Acquired lacrimal drainage obstruction: an etiologic classification system, case reports, and a review of the literature. Part 1. The cause of acquired lacrimal drainage obstruction may be primary or secondary. Primary acquired nasolacrimal duct obstruction results from inflammation of unknown cause that eventually leads to occlusive fibrosis. Secondary acquired lacrimal drainage obstruction, the theme of this report, may result from a wide variety of infectious, inflammatory, neoplastic, traumatic, or mechanical causes. An etiologic classification system for acquired lacrimal drainage obstruction is proposed, and it is illustrated by representative patients from the author's practice and discussed with reference to published reports.


Investigation of automated perimetry in the evaluation of patients for upper lid blepharoplasty. We investigated the application of automated perimetry in the evaluation of 17 patients for upper lid blepharoplasty. Visual fields were assessed by a 114 point threshold related screening test of the superior visual field on the Humphrey Allergan Model 640 visual field analyzer. Patients enrolled in the study underwent a complete oculoplastic evaluation prior to and at 4-6 weeks after their procedure. Postoperatively, the visual field as measured by the number of points seen, increased by 26.2% (p < 0.000001). Improvement in visual field results was most dramatic in patients whose margin reflex distance (MRD) was < or = 3.5 mm. This effect was related to excision of redundant eyelid tissue rather than a change in MRD after blepharoplasty. Above this MRD level, blepharoplasty did not significantly improve the patients superior visual field. These results suggest that automated perimetry provides valuable information to document visual field changes for medicolegal and insurance purposes.


On-table lavage in the management of sigmoid volvulus: a review. Sigmoid volvulus is a leading cause of bowel obstruction in many parts of Africa. Several aspects of management remain controversial, particularly the operative strategy to be adopted in patients in whom sigmoidoscopy has failed to deflate viable bowel. On-table lavage is especially useful in these circumstances, allowing safe primary resection and anastomosis. This short review summarizes the theoretical and clinical background to such an approach.


Eyelid avulsion: a clinical and experimental study. Traumatic eyelid avulsion is reported infrequently. We cared for an 18-year-old man who lost > 75% of his right upper eyelid. The tissue was recovered 10 h following the initial trauma. Successful surgical reimplantation resulted in a functional upper eyelid with extensive madarosis. An experimental study was undertaken to attempt to determine the optimal method for preservation of avulsed eyelid tissue. Experimental surgery was performed to simulate repair of eyelid avulsion. The postoperative changes in experimentally reimplanted eyelids parallel those noted in the clinical example of eyelid avulsion. This clinical example and experimental study suggested the following management principles for handling avulsed eyelid tissue: eyelid tissues should not be immersed in saline; avulsed eyelid tissues should be stored at 4 degrees C; if reimplantation time is < 6 h, storage in a cold moist environment is adequate.


Strategies to contain the spread of AIDS: A review. An attempt has been made to review the available strategies to contain the spread of the Acquired Immunodeficiency Syndrome (AIDS). Also options for clinical management of AIDS' patients are summarized. Development and production of a suitable vaccine is the ultimate goal in the attempts to stop the spread of AIDS. This however has been hampered by the continuous replication and mutation of the Human Immuno-deficiency Virus (HIV) within the body of an infected person. For now, effective health education is the most realistic method of controlling the spread of AIDS.


Mohs histographic surgery and ophthalmic plastic reconstruction. A retrospective analysis of 43 consecutive cases of primary and recurrent basal cell carcinomas is presented. Each patient's tumor was first managed by Mohs histographic surgery followed by opthalmic plastic reconstruction within 24 h. A review of the age distribution and gender of patients included in this study reveals a sizeably younger population and a increased incidence of females as compared to previous studies. The success rate was high and approached the experience of other authors. Invariably the Mohs failures were among those patients that required six to eight sequential layers but failures do occur in primary cases outside the medial canthus.


Venous engorged tissue flaps treated with medicinal leeches. We evaluated the ability of leeches to improve the tolerance of pedicle flaps to periods of venous congestion. Axial pedicle flaps were created on 14 rabbit ears; the venous circulation of each flap was compromised with a suture ligature. Medicinal leeches were applied to seven flaps; the other seven flaps were untreated. Tissue viability was assessed by both clinical examination and fluorometric analysis of fluorescein dye delivery. Leech-treated flaps showed poorer reperfusion than untreated flaps. No statistically significant difference was found in comparing the two groups.


Surgical treatment of thyroid-related lower eyelid retraction: a modified approach. A 15-year retrospective study was performed in 68 patients who underwent scleral implantation for correction of lower eyelid retraction related to Graves' disease. Three variations of the scleral implantation procedure were used over three time periods. Scleral grafting alone ("old" procedure) was performed in 53 patients from 1974 to 1985. Because of persistent lower lid retraction postoperatively, this procedure was modified. Beginning in 1986, a lateral canthal suspension consisting of either a lateral tarsal strip or a lateral tarsorrhaphy was added to the scleral implantation ("intermediate" procedure) and was performed in seven patients. Since 1988, the procedure has been further modified to include both a lateral tarsal strip and a lateral tarsorrhaphy ("new" procedure). Eight patients underwent this procedure. Analysis with Student's t test indicated a statistically significant reduction in lower lid retraction when using the new procedure, as measured by a reduction in the margin reflex distance-2, the distance from the corneal light reflex to the central lower lid (p = 0.02), and by a reduction in inferior central scleral show, the distance from the central lower lid to the inferior limbus (p = 0.02). An analysis of covariance, controlling for age, Hertel exophthalmometry readings, and length of follow-up, also indicated that the reduction in the postoperative margin reflex distance-2 was significant (p = 0.04).


Lid splitting with lash resection for cicatricial entropion and trichiasis. Lid margin splitting at the gray line with resection of the lash-bearing anterior lamella of the eyelid is a simple and effective treatment for cicatricial entropion and trichiasis. Twenty-six patients underwent this procedure with good results.


Collagen shield contact lens use after eyelid surgery. The use of collagen shields to enhance comfort and facilitate recovery after eyelid surgery was studied. Thirty-two patients undergoing various eyelid procedures were studied. In 10 patients, bilateral surgery was performed and the contralateral eye was used as a control. In patients with unilateral surgery, 20 of 22 patients exhibited comfortable postoperative courses, and in patients with bilateral surgery, eight of 10 patients had less conjunctival injection, chemosis, corneal staining, or lid edema on the side with the collagen shield. The only complications occurred with the 72-h lens, which tended to irritate the cornea and have a variable dissolution time.


The use of Q-switched Nd:Yag laser for removal of permanent eyeliner tattoo. We present the results of a pilot study of the use of Nd:Yag laser in the removal of permanent eyeliner tattoos. Fourteen eyelids were treated, and in all cases a reduction in pigmentation was achieved although responses were variable. The advantages of such therapy over existing techniques are described. The technique offers a useful reduction of permanent eyeliner pigmentation and is particularly suited to treatment of localized areas of imperfect application or pigment migration.


Acute dacryoadenitis and Crohn's disease: findings and management. Concurrent orbital pseudotumor and Crohn's disease, although rare, have been described. To the best of our knowledge, pseudotumor isolated to the lacrimal gland (dacryoadenitis) with concurrent Crohn's disease has never been reported. We present the clinical course and ultrasonographic and radiologic findings of an acute case of isolated bilateral lacrimal gland pseudotumor in a patient with Crohn's disease. The treatment and review of the literature are discussed.


Oncocytoma of the caruncle.

Oncocytoma of the caruncle. Oncocytomas of the ocular adnexa are rare, but when they occur, are most commonly located on the caruncle. Oncocytic carcinomas have been reported but the majority of caruncular oncocytomas are benign. The lesions present as small, cystic, tan-to-red lesions. Histologically, the oncocytes are arranged in an adenomatous pattern. The cells have central nucleoli surrounded by eosinophilic cytoplasm. Electron microscopically, the cytoplasm is filled with mitochondria. As the packing of mitochondria increases, the nucleoli become eccentric and pyknotic, possibly suggesting an end-stage process. A typical clinical case is presented.


Tension pneumoorbitus.

Tension pneumoorbitus. Posttraumatic tension orbitus developed in a young man causing subconjunctival emphysema and proptosis. Intraocular pressures were monitored as a means of indirectly measuring intraorbital pressure. The patient was serially examined for evidence of compressive optic neuropathy. Because of the possibility of orbital pressure increasing several hours from the time of injury, we recommend monitoring of these patients through intraocular pressure measurement and evaluation of the optic nerve for evidence of compression. Our findings, however, do support previous documentation that the intraocular pressure rise following orbital trauma with orbital emphysema is usually not of sufficient severity or duration to result in visual compromise.


Differential scanning calorimetric studies on bovine serum albumin: III. Effect of sodium dodecyl sulphate. Measurements of differential scanning calorimetry (d.s.c.) have been made on the complex bovine serum albumin (BSA)--sodium dodecyl sulphate (SDS) under various conditions. There are two peaks P1 and P2 in the d.s.c. curve for BSA at pH 7 and in the absence of NaCl, indicating the presence of the heat-induced transition of BSA. There are three peaks P1, P2 and P3 in the curve for the system with the molar mixing ratio SDS/BSA = 1. With the increase in the amount of SDS, the peak P3 grows at the expense of P1 and P2. There is only a single peak P3 in the curve for the systems SDS/BSA > 7, and no peak at SDS/BSA = 50 and 100. There is a single peak P12 in the curve for BSA at pH 7 and in the presence of 0.05 M NaCl, indicating that the heat-induced transition is suppressed. There are two peaks P12 and P3 for the systems SDS/BSA = 1-5; the area ratio of the peak P3 to P12 increases with the increase in the amount of SDS. There is only a single peak P3 when SDS/BSA > 7, and no peak at SDS/BSA = 50. It is concluded that the peak P3 is a product of SDS regardless of the presence or absence of NaCl. Values of thermal denaturation temperature (Td) and enthalpy (delta H) of thermal denaturation indicate that the complex AD12 (A = BSA, D = SDS) is in the most thermostabilized state.(ABSTRACT TRUNCATED AT 250 WORDS)


Solution conformation of a pectin fragment disaccharide using molecular modelling and nuclear magnetic resonance. In the present study, the conformational behaviour of methylated pectic disaccharide 4-O-alpha-D-galactopyranurosyl 1-O-methyl-alpha-D-galactopyranuronic 6,6'-dimethyl diester 1 has been completely characterized through combined n.m.r. and molecular modelling studies. The 1H-1H n.O.e. across the glycosidic bond was measured by both steady-state and transient 1D and 2D experiments. In parallel, the complete conformational analysis of the disaccharide has been achieved with the MM3 molecular mechanics method. The conformation of the pyranose ring is confirmed by the excellent agreement between the experimental and calculated intracyclic scalar coupling constants. The iso-energy contours displayed on the 'relaxed' map indicate an important flexibility about the glycosidic linkage. There is no significant influence of the methoxyl group on the conformational behaviour of the disaccharide. The theoretical n.m.r. data were calculated taking into account all the accessible conformations and using the averaging methods appropriate for slow internal motions. 3JC-H coupling constants were calculated using an equation suitable for C-O-C-H segments. The agreement between experimental and theoretical data is excellent. Within the potential energy surface calculated for the disaccharide, several conformers can be identified. When these conformations are extrapolated to a regular polymer structure, they generate pectins with right- and left-handed chirality along with a two-fold helix. These different types of helical structure are the result of small changes in conformation, without any drastic variation of the fibre repeat.


