The regioselective binding of CHCl3 reactive intermediates to microsomal phospholipids. Microsomal phospholipids (PL) are a good target for the reactive intermediates produced by either the oxidative or the reductive biotransformation of CHCl3 (Testai et al. (1990), Toxicol. Appl. Pharmacol. 104, 496-503). In order to preliminarily characterize the different PL with CHCl3 reactive intermediates, two common methods of PL breakdown have been exploited: the acid-catalyzed transmethylation and the enzymatic hydrolysis with phospholipase C. The results indicated that radioactivity derived from the adducts of PL with the oxidation metabolite, phosgene, partitioned preferentially in the aqueous phase (the ratio of aqueous to organic phase radioactivity contents was about 10); the opposite occurred (ratio about 0.1) when the PL adducts were produced by the reductive process metabolites (dichloromethyl radicals). Therefore, the two methods of PL adduct breakdown can be used to detect and quantitate selectively the two reactive intermediates of CHCl3 biotransformation. The use of phospholipase C, which specifically cleaves the bond between the glyceryl-oxygen and the phosphor atom of PL also gave some structural information. Indeed, the radioactivity partitioning in the aqueous phase after enzymatic hydrolysis of CHCl3 oxidation-associated PL adducts, indicated the selective covalent binding of phosgene residues with the PL polar heads. The clear-cut different partition of radioactivity observed after hydrolysis of PL adducts with CHCl3 reduction intermediates, analogously indicated that dichloromethyl radicals were selectively bound to the PL fatty acyl chains. Using this method we could confirm that in in vitro experimental conditions resembling the physiological status of the liver, both metabolic pathways were concurrently active in hepatic microsomes of B6C3F1 mice. Extents of reactive metabolites similar to those found in B6C3F1 mouse liver microsomes, could be measured in Sprague-Dawley rat liver microsomes only after pretreatment of the animals with PB and incubation with higher CHCl3 concentrations. The toxicological implications of these findings are discussed.


Effect of oxidative stress on receptors and signal transmission. Reactive oxygen metabolites affect binding of ligands to membrane receptors and also coupling of receptors to G-proteins and effector enzymes. Peroxidation of membrane lipids may lead to a lowered receptor density and also will alter the viscosity of the plasma membrane, which affects receptor coupling. Reactive oxygen species may also interact with thiol/disulfide moieties on receptor proteins or on other factors in the receptor system, which is responsible for alterations in receptor binding or coupling. Moreover, lipid peroxidation is associated with the phospholipase A2 pathway, which might indirectly affect receptor function. Moreover, oxidative stress may lead to a disturbance in cellular Ca(2+)-homeostasis. This might be related to an effect on Ca(2+)-mobilizing receptors, but there is also evidence for a decreased Ca(2+)-sequestration by ATPases. In addition, peroxidation of membrane lipids increases membrane permeability to Ca2+. Finally, reactive oxygen species interfere with actions of nitric oxide, thus affecting another pharmacological messenger system.


Thermal behavior and elastic properties of phospholipid bilayers under the effect of a synthetic flavonoid derivative, LEW-10. We have investigated the effect on phospholipidic bilayers of LEW-10, a synthetic flavonoid, derivative of diosmin. Two optical techniques, Quasi-elastic Light Scattering (QLS) and Fourier Transform Infrared Spectroscopy (FT-IR) were used. The results show that in the presence of LEW-10, the phase transition of the bilayers is lowered and that the elastic modulus is decreased. The FT-IR results indicate interactions in the aqueous interface regions of the bilayers. We also discuss LEW-10 comparatively with another derivative, LEW-7/S1, whose effect has been previously studied.


Modulation of bilayer structures derived from diacetylenic phosphocholines containing oxygen linker beta to diacetylene. Phospholipids with diacetylenes present in the acyl chains form tubules and helices in aqueous dispersions. In order to modulate the morphology of bilayer structures and to understand the role of diacetylene in lipid-bilayer assembly, two diacetylenic phosphocholines, 1,2-bis(9,16-dioxa-hexacosa-11,13-diynoyl)-sn-3-phosph ocholine and 1,2-bis(15-oxa-pentacosa-10,12-diynoyl)-sn-3-phosphocholine, in which the diacetylene is linked to the acyl chain by an oxygen spacer have been synthesized. Lipid dispersions were characterized by calorimetric, film balance and microscopic techniques. Placement of oxygen spacer influences the morphology of the bilayer assemblies formed in aqueous solution. When both ends of the diacetylene were linked to the acyl chain by oxygen atoms, liposomes (diameters ranging from 0.3-3.4 microns) were observed by optical microscopy. Linking only the terminal portion of the acyl chain to the diacetylene with an oxygen atom resulted in a lipid which formed tubular microstructures as well as vesicles. Diameter of the tubular structures ranged from 0.4-4.7 microns. Transmission electron microscopic (TEM) analysis of replicas of a freeze fractured sample of the dispersion revealed that the tubular structures were hollow cylinders consisting of an aqueous core surrounded by a wall of lipid.


Implications of a non-lamellar lipid phase for the tight junction stability. Part I: Influence of basic amino acids, pH and protamine on the bilayer-hexagonal II phase behaviour of PS-containing PE membranes. Inverted lipid micelles have been proposed, among other biological functions, to constitute the structural basis of the so-called tight junctions, a special cell cell contact found in epithelia and endothelial, which act as a barrier for the paracellular solute passage. As a model system for the opening and closing of this gate, we investigated the formation of the inverted hexagonal phase (HII phase) in lipid bilayer systems consisting of egg phosphatidylethanolamine (egg PE) and mixed egg PE/bovine brain phosphatidylserine (BBPS) membranes. The formation of the HII phase was modulated by Ca2+ ions, pH, basic amino acids and protamine. The lamellar-HII phase transition temperature TH of pure egg PE membranes at pH 7.0 was lowered with increasing Ca2+ concentration. This effect was attenuated by the presence of 50 mM lysine methyl ester. In the mixed lipid system, this effect was also observed, but even more pronounced. However this effect could be compensated for by raising the Ca2+ concentration from 2 to 10 mM. This was not observed in the pure PE system. In the absence of Ca2+, lysine methyl ester and protamine lowered TH in both monocomponent and mixed lipid systems, whereas lysine caused the opposite effect. The pH-dependence of mixed lipid systems, which were investigated up to a BBPS content of 20 mol%, clearly shows that increasing PS content stabilizes the lamellar phase even at low pH. The results obtained with model membranes are discussed with respect to biological implications of the lamellar-HII phase transition for the modulation of tight junction stability.


Fusion of lipid bilayers: a model involving mechanistic connection to HII phase forming lipids. A model for the molecular mechanism of the fusion of lipid bilayers is described. A crucial feature of this model and related to the lamellar-->hexagonal phase HII transition is a novel, hypothetical lipid conformation, tentatively referred to here as extended. During fusion this conformation could manifest itself in the contact site between two vesicles in close proximity and involves the extension of the acyl chains of a phospholipid molecule in opposite directions, i.e. embedded into the two opposing bilayers while maintaining the headgroup in the interface. Although evidence for the occurrence of the extended conformation for phospholipids is sparse this conformation appears to be compatible with currently available experimental data. Of importance also is that the extended conformation allows for the fusion of two bilayer membranes to proceed with minimal exposure of the lipid hydrocarbon chains to water. It can also account for other features of membrane fusion such as lipid mixing in the intermediate state without mixing of the vesicle contents as well as for the molecular basis of the action of fusogenic lipids.


Functional endoscopic sinus surgery on a day case out-patient basis. One hundred patients, aged 13-79 years, have undergone 195 endoscopic 'ethmoidectomies'. The operative method was entirely based upon the Messerklinger technique. In this study there were two main groups. (1) Patients with moderate to massive nasal/endonasal polyposis. (2) Patients with recurrent sinusitis. In the second group, the preoperative endoscopic findings were dominated by disease in the middle meatus and in the area of the anterior ethmoid, verified either by conventional hypocycloidal or computed tomography. Close to 90% of the patients were treated on an out-patient basis, under local anaesthesia. No serious peroperative complications (major bleeding, CSF leak, or visual problems) have been encountered. Thorough and meticulous post-operative care to avoid adhesions and renewed ostiomeatal obstruction, is felt to be important. The mean follow-up was 14 months. The post-operative results are encouraging, and correspond to larger European and American reports. The Messerklinger technique has proved to be suitable for smaller ENT departments, such as ours, especially as the patients can be treated on an out-patient basis using local/topical anaesthesia.


Distribution of eosinophils in the nose in patients with perennial rhinitis. The traditional method of classifying perennial rhinitis into eosinophilic and non-eosinophilic is by taking a single nasal smear from one nostril. In the light of personal experience it was felt that this method of sampling may be inadequate. The present study included 20 patients with perennial rhinitis undergoing nasal surgery. Serum total IgE levels were taken and those above 40 IU/ml had allergen specific IgE measured. Nasal smears and biopsies were taken from 5 sites on each side of the nose; middle and inferior turbinates and post nasal space. The smears significantly correlated with the biopsies (rs = 0.446, P < 0.001). The distribution of eosinophils between and within nasal cavities was found to differ. Representative sampling of the nose is important for accurate eosinophil expression. The definition of an eosinophil rich and poor nose requires greater clarification as it has great clinical relevance regarding management.


An evaluation of auricular prosthesis using osseointegrated implants. The purpose of this evaluation is to compare whether retention of auricular prostheses, through utilization of osseointegrated implants rather than by adhesive, provides any improvement in patient acceptance and prosthesis longevity. Forty-seven out of a total of 49 patients having facial prostheses, retained by means of Brånemark fixtures, were surveyed. Ease of retention was noted in 91% of the patients. Satisfaction with the shape of the prosthesis, colour and ease of positioning was 100, 85 and 98% respectively. None of the patients experienced skin irritation under the prosthesis and 94% of them wore their prosthesis daily. Of the 13 patients with previous prosthesis experience, 92% stated improved retention and all of them found ease of positioning and wearing comfort had improved. Durability was better in 62%, unchanged in 23% and worse in 15% of these 13 patients.


The latissimus dorsi flap in head and neck reconstructive surgery: a review of 121 procedures. The results of a prospective study of 121 latissimus dorsi flaps performed during head and neck reconstructive surgery at the Royal Marsden Hospital are presented. Three-quarters of the flaps were pedicled and one-quarter were free. All the patients underwent surgery for malignant disease. The flap failure rate was 5%, other flap related complications occurred in 19% and the overall rate of complications was 26%. Previous radiotherapy, site of reconstruction, type of flap (free or pedicled) and age of the patient were not significant risk factors. Men were more likely to have a complication than women.


