High-dose therapy with peripheral blood stem cell (PBSC) support using an innovative mobilization regimen in patients with high-risk primary or chemoresponsive metastatic breast cancers

BACKGROUND: Epidemiologic studies are necessary to determine the prevalence of allergic diseases. This varies widely depending on allergen preparations and patients studied. OBJECTIVE: To investigate the prevalence of atopic disease, skin test reactivity, total and specific IgE to common allergens, and other variables in a sample of students from Málaga, southern Spain. METHODS: Three hundred sixty-five students (age 17.9 +/- 1.18) were interviewed by an allergist. Skin prick tests were performed with Dermatophagoides pteronyssinus, Artemisia vulgaris, Plantago lanceolata, Chenopodium album, Olea europaea, Phleum pratense, Parietaria judaica, Cynodon dactylon, Alternaria tenuis, and cat dander. Total and specific IgE to D. pteronyssinus, Olea, and Parietaria were determined. RESULTS: Of all subjects studied, 19.9% suffered from rhinoconjunctivitis, 4.1% rhinoconjunctivitis plus asthma, 3.1% asthma alone, and 0.8% atopic dermatitis; 46.4% had a positive skin test to at least one allergen (28.2% to D. pteronyssinus, 20.4% to Olea, 13.8% to Phleum); and 43% had total IgE > 100 kU/L and 44.7% a family history of atopy. Allergic symptoms were strongly associated with skin test positivities and family allergic history. Patients with asthma or skin prick test positive had higher total IgE values than others (P < .01). There was a significant correlation between specific IgE values and wheal size in skin test. CONCLUSIONS: Our findings confirm the high prevalence of atopic diseases, and the close relationship of skin tests reactivity (or presence of specific IgE) to allergens with symptoms of asthma and rhinitis. The presence of a family history of allergic diseases influences the development of positive skin tests and atopic illness. Dermatophagoides pteronyssinus and pollen of Olea europaea were found to be the most common allergens.     

Analytical and clinical performance characteristics of Tandem-MP Ostase, a new immunoassay for serum bone alkaline phosphatase

The performance characteristics of the Tandem-MP Ostase assay, a new microplate immunoassay for bone-specific alkaline phosphatase (bone ALP; EC 3.1.3.1) in human sera, are described. Bone ALP is bound to streptavidin-coated microwells by a single biotinylated anti-bone ALP monoclonal antibody. Antigen is detected by the addition of p-nitrophenyl phosphate. The assay is performed at room temperature in <90 min. Imprecision was 2.3-6.1% with a detection limit of 0.6 microg/L. Method comparison of bone ALP measurements with the Tandem-MP Ostase assay and the mass-based Tandem-R Ostase assay (n = 285) indicated regression statistics of Tandem-MP Ostase = 1.03 Tandem-R Ostase + 0.22 microg/L, S(y/x) = 4.0 microg/L, r = 0.97. Serum bone ALP values in apparently healthy men and in pre- and postmenopausal women were also similar between the two Ostase assay formats. Liver ALP reactivity determined using the slope and heat inactivation methods was similar in both Ostase assays. Liver ALP reactivity ranged from 3 microg/L (heat inactivation) to 6 microg/L (slope method) per 100 U/L of liver ALP activity, whereas bone ALP reactivity was 37 microg/L per 100 U/L of bone ALP activity, indicating a liver ALP relative reactivity of 8.1-16.2%. Similar results were obtained with the Alkphase-B bone ALP immunoassay. The Tandem-MP Ostase bone ALP assay demonstrated increased concentrations of serum bone ALP in conditions where bone metabolism is increased and showed a rapid, temporal decrease in serum bone ALP in Paget disease patients on bisphosphonate therapy. In conclusion, the Tandem-MP Ostase assay for serum bone ALP is a rapid, simple, robust nonisotopic alternative to the Tandem-R Ostase immunoradiometric assay that provides an accurate and sensitive assessment of bone turnover.     