Biosynthesis of poly(3-hydroxyalkanoate) from amino acids. It was found that an optically active copolyester, poly(3-hydroxybutyrate-co-3-hydroxyvalerate), denoted as P(3HB-co-3HV), is synthesized by Alcaligenes eutrophus H16 from several amino acids under various fermentation conditions. The optimum condition for the biosynthesis from one amino acid, threonine, was investigated and its biosynthetic pathway was discussed on the basis of the relation between the fermentation condition and the co-monomer composition of the produced polyesters.


Unfolding and refolding of hen egg-white riboflavin binding protein. The unfolding and refolding of riboflavin-binding protein (RfBP) from hen egg-white induced by addition of guanidinium chloride (GdnHCl), and its subsequent removal by dialysis have been studied by c.d. and fluorescence for both the native and reduced protein. The reduction of its nine disulphide bonds causes a reduction in the secondary structure (alpha-helix plus beta-sheet) from 63% to 33% of the amino acid residues. Unfolding of the native protein occurred in two phases; the first involving a substantial loss of tertiary structure, followed by a second phase involving loss of secondary structure at higher GdnHCl concentrations. By contrast this biphasic behaviour was not discernible in the reduced protein. The loss of ability to bind riboflavin occurred after the first phase of unfolding. Comparison of unfolding of the holoprotein and apoprotein suggested that riboflavin has only a small stabilizing effect on the unfolding process. After removal of GdnHCl, the holoprotein, apoprotein and reduced protein assumed their original conformation. The significance of the results in relation to various models for protein folding is discussed.


A peptide from Tetrahymena disrupts subunit organization of E. coli RNA polymerase. Incubation of the E. coli RNA polymerase with a polypeptide factor from the protozoan Tetrahymena reduces the affinity of the holoenzyme for DNA. SDS-polyacrylamide gel electrophoresis of the peptide-treated RNA polymerase showed that the band pattern of the polymerase subunits was strongly altered. The three large subunits, beta', beta and sigma, disappear and a high number of rapidly migrating bands appeared. However, a brief heat treatment of the samples almost restored the original RNA polymerase subunit composition, and in addition a high molecular weight protein band approximately 240 kDa appeared. It is suggested that the Tetrahymena peptide specifically binds to the RNA polymerase and changes the structures of the large subunits.


Susceptibilities of bacterial cellulose containing N-acetylglucosamine residues for cellulolytic and chitinolytic enzymes. Detailed characterization of enzyme susceptibility of bacterial cellulose containing N-acetylglucosamine (GlcNAc) residues (N-AcGBC) which possess high susceptibility for cellulase and lysozyme and slight susceptibility for chitinase was studied. Turbidimetric lysozyme assay of N-AcGBC showed that (i) the susceptibilities of various N-AcGBCs for lysozyme were proportional to GlcNAc content, and (ii) N-AcGBC homogenates were divided into two groups based on the rate of turbidity reduction (not dependent on GlcNAc content). High reactivity of N-AcGBC for lysozyme would arise from fine microfibrils characteristic of bacterial cellulose (BC) and random distribution of GlcNAc residues in N-AcGBC because water soluble oligomers of N-AcGBC produced by lysozymic hydrolysis did not inhibit lysozyme activity; however, the random distribution of GlcNAc seemed to result in the slight susceptibility of N-AcGBC for chitinase. The rate of cellulolytic turbidity reduction of N-AcGBC was slower than that of BC, which arose from the inhibition for binding of cellulase by GlcNAc residues.


Pharmacophoric pattern matching in files of three-dimensional chemical structures: use of bounded distance matrices for the representation and searching of conformationally flexible molecules. This paper discusses the use of bounded distance matrices for the representation of conformationally flexible three-dimensional (3D) molecules. It is shown that pharmacophoric pattern searches of databases of flexible 3D molecules represented in this way can be carried out using screen and geometric searching algorithms that are analogous to those used for searching databases of rigid 3D structures. Molecules matching a query pattern after the geometric search must then undergo a final conformational search to determine whether they can, in fact, adopt a conformation that matches the query. An analysis of this three-stage searching procedure shows that searching databases of flexible 3D molecules is extremely demanding of computational resources.


Searching for geometric molecular shape complementarity using bidimensional surface profiles. The study presented herein is a bidimensional approach to the complementarity of two molecular surfaces. From two chosen sections we have established a methodology of generating the optimal matching of two shapes. Our approach consists in describing two molecular surface sections by a shape vector (the angular profile), in finding their matching patterns by comparison of the two profiles, and in optimizing the relative locations of the two sections in two-dimensional space, using rotations and translations defined by geometric characteristics. The set of optimal configurations are successively displayed on a screen. Satisfying results have been obtained for the matching of the complex kallikreine A-trypsin pancreatic bovin 2. This efficient method could be used as a preprocessing for a tridimensional shape complementarity approach between two molecular surfaces.


KEY, LOCK, and LOCKSMITH: complementary hydropathic map predictions of drug structure from a known receptor-receptor structure from known drugs. Three new routines (LOCK, KEY and LOCKSMITH) for the program HINT (hydrophobic interactions) are described and demonstrated. The KEY routine uses receptor structure to model the hydropathic profile of the ideal substrate for the receptor. The LOCK routine uses substrate or drug structure to model the hydropathic character of the receptor. LOCKSMITH is an algorithm designed to highlight the significant hydropathic features from a collection of agents. Ten allosteric modifiers of hemoglobin that have been characterized biologically and with X-ray diffraction to determine their protein binding sites/conformations illustrate the KEY and LOCKSMITH routines: The LOCKSMITH composite map correctly identifies the structural features and conformation of the more active modifiers. In addition, many hydropathic features of the "ideal" drug predicted by the KEY map overlap with actual structural features of the most active hemoglobin allosteric modifiers.


Photorealistic image generation of molecular structure on PC screen using the ray-tracing technique. A PC version of three-dimensional molecular graphics package has been developed to run under MS-DOS environment on IBM PC-compatible computers equipped with a VGA graphics board. The program consists of two parts: a menu-driven interactive system module in EGA mode, and a ray-tracing module in VGA mode. In the 256-color VGA mode, ray-tracing images are represented with a 4-color map, with 64 levels for each color: 32 levels of illuminance and 32 levels of saturation. Molecular structure can be analyzed along various directions with various light sources. Ray-tracing images are also represented in a 16-color EGA mode with the half-toning method, which can display 76 gray levels for each color. To obtain good photo-realistic images in an efficient way, we have used two light sources, with an intensity ratio of 7:3, which are located in front of the top right and bottom left corners of the screen.


An easily fixed error in the Nyburg algorithm for discovering the best fit between molecules. The extremely popular Nyburg algorithm for discovering the best fit between two molecules or fragments has an error that can give a false best fit under some circumstances. This error is described, and a simple fix is provided. The original Nyburg program (BMFIT) is compared to Sippl's program of 1991.


POCKET: a computer graphics method for identifying and displaying protein cavities and their surrounding amino acids. A new interactive graphics program is described that provides a quick and simple procedure for identifying, displaying, and manipulating the indentations, cavities, or holes in a known protein structure. These regions are defined as, e.g., the xo, yo, zo values at which a test sphere of radius r can be placed without touching the centers of any protein atoms, subject to the condition that there is some x < xo and some x > xo where the sphere does touch the protein atoms. The surfaces of these pockets are modeled using a modification of the marching cubes algorithm. This modification provides identification of each closed surface so that by "clicking" on any line of the surface, the entire surface can be selected. The surface can be displayed either as a line grid or as a solid surface. After the desired "pocket" has been selected, the amino acid residues and atoms that surround this pocket can be selected and displayed. The protein database that is input can have more than one protein "segment," allowing identification of the pockets at the interface between proteins. The use of the program is illustrated with several specific examples. The program is written in C and requires Silicon Graphics graphics routines.


Molecular illustration in black and white. Two-dimensional image processing techniques are used to create black and white illustrations from conventional z-buffer images. The illustrations appear to be composed of lines--outlines, contour lines, and hatched shading--but are calculated as grey-scale raster images. They have the advantage of faithful reproduction in publication and ease of display on workstations and laser printers. A FORTRAN source code is provided.


MOL3D--a modular and interactive program for molecular modeling and conformational analysis: II. Extended modules. The new release of MOL3D, a molecular modeling program written in FORTRAN, contains not only enhanced graphic capabilities, but also an improved module for intermolecular calculations that allows rigid and flexible docking. Various interfaces have been added to some well-known and widely diffused programs, such as MM2, AMBER and MOPAC, and to the Cambridge Crystallographic Database. Finally a graph manager and a samples database have been added, which allow efficient searches with various requirements concerning structural templates, pharmacophoric three-dimensional (3D) constraints, and the field of biological activity, if any.


SQUID: a program for the analysis and display of data from crystallography and molecular dynamics. SQUID is a flexible computer program that allows the analysis and display of molecular coordinates from crystallography, NMR, and molecular dynamics. The program can also display two-dimensional and three-dimensional data using many graph types, as well as perform array processing of data with numerous intrinsic functions. Graphics are based on the use of "move" and "draw" instructions, allowing easy development of new device drivers, including vector plotters.


Using a RIBBON program to illustrate lipid bilayer packing. We describe the use of the Priestle RIBBON program suite for the illustration of lipid bilayer packing. The hydrocarbon chains of lecithin-like molecules are representable by beta-sheet arrows. The lateral packing, packing across the bilayer midline and any twisting, bowing, or curling of the polymethylene chain are readily detectable.