Culture of human middle ear mucosal explants; mucin production. Middle ear mucosal biopsies could be maintained in culture for up to 7 days, the longest time attempted in this study. Mucin biosynthesis and secretion were measured by incorporation of 14C-glucosamine. Three peaks of radioactivity were present when the dialysed medium was chromatographed. Peak I which accounted for about 10% of the total radioactivity had properties characteristic of mucin. The other two peaks were not characteristic of mucins. Labelled macromolecules excluded on Sepharose 2B were also present in the tissue. Autoradiography of the explants showed that the labelled glucosamine was concentrated in the epithelial layer. Morphometry demonstrated that 1-2% of the epithelial cell volume consisted of goblet cells. The proportionate incorporation of radioactivity into macromolecules increased with increasing epithelial cell volume. This system will allow assessment of factors implicated in the pathogenesis of otitis media with effusion and the study of the action of pharmacological agents on biosynthesis and secretion.


Teflon injection for unilateral vocal cord paralysis and its effect on lung function. We present a prospective analysis of the lung function of 22 patients with unilateral vocal cord paralysis before and after Teflon injection. In the majority of patients the vocal cord paralysis was caused by an underlying malignant condition. Full spirometric and flow-volume loop studies demonstrated an increase in airway resistance after Teflon injection which was not clinically evident. The improvement in symptom score for aspiration was greater than that for dysphonia.


A phase II study of cisplatinum versus cisplatinum + nifedipine in end-stage carcinoma of the head and neck. Forty patients with end-stage carcinoma of the head and neck were admitted to a randomized double blind trial with cisplatinum in one arm and cisplatinum + nifedipine in the other. Nifedipine, a calcium channel blocking drug, inhibits the effect of acquired multidrug resistance in animal models. In the present study the addition of this agent had no effect on either response rate or survival in end-stage carcinoma of the head and neck. It is concluded that adding nifedipine to cisplatinum serves no useful purpose in the treatment of end-stage carcinoma of the head and neck.


The histopathology of mastoidectomy cavities, with particular reference to persistent disease leading to chronic otorrhoea. Open cavity mastoidectomy remains the principal surgical treatment of middle ear cholesteatoma in the United Kingdom. A significant proportion of mastoid cavities are prone to intermittent or continuous discharge. In this study the histopathological features of material removed from 159 mastoid cavities at revision surgery were reviewed. Findings included squamous epithelium with acute and chronic inflammation, foreign body granuloma and aural polyps. Of particular note was the very infrequent finding of discharging cavities lined with respiratory epithelium, suggesting that retained mucosa in mastoid air cells is not a common cause of persistent otorrhoea.


Higher surgical training in Otolaryngology. The views of the membership of the Association of Otolaryngologists in Training (all current UK Senior Registrars and Consultants in their first year of post) were sought on topical aspects of Higher Surgical Training. 80 members (72.3%) participated. The main points to emerge were that the intercollegiate exam is unpopular. 66% feel it is neither well suited to the developing career structure nor a good assessor of trainees, 80% of Senior Registrars for whom the exam is voluntary say they will not sit it, 66% have doubts about the confidentiality of the Specialist Advisory Committee (SAC) interview and 73% felt the need for a separate faculty for Otolaryngology at the Royal College of Surgeons.


The radio-opacity of fishbones.

The radio-opacity of fishbones. Plain radiographs are often taken to localize fishbones which lodge in the pharynx. In this study a pig's neck was used to determine the radio-opacity of 14 different species of fishbones. Radiographs were taken with bones placed in up to four of the common sites of impaction and assessed on two occasions independently by two previously uninvolved ENT consultants. The visibility of the fishbones was scored. Inter and intra-observer agreement for species and site was determined. There was excellent interobserver agreement at both sessions for species (rs1 = 0.96, P < 0.0001, rs2 = 0.95, P < 0.0001) and site (rs1 = 0.98, P < 0.05, rs2 = 0.95, P congruent to 0.05). Intraobserver agreement for species of fish were similarly significant but not for site. The most opaque bones were cod, haddock, grey mullet and lemon sole. The site most often detected was the laryngopharynx and that most often missed was the tonsil. This study is clinically relevant because it is useful to know which species of fishbone are radio-opaque when clinical examination fails to reveal a foreign body and may clarify the decision to proceed to endoscopy.


Post-tonsillectomy pain with diathermy and ligation techniques. A prospective randomized study in children and adults. 150 patients (80 children and 70 adults) were entered into a prospective randomized study to compare the post-tonsillectomy pain of unipolar diathermy as opposed to ligation for haemostasis. In children, we found no difference in post-operative pain between the diathermy and ligation techniques. However, in adults there was a significant difference, more post-operative pain occurring with diathermy. There was no significant difference in the incidence of secondary haemorrhage.


Ingested foreign bodies: patient-guided localization is a useful clinical tool. We prospectively studied the latest 60 patients who presented to the ENT Departments of St Mary's and St George's Hospitals with ingested foreign bodies. Localization of the foreign body by the patient was compared to the actual site of the foreign body at removal and graded accordingly. Localization was better the higher the object. When compared with objects above the cricopharyngeus muscle items impacted below this level were poorly localized (P < 0.0001) and lateralized (P < 0.0001). This suggests that for a patient who is able to lateralize a presumptive foreign body within the cervical region, then that object is likely to be above cricopharyngeus and on the side indicated. Further, it is likely to be visible on indirect laryngoscopy and amenable to removal in the casualty department. We hypothesize that the pharyngeal innervation by the vagus and glossopharyngeal nerves provides better sensation than in the oesophagus which is innervated less densely by the vagus and cervical sympathetic nerves.


The relief of snoring by nasal surgery.

The relief of snoring by nasal surgery. Patients with nasal obstruction may also complain of snoring. It is uncertain whether surgery which relieves the nasal obstruction will also relieve the snoring. We have reviewed 126 patients who complained of both nasal obstruction and snoring and who underwent nasal surgery. Snoring was completely relieved in 39 patients (31%), was less loud in a further 72 patients (57%), unchanged in 11 and louder in 4. It occurred on fewer nights post-operatively in 61, on the same number in 24 and more frequently in 2. Patients who had nasal polypectomy as part of their nasal surgery obtained the greatest snoring relief. This study suggests that when snoring and nasal obstruction coexist nasal surgery should be considered as the first line of surgical treatment.


The morbidity from nasal splints in 105 patients. The results of a randomized prospective trial investigating the morbidity from intranasal splints in 105 patients, were analysed. Intranasal splints are associated with considerable morbidity (significantly greater post-operative pain and a higher incidence of septal perforation and vestibulitis) and although they significantly reduce the likelihood of developing intranasal adhesions, a similar benefit can be obtained by careful nasal toilet at one week.


Bacteria and endotoxin in middle ear fluid and the course of secretory otitis media. To determine the influence of bacteria and bacterial products on the course of secretory otitis media (SOM) following ventilation tube insertion we examined 68 middle ear effusions from 57 children with SOM. Swabs were taken for bacteriological examination and the content of endotoxin was measured. The children were followed up for one year and relapse of SOM was recorded. Bacteria were present in 38% of effusions and endotoxin was detectable in 96%. Relapse occurred in 26% of the patients and was related to the presence of bacteria in the original effusion (P < 0.01). The concentration of endotoxin, however, did not correlate with the course of SOM.


The use of intra-nasal splints: a consultant survey. A questionnaire was sent to all United Kingdom consultants enquiring about their use of intra-nasal splints. 301 (70%) consultants replied. The commonest reason given for use of nasal splints was to try to prevent the formation of adhesions. Flat, pre-shaped silicone rubber splints were by far the most frequently used type. 64% used splints routinely for operations involving both walls of the nasal cavity. Just over one-third of respondents never or 'rarely' (less than 1 in 50 cases) used splints for procedures involving both walls of the nasal cavity. They reported an adhesion rate of 5.2% which was only 1.3% greater than that reported by those who always or 'sometimes' (at least 1 in 10 cases) used splints. Comments from some respondents and review of the literature suggests that early out-patient review with the use of nasal toilet is an effective alternative to using nasal splints in the prevention of intranasal adhesions.


Neck dissection for non-squamous malignancy. Of 1030 patients who underwent neck dissection (radical, modified or selective) in a 27-year period 103 had malignant neck nodes from a primary site in the head and neck with a histological diagnosis other than squamous carcinoma. There were 71 men and 32 women in this group with a mean age of 55 years. 28 patients had neck dissection as part of their initial treatment and 75 for later nodal recurrence. Five-year survival was 52% (40-63%). Survival was site dependent, best for thyroid tumours and worst for tumours of the major salivary glands (chi 1(2) = 6.52, P < 0.05). Histology significantly affected survival, best for papillary tumours and worst for melanoma and undifferentiated tumours (chi 1(2) = 3.85, P < 0.05). Survival was worse with advanced N stage but varied little with node level. The number of nodes invaded had a highly significant effect on survival (chi 4(2) = 23.94, P < 0.001), but extracapsular rupture had no effect. Advanced T stage at the time of surgery had a significant adverse effect on survival using univariate analysis, but this effect disappeared using multivariate analysis. In the 75 patients who had neck dissections for nodal recurrence the presence of a simultaneous recurrence at the primary site had no significant effect on survival. These patients had a better 5-year survival than patients having neck dissection for squamous disease, but the usual predictors of survival in squamous carcinoma do not always apply to non-squamous malignancy.


The management of early hypopharyngeal cancer: primary radiotherapy and salvage surgery. Carcinoma of the hypopharynx tends to present late and to occur in old age. Surgical treatment almost always involves a total laryngectomy as well as a major procedure to reconstruct the pharynx. Early tumours up to and including T3 tumours with no, or very early (nodes < 2 cm) nodal disease may be treated with radiotherapy with the option of salvage surgery if recurrence supervenes. In 106 previously untreated patients the 5-year recurrence rate was 50% and the 5-year survival rate was 41%. Sixty-nine patients were referred from other departments because of recurrent disease. The 5-year survival for those patients was 21%. The 5-year survival for those who developed a recurrence at the primary site was 23%. Seventy-eight patients had a resection and 42% suffered a major complication. Only 2 of the methods of reconstruction appear to be satisfactory: for disease confined to the neck free revascularized jejunal loop-repair is effective whereas for more extensive disease gastric transposition is recommended. Twenty-three per cent of patients developed neck node metastases and the 5-year survival rate for patients was 16%. Cox's regression showed that no host or tumour factors predicted survival. At 5 years, 46% of patients were alive with a larynx, 4% were alive without a larynx, 34% were dead of the original cancer and 16 were dead of other causes.


