Diaphragm fatigue during exercise at high altitude: the role of hypoxia and workload.

The effect of high altitude (HA) on exercise-induced diaphragm fatigue in normal subjects was examined. Eight normal subjects completed an incremental exercise test at sea level (SL) and at 3,325 m. Before (baseline), during, and after exercise (recovery), maximal transdiaphragm pressure (Pdi,sniff), breathing pattern, and diaphragmatic effort (PTPdi) were measured. Arterialized blood lactate was measured at baseline and during recovery. At maximal exercise (WRmax) Pdi,sniff fell to 72% and 61% of baseline at SL and HA respectively, recovering to baseline in 60 min at SL, and >60 min at HA. At the 5th min of recovery, circulating lactate was six-fold and seven-fold baseline at SL and HA, respectively. The time course of circulating lactate recovery was as for Pdi,sniff. At WRmax PTPdi was 80.74+/-9.87 kPa.s(-1) at SL and 64.13+/-8.21 kPa.s(-1) at HA. HA WRmax compared to isowork rate, SL data showed a lower Pdi,sniff (8.90+/-0.68 versus 11.24+/-0.59 kPa) and higher minute ventilation (117+/-11 versus 91+/-13 L.min(-1)), PTPdi being equal. To conclude, in normal subjects hypoxia-related effects, and not an increase in diaphragm work, hastens exercise-induced diaphragm fatigue and delays its recovery at high altitude compared to sea level.     

Association of INT2/HST1 coamplification in primary breast cancer with hormone-dependent phenotype and poor prognosis

The human proto-oncogene INT2 (homologous to the mouse INT2 gene, implicated in proviral induced mammary carcinoma) has been mapped to chromosome 11q13 and found to share band localisation with, among others, the HST1 proto-oncogene. Both genes are members of the fibroblast growth factor family. In the present study, coamplification (2-15 copies) of the INT2/HST1 genes was found in 27 (9%) of 311 invasive human breast carcinomas using slot blot and Southern blot analyses. Amplification was not correlated to tumour size, axillary lymph node status or stage of disease, neither to patient age nor menopausal status. However, 26 (96%) of the 27 amplified tumours were, often strongly, Oestrogen receptor positive compared to 65% of the unamplified cases (P = 0.001). These findings are in sharp contrast to the strong correlations of HER-2/neu proto-oncogene amplification with advanced stage and steroid receptor negativity, previously observed in the same series of tumours. Patients with INT2/HST1 amplified breast cancer had a significantly shorter disease-free survival compared to those with unamplified genes (P = 0.015, median follow up 45 months). This correlation was confined to node-negative patients and persisted in multivariate analysis. No significant correlation to survival from breast cancer was found. It is concluded that amplification of the 11q13 region in breast cancer occurs in a particular subset of aggressive tumours, quite different from that identified by HER-2/neu amplification. It still remains to be shown that the selection for amplified genes at 11q13 is due to the activity of INT2, HST1 or yet another, still unidentified, neighbouring gene. However, the results are potentially of clinical value in separating a group of node-negative breast cancer for more intense treatment.     

Putative periodontal pathogens, antibody titres and avidities to them in a longitudinal study of patients with resistant periodontitis

OBJECTIVE: To study changes in antibody titres and antibody avidities to putative periodontal pathogens in patients with resistant periodontitis and to compare these findings with the result of culture of these pathogens.
SUBJECTS AND METHODS: Patients meeting strict clinical criteria in whom periodontal therapy had failed to prevent disease progression were studied microbiologically and immunologically over a 75-week period. Particular reference was made to the isolation of Actinobocillus actinomycetemcomitons (Aa) and Porphyromonos gingivalis (Pg) together with changes in antibody titres and avidities to these organisms between baseline examination and week 75.
RESULTS: Pg was eliminated following antibiotic treatment but metronidazole and amoxycillin therapy failed to remove Aa in all cases. Antibody avidities to these pathogens were higher in patients than in matched controls but no change in avidity was noted during the course of treatment. Most antibody titres were not significantly higher in patients than in controls.
CONCLUSIONS: Continued disease progression characterised these patients who, nevertheless, mounted an immune response to the periodontal pathogens but this appeared to be inadequate to stop the disease.     

No effect of growth hormone on recovery of load-protected bone Cortical bone mass and strength studied in rabbits

The effect of human growth hormone on the recovery of a previously atrophied diaphyseal bone, stress-shielded by plating, was studied in 56 adult rabbits using the contralateral tibia as a control. At removal of the plates, an initial 40 per cent reduction of torsional strength was seen. The strength was normalized in 3 weeks. A concomitant reduction of bone mineral density was normalized in 1.5 weeks. No difference in the rate of strength regeneration was found between growth hormone-treated rabbits and controls. In the treated rabbits an increase in cortical bone area due to subperiosteal new bone formation was seen in previously plated bones, as well as in sham-operated bones.     

Respiratory depression during enflurane anaesthesia in children: influence of the nitrous oxide concentration

The author studied the rate of induction and recovery, occurrence of airway problems and the degree of respiratory depression in 30 children breathing spontaneously during inhalational induction for intubation. Two equi-anaesthetic gas mixtures were compared, 5.0% enflurane in 50% N2O (group E50) and 3.2% enflurane in 70% N2O (group E70). Induction time and time for 'partial recovery' were significantly shorter in group E70 than in group E50 (P less than 0.05). Airway problems during the excitational stage and during intubation were less common in group E70 than in group E50 (P less than 0.05). Also respiratory depression, as measured by end-tidal CO2 tension and by the occurrence of apnoea, was significantly less pronounced in group E70 than in group E50. It was concluded that 3.2% enflurane-N2O/O2 (70/30) was quite acceptable for mask induction for intubation in spontaneously breathing children, while 5.0% enflurane-N2O/O2 (50/50) caused a marked respiratory depression with delayed induction and offered less suitable conditions for intubation.     