Computerized prompts for cancer screening in a community health center

One hundred eleven (58%) of 191 adolescent inpatients previously admitted to the emergency wards at the Child and Adolescent Psychiatric Clinics in the cities of Uppsala and G?teborg participated in a 2-4 year follow-up evaluation. The prevalence, incidence, and stability of depressive symptoms, suicidal ideation, and suicide attempts among the adolescents, and predictors of follow-up functioning were examined. Although a majority of the patients substantially reduced their depressive symptoms over the 2-4 year period, a smaller group (13%), mainly girls (94%), continued reporting high symptom levels at follow-up, and one out of five adolescents had moderate-severe levels of suicidal ideation. The accumulated frequency of suicide attempts among the patients shortly prior to hospitalization and during the follow-up was 59% including two patients who committed suicide. Significant predictors of depressive symptom severity at follow-up were depressive symptom scores and V-diagnoses at inpatient assessment. Previous suicide attempts before hospitalization, high levels of self-reported depressive symptoms and nonintact family status at inpatient assessment predicted suicide attempts during the follow-up period. The high prevalence of attempted and completed suicide in this clinical group underscores the importance of developing effective treatments for suicidal adolescents.     

More effective suppression of hemostatic system activation in patients undergoing cardiac surgery by heparin dosing based on heparin blood concentrations rather than ACT

This study was designed to determine whether the maintenance of higher than usual patient-specific heparin concentrations during cardiopulmonary bypass (CPB) was associated with more effective suppression of hemostasis system activation. Thirty-one patients scheduled for repeat cardiac surgery or combined procedures (i.e., coronary revascularization + valve repair/replacement) were consented and enrolled in this study. All patients received porcine heparin and protamine and were randomly assigned to monitoring of anticoagulation by either celite ACT alone (Control, n = 16) or by kaolin ACT combined with on-site measurements of whole blood heparin concentration (Intervention, n = 15). Blood specimens collected before administration of heparin, before weaning from CPB and after administration of protamine were analyzed with a battery of coagulation assays. Patients in the intervention cohort received appreciably greater heparin doses than control patients, resulting in higher anti-Xa heparin levels at the end of CPB. Fibrinopeptide A and D-dimer levels were higher in the control group before discontinuation of CPB. Percent decrease during CPB were greater in the control group for factors V and VIII, fibrinogen and antithrombin III. Percent decrease in complement 3 was greater in the control group after protamine and bleeding times measured in the Intensive Care Unit were significantly more prolonged in this group. Maintenance of higher patient-specific heparin concentrations during CPB more effectively suppresses excessive hemostatic system activation than do standard heparin doses chosen based on measurement of ACT. These findings may explain, at least in part, the significant reduction in perioperative blood loss and blood product use when higher heparin concentrations are maintained.     

Trends in rates of occupational fatal injuries in the United States (1983-92)

Recent advancements in laparoscopic surgery have made laparoscopic splenectomy possible. We retrospectively compared the outcomes of laparoscopic versus open splenectomy in patients with idiopathic thrombocytopenic purpura (ITP) or beta-thalassemia. From July 1993 to July 1997, 52 patients (ITP, 43 cases; beta-thalassemia, 9 cases) underwent either laparoscopic (30 patients, 9 men, 21 women; average age, 36.9 years) or conventional open splenectomy (22 patients, 5 men, 17 women; average age, 34.3 years). The two groups were similar in terms of sex, age, diagnosis, duration of disease, preoperative platelet count, and spleen size. The mean surgical time, estimated amount of blood loss, duration of postoperative recovery, analgesic usage, and complications were compared between the two groups. Laparoscopic splenectomy was successful in 29 (97%) of the 30 patients. The mean surgical time in the laparoscopy group was longer than in the open splenectomy group (190.6 vs 113.9 minutes, p < 0.01). The laparoscopy group had earlier postoperative oral intake (15.2 vs 52.6 hours, p < 0.01), less usage of analgesics (meperidine 50 mg/unit, 1.1 vs 2.8 units, p < 0.01) and a shorter postoperative hospital stay (4.1 vs 6.8 days, p < 0.01). The estimated blood loss, incidence of accessory spleen, surgical complication rate, and recurrence rate of thrombocytopenia were similar in the two groups. Our findings show that laparoscopic splenectomy in patients with ITP or beta-thalassemia is as safe as the open approach. While laparoscopy required a longer surgical time, the recovery period was shorter, analgesic use was less, and physical discomfort was less severe.     