Orbital infection secondary to sinusitis in children: diagnosis and management. A series of 18 children with orbital infection secondary to sinusitis is described. The presenting symptoms were headache and periorbital swelling but it was found to be impossible to determine the stage of the orbital infection on clinical grounds. CT scanning can accurately identify the presence of a sub-periosteal abscess but both axial and coronal sections may be needed to diagnose abscesses in the superomedial portion of the orbit. Cellulitis may be managed by antibiotic treatment alone, but if an abscess is present it should be drained immediately with a formal ethmoidectomy to decompress the orbit if there is any evidence of reduced visual acuity.


Multiple primary malignant tumours in patients with head and neck cancer: the implications for follow-up. The pattern of second primary cancer occurrence in 518 Scottish patients with head and neck cancer was determined by a retrospective study. The overall incidence of second cancers was 9% but the true incidence increased steadily in the years following initial diagnosis to reach a maximum of 21% at 11 years. After 4 years of follow-up patients were more likely to die from a second primary cancer than from the effects of the initial tumour. The Scottish cohort differed from previously reported, overseas, study groups in having a high incidence of second primary cancers in sites outside the upper aerodigestive tract. This potential demographic difference suggests a need for local audit prior to design and implementation of screening protocols for second primary cancers.


Myringoplasty under local anaesthesia: day case surgery. Eleven patients underwent fat graft myringoplasty, using EMLA cream local anaesthetic, as day cases. 10 of them were followed up, and 3 months post-operatively, 8/10 (80%) of the perforations were completely closed, with an average improvement of the hearing threshold of 11 dB. All the patients were satisfied with the procedure and it is concluded that fat graft myringoplasty under local anaesthesia as a day case is safe, simple, reliable and cost effective. It should be considered for closure of small perforations (30% or less) of the tympanic membrane.


Detection of the Pro664-Leu mutation in the low-density lipoprotein receptor and its relation to lipoprotein(a) levels in patients with familial hypercholesterolemia of Dutch ancestry from The Netherlands and Canada. From a large cohort of hyperlipidemic patients, who attended the Lipid Research Clinic in Amsterdam, The Netherlands and in Vancouver, Canada, 915 consecutive patients with familial hypercholesterolemia (FH) of Dutch descent, were selected. This group of FH patients was screened for the presence of a cytosine to thymidine nucleotide substitution in exon 14 of the LDL-receptor gene, in order to determine the frequency of this mutation in patients of Dutch descent and to investigate the relationship between the mutation and the level of lipoprotein(a). The mutation was detected in seven individuals. All patients with this mutation shared the same haplotype, which is suggestive of an ancient mutation. The index patients and a large kindred with this mutation were further analyzed at the biochemical and clinical level. Except for total and LDL-cholesterol, there was no statistically significant difference in biochemical parameters between family members with and without FH. In contrast to previous reports, there was no difference in plasma levels of lipoprotein(a) between patients with the mutation in exon 14 and unaffected individuals.


The Wolf-Hirschhorn syndrome in fetuses. Wolf-Hirschhorn syndrome (WHS) with partial deletion of the short arm of chromosome 4 has been exceptionally diagnosed in fetuses. We report prenatal diagnosis of five cases of monosomy 4p. The fetuses were karyotyped for severe intrauterine growth retardation (IUGR) diagnosed on routine ultrasound (US). In addition, cleft-lip and palate and diaphragmatic hernia respectively were found in two cases. The quantity of amniotic fluid was normal in all cases. At autopsy, the fetuses showed the typical craniofacial dysmorphy but without microcephaly. Major renal hypoplasia was the only constant visceral anomaly. Midline fusion defects were observed in all the fetuses, ranging from minor abnormalities such as scalp defect, hypertelorism, pulmonary isomerism, common mesentery, hypospadias and sacral dimple, to cleft palate, corpus callosum agenesis, ventricular septal defect, and diaphragmatic hernia. On post-mortem X-rays, a delayed bone age was always observed. All the placentae were hypotrophic, and two exhibited vascular lesions, although there was no maternal hypertension. Chromosomal studies showed that the breakpoints were within the 4p16 band in three cases, the 4p15 band in one case, and the 4p14 band in one case. The deletion was de novo in four cases, and resulted from a paternal translocation in one case. This study emphasizes the importance of karyotyping all fetuses with IUGR, especially when the quantity of amniotic fluid is normal, and suggests the possibility of recognizing on US the particular phenotype of WHS in utero.


Screening for the apolipoprotein B-100 arginine3500-->glutamine mutation in patients with type III hyperlipoproteinemia. Forty-three patients with clinically and biochemically unequivocally defined type III hyperlipoproteinemia (HLP) were screened for the presence of the apolipoprotein (apo) B-100 arginine3500-->glutamine mutation. This receptor-binding defective apolipoprotein B variant is the cause of familial defective apo B-100 (FDB), an autosomal dominantly inherited disease, which leads to increased plasma cholesterol levels and premature atherosclerosis. Neither patient expressed FDB. It is concluded that the gene defect responsible for FDB is not involved in the pathogenesis of type III HLP.


Autosomal recessive gingival fibromatosis with distinctive facies. Hereditary gingival fibromatosis is a rare condition occurring as an isolated anomaly or as part of a genetic syndrome. The isolated or syndromic disorders are usually inherited in an autosomal dominant manner, but an autosomal recessive form has been suggested. We report on male and female siblings who have gingival fibromatosis in association with specific facial dysmorphism. Their phenotype is depicted and described to document this hitherto unreported autosomal recessive gingival fibromatosis syndrome.


Posterior scalp defects in Opitz syndrome. Another symptom related to a defect in midline development. In this report, we describe the presence of a large, posterior scalp defect as another, hitherto nonreported symptom related to a defect in midline development in a 1-year-old boy with Opitz syndrome.


The Simon nitinol inferior vena cava filter: preliminary experience in the UK. The Simon nitinol filter is one of a new range of inferior vena cava filters designed for percutaneous placement. It employs a thermal memory alloy allowing it to be introduced in a straight form via a 9F sheath when cool but transforming instantly into its predetermined filter shape at body temperature. It was placed rapidly and successfully in six patients via a femoral approach and one patient via an antecubital vein. The only complication was an asymptomatic IVC obstruction in one patient.


Thrombolysis of the occluded prosthetic graft with tissue-type plasminogen activator--technique, results and problems in 23 patients. Over a 12 month period all patients but one presenting to our hospital with occluded prosthetic grafts were treated by thrombolysis using local pulsed administration of tissue-type plasminogen activator (t-PA). There were 30 interventions in 23 patients but in one patient no thrombolytic was given after aspiration of pus from the graft. Thrombolysis was attempted in the remaining 29 procedures. 22/29 (76%) of these procedures were performed by direct puncture and catheterization of the occluded graft and in a further six (21%) access was from a non-occluded femoral artery or graft. In one case the graft was accessed surgically. Supplementary angioplasties were performed in 15 cases (52%). Complications requiring surgery occurred in four (14%) with a further seven minor complications. There were no deaths. A lower rate of complications occurred in the grafts entered by direct puncture. Thrombolysis was achieved in all but one case taking an average of only 2.5 h but was only maintained beyond the end of the procedure in 21/29 (72%). An underlying cause for occlusion was identified and treated where possible, e.g. haematological or clotting abnormalities or inflow or outflow stenoses. There was a high rate of reocclusion but with repeat procedures when necessary patency was maintained in 10/22 patients (45%) on follow-up at 1 to 12 months. The best results were obtained with lysis of occluded femoro-femoral crossover grafts.


Tuberculosis in HIV positive patients in South Africa: a comparative radiological study with HIV negative patients. The radiological appearances of active tuberculosis in human immunodeficiency virus (HIV) positive patients was reviewed. A study group of 61 Black HIV positive patients and a control group of 50 Black HIV negative patients were analysed. The chest radiographs of the HIV seropositive group showed a significantly higher percentage of lymphadenopathy (50%), pleural effusions (38%) and miliary (8%) or interstitial patterns (11%), as compared with those in the seronegative group (8%, 20%, 0% and 4% respectively). Cavitation (38%) and atelectasis (31%) were less common in the seropositive group than in the seronegative group (82% in each category). Thus in an endemic TB environment an awareness of this difference in appearances will allow the radiologist to alert the referring clinician to the possibility of concomitant HIV seropositivity.


Ultrasonography in traumatic splenic rupture. Ultrasound (US) findings and their significance for the clinical outcome were studied in a series of 56 patients hospitalized with a diagnosis of splenic trauma. US was abnormal in 50 cases (89.3%) on admission, revealing intraperitoneal fluid in 41 (73.2%) and a splenic parenchymal injury and/or subcapsular haematoma in 35 (62.5%). US was abnormal in 24/25 patients undergoing urgent surgery, 23/26 undergoing successful non-surgical treatment and 2/5 patients undergoing delayed surgery within 1 to 3 days of a repeat US (abnormal in all five). The presence of intraperitoneal haemorrhage preoperatively was shown accurately by US in 29 cases (96.7%), and the splenic origin of the haemorrhage in 19 (63.3%). Repeat US was of most value for confirming the diagnosis by demonstrating splenic lesions not visible initially. The need for laparotomy could not be predicted on the basis of the US findings alone, however.


Ultrasound diagnosis of testicular tumours presenting as epididymal disease. A prospective study of 1494 new referrals for scrotal ultrasound was performed over a 5 year period. In 610 patients referred with a clear clinical diagnosis of epididymal disease, and no clinical suspicion of malignancy, ultrasound diagnosed unsuspected testicular tumours (seven malignant, one benign) in eight patients. In this series one case was counted as false negative for ultrasound diagnosis of tumour, as tumour was the differential diagnosis and not the primary diagnosis. No other patients diagnosed as having benign disease by ultrasound have subsequently been shown to have malignant disease. Sensitivity and specificity of ultrasound for the diagnosis of testicular malignancy in this series is 98% and 99.8% respectively. It is concluded that all patients with scrotal symptoms should be examined by ultrasound in order to achieve the maximal clinical benefit from the early diagnosis of testicular tumours. The implications of this are discussed.


