Persistent and/or late complications of combined radiation therapy and hyperthermia.

Persistent and/or late complications were analysed in 64 patients (183 fields) that were treated with combined hyperthermia and radiation therapy for advanced, recurrent or metastatic cancer. The incidence and type of complications were evaluated over a minimum follow-up period of 2 years from the onset of treatment (mean 38.7 months; range 24-82.5 months). The primary malignancies included: breast (39), melanomas (6), adenoid cystic carcinomas of salivary glands (4), prostate (4), soft tissue sarcomas (3), squamous cell carcinoma of head and neck (3), lymphomas (3), transitional cell carcinoma of bladder (1) and basal cell carcinoma of the skin (1). The persistent complications noted included induration and fibrosis (39 hyperthermia fields, 22 patients), ulceration at the site of prior tumour (three patients, three fields), and ulceration in normal tissue (one patient, one field). Brachial plexopathy developed in one patient treated for recurrent breast cancer, but she had active disease at that time. A squamous cell carcinoma of the skin developed within the treatment field in a breast cancer patient. Radionecrosis of the mandible was seen in one patient treated for a floor of the mouth cancer, and osteomyelitis with septic arthritis developed in one patient treated for a soft tissue sarcoma of the thigh. Univariate logistic regression analyses of pretreatment and radiation-hyperthermia treatment parameters revealed that maximal tumour temperature had a borderline significant correlation with the development of complications (p = 0.07). Multivariate analyses of the pretreatment and treatment parameters revealed the best-two-covariate model to predict complications included mean maximal tumour temperature and tumour type (macroscopic tumours had greater incidence of complications than for microscopic residual disease). The rate and type of persistent and/or late complications seen following combined radiation and hyperthermia did not appear to dramatically differ from those that would be anticipated from irradiation alone in this patient population, with the exception of an increased incidence of areas of induration and tumour necrosis.


Potential hazards of radiative electromagnetic hyperthermia in the presence of multiple metallic surgical clips.

Three-dimensional computer simulations of a patient under consideration for heating by the BSD Sigma 60 phased array applicator showed marked specific absorption rate (SAR) enhancement in the region where there was a concentration of metallic surgical clips. Subsequent tests in tissue-equivalent phantom material confirmed that metallic objects much shorter than the wavelength in tissue of the radiative electromagnetic field can cause significant changes in the power deposition near the implanted metal. The placement of extensive numbers of surgical clips may therefore hinder the ability to subsequently utilize radiative electromagnetic heating modalities.


Lethal effects of the combination of hyperthermia and bromocriptine or a somatostatin analogue on normal pituitary cells and pituitary tumour cells.

Effects of hyperthermia alone and combined with bromocriptine (BC) or a somatostatin analogue (SMS 201-995) were studied in vitro on normal pituitary and pituitary tumour cells (GH3 cells). GH3 cells were more sensitive to heat than normal pituitary cells and a maximal difference in survival was obtained with hyperthermia at 42.5 degrees C for 6 h. BC had cytotoxic and antiproliferative effects on GH3 cells, whereas SMS 201-995 was not effective. Hyperthermia at 42.5 degrees C for 3 h in combination with BC enhanced selective cytotoxicity for GH3 cells. In contrast, combined treatment with hyperthermia and SMS 201-995 failed to enhance cytotoxicity for GH3 cells. The combination of hyperthermia and BC could provide improved therapeutic efficacy in patients with pituitary adenomas.


Utilization of a multilayer polyacrylamide phantom for evaluation of hyperthermia applicators.

A muscle-stimulating material made of polyacrylamide gel (PAG) for testing various kinds of hyperthermia applicators was investigated. The permittivity and conductivity dispersion of PAG, as well as an internal wavelength and penetration depth, were in good agreement with those of actual muscle at frequencies between 500 MHz and 3 GHz. A single formula for PAG covering three ISM bands, most commonly used for hyperthermia, 433, 915 and 2450 MHz, is presented. The physical properties of the PAG phantom allow any desired form or shape to be moulded, including shapes conforming to the actual geometry of an interstitial or intracavitary applicator. Utilization of a multilayer phantom makes possible the generation of experimental three-dimensional specific absorption rate (SAR) distributions composed from several two-dimensional SAR images at different depths or radial distances from the applicator. Spatial resolution of 1 mm can be achieved. The two-dimensional SAR distributions at different depth values for commercial superficial applicator, an interstitial antenna and a new oesophageal applicator are presented.


Combined radiation and hyperthermia: effects of the number of heat fractions and their interval on normal and tumour tissues.

The effect of one or more heat treatments at 43 degrees C combined with conventional multifraction irradiation was studied in murine normal and tumoral tissues. The endpoint of this study was the TCD50 of the C3H mammary carcinoma, inoculated into the foot. For normal tissue the reaction of the skin of the foot was assessed according to a graded scoring system. Twenty X-ray fractions delivered in 20 or 26 days were combined with one, four or eight fractions of quasi-simultaneous or sequential hyperthermia (i.e. heat applied 4 h after irradiation). Tumour dose-response curves show a decrease in TCD50 and in increase in TER linked to the increasing number of heat sessions. A qualitatively similar effect of the number of sessions was observed for the different protocols (quasi-simultaneous and sequential) and for the two overall times. No significant difference was measured between one and four HT sessions plus 20 fx of RT in the normal tissue damage, while a slight difference was observed between one, four and eight HT sessions delivered with 20 fractions of RT in 26 days.


Optimization of hyperthermia with CT scanning.

In a prospective study CT scanning was used to evaluate the precision of thermometry catheter placement in tumours in the head and neck or on the chest wall in 30 consecutive patients prior to hyperthermia treatment. Patients had variable-sized tumours from several primary sites. Thermometry catheter placement was guided by palpation with or without a prior CT scan. Catheter placement was confirmed by CT. All lesions were less than 8 x 8 x 6 cm (L x W x D) in size. A mean of 4.2 +/- 0.2 (+/- 1 SEM, range 2-7) closed-end polyurethane catheters were inserted orthogonally by the same experienced radiation oncologist. Horizontal thermometry catheters were intended to traverse the centre and base of the tumour mass, and a vertical catheter was often inserted to intersect a horizontal catheter. After catheter placement, wire cables with 1 cm spacings were inserted into the catheters and positions determined using orthogonal films and CT scans. The success of catheter placement was judged on the following criteria: (1) catheter distribution factor (CDF = proportion of tumour CT slices transected by at least one catheter); (2) catheter hit ratio (CHR = average number of catheters in tumour per CT slice); (3) catheter miss factor (CMF = average number of catheters out of tumour per CT slice); (4) catheter placement index, CPI = [(CHR)(CDF)]-CMF; and (5) distance of nearest catheter from the visually estimated centre of tumour in the most central tumour CT scan. In the first seven lesions with 3-6 cm depth catheter insertion was guided by palpation only. In the next 23 lesions catheter insertion was guided by a prior CT scan. In the latter group, 15 lesions had depth 3-6 cm while eight lesions had depth < or = 3 cm. Catheter placement by palpation only, without the benefit of CT scan, was much less accurate in terms of the nearest catheter to the centre of the tumour (p = .001), the proportion of CT slices with catheter in tumour (CDF, p = 0.04) and the probability of a catheter being outside the tumour (CMF, p = 0.01). The catheter placement index (CPI) was a good measure of the accuracy and adequacy of catheter placement in large tumours (p = 0.04). Displacement of normal tissue structures by tumour precluded accurate catheter placement and led to a low CPI. It was difficult to accurately instrument lesions < or = 3 cm depth even with the benefit of a prior CT scan.(ABSTRACT TRUNCATED AT 400 WORDS)


Whole-body hyperthermia as an adjuvant to treatment with platinum complexes with or without etanidazole in mice bearing the Lewis lung carcinoma or the FSaLL fibrosarcoma.

The response of s.c. primary and metastatic Lewis lung carcinoma to five antitumour platinum complexes with or without tolerable whole-body hyperthermia (60 min to reach temperature then 60 min at 42 degrees C) was examined. The whole-body hyperthermia treatment produced about 2.8 days of tumour growth delay in the s.c. tumours. The addition of whole-body hyperthermia to treatment with each of the platinum complexes was well tolerated by the animals and increases of 1.6-2.0-fold in tumour growth delay resulted with the combined treatment compared with the platinum complexes alone. The combination of etanidazole (1 g/kg) and the platinum complexes followed by whole-body hyperthermia produced marked increases in tumour growth delay ranging from 2.5- to 3.6-fold over the growth delays obtained with the platinum complexes alone. FSaLLC tumour cell survival and bone marrow CFU-GM experiments indicated that local hyperthermia (43 degrees C, 30 min) produced greater potentiation of the cytotoxicity of three platinum complexes than did whole-body hyperthermia (42 degrees C, 60 min). Only the complete treatments including whole-body hyperthermia/etanidazole and the platinum complexes were effective in significantly reducing the numbers of lung metastases formed from s.c. primary tumours. Serum urea nitrogen and creatinine levels were monitored over a time-course post-treatment. Although some treatment combinations caused elevations in these normal tissue parameters by day 12 post-treatment both serum urea nitrogen and serum creatinine returned to the levels of the untreated control animals.


Non-invasive thermometry using magnetic resonance diffusion imaging: potential for application in hyperthermic oncology.

The proposition to use non-invasive thermometry based on magnetic resonance diffusion imaging for applications in therapeutic hyperthermia is examined. The measurement of proton motion predominantly associated with the self-diffusion of water can be characterized by a Boltzmann temperature dependence (i.e. e-Ea/kT). The activation energy (Ea) is on the order of 0.2 eV and, for a restricted range (approximately 30 degrees) at a base temperature of approximately 300 K, the relationship between the effective diffusion coefficient and temperature is approximately linear. This response has been empirically demonstrated in water-based gel phantoms using magnetic resonance imaging (MRI). Additionally, it is feasible to have compatibility between radiofrequency (RF) heating devices and MRI equipment. An MRI-compatible heating applicator that includes a hexagonal array of coherently phased dipoles was assembled. This heating array easily fits into a standard 1.5 T head imaging coil (diameter 28 cm). The RF fields associated with heating (130 MHz) and imaging (64 MHz) were decoupled using bandpass filters providing isolation in excess of 100 dB. This isolation was sufficient to allow simultaneous imaging and RF heating without deterioration of the image signal-to-noise ratio. In this report temperature, spatial and time resolution achieved in phantom are examined in order to assess the potential for using this non-invasive temperature measurement in applications of hyperthermic oncology. Using this system and conventional multi-slice imaging techniques, 0.5 degrees C resolution in a voxel size of less than 1 cm3 has been achieved using an acquisition time of 4.15 min.


