Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi trial): study design and rationale.

Although lung volume reduction surgery improves survival in selected patients with emphysema, there has been ongoing interest in developing and evaluating bronchoscopic approaches to try to reduce lung volumes with less morbidity and mortality. The placement of endobronchial valves is one such technique, and although some patients have had a significant improvement, responses have been inconsistent because collateral ventilation prevents lobar atelectasis. We describe the protocol of a trial (ISRCTN04761234) aimed to show that a responder phenotype, patients with heterogeneous emphysema and intact interlobar fissures on CT scanning, can be identified prospectively, leading to a consistent benefit in clinical practice.

Long term follow-up of patients with Cushing's disease treated by interstitial irradiation.

The first 86 patients with Cushing's disease treated with interstitial irradiation (by needle implantation) as the sole therapy were reviewed. In the 82 patients who were reassessed 1 yr after treatment 63 (77%) achieved remission. This study comprises the outcome and complications in the 54 patients who had a remission and whom we were able to follow. The follow-up period ranged from 3-26 yr (mean, 10.5) from the time of remission. No instance of clinical or radiological relapse has occurred. Of these 54 patients, yttrium-90 alone was used in 32, of whom 12 (37%) required corticosteroid or T4 replacement therapy in a mean time of 3.5 months; in 7 of these 12 we elected to give an ablative dose. Gold-198 alone was used in 15 patients, of whom 7 (47%) developed hypopituitarism in a mean time of 76 months. Both isotopes were used in 7 patients. A diurnal serum cortisol rhythm was found in 28 of the 31 patients who were not receiving corticosteroid therapy. In 5 of the 7 patients with an initially abnormal pituitary fossa, serial radiological studies revealed remodelling in 3. There have been no complications in the last 17 years. Pituitary implantation with yttrium-90 is an effective alternative to transsphenoidal hypophysectomy, with a high remission rate, no recurrence (as yet), no operative complications, and avoidance of hormone replacement in the majority.

Effects of radiographic contrast media on leukocyte locomotion.

It has been shown that radiographic contrast media activate the complement system and release C3A and C5A, which, among other things, are chemotactic factors; ie, they increase the locomotion of leukocytes. The authors have examined the effects of contrast media on plasma, serum, neutrophilic (polymorphonuclear) leukocytes, and several standard chemoattractant proteins using modified Boyden chambers and micropore filters. Contrary to the results of others, which showed that contrast media increased the locomotion of neutrophils toward standard chemoattractants, the authors have shown that contrast media uniformly reduced neutrophil locomotion towards chemoattractant proteins by a combined effect on the proteins and on the neutrophils themselves. The exact inter-relationship between reduction in neutrophil locomotion and any possible adverse effects of radiographic contrast media remains to be clarified.

Trophoblast growth in the lungs of mice.

Trophoblast giant cells grow from ectoplacental cones of 7 1/2 days' gestation that are implanted in the lung from the surface, intrabronchially, or via the circulation. When blastocysts of 3 1/2 days' gestation are implanted in lung, their behavior varies according to the route of implantation and the ages of the recipient mice. Blastocysts produced trophoblast giant cells when implanted in the bronchial tree. Trophoblast giant cells were not seen in adult lungs when blastocysts were introduced via the circulation. However, they were seen in 12-day-old mice injected in the same way 10 days previously. Something is apparently liberated from adult lung vessels which interacts with the blastocyst or zona pellucida and causes rapid degeneration of trophoblast. Experiments designed to extract this agent are in progress in the hope that the agent may be useful in the treatment of human trophoblastic disease.

An experimental study of trophoblast growth in the lung.

Trophoblast can be grown from blastocysts or ectoplacental cones of the mouse in a variety of extrauterine sites. An attempt was made to grow trophoblast in the lung under various conditions. In 94 mice, blastocysts, or cones, were introduced into the lung through the vascular system. Trophoblast growth never occurred. However, when blastocysts, or cones, were introduced directly into the lung, trophoblast grew in 30-50% of mice, depending on technique. Failure to grow from the intravascular position does not appear to be due to liberation of common products of ischemia because blastocysts produced normal trophoblast in the liver when implanted via the portal system, even in the presence of extensive necrosis. The inhibiting factor, which is apparently produced in the lung, is being investigated.

Recent advances in the cytogenetic study of human spontaneous abortions.