Longitudinal stress fracture of the tibia: two cases. Stress fracture of the tibia occurs in individuals who subject their extremities to repeated trauma. They can arise in otherwise healthy bone that is subjected to excessive loads (as in the marathon runner) or in abnormal bone that is subjected to minor loads (as in osteoporosis). These fractures may be anywhere along the tibial shaft and tend to be either transverse or oblique in orientation. We report two cases of stress fracture that ran longitudinally in the distal one third of the tibia. Both patients were healthy and did not describe excessive physical activity prior to fracture. Both describe a repetitive twisting action prior to fracture. Computed tomography was diagnostic in both cases following abnormal bone scans and normal plain radiographs. This unusual pattern of fracture has been reported on only four occasions in five patients in the literature.


Case report: percutaneous transluminal angioplasty of the inferior mesenteric artery in the treatment of chronic mesenteric ischaemia. Percutaneous transluminal angioplasty (PTA) of the superior mesenteric artery (SMA) and coeliac axis (CA) is a well recognized form of treatment for patients with chronic intestinal ischaemia and carries a low morbidity and mortality. We report a case where PTA of the inferior mesenteric artery in the presence of occluded SMA and CA proved both feasible and highly effective in abolishing the patient's symptoms.


Case report: pneumatosis intestinalis occurring in association with cryptosporidiosis and HIV infection. We report a case of pneumatosis intestinalis (PI) occurring in association with cryptosporidiosis in a patient documented as being HIV-seropositive. Chest and abdominal radiographs taken 2 months previously were normal and the patient did not have any evidence of gastrointestinal infection at that time. The case was complicated by cyst rupture resulting in a pneumoretroperitoneum and pneumomediastinum. The association of pneumatosis and cryptosporidiosis has not been previously reported.


[The physiopathological aspects and new therapeutic approaches in cardiac-circulatory failure]. Pathophysiological mechanisms are reviewed concerning the onset and the perpetuation of the clinical features of congestive heart failure. This syndrome is a severe condition of poor prognosis and bad life quality which in the last decades has reached, in the western industrial countries, the highest levels of general mortality, mainly due to the high prevalence of hypertensive and ischaemic myocardiopathies in the last years. To the clinical features of heart failure mainly contributes a deregulation of the physiological compensatory mechanisms contemporarily and concurrently activated following the primary deficiency of the heart pump function. In physiological conditions, following the myogenic adapting mechanisms reflex mechanisms intervene, activated by intracardiac and aortic and carotid-sinus mechanoreceptors following the variations in intracardiac and intravascular pressure and generally evoking negative feed-back effects. In patients with heart failure arterial high pressure mechanoreceptors respond to the reduction in effective arterial pressure thus provoking a deactivation of the tonic inhibition on the sympathetic cardiovascular drive. This leads to an activation of peripheral and renal vasoconstrictor tone, to a raised medullary catecholamine incretion, to heart rate and inotropism stimulation, and to an increase in pituitary gland ADH production as well as to an activation of renin-angiotensin-aldosterone system (RAAS). Analogous vasoconstrictive, and sodium and water retentive effects can be elicited by endothelin produced by endothelial cells and found in high plasma levels in CHF. These excitatory effects, leading to a rise in systemic vascular resistance and to hydro-electrolytic retention with volume expansion, are not efficiently counteracted by the opposite effects triggered by cardiopulmonary vagally mediated mechanoreceptors activated by the raised cardiac filling pressure and leading to sympathetic nervous inhibition, peripheral and renal vasodilation, ADH and RAAS inhibition. Analogous effects should be provoked by the raised production, due to enhanced heart wall distension, of atrial natriuretic factor leading to vasodilation, natriuresis and diuresis. Reduced sensitivity of cardiopulmonary baroreceptors and lowered production of ANF due to structural cardiac changes could represent, according to most opinions, the main factors responsible for the prevailing sympathetic activation and hydro-saline retention in CHF. The activation of cardiopulmonary sympathetic positive-feed back afferents, could be also involved in the characteristic alteration of the vago-sympathetic balance in heart failure. The persistent reduction in heart pump function could lead to the instauration of vicious circles among the various regulatory systems and create an overcompensation condition.(ABSTRACT TRUNCATED AT 400 WORDS)


[Preclinical changes in left ventricular function in obesity. An angioscintigraphic study]. Equilibrium pool scintigraphy was performed in 11 obese subjects (BMI 34 +/- 2) and in 14 normal control subjects. Temporal and spatial smoothing of the data was then performed followed by time-activity curve generation using a semiautomatic second derivative edge-detection algorithm. The increase in counts during the first third of diastole divided by the total change in number of counts during diastole was determined as the one-third filling fraction. This index of diastolic filling was significantly decreased in obese subjects as compared to the control group. These findings indicate that diastolic abnormalities may be an early finding in obesity-linked heart disease, occurring in the presence of normal systolic function (E.F. = 65 +/- 5%).


[The clinical and hemodynamic effects of propionyl-L-carnitine in the treatment of congestive heart failure]. In order to evaluate the clinical and hemodynamic effects of propionyl-L-carnitine (PLC) a randomized, double-blind study versus placebo was performed in 50 patients of both sexes, between 48 and 69 years of age, affected by mild-moderate congestive heart failure. All patients participating in said study were on digitalis and diuretic treatment. 25 of these belonged to the control group, while the other 25 were treated with an oral dose of 1 g b.i.d of propionyl-L-carnitine. At the end of six months of treatment maximum exercise time on the treadmill increased 11.1% after 90 days and 16.4% after 180 in the group treated with PLC. From a hemodynamic standpoint, after 30, 90 and 180 days the ejection fraction increased by 7.3%, 10.7% and 12.1%. At the same time, moreover, the systemic vascular resistances were reduced by 14.9%, 20% and 20.6%. In the patients treated with placebo, however, the above-mentioned parameters showed no significant variation. Finally, no unexpected events or toxic effects were observed in any of the patients in either group. As a consequence of these results it is possible to affirm that propionyl-L-carnitine, due to its clinical and hemodynamic effects, represents a drug of notable therapeutic interest in patients with congestive heart failure, in whom it may be usefully combined with the usual pharmacological therapy.


[A comparison between intraurethral echography, computed tomography and magnetic resonance in the staging of bladder tumors]. The purpose of our study was to assess the utility of CT and MRI in the staging of bladder carcinoma. The overall accuracy of MR is in the range of 66 to 85%. T2 weighted and post-Gadolinium T1 weighted images allow one to differentiate T1-T2 from T3a type of neoplasms. Perivesical fat invasion is well shown with T1w images while pelvic wall invasion is better seen on T2w--images. The overall accuracy of CT ranges from 64 to 92%. CT cannot distinguish stage T1 from stage T3a tumors CT is accurate for demonstrating perivesical fat invasion. In the assessment of lymph node metastases CT and MRI have low sensitivity but high accuracy. Trans-urethral sonography is more accurate than CT and MRI in the staging of parietal invasion and it permits the differentiation between T1, T2 and T3a stages even though the distinction between T2 and T3a type of tumors is not always possible. Trans-urethral sonography is not useful in assessing extravesical extension and lymph node metastases. In summary, trans-urethral sonography is the method of choice for evaluating parietal invasion. CT and MR are very accurate for evaluating perivesical fat invasion and are also quite accurate for evaluating lymph nodes. MRI is superior to CT in distinguishing tumors limited to superficial muscle from those that invade deep muscle. MRI can also be helpful in distinguishing the tumor from fibrosis and edema.


[Intestinal volvulus in pregnancy].

[Intestinal volvulus in pregnancy]. Intestinal occlusion is a rare pathologic event during pregnancy occurring mostly in the second and third trimenon when increased volume of the uterus and the consequent displacement of abdominal organs cause complications of pathologies which would otherwise escape notice, such as intestinal adhesions, to become manifest. Diagnosis is difficult for a number of reasons. Vomiting during the first trimenon and mild abdominal pain during the third are often neglected or considered to be part of the normal course of pregnancy; pain is sometimes referred to atypical sites due to the displacement of abdominal organs; in other cases, the high endorphin tonus is apt to reduce the customary defence reaction. All this should not cause time to be lost, and whenever intestinal occlusion is suspected all the necessary diagnostic procedures must at once be carried out and appropriate therapy must speedily be started so as to reduce the risk of mortality and morbidity for mother and fetus. Management of ileus in pregnancy is identical to that for the non pregnant woman, except for the need to empty the uterus in cases in which it prevents treatment or if the fetus has reached a sufficient degree of pulmonary maturity. The paper describes a case of ileal volvulus and revisits the literature analyzing the diagnostic and therapeutic options suggested.


[Cardiac and renal sodium-modulating hormones in juvenile arterial hypertension. The physiopathological aspects and therapeutic results of a trial at the Policlinico Militare Celio in Rome]. Sodium balance plays a primary role in blood pressure regulation. Atrial natriuretic peptide, a recently discovered natriuretic substance, seems to participate in renal sodium handling, but its behavior in essential hypertension has not been fully defined. In our study, to avoid the "contamination" of factors other than hypertension, we evaluated the plasma levels of atrial natriuretic peptide in young men at military draft age. Our main results showed that plasma atrial natriuretic peptide levels are higher in young hypertensives with low plasma renin activity and low urinary excretion of active kallikrein. The influence of a positive genetic background for essential hypertension on plasma atrial natriuretic peptide levels was also investigated. Our data showed slightly elevated levels of the atrial hormone in young normotensives with a family history of hypertension.


[The efficacy and tolerance of heparin-calcium at low doses in postinfarct ischemic cardiopathy]. The above study was undertaken in order to evaluate the efficacy and tolerability of low dose calcium heparin for postinfarct ischemic heart disease (CIPI). In particular, the incidence was checked of: cardiovascular death, reinfarction, angina pectoris, TIA or RIND, stroke, arterial thromboembolism, venous thromboses, heart failure, complex ventricular arrhythmias, silent myocardial ischemia. Eighty patients with CIPI were divided into two groups similar for age, sex, physical features, cardiovascular risk factors, site of infarction, length of hospitalization, complications during hospitalization, clinical and instrumental findings at discharge, concomitant pathology. Upon discharge, patients were randomized into group 1 for traditional treatment and group 2 which in addition received 12,000 U calcium heparin s.c. every 24 h. After 12 months, during which patients were submitted to periodical laboratory and instrumental (standard and dynamic ECG, echoG) evaluation, group 2 had significantly fewer cardiovascular events than group 1 both as to overall number of events and as to number of events per individual patient. Especially, silent myocardial ischemia and ventricular arrhythmias were less frequent in group 2 patients and these two events, especially if coincident, are known to have severe prognostic implications. The efficacy of low-dose calcium heparin must be attributed to the enhancement of physiological antithrombotic mechanisms with compensation of blood clotting disorders that are fairly frequent in CIPI patients. Long-term s.c. administration was well tolerated.