A unique structural feature of a phospholipase A2 is probed by molecular dynamics. The unusual catalytic network, revealed by the crystal structure of one of the two phospholipases A2 (PLA2) from the venom of the crotalid A.p.piscivorus has been probed using molecular dynamics. The catalytic network has been remodeled to a conformation similar to that found in all other PLA2, and the modeled structure has been submitted to energy minimization and molecular dynamics simulation, to explore the conformational space of the network. The calculations have yielded a large reorganization of the catalytic network, which gets a conformation close to that of the crystal structure. These results suggest that the unusual catalytic network observed in the studied PLA2 is a structural feature of the protein and not a crystal artifact.


The usage of pregnancy tests in one health district. To investigate the total number of pregnancy tests performed and the proportion that are repeated in one health district. To relate these results to the number of conceptions. Collection of data related to the numbers of pregnancy tests performed from all sources. Surveys of women booking for antenatal care or undergoing nonroutine obstetric ultrasound examination. One health district in the south of England. About five pregnancy tests were performed for each proven pregnancy. Nearly two-thirds of tests were purchased over the counter, the remainder being carried out by hospital laboratories and pregnancy advisory services. Very few women had their pregnancy diagnosed on clinical grounds alone and a small number of ultrasound examinations were apparently performed in lieu of chemical tests. Repeated testing was more likely in primiparous women (P < 0.005). Chemical pregnancy tests appear to be trusted more than clinical examination for the diagnosis of pregnancy by women and doctors. When there is no medical urgency, women who want formal confirmation of pregnancy should be advised that home testing kits will provide the quickest results.


Induction of abortion with mifepristone and misoprostol in early pregnancy. To investigate the clinical efficacy of the combination of mifepristone and an orally active prostaglandin, misoprostol, for early medical termination. Women with amenorrhoea < or = 56 days were given 200 mg mifepristone. 48 h later, 600 micrograms misoprostol was given orally. Medical Termination Unit, Simpson Memorial Maternity Pavilion, Edinburgh. 100 women requesting medical termination of pregnancy. Evacuation of uterus for incomplete abortion or on-going pregnancies. One woman had an incomplete abortion prior to administration of misoprostol. 92 (93%) out of 99 women had complete abortion following administration of misoprostol. There were three on-going pregnancies (3.0%, 95% confidence limits (CL) 0.6-8.6) and four incomplete abortions with this regimen (4.0%, 95% CL 1.1-10.0). 24% women vomited and 7% had diarrhoea following administration of misoprostol. 62% did not require any analgesia. The combination of misoprostol with mifepristone is inexpensive, simple, effective, noninvasive and an acceptable alternative to current regimens for medical termination.


A prospective, randomised, cross-over study comparing the effects of clomiphene citrate and cyclofenil on endometrial morphology in the luteal phase of normal, fertile women. To examine the effect of two anti-oestrogens, clomiphene citrate and cyclofenil, on endometrial morphology in the luteal phase. A prospective, randomised, cross-over study. Jessop Hospital for Women, Sheffield, UK. 10 women who were previously fertile and regularly cycling. The administration of clomiphene citrate or cyclofenil in the treatment cycles. A LH timed endometrial biopsy was taken on day LH + 6. Histological dating and morphometric analysis of the endometrial sample. Only one out of 10 subjects had abnormal endometrium. There was no difference in the results between cycles treated with clomiphene citrate and cyclofenil. Clomiphene citrate or cyclofenil does not have a major adverse effect on endometrial morphology in the luteal phase of normal fertile subjects. The possible adverse effects of anti-oestrogens on endometrium may have been previously overestimated.


The relation between bone mineral density and early pregnancy loss. To determine if women who suffer from early pregnancy loss are at increased risk of osteoporosis later in life. Part of a community screening project for bone mineral density (BMD). 392 women aged 50-54 who had had from 0 to 6 miscarriages out of 0 to 8 term pregnancies. BMD measured using dual energy X-ray absorptiometry at both the lumbar spine and the proximal femur. The mean BMD in nulligravid women was not significantly different from those whose only pregnancies ended in early loss. There was no significant correlation between the BMD at either the lumbar spine or the proximal femur and the number of miscarriages (r = 0.03 and 0.01, respectively). The BMD of the lumbar spine and femoral neck were not affected by parity (P = 0.08 and P = 0.87, respectively). The risk of osteoporosis was not influenced by parity or the number of previous miscarriages.


Episiotomy and perineal lesions in spontaneous vaginal deliveries. To evaluate the influence of mediolateral episiotomy on the perineal state after spontaneous, singleton vaginal deliveries with fetus in the occiput anterior position. The study was a population based, observational study. Two approaches were used in the analyses. Initially, we considered the parturients as quasi-randomised to one of three equally sized groups of midwives with different attitudes towards episiotomy. Secondly, we studied the effect of episiotomy on the state of the anal sphincter, controlling for birthweight, parity, and duration of second stage of labour. 2188 pregnant women delivering consecutively. Perineal lacerations and tear of the anal sphincter. Women allocated to the group of midwives with the lowest rate of episiotomy were more likely to have intact perineum after delivery (OR = 1.8 (1.4-2.2)), had a slight tendency towards more perineal lacerations (OR = 1.3 (1.0-1.5)), but no increase risk of having tear of the anal sphincter, compared with the women allocated to the two groups of midwives with higher frequencies of episiotomy. The second approach showed that episiotomy was related to an increased risk of tear of the anal sphincter (OR = 2.3 (1.2-4.6)). However, this relation was not found among the group of parturients delivered by the midwives with the lowest rate of episiotomy (22%). Our results encourage a conservative approach to the use of mediolateral episiotomy, and in the light of previous findings, it seems reasonable to suggest that episiotomy should ideally be used in about one in five spontaneous vaginal deliveries.


A comparison of perinatal outcome, antenatal and intrapartum care between England and Wales, and France. To compare the national statistics of England and Wales with the national statistics of France, and see if there are significant differences in obstetric care resulting in a significantly different perinatal outcome. Retrospective analysis of national statistics 1970-1989 (latest available figures) relating to perinatal outcome, antenatal and intrapartum care. HIPE and DoH statistics (England and Wales); INSERM statistics (France). Pregnant women residents of England and Wales, and of France. Different aspects of obstetric care for which comparable data were available from national statistics. Perinatal mortality rate, incidence of low birth weight and preterm delivery; type of antenatal care, number of antenatal visits and in-patient admission rate; induction of labour rate, incidence of acceleration of labour with oxytocin, incidence of spontaneous and operative deliveries and person undertaking delivery; episiotomy rate and postnatal in-patient stay. More antenatal intervention and marginally less intrapartum intervention in England and Wales as compared with France. No significant difference in the perinatal mortality rate, in the incidence of low birth weight or preterm delivery, with similar trends being observed over the two decades. Significant differences in obstetric practices between the two countries without a major difference in perinatal outcome.


Perinatal outcome of pregnancies complicated by vaginal bleeding. To examine the effect of first and/or second trimester vaginal bleeding on pregnancy outcome. A prospective one-year birth cohort. Two northernmost administrative districts of Finland. 8718 singleton pregnancies, of whom 807 (9.3%) reported bleeding during the first (601) and/or second trimester (206); light bleeding in 595 cases and heavy bleeding in 212. The remaining 7911 women served as a reference group. Low birth weight rate (LBW), preterm birth rate, congenital malformations and perinatal mortality rate. Bleeding was most frequent in women of more advanced age (> or = 35 years old), with previous miscarriages, with infertility problems or using an IUCD prior to the pregnancy. Parity, smoking and social status were not associated with bleeding. Caesarean section rate and placental complications during the third trimester and at delivery were more common among the bleeders than in the reference group. The LBW rate was three-fold among the bleeders and the preterm birth rate two-fold. The risk (OR) of a LBW infant among second trimester bleeders was 4.1 (95% CI 2.6-6.4), that of preterm birth 2.9 (95% CI 1.9-4.6), and that of congenital malformations 2.9 (95% CI 1.7-4.7). No association existed between bleeding and perinatal mortality. Bleeding during the second trimester indicates a poor pregnancy outcome and an increased risk of LBW, and preterm birth and/or congenital malformation.


A randomised placebo controlled trial of labetalol in the treatment of mild to moderate pregnancy induced hypertension. To determine the need for, and efficacy of, treatment with labetalol in women with mild-to-moderate pregnancy induced hypertension (PIH). Prospective double-blind randomised placebo controlled study. Maternity units of five hospitals in the Trent Region. 144 women (86 primigravid) who developed PIH after 20 weeks gestation. Treatment with oral labetalol up to 600 mg daily or placebo with subsequent care of treatment failures in accordance with the attending obstetrician's practice. Number of days spent as an antenatal inpatient; the development of proteinuria; the perceived need for induction of labour or elective caesarean section; and gestation age at delivery. Labetalol significantly lowered the blood pressure and reduced the incidence of proteinuria. However, neither the number of days spent as an antenatal inpatient, nor the perceived need for induction of delivery or elective caesarean section, nor the gestation age at delivery differed significantly between the two treatment groups. Post-randomisation consideration of early (< or = 32 weeks) and late (> 32 weeks) onset groups showed the placebo treated early-onset group (n = 15) to have more patients with severe hypertension (> 150/110 mmHg) and a greater requirement for additional antihypertensive therapy prior to labour than the group treated with labetalol (n = 16). Anti-hypertensive intervention therapy in pregnancy induced hypertension has been examined using a placebo controlled randomised double-blind trial of labetalol in pregnancy. The maximum blood pressure prior to labour and the incidence of proteinuria was reduced in women on active therapy. However, the length of gestation was not significantly prolonged and indices of clinical outcome were not significantly altered. The appropriateness of pharmacological therapy for late-onset PIH may be questioned.


Early teenage pregnancies in Hull.