Radiofrequency capacitive heating of deep-seated tumours using pre-cooling of the subcutaneous tissues: results on thermometry in Dutch patients.

The capacity of a radiofrequency, 13.56 MHz, capacitive hyperthermia system using extensive pre-cooling of the subcutaneous tissue to induce locoregional deep heating has been investigated in 11 patients. Tumour location was presacral in nine--and eccentric towards the lateral side of the pelvis in two patients. For thermometry multiple catheters (mean 2.7) were inserted into the treatment volume. The mean numbers of temperature measuring points per treatment were 9.4 in tumour, 5.5 in muscle and 7.2 in subcutaneous fat. RF energy was applied after 30 min of cooling through two flexible boli perfused with saline water at 5-10 degrees C. Patient tolerance to pre-cooling was very good and after some initial discomfort the patient became rapidly accustomed to the cold water boli. For some patients better temperatures were achieved when the conventional anterior-posterior applicator set-up was replaced by a set-up with an applicator on each lateral side of the patient. As patients can tolerate temperatures within the fat tissue as high as 45.5 degrees C without complaining it appears important to monitor the temperature at the transition of fat to muscle tissue to prevent subcutaneous burns. The study shows that pre-cooling cannot avoid preferential heating at the interface from fat to muscle tissue. In this patient group the quality of the hyperthermia treatment appeared to be rather poor: 60% of the measured tumour temperatures were below 40 degrees D.


Insonation of fixed porcine kidney by a prototype sector-vortex-phased array applicator.

The sector-vortex applicator, an ultrasound phased array with a geometric focus having multiple sectors and tracks, can directly synthesize, without scanning, diffuse focal patterns useful for hyperthermia. A perfused tissue phantom, consisting of an alcohol-fixed porcine kidney with thermocouples placed in the cortex, is insonated by a prototype sector-vortex applicator with 16 sectors and two tracks at an ultrasound frequency of 750 kHz. Steady-state temperature distributions are measured for a wide range of perfusion rates. Results demonstrate that the radius of the heated region can be controlled effectively by choosing the focal mode of the applicator as it is predicted by theoretical analysis.


Removal of cancellous bone graft through the base of the excised radial styloid process.

In performing STT arthrodesis, the excision of the tip of the radial styloid avoids further radial styloid impingement. Cancellous bone graft can be obtained through the base of the excised radial styloid, using a trephine or a curette. The amount of bone removed is sufficient for intercarpal arthrodesis.


The reverse radial forearm flap in the severely injured hand: an anatomical and clinical study.

An anatomical study in 25 cadaveric upper limbs quantified the communications between the radial and ulnar arteries immediately proximal to the carpus. These studies suggest that the reverse radial forearm flap can safely be used in severe hand trauma where reliable pre-operative assessment of the palmar collateral circulation is not possible. It is recommended that the pedicle is pivoted 4 cm from the styloid process at which point there is a 96% probability of leaving the superficial palmar branch and one other communication intact and a 77% probability of leaving two other communications intact. Two clinical cases are outlined for illustration.


Three-dimensional CT imaging of the wrist. A practical system.

Three-dimensional computerized tomography provides a new approach to radiological imaging. Raw data from sequential two-dimensional scans have been reconstructed as a three-dimensional model of the carpal area using the Medical Graphics and Imaging Workstation. This study demonstrates the anatomical accuracy and potential diagnostic qualities of a reconstruction of the carpus using this system. The advantages, pitfalls and suggested applications of this technique of carpal imaging are discussed. Three-dimensional imaging is shown to provide a great deal of information which cannot be viewed on conventional radiographs or CT images.


An anomaly of the median artery associated with the anterior interosseous nerve syndrome.

The anterior interosseous nerve syndrome is characterized by paralysis of the flexor pollicis longus muscle, the flexor digitorum profundus muscle to the index and middle fingers, and the pronator quadratus muscle. The most common cause is entrapment of the anterior interosseous nerve near its origin from the median nerve by a variety of structures. Compression is most frequently caused by the deep head of the pronator teres muscle, or the fibrous arcade of the flexor digitorum superficialis muscle. Vascular compression has been reported infrequently. A patient with anterior interosseous nerve syndrome was found at operation to have the median artery passing through the anterior interosseous nerve just below the elbow. This artery has not previously been associated with the syndrome. A cadaver dissection confirmed the relationship.


The anterior interosseous nerve syndrome.

A follow-up examination of 21 cases of anterior interosseous nerve syndrome in 20 patients is presented. In 15 patients the anterior interosseous nerve was explored, with objective signs of compression in nine. 11 of these patients showed satisfactory function and three had a tendon transfer. Five cases were not operated on. Two recovered and three had continuous paralysis after more than four years. One patient had a primary tendon transfer. We conclude that exploration of the anterior interosseous nerve is the treatment of choice, and that expectant treatment can be reserved for patients with slight disability or poor general health. As recovery may take over a year, tendon transfer should be postponed until after this period in patients who do not show satisfactory recovery.


A simple clinical test to differentiate rupture of flexor pollicis longus and incomplete anterior interosseous paralysis.

Incomplete anterior interosseous nerve paralysis and spontaneous rupture of flexor pollicis longus tendon are conditions which mimic each other closely and have been mistaken for each other, leading to unnecessary surgery. This is a report of a simple and reliable clinical test to differentiate between the two conditions. A search of the literature has not revealed a previous description of this test.


Seventh cervical nerve root transfer from the contralateral healthy side for treatment of brachial plexus root avulsion.

Cervical root nerve transfer from the contralateral side has been used for the treatment of brachial plexus root avulsion in 49 patients. Resection of C7 root from the healthy side has produced no long-term symptoms or signs. Nine patients with ten recipient nerves have been followed up for more than two years and seven have obtained a functional recovery. This operation offers a new approach for the treatment of brachial plexus root avulsion.


Elbow flexorplasty: a comparison between latissimus dorsi transfer and Steindler flexorplasty.

The latissimus dorsi transfer and the Steindler flexorplasty were compared to restore elbow flexion in seven cases. All patients had sustained upper trunk brachial plexus injuries and were adults of productive age. Both operations were successful. The results showed that the latissimus dorsi transfer provides more powerful elbow flexion and a greater range of movement one year post-operatively. The criteria for selection of candidates for both operations are set out.


Freeze-thawed skeletal muscle autografts used for brachial plexus repair in the non-human primate.

An experimental study undertaken in the marmoset is reported. A defect in the lateral cord of the brachial plexus was repaired with a longitudinally aligned freeze-thawed skeletal muscle autograft. Recovery was assessed after one year using sensory and motor electrophysiological and also histological examination of the nerve. The results show that this is a satisfactory method of peripheral nerve repair in the marmoset. It is suggested that the technique may be applicable to repair of the human brachial plexus.


Is early vascularization of nerve grafts necessary?

Revascularization and regeneration through vascularized and non-vascularized nerve grafts were compared on optimal and adverse graft beds in 76 rabbit sciatic nerves. A delay in revascularization of more than 14 days was found to occur in 30 mm long, non-vascularized nerve grafts placed on completely avascular graft graft beds. However, over a period of 44 weeks, this prolonged ischaemia did not adversely affect nerve regeneration. The vascularized nerve grafts did not differ significantly with respect to the rate of regeneration, motor conduction velocity, fibre diameter and thickness of myelin sheath. In rabbits, the provision of early vascularity does not appear to confer superior regeneration through nerve grafts. The clinical use of vascularized nerve grafts is discussed in the light of these results.


The role of an adhesive (Histoacryl) in tendon repair.

Two in vitro experiments have been done comparing various techniques of tendon repair. These include repairs using an adhesive, 2-butyl cyanoacrylate (Histoacryl), and repairs by the modified Kessler technique, using 4/0 braided polyester and 4/0 stainless steel. Mechanical analysis has shown that by replacing the circumferential suture of a modified Kessler tendon repair with Histoacryl, the tensile strength of the repair and the force needed to produce a gap can be increased by 30% to 40%. This improvement was statistically significant (P < 0.05).


Factors affecting the strength of flexor tendon repair.

The effects of different thicknesses and configurations of core sutures were studied in human cadaveric flexor tendon repairs. Both straight and cyclic load tests were employed. To exploit the full strength of 4/0 suture material, the Kessler repair using four locked single knots would seem to be appropriate.


Restoration of the injured flexor tendon surface: a possible role for endotenon cells. A morphological study of the rabbit tendon in vivo.

The ability of rabbit deep flexor tendons to restore the gliding surface and to heal, without the normal contribution of the superficial epitenon layer of the tendons, was studied by light and scanning electron microscopy. The epitenon layer was carefully removed from defined segments of the tendons. The remaining central tendon tissue was divided, sutured and placed in diffusion chambers subcutaneously in the back of the rabbits. After two weeks of culture, most of the sutured gaps were bridged and the tendons were encapsulated by flattened and spindle-shaped cells which covered a random network of thin collagen fibres. After five and 11 weeks, fibroblast-like cells in multiple layers formed a cobblestone-like surface. Thus, a tendon deprived of its epitenon layer still contains cells which can produce collagen, bridge the gap and restore the injured tendon surface.


Healing of canine tendon in zones subjected to different mechanical forces.

The effect of external force environment on the healing of a partial thickness injury to canine flexor tendon was studied. A 50% laceration was made in either the fibrocartilaginous (compressive) zone or in the tendinous (tensile) zone of canine flexor digitorum profundus tendons. After three or six weeks, the tendons were harvested. An optical method for determining zone-specific material properties showed that, in response to injury, the structural stiffness decreased in the tensile zone of the tendon but increased in the compressive zone. The mechanical properties and failure mechanism of canine tendon and their changes in response to injury vary according to tendon zone, and differences in the healing process in mechanically specialised zones of the flexor tendon are discussed.