A cytogenetic study of 27 spontaneous abortions was carried out using the Q-banding technic. The specimens were selected for study in order to increase the likelihood of finding a chromosome anomaly. Sixteen of 27 specimens (59%) showed a chromosome abnormality. Trisomy was found in 9 of the specimens, and the chromosomes involved were Nos. 2, 8, 14, 16, and 22. There were 5 triploids and 2 tetraploids. Using marker chromosomes, it was found that the extra haploid set was paternally derived in two of the triploids which were favorable for study. The Q-banding technic provides accurate identification of the extra chromosomes in trisomy. When favorable markers are present in the parents, the source of the extra haploid set can be identified in triploid abortuses.

PIP: A cytogenic study of 27 spontaneously aborted fetuses using the Q-binding technique is presented. Chromosomal abnormalities were detected in 59% of the specimens. Trisomy was indicated in 9 specimens, with chromosomes Nos. 2, 8, 14, 16, and 22 being involved. There were 5 cases of triploids and 2 cases of tetraploids. Extra haploid sets were paternally derived in 2 of the triploids. The Q-binding technique can accurately identify the parental source of the extra haploid set in triploids when favorable markers are present in the parents.

Peripheral airways obstruction on high-resolution computed tomography in chronic severe asthma.

Long-standing chronic severe asthma may be associated with structural changes of both proximal and distal airways. To assess these changes, high-resolution computed tomography (CT) using an Imatron Ultrafast CT scanner with 3 mm thick sections at 10 min intervals was performed at full inspiration. A limited set of CT sections was also obtained on full expiration. Twenty-four chronic severe asthmatic patients (age, 47.0 +/- 2.4 years; FEV1, 56.5% +/- 4.1% of predicted) were studied. The scans were assessed independently by two radiologists. While concomitant dilatation and thickening of intrapulmonary airways were observed in 12 patients, air trapping as assessed by areas of increased lucency on expiratory scans was noted in 20. The mean expiratory-to-inspiratory cross-sectional area (Exp/Ins) was 75.9% +/- 2.0%, compared with 44.6% +/- 1.0% in historical non-asthmatic subjects. FEV1 (% predicted) correlated with Exp/Ins and with CT features of air trapping (both rs = 0.60; P < 0.001) but not with airway dilatation or thickening. Our data indicate the presence of peripheral airways obstruction in chronic severe asthma, which may be one of the underlying reasons for increased severity of asthma.

Reactions to radiographic contrast media: an attempt to detect specific anti-contrast medium antibodies in the sera of reactor patients.

A radioimmunoassay was used in an attempt to detect specific anti-contrast medium antibodies in the sera of a group of 68 patients who reacted to radiographic contrast media and a group of 30 age-, sex- and disease-matched control patients who did not react. No evidence of specific antibodies of the IgG or IgE classes was demonstrated in these two groups. The results suggest the lack of an antibody-mediated aetiology for reactions to radiographic contrast media.

Comparison of barium and diatrizoate bowel labelling agents in computed tomography.

A new suspension of barium sulphate, E-Z-CAT, for use as a bowel labelling agent in computed tomography (CT) of the abdomen and pelvis, has been compared with diatrizoate (Gastrografin) in 111 patients. The E-Z-CAT labelled the duodenum more efficiently and patients preferred its taste. Both substances are satisfactory bowel-labelling agents.

Contrast media reactions: experimental evidence against the allergy theory.

In order to clarify whether adverse reactions to radiographic contrast media may be allergic in nature, it is essential to show that contrast media can act as haptens and induce antibody formation in vivo. Experiments in Hooded Lister rats have been carried out using techniques specifically designed to produce favourable conditions for the production of antibodies. No evidence of any antibody formation was found in any of the experiments. These experiments suggest that radiographic contrast media in their native form do not act as haptens, contrary to previously published data, and it therefore seems unlikely that the majority of adverse reactions to radiographic contrast media are allergic in nature.

Percutaneous catheter nephrostomy drainage--results of 70 procedures.

Percutaneous nephrostomy (PCN) was performed 70 times in 46 patients. In the majority of cases the procedure was carried out as an emergency to relieve urinary obstruction. 20 of the patients had subsequent elective surgery, in others PCN allowed time for other forms of treatment to become effective. The technique carries a low mortality and morbidity, can be performed using either fluoroscopic or ultrasound imaging and should be available in all radiology departments.

Paramagnetic contrast media for magnetic resonance imaging of the mediastinum and lungs.

