A screening and intervention program aimed to reduce mortality and serious morbidity associated with severe neonatal alloimmune thrombocytopenia

The study's objective was to identify HPA 1a-negative women and to offer them an intervention program aimed to reduce morbidity and mortality of neonatal alloimmune thrombocytopenia (NAIT). HPA 1 typing was performed in 100 448 pregnant women. The HPA 1a-negative women were screened for anti-HPA 1a. In immunized women, delivery was performed by Cesarean section 2 to 4 weeks prior to term, with platelets from HPA 1a-negative donors reserved for immediate transfusion if petechiae were present and/or if platelet count was less than 35 x 10(9)/L. Of the women screened, 2.1% were HPA 1a negative, and anti-HPA 1a was detected in 10.6% of these. One hundred seventy pregnancies were managed according to the intervention program, resulting in 161 HPA 1a-positive children. Of these, 55 had severe thrombocytopenia (< 50 x 10(9)/L), including 2 with intracranial hemorrhage (ICH). One woman with a twin pregnancy missed the follow-up and had one stillborn and one severely thrombocytopenic live child. In 15 previous prospective studies (136 814 women) there were 51 cases of severe NAIT (3 intrauterine deaths and 7 with ICH). Acknowledging the limitation of comparing with historic controls, implementation of our screening and intervention program seemed to reduce the number of cases of severe NAIT-related complications from 10 of 51 to 3 of 57.     

Woodchip sampling for the nematode Deladenus siricidicola and the relationship with the percentage of Sirex noctilio infected

Nematode levels were assessed for woodchips taken from sirex-infested trees in South Australia during July 1988. These trees were sampled to determine the percentage of sirex infected with nematodes that emerged during January to April 1989. A logistic equation was fitted to the data from 20 trees to quantify the relationship between the nematode level for woodchips and the percentage of sirex infected with nematodes. Knowledge of this relationship will allow an assessment of the nematode level in a plantation immediately before the inoculation period. Managers can prescribe nematode inoculations based on these results. An operational procedure for woodchip sampling is suggested. However, further testing is needed to verify the relationship in other regions and to determine a reliable period for sampling.     

The relationship between CR3 deficiency and neutrophil actin assembly

Polymorphonuclear leukocytes (PMN) with a deficiency of the complement receptor type 3 (CR3) membrane glycoprotein family have impairments in the ability to adhere to surfaces as well as chemotactic and phagocytic defects, processes that require a functional contractile apparatus. PMN from the patient with neutrophil actin dysfunction (NAD) displayed similar functional characteristics to those with CR3 deficiency suggesting the two disorders may be the same disease. In order to evaluate the relationship between CR3 deficiency and actin assembly, actin filament assembly was measured in PMN from six previously reported homozygotes (two severe and four moderate CR3-deficient patients) as well as five heterozygotes for CR3 deficiency. PMN from all patients had normal unstimulated concentrations of F-actin and after exposure to the chemotactic peptide FMLP (5 x 10(-7) mol/L for 5 to 40 seconds at 25 degrees C) assembled actin normally. Pretreatment of normal PMN with concentrations of monoclonal anti-alpha CR3 antibody, capable of blocking PMN adherence, also failed to impair FMLP- induced actin filament assembly. CR3 glycoprotein expression was measured in PMNs from the mother, father, and older sister of the NAD patient (N Engl J Med 291:1093, 1974). Actin filament assembly was recently shown to be defective in PMNs from all three family members. The total concentrations of the alpha and beta CR3 subunits were below normal in PMN detergent extracts from the mother (25% of simultaneous controls) and older sister (56% of control). PMN surface expression of these two subunits was also found to be depressed (mother, 50%; older sister, 63% of control). These findings suggest these two NAD family members are heterozygote carriers for CR3 deficiency as well as NAD. Simultaneous studies of the father, however, demonstrated normal total concentrations of both the alpha and beta CR3 subunits (126% of controls) as well as normal surface expression of both subunits after phorbol myristate acetate stimulation and incubation at 37 degrees C (mean, 112% of controls) but slightly lower than normal levels after FMLP stimulation (mean, 83%). These findings indicate that CR3 deficiency generally is not associated with defective actin filament assembly and support the conclusion that NAD represents a unique kindred in which PMN actin function differs from previously reported genotypes of CR3 deficiency.     

