Familial Q fever clustering with variable manifestations imitating infectious and autoimmune disease.

Q fever, caused by Coxiella burnetii, can present as an outbreak of acute disease ranging from asymptomatic disease, pneumonia, hepatitis or fever of unknown origin, which can progress to a chronic disease, most frequently endocarditis. The occurrence of Q fever within families is rarely described, and in most cases presents with uniform acute disease manifestations. Here we present a familial cluster of Q fever presenting as highly variable synchronous manifestations in four of five family members, including prolonged fever of unknown origin, asymptomatic carrier state, hepatitis, and chronic endocarditis developing in the absence of previous symptoms. This case series highlights the possibility of Q fever developing in cohabitated individuals with highly variable symptoms masking the common disease etiology. Screening of all exposed individuals, even those not clinically suspected to be infected, may enable to better identify, treat and prevent progression to chronic disease.

Evaluation of a prospectively administered written questionnaire to reduce the incidence of suspected latex anaphylaxis during elective cesarean delivery.

BACKGROUND: Life-threatening anaphylaxis has been reported in women exposed to latex during surgery. We compared a written screening questionnaire to identify suspected latex sensitivity with a verbal inquiry used previously in a historical control group of women undergoing cesarean delivery to determine if the incidence of suspected latex anaphylaxis could be reduced. METHODS: To identify suspected latex sensitivity among women undergoing elective cesarean delivery in a single-site tertiary unit, a nine-item written screening questionnaire was compared to historical use of a standard verbal inquiry "Are you allergic to medications or latex?". Women who had suspected latex sensitivity risk factors, or who had known latex allergy, underwent latex-free surgery. Women with suspected anaphylaxis during cesarean delivery were recommended to undergo allergen testing. The primary study outcome was suspected anaphylaxis incidence during the two periods: historical control January to December 2008, questionnaire March 2010 to April 2011. RESULTS: The questionnaire identified suspected latex sensitivity in 66 of 453 women (14.6%) who completed the questionnaire. The standard verbal inquiry group had identified 12 of 460 women (2.6%) with self-reported latex sensitivity. The incidence of suspected anaphylaxis during cesarean delivery was significantly lower during the questionnaire period when compared to historical controls (3/516, 0.6% vs. 11/460, 2.4%, P=0.015). For both groups, 13 of 14 women (92.9%) with suspected latex anaphylaxis were contactable; five of 13 (38.5%) had undergone allergen testing and all were positive for latex. CONCLUSIONS: Use of the written screening questionnaire was associated with fewer cases of suspected anaphylaxis during cesarean delivery compared with the historical control. Most women with suspected anaphylaxis did not perform allergy testing; however, all who did were positive for latex.

Dapsone induced eosinophilic pneumonia.

Eosinophilic lung diseases (ELD) are a variety of several clinical entities, which may result from different etiologies, including drug treatment. Dapsone, a sulfone antibiotic widely used in leprosy (among other indications), has been described as a possible cause of ELD. We report a patient with leprosy who presented with respiratory symptoms and pulmonary infiltrates and was diagnosed as suffering from eosinophilic pneumonia. To the best of our knowledge, this is the first report in which the diagnosis of dapsone-induced eosinophilic pneumonia was supported by bronchoalveolar lavage, lung biopsy and typical response to therapy.

Heparin-induced recurrent anaphylaxis.

