter receptors blocked, resulted in K+ release. Ouabain also allowed extensive K+ release which was in addition to, and hence independent of, that elicited by epinephrine and carbamylcholine. Ethacrynic acid, a potent inhibitor of salivary secretion in vivo, had no influence on K+ movement. K+ was released by both physalaemin and an eledoisin-related peptide independently of normal neurotransmitter receptors. The activity of the eledoisin-related peptide did not require the presence of extracellular Ca2+. The implication of cyclic GMP at some stage of K+ release was suggested by experiments with a phosphodiesterase inhibitor. The results support an hypothesis where the initial stimulus at either alpha-adrenergic or muscarinic cholinergic receptors causes an immediate permeability change such that Ca2+ enters the cells resulting in K+ release. The loss of K+ is quickly countered by the ouabain-sensitive (Na+ + K+) ATPase which would be activated by the lowered intracellular K+ levels.

Biphasic modulation of platelet phospholipase A2 activity and platelet aggregation by mepacrine (quinacrine).

The modulation of rat platelet phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) and rat platelet aggregation by mepacrine was investigated. The 2-acyl specificity of phospholipase A2 activity was confirmed by using 1-[14C]palmitoyl-2-[3H]arachidonylphosphatidylcholine as substrate. Under optimal pH, phospholipase A2 activity was not affected by aspirin but was inhibited by indomethacin. Contrary to previous reports, a biphasic modulatory role of mepacrine on phospholipase A2 activity and platelet aggregation was demonstrated. The data suggest that platelet aggregation is mediated via phospholipase A2.

Collagen and prostaglandin synthesis in force-stressed periodontal ligament in vitro.

A periodontal organ culture system capable of receiving orthodontic type forces was developed. Histological, radioautographical, collagen, and prostaglandin synthetic data demonstrated the vitality of the organ over a 24-hour period of culture. Significant increases in the proportion of type III collagen synthesized during periods of active stress were found, but no alterations in relative levels of prostaglandins synthesized during periods of force application were discernible.

Intermittent and continuous ceftazidime infusion for critically ill trauma patients.

BACKGROUND: The adequacy of intermittent and continuous infusion ceftazidime for the treatment of nosocomial pneumonia in critically ill trauma patients was assessed by analyzing ceftazidime pharmacokinetics in relation to the minimum inhibitory concentration (MIC) and treatment outcome. METHODS: Serial blood samples were obtained during ceftazidime therapy in 31 trauma patients. Ceftazidime pharmacokinetics were compared with that of previously studied healthy volunteers. Ceftazidime pharmacokinetics were analyzed according to the time above the MIC and treatment outcome. RESULTS: Critically ill trauma patients had a significantly increased volume of distribution and clearance (0.32 +/- 0.14 L/kg and 2.35 +/- 0.89 mL. min(-1). kg(-1), respectively) compared with healthy volunteers (0.21 +/- 0.03 and 1.58 +/- 0.23 mL. min(-1). kg(-1)). The time above the MIC was >/=92% of the dosing interval for all patients and treatment outcomes were similar between the two treatment groups. CONCLUSIONS: Ceftazidime pharmacokinetics are significantly altered in critically ill trauma patients. Both intermittent and continuous ceftazidime regimens were equally effective for the treatment of nosocomial pneumonia caused by less virulent bacteria.

Risk of abdominal septic complications after feeding jejunostomy placement in patients undergoing splenectomy for trauma.

Compared with total parenteral nutrition, enteral feeding via jejunostomy reduces septic complications in patients with severe trauma. However, violation of the bowel with insertion of a jejunostomy tube may increase the risk of intra-abdominal abscess (IAA), particularly if no simultaneous gastrointestinal tract injury exists. The records of 123 patients requiring splenectomy for trauma at a level I trauma center during a 6-year period (1986 to 1992) were reviewed to examine the incidence of IAA in patients with and without simultaneous jejunostomy placement in the presence and absence of gastrointestinal tract injuries. Thirty patients had jejunostomies placed (J), and 93 did not (NoJ). There were no significant differences between the groups in age, Abdominal Trauma Index, Injury Severity Score, or transfusion requirements. The incidence of IAA was not significantly different between the J and NoJ groups in the presence or absence of gastrointestinal tract injuries. Thus, jejunostomy placement does not increase the incidence of IAA after splenectomy regardless of the presence of a gastrointestinal tract injury.