[Atherosclerosis: the risk factors].

[Atherosclerosis: the risk factors]. A group of 196 outpatients among whom 112 non-insulin-dependent diabetics were divided into 4 subgroups according to whether they had vascular disorders or not. For statistical evaluation by means of correlation coefficient and chi-square test both risk factors (smoking, family history, arterial hypertension, BMI) and laboratory values (total and HDL cholesterol, triglycerides, fibrinogen, HbA1c, factor VIII, PF4, BTG) were taken into account. Our findings confirm the relevance of risk factors and the need for diabetic patients to be metabolically well balanced; PF4, BTG, and factor VII were normal in all patients which suggests that these are not suitable, as far as the present study is concerned, to be considered markers of vascular disorders. An interesting correlation was found between these factors and serum triglycerides, especially in the subgroup of diabetics with vascular disorders. An interesting finding was the increase of fibrinogen in subjects with vascular disorders especially in non-diabetics.


[Ketanserin, an antagonist of 5-HT2 serotoninergic receptors and free-radical scavenger]. The authors describe an original clinical method of auscultatory percussion which is easily performed and reliable for bedside evaluation of tissue Co Q10, tissue acidosis, endothelial damage, free radicals and microcirculatory functional reserve. They report data observed in 25 arteriosclerotic patients treated with ketanserin which show the drug to be an excellent scavenger of free radicals.


[Captopril versus placebo in the prevention of hemicrania without aura. A randomized double-blind study]. Endogenous opioids are known to be involved in the pathophysiology of idiopathic headache. In fact, decreased levels of enkephalin (E) or endorphin (BE) during headache attacks might be a marker of an altered pain-inhibiting system of central neurotransmission or could be secondary to alterations of brain circulation that often occur during the headache crisis. Recently, captopril (C) has been shown to be apt to restore the availability of endogenous opioids, to improve cerebral blood flow via the inhibition of both the cerebral and systemic renin-angiotensin system or of catecholamine release. It has also been reported to be able to restore the nociceptive-antinociceptive balance through an increase of serum kinin (K) or prostaglandin (Pr) levels. In the present study, the efficacy of C in reducing the frequency (F), duration (D), or severity (S) of headache paroxysm were investigated in a double blind trial vs. placebo (P). Twenty-six subjects (5 males and 21 females; mean age 37 +/- 11 years) suffering from idiopathic headache at least for one year have been allocated to treatment with C (25 mg three times/day) or P according to a double-blind randomized protocol for 4 months. The effects of C or P have been evaluated with Migraine Index Correct, related to changes in F, D or S of headache attacks. Our results indicate that C is effective in reducing F, D or S in subjects with idiopathic headache.


[Median-term (4 months) treatment with glibenclamide + metformin substituting for glibenclamide + fenformin lowers the lacticemia levels in type-2 diabetics (NIDDM)]. 60 NIDDM patients, mean age (68 +/- 3 years), BMI (25 +/- 5.1 kg/m2), fasting blood glucose (FG) (170 +/- 10 mg/dl), mean daily blood glucose (MDBG) (180 +/- 10 mg/dl), daily glycosuria (GLU) (15.6 +/- 9 g/24 hours), HbA1c (7.9 +/- 0.6%), basal (1.2 +/- 0.2 ng/ml) and stimulated (3.89 +/- 1.3 mg/ml) C peptide (CP) treated by ASS (7.5 +/- 75 mg), after a strict 4 months follow-up period, were assigned to G + M treatment (7.5 +/- 1.500 mg) during a 4 months period. During G+M treatment FG (171 +/- 13 at t0 to 165 +/- 11 mg/dl: p < 0.01 at t4) varied significantly. MDBG (180 +/- 10 at t0 to 175 +/- 12 mg/dl at t4:p < 0.05), GLU (16 +/- 9 at t0 to 11 + 6 g/24 hours at t4; p < 0.01), HbA1c (8.1 +/- 0.4 at t0 to 7.6 +/- 0.3% at t4; p < 0.01). Basal CP remained unchanged in G+M period and varied significantly during ASS period (1.3 +/- 0.3 ng/ml at t4; p < 0.01) and stimulated CP (unchanged during ASS) was reduced during G+M (4.19 +/- 0.4 to 4.04; p < 0.05). Highly significant variations were observed for LAC (28.4 +/- 2.1 at t0 to 14.9 +/- 0.6 mg/dl: p < 0.01 during G+M treatment). G+M therapy was found to be more effective and safer than ASS therapy in regard to glucose metabolism and lactate production in a selected group of NIDDM patients.


[Computed tomography and magnetic resonance in the TNM staging of pulmonary carcinoma]. On the basis of a review of the literature and of the authors' personal experience, the usefulness was evaluated of CT and MR for the staging of lung carcinoma. Neither method was found to be useful for diagnosis; as to staging, neither is capable to distinguish between simple adhesion and infiltration of adjacent structures by the tumor. As compared to CT, MR has the advantage of showing many layers and better contrast resolution but spatial resolution is poorer. MR was superior to CT for the study of hilar lesions (easily differentiated from vessels) and for those involving the upper pulmonary sulcus. The accuracy of evaluation of the N parameter was the same for both methods whereas for the M parameter RM was more accurate than CT. Considering the wide margins for technological improvement of MR, a more important role for this method compared to CT can be hypothesized.


Influence of area of application of allergen on sensitization in contact dermatitis. There are at least 2 quantitative variables when applying allergens to obtain sensitization: the absolute amount of allergen and the surface concentration. This review analyzes the limited studies on surface concentration and determines surface area threshold levels for the allergens documented in the literature.


Photosensitivity to piroxicam: absence of cross-reaction with tenoxicam. We studied 2 groups of patients. One group of 10 patients had a photosensitive eruption to piroxicam. Another group of 24 patients had positive patch test reactions to thimerosal and thiosalicylic acid and had never taken piroxicam or tenoxicam. Patients were patch tested with thimerosal 0.1% pet., thiosalicylic acid 0.1% pet., salicylic acid 2.0% pet., piroxicam 1 and 5% pet. and tenoxicam 1 and 5% pet. Photopatch tests were also performed with piroxicam and tenoxicam. All 10 patients with photosensitivity to piroxicam had positive patch tests to thimerosal and thiosalicylic acid and 9 of them had positive photopatch tests to piroxicam. 20 out of 24 patients with positive patch tests to thiosalicylic acid also had positive photopatch tests to piroxicam. All the patients tested with salicyclic acid were negative. Out of the 29 patients with positive photopatch tests to piroxicam, none reacted to tenoxicam. In countries with a high incidence of contact sensitivity to thimerosal/thiosalicylic acid, the use of piroxicam should be avoided and replaced by tenoxicam, a drug without reported photosensitivity.


Dithranol allergy: fact or fiction?

Dithranol allergy: fact or fiction? A case of a psoriatic patient allergic to dithranol and coal tar is described. It is suggested that dithranol 0.001% pet. is a suitable concentration to test for dithranol allergy, as higher concentrations may produce irritant reactions. The literature on dithranol allergy is reviewed and the frequent simultaneous reactions to dithranol and coal tar discussed.


Changes in transepidermal water loss and cutaneous blood flow during the menstrual cycle. This study quantified irritant susceptibility and blood vessel reactivity in normal women over the course of the menstrual cycle. Such alterations were studied by observing vasodilation from topical application of methyl nicotinate (MN) on the following days of the menstrual cycle: (i) the day of putative maximal estrogen secretion; (ii) the day of maximal progesterone secretion; (iii) the day of minimal estrogen/progesterone secretion. These responses were evidenced by changes in the following dose response characteristics: the initial response (IR), the peak response (PR) and the area under the curve (AUC). Baseline laser Doppler velocimetry (LDV) blood flow values and transepidermal water loss (TEWL) values on normal skin were also obtained. No significant differences existed for any of the dose-response characteristics (IR, PR, AUC) when the values for the 3 testing days were compared to one another. Significant differences did exist for baseline TEWL values when comparing the day of maximal estrogen secretion to the day of minimal estrogen/progesterone secretion. TEWL was higher on the day of minimal estrogen/progesterone secretion as compared to the day of maximal estrogen secretion on both back (p = 0.037) and forearm (p = 0.021) sites, suggesting that the skin barrier function is less complete on the days just prior to the onset of the menses as compared to the days just prior to ovulation. Significant differences in baseline blood flow also existed for the day of maximal estrogen secretion as compared to the day of maximal progesterone secretion, with higher baseline blood flow recorded on the day of maximal progesterone secretion on both the back (p = 0.021) and forearm (p = 0.009) sites.


Permeation of chromium salts through human skin in vitro. Chromium permeation studies were performed on full thickness human skin in diffusion cells. All samples were analysed for the total chromium content by graphite furnace Zeeman-corrected atomic absorption spectrometry. Some samples were analysed by an ion chromatographic method permitting the simultaneous determination of Cr(VI) and Cr(III) as well. The amounts of chromium found in all skin layers were significantly higher when potassium dichromate was applied to the skin compared with chromium chloride or chromium nitrate. Chromium could only be detected in the recipient phase after application of the dichromate solution. Chromium skin levels increased with increasing concentrations of applied chromium salts up to 0.034 M Cr. The amount of chromium in recipient phase and skin layers increased with increasing pH when the applied solution contained potassium dichromate. This was ascribed to a decreased skin barrier function of the skin. The amount of chromium found in all skin layers after application of chromium chloride decreased with increasing pH due to lower solubility of the salt. The % of chromium found in the recipient phase as chromium(VI) increased with increasing total chromium concentration indicating a limited reduction ability of the skin in vitro.