Subungual exostosis in the hand.

Although it is thought to be a relatively common tumour, only 34 positively identified cases of subungual exostosis in the hand have been found in the literature to date. 16 further cases are reported, making this the largest published series. Seven cases presented with an incorrect diagnosis. An X-ray easily differentiates the tumour from an osteochondroma of the distal phalanx, a spike of bone from a crush injury, or a response to a penetrating injury called a turret exostosis. Removal of the deformed nail and excision of the mass from the distal phalanx produces a useful finger without pain, tender scar, or resultant nail deformity. No case of malignancy has ever been reported.


Nail gun injuries to the hand.

Three cases of nail gun injury to the non-dominant hand are reported. The hazards of using this high powered tool are stressed and a possible pitfall in the surgical removal of the nails is outlined.


Phalangeal fractures resulting from finger wrestling.

Two cases of proximal phalangeal fracture following finger wrestling are described. The mechanism of the injury is discussed.


Pivot osteotomy for the correction of malunion of metacarpal neck fractures.

A new configuration of osteotomy has been developed which combines the principles and benefits of opening and closing wedge osteotomies without the degree of shortening associated with the closing wedge osteotomy and the tension imposed on the soft tissues by the opening wedge osteotomy. It is ideally suited to the correction of angular malunions in the long bones of the hands. Ten osteotomies of malunions of the metacarpals have been performed in nine hands giving good correction of the malunion in all cases.


Arthroplasty of the proximal interphalangeal joint using costal cartilage grafts.

Seven intra-articular fractures in five patients with partial bone loss at the PIP joint were reconstructed using a graft of costal cartilage. In all cases there were total or partial cartilagenous defects of the proximal phalangeal side of the joint. Early treatment of two joints, using only costal cartilage grafts, resulted in bony ankylosis due to necrosis of the grafted cartilage. In five joints the grafted cartilage included osseous portions using the costo-osteochondral junction, leading to an average range of movement of 64 degrees with satisfactory clinical results. The technique is a useful alternative to other forms of arthroplasty or arthrodesis, and can provide satisfactory functional results when there is a partial defect of the head of the proximal phalanx.


Dorsal fracture subluxation of the proximal interphalangeal joints treated by extension block splintage.

In a prospective study, 27 consecutive patients with dorsal fracture subluxation of the PIP joint were treated conservatively using an extension block splint, with good results in 70%. The percentage surface involved with the fracture varied considerably (19-77%) the average being 55%. Three patients initially managed with splintage proceeded to surgery because the splint failed to hold the joint in reduction. These patients had a less favourable outcome. We feel that all such fractures can be treated by splintage, provided that early reduction is maintained in the splint and checked by serial radiology.


Dorsal fracture subluxation of the distal interphalangeal joint of the finger and the interphalangeal joint of the thumb treated by extension block splintage.

In a prospective study six patients with dorsal fracture subluxation of the IP joint of the thumb or the DIP joint of the finger were treated conservatively using an extension block splint. The fracture size varied from 22% to 47% of the articular surface of the volar base of the terminal phalanx. Good or excellent results were reported in all cases except for one, which was fair. Only one case in the study complained of any pain, and this was minimal. Conservative treatment using extension block splintage for this injury is as good as a surgical approach.


Blastomycosis: a reminder of Kentucky's other fungus.

Although not as common as Histoplasmosis, the disease caused by Blastomyces dermatitidis is also endemic in the Commonwealth of Kentucky. Greater clinical awareness of this systemic mycosis and the newer effective forms of treatment may lessen the significant morbidity and mortality of this potentially serious infection. To illustrate the varied manifestations of this illness, we contrast the presentation of an urban female with blastomycosis and atypical chest radiographic changes to the more classic features of blastomycosis described in the literature.


Acute peritonsillar abscess caused by Arcanobacterium haemolyticum.

A patient is reported with a peritonsillar abscess yielding Arcanobacterium haemolyticum. This appears to be only the fifth such case described in the medical literature and the first from Europe. The organism has been reported as an occasional cause of tonsillopharyngitis with rash, resembling infection with Streptococcus pyogenes but often unresponsive to penicillin therapy. A. haemolyticum easily passes unrecognized in bacteriological cultures as a result of its slow growth, coryneform appearance in the Gram's stain and weak haemolytic activity on conventional laboratory media.


An unusual pharyngeal pouch.

The third case of a double pharyngeal pouch is reported. It was excised and the patient made an uneventful recovery.


Inhalation of a Montgomery Safe T-tube plug.

The first case of an inhaled Montgomery Safe T-tube plug is reported. Both the surgeon and the patient should be aware of this possible complication and regular inspection of the plug is recommended. More than one plug should be provided with each T-tube.


Branchial cyst--to endoscope or not?

Cervical cystic metastases are uncommon, originating predominantly from an oropharyngeal primary. Pre-operative differentiation from a branchial cyst can prove difficult. Three cases which presented clinically as branchial cysts but were subsequently found to be cystic metastases are described, and the literature is reviewed. Endoscopy, ipsilateral tonsillectomy and blind biopsies of Waldeyer's ring, combined with excision of the cervical lesion are recommended in patients over 40 years old.


Necrotizing fasciitis of the neck.

Necrotizing fasciitis (N.F.) is a rare but serious infection of subcutaneous tissues and deep fascia with resulting skin gangrene and septicaemia. It is due to mixed anaerobic and aerobic organisms. It has been reported under a variety of synonyms. We describe two cases of necrotizing fasciitis of the neck probably secondary to chronic dental infection, one was diagnosed early and the other late with very different outcomes. We highlight the importance of early and aggressive surgical treatment to complement parenteral antibiotics covering both aerobic and anaerobic organisms.


Benign nasal schwannoma.

Nerve sheath tumours of the head and neck region mainly involve the eighth cranial nerve with only 4 per cent occurring in the paranasal sinuses. Only 32 cases of benign schwannomas occurring in the paranasal sinuses have been reported. We present a further case, review the current literature, and discuss the clinical details and specific histological features.


Ionomeric bone cement in neuro-otological surgery.

The use of a polymaleinate glass ionomer cement in 80 neuro-otology cases is described. It has proved of great value in translabyrinthine acoustic neuroma surgery, reducing the incidence of CSF fistula to nil. It is the method of choice for fixation of the Nucleus cochlear implant, and has many other applications in the field of otology and neuro-otology. It is easy to use and appears to have no side effects.


Closure of tympanic membrane perforation after the removal of Goode-type tympanostomy tubes: the use of silastic sheeting.

The reported incidence of persistent tympanic membrane perforation after the extrusion or removal of Goode-type tympanostomy tubes varies from 3 per cent to 47.5 per cent. A prospective randomized study of 152 Goode-type T-tube removals is presented. In one group of 79 ears, the edge of the defect was just freshened, but in the other 73 ears, the edge was freshened and a small piece of 0.13 mm silastic sheeting placed over the defect. Follow-up was performed at six weeks and three, six and nine months and shows that the use of silastic sheeting increases the rate of closure of the perforation and also significantly decreases the number of persistent perforations at nine months.


Prescription of hearing aids for the elderly: the views of general practitioners.

A questionnaire survey was carried out to examine the views of general practitioners in one Northern city regarding whether or not they thought that hearing aids should be prescribed from general practice, who they thought should prescribe them and whether or not additional resources and training would be needed if the responsibility for hearing aid prescription for the elderly was placed upon general practitioners. The survey indicated that whereas many general practitioners would be in favour of prescribing hearing aids from Health Centres, many would need extra training and resources to enable them to do so.


Cochlear implants for congenital deformities.

There have been few accounts of multi-channel cochlear implants in patients with congenital structural deformities of the inner ear which are associated with severe and sometimes progressive deafness. These malformations can now be recognized easily on 2 plane thin section high resolution CT studies which are mandatory for the pre-implantation assessment. However, no attempt seems to have been made to describe which of these malformations would be suitable for an implant or for which would this procedure be contra-indicated. True Mondini deformity of both the cochlea and dilated vestibular aqueduct type would appear suitable for a multi channel implant, but this type of implant should not be used for a primitive otocyst, severe labyrinthine dysplasia or the characteristic X-linked deformity.


Long-term results of revision stapes surgery.

Results of 45 re-operations for persistent or recurrent conductive deafness after primary stapes surgery were studied. The mean follow-up period after the revision surgery was 7.6 years. Long-term hearing results were found to be disappointing, air-bone gap to within 10 dB was achieved in only 46 per cent of the patients. Mean hearing levels improved by 11 dB or more in 73 per cent. Outcome of surgery was dependent on the surgical pathology, the best hearing results were obtained in cases with re-fixation after stapes mobilization operation. Sensorineural hearing loss as a result of surgical trauma to the inner ear occurred in revision surgery more frequently than in primary operations, cases with regrowth of otosclerotic bone to the oval window after stapedectomy having the greatest risk of labyrinthine trauma.


Glue under pressure: a bad prognostic sign for recurrence of otitis media with effusion.

One hundred and thirteen children with bilateral otitis media with effusion (OME) underwent myringotomy and insertion of Shah grommets. They were classified into three groups according to the presence or absence of 'glue under pressure' unilaterally or bilaterally. The follow up period ranging between 18 and 32 months determined the comparative rate of recurrence of OME and the number of grommet reinsertions. This study shows a significantly higher incidence of recurrent OME, requiring grommet reinsertion, in ears with glue under pressure (60 per cent) compared to those with glue not under pressure (7.4 per cent). Thus it was possible to identify a subset of children with OME who have a poorer prognosis for recurrence and who should be treated with long-stay grommets in the first instance.


Endoscopic management of posterior nasal obstruction.

The use of the rigid endoscope has been investigated in the management of 63 cases with posterior nasal obstruction. It was found to be a true advance in rhinology, since it visualizes and localizes the site of the obstruction which is classified into pre-choanal, and post-choanal. Moreover, the nasal endoscope allowed complete and safe removal of most of the obstructing lesions under direct endoscopic vision.


Rhinocerebral aspergillosis.