Metabolic profiles in closely controlled diabetic pregnancies during the third trimester

Summary In 5 closely controlled pregnant diabetics (duration of pregnancy 237–266 days) and 5 pregnant non-diabetics (duration of pregnancy 210–278 days) 4-hourly blood samples were taken throughout a 24 h period and analyzed for blood glucose, lactate, pyruvate, 3-hydroxybutyrate and acetoacetate, plasma non-esterified fatty acids (NEFA), glucagon and cortisol. 24 h urine specimen was analyzed for total catecholamines and 4-hydroxy-3-methoxymandelic acid. There were few significant differences in concentrations of metabolites and hormones in the two groups at any time, although the variations about the mean was usually greater in the diabetics. Thus for blood glucose in diabetics, mean value was 4.4 mmol/l, coefficient of variation 43%; in non-diabetics 4.1 mmol/l and 10% respectively. Mean plasma 3-hydroxybutyrate in diabetics was 0.47 mmol/l, coefficient of variation 55%; in non-diabetics 0.44 mmol/l and 37% respectively. Plasma non-esterified fatty acid levels were significantly higher in the diabetics (0.47 mmol/l) than in the non-diabetics (0.26 mmol/l). Coefficients of variation were 46% and 33% respectively. Two conclusions can be drawn; first, when near normal mean values for blood glucose are achieved, other metabolite and hormone levels are also near normal; second, even when the available means for diabetic control, strict diet and insulin-mixtures twice daily, are used at their maximum, metabolism in diabetics is more unstable than in non-diabetics.     

Assessing neuropathic pain in patients with low back‐related leg pain: Comparing the painDETECT Questionnaire with the 2016 NeuPSIG grading system

Background

Low back‐related leg pain with nerve root involvement is conceptually regarded as a neuropathic condition. However, it is uncertain to what extent patients with this condition can be formally classified with neuropathic pain.

Method

First, we used the 2016 revision of the IASP Special Interest Group on Neuropathic Pain (NeuPSIG) grading system for neuropathic pain to grade patients suffering from low back‐related leg pain and a corresponding disc herniation with either unlikely, possible, probable or definite neuropathic pain. Examination included bedside quantitative sensory testing. Next, we used the clinical classification based on the 2016 NeuPSIG grading system as a reference standard to assess the ability of the painDETECT Questionnaire to identify patients with neuropathic pain.

Results

Of the 50 included patients, six (12%) fulfilled the clinical classification criteria for probable and 44 (88%) for definite neuropathic pain, while none were graded unlikely or possible. According to painDETECT, 23 patients (46%) were classified with unlikely neuropathic pain, 18 patients (36%) had an uncertain condition and in nine patients (18%) neuropathic pain was likely. Among the 44 patients graded as having definite neuropathic pain by the clinical classification, eight were classified as likely neuropathic pain by painDETECT, resulting in an agreement of 18%. Of these 44 patients graded with definite neuropathic pain, painDETECT classified 21 patients (48%) as unlikely and 15 (34%) as uncertain.

Conclusion

Our results do not support the use of painDETECT as a screening tool to classify or grade neuropathic components in patients with low back‐related leg pain.

Significance

The painDETECT Questionnaire performed poorly at detecting neuropathic pain among patients with low back‐related leg pain, compared to clinical examination based on the 2016 NeuPSIG grading system as a reference standard. Our results do not support the use of painDETECT as a screening tool to classify or grade neuropathic components in this population.     

Outcomes of patients with differentiated thyroid carcinoma following initial therapy.

This analysis was performed to determine the effect of initial therapy on the outcomes of thyroid cancer patients. The study setting was a prospectively followed multi-institutional registry. Patients were stratified as low risk (stages I and II) or high risk (stages III and IV). Treatments employed included near-total thyroidectomy, administration of radioactive iodine, and thyroid hormone suppression therapy. Outcome measures were overall survival, disease-specific survival, and disease-free survival. Near-total thyroidectomy, radioactive iodine, and aggressive thyroid hormone suppression therapy were each independently associated with longer overall survival in high-risk patients. Near-total thyroidectomy followed by radioactive iodine therapy, and moderate thyroid hormone suppression therapy, both predicted improved overall survival in stage II patients. No treatment modality, including lack of radioactive iodine, was associated with altered survival in stage I patients. Based on our overall survival data, we confirm that near-total thyroidectomy is indicated in high-risk patients. We also conclude that radioactive iodine therapy is beneficial for stage II, III, and IV patients. Importantly, we show for the first time that superior outcomes are associated with aggressive thyroid hormone suppression therapy in high-risk patients, but are achieved with modest suppression in stage II patients. We were unable to show any impact, positive or negative, of specific therapies in stage I patients.     

