Thromboprophylaxis improves the live birth rate in women with consecutive recurrent miscarriages and hereditary thrombophilia

Summary.  The effect of thromboprophylaxis with low molecular weight heparin (LMWH), on the subsequent live birth rate, in thrombophilic women with recurrent miscarriage has not been sufficiently assessed. The present study is a cohort study undertaken to assess the effect of enoxaparin on the subsequent live birth rate in women with hereditary thrombophila. Eighty-five patients with three or more consecutive pregnancy losses and a hereditary thrombophilia subsequently conceived. Thirty-seven were treated with daily subcutaneous injections of enoxaparin 40 mg and 48 were not treated. The outcome of the subsequent pregnancy was assessed in both groups of patients in terms of live births or repeat miscarriage. Forty-seven of the 85 patients were subsequently delivered, 38 have miscarried. Twenty-six of the 37 pregnancies in treated patients (70.2%) resulted in live births, compared with 21 of 48 (43.8%) in untreated patients ( P  < 0.02, OR 3.03, 95% CI 1.12–8.36). The beneficial effect was seen mainly in primary aborters, i.e. women with no previous live births ( P  < 0.008, OR 9.75, 95% CI 1.59–52.48). This benefit was also found in patients with a poor prognosis for a live birth (five or more miscarriages), where the live birth rate was increased from 18.2% to 61.6%. However, the benefit was not statistically significant, probably due to the small number of patients. If the beneficial effects of enoxaparin are confirmed by additional studies, thromboprophylaxis can be recommended for patients with hereditary thrombophilia and recurrent pregnancy loss.     

Immunopotentiation reverses the embryotoxic effect of serum from women with pregnancy loss.

OBJECTIVE: To assess the effect of sera of women with habitual abortions (AB) on attachment and spreading of mouse blastocysts in vitro. DESIGN: Expansion, attachment, and spreading were the mouse blastocyst parameters utilized. Deoxyribonucleic acid (DNA) synthesis and cell markers expression were also assayed by autoradiography analysis and the indirect immunofluorescent technique. SETTING: Sera were drawn from patients attending a habitual AB clinic in a tertiary care university hospital. PARTICIPANTS: Thirty-nine serum samples were drawn from habitually aborting women and the effect compared with 17 control AB sera. INTERVENTION: Habitually aborting women were immunized with paternal leucocytes; 18 post-immunization sera were also assessed. OUTCOME AND RESULTS: After 48 hours, there was delayed attachment and spreading (4% of test blastocysts spread as compared with 50.5% of controls). This was more profound after 72 hours culture (7.5% spread as compared with 72.8% of controls). Experimental sera were capable of reducing DNA synthesis, cytokeratin, fibronectin, or placental alkaline phosphatase expression by blastocyst cells. Leucocyte immunization of women with habitual ABs, clearly reversed the embryotoxic effect of the sera and enhanced cell markers expression. CONCLUSIONS: These data suggest that immunopotentiation may improve blastocyst survival in utero.     

Pseudomonas aeruginosa exotoxin A: its role in retardation of wound healing: the 1992 Lindberg Award.

Bacterial concentrations greater than 10(5) colony-forming units/gm of tissue prevent wound healing. However, it has not been determined whether it is the number of bacteria or a toxin produced by these organisms that impedes the wound healing process. Pseudomonas aeruginosa (PSAR), a burn wound pathogen, produces a dermonecrotic toxin, exotoxin A. Studies have indicated a role for exotoxin A in the pathogenicity of PSAR. We investigated the role of exotoxin A in the retardation of contraction. Acute granulating wounds were created on 90 Sprague-Dawley rats. The animals were equally divided into six groups and were treated topically as follows: group 1, sham: no infection, no treatment; group 2, exotoxin A; group 3, exotoxin A and antiexotoxin; group 4, autoclaved PSAR 10(6); group 5, 10(6) viable PSAR inoculated in the wound; group 6, 10(6) viable PSAR and antiexotoxin. Wound contraction was measured with the use of planimetry twice a week. Serial biopsies were performed on all wounds. Contraction rates revealed significantly (p < 0.05) retarded closure in the animals treated with exotoxin A and in the viable PSAR group when compared with the rates of the noninfected control groups. Animals treated with exotoxin A plus antiexotoxin A and those treated with live PSAR and antiexotoxin showed contraction rates identical to the control groups. These data suggest that exotoxin A in PSAR infections retards wound healing and that neutralization of the toxin restores the normal healing process.     

Immunotherapy of habitual abortion.

Many cases of habitual abortion have been assumed to be due to hyporesponsiveness to the spouse's antigens encountered in pregnancy. Immunization by paternal leukocytes has been used to potentiate the immune response and prevent further miscarriages. This treatment has been highly controversial in terms of efficacy, mode of action, and side effects. More recently immunoglobulin has been used as passive immunization for similar indications. In our experience immunotherapy is effective; 80% of patients have subsequent live births. The most significant results are seen in patients with five or more abortions, in whom 66% of subsequent pregnancies develop normally compared to 20% in a control group. We have used antipaternal complement-dependent antibody (APCA) production after immunization as a marker of immune response. APCA correlates with beneficial outcome in the next pregnancy. APCA may also be associated with cytokines, which may enhance embryonic and trophoblast development. Immunoglobulin may similarly provide the relevant antibodies or cytokines. At present a large scale meta-analysis is being performed to confirm or refute the efficacy of this treatment. This meta-analysis may resolve the controversy.     