Occupational dermatitis in the aircraft industry: 35 years of progress. A comparison of the occupational dermatitis occurring in the same aircraft factory during 2 separate decades, 1955-1965 and 1981-1990, is presented. Subungual pulpitis is highly specific to this industry, because of the handling of resins and sealing agents. The number of cases dropped from 122 to 40, in accordance with progress in preventive medicine and technological changes in the factory. Irritant contact dermatitis nevertheless remained appreciable, while allergic contact dermatitis greatly decreased.


FDA requirements for nonclinical testing of contraceptive steroids. Written guidelines for the preclinical testing of contraceptive steroids have not been revised since 1968 despite the fact that many important changes have been implemented by the FDA's Division of Metabolism and Endocrine Drug Products. This paper describes the new preclinical testing requirements and the rationale for their implementation.


Acceptability of a new intravaginal barrier contraceptive device (Femcap). A comprehensive questionnaire to assess acceptability was sent to 106 participants (and their partners) in a study on the safety and effectiveness of the Femcap. Participants were asked to rate their satisfaction with various aspects of the method, and were also asked about complaints such as vaginal infections, urinary tract infections, or other irritation. Eighty-one percent of the study sample either returned the mailed questionnaires or completed telephone interviews. Results were encouraging in that none of the study subjects or their partners reported any discomfort, trauma, or interference in sexual spontaneity with the cap. Vaginal irritation and infections were infrequently reported. The feature best liked by most participants was the absence of hormones associated with the method; the feature least liked was removal of the device. The Femcap may be an acceptable alternative to currently available barrier contraceptive devices.


A comparison of open-end versus closed-end vasectomies: a report on 6220 cases. This study was done to determine if there was a difference in results when both vas ends were closed or when the prostatic end was closed and the testicular end left open. The author performed 6220 vasectomies between June 1, 1972 and June 1, 1992. The first series consisted of 3081 vasectomies in which both ends of the vas deferens were closed. The second series consisted of 3139 vasectomies in which the testicular end of the vas deferens was left open while the prostatic end only was closed. No portion of the vas was excised. Congestive epididymitis was diagnosed in 6% of cases utilizing closed-end vasectomy and 2% of cases where the open-end vasectomy was performed. Open-end vasectomy is recommended because the incidence of congestive epididymitis is reduced.


The immobilization of all spermatozoa in vitro by bitter lemon drink and the effect of alkaline pH. This study investigated the effects of increase in temperature and in pH of Coca-Cola, Afri-Cola, Pepsi-Cola and Krest bitter lemon drinks ("soft drinks") produced in Nigeria on the in vitro motility of spermatozoa. Semen was collected from 7 men, average age 28 years, of proven fertility, after 5 days' abstinence from sexual intercourse. The temperature and pH of the drinks were adjusted from 22 degrees C (room) to 37 degrees C, and pH 2.4 (acid) to 7.5 (alkaline), respectively. The mean % motility of spermatozoa in the adjusted and in the unadjusted drinks was compared for significant differences at the 1% level using the student's t-test. The results showed no significant differences in mean % motility in the drinks at 22 degrees C and at 37 degrees C. The mean % motility in all the drinks, except Coca-Cola, was significantly greater at alkaline than at acid pH; for Coca-Cola, motility was significantly greater at acid than alkaline pH. Of the drinks, Krest bitter lemon (unadjusted) immobilized all spermatozoa within 1 minute of addition. i) alkalinity decreases the spermicidal action of all drinks except Coca-Cola, and ii) Krest bitter lemon may achieve very high efficacy if used as post-coital douche, especially in the impoverished, densely populated Third World.


Plasma prolactin in relation to menstrual cycle phase, oral contraceptive use, arousal time and smoking habits. The study was designed to investigate if modern low dosage combined oral contraceptives were associated with changes in plasma prolactin levels in healthy nulliparous women aged 19-25. Plasma prolactin was not significantly correlated to oral contraceptive use, nor to smoking habits. Plasma prolactin was, however, significantly negatively correlated to time since awakening. A significant two-way interaction on prolactin was also seen between smoking and present oral contraceptive use. In our material the mean values of plasma prolactin were higher in the follicular phase than in the luteal phase, although not significantly.


Descriptive epidemiology of induced abortion in Italy 1979-1990. Trends of induced abortions in Italy from 1979 to 1990 have been analysed in terms of overall age-standardised rates and ratios, and according to various characteristics of the women. Temporal trends were characterised by an increase of rates from 11.3/1,000 women aged 15-49 in 1979 to 16.5 in 1982 and then followed by a steady decrease to 11.1/1,000 in 1990. Ratios increased from 228/1,000 livebirths in 1979 to 389 in 1984 and then declined to 286 in 1990. Thus, the overall declines from the early 1980's to 1990 were 33% in rates and 26% in ratios. The same pattern was followed by rates and ratios in various age groups. The highest rates were observed in women aged 25-29 years (27.0/1,000 in 1982 and 17.9/1,000 in 1988) and 30-34 years (25.5/1,000 in 1982 and 19.0/1,000 in 1988), and the lowest ones were in women aged 45-49 (1.0/1,000 in 1982 and 0.8/1,000 in 1988). Ratios reached the highest values in 1984 in most age groups, particularly in women between 40 and 49 years and under 20 years. Ratios increased constantly with number of previous deliveries. At all levels of education, a decline in rates has been observed since 1982, but in the highest educational level, the decline started earlier and was more substantial. The decline in rates among more educated women from 1982 to 1987 was 36%, but it was only 9% among less educated ones. Scope for further preventive action is indicated by the differences according to education and by the slowing down of the decline in the more recent years. This preventive intervention should be focused particularly to women of lower educational level and to those with two or more births.


Dihydrospirorenone (ZK30595): a novel synthetic progestagen--characterization of binding to different receptor proteins. Dihydrospirorenone (6 beta, 7 beta, 15 beta, 16 beta-dimethylen-3-oxo-17a-pregn-4-en-21, 17-carbolacton) is a new type of progestin with no other agonistic activities, in particular no estrogenic, androgenic or glucocorticoid activity. Dihydrospirorenone is a potent aldosterone antagonist 8 times as potent as spironolactone and antiandrogenic (0.3 times cyproterone acetate). The aim of the present study is to make a broad characterization of dihydrospirorenone at the receptor level and to discuss the results in comparison to those of established progestins. Kinetic studies of 3H-dihydrospirorenone uptake show a rapid increase in the amount of specific binding during the first three hours. The dissociation of 3H-dihydrospirorenone from the cytoplasmic human uterine progesterone receptor, measured by displacement of labeled steroid with dextran-coated charcoal treatment at 4 degrees C at various times, showed a monophasic or one-component, first order dissociation curve like progesterone. Sucrose density gradient centrifugation of the 3H-dihydrospirorenone-labeled myometrial cytosol showed that the dihydrospirorenone binding components sedimented in the 4S and 8S region which is typical for the progesterone receptor under low salt conditions. The high binding affinity of dihydrospirorenone to the binding sites of the mineralocorticoid receptor of rat kidney with an RBA value of 230% compared to aldosterone is remarkable. This reflects the strong antimineralocorticoid activity of this compound which was evaluated in adrenalectomized rats. Furthermore, competitive studies indicated that dihydrospirorenone also displays high affinity for the androgen and some affinity for the glucocorticoid receptors but no measurable affinity for the estrogen receptor.


Return to fertility after removal of a levonorgestrel-releasing intrauterine device and Nova-T. In a European randomized multicenter study, the efficacy and safety of an intrauterine contraceptive device releasing 20 microgram levonorgestrel/24 hours (LNG-IUD) have been evaluated and compared to the Nova-T. Because the LNG-IUD has a strongly suppressive effect on the endometrium and in some women affects ovarian function, the return to fertility after removal of the IUD was studied. Two-hundred-nine women (71 in the Nova-T and 138 in the LNG-IUD group), who had their IUDs removed because of planning pregnancy, were followed at least 24 months or until termination of pregnancy. For the Nova-T, the cumulative conception gross rate was 71.2/100 women after 12 months (79.7 after 24 months) and for the LNG-IUD 79.1 (86.6 after 24 months). The difference between the devices is not statistically significant, and in spite of the endometrial suppression during use of LNG-IUD, there is no delay of return to fertility and in both groups 96% of the pregnancies occurred during the first year after removal of the device. Eighty-four % of the pregnancies in the Nova-T group and eighty-six % in the LNG-IUD group ended in live births. The results suggest that the endometrium recovers quickly, normal ovulations are established and the fertility seems to be unaffected after use of an LNG-IUD.


Storage mites.

Storage mites. The interest in allergy to storage mites has increased over the past few years. Storage mites feed on a variety of substances and they can be found in many different products such as grain, flour, hay and straw, but also in house dust samples. The more common genera are Lepidoglyphus, Tyrophagus, Glycyphagus, Acarus and Blomia. Several species of storage mites have been shown to cause IgE-mediated sensitization among rural workers, who to a varying extent develop asthma, rhinitis or conjunctivitis when exposed to barn dust. However, a number of studies have reported on sensitization to storage mites also among urban people, indicating that sensitization is not restricted to individuals with occupational exposure. Regarding the allergenic relationship between storage mites and house dust mites, there appears to be a limited allergenic cross-reactivity between the two species. However, both species also possess their own unique allergens. Further research on identification and characterization of storage mite allergens and their cross-reactivity is required to understand the complexity of epitopes and allergens.


A review of recent immunochemical studies of Blomia tropicalis and Euroglyphus maynei allergens. Exposure to mites other than Dermatophagoides spp., particularly Blomia tropicalis and Euroglyphus maynei, has been increasingly recognized as a cause of asthma. Positive skin tests and serum IgE antibodies to B. tropicalis have been reported in asthmatic patients from several areas of the world, including São Paulo (Brazil), Hong Kong and Tampa (Florida, USA). Analysis of B. tropicalis extracts showed undetectable levels of the major Group I and Group II Dermatophagoides spp. allergens. Immunoabsorption experiments showed that most of the IgE antibodies to B. tropicalis (approximately 70%) reacted with species-specific allergens. Murine monoclonal antibodies to B. tropicalis could present antigens that were recognized by human IgG antibodies. Sensitization to E. maynei has been reported in Europe, North and South America and Australia. Analysis of four different E. maynei extracts by ELISA and RIA showed that E. maynei produces an allergen that is antigenically related to Dermatophagoides Group I allergens. The amino acid sequence of this allergen (Eur m I) has recently been reported. Further identification and purification of B. tropicalis and E. maynei allergens is required to develop specific assays for measuring these allergens in dust samples. This will make it possible to investigate the relationship between exposure to B. tropicalis or E. maynei and the development of sensitization and allergic disease.