Aspergillosis is increasingly being recognised as a common fungal infection of the paranasal sinuses. Although the disease is almost endemic in neighbouring Sudan, there are few reported cases from the Kingdom of Saudi Arabia. We report four cases of sinus aspergillosis with involvement of the skull bases and/or intracranial spread; a condition we have termed rhinocerebral aspergillosis. Invasive aspergillosis in our subgroup of patients occurs in otherwise healthy patients with normal immune status, quite unlike most reported cases in the western literature. The causative agent in all our patients was identified as aspergillus flavus, similar to patients reported from Sudan. This is again at variance with the case reports from other geographical locations, where aspergillus fumigatus is the commonest causative agent. Saudi Arabia would appear to represent a distinct geographical enclave, together with Sudan, where rhinocerebral aspergillosis of the sinuses and skull base may be more common than has previously been realised.


The management of quinsy--a prospective study.

A prospective study for the treatment of quinsy was undertaken between January 1989 and September 1991. This was to determine whether abscess tonsillectomy reduces inpatient stay without increasing operative risk compared to incision and drainage combined with interval tonsillectomy. Fifty-three patients were entered into the study. Twenty-one had abscess tonsillectomy and 32 had incision and drainage. This study showed that there is a 95 per cent probability that abscess tonsillectomy reduces hospital stay by between 2.04 and 4.84 (Student's test t = 5.01; df = 31, p < 0.001) days compared to incision and drainage followed by interval tonsillectomy. This is a significant saving in time and resources. Abscess tonsillectomy reduces patients lost to follow-up, avoids the social inconvenience of a second admission, effectively relieves symptoms, treats a contralateral abscess and is the only method of treating children with a quinsy. We recommend abscess tonsillectomy should be performed for quinsy where expertise and facilities are available.


Acute tonsillectomy in the management of infectious mononucleosis.

Life-threatening upper airway obstruction can be caused by tonsillopharyngitis secondary to infectious mononucleosis (IM). The administration of corticosteroids, emergency tracheostomy and acute tonsillectomy have been advocated as ways of managing this problem. In a series of 25 patients admitted over a five-year period with IM, 15 were judged to have symptoms severe enough to warrant the administration of corticosteroids. Six of these 15 patients had little improvement in their condition and thus underwent acute tonsillectomy. There were no significant complications of this surgery. A further three patients who received corticosteroids required tonsillectomy for recurrent tonsillitis later in the study period. By contrast, only one of the ten patients who did not receive corticosteroids subsequently required tonsillectomy. Acute tonsillectomy is of value in selected cases of IM tonsillopharyngitis. It may decrease the morbidity of recurrent tonsillitis after IM, in addition to averting the immediate risk of respiratory obstruction.


Infra red coagulation for bleeding mucosal telangiectasia.

The technique of infra red coagulation is well suited to the destruction of superficial blood vessels in the skin and/or mucosal surfaces. A method is described here for the destruction of resistant bleeding telangiectasia of the palate and lip in Osler-Weber-Rendu syndrome.


Fistula between the external auditory canal and the temporomandibular joint: a rare complication of otitis externa.

Otitis externa is a relatively common complication of ear syringing. Temporomandibular joint complications of otitis externa are rare. A case of otitis externa with communication between the external auditory canal and the temporomandibular joint is described.


Dyskeratosis congenita and nasopharyngeal atresia.

Dyskeratosis congenita is a multisystem disorder with an increased incidence of neoplasia and opportunistic infections. A case is reported as a cause of complete nasopharyngeal atresia.


Sphingomyelinase treatment of low density lipoprotein and cultured cells results in enhanced processing of LDL which can be modulated by sphingomyelin.

The addition of neutral sphingomyelinase from S. aureus to the medium of rat intestinal epithelial cell cultures (IEC-6) containing added human low density lipoprotein (LDL) resulted in two- to fivefold increases in LDL uptake and degradation. This overall effect was shown to be the combined result of sphingomyelinase activity on the composition of the LDL particle and a separate action directly on the cells when native LDL was incubated with sphingomyelinase from S. aureus followed by removal of the sphingomyelinase. Analysis of sphingomyelinase-treated LDL showed that > 95% of the sphingomyelin (SM) was hydrolyzed, but no changes were observed in all the other components of the LDL particle. This modified LDL particle (SM(-)LDL) was also bound and degraded at higher rates than control LDL in a variety of cell lines, e.g., HepG2, GM-43, and CHO-K1 cells. No evidence of increased aggregation of SM(-)LDL could be observed. The increased processing of SM(-)LDL was due to enhanced affinity to LDL receptors and not to an increase in LDL receptor number. When sphingomyelinase from S. aureus was added to the medium of IEC-6 or GM-43 cells, which were processing SM(-)LDL, further increases in SM(-)LDL processing were observed, which were primarily due to greatly enhanced cellular degradation of SM(-)LDL, with little change in receptor binding and cell association. Since there was little sphingomyelin remaining in SM(-)LDL, it was assumed that the action of sphingomyelinase on the cells resulted in the enhanced degradation. In support of this concept, previous addition of sphingomyelin to cells growing in lipoprotein-deficient medium followed by addition of SM(-)LDL greatly inhibited the degradation of the apolipoprotein of SM(-)LDL. On the other hand, addition of sphingomyelin concomitantly with SM(-)LDL did not inhibit degradation. These results are interpreted to indicate that there may be two pathways for cellular processing of sphingomyelin, one of which may be a determinant in the lysosomal processing of the apolipoprotein of LDL. In support of this concept, addition of desipramine, an inhibitor of lysosomal sphingomyelinase, to IEC-6 cells in culture greatly inhibited the degradation of 125I-labeled LDL without affecting the receptor binding and cell association. Overall, these results suggest that sphingomyelin may play a modulatory role in cellular cholesterol homeostasis by regulating uptake of LDL as well as LDL processing.


Developmental and age-related changes in apolipoprotein B mRNA editing in mice.

Apolipoprotein B (apoB) mRNA is modified by a post-transcriptional editing reaction (C to U) changing a glutamine (CAA) to a translational stop codon (UAA) and producing apoB-48 mRNA in mammalian liver and intestine. Developmental and age-related changes in apoB mRNA editing were studied using two mouse strains with different aging processes (SAM-R/1 with a normal aging process and SAM-P/1 with an accelerated aging process). During growth of both strains, the proportion of unedited (apoB-100) mRNA decreased from 80% in the fetal liver at the 17th day of gestation to 30% in the liver of mature 2-month-old mice. Age-associated increase in the proportion of hepatic apoB-100 mRNA was observed from the age of 18 months in the SAM-R/1 strain. In the SAM-P/1 strain, apoB-100 mRNA in the liver continued to increase from the age of 10 months to death. The profiles of developmental and age-related changes in the proportion of two serum apoB isoproteins (apoB-100 and apoB-48) followed the extent of hepatic apoB mRNA editing. Age-related changes in the extent of apoB mRNA editing in the small intestine were not observed in either strain. A slight expression of apoB was detected by reverse transcriptase-polymerase chain reaction in the kidney, stomach, and colon, and age-associated change in the extent of editing was observed in the kidney. These correlated changes in apoB mRNA editing and serum apoB proteins suggest that RNA editing may be one mechanism involved in the regulation of lipoprotein biogenesis in biological development and in senescent mice. An age-associated decrease in the extent of hepatic apoB mRNA editing and increases of the proportion of serum apoB-100 protein were observed in senescent mice.


Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance.

Hyperlipidemia frequently accompanies infectious diseases and may be due to increases in lipoprotein production or decreases in lipoprotein clearance. The administration of endotoxin (LPS) has been used to mimic infection and prior studies demonstrate that LPS produces hypertriglyceridemia. In the present study in rodents, the dose of LPS necessary to induce hyperlipidemia was orders of magnitude less than that necessary to induce shock and death. As little as 10 ng/100 g body weight induced hypertriglyceridemia and this increase in serum triglyceride levels occurred rapidly (78% increase at 2 h). At high doses of LPS (50 micrograms/100 g body weight), the clearance of triglyceride-rich lipoproteins was decreased. At low doses of LPS (100 ng/100 g body weight), triglyceride clearance was not altered but the hepatic secretion of triglyceride was increased. Low dose LPS stimulated hepatic de novo fatty acid synthesis and lipolysis, both of which provided a source of fatty acids for the increase in hepatic triglyceride production. High dose LPS did not increase hepatic fatty acid synthesis or peripheral lipolysis, and hepatic triglyceride secretion was not stimulated. Thus, low dose LPS produces hypertriglyceridemia by increasing hepatic lipoprotein production, while high dose LPS produces hypertriglyceridemia by decreasing lipoprotein catabolism. Administration of anti-tumor necrosis factor (TNF) antibodies or interleukin 1 (IL-1) receptor antagonist did not prevent the increase in serum triglyceride levels induced by LPS. However, anti-TNF antibodies and interleukin 1 receptor antagonist (IL-1ra) blocked the increase in serum triglycerides induced by TNF or IL-1, respectively. These data suggest that neither of these cytokines is absolutely required for the increase in serum triglycerides induced by LPS, raising the possibility that other cytokines, small molecular mediators, or LPS itself may play a crucial role.


Characterization of lipoprotein lipase activity, secretion, and degradation at different sites of post-translational processing in primary cultures of rat adipocytes.

The regulation of adipose tissue lipoprotein lipase (LPL) by feeding and fasting occurs through post-translational changes in the LPL protein. In addition, LPL activity and secretion are decreased when N-linked glycosylation is inhibited. To better understand the role of oligosaccharide processing in the development of LPL activity and in LPL secretion, primary cultures of rat adipocytes were treated with inhibitors of oligosaccharide processing. LPL catalytic activity from the heparin-releasable fraction of adipocytes was inhibited by more than 70%, with similar decreases in LPL mass, when cells were cultured for 24 h in the presence of either tunicamycin or castanospermine. On the other hand, deoxymannojirimycin (DMJ) and swainsonine had no effect on LPL activity. LPL secretion was examined after pulse-labeling cells with [35S]methionine. The appearance of 35S-labeled LPL in the medium was blocked by treatment of cells with tunicamycin and castanospermine, whereas secretion was not affected by DMJ or swainsonine. To examine the effect of oligosaccharide processing on LPL intracellular degradation, adipocytes were treated with tunicamycin, castanospermine, and DMJ and then pulse-labeled with [35S]methionine, followed by a chase with unlabeled methionine for 120 min. The unglycosylated [35S]LPL that was synthesized in the presence of tunicamycin demonstrated essentially no intracellular degradation. In the presence of castanospermine and DMJ, the half-life of newly synthesized LPL was increased to 81 and 113 min, as compared to 65 min in control cells. Thus, castanospermine-treated adipocytes demonstrated a decrease in LPL activity and secretion, suggesting that the glucosidase-mediated cleavage of terminal glucose residues from oligosaccharides is a critical step in LPL maturation.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of disulfide-linked heterodimers containing apolipoprotein D in human plasma lipoproteins.

