Campylobacter jejuni proteomics for new travellers' diarrhoea vaccines.

Travellers' diarrhoea is defined as diarrhoea that develops while a person is abroad in or shortly after return from a developing country. Different pathogens cause diarrhoea in travellers. Campylobacter jejuni is one of the most prominent agents for this illness. Diarrhoea is defined as an abnormally increased frequency or decreased consistency of stools for less than one week. Antibiotics are effective in preventing travellers' diarrhoea, but routine prophylaxis with antibiotics, should be discouraged. Vaccination is promising but no vaccine against C. jejuni is available at the moment. This article presents the ACE BioSciences strategy for the discovery of protein based vaccine candidates using a cell surface proteomics approach of C. jejuni. New targets for C. jejuni protein vaccines were identified. As proof of concept, we could demonstrate decreased colonization of C. jejuni in mice after vaccination with some of these candidates. It is likely that the proteomics based ACE-Biosciences approach will result in reliable travellers' diarrhoea protein-vaccines in the future.

Ventilatory patterns during hypoxia, hypercapnia, and exercise in adolescents with mild scoliosis.

Adolescents with mild, asymptomatic scoliosis (thoracic curvature less than 35 degrees) may have little or no impairment of resting lung volumes. Progression to more severe disease may, however, be accompanied by lung restriction, impaired exercise tolerance, and respiratory failure with CO2 retention. We wished to see whether adolescents with mild scoliosis and minimally abnormal resting pulmonary mechanics had impairment of their responses to hypercapnia, hypoxia, and progressive cycle exercise. Forty-four adolescents with idiopathic scoliosis were studied. The mean forced vital capacity (FVC), expressed as a percentage of the predicted value, was 94.3 +/- 2.2 (SE). The mean ventilatory response to hypercapnia (2.57 +/- 0.24 L/min/mm Hg) was within the normal range but was achieved with a tidal volume response (1.87 +/- .17% vital capacity [VC]/mm Hg) that was significantly lower than that previously reported in healthy young adults. Ventilatory responses to exercise were also within the normal range, the mean dyspnea index (VE-max/maximal voluntary ventilation) = 0.92 +/- 0.04. However, at a ventilation of 30 L/min, the tidal volume was 0.38 +/- 0.01% FVC, which was considerably lower than predicted. The tidal volume response to hypoxia was also abnormally low, the mean response being 0.52 +/- 0.059% VC/% decrease in arterial O2 saturation. These findings indicated that, even when scoliosis is asymptomatic and associated with minimal impairment of resting pulmonary function, abnormal patterns of ventilation occur during exercise or in response to chemical stimuli.

Binding of bromosulphthalein sodium by human serum albumin using a continuous diafiltration technique.

1. The recently introduced ultrafiltration-cum-dialysis technique termed continuous diafiltration has been used to obtain detailed binding isotherms of equilibrium solution concentration of bromosulphthalein (BSP) versus the number of molecules of BSP bound per molecule of human serum albumin for pure human serum albumin solutions (albumin concentrations: 1.59-3.39 g/100 ml) and for three dilutions of pooled human serum (albumin concentrations: 1.45-2.85 g/100 ml) in 310 ideal milliosmolar phosphate buffer at pH 7.4 and 22 degrees C.2. Qualitative analysis of the isotherms seems to indicate that there is a competition between the polymerization of the albumin to dimers and high oligomers and the binding of BSP by albumin.3. The binding capacity of pure human serum albumin at total BSP (bound and free) concentrations below 2.3 mM is greater than that of the pooled serum at an equivalent albumin concentration, possibly indicating the blockage of binding sites by more strongly binding ligands.4. The binding capacity of pure albumin at total BSP concentrations greater than 2.3 mM is less than that of pooled serum at an equivalent albumin concentration, suggesting the presence of other non-ultrafilterable materials in the serum capable of binding BSP.

Secretion of genetically engineered human/mouse class I antigens.