Epidemiology of dust-mite-related disease. For many years it has been suggested that allergens derived from the house dust mite played a major role in the pathogenesis of asthma, eczema and some cases of allergic rhinitis. Recently, house dust mite allergens have been purified and specific immunoassays developed with which exposure to house dust mites and their allergens can be more easily determined. Using these tools, epidemiological studies have provided confirmatory evidence that not only is house dust mite exposure associated with the majority of cases of asthma in children and young adults, but that it is causally related to the development of asthma.


Water balance and humidity requirements of house dust mites. The house dust mites, Dermatophagoides farinae, D. pteronyssinus and Euroglyphus maynei, are prevalent in homes in humid geographical areas throughout the world. These mites thrive in humid environments in human dwellings where there is no liquid water to drink. However, their bodies contain 70-75% water by weight, which must be maintained in order to reproduce. Their primary source of water is water vapor which is actively extracted from unsaturated air. At relative humidities above 65-70%, adequate amounts of water can be extracted from unsaturated air to compensate for that lost by all avenues. Active uptake is associated with ingestion of a hyperosmotic solution which is secreted by the supracoxal glands. Active mites do not survive longer than 6-11 days at RHs < or = 50%. They survive extended dry periods by forming a desiccation-resistant protonymphal stage which can survive for months at RHs below the critical humidity for active stages. Feeding rate and allergen production is directly influenced by RH. Mites feed, multiply, and produce more fecal matter at higher RHs than at lower ones.


Molecular polymorphisms of house dust mite allergens. Previous studies from this laboratory have described the primary amino acid sequences of the group I and group II allergens from Dermatophagoides pteronyssinus and D. farinae. This report concentrates on polymorphisms of allergens within a species. Firstly, four cDNA clones of Der fII produced by polymerase chain reaction have been sequenced and are compared to the sequences published previously by ourselves and others. Although the sequences come from different sources, Australia and Japan, the overriding conclusion is one of similarity, with only two possible non-conservative changes in the six sequences. The nucleotides were also very conserved including the 3' untranslated regions, although some non-coding differences could be found which may provide a genetic marker. Experiments are reported to help define the group III D. pteronyssinus allergens. Previous studies have characterised the group III of D. farinae as a Mr 29-kDa molecule which can be defined by monoclonal antibodies. A Mr 17-kDa molecule of D. pteronyssinus has been reported with an almost identical N-terminal sequence. Here it is described that Der fIII isolated from different preparations of spent mite media by affinity chromatography have predominantly Mr 32-, 28- and 21-kDa forms which vary in degree from batch to batch. 83% of adults and 38% of children react with the preparation by radioimmune dot-blot. The difference between the children and adults is statistically significant and reactivity can be to at least the 32- and 28-kDa form. Antisera produced in mice against the Der fIII react to D. pteronyssinus mite extract by Western blotting primarily to a 32-kDa moiety, but also 28- and 21-kDa forms in some extracts.


Allergen exposure and control.

Allergen exposure and control. Allergens produced by the house dust mites (family Pyroglyphidae) are probably the single most important allergens associated with asthma world wide. If exposure to these allergens in houses could be sufficiently reduced, then asthma symptoms may be markedly reduced and even prevented from being initiated. Only about half of the many attempts to reduce mite allergens in houses have shown any clinical benefit. One reason may be that exposure was not reduced enough--however exposure to mite allergens has never been measured in any trial. This review summarises previous allergen control trials and then provides an outline of allergen exposure, including the nature of exposure, the analytical methods available and the recognised risks of allergen exposure. This provides a perspective to evaluate the individual methods used to kill mites and to reduce exposure to the allergens. The object is to provide a framework to improve and develop allergen avoidance as an effective component of asthma management.


How relevant are house dust mite-fungal interactions in laboratory culture to the natural dust system? Both house dust and house dust mites Dermatophagoides pteronyssinus contained a wider range of fungi than laboratory mite cultures. In total, nine species of fungi were isolated from D. pteronyssinus in house dust, and these included three xerophilic species (Eurotium amstelodami, Aspergillus penicillioides and Wallemia sebi) commonly found in laboratory cultures of D. pteronyssinus. It is concluded that mites do interact with a similar range of fungi in natural dust and in laboratory culture, but that the diversity of fungal species in the laboratory is reduced and the density of individual fungal species in culture exceeds that of house dust. In a second experiment, dust samples were incubated at room temperature with 75% relative humidity. The diversity of fungi invariably declined from up to 13 genera to the few species recorded in laboratory culture. This suggests that the dominance of xerophilic fungi in laboratory mite rearings is mediated primarily by low relative humidity, and the exclusion of air-borne spores.


The colonisation of new houses by house dust mites (Acari: Pyroglyphidae). House dust mites, Dermatophagoides species (Acari: Pyroglyphidae), produce allergens, known for the provocation of asthma and other allergic reactions. To determine the time needed for complete colonisation of a new house by house dust mites, dust samples were collected from carpets of houses varying from 2 weeks to 2 years in age. In contrast to the expectation, no relation was found between age of the houses on the one hand and average levels of mite-allergens Der pI and Der pII and mite numbers on the other. However, presence of dogs appeared to be positively related to allergen levels. Furthermore, carpets in bedrooms appeared to contain more allergens than carpets in living-rooms. Finally, the age of the mattress was not related to allergen levels of bedroom floors.


Ultrastructure of the reproductive system of the house dust mites Dermatophagoides farinae and D. pteronyssinus (Acari, Pyroglyphidae) with remarks on spermatogenesis and oogenesis. Several parts of the reproductive system of both sexes of Dermatophagoides farinae and D. pteronyssinus are investigated and compared by light-, scanning electron-, and transmission electron microscopy. New techniques have been employed for scanning of the internal structures of these mites. The male reproductive system consists of unpaired testis, paired vasa deferentia, an accessory gland, ejaculatory duct, and copulatory organ. The female reproductive system consists of bursa copulatrix, ductus bursae, receptaculum seminis, paired ducti receptaculi, ovaries, oviducts, one chorion gland, ovipositor, and oviporus. Testis as well as ovaries are characterized by syncytia of nutritional function. The specifics of spermatogenesis are discussed in connection with sperm transfer. Similarities between the construction of the ovaries and oogenesis in astigmatic mites and telotrophic meroistic ovaries in insects are discussed.


New directions in early intervention: P.L. 99-457. In conclusion, P.L. 99-457 has important implications for professionals who serve hearing-impaired infants and toddlers. The law challenges traditional, child-focused intervention models, and requires professionals to develop programs that are responsive to families' needs. Professionals will need to become familiar with family systems theories, useful family assessment tools, and strategies for collaborative service delivery. Professionals are challenged to determine how enabling relationships can be built with family members. Empowerment of the family system could have far-reaching, positive consequences for the hearing-impaired child.


Spontaneous retraction pockets in chronic otitis media medical and surgical therapy. Results of a series of 228 spontaneous retraction pockets in chronic otitis media are reported and a classification is proposed. Under medical therapy, 78 retraction pockets of stage I and II (out of 95) were followed for five years. Sixteen percent deteriorated into stage III and were operated on; the others stabilized or improved towards normal tympanic membrane (23%). Different methods of surgical therapy were used in 150 retraction pockets (all the stages III and many stages II). Even with silastic sheeting and strengthening of the tympanic membrane, a recurrent retraction pocket was observed in 24 cases (16%). Functional results were obviously better when the ossicular chain was rebuilt from an intact malleus to an intact stapes and either from an intact malleus to a mobile footplate or from the tympanic membrane to an intact stapes. Surgery of retraction pockets must be used not only to prevent cholesteatoma formation but also to prevent erosion of the stapes.


The rotary door flap a breakthrough in laryngotracheal reconstruction. The sternohyoid myocutaneous vascularized flap--the Rotary Door Flap (RDF),--is optimally oriented to serve in laryngotracheal reconstruction. It provides immediate highly vascularized lining and structural support to the augmented airway. Therefore it is one of the most versatile alternative methods available for surgical reconstruction of the stenosed larynx and trachea. This technique has been applied in 46 patients, of whom 14 were in the pediatric group. The features of the flap and the surgical technique are described.


Laser surgery of the larynx: the case for caution. Laser surgery has been advocated for treatment of many laryngeal lesions. Although the CO2 laser has many advantages, its safe use requires special education of the surgeon and operating room team, and considerable surgical skill. Several dangers inherent in laser use for laryngeal surgery must be considered. These include vocal fold scarring secondary to thermal injury, loss of histopathologically important tissue through vaporization, airway fire and others. Laser-related complications must be considered whenever use of this instrument is contemplated.


Orbital impalement by a gearshift knob: case report. Penetrating trauma to the orbit may cause complex injuries involving the bone, globe, and brain. Successful treatment requires a strategic scheme for preoperative assessment and management and a multidisciplinary surgical approach. These principles are demonstrated by report of a motor vehicle accident in which the driver sustained orbital impalement by a gearshift knob.


Frontal sinusitis with chronic epidural abscess: a case presentation. The incidence of intracranial complications from acute frontal sinusitis has decreased with improved antimicrobial and surgical therapy. However, the physician must maintain a keen awareness and thoroughly investigate any possible signs of intracranial spread. This article discusses a case in which a chronic epidural abscess developed after inadequate therapy was rendered. It also reviews the presentation of and the factors leading to the development of intracranial complications. The treatment required is to eradicate the disease present and prevent future sinusitis.


Estimation of hepatic hematopoiesis in second and third trimester singleton gestations using flow cytometric light scatter analysis of archival autopsy tissue. The purpose of this investigation was to develop a simple, quantitative, reproducible and objective method for estimating fetal hepatic hematopoiesis using flow cytometric light scatter measurements and to use this methodology to determine standard values for singleton gestations. Percent hepatic hematopoiesis was estimated from autopsy tissue both flow cytometrically using forward angle and side light scatter characteristics and histologically (single observer) in 67 s and third trimester singleton gestations without evidence of infection, congenital malformation, chronic maternal or placental disorders, or growth retardation. Correlation of flow cytometric and histologic estimates was 0.70 with flow cytometric estimates showing less variability than histologic estimates, especially during the second trimester. Flow cytometric estimates of hepatic hematopoiesis were relatively constant at 50-70% between 16 and 27 weeks gestational age and decreased during the third trimester to a level of approximately 25-30% at term. These results confirm and quantitate the predicted decrease in hepatic hematopoiesis between the second and third trimesters of gestation as well as its persistence at term. In addition, they demonstrate that flow cytometric light scatter analysis is an objective, valid and simple method for estimating hepatic hematopoiesis in archival autopsy tissue and provides objective standard values for comparison with estimates in pathologic gestations.