Human plasma apolipoprotein (apo) D is a glycoprotein with an apparent molecular weight of 29,000 M(r). It is present, mainly, in high density lipoproteins (HDL) and very high density lipoproteins (VHDL). Western blot analysis of HDL and VHDL using rabbit antibodies to human apoD revealed major immunoreactive bands at 29,000 and 38,000 M(r), with minor bands ranging from 50,000 to and 80,000 M(r). Only the 29,000 M(r) band corresponding to apoD remained when the electrophoresis was conducted under reducing conditions, demonstrating that apoD is cross-linked to other proteins via disulfide bonds. The broad pattern of immunoreactivity was also observed under nonreducing conditions when the blood was collected into a solution of sulfhydryl-trapping reagents, or when these reagents were added to the isolated lipoproteins. These results indicated that the disulfide bonds were not the result of disulfide exchange during the experimental procedures. On the basis of amino acid sequencing and reactions to antibodies, the 38,000 M(r) band was identified as an apoD-apoA-II heterodimer. The apoD-apoA-II was also demonstrated in plasma. In both HDL and plasma, the apoD-apoA-II heterodimer constituted the major form of apoD. Disulfide-linked heterodimers of apoD and apoB-100 were also found in low and very low density lipoproteins, and in whole plasma. It is concluded that a fraction of human apoD, like other cysteine-containing apolipoproteins, exists as a disulfide-linked heterodimer with other apolipoproteins in all major human lipoprotein fractions.


Fatty acid composition in deep hydrothermal vent symbiotic bivalves.

Fatty acids in deep hydrothermal vent bivalves have been analyzed. Their composition is completely different from that of a littoral mussel collected in the Mediterranean sea. The distribution of fatty acids in the littoral mussel is characterized by a predominance of polyunsaturated fatty acids (20:5n-3, 22:6n-3) reflecting the planktonic origin of the food. Vent bivalve fatty acid distribution is dominated by an abundance of the monounsaturated acids (double bond in the n-7 position) 16:1n-7, 18:1n-7, and 20:1n-7 which are clearly of bacterial origin and give an indication of the symbiotic bacterial activity in the bivalves. Differences between the fatty acid composition of the bivalves from two hydrothermal sites (13 degrees N and Galapagos) and differences between the mantle and the gill were observed and are discussed with respect to vent activities at the two sites and species metabolic capacities as a function of ecological conditions.


Interconversion between apolipoprotein A-I-containing lipoproteins of pre-beta and alpha electrophoretic mobilities.

Apolipoprotein (apo) A-I-containing lipoproteins can be separated into two subfractions, pre-beta HDL and alpha HDL (high density lipoproteins), based on differences in their electrophoretic mobility. In this report we present results indicating that these two subfractions are metabolically linked. When plasma was incubated for 2 h at 37 degrees C, apoA-I mass with pre-beta electrophoretic mobility disappeared. This shift in apoA-I mass to alpha electrophoretic mobility was blocked by the addition of either 1.4 mM DTNB or 10 mM menthol to the plasma prior to incubation, suggesting that lecithin:cholesterol acyltransferase (LCAT) activity was involved. There was no change in the electrophoretic mobility of either pre-beta HDL or alpha HDL when they were incubated with cholesterol-loaded fibroblasts. However, after exposure to the fibroblasts, the cholesterol content of the pre-beta HDL did increase approximately sixfold, suggesting that pre-beta HDL can associate with appreciable amounts of cellular cholesterol. Pre-beta HDL-like particles appear to be generated by the incubation of alpha HDL with cholesteryl ester transfer protein (CETP) and either very low density lipoproteins (VLDL) or low density lipoproteins (LDL). This generation of pre-beta HDL-like particles was documented both by immunoelectrophoresis and by molecular sieve chromatography. Based on these findings, we propose a cyclical model in which 1) apoA-I mass moves from pre-beta HDL to alpha HDL in connection with the action of LCAT and the generation of cholesteryl esters within the HDL, and 2) apoA-I moves from alpha HDL to pre-beta HDL in connection with the action of CETP and the movement of cholesteryl esters out of the HDL. Additionally, we propose that the relative plasma concentrations of pre-beta HDL and alpha HDL reflect the movement of cholesteryl esters through the HDL. Conditions that result in the accumulation of HDL cholesteryl esters will be associated with low concentrations of pre-beta HDL, whereas conditions that result in the depletion of HDL cholesteryl esters will be associated with elevated concentrations of pre-beta HDL. This postulate is consistent with published findings in patients with hypertriglyceridemia and LCAT deficiency.


Increased concentration of plasma cholesteryl ester transfer protein in nephrotic syndrome: role in dyslipidemia.

Hyperlipidemia is a prominent feature of the nephrotic syndrome. Lipoprotein abnormalities include increased very low and low density lipoprotein (VLDL and LDL) cholesterol and variable reductions in high density lipoprotein (HDL) cholesterol. We hypothesized that plasma cholesteryl ester transfer protein (CETP), which influences the distribution of cholesteryl esters among the lipoproteins, might contribute to lipoprotein abnormalities in nephrotic syndrome. Plasma CETP, apolipoprotein and lipoprotein concentrations were measured in 14 consecutive untreated and 7 treated nephrotic patients, 5 patients with primary hypertriglyceridemia, and 18 normolipidemic controls. Patients with nephrotic syndrome displayed increased plasma concentrations of apoB, VLDL, and LDL cholesterol. The VLDL was enriched with cholesteryl ester (CE), shown by a CE/triglyceride (TG) ratio approximately twice that in normolipidemic or hypertriglyceridemic controls (P < 0.001). Plasma CETP concentration was increased in patients with untreated nephrotic syndrome compared to controls (3.6 vs. 2.3 mg/l, P < 0.001), and was positively correlated with the CE concentration in VLDL (r = 0.69, P = 0.004) and with plasma apoB concentration (r = 0.68, P = 0.007). Treatment with corticosteroids resulted in normalization of plasma CETP and of the CE/TG ratio in VLDL. An inverse correlation between plasma CETP and HDL cholesterol was observed in hypertriglyceridemic nephrotic syndrome patients (r = -0.67, P = 0.03). The dyslipidemia of nephrotic syndrome includes increased levels of apoB-lipoproteins and VLDL that are unusually enriched in CE and likely to be atherogenic. Increased plasma CETP probably plays a significant role in the enrichment of VLDL with CE, and may also contribute to increased concentrations of apoB-lipoproteins and decreased HDL cholesterol in some patients.


Molecular basis of familial chylomicronemia: mutations in the lipoprotein lipase and apolipoprotein C-II genes.

The molecular basis of familial chylomicronemia (type I hyperlipoproteinemia), a rare autosomal recessive trait, was investigated in six unrelated individuals (five of Spanish descent and one of Northern European extraction). DNA amplification by polymerase chain reaction (PCR) followed by single strand conformation polymorphism (SSCP) analysis allowed rapid identification of the underlying mutations. Six different mutant alleles (three of which are previously undescribed) of the gene encoding lipoprotein lipase (LPL) were discovered in the five LPL-deficient patients. These included an 11 bp deletion in exon 2, and five missense mutations: Trp 86 Arg (exon 3), His 136 Arg (exon 4), Gly 188 Glu (exon 5), Ile 194 Thr (exon 5), and Ile 205 Ser (exon 5). The Trp 86 Arg mutation is the only known missense mutation in exon 3. The other missense mutations lie in the highly conserved "central homology region" in close proximity with the catalytic site of LPL. These and other previously reported missense mutations provide insight into structure/function relationships in the lipase family. The missense mutations point to the important role of particular highly conserved helices and beta-strands in proper folding of the LPL molecule, and of certain connecting loops in the catalytic process. A nonsense mutation (Arg 19 Term) in the gene encoding apolipoprotein C-II (apoC-II), the cofactor of LPL, was found to underlie chylomicronemia in the sixth patient who had normal LPL but was apoC-II-deficient.


Apolipoprotein B messenger RNA editing in rat liver: developmental and hormonal modulation is divergent from apolipoprotein A-IV gene expression despite increased hepatic lipogenesis.

Rat hepatic apolipoprotein B (apoB) mRNA editing is regulated developmentally as well as by hormonal and nutritional modulation of hepatic lipogenesis, changes previously associated with coordinate modulation of hepatic apoA-IV gene expression. We have examined the effects of dexamethasone administration on apoB mRNA editing and the expression of other apolipoprotein genes in both neonatal and adult rats. Administration of dexamethasone increased hepatic triglyceride content in neonatal rats and increased hepatic but not intestinal apoA-IV mRNA abundance. However, neither the developmental profile nor the extent of hepatic apoB mRNA editing was changed after hormone administration. Dexamethasone produced a dose-dependent increase in adult hepatic triglyceride content and a coordinate fourfold increase in hepatic but not intestinal apoA-IV mRNA abundance, and hepatic and serum apoA-IV protein concentrations. Immunocytochemical localization revealed apoA-IV to be expressed in hepatocytes around the central vein while dexamethasone treatment produced a dose-dependent appearance of fat-filled hepatocytes throughout the lobule that were immunoreactive for apoA-IV. Despite these changes in hepatic triglyceride accumulation there was no change in the extent of hepatic apoB mRNA editing at any dose of dexamethasone. The data suggest that hormonal and metabolic modulation of hepatic apoB mRNA editing may be independent of factors that modulate apoA-IV gene expression despite alterations in hepatic triglyceride content.


Separation of dolichol from dehydrodolichol by a simple two-plate thin-layer chromatography.