BACKGROUND: Heparin-related immediate-type hypersensitivity reactions like urticaria, angio-oedema or bronchospasm are very rare, and only a few cases of anaphylaxis-like responses because of heparin have been described. However, the mechanisms underlying these reactions and the role of mast cells in their pathogenesis have not been elucidated. OBJECTIVES: We report a patient with end-stage renal disease who presented with recurrent anaphylaxis after receiving heparin during haemodialysis. The underlying aetiology was obscured by the initiation of haemodialysis with its known anaphylactic-like side-effects. The diagnosis of hypersensitivity to heparin was confirmed by the clinical picture, positive skin tests and elevated serum tryptase levels. MATERIALS AND METHODS: We performed prick and intradermal skin tests with heparin, enoxaparin and danaparoid heparinoid. Total and mature tryptase levels were measured in serum by ELISAs at 1, 24 and 36 h following the reaction. RESULTS: An elevated mature tryptase level was found at 1 h, which returned to normal levels at 24 and 36 h. A high total tryptase level was detected at 1 h, but remained somewhat elevated at 24 h. Prick tests were negative with the three compounds. Intradermal skin tests with heparin and enoxaparin were both positive, while with danaparoid negative. Following negative skin test results, danaparoid was used as an anticoagulant during dialysis for the next 3 years without any adverse effects. CONCLUSIONS: In conclusion, we report the first case of heparin-induced anaphylaxis confirmed by an elevated level of mature tryptase in serum. Following skin tests, the patient was treated with danaparoid during haemodialysis sessions three times a week without any adverse effects. Because of increasing use of heparin in daily medical practice, physicians should be aware of possible immediate hypersensitivity reactions to this medication and know how to diagnose and treat them.

Allergy development after bone marrow transplantation from a non-atopic donor.

BACKGROUND: Transfer of allergy from atopic bone marrow donors to recipients is known to occur. Development of allergy in a non-atopic patient transplanted from a non-atopic donor is an unfamiliar phenomenon in clinical practice. OBJECTIVES: To clarify the course of events causing a bone marrow recipient to acquire an allergic disease in such non-conducive circumstances. METHODS: Full medical history, prick and intradermal skin tests, and serum IgE levels were obtained from both donor and recipient patients. DNA and red blood cell phenotype analyses were used to detect the degree of chimerism. RESULTS: Only the recipient patient showed positive specific IgE antibodies and skin tests to house dust mite. The recipient patient displayed 100% donor chimera, based on all engraftment markers sought. CONCLUSION: Full engraftment after allogeneic bone marrow transplantation may be associated with modulation of T and B cell function, which in turn could cause the onset of allergic disease after bone marrow transplantation.

The hypereosinophilic syndrome associated with CD4+CD3- helper type 2 (Th2) lymphocytes.

We describe herein the clinical and laboratory manifestations of a unique group of patients (pts) presenting with hypereosinophilic syndrome (HES) who were treated in our medical centers for 4-13 years. Skin biopsies, flow cytometry of peripheral blood mononuclear cells (PBMC), assays for cytokines and immunoglobulin (Ig) production in vitro, and Southern blots of T-cell receptor (TCR) genes were performed. All four pts had a persistent hypereosinophilia (> 1.9 x 10(9)/L) and chronic skin rash. Three of four had elevated IgE, thrombotic manifestations and lung involvement (asthma and/or infiltrates), and one had deforming sero-negative arthritis of the hands. 66-95% of their peripheral T-cells expressed CD4 but not CD3 or TCR molecules on the cell surface membrane. Activated CD4+CD3- cells secreted interleukin (IL)-4 and/or 5, and were required for maximal IgE secretion by autologous B-cells. Two pts had evidence of rearrangement of TCR genes of the CD4+CD3- cells, one of whom died of anaplastic lymphoma. In conclusion, HES with CD4+CD3- lymphocytosis may be associated with high serum IgE, dermatological, pulmonary, thrombotic and rheumatic manifestations which may be due to Th2 effects of CD4+CD3- cells migrating to end organs. Fatal systemic lymphoid malignancy may also develop in some pts with monoclonal expansion of the CD4+CD3- T-cells.

Hereditary angioedema first apparent in the ninth decade during treatment with ACE inhibitor.

BACKGROUND: Hereditary angioedema ordinarily manifests itself in childhood. The development of angioedema in this disease and as a side effect of angiotensin-converting enzyme inhibitor treatment is caused by similar mechanisms. METHODS: We report a case of female patient, diagnosed with hereditary angioedema at age 90, who experienced the first attack 8 years earlier during angiotensin-converting enzyme inhibitor use. CONCLUSIONS: This patient presented with her first episode of hereditary angioedema at the oldest age ever reported. A careful family history, especially for angioedema, should be taken in patients of all ages before initiating treatment with angiotensin-converting enzyme inhibitor.

Safety of perioperative minidose heparin in patients undergoing brain tumor surgery: a prospective, randomized, double-blind study.