Early teenage pregnancies in Hull. To determine the pattern, obstetric outcome and factors that predispose to pregnancies in young teenagers in Hull. Retrospective study of case records of pregnancies from 1977 to 1988 in girls aged 16 years or less and in a control group of nulliparous women aged 20-24 years. Hull health district hospitals. 1,660 pregnant teenagers and 3,576 nulliparas aged 20-24 years. Ages at pregnancy, number of pregnancies per year, gestational age at booking and delivery, antenatal complications, mode of delivery, utilization of contraceptives and some social factors. Of the 1,660 pregnancies in the young adolescents, 59-6% were terminations. The youngest girl was 11. The average annual incidence of early teenage pregnancies was 10.5 per 1,000 girls aged 10-16 compared to 6.4 per 1,000 in England and Wales. Physical characteristics and pattern of antenatal care were similar in the study and control groups. Anaemia was 2.53 times as common in teenagers (95% CI 2.19-2.9; P < 0.0001) while hypertension alone was 1.7 times as frequent (95% CI 1.28-2.4; P = 0.002). Pre-eclampsia and proteinuric disorders were similar in the two groups. Apart from prolonged pregnancy, which was significantly less common in the index group, other gestational ages at delivery and birthweights were the same in both groups. The caesarean section rate in the index group was 0.56 times that in the control group (95% CI 0.4-0.75; P < 0.0001) but forceps deliveries were 2.37 times as common in the index group (95% CI 1.80-3.12; P < 0.0001). The uncorrected perinatal mortality rates were 13.6/1000 and 15.7/1000 in the index and control groups respectively. Early teenage pregnancies are common in Hull and, contrary to previous reports, are physically well tolerated by the early adolescents who book early and attend antenatal clinics regularly. Ineffective utilization and ignorance of contraceptive methods are contributory factors. We recommend that emphasis should be placed on providing contraceptive services for teenagers and adopting a more purposeful and holistic approach to sex education.


Erythropoietin levels in amniotic fluid and extraembryonic coelomic fluid in the first trimester of pregnancy. The aim was to measure erythropoietin levels in amniotic fluid and extraembryonic coelomic fluid from 7-12 weeks' gestation. Twenty healthy women with ultrasonographically normal first trimester pregnancies prior to surgical termination. Paired samples of amniotic fluid and extraembryonic coelomic fluid were collected by transvaginal ultrasound guided needling. Erythropoietin was measured in both pregnancy fluids using a radioimmunoassay. There was a highly significant difference between erythropoietin levels in extraembryonic coelomic fluid (median level 15.45 mU/ml; range 6.8-32.1 mU/ml) and those in amniotic fluid (median 5.0 mU/ml; range < 5.0-5.8 mU/ml) (P < 0.0001; Mann-Whitney U-test). The levels of erythropoietin in maternal serum (median 15.4 mU/ml; range 5.6-29.4 mU/ml) were similar to those in the extra-embryonic coelom (P = 0.81; Mann-Whitney U-test). No relation was demonstrated between erythropoietin levels in amniotic fluid or coelomic fluid and stage of gestation. High levels of erythropoietin in coelomic fluid suggests that the hormone is involved in the process of human extraembryonic erythropoiesis. The exact regulatory role remains unknown.


Pulsatile umbilical venous flow and its clinical significance. To determine the prevalence and significance of pulsatile waveforms from the umbilical vein. A tertiary referral clinic for high risk pregnancies. 209 fetuses from 24-41 weeks gestation. The presence of pulsatile waveforms in the umbilical vein and the pregnancy outcome. 9/209 fetuses demonstrated pulsatile waveforms and seven had severe growth retardation or congenital anomalies of the heart. Pulsatile flow and abnormalities of the inferior vena cava waveforms were observed in these seven but not in the two infants who were born at term. Double pulsations are described for the first time. Examination of the umbilical venous waveform for pulsatile flow is a useful test as it indicates the presence of asphyxial cardiomyopathy or congenital heart lesions.


Serum prolactin concentration in normal and small for gestational age fetuses. To study fetal and maternal serum prolactin concentrations in appropriately-grown (AGA) fetuses and in small for gestational age (SGA) fetuses. A cross-sectional study of 27 AGA and 27 SGA fetuses undergoing cordocentesis for prenatal diagnosis or for determination of fetal karyotype and acid-base balance. Serum prolactin concentration was measured by radioimmunoassay. Harris Birthright Research Centre for Fetal Medicine. In the AGA group, both fetal and maternal serum prolactin concentration increased significantly with gestation (P < 0.001 and P < 0.01, respectively). In the SGA group, the fetal concentration of prolactin was significantly higher (P < 0.05), but the maternal serum prolactin concentration was not different from that of the AGA group. The finding of prolactin in the fetal circulation suggests that the anterior lobe of the pituitary is functioning from at least 12 weeks gestation. The increased serum prolactin concentration in SGA fetuses may be the consequence of hypoglycemic stress on the pituitary or the relative immaturity of the inhibitory hypothalamic-pituitary pathways.


Alpha thalassaemia hydrops fetalis in the UK: the importance of screening pregnant women of Chinese, other South East Asian and Mediterranean extraction for alpha thalassaemia trait. Alpha zero (alpha 0 or alpha-1) thalassaemia is an important genetic risk for women originating from Hong Kong, Singapore, Vietnam, Thailand, the Philippines or South China. Cypriots are also at risk. Carriers of alpha zero thalassaemia trait can be detected by routine haemoglobinopathy screening. When a couple are both carriers, in each pregnancy there is a 25% risk that the fetus will have alpha thalassaemia hydrops fetalis; this is fatal for the fetus and carries serious obstetric and psychological risks for the mother. Most informed couples at risk request prenatal diagnosis and selective abortion. This study investigates the effectiveness of screening, counselling and prenatal diagnosis for alpha thalassaemia hydrops fetalis in the UK. Retrospective analysis of the notes. 18 couples attending University College Hospital London for prenatal diagnosis of alpha thalassaemia hydrops fetalis since 1982. The study shows underdiagnosis of both alpha zero thalassaemia trait and alpha thalassaemia hydrops fetalis leading to avoidable stillbirths and complications in pregnancy. We recommend early screening for alpha zero thalassaemia trait for all women of Southeast Asian or eastern Mediterranean origin and the offer of prenatal diagnosis when indicated. The diagnosis of alpha thalassaemia hydrops fetalis should be considered in women of the relevant ethnic origin who have a stillbirth, neonatal death, abnormal ultrasound findings at fetal anomaly scanning (especially a large placenta), or who develop pre-eclampsia.


Histological incomplete excision of CIN after large loop excision of the transformation zone (LLETZ) merits careful follow up, not retreatment. To quantify and analyse the influence of a histological report of incomplete excision of CIN after LLETZ on frequency of detection of residual CIN. Review of a computerised database of sequential women treated by LLETZ. Initial follow-up was three months post-treatment. The Colposcopy Clinic, Regional Department of Gynaecological Oncology, Queen Elizabeth Hospital, Gateshead, Tyne and Wear, UK. 721 women with CIN diagnosed histologically on LLETZ specimens. In spite of a first time treatment success rate of 95% at 3 months, only 56% of the women were reported to have complete histological excision of CIN. A report suggesting incomplete excision was more likely with more severe CIN, extensive lesions and involvement of the endocervical canal. Furthermore, 21% with residual CIN had apparent complete excision of CIN at LLETZ. A histological report of incomplete excision of CIN at LLETZ does not equate with residual disease. The high treatment success rate of LLETZ means that a report of incomplete excision should stimulate close colposcopic and cytologic follow-up to identify the small number of women with residual CIN after therapy.


A longitudinal study of pelvic inflammatory disease. To study the microbiology and long term prognosis of pelvic inflammatory disease (PID). A prospective study of women with laparoscopically confirmed PID. Teaching hospital in central London. 23 women with PID. Microbiological investigations at the time of diagnosis and at follow up; subsequent fertility and the occurrence of pelvic pain. PID diagnosed by laparoscopy was regarded as moderate to severe in 15 cases. Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum or a combination of these micro-organisms were detected most frequently in the cervix, less often in the endometrium and least in the tubes, C. trachomatis being the micro-organism found most commonly in the tubes. There was serological evidence of acute chlamydial infection in 13 of 20 cases in which paired sera were available and a serological response to M. hominis in 9 of 12 cases in which it was possible to evaluate the results. On the basis of microbiological and serological results, C. trachomatis appeared to be the most important aetiological agent in 10 cases, N. gonorrhoeae in four cases, M. hominis in three cases and U. urealyticum in none; in five cases, two of these micro-organisms appeared to be of equal importance. After 1 to 3 years, 33% of the women were having difficulty conceiving and 56% continued to complain of pelvic pain. It is difficult to be certain of the infectious cause of PID in any given case. However, the evidence that N. gonorrhoeae and C. trachomatis are pathogens is very strong. M. hominis may be responsible for a few cases on its own or together with other micro-organisms.


Distribution of prostaglandin E2 in gastric and duodenal mucosa: possible role in the pathogenesis of peptic ulcer. Prostaglandin E which is present abundantly in the gastric mucosa is a powerful inhibitor of gastric acid secretion and a stimulus to gastric mucus production. In addition, prostaglandin E2 inhibits ulcer formation in animals, and the synthetic analogues of prostaglandin E have successfully been used in the treatment of patients with gastric and duodenal ulcer disease. To evaluate the role of endogenous prostaglandin E2 in the pathogenesis of the peptic ulcer disease, we measured mucosal prostaglandin E2 levels in patients with gastric and duodenal ulcer disease and compared with that of non-ulcer control persons. The study population was made up of 44 non-ulcer persons, 36 patients with a benign gastric ulcer, and 48 with a duodenal ulcer. Every mucosal specimen, taken from the antrum and from the duodenal bulb, were homogenized, mixed with 1 M HCl, and centrifuged. After removal of the supernatant, precipitate was eluted with ethyl acetate in the Amprep C18 minicolumn. Then the extracted prostaglandin E2 in the ethyl acetate fractions was converted into its methyl oximate derivatives, and the prostaglandin E2 level was measured by radioimmunoassay. During the procedure any homogenized specimen which was looking grossly bloody was removed from the assay in order to avoid any possible contamination or prostaglandin E2 in blood. In non-ulcer persons, the mean values was 258.17 +/- 127.03 pg/mg. tissue in antrum and 121.07 +/- 67.46 pg/mg. tissue in duodenal bulb. The corresponding values were 186.42 +/- 70.51 pg/mg. tissue, 79.44 +/- 39.04 pg/mg. tissue in gastric ulcer patients and 204. 94 92.03 pg/mg. tissue, 99.66 +/- 56.10 pg/mgl. tissue in duodenal ulcer patients respectively. Gastric ulcer patients have the significantly lower level of the antral and duodenal prostaglandin E2 (p < 0.005). Those levels of duodenal ulcer patients were also significantly lower than those of non-ulcer persons (p < 0.025 & 0.05). Antral prostaglandin E2 level increased to 305.21 +/- 104.91 pg/mg. tissue in the gastric ulcer patients (p < 0.005) and to 271.02 +/- 93. 23 pg/mg. tissue in the duodenal ulcer (p < 0.005) when the ulcer crater was healed. The duodenal bulb prostaglandin E2 level was also increased in the healed stage of ulcer, e. g., 128.84 +/- 57.62 (p < 0.005) and 112.60 +/- 42.25 pg/mg. tissue, respectively. These results suggest that prostaglandin deficiency in the antral and duodenal bulb mucosa may have an important role in the pathogenesis of peptic ulcer disease.