A novel thin-layer chromatographic procedure was devised to separate dolichol and dehydrodolichol from each other with the concomitant separation of each family with respect to the carbon chain length. This method involves development of the polyprenols successively on two different plates, a silica gel plate and a reversed-phase plate.


Continuous fluorescence assay for lecithin:cholesterol acyltransferase using a water-soluble phosphatidylcholine.

A water-soluble fluorescent phosphatidylcholine, 1,2-bis[4-(1-pyreno-butanoyl]-sn-glycero-3-phosphocholine (DPybPC) has been used to develop a sensitive, continuous assay for pure lecithin:cholesterol acyltransferase (LCAT) in solution. The monomeric substrate allowed us to examine the reaction of LCAT in the absence of a lipid/water interface in terms of the sensitivity of the enzymatic reaction to anions, ionic strength, apolipoproteins A-I and A-II, and a series of lysophosphatidylcholines and fatty acids. In contrast to the reaction of LCAT with aggregated phosphatidylcholines, the reaction of DPybPC with LCAT was not significantly affected by anions, ionic strength, nor apolipoproteins, indicating that these are only effectors of the interfacial reaction. Lysophosphatidylcholines and fatty acids inhibited LCAT in a chain-length-dependent manner below the critical micellar concentrations of these amphiphiles, indicating that the products of the LCAT reaction can bind to the enzyme and affect its kinetics even in the absence of an interface.


Rapid separation of serum lipids for fatty acid analysis by a single aminopropyl column.

A rapid and simple method for separation of serum lipid classes for fatty acid analysis with a single aminopropyl solid phase glass column is described. The recoveries of cholesteryl esters, triglycerides, free fatty acids, and phospholipids were all at least 98%. Coefficients of variation less than 10% were obtained for absolute and relative amounts of most individual fatty acids analyzed after separation of serum lipid classes. This method provides an efficient and convenient tool to follow fatty acid patterns in serum lipid fractions.


Production of polyacrylamide gradient gels for the electrophoretic resolution of lipoproteins.

We describe a protocol to cast nondenaturing polyacrylamide gradient gels (SFBR3/31) for the size resolution of lipoproteins. The protocol yields gels with minimal lot-to-lot variation in length and electrophoretic properties. Absorbance profiles of cholesterol-stained lipoproteins in baboon sera were used to estimate the relative amounts of stain in four lipoprotein size classes (VLDL+LDL, HDL1, HDL2, and HDL3). When compared with gels from a commercial source, the SFBR3/31 gels gave very similar results in terms of precision (coefficients of variation) and of estimated amounts of lipoproteins in the four size classes. In other studies, we estimated peak diameters of protein-stained human lipoproteins after calibrating the gels with size standards. Peak diameters estimated using SFBR3/31 gels were highly correlated (r2 = 0.99, n = 33) with those estimated using gels from a commercial source. We conclude that the protocol reliably produces gradient gels that are suitable for the analysis of lipoprotein phenotypes.


Experimental and clinical gnotobiotics: influence of the microflora on graft-versus-host disease after allogeneic bone marrow transplantation.

One of the major complications of allogeneic bone marrow transplantation (BMT) is graft-versus-host disease (GvHD), which is caused by donor type lymphocytes which react against the recipient's tissues. An important factor which influences GvHD is the recipient's gastrointestinal microflora. This was originally observed in gnotobiotic mice. Infusion of 10(7) H-2 incompatible bone marrow cells into lethally irradiated (9.0 Gy X-rays) conventional mice results in a late onset type GvHD which causes the death of the majority of the recipients during the first two months after BMT. This mortality can be completely prevented if the recipients are germfree mice, or when they are conventional animals which have been subjected to complete or selective gastrointestinal decontamination (GID). In a mouse model, the mechanism responsible for the influence of the microflora on GvHD after allogeneic BMT was investigated. These studies indicate that GvHD can be induced by activated T-lymphocytes from donor origin reacting against bacterial antigens which might be cross-reactive with the recipient's epithelial tissue antigens. Activation of these T-lymphocytes is confined to antigens of certain bacterial species of the recipient which are not present in the indigenous microflora of the donor mice. These bacteria most likely belong to the anaerobic flora of the recipient. The latter hypothesis is strongly supported by the observation in human patients that, in contrast to complete GID, selective decontamination of the gastrointestinal tract did not have any beneficial effect on moderately severe to severe GvHD after transplantation with MHC-matched sibling donor bone marrow grafts.


The acute phase response in autologous bone marrow transplantation.

Due to the stress imposed by the process of bone marrow transplantation (BMT), we hypothesized that individuals receiving such a transplant underwent an acute phase response (APR). Circulating levels of C-reactive protein (CRP), haptoglobin (HAP), alpha-1 acid glycoprotein (AAG), ceruloplasmin (CER), zinc (Zn), copper (Cu), interleukin-6 (IL-6), albumin (ALB), and thyroxine-binding prealbumin (TBPA), were measured at baseline (Day -7), Day -4, Day 0 (Transplant Day), Day +2, +7, and weekly until day 28 in 14 adults receiving an autologous bone marrow transplant as Phase 1 treatment for various hematologic or solid tumor malignancies. Ten of 14 recipients survived, 9 of which had a significant increase in CRP (p = 0.012), HAP (p = 0.011), AAG (p = 0.002), and decrease in ALB (p = 0.002) and TBPA (p = 0.004) on Day +7, but not Day 0, after bone marrow reinfusion. These findings document the presence of an APR and suggest that the bone marrow transplant process (post reinfusion) initiates a stress response in the recipient.


Lithium and hematopoiesis: effective experimental use of lithium as an agent to improve bone marrow transplantation.

Bone marrow transplantation (BMT) has become a widely used procedure in the treatment of numerous hematological and non-hematological clinical disorders. The preparative regimen used for marrow recipients is not without risk as the immunodeficient recipient is susceptible to life-threatening infections due to the inability of the marrow to engraft properly. The monovalent cation lithium has been demonstrated to influence regenerating hematopoiesis following the use of several agents known to suppress hematopoiesis. The following report summarizes our studies which have been designed to determine the rate of hematopoietic reconstitution in lethally irradiated mice that were transplanted with bone marrow cells, harvested from either syngeneic or allogeneic donor animals, treated with lithium or phosphate buffered saline (PBS). Transplanted recipients receiving marrow cells from lithium treated donors were evaluated for their survival, peripheral blood indices and several classes of hematopoietic progenitors (granulocyte, erythroid, and megakaryocyte). Transplanted animals that received marrow cells from either syngeneic or allogeneic donors treated with lithium demonstrated greater survival, increased recovery of peripheral indices and hematopoietic progenitors compared to PBS-treated controls. These results indicate that the use of lithium to treat the donor may be an effective procedure to enhance hematopoietic recovery and engraftment in the transplanted recipient. Because of its wide-ranging effects, the use of lithium as a single agent, may be more efficacious than administering several hematopoietic growth factors in order to achieve a similar response.


Bacterial translocation from the gastrointestinal tract.

Bacterial translocation is defined as the passage of viable bacteria from the gastrointestinal tract to extraintestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. The major mechanisms promoting bacterial translocation in animal models are: (a) disruption of the ecologic equilibrium to allow intestinal bacterial overgrowth, (b) deficiencies in host immune defenses, and (c) increased permeability of the intestinal mucosal barrier. These mechanisms can act in concert to promote synergistically the systemic spread of indigenous translocating bacteria to cause lethal sepsis. Studies are presented of attempts to delineate the mechanisms promoting bacterial translocation utilizing animal models of intestinal bacterial overgrowth, immunosuppression, T-cell deficiencies, solid tumors, leukemia, diabetes, endotoxemia, hemorrhagic shock, thermal injury, bowel obstruction, bile duct ligation, protein malnutrition and parenteral nutrition. Also described are the use of selective antibiotic decontamination or nonspecific macrophage immunomodulators in attempts to reduce bacterial translocation from the gastrointestinal tract.


The life cycle of Trypanosoma cruzi under axenic conditions.

The complete life cycle of Trypanosoma cruzi under germfree (GF) conditions was achieved. The Reduvidae insects Dipetalogaster maximus, reared under axenic conditions were infected with Trypanosoma cruzi, strain CL, by feeding on GF infected mice. Axenic trypomastigotes from macerated gnotobiotic insects were used to infect GF and conventional (CV) mice by intraperitoneal, ocular, and oral routes. Infection, followed by blood parasitemia, was obtained in almost all the cases. However, Chagas' disease was more severe in GF animals when compared with CV mice.


Synthetic trehalose dicorynomycolate and antimicrobials increase survival from sepsis in mice immunocompromised by radiation and trauma.

When mammalian antimicrobial defenses are compromised by radiation, death from sepsis may occur. Tissue trauma in irradiated hosts significantly increases mortality from bacterial infections and makes antimicrobial treatments more difficult than when individuals are subjected to trauma or radiation alone. We determined that postirradiation therapy with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) and antimicrobials increases survival in mice after lethal irradiation and tissue trauma. Single agent therapy with systemic oxacillin, gentamicin, ofloxacin, and S-TDCM did not increase survival. Topical treatment of the injury with gentamicin cream in addition to systemic therapy with oxacillin or S-TDCM was necessary to enhance survival. Therapy with gentamicin and S-TDCM had a synergistic effect on survival. Therapies combining augmentation of non-specific host defense mechanisms with antimicrobials may be valuable in treating irradiated patients also sustaining tissue trauma.


The relative lethality of intestinal bacteria for gnotobiotic rats with experimental intestinal strangulation.

In eight experiments utilizing 28 animals each, germfree rats with and without ischemically or hemorrhagically strangulated closed loop intestinal segments were contaminated with either one of four common intestinal anaerobic bacteria, or a combination of two or three bacteria previously found to be innocuous in pure culture. The results showed that: a) in pure culture, Bacteroides fragilis, Bacteroides melaninogenicus, and Peptostreptococcus anaerobius were innocuous; b) Fusobacterium necrophorum alone was a very lethal organism that produced intense, confluent, intraperitoneal, fibrous adhesions after four to six days; and c) mixed inoculum of Klebsiella pneumoniae, Bacteroides fragilis, and/or Streptococcus faecalis was found to be lethal for gnotobiotic rats with intestinal strangulation. It is concluded that Fusobacterium necrophorum is so patent that it should be specifically treated with antibiotics when suspected or known to be present in clinical specimens. This gnotobiotic animal model will be useful to delineate the lethality of known combinations of intestinal bacteria.