OBJECT: Thromboembolic phenomena (TEPs) continue to be a significant source of morbidity and mortality in patients undergoing neurosurgery. Although the efficacy of low-dose heparin in preventing TEPs in neurosurgical patients is well established, neurosurgeons are reluctant to use it perioperatively because of concern for increased bleeding complications. To clarify this issue, the authors used a prospective, randomized, double-blind design to evaluate the safety of minidose heparin treatment in patients undergoing surgery for supratentorial brain tumors. METHODS: One hundred three patients, all 40 years of age or older, were treated with either 5000 U of heparin (55 patients) or placebo (48 patients) starting 2 hours before surgery and continuing until full mobilization or for 7 days. Both groups were well matched for sex, weight, duration of surgery, and tumor diagnosis. Subjective and objective parameters were used to estimate and calculate the perioperative bleeding tendency in all patients. Red blood cell mass loss was calculated by assessing the preoperative and postoperative hematocrit and the patient's weight. Intraoperative blood loss was determined by measuring the quantity of blood in the suction containers and subtracting the amount of irrigation fluids. Postoperative bleeding was measured by determining the amount of fluid in the subgaleal drain, and blood cell replacement was monitored during and after the procedure. Intracranial bleeding was graded according to findings on the postoperative computerized tomography scan obtained 48 to 72 hours after surgery. In addition, the senior surgeon in each case was asked to assess each patient's bleeding tendency during the operation. The results showed that perioperative administration of heparin did not significantly alter bleeding tendency by any measured parameter. The surgeon was blinded to which group individual patients had been allocated. CONCLUSIONS: Perioperative minidose heparin is safe for use in patients undergoing craniotomy for supratentorial tumors. This relatively simple and inexpensive measure is recommended as a routine regimen for the prevention of TEPs in patients undergoing neurosurgery.

Acetyl-coa: alcohol acetyltransferase activity and aroma formation in ripening melon fruits.

Melon varieties (Cucumis melo L.) differ in a range of physical and chemical attributes. Sweetness and aroma are two of the most important factors in fruit quality and consumer preference. Volatile acetates are major components of the headspace of ripening cv. Arava fruits, a commercially important climacteric melon. In contrast, volatile aldehydes and alcohols are most abundant in cv. Rochet fruits, a nonclimacteric melon. The formation of volatile acetates is catalyzed by alcohol acetyltransferases (AAT), which utilize acetyl-CoA to acetylate several alcohols. Cell-free extract derived from Arava ripe melons exhibited substantial levels of AAT activity with a variety of alcohol substrates, whereas similar extracts derived from Rochet ripe melons had negligible activity. The levels of AAT activity in unripe Arava melons were also low but steadily increased during ripening. In contrast, similar extracts from Rochet fruits displayed low AAT activity during all stages of maturation. In addition, the benzyl- and 2-phenylethyl-dependent AAT activity levels seem well correlated with the total soluble solid content in Arava fruits.

Natural course of insulin edema.

Generalized edema due to water retention is a very rare complication of insulin therapy. It affects mainly patients with newly diagnosed diabetes or patients with chronic hyperglycemia following initiation of insulin therapy. When it occurs, it is treated effectively with diuretics. This case report describes a female patient, who developed severe insulin edema following initiation of insulin. Diuretics were not given due to severe side effects, thus the natural outcome of insulin edema was observed. Edema was gradually replaced by fat tissue with persistent weight gain. Physicians treating diabetic patients should be aware of "insulin edema" in the differential diagnosis of weight gain in patients treated with insulin.

Subterranean medicine: an inquiry into underground medical treatment protocols in cave rescue situations in national parks in the United States.

Caving and spelunking have become increasingly popular over the years, with hundreds of thousands of amateur spelunkers across the country visiting caves. National parks in the United States offer hundreds of caves for all levels of spelunkers and, in fact, many national parks boast caves as either their main or major attraction. In an effort to increase visitor safety and establish subterranean medical treatment protocols, we began an investigation into cave rescue, medical protocols, previously published recommendations concerning cave safety, and visitor and rescue statistics in the national parks. Our inquiry provided little guidance from either the literature or the present US National Parks database for treating underground injuries. However, 2 predominant trends did appear. First, despite the nearly 2 million visitors to the caves in the 14 parks surveyed, there were only about 200 total calls for medical care. The vast number of those calls were for minor injuries. Second, no strict evidence-based treatment protocols for underground injuries exist, probably because they are not feasible. A caving incident database for the national parks would facilitate suggestions for preventative measures for the minor injuries and would help catalog the creative solutions for the rare serious subterranean medical incident.