Carcinoma of the ovary, stages I and II. A prospective randomized study of the effects of postoperative chemotherapy and radiotherapy

A prospective randomized trial for comparing the effects of chemotherapy and radiotherapy on survival in malignant epithelial ovarian tumours was carried out during the years 1975-1978 in 142 (90%) of a total material of 157 patients in Stage I and Stage II of this disease. Stratification was done according to the state of the tumour capsule and the type of histology found in Stages Ia and Ib. Two types of randomized treatment were given: A. Patients with no extracystic excrescences and intact tumour capsule with mucinous tumours in Stages Ia and Ib were given Melphalan or were not treated, while those with non mucinous tumours were given Melphalan or radiotherapy; B. All of the other patients with tumours in Stage I and Stage II were treated with radiotherapy alone, or were irradiated in combination with Melphalan treatment. Both of these treatment groups had about the same rates of 2- and 5-year survival. It was seen that the histological grade and the amount of residual tumour left at surgery are important prognostic factors. Postoperative treatment does not seem to improve cases of well differentiated, early mucinous tumours in Stage Ia. Acceptable results were obtained, however, irrespective of histological type, in early Stage I, moderately differentiated tumours treated with Melphalan or radiation therapy, and in well- or moderately differentiated tumours in Stage I or Stage IIa using irradiation alone or in combination with chemotherapy. Stages IIb and IIc, and all poorly differentiated tumours in Stages I and II, require more aggressive treatment.     

Periodontal repair in dogs: effect of recombinant human transfornning growth factor-β1 on guided tissue regeneration

Abstract. This study evaluated alveolar bone and cementum regeneration following surgical implantation of recombinant human transforming growth factor- β₁ (rhTGF-β₁) in conjunction with guided tissue regeneration (GTR). Supraalvcolar, critical size, periodontal defects were surgically created around the 3rd and 4th mandibular premolar teeth in right and left jaw quadrants in 5 beagle dogs. Alternate jaw quadrants in consecutive animals received rhTGF-β₁ in a CaCO₃/ hydroxyethyl starch carrier with GTR, or carrier with GTR alone (control), 20μg of rhTGF-/A in buffer solution was incorporated into approximately 0.8 ml of carrier for each defect scheduled to receive rhTGF-β₁. Animals were sacrificed at week 4 postsurgery and tissue blocks were harvested and processed for histo-metric analysis. Clinical healing was generally uneventful. Minor membrane exposures were observed. Defects with membrane exposure displayed an inflammatory infiltrate underneath the membrane. Bone regeneration of trabecular nature, apparent in all animals, was generally limited to the very apical aspect of the defects. Cementum regeneration was limited without obvious differences between experimental conditions. Comparing rhTGF-β to control defects, statistically significant differences were found for area (1.8±0.4 and 1.3±0.6 mm², respectively: p<0.05) and density (0.3±0.1 and 0.2±0.03. respectively: p<0.05) of alveolar bone regeneration. Observed differences are small and represent a clinically insignificant potential for enhanced regeneration in this preclinieal model. Within the limitations of study, it may be concluded that rhTGF-β₁ has a restricted potential to enhance alveolar bone regeneration in conjunction with GTR.     

Effects of the beta-2 receptor agonist terbutaline on hemodynamics and gas-exchange in endotoxin shock

The effects of the beta-2 receptor agonist, terbutaline, on hemodynamics and gas-exchange were evaluated in sheep exposed to endotoxin shock. Terbutaline was not given until signs of shock and lung injury had developed. Twenty sheep were anesthetized and ventilated without PEEP. After 90 min of stabilization (t = 0) all animals received E. coli endotoxin 10 micrograms/kg by i.v. infusion during 15 min. Thirty minutes later (t = 30) 10 animals (group TER) received i.v. infusion of terbutaline, 20 micrograms/kg/h, during 4 hours, while the other 10 served as controls (group S). The endotoxin infusion resulted in marked increase in pulmonary artery pressure (PAP) and a significant decrease in mean arterial pressure (MAP), respiratory compliance, arterial oxygen tension (PaO2) and oxygen delivery index (DO2) in both groups (t = 15 and t = 30). After 4 hours the PAP had decreased significantly in the terbutaline treated animals, but remained high in the controls (p less than 0.01). Also, MAP, PaO2, DO2 and compliance improved significantly in the terbutaline treated animals. The wet to dry weight ratio of the lungs was 4.85 +/- 0.2 in the terbutaline treated and 5.35 +/- 0.5 in the controls (p less than 0.05). It was concluded that terbutaline treatment improves gas-exchange and hemodynamics in sheep exposed to endotoxin shock.     

Vertebral bone density in icelandic women using quantitative computed tomography without an external reference phantom

Vertebral trabecular bone mineral density (BMD) was measured in 187 healthy Icelandic women, age 35–64 years, by quantitative computed tomography (QCT) with the use of internal references (muscle and subcutaneous fat) instead of the traditional external references (phantoms). We found a mean 2.4 mg/cm³ (1.8%) bone loss per year in the age range 35–64 years. There was an accelerated phase (exponential) after menopause, with 4% loss per year for the first 1–5 years after menopause or 5-fold trabecular bone loss compared with the subsequent 11–15 years after menopause. Reproducibility was found to be 1.9%. This method thus compares with traditional QCT measurements and is highly reproducible. We find QCT using internal references a promising method for assessing fracture risk in perimenopausal women and for follow-up in osteoporotic patients.