The natural course of Clostridium perfringens--induced pneumatosis cystoides intestinalis.

Primary pneumatosis cystoides intestinalis (PCI) is an uncommon, usually benign condition whose natural course is poorly understood and which can sometimes produce significant changes in a patient's cecum and sigmoid colon. In this study, PCI was produced by monocontaminating the peritoneal cavities of adult germfree rats with Clostridium perfringens. These animals were then observed for up to 26 weeks. PCI took up to two weeks to develop, lasted at least ten weeks in most animals, and presumably disappeared from 42% of 26 animals killed during the final 16 weeks. PCI was usually benign, but in some animals produced extensive and persistent subserosal and submucosal air cysts of the cecum and sigmoid colon without evidence of intra-abdominal sepsis. These profound segmental colonic lesions suggest a possible etiology for other segmental inflammatory bowel diseases.


The right to die as a case study in third-order decisionmaking.

Using the right to die and the United States Supreme Court case of Cruzan v. Director, Missouri Department of Health as exemplars, this article explores the notion of third-order decisionmaking. If first order decisionmaking is about what should happen, and second-order decisionmaking is about who should decide what should happen, then third-order decisionmaking is about who should decide who decides. This turns out to be an apt characterization of constitutionalism, which is centrally concerned with the allocation of responsibility for making decisions about the allocation of responsibility. Deference to erroneous second-order decisions, as in the Cruzan case itself, may merely be an example of this central feature of constitutionalism.


Cruzan and the constitutionalization of American life.

In America today, public policy governing an increasing number of social issues is made through the judicial enforcement of constitutional rights. Cruzan raised the question whether policy regarding the withdrawal of medical care from incompetent patients is to be handled similarly. This essay argues that privacy-rights doctrine provides a poor basis for constructing public policy in this area. It suggests that the Court has been unable to articulate a convincing basis for privacy rights and that the basis the Court seems to assume poorly fits many circumstances to which it is applied. The essay further contends that the Court has been unable to describe a persuasive method of analyzing the state interests that are at stake in privacy cases and to accommodate those interests in a reasonable way. The essay concludes that these are issues as to which policy is better formed through a political, not judicial, process.


The concept of the person in the parens patriae jurisdiction over previously competent persons.

This article reviews the medieval law background of the parens patriae jurisdiction of the state as it has been exercised over incompetent persons who formerly were competent adults, concluding that the fiduciary standard implied in the statute De Prerogative Regis (1324), which is the basis for modern guardianship status, requires that the court and guardian adopt an attitude of respectful friendship toward the incompetent person, just as though they were to be accountable to the person himself, were he to recover his faculties and become competent once more. This fiduciary responsibility, originating in the device of the "use" or trust employed for the management of the estates of lunatics, contrasts with the self-interested feudal guardianship used for the custody of "natural fools" or "idiots", who were under paternalistic arrangements. The article argues that because the determination of legal incompetence and the consequent transfer of custody of the person and property of an incompetent person to the state would result in a drastic forfeiture of liberty and property interests were it not for the fiduciary obligation owed by the state to the incompetent, the state is under an obligation to exercise its fiduciary duties in good faith and may not impose states policies or advance state interests of its own in the supervision of the affairs of incompetent persons, apart from interests arising legitimately out of the state's institutional interest in providing competent administration for the benefit of the incompetents themselves.


Practicing medicine, fiduciary trust privacy, and public moral interloping after Cruzan.

The Supreme Court decision in Cruzan reaffirmed the power of the states to set procedural standards for due process regarding the individual's exercise of his liberty interest. As a result, to effect an autonomous decision to refuse treatment when one becomes incompetent requires an affirmative articulation by means of an advance directive. This article argues against simplified advance directives in that they fail to enhance individual liberty and responsibility and fail to provide physicians with needed information. A model protective advance directive is advocated with direction to terminate personal and health insurance payments for health care that is not desired by the patient.


Against the right to die.

For some patients, a right to receive euthanasia will not enhance autonomy in the morally relevant sense. Even if these patients choose wisely whether to exercise their right to die, they will still be harmed by having been given it. Perhaps, then, physicians should have permission to administer voluntary euthanasia, but patients should not have a right to receive it.


Plasma lipids and their interrelationship in Turkish adults.

The aim was to describe the plasma total cholesterol and triglyceride profiles in a random sample of Turkish adults and analyse the effects of certain coronary risk factors on these levels. This was a cross sectional population based survey. 59 communities scattered in all seven geographical regions of Turkey were surveyed in the summer of 1990. A random sample of 3689 men and women 20 years of age and over was studied. Plasma total cholesterol, triglycerides, glucose (using Reflotron and with partial validation in reference laboratory), weight, height, and blood pressure were measured, and information on smoking, physical activity, and family income obtained. Hypercholesterolaemia (> or = 6.5 mmol/litre, 250 mg/dl) prevailed in 8.5%, and hypertriglyceridaemia (> 2.25 mmol/litre, 200 mg/dl) in 16.6% among men and women aged 40-59 years of age. Age adjusted total cholesterol values were 4.8 mmol/litre (185 mg/dl) in men and 5 mmol/litre (192 mg/dl) in women. A steep rise appeared in mean cholesterol levels between the ages of 20-29 and 40-49 years, in a ratio greater than the available data from some other populations indicated. Mean total cholesterol values increased substantially in both genders with diminishing grades of physical activity, rising serum triglyceride levels, in urban (opposed to rural) residents, in men with increasing income levels, and in the younger adults with rising body mass index. Turkish adults have comparatively low levels of total cholesterol and medium to moderately high levels of triglycerides. Lifestyle factors affect these levels in Turks as in other populations.


An epidemiological survey of rheumatic fever and rheumatic heart disease in Sahafa Town, Sudan.

The aim was to determine the prevalence of rheumatic fever and rheumatic heart disease and to initiate a programme of secondary prophylaxis in Sahafa Town, Sudan. The study was a prospective case finding survey, carried out by a specially trained team headed by a cardiologist. The study involved high risk school children (5-15 years of age) from Sahafa Town in the period 1986-1989. A total of 13,332 children on the school registers (7892 boys and 5430 girls) were examined generally and specifically for evidence of rheumatic fever or rheumatic heart disease. Out of the 13,322 children screened 351 were suspected cases and 146 were confirmed cases of rheumatic fever or rheumatic heart disease. The prevalence rates for all ages were 10/1000 for boys and 14/1000 for girls. The overall prevalence rate of the whole programme area was 11/1000, prevalence of rheumatic fever was 8/1000, and prevalence of rheumatic heart disease was 3/1000. The prevalence rate was significantly increased among the inner town inhabitants (15/1000) compared to the outer town inhabitants 4/1000 (p < 0.001). Monthly prophylactic benzathine penicillin in a dose of 1,200,000 IU was given to both suspected and confirmed cases. Penicillin coverage rate was 72%. Rheumatic fever continues to be a serious health problem. With economic pressures causing impending change in socioeconomic conditions in most Third World countries in the immediate future, rheumatic fever will continue to have a high prevalence rate and rheumatic fever and rheumatic heart disease prevention programmes will remain a central goal.


Social class differences in child mortality, Sweden 1981-1986.

The aim was to analyse social class differences in mortality among Swedish children, 1-19 years old, during the period 1981-86. In order to study the development of these differences, mortality differences during the study period were compared with those 20 years earlier, ie, 1961-66. The study used data from two census linked death registries (CDR80 and CDR60). These were constructed by linkages between the 1980 and 1960 population censuses, respectively, and the corresponding national cause of death registries. Age specific and age standardised death rates, for total and cause specific mortality, were calculated for each social class and for the genders separately. To compare the death rates of social classes, relative risks with approximately 95% confidence limits were calculated. The study included children younger than 16 years at the time of the censuses and all deaths in the age range 1-19 years. The children were followed up for a period of six years after the censuses with respect to mortality. During the period 1981-86, children in families of both manual workers and self employed persons had a significantly higher mortality than children in families of non-manual workers. Although there has been a marked decrease in child mortality during the last decades the study shows that social class differences in child mortality still exist and show little tendency to disappear.


Sudden infant death syndrome: does winter affect poor and rich babies equally?

The aim was to investigate whether the winter increase in risk of sudden infant death was similar across social classes. This was an unmatched case-control study using routine data. Cases and controls were selected from files holding routine birth and death certificate data for England and Wales for 1986. Cases were deaths in the first year of life occurring in the summer or the winter of 1986 with mention of sudden infant death or SIDS in the death certificate. Controls were a 1% random sample of all children born in the same year. Only children whose parents were married or living together at the time of birth registration were included. Data on age and season of death for cases, and on date of birth, social class of father, and birth weight were abstracted from the file. Season of birth and birth weight were treated as confounding variables. The increase in risk of SIDS in winter was calculated for each age group and social class. The winter increase in SIDS was more marked among the higher social classes for all ages, but not to a statistically significant degree: the p values for heterogeneity were 0.26 for age 0-3 months, 0.42 for 4-7 months, and 0.41 for 8-12 months. There is no direct association between seasonal variation in sudden infant death and social class.


Trends in "avoidable" mortality in Sweden, 1974-1985.

The aim was to analyse trends in "avoidable" mortality in Sweden, and to contribute to the methodology of avoidable mortality as an index of the quality of care. All deaths of Swedish citizens and other residents in Sweden during the period 1974-1985 were analysed as to causes of death between ages 0 and 64 years. Total mortality delined during the 12 year period studied. Avoidable causes of death were grouped into preventable and treatable causes according to Rutstein's classification. In men, treatable diseases declined more during the 12 year period studied than did total mortality. When lung cancer was excluded, preventable diseases declined for both sexes. Certain avoidable causes of death decreased compared to total mortality, while some others showed an increase. The death rate increased for some avoidable causes of death such as pneumonia other than viral. In women death rates increased for chronic bronchitis and emphysema as well as for malignant neoplasms of trachea, bronchus, and lung, while for boys aged 1-14 years bronchitis NOS and asthma showed an increasing death rate. The study indicates that the avoidable mortality method is sensitive enough to describe important changes in the mortality pattern. The explicit definition of treatable and preventable causes of death constitutes a methodological development in epidemiological analysis of this type. Further studies on the quality of care should combine this method with other methods examining the structure and process of health care.