Combined high-performance liquid chromatographic procedure for measuring 4-hydroxypropranolol and propranolol in plasma: pharmacokinetic measurements following conventional and slow-release propranolol administration.

An assay is described for the simultaneous determination of propranolol and its active metabolite, 4-hydroxypropranolol, in human plasma. Both compounds were separated from an ethereal extract by high-performance liquid chromatography employing a C18 bonded-phase column. Detection of the effluent was by fluorescence. Suitable fluorescent spectrometers and wavelength settings that allow optimum detection of both compounds have been described. The limit of sensitivity was 2 ng/ml for both propranolol and 4-hydroxypropranolol. Mean peak plasma levels of propranolol and 4-hydroxypropranolol in six patients receiving a single dose of a slow-release 160-mg formulation of propranolol were 28 and 6 ng/ml, respectively. These levels were about one-tenth the level obtained following a single conventionally prepared dose of propranolol (160 mg). Peak levels were delayed and plasma levels of propranolol persisted for a longer period with the slow-release formulation. Area under the curve estimates suggested that the bioavailability of the slow-release formulation following single-dose administration was about one-third that of the conventional preparation.

Activation of rutin by human oral bacterial isolates to the carcinogen-mutagen quercetin.

Oral streptococci, isolated from the mouths of 2 healthy subjects, hydrolysed innocuous rutin, a flavonoid glycoside, to its genotoxic aglycon quercetin, in vitro. The isolates were identified as Streptococcus milleri. The glycosidase, rutinase, was studied in cell-free extracts derived from one of the isolates, grown anaerobically in batch cultures by the use of a bioassay, the Ames test, in which S-9 was replaced by the cell-free extracts. This streptococcal rutinase was: constitutive, partly inducible, cytosolic, most active for rutin and most active at pH 6.5. Type-culture collection strains of other oral streptococci (Streptococcus salivarius ATCC 25975 and Streptococcus mutans strain 6715-10) showed no capacity for rutin degradation. A hypothesis for a novel role of the oral microflora in a disease process other than caries and periodontal disease, namely intra-oral cancer, is presented. The possibility of a bacterial liberation of the genotoxic quercetin in situ could be but one example of its involvement in the local carcinogenic process.

Effect of dietary vitamin E on sulfolipid synthesis in rat submandibular salivary gland.

The effect of feeding diets containing various levels of vitamin E for 6 months on the in vitro synthesis of sulfolipids in rat submandibular salivary glands (SMG) was elucidated. The incorporation of [35S]sulfate into sulfolipid of SMG from rats on deficient or "normal" vitamin E diets was quite similar, however, the uptake was significantly increased in glands from rats on diets high in vitamin E. Whereas, in many instances, antioxidants can mimic the effect of vitamin E, in the present study, the antioxidant N,N'-diphenyl-p-phenylene diamine (DPPD) was actually found significantly to depress sulfolipid-labeling below that noted in SMG from all other diets. The results suggest that in the synthesis of SMG sulfolipid the action of vitamin E may be more than that of a simple antioxidant.

Acrosome reaction and concentration of prostaglandin E2 in semen of rams treated with flunixin meglumine (Banamine).