A 1-year follow-up of low birth weight infants with and without bronchopulmonary dysplasia: health, growth, clinical lung disease, cardiovascular and neurological sequelae. A cohort of 86 low birth weight (LBW infants (< 1751 g) including 23 subjects with bronchopulmonary dysplasia (BPD) and 23 matched controls without BPD were checked up at corrected ages of 1, 2, 4, 6, 8 and 12 months. Thirty-six of the subjects were re-hospitalized, mostly because of infections, there being no significant difference in the number of hospitalizations between BPD cases and their controls. Delayed growth was frequent, but a catch-up growth was seen. Eighteen of the subjects (5 with BPD and 7 of controls) were of height below 2 SD at a corrected age of 12 months. Twenty-four (14 with BPD and 3 controls) had persistent respiratory symptoms during the follow-up period and 4 of the BPD subjects still had such symptoms at the age of 1 year. Hoarseness was more frequent in BPD cases than in the controls (8/1 cases). One subject with BPD had transient symptoms of cor pulmonale and 1 without BPD developed transient systemic hypertension. Nine subjects (4 with BPD and 2 controls) had a diagnosis of cerebral palsy at the age of 1 year.


Current concepts in retinopathy of prematurity. Significant advances regarding understanding the etiology and treatment of retinopathy of prematurity have occurred in the 50 years since its discovery. Nevertheless, there is still a great deal to be learned. In spite of major technological advances in neonatal care, retinopathy of prematurity is a multi-factorial disease and probably cannot be completely prevented. Early intervention in the diagnosis and management of these infants has greatly improved their visual prognosis. Further studies may help pediatricians and neonatologists to understand and control associated risk factors. Ophthalmologists must continue to examine these patients early and follow them closely to control the associated treatable aspects of the disease, such as strabismus and amblyopia.


Judging fetal growth from body proportions at birth. Fetal growth velocity from 27 weeks until birth was calculated in 378 infants born after high risk pregnancies from at least three ultrasound measurements of estimated fetal weight and the weight at birth. Anthropometric measurements at birth (weight, head circumference, length, ponderal index and skinfolds), after correction for differences in gestational age, were significantly related to fetal growth velocity. The relation between fetal growth velocity and ponderal index was significant (correlation coefficient = 0.34, P < 0.001). However, the correlations between fetal growth velocity and each of the anthropometric measures disappeared when birth weight relative to gestational age was accounted for. This means that given the birth weight and the gestational age of a newborn infant, body proportions, e.g. ponderal index or skinfold thickness, do not contribute further to the judgment about fetal growth rate.


The epidemiological characteristics of unexplained antepartum stillbirths. All antepartum stillbirths weighing 1000 g or more born in Western Australia from 1980 to 1983 were categorised as 'unexplained' or 'explained' based on information from Perinatal Death Certificates. Using data from hospital and doctors' antenatal records a number of variables in each stillbirth category were compared by unconditional logistic regression. Significant differences were observed between the two groups in medical disorders and abnormalities of pregnancy, thus confirming our classification system. Compared with mothers of 'explained' antepartum stillbirths, mothers of unexplained antepartum stillbirths tended to have younger ages at delivery and had associated lower parity, more antenatal visits to the medical practitioner, fewer hospital admissions, a greater chance of having received care by a general practitioner than by a specialist obstetrician and were of more advanced gestation at the time of diagnosis. The results of this study indicate that the epidemiological characteristics of pregnancies resulting in unexplained antepartum stillbirths differ from those resulting in explained antepartum stillbirths. This suggests that unexplained antepartum stillbirths are not merely the result of inadequate obstetrical management but consist of a series of fetal disease states which are not currently amenable to detection.


Comparison of enteral and intramuscular vitamin A supplementation in preterm infants. Vitamin A deficiency associated with preterm delivery is not readily reversible using the recommended supplement of 1500 IU per day. It has been reported that 2000 IU of intramuscular vitamin A administered on alternate days for 28 days will correct the deficiency. The objective of this study was to compare this regime with the practice in our nursery of giving 5000 IU of vitamin A per day with the early introduction of feeds. The vitamin A status of ten preterm infants (mean gestation 30.5 weeks) who received intramuscular vitamin supplementation was compared with that of nine infants (mean gestation 30.7 weeks) given enteral vitamin A. Vitamin A status was evaluated on the 32nd day of life using plasma retinol and retinol-binding protein (RBP) concentrations and a modified relative dose response (RDR) test. Plasma retinol and RBP concentrations were similar in the two groups shortly after birth revealing vitamin A deficiency. By the 32nd day of life, plasma retinol and RBP concentrations had risen significantly in both groups and in 70% the modified RDR was normal. Differences between the groups were not observed irrespective of the method of vitamin A administration. None of the infants developed clinical or biochemical vitamin A toxicity. In most preterm infants who tolerate feeds, vitamin A deficiency can be corrected safely by supplementing the feeds with 5000 IU of vitamin A per day.


The effects of hypoxanthine, xanthine oxidase and hyperoxia on the accumulation of bilirubin and albumin in young rat brain. Hyperoxia has been suggested as a risk factor for kernicterus. The toxicity of hyperoxia may be mediated by free radicals. We investigated the effects of free radicals, formed by the hypoxanthine/xanthine oxidase system, with and without additional hyperoxia, on the accumulation of bilirubin and albumin in rat brain. Hypoxanthine was infused for 60 min into retrograde carotid catheters in awake, young, male SPRD rats. After 30 min the infusion was briefly interrupted to inject xanthine oxidase 1 U/kg through the same catheter. Group I (controls) received 0.9% NaCl in lieu of hypoxanthine/xanthine oxidase. Groups I and II breathed room air at all times, while group III breathed 90% O2. After 60 min all groups received a bolus dose of 125I-albumin through a peripheral venous catheter, followed by bilirubin 25 mg/kg for 5 min, then bilirubin 35 mg/kg for 55 min. There were no significant differences between the groups as regards serum bilirubin, serum albumin, brain bilirubin, or brain albumin. Neither during normoxic nor hyperoxic conditions did the hypoxanthine/xanthine oxidase system increase the accumulation of bilirubin or albumin in rat brain.


The relationship between heart rate and eye movement in the human fetus at 38-40 weeks of gestation. The purpose of this study was to compare two different methods for assessing fetal heart rate (FHR)--fetal eye movement (FEM) synchronization: (1) periods of high (HV) and low (LV) variability in the FHR and the presence (EM) and absence (NEM) of FEM were determined by visual inspection and the degree of association between FHR and FEM was assessed in terms of the fraction of study time for which no periods of LV-NEM and HV-EM could be identified; and (2) the maximum cross-correlation coefficient (rmax) and the lag at rmax (Lmax) were determined by direct computer analysis of FHR and FEM data for each fetus. Twenty normal human fetuses between 38 and 40 weeks of gestation were examined for a total of 2051 min (mean 103 min, range 72-150 min). In general, the state HV-EM was observed approximately twice as often as was the state LV-NEM; neither of these two states could be identified during 12.4% of the study time. The coefficient rmax was calculated assuming a sliding 3-min moving window, using either the average FHR (mean 0.53, range 0.31-0.85) or the variability in the FHR (mean 0.52, range 0.18-0.77). No relationship was found between rmax and Lmax calculated using the mean FHR and the fraction of time for which no state could be identified (P = 0.995). When the cross-correlation analysis was performed using FHR variability, a statistically significant relationship was found between the periods of no coincidence (of states LV-NEM and HV-EM) and rmax and Lmax (r2 = 0.32; P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)


A possible collicular component of the auditory evoked potential and its relationship to brainstem and cerebellar auditory potentials. Auditory evoked potentials were recorded from the rat using skull screw electrodes inserted over the inferior colliculus and the cerebellum. In addition, brainstem auditory evoked potentials (BAEPs) were also recorded. The response recorded from over the inferior colliculus consisted of a slow positive potential with one of two possible peak latencies. The mean latency of the earlier potential was 5.6 ms and that of the later potential was 6.4 ms. A hypothetical generator for the first collicular potential is the termination of the lateral lemniscus in the ventrolateral inferior colliculus, while the later collicular potential could have its origins within the brachium of the inferior colliculus. None of the principal nor minor BAEP waves corresponded to either of the collicular responses. Nor did the trough of negativity between BAEP waves IV and V which is often thought to reflect activity generated within the midbrain. The potential recorded over the cerebellum also consisted of a slow positivity but with a slightly sharper contour than that of the collicular response. The mean latency of the cerebellar potential was 4.9 ms. As there was no temporal relationship between collicular and cerebellar potentials, the present study provided no support for the theory that cerebellar auditory potentials are artefactual and simply far field reflections of activity generated in the inferior colliculus. Judging by the timing of the BAEP waves, it is also concluded that the afferent volley most likely projects to the cerebellum via a collateral pathway branching off the caudal part of the lateral lemniscus.


Electromyographic recording of the jaw reflex in Friedreich ataxia. Jaw jerk was studied in 10 subjects with Friedreich ataxia, and 10 normal subjects for comparison. Electromyographic recording from the right masseter muscle showed a reflex response in all cases, in contrast to the absence of tendon reflexes in the four limbs for the ataxics. The mean latency of the jaw jerk was normal. These observations indicate that the jaw reflex arc is preserved, and that no damage to the trigeminal neuromuscular pathway exists for all the patients observed.


Stretch reflex of quadriceps femoris in normal man: methodological considerations and normative data. Short- and long-latency responses to stretching have been evoked in various muscles in the healthy subject. The quadriceps femoris, however, has never been investigated in this connection, despite its functional importance. We studied its stretch reflex in 17 healthy subjects with a torque motor to determine its morphological features in relation to the level of background EMG activity, the stretching velocity and duration and the instructions given to the subject. Two bursts of EMG activity were constantly evoked when the muscle was voluntarily activated. Response magnitude was proportional to the background activity and displacement velocity. Short stretching evoked only one EMG burst. These findings are similar to those from other muscles. Intra-individual variability was evaluated repeating the experiment in the same session without changing position of the electrodes, and then after two months. The long-latency response showed a good intra-individual reproducibility.