Biliary proteins in patients with and without gallstones. Nucleation from supersaturated bile of calcium salts of cholesterol and bilirubinate is essential in the formation of gallstone. Nucleation requires gallbladder mucin and its main component, glycoprotein, may contribute to gallstone formation by providing a nidus or matrix for precipitation of lipid components. However, biliary protein patterns of patients with gallstones have not been completely explored. We have tried to extract, isolate and characterize the proteins in patients with gallstones and without gallstones. 21 bile samples were obtained from patients with different types of gallstones and with no stones at cholecystectomy. Biliary protein concentrations were measured by Lowry and Bensadoun methods, and individual glycoproteins from each of the patients were compared by silver staining and densimetric quantification of Sodium Dodesyl Sulfate Polyacrylamide Gel Electrophoresis. 1) Among 16 gallstones, 5 were cholesterol stones, 5 were calcium bilirubinate stones, and 6 were black pigment stones. 2) The mean protein concentration was highest in bile with cholesterol stones (47.6 mg/ml), 24.2 mg% in bile without gallstones, and 15.9 mg/ml in brown pigment stones. 3) Cholesterol gallstones were found to have 14.2 KD glycoproteins, whereas pigment stones were found to have 66 KD glycoproteins. Gallbladder proteins from both cholesterol and pigment stones play an important role in the nucleation and growth of calcium salt crystals.


Extracorporeal shockwave lithotripsy of primary intrahepatic stones. Extracorporeal shockwave lithothripsy (ESWL) was performed in intrahepatic stone patients (n = 18) by Dornier MPL 9,000 with ultrasound guidance. The patients had T-tube (n = 9) or percutaneous transhepatic biliary drainage tube (n = 9). Average treatment session was four and shock-wave numbers were in the range of 3,064 to 12,000 (average 6,288 shocks). Intrahepatic stones were removed completely in 16 patients over a 3 month period by ESWL and combined stone extraction maneuver such as cholangioscopic or interventional radiologic method. Extracorporeal shockwave lithothripsy was very helpful in facilitating extraction of stones in unfavorable locations or located above the severe stricture. In summary, extracorporeal shockwave lithotripsy, followed by percutaneous stone extraction, will provide an improvement in the success rate and duration of treatment required for complete removal of primary hepatolithiasis.


Production of interleukin-2 (IL-2) and expression of IL-2 receptor in patients with IgA nephropathy. IL-2 production has been measured in several disease including type I diabetes mellitus, systemic lupus erythematosus, acquired immunodeficiency syndrome and active pulmonary sarcoidosis and its pathogenetic role was suggested. In IgA nephropathy, altered T cell subsets were reported to be associated with increased synthesis of IgA. The altered IL-2 production and the expression of IL-2 receptor might be involved in the pathogenesis of IgA nephropathy. To investigate the role of T cell mediated immunity in the pathogenesis of IgA nephropathy, the immune parameters such as T cell subsets, NK cell activity, interleukin-2 (IL-2) production and IL-2 receptor expression on peripheral blood mononuclear cells (PBMC) were measured before and/or after phytohemagglutinin (PHA) stimulation in 15 patients with IgA nephropathy. Age and sex matched 15 healthy controls and the correlations between the IL-2 production and immune parameters were evaluated. The mean percentages of T helper/inducer cells (CD4), T suppressor/cytotoxic cells (CD8) and the CD4/CD8 ratio of the patients were not different from those of controls and the proportions of CD8 CD11b cell in the patients (21.0 +/- 3.6%) were significantly lower than those in controls (30.5 +/- 5.3%) (p < 0.005). The production of IL-2 by fresh PBMC of both patients and controls was in undetectable ranges. The production of IL-2 by PHA stimulated PBMC of patients was significantly higher than that of controls (140.03 +/- 43.2 U/ml vs 106.5 +/- 42.1 U/ml, p < 0.05). The proportions of lymphocytes expressing the IL-2 receptor (CD25) before the stimulation with PHA in patients were 1.22 +/- 1.00 percent and were not different from those in controls (1.12 +/- 0.78 percent). The correlations between the production of IL-2 and the concentrations of serum IgA, the degrees of histologic alterations and the proportions of CD8 and CD8CD11b cells were not significant. There was a weak tendency of a positive correlation (p < 0.1) between the production of IL-2 and the proportions of CD4 cells, and the CD4/CD8 ratio showed a significant correlation with the production of IL-2 (p < 0.05). After PHA stimulation, the mean percentages of lymphocytes expressing the IL-2 receptors in patients were increased to 47.6 +/- 8.9 percents which is higher than those (40.4 +/- 9.9%) in controls (p < 0.05). The NK cell activity of the patients was higher than that of controls (75.6 +/- 19.6% vs 56.1 +/- 16.2%, p < 0.005), and was well correlated with the production of IL-2 by PBMC (r = 0.89, p < 0.05). It seemed that patients with IgA nephropathy have an 'latent' cellular immunoregulatory dysfunction that becomes apparent on the stimulation of extrinsic antigens or mitogens.


Heterogeneous changes of serum potassium levels in NIDDM patients on oral glucose load. Ten noninsulin dependent diabetic patients (NIDDM) without baseline hyperkalemia and with normal aldosterone levels when given 100 g of glucose orally revealed heterogeneous responses in serum potassium changes. Six diabetics had paradoxical increases in serum potassium levels averaged 0.44 mEq/L (range, 0.1 to 1.1 mEq/L) and were accompanied by increases in plasma aldosterone levels. On the contrary, four other noninsulin dependent diabetics and four nondiabetic control subjects had gradual decreases in serum potassium levels with simultaneous decreases in plasma aldosterone levels. These rises and falls in serum potassium concentrations coincided with changes in serum osmolality related mostly to the degree of increases in serum glucose following oral glucose administration. pH of venous blood didn't show any relevant and significant changes with changes of serum potassium levels following oral glucose load. This finding suggests that osmotic mechanisms with various degree of well known abnormal insulin secretion and resistance to insulin action in target tissues in NIDDM patients may account for these heterogeneous responses in serum potassium changes after glucose load, and normal aldosterone levels may not be sufficient to prevent glucose induced increases in serum potassium in NIDDM patients.


Computed tomographic correlation with pituitary function in Sheehan's syndrome. Twenty six patients with Sheehan's syndrome were studied with high-resolution computed tomography (CT) and the sequential pituitary stimulation test in order to correlate the CT findings of the sella turcica with the pituitary reserve functions. CT revealed 21 completely empty sella (CES), 4 partially empty sella (PES) and 1 normal sella. Panhypopituitarism occurred in 1 of 4 patients with PES and 20 of 21 with CES. One patient showing normal sella had a normal preservation of prolactin (PRL), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH) and lutenizing hormone (LH). In all patients with PES and CES, growth hormone (GH) responses to hypoglycemia and PRL responses to thyrotropin releasing hormone (TRH) were blunted. Three (75.0%) with PES had normal basal cortisol levels, which were more frequent than two (9.6%) with CES; however, most of the PES (3 of 4) and CES (20 of 21) demonstrated blunted cortisol responses to hypoglycemia. Three (75.0%) with PES and only one (4.8%) with CES had normal thyroxine levels and TSH responses to TRH. None with PES showed decreased basal and stimulated levels of FSH and LH, whereas 15 of 21 with CES did. The pituitary functions of the patients having considerable amounts of pituitary remnants visualized by CT were relatively preserved for TSH, cortisol, FSH and LH. Considering the above results, changes in the amounts of pituitary remnants detected by CT might correlate with hormonal secretory capacity.


The effect of Dermatophagoides pteronyssinus allergens on proliferation and CD23 antigen expression of peripheral blood lymphocytes from atopic patients. The low affinity IgE receptor (Fc epsilon RII/CD23) has been proposed to be involved in the regulation of IgE synthesis. The present study was undertaken to investigate the responses to in vitro stimulation by allergen (Dermatophagoides pteronyssinus; D.p) and/or interleukin-4 (IL-4) of peripheral blood lymphocytes (PBLs) isolated from atopic and non-atopic subjects. IL-4 induced up to 5 fold increase in CD23 expression on PBLs from both atopic patients and normal controls, whereas the D.p extract increased CD23 expression on cells from 7 of 8 atopic donors and from 2 of 8 normal controls. The combination of IL-4 and allergen had an additive effect of CD23 expression. PBLs from 6 of 8 atopic patients but 1 of 8 normal controls showed significant proliferative responses to D.p extract whereas IL-4 did not induce any cell proliferation. The dose of D.p extract required for the maximal CD23 expression was 20 fold higher than that for cell proliferation. These results imply that allergen stimulation, presumably through proliferating allergen specific T cells which secrete IL-4, activates B cells from most atopic donors and a few non-atopic donors resulting in increased CD23 expression. This allergen-mediated CD23 expression may play an important role in specific IgE production.


Percutaneous mitral valvuloplasty in a mid-term pregnant woman with severe rheumatic mitral stenosis. A 28-year-old woman with severe mitral stenosis underwent percutaneous mitral valvuloplasty at 26 weeks' gestation. Balloon dilation using a double 18-18 mm balloon resulted in improvement in mean mitral pressure gradient (32 to 8 mmHg) and in calculated mitral valve area (0.9 to 2.4 cm2) without complications and any evidence of fetal distress during procedures with an estimated radiation exposure to the fetus of 0.13 rem. This procedure resulted in the disappearance of symptoms of congestive heart failure and allowed for normal full term spontaneous delivery of a 3.51 Kg boy without any complication.


Diastolic mitral regurgitation in intact mitral valve detected by color Doppler echocardiography in a patient with acute aortic regurgitation. A 38-year-old man was admitted with coingestive heart failure due to infective endocarditis. Echocardiography with color Doppler imaging revealed severe aortic regurgitation, mitral valve premature closure and diastolic mitral regurgitation. The flow of the diastolic mitral regurgitation was directed to the posterior wall of the left atrium through just behind the posterior mitral leaflet. The diastolic mitral regurgitation was observed only in the period of late diastole and no mitral regurgitation could be detected in the systolic phase. After successful aortic valve replacement, the diastolic mitral regurgitation disappeared completely.


Nosocomial Legionnaire's disease--a case report and review of the literature. We report a case of nosocomial legionellosis in a 63 year-old man who was managed with neurosurgery under the diagnosis of subarachnoidal hemorrhage and complicated pneumonia in the intensive care unit. A legionella species was reported from sputum culture and direct immunofluorescent antibody test revealed L. pneumophila (serogroup 2). Our patient's pneumonia was cured with medical therapy including erythromycin and was the first case of microbiologically confirmed legionellosis in Korea.