The influence of fast and vegetarian diet on parameters of nutritional status in patients with rheumatoid arthritis

Summary Nutritional status was studied over a period of 13 months in 34 patients with rheumatoid arthritis (RA). Seventeen patients fasted for 7–10 days, were then transferred to a gluten-free vegan diet for 3.5 months and finally to a lactovegetarian diet for 9 months. The remaining 17 patients followed a normal diet. After one month, the values for body mass index (BMI) and triceps skinfold thickness (TSF) were significantly reduced in the diet group compared with the values at inclusion (p<0.001), whereas upper arm muscle area (UAMA) was not significantly reduced. Evaluation of the whole study course revealed a significantly lower BMI (p=0.04) and TSF (p<0.01) in the diet group compared with the control group. The concentration of insulin-like growth factor 1 (IGF1) was significantly reduced in the diet group after one month compared with the value at inclusion (p=0.01), but the overall difference between the two groups was not significant. There were no overall significant differences with regard to VAMA, concentration of serum albumin, haemoglobin, ferritin, zinc and copper between the two groups. Thus fast, followed by diet manipulations for one year, had a minor impact on nutritional status in patients with RA.     

Phenotypic properties of neoplastic cell lines developed from fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo

Summary We have recently reported that fetal BD IX-rat brain cells (FBC), transferred to long-term culture after a transplacental pulse of EtNU on the 18th day of gestation, undergo neoplastic transformation in vitro (BT-cell lines). Tumors developed upon s.c. reimplantation of BT-cells into baby BD IX-rats, appeared histologically as neurinoma-, glioma- or glioblastoma-like, and frequently as pleiomorphic neoplasms. In spite of a more atypic cellular morphology, these tumors grossly resembled the different types of neuroectodermal rat neoplasms induced by EtNU in vivo. Like the neoplastic cell culture lines derived from EtNU-induced, neuroectodermal BD IX-rat tumors (V-cell lines), the BT-lines contained multipolar glia-like cells, but also flat cells with fewer and shorter cytoplasmic processes, and occasionally giant cells. Both the V- and BT-lines showed different levels of aneuploidy. They contained multiple subpopulations of cells, as reflected, e.g., by plurimodal pulse-cytophotometric DNA distributions. All lines contained, to varying degrees, the nervous system specific protein S-100, a marker not yet expressed in FBC. There was no indication of more than borderline neurotransmitter activity, suggesting that proliferating (precursor) cells of glial lineages may preferentially undergo malignant transformation after exposure to EtNU during this stage of brain development.

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Zusammenfassung Gehirnzellen der fetalen (18. Tag der Gravidität) BD-IX-Ratte, nach einem transplacentaren N-Äthyl-N-Nitrosoharnstoff (ÄNH)-Puls in vivo in ein Langzeit-Zellkultursystem überführt, durchlaufen den Prozeß der neoplastischen Transformation in vitro (BT-Zellinien). Die nach s.c. Rückimplantation von BT-Zellen in neugeborene BD IX-Ratten entstandenen Tumoren (histologisch vom Neurinom-, Gliomoder Glioblastomtyp, häufig auch pleomorph) waren insgesamt den verschiedenen Arten neuroectodermaler Neoplasmen vergleichbar, die bei BD IX-Ratten nach ÄNH-Applikation in vivo beobachtet werden. Ebenso wie Zellkultur-Linien (V-Zellinien), die von ÄNH-induzierten Tumoren des Nervensystems der BD IX-Ratte abgeleitet wurden, enthielten die BT-Linien multipolare, gliaähnliche Zellen, neben wenigen Riesenzellen aber auch flache Zellen mit vergleichsweise wenigen, kürzeren cytoplasmatischen Fortsätzen. Die V- und BT-Linien waren verschiedengradig aneuploid und aus multiplen Subpopulationen von Zellen zusammengesetzt, widergespiegelt u.a. durch plurimodale impulscytophotometrische DNS-Verteilungen. Alle Linien enthielten das vorwiegend gliaspezifische Marker-Protein S-100, welches im fetalen Gehirn noch nicht exprimiert ist. Eine nennenswerte Neurotransmitter-Aktivität wurde nicht gefunden. Nach Applikation von ÄNH während der perinatalen Phase der Gehirnentwicklung werden offenbar vorwiegend proliferative Zellen glialer (Vorläufer-) Populationen neoplastisch transformiert.

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Abbreviations EtNU N-ethyl-N-nitrosourea - i.V. intravenous - s.c. subcutaneous - FBC fetal BD IX-rat brain cells - PBS phosphate buffered saline - BSA bovine serum albumin This is communication No. 14 on a research program devoted to molecular and cellular mechanisms in pulse-carcinogenesis by N-ethyl-N-nitrosourea in the rat nervous systemResearch supported by the Deutsche Forschungsgemeinschaft (Ra 119/5-6; SFB 51/E-13), the C. Bohnewand-Foundation and by the Norwegian Cancer SocietyOn leave from the Institute of Pathology, Sect. B., University of Oslo, Rikshospitalet, Oslo 1, Norway.