Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease.

Immunoglobulin A (IgA) is generally considered as a non-inflammatory regulator of mucosal immunity, and its importance in diversifying the gut microbiota is increasingly appreciated. IgA autoantibodies have been found in several autoimmune or chronic inflammatory diseases, but their role in pathophysiology is ill-understood. IgA can interact with the Fc receptor FcαRI on immune cells. We now established a novel IgA autoimmune blistering model, which closely resembles the human disease linear IgA bullous disease (LABD) by using genetically modified mice that produce human IgA and express human FcαRI. Intravital microscopy demonstrated that presence of IgA anti-collagen XVII, - the auto-antigen in LABD-, resulted in neutrophil activation and extravasation from blood vessels into skin tissue. Continued exposure to anti-collagen XVII IgA led to massive neutrophil accumulation, severe tissue damage and blister formation. Importantly, treatment with anti-FcαRI monoclonal antibodies not only prevented disease, but was also able to resolve existing inflammation and tissue damage. Collectively, our data reveal a novel role of neutrophil FcαRI in IgA autoantibody-mediated disease and identify FcαRI as promising new therapeutic target to resolve chronic inflammation and tissue damage.

Inadequacy of iridium implant as sole radiation treatment for operable breast cancer.

In order to avoid a prolonged course of external irradiation as part of breast conservation therapy, 27 patients received an iridium implant to the primary tumour bed as sole radiation treatment. Surgery was standardised comprising tumourectomy and axillary clearance. Using a rigid implant afterloading with iridium192 wires, 55 Gy was delivered on a continuous basis over 5 days. After 6 years median follow-up, relapse of cancer within the treated breast has occurred in 10 of the 27 patients (37%). Compared with historical controls treated by similar surgery and iridium192 implant (20 Gy) with external radiotherapy (46 Gy), there was a significantly increased breast relapse rate in those treated by iridium implant alone. However, the incidence of distant metastases and overall survival was similar. Thus, a continuous iridium192 implant delivering 55 Gy in 5 days is not an effective means of achieving local control in patients with operable breast cancer.

Influence of the oestrous cycle on experimental intrauterine E. coli infection in the sow.

The influence of the oestrous cycle on the onset of endometritis in the sow was studied. Ten pubertal, unmated gilts of the Belgian Negative Landrace were used. Nine gilts were inoculated into the uterus by laparotomy with a suspension of an E. coli strain isolated from the uterus of a discharging sow from a herd having many problems with vaginal discharge and a lowered fertility. One gilt was as a control inoculated with 2 ml of a PBS-solution. All sows inoculated during dioestrus developed clinical symptoms, but only 1 of the 5 gilts inoculated at standing oestrus developed a vaginal discharge. These data confirm the hypothesis that the stage of the oestrous cycle has an important influence on the onset of endometritis. The resistance to E. coli infections was higher when the gilts were inoculated during oestrus.

Water-sealed spirometer for measurements in newborns and infants.

Details are given of two spirometers for use in neonates and infants < 12 mo old. The minimum volumes are 520 and 670 ml, respectively. The maximum volume changes that can be recorded are 250 and 450 ml, respectively. The minimal detectable volume changes are 0.4 and 0.6 ml, respectively. Rebreathing of dead space gas is prevented by a fan producing a flow of 6.2 and 10.2 l/min, respectively; 100% gas mixing after injecting a gas bolus in the two spirometers is achieved in 5.7 and 6.6 s, respectively. Resistance to airflow is 0.2 kPa.l-1.s (2 cmH2O.l-1.s) at 150 ml/s in both spirometers. The frequency response of both instruments is flat to 6 cycles/s. The instruments can be easily cleaned and are suitable for bedside measurements.

Cerebral and aortic blood flow velocity patterns in preterm infants receiving prophylactic surfactant treatment.

Blood velocity in the internal carotid artery (ICA) and in the descending thoracic aorta (DAo) was investigated used Duplex-Doppler ultrasound in 14 infants of less than 30 weeks gestation, treated prophylactically with surfactant, and in 11 comparable infants with relatively mature lungs who served as controls. After surfactant administration, blood gases, pH or FiO2 were not different between the groups. Temporal mean blood velocity in the ICA was used as a relative measure of cerebral flow (TMFV-cer), and its coefficient of variation (CV-cer) was used to assess fluctuations in cerebral blood velocity. The pulsatility index (PI) in the ICA (PI-cer) and DAo (PI-DAo) was used to estimate if a left-to-right shunt was present. During surfactant instillation TMFV-cer was abnormally low and CV-cer indicated a fluctuating cerebral blood velocity. At 10 min after surfactant administration, TMFV-cer of the treated infants was higher compared to the controls, while CV-cer was stable in both groups. PI-cer and PI-DAo were abnormally high during the first hour of life after surfactant treatment, suggesting a left-to-right shunt without, however, clinical signs of a hemodynamically important ductus arteriosus. We suggest that cerebral perfusion is affected during and at 10 min after surfactant instillation. Left-to-right shunting appears to be a common event following surfactant treatment.

