A rational clinical approach to suspected insulin allergy: status after five years and 22 cases.

AIMS: Allergy to recombinant human (rDNA) insulin preparations is a rare complication of insulin therapy. However, insulin preparations contain several allergens, and several disorders can resemble insulin allergy. Studies evaluating the diagnostic procedures on suspected insulin allergy are extremely few. METHODS: Since January 1998, we have used a standardized investigative procedure during admittance to the medical ward allowing observation and repeated recording of reactions to intradermal skin test (performed with a commercially available kit containing isolated insulin allergens). Data on all investigated cases until April 2003 were collected retrospectively, and self-reported efficacy of intervention was compared to clinical data. RESULTS: Twenty-two patients were included. In nine (41%) cases, non-insulin allergic causes were discovered and successfully treated: poor injection technique (n = 5), skin disease (n = 3) and other systemic allergy (n = 1). Nine other patients were found to be allergic to protamine (n = 3) or rDNA insulin (n = 6), and specific treatment was associated with relief in 8 patients (89%). Four patients had local reactions of unknown causes but symptom relief was obtained in three cases by unspecific therapy. Overall, 20 (91%) reported relief of symptoms. CONCLUSION: Our standardized investigative procedure of suspected insulin preparation (IP) allergy was associated with relief of symptoms in > 90% of patients. IP allergy was diagnosed in 41%, and intradermal testing with isolated insulin allergens was a prerequisite in identification of culprit allergen and targeting of treatment.

Expression of the receptor for urokinase-type plasminogen activator in normal and neoplastic blood cells and hematopoietic tissue.

Expression of the receptor for the urokinase type plasminogen activator (uPAR) has been studied by flow cytometry and immunohistology in normal blood and bone marrow cells, in vitro activated lymphoid cells, and tissue samples from reactive lymph nodes (n = 6), thymus (n = 2) and malignant lymphomas (n = 82), or leukemias (n = 32). HL-60 myeloid precursor cells and CD34-positive normal stem cells also were analyzed. In the normal cells, staining was confined to monocytes, macrophages, neutrophils, and myeloid precursors. No labelling was seen of normal or activated lymphoid cells. Purified CD34-positive hematopoietic progenitors were uPAR negative, but expressed uPAR during differentiation in short-term liquid culture stimulated in vitro by recombinant interleukin (IL)-1, IL-3, IL-6, granulocyte-macrophage colony stimulating factor (CSF), granulocyte-CSF, and stem cell factor. Enhanced uPAR expression was also seen in HL-60 cells after induction of differentiation with dimethyl sulfoxide or 1 alpha,25-dihydroxyvitamin D3. In lymphomas and leukemias, the staining pattern was similar to that seen in the normal cells with labelling of monocytic and myeloid that seen in the normal cells with labelling of monocytic and myeloid malignancies, but not of the neoplastic cells in B-cell or T-cell lymphomas or Hodgkin's disease. In conclusion, uPAR is a differentiation marker for myeloid and monocytic cells, and may act to facilitate migration of these cells in normal and pathologic conditions by cell-associated plasminogen activation. Whether expression of uPAR in myeloid and monocytic malignancies relates to their growth and behavior will be an important topic for investigations in the future.

[Increased risk of preterm delivery in women with earlier conization]. / Oget risiko for praeterm fødsel hos koniserede kvinder.

The object of the study was to determine the relation between cervical conization and preterm birth. All Danish women with singleton pregnancies who gave birth to their first infant in 1982 and second infant in 1982-1987 were included in a register-based cohort study. Information on pregnancy outcome and cervical conization in 1977-1987 was obtained from the Medical Birth Register and the National Register of Hospital Discharges. It was found that in a cohort of 14.233 women, 170 had had cervical conization. Thirty-four had had cervical conization before the first delivery, 62 between the first and the second, and 74 after the second delivery. Women with cervical conization had a significantly higher risk of preterm birth. Also, women with subsequent cervical conization had a higher risk of preterm birth in previous pregnancies. However, the risk of preterm birth was higher in women with previous than with subsequent cervical conization. It is concluded that cervical conization is correlated with preterm birth. Since women with subsequent cervical conization are at increased risk of preterm birth in preceding pregnancies, other factors than the surgical intervention may contribute to the significantly increased risk of preterm birth.

