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Homologous chromosomes are segregated during the first meiotic division (meiosis I). Unfortunately, human oocytes are particularly susceptible to mis-segregation errors, so generating aneuploid, often non-viable, embryos. Here we review the cell biology of meiosis I and how homolog disjunction is regulated for mammalian oocytes. We focus on the activity of the anaphase-promoting complex/cyclosome (APC/C), which is responsible for timely degradation of the cohesin component, REC8 and the cyclin B regulatory subunit of maturation-promoting factor, both essential steps for meiosis I completion. In particular, we examine the role played by the spindle assembly checkpoint in controlling the APC/C activity, and in so doing ensuring accurate disjunction of homologs.

Access to nuclear genes in eukaryotes is provided by members of the importin (IMP) superfamily of proteins, which are of alpha- or beta-types, the best understood nuclear import pathway being mediated by a heterodimer of an IMP alpha and IMP beta1. IMP alpha recognises specific targeting signals on cargo proteins, while IMP beta1 mediates passage into, and release within, the nucleus by interacting with other components of the transport machinery, including the monomeric guanine nucleotide binding protein Ran. In this manner, hundreds of different proteins can be targeted specifically into the nucleus in a tightly regulated fashion. The IMP alpha gene family has expanded during evolution, with only a single IMP alpha (Srp1p) gene in budding yeast, and three (IMP alpha1, 2/pendulin and 3) and five (IMP alpha1, -2, -3, -4 and -6) IMP alpha genes in Drosophila melanogaster and mouse respectively, which fall into three phylogenetically distinct groups. The fact that IMP alpha3 and IMP alpha2 are only present in metazoans implies that they emerged during the evolution of multicellular animals to perform specialised roles in particular cells and tissues. This review describes what is known of the IMP alpha gene family in mouse and in D. melanogaster, including a comparitive examination of their mRNA expression profiles in a highly differentiated tissue, the testis. The clear implication of their highly regulated synthesis during the course of spermatogenesis is that the different IMP alphas have distinct expression patterns during cellular differentiation, implying tissue/cell type-specific roles.

The molecular mechanisms behind the entry of the primordial follicle into the growing follicle pool remain poorly understood. To investigate this process further, a microarray-based comparison was undertaken between 2-day postpartum mouse ovaries consisting of primordial follicles/naked oocytes only and those with both primordial follicles and newly activated follicles (7-day postpartum). Gene candidates identified included the chemoattractive cytokine stromal derived factor-1 (SDF1) and its receptor CXCR4. SDF1 and CXCR4 have been implicated in a variety of physiological processes including the migration of embryonic germ cells to the gonads. SDF1-alpha expression increased with the developmental stage of the follicle. Embryonic expression was found to be dichotomous post-germ cell migration, with low expression in the female. Immunohistochemical studies nonetheless indicate that the autocrine pattern of expression ligand and receptor begins during embryonic life. Addition of recombinant SDF1-alpha to neonatal mouse ovaries in vitro resulted in significantly higher follicle densities than for control ovaries. TUNEL analysis indicated no detectable difference in populations of apoptotic cells of treated or control ovaries. Treated ovaries also contained a significantly lower percentage of activated follicles as determined by measurement of oocyte diameter and morphological analysis. Treatment of cultured ovaries with an inhibitor of SDF1-alpha, AMD3100, ablated the effect of SDF1-alpha. By retaining follicles in an unactivated state, SDF1/CXCR4 signaling may play an important role in maintaining the size and longevity of the primordial follicle pool.

The control of primordial follicle recruitment into the growing follicle population is a major limiting process in female reproduction. In order to gain insight into the molecular processes occurring at the time of primordial follicle activation, a subtractive hybridization analysis was performed between cDNAs prepared from temporally distinct mouse neonatal ovarian tissues that differed according to the state of primordial follicle activation. One highly represented clone associated with activation was an Mt retrotransposon-like sequence designated Mtfull, which was subsequently cloned and determined to be novel and restricted in expression to the ovary. The polyadenylated 1684-bp sequence has long terminal repeats, is predicted to be noncoding, and is the predominant Mti-related sequence present in the mouse ovary. In situ hybridization further localized Mtfull expression to the oocyte and confirmed that expression is concomitant with follicle activation. Together with in silico data, we predict Mtfull plays an essential role in folliculogenesis through regulation of gene expression.

A transcript encoding a rat homologue of DZIP1 (DAZ-interacting protein) was isolated from testis RNA. Like human DZIP1, it contains a C(2)H(2) zinc finger domain. A predicted mouse homologue of DZIP1 was found in the GenBank database. Genome analysis indicated that while DZIP1 and mouse Dzip1 contain 22 and 20 exons, respectively, the rat sequence was intronless, confirmed by PCR on genomic DNA. This rat Dzip1 sequence is homologous to mouse Dzip1 exons 1-6 and DZIP1 exons 5-9. As this rat sequence was shorter than DZIP1 it was designated rat Dzip1S. The rat genome also contained a further predicted homologue of DZIP1 displaying conserved linkage homology with mouse Dzip1 and DZIP1. This sequence, if expressed, is the true rat homologue of DZIP1, designated rat Dzip1. Rat Dzip1S mRNA was present in all tissues examined by qualitative RT-RCR, and in situ hybridization of rat testis confirmed that expression of rat Dzip1S mRNA was confined to the spermatogenic lineage, specifically premeiotic spermatogonia.