Myopia following penetrating keratoplasty for keratoconus. The frequent occurrence of spherical myopia after penetrating keratoplasty for keratoconus is partly the result of the excessive dioptric power of the grafted cornea which occurs when the diameter selected for the donor button is greater than the diameter of the host incision. This excessive power could be reduced by eliminating disparity between the diameters of the graft and host. To determine what proportion of the myopia in these eyes would persist as a result of axial myopia the axial lengths of 60 patients grafted for keratoconus and 25 emmetropic controls were compared. A keratometry, objective refraction, and contact probe ultrasonic biometry were performed on all eyes. A comparison of the results with a representational schematic eye indicated that the mean spherical refractive error of the grafted keratoconic eyes (-4.83 dioptres) was the combined effect of steepness of the corneal graft (mean radius of curvature 7.46 mm) and an abnormally great axial length (mean 24.84 mm). The increased axial length was mainly the result of elongation of the posterior segment of the globe with a small contribution from an increased anterior chamber depth. Though axial myopia is common in keratoconus, a further study of 70 keratoconic eyes that had not been grafted showed no statistically significant correlation between the posterior segment length and the severity of corneal ectasia. These data suggest that even if excessive corneal power is eliminated after penetrating keratoplasty for keratoconus the associated axial myopia would still produce a mean spherical refractive error of at least -2.8 dioptres.


Deep lamellar keratoplasty on air with lyophilised tissue. Deep lamellar keratoplasty on air involves injecting air into the corneal stroma to expand it to several times its normal thickness. This method is designed to facilitate dissection of the deep stroma and reduce the risk of perforation of Descemet's membrane when carrying out deep lamellar keratoplasty. We have modified the technique by using prelathed freeze-dried donor tissue and report our results in a series of patients with corneal stromal scarring owing to a variety of corneal problems, namely, keratoconus, pterygium, and herpes zoster ophthalmicus. All patients achieved best corrected postoperative visual acuity of 6/12 or better without problems associated with graft failure or rejection. Histopathological examination of corneal tissue following air injection showed surgical emphysema within the cornea and separation of deep stromal fibres from the underlying Descemet's membrane.


Prognostic importance of ophthalmic manifestations in childhood leukaemia. In order to assess the systemic prognosis of children with leukaemic ocular involvement, 63 of 131 patients admitted to hospital with acute leukaemia were evaluated ophthalmically. A total of 28 of 63 showed ophthalmic involvement and were followed up for up to 84 months. Twenty seven of 28 patients (96.4%) died within 28 months after the onset of ocular involvement and within 83 months after the onset of leukaemia. The 5 year survival rate of patients with ophthalmic manifestations was 21.4% (6/28). This survival rate was significantly lower than that of those who lacked ophthalmic manifestations (16/35: 45.7%, p < 0.05). All of the patients with ophthalmic manifestations had either bone marrow relapse or central nervous system leukaemia. The prognosis was related to risk factors such as central nervous system leukaemia or bone marrow relapse in most cases.


Ultrasound morphology of carotid lesions in retinal ischaemia. The extracranial carotid arteries of 165 patients with retinal ischaemic symptoms were examined with duplex ultrasound. Both the degree of stenosis and the morphological appearance of the lesions were examined. Ipsilateral carotid artery disease was found in 88% of patients. Degrees of stenosis of between 50-99% were found in 33% of patients, the majority of these lesions being complex heterogeneous in nature. Stenosis of < 50% was found in 40% of arteries. The majority of lesions causing < 20% stenosis were homogeneous in nature. However, in stenosis of 20-49%, 63% of lesions were found to be complex heterogeneous. A similar distribution of lesions was found in the contralateral carotid arteries. It is important to examine both ipsilateral and contralateral arteries, and to evaluate the morphological characteristics of all lesions causing > 20% stenosis.


Amaurosis fugax in young people.

Amaurosis fugax in young people. Nine young adults (median age 19.5 years) who suffered from amaurosis fugax (AF) are described. The attacks of AF were short in duration and preceded by premonitory symptoms in five cases and by a migrainous headache in two. In five patients the visual loss progressed in a lacunar pattern unlike the 'curtain' pattern characteristic of AF in older patients. Investigation revealed no evidence of an embolic or atheromatous aetiology. In two cases a minor abnormality was found on echocardiography. We conclude that AF in young adults has a different clinical pattern and may have a different aetiology, possibly migrainous, compared with that seen in older patients. The pattern of visual loss in some of the cases suggests that the choroidal circulation rather than the retinal circulation is primarily affected.


Endoscopic visualisation of the human nasolacrimal system: an experimental study. Orthograde and retrograde endoscopy of the upper and lower nasolacrimal system was performed using two prototype ultrathin (0.5 mm and 1.1 mm diameter) fibrescopes on four cadaver heads. Appearances were verified by subsequent dissection. The procedure, which we term 'dacryocystoscopy' is described. With modifications this technique may have clinical applications in the treatment of nasolacrimal disorders.


Copper levels in human mixed, nuclear brunescence, and posterior subcapsular cataract. The study was undertaken to determine the copper content in different human cataractous lenses. The level of copper increased with increasing age in nuclear brunescence and mixed cataractous lens and a low amount of copper was observed in the posterior subcapsular cataractous lens with increasing age. Cataractous lenses of females have greater amounts of copper compared with males.


A new local anesthesia technique for cataract extraction by one quadrant sub-Tenon's infiltration. A new technique of local anesthetic administration has been used for 50 patients undergoing cataract extraction. The simple technique involves direct transconjunctival infiltration of local anaesthetic directly to the sub-Tenon's space, in the inferior-nasal quadrant, using a blunt 19-gauge Southampton cannula. This method seeks to avoid the risks of retrobulbar haemorrhage, perforation of the globe, damage to the optic nerve, and injection into the subarachnoid space, whilst providing prolonged and reliable anaesthesia. Akinesia is achieved by the inferior-nasal placement of solution and if not sufficient, a top-up can easily be given. Patients graded any discomfort or pain using a 10 cm visual analogue graphical pain score chart with numerical and descriptive rating scale. The delivery of 50:50 mixture of lignocaine 2% and bupivacaine 0.5% anaesthetic was evaluated by patients with a median response of 'slight discomfort'. The operative procedure was graded with a median of 'no pain or discomfort', both for extracapsular cataract extraction and phakoemulsification. This is a new, modified, sub-Tenon technique which is simple, reliable, and which offers excellent anaesthesia and akinesia and avoids a sharp instrument being passed into the orbit.


One stage adjustable sutures: practical aspects. Strabismus surgery using one stage adjustable sutures was carried out under local anaesthesia in six patients with good results. The criteria for patient selection and the surgical technique are discussed.


A photometric study of the effect of pupil dilatation on Nd:YAG laser iridotomy area. A photometric study of the effect of pupil dilatation on Nd:YAG laser iridotomy area was performed in 21 eyes of 21 patients. The iridotomy area was 0.075 (0.055) mm-2 (mean (SD)) before pupil dilatation and 0.073 (0.070) mm-2 after pupil dilatation (t test NS). Iridotomy area after pupil dilatation correlated with iridotomy area before pupil dilatation (r = 0.815, p < 0.01) but did not significantly correlate with measures of iridotomy shape or position, or with changed iris area following pupil dilatation. Two iridotomies became reduced to less than 20% of their initial area following pupil dilatation. Our findings suggest that the only effective method of avoiding development of unacceptably small iridotomy area after pupil dilatation is to create a sufficiently large iridotomy at the time of initial laser surgery.


A case of amniotic band syndrome with bilateral epibulbar choristoma. An autopsy case of amniotic band syndrome with bilateral epibulbar choristoma is described. The left eye reveals a complex choristoma and the right eye a dermis-like choristoma. Both choristomatous lesions included lenticular tissue suggesting that rupture of the amnion, which is the initial event of amniotic band syndrome, might have occurred at about the fourth week of gestation. Since the other systemic manifestations of amniotic band syndrome are considered to be compression deformities of the fetus caused by oligohydramnios or amniotic band, the occurrence of epibulbar choristomas in both eyes in this case suggests that a compression mechanism may play a role in the pathogenesis of epibulbar choristoma.


Periocular migration of an intraocular lens. A woman presented with a painful eye 6 weeks after cataract extraction and intraocular lens implantation. In the past she had had a sector iridectomy for iris bombé caused by chronic anterior uveitis. On examination the three central corneal sutures were absent, whilst the medial and lateral sutures had broken and were protruding from the section. The eye was quiet and the section intact. Combined clinical and ultrasound examination failed to locate the intraocular lens. Four months postoperatively, while being fitted for contact lenses for the correction of aphakia, the intraocular lens appeared from the superior fornix.


Colour Doppler ultrasound in the management of a case of cranial arteritis. Colour Doppler ultrasound allows simultaneous B scan and Doppler imaging and can be employed to determine the velocity of blood flow in the vasculature of the eye and orbit. We describe a case of cranial arteritis (giant cell arteritis) in which serial velocimetry recordings were obtained. At one stage in the disease process no blood flow was detectable in the orbit despite previously reliable recordings. This coincided with a deterioration of the clinical state of the patient as signified by recurrent anterior ischaemic optic neuropathy despite controlled symptomatology and erythrocyte sedimentation rate by prednisolone therapy. Subsequent increase in the immunosuppressive therapy was accompanied by a return of blood flow in the orbit. Colour Doppler ultrasound may prove to be a useful examination technique in the diagnosis and management of cranial arteritis.


Complicated extracapsular cataract surgery in pseudoexfoliation syndrome: a case report. Crystalline lens dislocation and zonular dialysis during intraocular surgery are recognised features of the pseudoexfoliation syndrome (PES). A case is reported in which zonular dialysis occurred in both eyes during extracapsular cataract extraction. In particular surgery was complicated by difficulty in performing anterior capsulotomy. Careful preoperative assessment and peroperative technique may help to reduce the risk of surgical complication in PES.


Nocardia choroidal abscess.