Two soluble, secreted forms of HLA-B7 were engineered by the creation of hybrid human/mouse molecules containing the polymorphic 5' region of the HLA-B7 gene and the secretory 3' region of the mouse Q10d gene. The hybrid, designated F1, is the first construct with only human extracytoplasmic domains, consisting of exons for the leader peptide and the three extracellular domains (alpha 1, alpha 2, alpha 3) of B7 spliced to the exons for the Q10d truncated transmembrane and 3' untranslated (3'UT) sequences. The second construct, designated C2, is similar but has the human alpha 3 replaced by the Q10 alpha 3 domain. Protein product from each construct was best demonstrated after gene transfection into the J27.2 cell line. In particular, secretion of the F1 product proves that the Q10 alpha 3 domain is not necessary for secretion of class I/Q10 hybrids. Moreover, the two soluble B7 forms, which differ only in their alpha 3 domain, are similarly recognized by monoclonal antibodies W6/32 (anti-HLA-ABC), BBM.1 (anti-human beta 2 microglobulin), and allo-B7-antibody, but differentially recognized by monoclonal antibody Q1/28 (anti-HLA class I heavy chain). Production of such soluble hybrid class I molecules in large amounts should allow critical structural and functional studies of these proteins.

Correction of upper eyelid retraction using tissue removed in blepharoptosis repair.

Five patients (four women, 41, 51, 66, and 78 years old, and a 5-year-old boy) had blepharoptosis of one upper eyelid and an abnormal retraction of the other eyelid. Both anomalies were corrected at the same operation by using the tissue removed during blepharoptosis repair in one eyelid to correct the retraction in the other eyelid. As a result, both upper eyelids had a more normal, symmetric appearance and eyelid function was maintained.

Surgical treatment of true Brown's syndrome.

In 1950 H. W. Brown reported the superior oblique tendon sheath syndrome and cut the sheath as treatment for the condition. My results (as well as those of other surgeons) with similar surgery have been disappointing. Consequently, I carried out different operations consisting of Z tenotomy of superior oblique tendon in nine patients, split tendon lengthening in two patients, complete tenotomy in 16 patients, and a tenectomy in two patients. One of the latter was done on a patient after an unsatisfactory tenotomy where I missed the tendon. Tenotomy of the superior oblique tendon gave the best results. Experiments with the superior oblique tendon in cadavers several hours after death showed that after cutting the tendon just medial to the superior rectus muscle, the cut end of the tendon moved medially only about 8 to 10 mm due to restrictions of the capsular attachments to the trochlea. The cause of "true" Brown's syndrome is a tight tendon, and a safe and effective surgical treatment consists of cutting it just medial to the superior rectus muscle.

Surgical correction of lens dislocation in children.

We treated nontraumatic ectopia lentis with the irrigation and aspiration method in 30 children and the Keeler/SITE instrument in three. Preoperative visual acuities were 6/21 (20/70) or worse in all patients; postoperatively, visual acuities improved in 29 of the 30 eyes and were 6/18 (20/60) or better in 24 (80%). Amblyopia was the major preoperative and postoperative complication. Results were also good in the three eyes in which we used the Keeler/SITE instrument. The prognosis for postoperative visual acuity in nontraumatic cases of ectopia lentis is good when either the irrigation and aspiration method or the Keeler/SITE instrument is used.

The quantification, natural course, and surgical results in 57 eyes with Marcus Gunn (jaw-winking) syndrome.

Subjective findings and objective surgical results in 55 individuals with the Marcus Gunn (jaw-winking syndrome indicated that bilateral fascial suspension is the best procedure in most cases. Levator muscle resection treats only the blepharoptosis (often undercorrecting it), may exacerbate the jaw-winking, and is associated with significant eyelid lag in many cases. In the 17 patients who had not undergone surgery, there was no significant spontaneous reduction in the degree of jaw-winking. Additionally, the patient's belief that the jaw-winking had improved with time was often inaccurate, indicating that objective measurements are necessary before conclusions can be drawn about the natural course of this phenomenon. We also found that high incidences of strabismus (36%) and amblyopia (34%) are associated with this syndrome.