The receptor for urokinase-type plasminogen activator and urokinase is translocated from two distinct intracellular compartments to the plasma membrane on stimulation of human neutrophils.

The cellular receptor for urokinase-type plasminogen activator (uPAR) binds pro-urokinase (pro-uPA) and facilitates its conversion to enzymatically active urokinase (uPA). uPA in turn activates surface-bound plasminogen to plasmin, a process of presumed importance for a number of biologic processes including cell migration and resolution of thrombi. We have previously shown that uPAR is expressed on the plasma membrane of circulating neutrophils, and we now report that stimulation with phorbol myristate acetate (PMA), FMLP, or tumor necrosis factor-alpha results in a rapid increase in the expression of uPAR. This process is accompanied by an increased cell-associated plasminogen activation after preincubation of neutrophils with pro-uPA in vitro. By subcellular fractionation of unstimulated neutrophils, 50% of uPAR is recovered in fractions containing latent alkaline phosphatase, corresponding to an intracellular compartment of easily mobilizable secretory vesicles distinct from both primary and specific granules, whereas the remaining 50% of uPAR is associated with a compartment eluting close to the specific granules. In contrast, the ligand pro-uPA is primarily (approximately 80%) found in the specific granules, but small amounts of pro-uPA/uPA (approximately 20%) coelute with latent alkaline phosphatase. Stimulation of neutrophils with FMLP results in translocation of uPAR as well as of pro-uPA from the secretory vesicles, whereas stimulation with PMA is required to translocate material from specific granules. Flow cytometry of neutrophils saturated with exogenous diisopropyl fluorophosphate-uPA shows a large excess (approximately 90%) of unoccupied uPAR on resting as well as FMLP- and PMA-stimulated neutrophils, suggesting a possible role for exogenous pro-uPA in providing neutrophils with a potential for plasminogen activation. These processes may be important for neutrophil extravasation and migration through extracellular matrix and for the contribution of neutrophils to resolution of thrombi.

Cervical conization and preterm delivery/low birth weight. A systematic review of the literature.

OBJECTIVE: Evaluate the effect of cervical conization on preterm birth/low birth weight (LBW). DESIGN: A systematic review of the literature using external or internal controls. RESULTS: The typical odds ratio for preterm delivery in women with prior cervical conization using external controls was 3.23 (95% confidence interval 2.29-4.55). Using internal controls the typical odds ratio for LBW was 2.97 (95% confidence interval 1.09-8.05). Using external controls the typical odds ratio for LBW was 2.31 (95% confidence interval 1.33-3.99). CONCLUSION: Women with cervical conization are at higher risk for preterm birth than external controls, and the surgical intervention as such is a major determining factor.

Hypoxemia in the postanesthesia care unit: an observer study.

To determine the incidence and duration of hypoxemia in the postanesthesia care unit (PACU), 200 patients were investigated in a single-blind observer study. The number of unrecognized hypoxemic episodes, as well as risk factors and possible association between hypoxemia and postoperative morbidity, were studied. Oxygenation was monitored continuously with a pulse oximeter. One or more hypoxemic episodes (SpO2 less than or equal to 90%) were noted in 55% of the patients. SpO2 values less than or equal to 80% were noted in 13% of the patients. Supplementary oxygen was given during 55% of the 447 hypoxemic episodes registered. The hypoxemic episodes were unrecognized by the staff in 95% of the cases. With stepwise multiple logistic regression analyses, risk factors associated with a higher incidence of hypoxemia were: duration of anesthesia (P less than 0.0001), age (P less than 0.002) and a history of smoking (P less than 0.01). Patients who had undergone regional anesthesia had a lower risk of hypoxemia (P less than 0.0002). The occurrence of hypoxemia in the PACU could not be correlated to postoperative morbidity. We conclude that hypoxemic episodes in our PACU are common and that the routine use of supplemental oxygen combined with normal clinical surveillance did not prevent hypoxemic episodes.