The use of paramagnetic contrast agents in magnetic resonance imaging (MRI) of the lungs and mediastinum has been the subject of preliminary investigation. Gadolinium-DTPA (Gd3+-DTPA) is a suitable intravenous paramagnetic contrast agent for imaging cerebral tumors and liver tumors. Its use in the thorax is more speculative, but early animal experimental data suggest that contrast-enhanced MRI may have a place in the assessment of pulmonary edema and lung parenchymal damage.

The afferent innervation of the face of sheep and goats.

The sensory innervation of the maxillary hairy skin and buccal mucous membrane was studied in anaesthetised sheep and goats. An electrophysiological technique isolated 47 single afferent units from the infraorbital nerve under chloralose or halothane anaesthesia. Mechanoreceptors of hairy skin were located in association with the following features: sinus hairs (n = 9); central primary hairs (n = 18); clear marginal hairs (n = 7) and skin-not-hair (n = 3). Units responded to hair tip displacement of 35 to 50 microm. Afferent units were also located in the mucous membrane of the cheek either associated with conical papillae (n = 8), or unassociated with papillae (n = 1). Receptor responses associated with hairs were classified as rapidly adapting (n = 18) and slowly adapting (n = 18) mechanoreceptor responses during sustained hair deflection. Seven mechanoreceptors of hairy skin and mucous membrane were excited by a fall in surface temperature. Two specific cold thermoreceptors were found: one in hairy skin and one in the mucous membrane. These units had phasic discharges during abrupt thermal depression and static discharges at constant surface temperatures. All afferent units had myelinated axons as indicated by their conduction velocities (range 20 to 57 m sec-1, mean 34 m sec-1). It is concluded that the mechanoreceptors identified had similarities with those of other mammalian species and some distinct differences. An interesting feature of mechanoreceptors in the buccal mucosa was their cold sensitivity. They therefore shared characteristics with mechanoreceptors in the penile mucosa of the ram and tongue of the sheep.

Neurophysiologic maps of cutaneous innervation of the external genitalia of the ram.

The area of skin innervated by the afferent fibers in a peripheral nerve is called the cutaneous area (CA) of that nerve. Mapping of those areas that were responsive to movement of wool/hairs in the genital region of 18 anesthetized rams, combined with subsequent identification of spinal nerves and dissection of the pudendal nerve plexus, indicated considerable differences in the extent of the CA and the origins of cutaneous branches from the pudendal plexus. The CA of the proximal and distal cutaneous branches of the pudendal nerve (or plexus) overlapped craniocaudally by approximately one-half, and the latter included most of the skin of the ipsilateral half of the scrotum. The CA of the deep perineal and caudal rectal nerves lay immediately adjacent to the anus. The CA of the scrotal branches of the pudendal nerve were restricted primarily to the scrotum. Fascicles in the dorsal nerve of the penis irregularly supplied CA along the length of the prepuce and consistently supplied the cranial free end of the prepuce. The CA of the ventral cutaneous branches of the caudal thoracic spinal nerves, the first 2 or 3 lumbar spinal nerves, and the genitofemoral nerve extended to the midline of the prepuce. Overlapping of CA was extensive, especially on the prepuce.

The effect of different methods of electrical stunning of lambs on blood pressure and muscular activity.

The effect on blood pressure and muscular activity of a 'head-only' and a 'head-to-body' method of electrical stunning was measured in groups of lambs. A two- to three-fold increase in arterial pressure followed 'head-only' stunning, along with moderate increases in venous pressure. By contrast, after 'head-to-body' stunning, arterial pressure decreased, but venous pressure increased to above 50 mm Hg. Electromyographic recordings showed there was a greater increase in the intensity of muscular activity following 'head-to-body' stunning compared with 'head-only' stunning and there was a direct correlation between the degree of muscular activity and the increase in venous pressure. It is argued that the resultant pressure changes in the microcirculatory bed are likely to be associated with the occurrence of haemorrhagic defects following stunning by electrical methods.

The use of iron and gadolinium chelates as NMR contrast agents: animal and human studies.

Rapid development of paramagnetic NMR contrast agents has occurred over the past 3 years. Useful agents include chelates of iron and gadolinium. Gadolinium-DTPA was used safely in 23 human subjects with brain tumors, hepatic tumors and cysts, and a variety of abdominal and pelvic tumors. Various patterns of contrast-enhancement were noted. These agents can radically alter NMR image contrast. Optimum doses, pulse sequences and timing of imaging remain to be determined.