Silicone tube intubation in disorders of the lacrimal system in children.

We analyzed the results of 81 silicone intubations of the lacrimal system in 56 patients aged 6 months to 16 years after posttreatment follow-up of at least two months. Standard probing just before intubation allowed us to group cases by obstruction sites: proximal, distal, or combined. Overall, the outcome was successful in 65 (80.3%) cases. In cases of trauma, success was achieved in two of five patients with proximal, five of nine patients with distal, and two of two patients with combined obstructions. In nontraumatic blockages, we achieved success in 13 of 16 proximal, 30 of 35 distal, and 13 of 14 combined obstructions.

The effect of aspirin on rebleeding in traumatic hyphema.

Often used as an oral analgesic in the management of pain associated with traumatic hyphema, aspirin has an inhibitory effect on the blood clotting mechamism by its action on platelets. We carried out a retrospective study of patients with traumatic hyphema treated with aspirin and showed that the incidence of rebleeding significantly increased with aspirin administration.

Late results of superior oblique muscle tenotomy in true Brown's syndrome.

We re-assessed nine patients (aged 2 to 28 years) in whom true Brown's syndrome had been diagnosed and superior oblique muscle tenotomy performed. The postoperative period ranged from three to 12 years. The final results were divided into three groups: (1) Patients with partial residual Brown's syndrome postoperatively who gradually improved spontaneously over several years, with one exception. (2) Patients who had minimal or moderate superior oblique muscle paresis, secondary overaction of the homolateral inferior oblique muscle, and excellent binocular single vision postoperatively who improved spontaneously. In Groups 1 and 2, the study showed that the long-term results are better than those immediately after surgery, and the surgeon should not be too hasty in reoperating. (3) Patients with marked superior oblique muscle paresis and secondary homolateral inferior oblique muscle overaction postoperatively did not improve spontaneously and required a weakening procedure on the homolateral inferior oblique muscle.

Ophthalmic sequelae of infantile hemangiomas of the eyelids and orbit.

The major findings in a study of 51 infants and children with infantile hemangioma of the eyelid were as follows: Visual complications occurred in 27 patients. The most common complications were amblyopia (in 22) and strabismus (in 17). Amblyopia of 6/60 (20/200) or less was probably caused by stimulus-deprivation, but amblyopia in the range of 6/30 (20/100) to 6/12 (20/40) was likely caused by anisometropia or strabismus. Eyelid occlusion of six months or more invariably resulted in amblyopia of 6/60 (20/200) or less. Occlusion for even one month carried a risk of amblyopia. Each child must be considered individually for therapy, which must be started as early as possible. Patients should receive careful follow-up from the beginning to prevent severe amblyopia. For difficult cases, we need more efficacious, safe methods to induce regression of these tumors.

Ocular abnormalities in the Freeman-Sheldon syndrome.

Ocular abnormalities were present in five of 11 patients with Freeman-Sheldon syndrome. The predominant ocular findings were strabismus and blepharoptosis. Stiffness of the extraocular muscles, demonstrated in three patients by forced duction testing, made surgery difficult. Two patients underwent frontalis muscle sling surgery and a third underwent levator palpebrae superioris muscle resection. Although all three remained exotropic, the cosmetic results were good.

A longitudinal study of cardiovascular dynamic changes throughout pregnancy.

Systemic blood pressure (measured with a zero-randomized sphygmomanometer), stroke volume and heart-rate (measured with a Minnesota Impedance Cardiograph), hematocrit, and their derivatives -- cardiac output and peripheral vascular resistance--have been assessed in three groups of subjects. First, a control group of 19 nonpregnant women were matched for age and weight with the subjects in the second group, which consisted of 19 patients who were seen at regular intervals on 12 to 15 occasions from 8 to 11 wk of pregnancy until 6 wk postpartum. The third group consisted of 8 patients seen from before conception, throughout pregnancy and to several months postpartum. Readings were made with the subject in each of six positions: supine, reclining, left and right lateral, left and right tilt. This paper concerns the readings obtained in the left lateral position. The data showed that pulse rate rose throughout pregnancy. Stroke volume and cardiac output rose shortly after conception, the increase over the prepregnancy level being statistically significant by 12 wk. Thereafter both values fell throughout the rest of pregnancy and were below prepregnancy levels by about term, taking some weeks to regain the prepregnancy value. There were irregular fluctuations in the level of systolic blood pressure; diastolic blood pressure fell during the first 16 wk and then rose to reach almost the prepregnancy value by term. Peripheral resistance fell during the first trimester, then increased markedly throughout the remainder of pregnancy.