Extensive degeneration of catecholaminergic neurons to scrapie agent 87V in the brains of IM mice

Scrapie is a degenerative disease of the central nervous system of sheep and goats. The causative agent has been passaged to a number of laboratory species, including mice and hamster. Amyloid plaque formation and vacuolation, the signs of senile dementia, are found in the brains of mice infected with 87V scrapie agent. Dopamine (DA) and norepinephrine (NE) concentrations in the brains of scrapie-infected mice were measured with high-performance liquid chromatography-electrochemical detector (HPLC-ECD). A significant decrease in NE level was exhibited in all regions tested, whereas the level of DA decreased significantly only in cerebral cortex. Immunohistochemistry was used to examine immunoreactive catecholamine neurons in substantia nigra and locus ceruleus using antisera against tyrosine hydroxylase (TH). The population of TH-immunoreactive neurons in the substantia nigra and locus ceruleus were significantly decreased in scrapie-infected mice compared to controls. These data suggest that both the noradrenergic and dopaminergic system are sensitive to the action of scrapie agent 87V and that changes in the catecholamine levels in the brains of scrapie-infected mice may contribute to some of the clinical symptoms of the diseases, such as ataxia and apraxia.     

Scrapie incubation periods and end-point titers in mouse strains differing at the H-2D locus

In extending findings on the influence of the mouse H-2D locus on the scrapie incubation period, we showed that with the intracerebral (i.c.) route of injection, SJL and NZW mice (s and z alleles, respectively) had shorter incubation periods than C57BL mice (b allele) at several concentrations of two scrapie strains, ME7 and 139A. The three mouse strains have the same Sinc genotype, s7s7. Incubation period data among the three mouse strains after intraperitoneal (i.p.) injection revealed a different rank order of incubation periods from that seen after i.c. injection. End-point titers in the three mouse strains were similar after i.c. injection, but both scrapie strains yielded very low titers in NZW mice after i.p. injection. There were marked differences between 139A and ME7 incubation periods after both i.c. and i.p. injections in the three mouse genotypes, providing an additional parameter that distinguishes these two scrapie strains.     

The effect of patient position and obesity on the spread of epidural analgesia

The aim of this study is to assess the effect of patient positioning and obesity on the height of block achieved during routine labor epidural analgesia. Forty patients weighing <80 kg were allocated to a control group and a further 40 weighing >100 kg to a study group. Half the patients in each group received an epidural injection in the lateral position, the remainder were in the sitting position. After insertion of an epidural catheter and injection of 12 ml of 0.25% bupivacaine plain the patients remained in position for a further 5 min. The height of block achieved, as assessed by loss of cold sensation, showed no difference between any of the groups. The results indicate that, for routine labor epidural analgesia, using 12 ml of 0.25% plain bupivacaine, neither patient positioning nor obesity affects the height of block achieved.     

FDG-PET/CT for treatment response assessment in head and neck squamous cell carcinoma: a systematic review and meta-analysis of diagnostic performance

Purpose

18-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) is increasingly used to evaluate treatment response in head and neck squamous cell carcinoma (HNSCC). This analysis assessed the diagnostic value of FDG-PET/CT in detecting nodal disease within 6 months after treatment, considering patient and disease characteristics.

Methods

A systematic review was performed using the MEDLINE and Web of Knowledge databases. The results were pooled using a bivariate random effects model of the sensitivity and specificity.

Results

Out of 22 identified studies, a meta-analysis of 20 studies (1293 patients) was performed. The pooled estimates of sensitivity, specificity and diagnostic odds ratio (with 95% CI) were 85% (76–91%), 93% (89–96%) and 76 (35–165), respectively. With the prevalence set at 10%, the positive and negative predictive values were 58% and 98%. There was significant heterogeneity between the trials (p <?0.001). HPV positive tumors were associated with lower sensitivity (75% vs 89%; p =?0.01) and specificity (87% vs 95%; p <?0.005).

Conclusion

FDG-PET/CT within 6 months after (chemo)radiotherapy in HNSCC patients is a reliable method for ruling out residual/recurrent nodal disease and obviates the need for therapeutic intervention. However, FDG-PET/CT may be less reliable in HPV positive tumors and the optimal surveillance strategy remains to be determined.

     

Tumor volume as a prognostic marker in p16-positive and p16-negative oropharyngeal cancer patients treated with definitive intensity-modulated radiotherapy

Purpose

To investigate the impact of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) in oropharyngeal squamous cell carcinoma (OPSCC) and the difference in their role between human papillomavirus (HPV)-positive and HPV-negative patients.

Methods

The patient cohort consists of 91 OPSCC patients treated with definitive radiochemotherapy or radiotherapy using intensity-modulated radiotherapy (IMRT). All patients had a minimum follow-up of 31 months. Volume measurements were made from computer tomography (CT) scans and HPV status was assessed by p16 immunohistochemistry. The end points were as follows: overall survival (OS), disease-free survival (DFS) and locoregional control (LRC).

Results

pGTV was a significant independent prognostic factor for overall survival (OS; p?=?0.020) in p16-negative patients. nGTV of p16-negative tumors had significant prognostic value in all end points in multivariate analyses. High-stage (III–IVc) p16-negative tumors were only associated with significantly poorer OS (p?=?0.046) but not with poorer LRC or DFS when compared with the low-stage (I–II) tumors. nGTV of p16-positive tumors was an independent prognostic factor for DFS (p?=?0.005) and LRC (p?=?0.007) in multivariate analyses.

Conclusion

pGTV may serve as an independent prognostic factor in p16-negative patients and nGTV may serve as an independent prognostic factor both in p16-positive and p16-negative patients treated with radiochemotherapy or radiotherapy using IMRT. Tumor volume may have an impact on selecting patients for de-escalation protocols in the future, both in p16-positive and p16-negative patients.