Coronary vasospasm associated with uncontrolled carcinoid tumour.

We report on a 74-year-old carcinoid patient who, following acute myocardial infarction (MI) and percutaneous transluminal coronary angioplasty, suffered recurrent episodes of chest pain and ST-segment elevation on ECG. This was accompanied by elevation of urinary 5-hydroxy-indole acetic acid. A review of the patient's file revealed that during the 3 weeks prior to the MI, she had been treated inadvertently with a fivefold lower dosage of octreotide. Following the correction of octreotide dosage, episodes of chest pain resolved immediately. We therefore suggest that this patient suffered from recurrent coronary vasospasm due to uncontrolled carcinoid tumour.

The Mt. Tyndall incident.

The authors describe the 53-hour rescue of a 6-foot, 1-inch tall, 250-pound hiker in the face of harsh environmental conditions in Sequoia National Park. This 43-year-old man fell 25 feet, injured his leg, and was noted to be hypothermic and hypovolemic. Weather, altitude, and the patient's size delayed and complicated his evacuation. After being carried down 1,500 vertical feet, he was hoisted into a hovering helicopter and flown to University Medical Center in Fresno, California. On arrival, the patient was determined to have a comminuted subtrochanteric right femur fracture, which was ultimately repaired surgically. The authors also discuss some of the unique aspects of wilderness and National Park Service EMS.

Computerized surveillance of adverse drug reactions in hospital: implementation.

OBJECTIVE: To implement and measure the effects of automatic computerized laboratory signals (ALS) as a detection support tool of adverse drug reactions (ADRs) in hospital. METHODS: This was a prospective observational study of a total of 192 patients (199 sequential medical admissions) during a 2-month period in a 34-bed medical ward at the Hadassah University Hospital, Jerusalem, Israel. The study involved the routine (daily) distribution to staff physicians of lists of automatic signals generated from computerized laboratory data as potential indicators of ADRs. Patient charts were reviewed by the clinical pharmacology team for ADRs and to see whether these were recognized by the staff physicians. RESULTS: Seventy-one ADRs were detected in 64 of the 199 (32%) admissions. Twenty-seven per cent of the ADRs were serious, 9% of the admissions were due to ADRs. Two hundred and ninety-five ALS were generated involving 69% of the admissions. Sixty-one per cent of the ADRs were identified by ALS. ALS were present in 58% of the ADR negative admissions. Eighty-five per cent of the ADRs were recognized as such and 19% of the ALS-positive ADRs were not recognized by the staff physicians. CONCLUSIONS: The routine implementation of ALS doubled the number of ADRs recognized by the physicians while patients were hospitalized in the medical ward. The use of the system appeared valid, simple and potentially cost-effective.

Responsiveness of human skin mast cells to repeated activation: an in vitro study.

To assess human mast-cell (MC) behavior after repetitive activation, we cocultured human foreskin MC (SMC) with human foreskin fibroblasts (F). Under these conditions, we have previously demonstrated that SMC keep their viability and functional activity for up to 8 days. SMC were presensitized with atopic serum and repeatedly activated by consecutively increasing concentrations of anti-IgE antibodies (alpha-IgE, 0.0002-0.1%). This treatment, which mimics the "rush desensitization" procedure, led to complete SMC unresponsiveness to activation by alpha-IgE at optimal concentrations, as evaluated by histamine release. However, presensitization of SMC with IgE antibodies before exposure to alpha-IgE restored their sensitivity to this stimulus. These data indicate that desensitization was probably due to lack of membrane-bound IgE rather than to downregulation of intracellular mechanisms. In fact, SMC challenged by an optimal concentration of alpha-IgE could release histamine upon a second activation by 2 h after the first activation, if the cells had been presensitized before the second challenge. SMC incubation with increasing concentrations of compound 48/80 (0.2-10 micrograms/ml) led to MC unresponsiveness to an optimal concentration of this stimulus. Furthermore, SMC activated by an optimal concentration of compound 48/80 and rechallenged with the same agent were insensitive to the second activation for at least 24 h. In summary, we have shown that it is possible to induce "desensitization" in SMC to both IgE-dependent and IgE-independent stimuli by incubating the cultures with consecutively increasing concentrations of the activator. SMC can release histamine when reactivated with alpha-IgE antibodies after presensitization by 2 h after the first challenge, while they reacquire their susceptibility to reactivation with compound 48/80 in only 2-3 days.