Nocardia choroidal abscess. Nocardia is a Gram positive, aerobic, filamentous branching micro-organism that rarely causes human infection. When infection does occur it usually takes the form of a subcutaneous abscess or a pneumonia-like illness. We describe a case of a patient with chronic lymphocytic leukaemia who developed painless loss of vision in the right eye secondary to a choroidal abscess after a prolonged course of treatment on several immunosuppressive agents. The patient also complained of right shoulder pain that was unresponsive to conventional therapy, and had been admitted and treated for several episodes of 'pneumonia'. A diagnostic transvitreal fine-needle aspiration biopsy of the ocular lesion was performed which demonstrated Nocardia asteroides. This allowed for appropriate antibiotic therapy to be instituted early in the course of the infection and prompted the systemic work-up which also demonstrated central nervous system and arthropic nocardial infection.


Eye movement tics.

Eye movement tics. An 8-year-old girl presented with opsoclonus-like eye movement and an 18 month history of intermittent facial tics. Investigations were all normal. Electro-oculography showed the eye movements to be of variable amplitude (10-40 degrees), with no intersaccadic interval, and with a frequency of 3-4 Hz. Saccades, smooth pursuit, optokinetic, and vestibular reflexes were all normal. These abnormal eye movements eventually disappeared. It is thought that they were a form of ocular tics.


Primary uveal B immunoblastic lymphoma in a patient with AIDS. A case of primary intraocular malignant lymphoma without cerebral involvement is reported in a 30-year-old man with acquired immunodeficiency syndrome. The study of the enucleation specimen showed a B immunoblastic lymphoma with a CD30 positive anaplastic large cell component. There was no involvement of the adnexal structures of the orbit. The patient subsequently completed non-surgical staging showing no extension of the tumour. The clinical course was rapidly fatal with dissemination to the pericardium and pleura.


The physiology and pathology of the esophagus. The esophagus and trachea derive from the foregut during the 4th week of development and is constructed as a part of the gut: longitudinal and circular muscle bundles are connected to a functional system together with collagen and elastic fibers. The action of the cricopharyngeal "pinch-cock" is pronounced in the newborn. In the region of the upper orifice ganglion cells are absent and venous vessels are oriented in a longitudinal direction. The myoelastic fiber system is in the lower part of the esophagus arranged as a stretching system, and the esophagus becomes longer and narrower by traction. The blood vessels derive from the thyroid arteries, the aorta, the bronchial arteries, the left gastric artery and the left inferior phrenic artery. Poor zones of vascularity are in the middle of the ventral and dorsal plane.


Diaphragmatic hernia in infancy and childhood--20 years experience. Congenital diaphragmatic hernia through the foramen of Bochdalek usually presents with severe respiratory symptoms soon after birth. Despite successful repair of the defect the mortality rate still remains high. This may be due to co-existing pulmonary hypoplasia with pulmonary hypertension and concomitant right-to-left shunting. In order to find factors that predispose for good or bad outcome as well as to compare different modalities of treatment being used at our hospital, this twenty-year retrospective study was undertaken. It is confirmed that the extent of pulmonary hypoplasia at birth rather than the promptness of surgical repair and the skill of intensive care appears to be the major mortality factor. Initial experiences from extracorporeal membrane oxygenation (ECMO) are promising.


Nissen fundoplication for gastro-esophageal reflux in repaired tracheo-esophageal fistula. One hundred and fifty three patients had repair of tracheo-oesophageal fistula in a 15 year period of observation. Of these 55 had associated gastro-oesophageal reflux and of these 12 (8%) underwent a Nissen fundoplication. All patients manifested significant failure to thrive but weight-gain was documented in all patients following their fundoplication. Twenty five percent of patients demonstrated recurrent reflux in this study and emphasises the difficulty of treating gastro-oesophageal reflux in repaired tracheo-oesophageal fistula patients. Careful selection is important.


Laparoscopic surgery in children and adolescents with suspected appendicitis: results of medical technology assessment. Laparoscopy has been performed in 43 patients aged up to 18 years with suspected appendicitis; 20 were children 8-15 years and 23 adolescents 16-18 years of age. Diagnostic laparoscopy was successful in 36 (84%) patients; in 7 (16%) subsequent laparotomy was necessary to establish the diagnosis, in 4 (9%) because the appendix was not visualized. Laparoscopic appendectomy was done in 33 (77%) patients, additional laparoscopic adhesiolysis in four and inversion of a diverticulum in one. Changing to laparotomy during the laparoscopic operation was necessary in one patient because of a technical problem and in another because of bleeding of the appendicular artery. Laparoscopy was totally free of complications in 33 (77%) patients; another 9 (21%) had surgical or technical problems without negative outcome for the patient. In one (2%) patient a wound infection led to a negative outcome; there were no other laparoscopy-related events. The mean intensity of pain on the first day after laparoscopic appendectomy was 31 points (Visual Analogue Scale with 100 points) and decreased to nearly zero on the third day; 37% of patients needed opioids on the first and none on the third day. There was no statistical difference for pain intensity and consumption of analgesics after appendectomy via laparoscopy versus laparotomy. We conclude that diagnostic and therapeutic laparoscopy in children and adolescents with suspected appendicitis is a safe and effective procedure.


Isolated bowel injury in blunt abdominal trauma in childhood. From a total of 734 children with a blunt abdominal trauma admitted to the hospital in the past 15 years, 21 patients (3%) sustained an isolated injury of the bowel (8 duodenal, 9 jejunal and 4 colon ruptures). All patients were laparotomized without a postoperative mortality. Accompanying abdominal injuries were seen only in duodenal ruptures (pancreatitis and one choledochal and pancreatic ruptures). In 85% the blunt violence was caused by bicycle accidents due to the handle bar, in one case by a car accident and in 3 children by falls. Accurate diagnosis was only possible regarding the history, the mechanism of the accident and an exact repeated clinical examination. Despite further investigations of blood chemistry laboratory findings, ultrasound and x-ray, no further confirmation of the diagnosis could be achieved. Complications, occurring in 14% of our patients, were not related to the trauma itself, but caused by a delayed diagnosis and therapy.


The significance of multiple trauma in children. Accident-related injuries, mainly traffic-connected, are the most serious threat to health and most-frequent cause of death in the pediatric age group. Usually these are multi-system injuries. While the total number of accidents has decreased over the last 20 years, traffic accidents have become more serious. Conventional prognostic scores are not applicable in children with multiple injuries because of their essential pathophysiologic differences with adults. The Pediatric Trauma Score closes this gap. It is simple to use and provides high reliability.


Treatment of ruptures of the symphysis and iliosacral joint in pediatric patients. The three osseous parts of the human pelvis form a continuous structure because of the symphysis and both iliosacral joints that-owing to their mobility-make possible a shock-absorption of vertical forces. The goal in the treatment of ruptures of the symphysis and/or of the sacroiliac joints is the restoration of functioning joints. Especially in the adolescent, a stiffening of these joints has to be avoided. Therefore, we treat ruptures of the pelvic joints with an overbridging banding that preserves the function of shock absorption. Due to utilisation of a banding, made up of polydioxanone, another operation to remove internal fixation material is not necessary. Rupture of the symphysis or iliosacral joint in the pediatric patient is very rare. Only three among the 67 patients whom we operated on because of a rupture of the symphysis or iliosacral joints between 1984 and 1990 were children. These were an eleven-year-old girl and a nine-year-old boy, who had suffered a rupture of the symphysis, and an eight-year-old boy with a disrupted iliosacral joint. In these children a banding with PDS suture was performed. At a follow-up examination, the children were free from pain and did not feel restricted in their daily routine or their physical activities.


Elective testicular biopsy at the end of maintenance treatment for acute lymphoblastic leukemia. A prospective study. Open testicular wedge biopsy has electively been performed prior to completion of maintenance therapy for acute lymphoblastic leukemia. 25 boys during 6 years were included in this prospective study. Three boys developed testicular enlargement while on maintenance therapy and biopsies confirmed testicular leukemia. The remaining 22 boys were biopsied at termination of maintenance therapy. Occult testicular relapse was revealed on histologic examination in only one boy with normal testicular size. During the follow-up period, one boy developed overt testicular relapse two months after negative biopsy. These results will not justify electively performed routine biopsy prior to termination of chemotherapy. Instead, careful and minute clinical examination of the testicles, estimating their size and consistence, should be performed regularly at short intervals.


Incomplete bilateral transverse facial cleft--a previously unreported associated defect of the Kallmann's syndrome. In 1944 Kallmann et al described sex-linked inheritance of hypogonadotropic hypogonadism with anosmia and noted the co-occurrence cleft lip, cleft palate and cranio-facial asymmetry. Since then, other clinical cases associated with various skeletal, ophthalmic, urogenital, cardiovascular and central nervous system disorders have been reported. This article presents the case of a 17-year-old girl with a bilateral incomplete facial cleft in association with the Kallmann's syndrome, a previously unreported connection. We describe the plastic surgical reconstruction of the bilateral incomplete facial cleft. The mechanism of this embryopathologic association of the Kallmann's syndrome is, we suggest, due to a developmental disturbance in the region of the median forebrain organizer and associated structures, possibly in connection with a pleiotropic genetic mechanism.


Echocardiographic proof of pulmonary hypertension with irreversible increased resistance in the pulmonary circulation as a complication after placement of a ventriculo-atrial shunt for internal hydrocephalus. Increased resistance in the pulmonary vessels in children with ventriculo-atrial shunts is a rare and often unrecognized permanent complication. We report 2 children in whom this diagnosis was detected by two-dimensional echocardiography. The first patient received a ventriculo-atrial shunt at age 9 days for congenital internal hydrocephalus. At 17 months it had to be replaced because of infection of the efferent catheter limb. At 22 months at a routine follow-up the echocardiographic diagnosis of pulmonary hypertension was made. Invasive studies confirmed the presence of irreversible increased resistance in the pulmonary circulation. The second patient received a ventriculo-atrial shunt at age 13 months because of a cerebral cyst. After repeated catheter infections, at 28 months a ventriculo-peritoneal shunt was placed. At age 4 years the diagnosis of pulmonary hypertension was made by routine echocardiography. This finding was confirmed by invasive studies. The left pulmonary artery was completely occluded. Both patients had developed microemboli, caused or aggravated by catheter sepsis, in the second case probably through contiguous clot growth up to complete occlusion of the left pulmonary artery. Therapeutic measures seemed not to be indicated. Two-dimensional echocardiography proved to be a reliable method for diagnosing increased resistance and pulmonary hypertension. We recommend routine echocardiography for follow-up in all children with ventriculo-atrial shunts.


Chronic organoaxial malrotation of the stomach in childhood. During a six-month period five patients presented to The Royal Belfast Hospital for Sick Children between the ages of three weeks and three years with recurrent vomiting and failure to thrive. All were diagnosed as having organoaxial malrotation of the stomach by barium meal examination. Symptoms were refractory to conservative management but combined gastropexy and fundoplication was successful in all cases.