The objectives of this study were to determine 1) the effect of Banamine on the seminal concentration of PGE2 and 2) the ability of sperm cells from treated rams to undergo acrosome reaction in vitro as an indirect measure of their fertilizing capacity. Seven rams, approximately 55 kg bodyweight and 2 to 5 yr of age, were divided into two groups: Group 1, treated (n = 4) and Group 2, controls (n = 3). Treatment consisted of administration of 75 mg i.m. Banamine twice daily, 6 to 8 h apart, for 45 d. On Day 0 (first day of treatment) and on Days 2, 9, 11, 16, 23, 25, 28, 30, 36, 39, 43 and 46 semen samples were collected from both groups using an electroejaculator. Blood samples were obtained for determination of serum levels of Banamine using high-performance liquid chromatography. Semen samples were examined for motility and morphology. Highly motile (>/=85%), normal-appearing semen samples were pooled on each day of collection and 25 ul of the pooled sample (1x10(6)/ml) of each group were induced to undergo acrosome reaction in vitro using ionophore A23187. Acrosome reaction was demonstrated using a staining technique designed for demonstrating the process in bull sperm cells. The percentage of acrosome-reacted and non-acrosome-reacted sperm was determined by random microscopic examination of 100 sperm cells using a double-blind approach. The supernatants of the remainder of the semen samples were assayed for levels of PGE2 using RIA. Values for acrosome-reacted sperm cells and PGE2 levels on the first day of treatment from both groups were compared with corresponding values from each day of sampling using Wilcoxon Rank Sums test (P<0.05). In Group 1, the mean serum level of Banamine was 3.02+/-0.58ug/ml. There was a significant increase in the ability of sperm cells from rams in Group 1 to undergo acrosome reaction as treatment progressed compared with the sperm cells from rams in Group 2. However, there was a significant decrease in concentration of PGE2 in semen from rams in Group 1 compared with those from Group 2. The results of this study suggest an inverse relationship between the capacity of sperm cells to undergo acrosome reaction and concentration of PGE2 in semen of rams treated with a nonsteroidal anti-inflammatory drug.

Factors that influence passive transfer of immunoglobulins in foals.

Effects of farm management, breed, mare age, gestation duration, and climatologic factors on colostral specific gravity, colostral IgG concentration, and foal serum IgG concentration were evaluated. Climatologic variables measured were daily maximal, minimal, and mean air temperature, precipitation, average relative humidity, and total solar radiation. Presuckle, postpartum colostrum samples were collected from 140 Standardbred, 94 Thoroughbred, and 59 Arabian mares from January through June during 1985 and 1986. Thoroughbred (farm A, n = 61; farm B, n = 33) and Arabian (farm C, n = 45; farm D, n = 14) mares were located in Ocala, Fla; Standardbred mares (farm E) were in Montgomery, NY. Mares from farms A, B, D, and E foaled in box stalls, and mares from farm C foaled in sand paddocks. Mares with premature lactation greater than 12 hours were not included in the study. Foals were clinically normal at birth and suckled colostrum without assistance within 2 hours of parturition. Specific gravity of presuckle colostrum samples was measured by use of an equine colostrometer. Blood samples were collected 18 hours after parturition from 253 of the 293 foals (n = 45, 25, 32, 13, 138 on farms A through E, respectively) to determine serum concentration of IgG. The IgG concentrations in colostrum and serum were measured by single radial immunodiffusion. Data were analyzed by multiple regression or chi 2 analysis. The most important determinants of foal serum IgG concentration were the IgG content and specific gravity of presuckle colostrum samples (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Screening for dementia and depression in older people.

Nurses have a valuable role to play in screening for dementia and depression in older people but they must be confident, adequately trained and supported. The authors conclude that screening and assessment is vital for older people to gain access to specialist mental health services.

Gerontological nurse specialists.

This article focuses on the development of a new role highlighted in The NHS Plan (DoH 2000a), nurse specialist for older people or gerontological nurse specialist.

Dementia. Part 2: Person-centred assessment.

A positive attitude towards people with dementia will enable the nurse to ascertain their strengths and abilities. Person-centred assessment can enhance the patient's experience and lead to more accurate information. Nurses should also consider the needs and role of the patient's carer.

Older people with dementia in acute settings.

This article suggests that screening and assessing for dementia can be incorporated into nurses' roles, as can a range of strategies to address some of the common challenges that nurses face when working with older people with cognitive impairment in acute settings.