Activation of the genetically defined m1 muscarinic receptor potentiates N-methyl-D-aspartate (NMDA) receptor currents in hippocampal pyramidal cells

Evidence suggests that cholinergic input to the hippocampus plays an important role in learning and memory and that degeneration of cholinergic terminals in the hippocampus may contribute to the memory loss associated with Alzheimer's disease. One of the more prominent effects of cholinergic agonists on hippocampal physiology is the potentiation of N-methyl-D-aspartate (NMDA)-receptor currents by muscarinic agonists. Here, we employ traditional pharmacological reagents as well as m1-toxin, an m1 antagonist with unprecedented selectivity, to demonstrate that this potentiation of NMDA-receptor currents in hippocampal CA1 pyramidal cells is mediated by the genetically defined m1 muscarinic receptor. Furthermore, we demonstrate the colocalization of the m1 muscarinic receptor and the NR1a NMDA receptor subunit at the electron microscopic level, indicating a spatial relationship that would allow for physiological interactions between these two receptors. This work demonstrates that the m1-muscarinic receptor gene product modulates excitatory synaptic transmission, and it has important implications in the study of learning and memory as well as the design of drugs to treat neurodegenerative diseases such as Alzheimer's.     

Attitudes toward service use among wife caregivers of frail older veterans

This study investigated (a) attitudes toward service use among wife caregivers of frail older veterans; and (b) the relationship between those attitudes and service utilization by the wives. The study focused on three sets of attitudinal variables: attitudes towards various kinds of dependencies; individual and family ethos concerning service use; and perceptions of responsibility for care. Respondents were 80 wife caregivers of frail older (age 55+) veterans at a Department of Veterans Affairs Medical Center in a Midwestern state. Most caregivers agreed that it is acceptable to get help with the physical care of the husband and to get help themselves for the emotional strains caused by caregiving. Acceptability of a wife's getting help with the physical care of her husband was a positive predictor of number of services ever used and frequency of in-home service use. Wives' view that help from outside agencies should be used only as a last resort was the strongest and most consistent negative predictor of both number of services ever used and frequency of service use.     

Mutations in the hepatocyte nuclear factor-1alpha gene in Caucasian families originally classified as having Type I diabetes

Mutations in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene are the cause of maturity-onset diabetes of the young type 3 (MODY3), which is characterised by a severe impairment of insulin secretion and an early onset of the disease. Also at onset of diabetes some MODY patients show similar clinical symptoms and signs as patients with Type I (insulin-dependent) diabetes mellitus. The objective of this study was to estimate the prevalence of MODY3 patients misclassified as Type I diabetic patients. From a large population-based sample of unrelated Danish Caucasian Type I diabetic patients with an affected first degree relative, 39 patients (6.7%) who did not carry any high-risk HLA-haplotypes, i.e. DR3 or DR4 or both were examined by single-strand conformational polymorphism scanning and direct sequencing of the coding region and the minimal promoter of the HNF-1alpha gene. Four of the 39 Type I diabetic patients (10%) were identified as carrying mutations in the HNF-1alpha gene. One patient carried a missense mutation (Glu48Lys) in exon 1, two patients carried a missense mutation (Cys241Gly) in exon 4 and one patient carried a frameshift mutation (Pro291fsdelA) in exon 4. The mutations were all identified in heterozygous form, segregated with diabetes, and were not identified in 84 unrelated, healthy subjects. Furthermore, family history in three of the four families showed diabetes in four consecutive generations, suggestive of an autosomal dominant inheritance. In conclusion, about 10% of Danish diabetic patients without a high-risk HLA-haplotype, originally classified as having Type I diabetes could have diabetes caused by mutations in the HNF-1alpha gene. Clinical awareness of family history of diabetes and mode of inheritance might help to identify and reclassify these diabetic subjects as MODY3 patients.