Iridium implant treatment without external radiotherapy for operable breast cancer: a pilot study.

A pilot study has been conducted to examine a new approach to the treatment of operable breast carcinoma. 27 patients with tumours measuring up to 4 cm in diameter have been treated by tumourectomy, axillary clearance and high dose iridium-192 implant (55 Gy) without any external beam radiotherapy. This enabled the entire local primary treatment of the breast carcinoma to be given in five days. The technique was compatible with adjuvant chemotherapy for those with involved axillary nodes. Local complications have been few and locoregional control has to date been satisfactory. With a relatively short median follow-up of 27 months, cosmesis was objectively rated as good or excellent in over 80% of cases and subjectively rated good/excellent in 96%. High dose brachytherapy now requires testing in a prospective clinical trial to determine whether it is as effective as standard breast conservation techniques for management of early breast cancer.

Replication of human occlusal tooth attrition surfaces for scanning electron microscopic study.

Silicone negative replicas of dentine islands exposed by occlusal attrition were examined on extracted human teeth using the scanning electron microscope. Because the details of the dentinal tubules were reproducible on the silicone impression, the replication technique was applied in vivo to occlusal attrition to demonstrate patent dentinal tubules in cases with symptomatic exposed dentine islands. using this replication technique, it should be possible to monitor the effect of the therapeutic management of symptomatic tooth attrition on dentinal tubule closure.

Influence of radiotherapy on the dose of adjuvant chemotherapy in early breast cancer.

399 patients with early breast cancer were randomly allocated to treatment by either modified radical mastectomy or lumpectomy and radiotherapy. 169 had histologically involved axillary nodes and were randomised to receive either adjuvant cytotoxic chemotherapy (76 patients) or no systemic adjuvant treatment (93 patients). Chemotherapy comprised a combination of oral cyclophosphamide and intravenous methotrexate and 5-fluorouracil (CMF) for 12 cycles over one year. Patients in the mastectomy group received a significantly higher percentage of the planned chemotherapy dose compared with those in the radiotherapy group (median 85% v. 71% p less than 0.05). Patients treated with radiotherapy were more frequently nauseated and developed more severe alopecia, but these differences were not statistically significant. At median follow-up of 37 months the relapse-rate and pattern of relapse were similar in both groups of patients receiving CMF.

Prednisolone improves the response to primary endocrine treatment for advanced breast cancer.

Two hundred and twenty patients with progressive advanced breast cancer were given primary endocrine treatment (PET) according to menstrual status. Pre-menopausal patients received ovarian irradiation (O) and post-menopausal tamoxifen 10 mg bd (T). Patients were randomised to receive either no additional treatment or prednisolone 5 mg bd (P). Similar results were observed in each menstrual subgroup. In 194 evaluable patients, the response to PET + P was 49% and to PET alone 30% (P less than 0.01). P increased the median duration of response from 9 to 14 months (P less than 0.002) and the median time to disease progression from 5 to 9 months (P less than 0.001). Response to P after O or T alone occurred in only 2/62 (3%). Median survival in patients randomised to receive P at the outset of PET was prolonged by 4 months (P less than 0.05). The addition of P significantly improves the response to O or T in the treatment of advanced breast cancer.

The relationship between intestinal Campylobacter species isolated from animals and humans as determined by BRENDA.

Intestinal thermophilic Campylobacter species produce stable patterns when subjected to bacterial restriction endonuclease DNA analysis (BRENDA); this technique is therefore of considerable value in epidemiological studies. BRENDA was used to examine thermophilic Campylobacter species from humans, wild and domestic animals. One hundred and ninety-four (61%) of 316 isolates of Campylobacter jejuni from humans had BRENDA patterns which could be matched to those of animal isolates. Poultry appear to be a major source of infection for C. jejuni in humans with nearly half (49.7%) of the human isolates giving patterns which were indistinguishable from those isolated from poultry. A total of 60 BRENDA types were identified from 316 human isolates and 11 of these had the same pattern as those isolated from poultry. One of the three Campylobacter coli BRENDA types recovered from poultry was indistinguishable from a human isolate type. Pigs appear to be only a minor source of C. coli infection for humans in New Zealand. Rats were found to be infected with strains of C. jejuni with BRENDA patterns indistinguishable from those infecting humans, poultry and a horse. None of the 102 isolates of Campylobacter species from wild birds gave BRENDA patterns similar to those of isolates from humans.