Computerized survelliance of adverse drug reactions in hospital: pilot study.

AIMS: To develop and assess the use of computerized laboratory data as a detection support tool of adverse drug reactions (ADRs) in hospital. METHODS: This was a retrospective observational study of 153 sequential medical admissions during a 2-month period to the 34-bed medical ward at the Hadassah University Hospital, Jerusalem, Israel. Measurements made were 1) Retrospective chart review for recognized and unrecognized adverse drug reactions (ADRs) and 2) Analysis of computerizied laboratory data according to defined automatic laboratory signals (ALS) for adverse reactions. RESULTS: Forty ADRs have been detected in 38 out of the 153 hospital admissions (24.8%). Nine reactions were considered severe. Altogether 212 ALS were generated involving 86 admissions. In 25 (65.8%) of the ADR-positive admissions ADRs were detected through automatic signals generated from the laboratory data. ALS were detected in 56 out of the 115 (48.7%) ADR-negative admissions. Twenty-four (60%) of the ADRs were not recognized as such by the attending physicians. Two of these reactions were severe. ALS could have generated an alert for 19 (79.2%) of the unrecognized reactions. CONCLUSIONS: Application of automatic laboratory signals can increase the rate of recognition of the ADRs and thereby improve medical care. The sensitivity and specificity of the method might be increased by refinement and redefinition of the signals.

Growth and differentiation of eosinophils from human peripheral blood CD 34+ cells.

Small numbers of CD34+ primitive hematopoietic progenitors are found in normal human peripheral blood. These cells differentiate to myeloid or lymphoid lineage under the influence of growth factors. We investigated the effects of IL5 and other growth factors on the production of eosinophils from peripheral blood CD34+ cells. CD34+ cells were plated in agarose with different combinations of cytokines. At 14 days of growth a triple stain technique was used to identify eosinophil, monocyte and neutrophil colonies. IL5 alone did not support colony growth. In contrast GM-CSF and IL3 alone or together supported the generation of more than 50% eosinophil colonies. Addition of IL5 increased the fraction of eosinophil colonies to over 70%. Under the best conditions (IL3 + GM-CSF + IL5), the addition of interferon-a or LPS inhibited colony growth by 51% and 58%, respectively. Since IL5 alone did not support colony growth from CD34+ cells, we determined when IL5 responsive cells appeared in culture. Cells were grown initially with IL3 + GM-CSF, washed, and plated with IL5 alone. Only when progenitors were grown at least 3 days, could IL5 serve as the single growth factor supporting pure eosinophil colony growth (47 colonies/104 cells plated at day 3 and 134 colonies/104 cells at day 7). Growth of CD34+ in liquid culture for 28 days in the presence of IL3, GM-CSF and IL5 resulted in almost 250 fold increase in cell number, yielding a population of 83% maturing eosinophils. We used our culture system and the sensitive technique of RT-PCR to analyze the kinetics of production of mRNA transcripts encoding several eosinophil proteins. Freshly isolated CD34+ cells contained no eosinophil granule protein transcripts and barely detectable amounts of some oxidase protein transcripts. At day 3 of culture no cells recognizable by histochemical staining as eosinophils could be detected, but transcripts for all five eosinophil granule proteins were present. These transcripts increased several fold during the entire culture period. Similar kinetics were seen for the NADPH oxidase protein transcripts. These studies demonstrate that within 3 days of culture, peripheral blood CD34+ cells can become committed to the eosinophil lineage as demonstrated by responsiveness to IL5 and production of specific protein transcripts.