Continuous arteriovenous hemofiltration (CAVH) in a premature newborn as treatment of overhydration and hyperkalemia due to sepsis. If renal replacement therapy is required in the neonatal period, peritoneal dialysis is generally applied. In some cases, for example after extensive abdominal surgery, peritoneal dialysis is not possible. Continuous arteriovenous hemofiltration may then be an attractive alternative. The present paper describes the positive results in a 1265 g premature baby.


Malignant melanoma in a three-year-old child. Malignant melanoma is an uncommon tumor in childhood. We report on a case occurring in a 3-year-old child with congenital multiple melanocytic nevi.


Cystic degeneration in non-ossifying fibroma. Two unusual cases of non-ossifying fibromas in boys of 4 years with partial cystic degeneration are presented. The osseous cavities did not respond to corticosteroids.


Report on a case of Hutchinson-Gilford progeria, with special reference to orthopedic problems. Hutchinson-Gilford progeria is a very rare syndrome of premature aging and often features many orthopedic abnormalities. This is a case report on a young boy suffering from progeria. His orthopedic history included bilateral talus deformities of the feet, bilateral dislocated hips, pes planus, a fractured femur (which healed without complications), aseptic necrosis in the left nuclear head of the femur, bilateral fixed hip flexion deformities, bone dysplasia, osteoporosis and osteolysis.


Improving responses in hepatomas with circadian-patterned hepatic artery infusions of recombinant interleukin-2. Previous studies on continuous hepatic artery infusions of recombinant interleukin-2 (IL-2) have shown that in a nontumor-bearing animal a continuous infusion given in a circadian "day cycled" pattern was much less toxic and could be given with 10 times higher doses of IL-2 than if the constant pattern of infusion was used. In the present study, circadian-patterned continuous hepatic artery infusions of IL-2 were used in hepatoma-bearing rats. Doses of 10 mg/m2/day could be tolerated when IL-2 was given in a "day cycle" rhythm. Control animals were given 1 mg/m2/day of constant infusion IL-2, which was the highest hepatic artery infusion dose tolerated at a constant rate without mortality in nontumor-bearing animals. Animals treated with the constant infusions of IL-2 had a 37.5% mortality rate and a 25% objective response rate in measurable tumor size. Animals receiving the "day cycle" had no mortality and a 100% objective response rate. The conclusion was that "day cycled" circadian-patterned continuous hepatic artery infusions of IL-2 could be given with much lower toxicity and much improved tumor response rates than constant continuous infusions.


Interleukin-6 increases carcinoembryonic antigen and histocompatibility leukocyte antigen expression on the surface of human colorectal carcinoma cells. Human colorectal carcinoma cells that were treated in vitro with interleukin-6 (IL-6) expressed increased levels of carcinoembryonic antigen (CEA) and normal histocompatibility leukocyte antigen (HLA) class I on their cell surface. The IL-6 mediated increase of CEA expression on the surface of a moderately differentiated colon carcinoma cell line (WiDr) was time- and dose-dependent. A 5-day treatment of the WiDr cells with 100 U IL-6/ml increased the percentage of cells that expressed CEA from 29 to > 80% and enhanced the level of HLA class I expression. The increase in CEA expression as a result of IL-6 treatment was also observed using SDS-PAGE/Western blot analyses, and subsequent Northern blot analyses revealed concomitant increases in CEA-related mRNA transcripts. A comparison of the increases in CEA expression after IL-6, interferon-beta, and interferon-gamma on a nanomolar basis revealed that IL-6 was more potent than either of the interferons. Of 11 different human colorectal tumor cell lines that were treated with IL-6, CEA and/or HLA class I expression were increased in five. Thus, IL-6 can act directly on human colon carcinoma cells and selectively increase the expression of CEA and HLA class I antigens, which may provide some insight into the mechanisms involved in the ability of IL-6 to suppress in vivo tumor growth.


Induction of circulating phospholipase A2 activity by intravenous infusion of endotoxin in patients with neoplasia. The purpose of this study was to evaluate the impact of repeated intravenous infusions of endotoxin (EN) in patients with cancer on the systemic release of extracellular proinflammatory phospholipase A2 (PLA2) and its relationship to the release of tumor necrosis factor (TNF) and interleukin-6 (IL-6). Six patients received 15 infusion of EN isolated from Salmonella abortus equi at a dose of 4 ng/kg. Marked increase in the activity of circulating PLA2 was noted within 3 h after the first EN infusion and reached a maximal level of 20.4-fold greater than baseline 24 h after infusion. In five patients challenged with EN 2 weeks later, PLA2 reached peak levels 15.5-fold greater than baseline. In two patients who received three sequential daily infusions, the incremental increase in PLA2 activity after the second and third challenge reached maximum levels 6 h after EN infusion. PLA2 response followed those of TNF and IL-6 but was quantitatively different. Whereas maximal levels of TNF and IL-6 declined substantially after repeat EN challenges, no such decline occurred in PLA2 activity. Since, in the clinical setting of gram-negative sepsis, there is recurrent increase in circulating EN, our study approximates this clinical situation and shows that extracellular release of PLA2 follows temporally that of proximal cytokines such as TNF and IL-6. These cytokines may be related to PLA2 release and sustained high activity in the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)


Cytokine induction and therapeutic synergy with interleukin-2 against murine renal and colon cancers by xanthenone-4-acetic acid derivatives. Derivatives of xanthenone-4-acetic acid (XAA) have been found to have similar activity to flavone-8-acetic acid against transplantable solid tumors. Some of these compounds were compared to flavone acetic acid (FAA) in their ability to induce cytokines as well as to mediate antitumor effects against murine renal cancer (Renca) and a mouse colon cancer (MCA-38). 5-Methyl-XAA and 5-chloro-XAA proved to be more potent than FAA on a mg/kg basis for induction of the genes for IFN alpha, IFN gamma, and TNF alpha, and for IFN and TNF activities in the sera of treated mice. These effects were sharply dose dependent. On the other hand, 7-methyl-XAA, which has no antitumor activity, did not induce these genes. In addition, 5-methyl-XAA and 5-chloro-XAA but not 7-methyl-XAA synergized with recombinant human interleukin-2 (rhIL-2) for the treatment of Renca and MCA-38. Doses of the active derivatives that failed to induce cytokines also exhibited no therapeutic synergy with rhIL-2. These results suggest that at least some of the antitumor effects of these XAA derivatives are related to their ability to induce cytokines.


A pilot study of the combination of interleukin-2-based immunotherapy and radiation therapy. A clinical trial was undertaken to evaluate the feasibility of combining radiation therapy and immunotherapy. Twenty-eight patients with metastatic cancer were treated with rapid fractionation radiation up to 2,000 cGy, followed within 24 h by a course of interleukin 2 (IL-2) at 720,000 IU/kg or tumor-infiltrating lymphocytes (TILs) and IL-2 at 720,000 IU/kg. All patients tolerated treatment without any apparent increase in toxicity referable to the irradiation. Four patients had significant shrinkage of tumor at the irradiated site. Only two patients showed significant tumor shrinkage both inside and outside of the irradiated field. While rapid fractionation radiation can be safely administered in combination with immunotherapy, we observed no apparent synergy in antitumor effect in this small number of patients.


Sequential chemotherapy and immunotherapy for the treatment of metastatic melanoma. Interferon (IFN) has numerous biological properties, and more recently a new role for interferon has emerged, as a modulator of cytotoxic chemotherapeutic agents. This is based upon preclinical data that demonstrate additive and/or synergistic effects of IFN with a number of anticancer drugs including cisplatin against human cancer cell lines. Therefore, we evaluated the outpatient use of recombinant alpha 2a-interferon, 3-15 MU/m2 given on 3 consecutive days, subcutaneously, followed by intravenously administered cisplatin, 25-60 mg/m2, every 21 days. In this phase I clinical study, 23 patients with advanced malignant melanoma were treated. Dose-limiting toxicities included decline in performance status, fatigue, and anorexia. No synergistic or unpredictable toxicities were seen. Of the 20 patients who completed two cycles of therapy, there were three partial responses, for an overall response rate of 15%. Interestingly, responses occurred at the intermediate dose levels.


Repetitive weekly cycles of 4-day continuous infusion of recombinant interleukin-2: a phase I study. A phase I trial was performed with a new interleukin-2 (IL-2) given as a continuous intravenous infusion in patients with solid tumors. The objectives of the study were to examine the feasibility of administering IL-2 in 4-day cycles for 4 consecutive weeks, and to investigate the response pattern of peripheral blood lymphocytes. Tumor necrosis factor (TNF) and IL-2 serum concentrations were also measured. Prior to this study, IL-2 had been tested at increasing dosages during one 4-day cycle, and it appeared that a dose of 1300 mcg/m2/day was tolerated. However, when this treatment schedule was maintained for 4 consecutive weeks, the maximum tolerated dose was 430 mcg/m2/day. In this schedule, a dose-dependent progressive increase in rebound lymphocyte count occurred after each weekly cycle, resulting in a 5-70-fold increase after the 4th cycle. Serum TNF peak concentrations also showed a tendency to increase during each subsequent cycle, while serum IL-2 peak concentrations showed a paradoxical decrease. Clinical toxicity comprised several events, which, possibly, could be ascribed to autoimmune phenomena. Myocardial infarction as a late toxicity of IL-2 is suggested. One complete response (renal carcinoma) and two partial responses (renal and breast carcinoma) were documented, one of these occurring in a patient who previously had shown a transient response on interferon therapy.


[Pathology of the placenta. XII. Tumors of the umbilical cord and placenta]. Benign and malignant tumours of the umbilical cord and placenta are the topics covered in Part XII of this general account under the above heading. Angiomas, angiofibromas and teratomas, all of them of rare occurrence, are the benign tumours, with the chorioangioma being the best known of them. The trophoblast tumours proper include chorionic epitheliomas and choriocarcinomas. While histological differentiation is not possible between these two, they still are biologically benign or malignant. They may develop in the wake of normal pregnancy or abortion or hydatidiform mole. Southeast Asia is a geographically preferred region for hydatidiform mole and chorionic epithelioma. Differentiated growth behaviours of trophoblast tumours are attributable to immunological aspects. It is certainly a rare event to have a high degree of tissue compatibility (HLA antigens) between tumour and maternal organism. This may at least offer an explanation for the low incidence of choriocarcinomas in the northern hemisphere. In Southeast Asia, efforts should be made to clear up the causative background of high incidence of hydatidiform mole, since the latter most probably is the basis for development of choriocarcinoma.