Trends in peptic ulcer mortality in Italy, 1955-1985.

The aim was to analyse trends in mortality from peptic ulcer in Italy between 1955 and 1985, disentangling the role of age, cohort of birth, and period of death. This was a descriptive epidemiological survey. Death certification numbers from peptic ulcer and estimates of the resident population were obtained from official sources. From these data, age specific and age standardised mortality rates from peptic ulcer were computed. A log-linear age, period, and cohort model with arbitrary constraints on the parameters was applied to the matrices of age specific rates between 25 and 74 years of age. This was a national survey. For males, overall peptic ulcer mortality was constant or moderately upwards (from 9.0 to 9.4/100,000, on the basis of World Standard Population) from 1955 to the mid-1970s, but declined considerably afterwards to 3.7/100,000 in 1985. Truncated (35-64 years) rates were slightly more favourable, even in earlier calendar periods, but a substantial drop was observed only from the late 1970s onwards. In 1985 the standardised rate was 3.3/100,000 compared to 18.3 in 1955-1959. For females, the time pattern was similar, although the extent of the decline was smaller in absolute terms (from 1.6 to 1.2/100,000, all ages; from 2.3 to 0.7, truncated). Age specific rates showed an earlier decline in the young, while the fall started only after the mid-1970s in older age groups. On the basis of a log-linear age, period, and cohort model, the Italian generations born in the first decade of this century had the highest risk of dying from peptic ulcer, with a substantial decline for each subsequent cohort. Period trends were stable between 1955 and the mid-1970s, but declined appreciably afterwards. In Italy the peak rate of peptic ulcer mortality was observed in the early 1970s, with a delay of around two decades in comparison with northern Europe and the USA. This can be related to the later process of industrialization in Italy, with the consequent changes in lifestyle habits, and to a later pattern of rise and decline of cigarette smoking. A likely explanation of the falls in mortality on a period of death basis over the last decade is the introduction of new drugs (histamine-2 receptor antagonists) for the treatment of peptic ulcer, with a reduction of complications of the disease and related mortality. This decline in mortality from peptic ulcer corresponds to the avoidance of over 1500 deaths per year in the whole of Italy.


Mortality in Glasgow and Edinburgh: a paradigm of inequality in health.

The aim was to describe, predict, and interpret mortality in Glasgow and Edinburgh. The study was an analysis of all cause and cause specific mortality data for quinquennia based on census years between 1931 and 1981, linking age and sex specific mortality rates by year of birth, for people dying between the ages of 25 and 74 years. Glasgow and Edinburgh, Scotland. Age and sex specific mortality rates declined steadily in Edinburgh and Glasgow during the period 1931-1981, with rates always being lower in Edinburgh than in Glasgow. Since 1961 log mortality rates have tended to rise linearly with age in both cities. In 1979-83, the population of Glasgow reached a given all cause mortality rate 3.9 years earlier in men and 3.6 years earlier in women than did the population of Edinburgh. These differences have increased, and are predicted to increase further, especially in men. The current 40% cross sectional difference in mortality rates between the cities is largely determined by levels of mortality in early adulthood which provide a baseline for the subsequent rise in log mortality. Disease specific epidemiology provides a limited view of inequalities in health, and a partial basis for health promotion. Campaigns to alter disease risk profiles in adults should be complemented by measures operating earlier in life to reduce susceptibility to risk. Maternal and child health require greater priority in public health policy, particularly in areas of socioeconomic disadvantage.


Physical diability after retirement and occupational risk factors during working life: a cross sectional epidemiological study in the Paris area.

The aim was to examine the relationship between exposure to occupational risk factors during working life and physical disability after retirement. The study was a cross sectional epidemiological survey of a representative sample of retired subjects belonging to a supplementary pension fund in the Paris area. The study took place in the general community. 307 men and 320 women (63.1% of those approached) answered a questionnaire during home interviews. Their average age was 69 (SD4) years at the beginning of the survey. Whether or not subjects had been exposed to occupational risks was determined from their statements concerning the presence or absence of eight harmful environmental conditions while at work. Physical disability was defined as difficulty in carrying out seven basic activities of daily life. The results of univariate analyses showed significant relationships between exposure during working life to occupational risks including noise, heat, dust, carrying heavy loads, and awkward postures on the one hand, and the presence of a physical disability after retirement on the other. Multivariate analysis based on logistic regression models that took account of age, sex, and health impairments revealed a specific link between exposure to carrying heavy loads and physical disability after retirement. These results suggest that occupational risk factors might be important in determining such disability in retired people.


Dermatoglyphic patterns in dementia of the Alzheimer type: a case-control study.

The aim was to compare digital and palmar dermatoglyphics in subjects with dementia of Alzheimer type and in mentally healthy elderly controls. This design was a case-control study. The study was carried out in geriatric units and retirement communities in the Paris area. Cases were women with clinically diagnosed Alzheimer type dementia according to DSM III-R criteria (n = 82), mainly with late onset of the disease. Controls were women aged 85 years or older without cognitive deterioration (n = 76). Finger and palm prints obtained from both hands by the classical ink method were examined. Fingerprints were classified into four types of figures. On palms, palmar flexion creases, palmar axial triradii, true patterns of the hypothenar area, and main line terminations were described. Examinations were performed by two examiners blind to the subjects's diagnostic category. For the different patterns studied, no major differences between dementia patients and elderly controls were found. Nor was there evidence of high frequencies of features commonly observed in Down's syndrome (trisomy 21), which have previously, though sporadically, been reported. On one of the largest samples of Alzheimer dementia patients studied, and with evaluation blind to diagnosis, no evidence has been found that particular dermatoglyphic patterns occur like those observed in Down's syndrome, a disease which is related to dementia of the Alzheimer type.


Accuracy of death certificate diagnosis of amyotrophic lateral sclerosis.

The aim was to determine the reliability of official mortality statistics in estimating long term trends of amyotrophic lateral sclerosis (ALS) in Italy. The study was a mortality follow up of cases of ALS. Piedmond Region, northern Italy. Cases of ALS were identified from multiple sources between 1966 and 1985. Cause of death was determined for the cases who died between 1970 and 1985. Death certificates were obtained in 488 out of 510 cases (95.7%). ALS was mentioned in 365 (74.8%) of cases. The most frequent erroneous diagnoses were multiple sclerosis and malignant tumours. Demographic variables, such as sex, age at death, province of death, and calendar year of death, did not influence the percentage of true positive cases significantly. The death certificate diagnosis of ALS appears to be adequate for use in descriptive and analytical epidemiology.


Paternal occupational lead exposure and congenital malformations.

The aim was to investigate whether occupational exposure to lead in fathers is associated with congenital malformation in their children. The study was a retrospective case-control study, nested within the wives of men biologically monitored for inorganic lead. Information on pregnancy outcome was obtained from medical registers. Cases were defined as wives with malformed child during 1973-82. Three age matched controls were selected for each case from the wives who had given birth during 1973-1983. The final study population was 27 cases and 57 controls. Paternal lead exposure was assessed with blood lead measurements and data obtained from a questionnaire. The response rate was 67% among the cases and 76% among the controls. The odds ratio (OR) of congenital malformation for paternal lead exposure was increased (OR 2.4, 95% confidence interval 0.9-6.5), although not reaching statistical significance. The odds ratios varied from 1.9 to 3.2, when adjusted for one potential confounding variable at a time. Because of the small numbers and low participation, this study offers limited support for the hypothesis that paternal lead exposure is associated with congenital malformation. Further epidemiological studies on the reproductive hazards of paternal lead exposure are needed.


Does the offer of cervical screening with breast screening encourage older women to have a cervical smear test?

The aim was to determine what effect the offer of a cervical smear test when attending for breast screening has on the uptake of cervical and breast screening. The study involved randomisation to compare uptake in those women invited for cervical screening in advance with their breast screening invitation (group 1) with those invited for breast screening only and then offered a smear test upon arrival for breast screening (group 2). The main outcome measure was improvement in the uptake of cervical screening among older women without detriment to the breast screening service. The study took place at the Northern Hospital in North Manchester. Participants were 2131 women aged 50-64 years invited for breast screening at the Northern Hospital in the summer of 1990. Overall, 54% of the women who were eligible attended for breast screening, 52% attended from group 1 and 55% from group 2. Of those attending for breast screening, 957 were eligible for cervical screening and 193 (20%) had a smear test. There was a difference in the proportion tested from each group (p < 0.001), 28% had a smear test from group 1 and 13% from group 2. Forty five percent of the 193 had not had a cervical smear for at least five years. The cervical screening facility did attract some women who were overdue for a smear test and who might not normally have attended for cervical screening, and there was no evidence to suggest that it had a detrimental effect on the breast screening uptake. An advanced cervical screening invitation seemed preferable to an invitation upon arrival at the breast screening unit.


A case-control study of benign ovarian tumours.

The aim was to investigate the association between reproductive, contraceptive, and menstrual factors and risk of benign ovarian tumours. This was a case-control study carried out in six London Hospitals. An interviewer administered questionnaire was used. 62 women with a benign epithelial ovarian neoplasm, 37 women with a functional ovarian cyst, and 20 women with a dermoid cyst presenting between 1983 and 1985, together with 132 controls, took part in the study. On average, women with a benign epithelial ovarian neoplasm were older than those with a functional ovarian cyst, who in turn were older than those with a dermoid cyst. Nulliparity and infertility were associated with an increased risk, and multiparity with a reduced risk, of benign epithelial ovarian neoplasms. Infertility and pelvic inflammatory disease were associated with increased risks of functional and dermoid cysts. Recent use of oral contraceptives was associated with a reduced risk of all three tumour types. The findings suggest that the aetiology of ovarian cysts and benign epithelial ovarian neoplasms may differ. The aetiology of benign and malignant epithelial ovarian neoplasms may be similar, however, since some risk factors are shared.