The influence of posture upon cardiovascular dynamics throughout pregnancy.

Systemic blood pressure (measured with a zero-randomized sphyngmomanometer), stroke volume and heart-rate (measured with a Minnesota Impedance Cardiograph), hematocrit and their derivatives--cardiac output, pulse pressure, mean arterial blood pressure and peripheral vascular resistance, were assessed in 19 nonpregnant women of child-bearing age and in 27 patients who were examined at regular intervals on 12 to 15 occasions from 8 to 11 wk of pregnancy until 6-wk postpartum. Readings were made with the subjects in each of six positions: supine, reclining, left and right lateral, left and right tilt. The purpose of this paper is to compare the results of these different postures. Systolic and diastolic blood pressure readings were lowest in the left lateral and second lowest in the left tilt. We suggest that this reflects a hydrostatic pressure difference. Stroke volume and cardiac output were lowest in the right lateral and second lowest in the right tilt. Thus, the derived values of peripheral resistance were lowest when subjects were turned towards the left and highest when turned towards the right. The rank orders of values were maintained with impressive consistency between subjects (pregnant and nonpregnant) and throughout pregnancy, reaching levels of statistical significance in almost all instances. No evidence was found that aortocaval compression led to a change in the measured attributes of central cardiovascular dynamics. For the 'normal unembarrassed parturient' it is suggested that aortocaval compression is rapidly succeeded by a restablization of these attributes to their previous levels, reflecting the prompt establishment of a suitably diminished circulating blood volume within a reduced vascular capacity. It is nevertheless likely that aortocaval compression will interfere markedly with uteroplacental vascular dynamics and hence pose a hazard to the fetus.

Hemangiomas of the eyelid: visual complications and prophylactic concepts.

We describe a late survey of 51 patients who had hemangiomas of the eyelid in infancy, together with the visual complications found and a program designed for prevention of the latter.

Twins, immuno-incompatibility and pre-eclampsia.

A survey of 417 twin pregnancies is reported. Examination of the data revealed no difference in the incidence of pre-eclampsia referable to the zygosity of the twins. The findings thus lends no support to the hypothesis that immuno-incompatibility contributes to the aetiology of pre-eclampsia.

A suggested set of working definitions and criteria applicable to induction of labour.

A list of prerequisites, essential items of information and definitions applying to studies on induction of labour is presented. It is suggested that their use would permit proper analysis and comparison of results obtained by different investigators.

Intubation of obstructions in the lacrimal system.

It maybe difficult to maintain the patency of the lacrimal system in some cases of congenital obstruction after chronic infection or after trauma. Intubation is carried out using silicone tubing to which is attached a stainless steel wire probe which has a knob on the end. This is engaged by a special hook which is used to draw the wire out from under the inferior turbinate. After leaving the tubes in place for 4 to 6 months the obstructed area is usually epithelialised.

The use of bank sclera to correct lid retraction.

Twenty-two scleral grafts were inserted in patients with retracted lids, the youngest patient was two years old at time of surgery. Two patients were operated on under local anaesthesia and the remainder under general anaesthesia. In the patients with thyroid disease larger grafts were required, the temporal side of the graft being 3 mm greater vertically than the nasal. Our first cases were undercorrected, so we used grafts of a size at least twice that required to lower the lid. Other complications were rare. For ptosis overcorrections, and congenital lid retraction, the graft should be 2 mm bigger horizontally and vertically than the amount required to lower the lid.