In the dog, attempts to localize the expression of zona pellucida (ZP) proteins during folliculogenesis have failed to demonstrate conclusively whether any or all of the zona proteins are synthesized in the oocyte or the granulosa cells. Probing of paraformaldehyde-fixed prepubertal canine ovarian tissue sections with a panel of fluorescently conjugated lectins localized the expression of glycoproteins during folliculogenesis. We confirm that six lectins (PSA, s-WGA, ECL, GSL-II, LEL, and STL) consistently labeled the ZP and adjacent granulosa cells of the developing follicle and that canine ZP expresses beta-gal(1,4)glcNAc, beta-gal(1,3)galNac, alpha-mannose, and terminal sialic acid residues in a developmentally specific manner. Riboprobes for canine ZPA and ZPC genes were produced and used for in situ hybridization studies of mRNA expression in canine folliculogenesis. In addition, we isolated a partial cDNA transcript from total ovarian RNA for the canine ZPB gene having a high degree of sequence identity with the felid and porcine ZPB homologues. Subsequently, the ZPA gene transcripts were localized to the cytoplasm of oocytes in primordial, primary, and early secondary follicles. We then localized expression of ZPB and ZPC gene transcripts to the granulosa cells of growing follicles, but not in squamous granulosa cells of primordial follicles or oocytes. These observations indicate that in the juvenile canine ovary, the oocyte is responsible for synthesis of the ZPA protein and directing synthesis of the ZPB and ZPC proteins by the granulosa cells and that ZP gene transcription occurs in a sequential manner during folliculogenesis.

Traumatic arteriovenous malformations (AVM) are formed by an abnormal and usually complex communication between arteries and veins. In contrast to congenital AVMs which occur most commonly in the head and neck, traumatic AVMs are usually reported in the extremities and are commonly the result of military conflicts. In 1757, William Hunter delivered his classical treatise on true and false aneurysms and described a traumatic fistula between the brachial artery and vein following phlebotomy. Approximately thirty cases of acquired traumatic AVMs of the facial region appear in the literature. Only two cases of acquired AVMs of the eyelid region have been reported--one of a post inflammatory origin and one which developed spontaneously. This paper presents the case of a large traumatic AVM of the right lower eyelid along with a discussion of the principles and management of these vascular lesions.

Full-thickness eyelid defects resulting from trauma, tumor destruction, surgical excision, or congenital anomalies present a dilemma to the reconstructive surgeon. Full-thickness eyelid replacement requires composite grafting of skin, muscle, tarsal support or its substitute, and mucosa. A temporalis fascia sling hammock can be used to support the reconstructed eyelid. This static suspension assists in maintaining proper globe apposition to the eyelid and in preventing sagging of the reconstructed structures.

The longest recorded recurrence of a frontal sinus cholesteatoma with involvement of the orbit, frontal bone, and floor of the anterior cranial fossa is presented. Radical surgery is required and often craniotomy is necessary. Bony reconstruction of defects should not be undertaken until recurrence has not been present for at least a year. A review of the literature and a discussion of the origin of cholesteatomas is given.

In October 1979 a surveillance system was set up at the International Centre for Diarrhoeal Disease Research, Bangladesh, Hospital at Dacca to study a 4% systematic sample of the 100 000 patients with diarrhoea who come to the hospital for care each year. From December 1979 to November 1980 inclusive, 3550 patients were studied. A recognised pathogenic organism was identified for 66% of patients screened for all pathogens, one-third of whom had a mixed infection with two or more agents. Enterotoxigenic Escherichia coli was the most common enteropathogen detected in all age groups (detection rate 20%), followed by rotavirus (19%), Campylobacter jejuni (14%), and Shigella (12%). Infants and young children (up to 5 years) were most often infected with rotavirus, enterotoxigenic E coli, and C jejuni and older children (5-14 years) had more infections with enterotoxigenic E coli, Shigella, and E histolytica. Surveillance has helped to define the range of disease among patients attending the Dacca Hospital. Sixty-five per cent of patients complained of watery diarrhoea, a presentation that was significantly more common in patients with Vibrio cholerae 0:1 (91%), enterotoxigenic E coli (78%), rotavirus (77%), and C jejuni (71%) than in all patients studied. Dysentery, defined as a history of diarrhoea with blood, was the presenting complaint of 20% of all patients but 55% of those with Shigella. Only patients with V cholerae 0:1 and enterotoxigenic E coli were at increased risk for severe dehydration. In addition surveillance has been used to identify areas where patient care can be improved and to generate new ideas for research.

We reviewed a series of 137 cataract extractions with intraocular lenses (IOLs) in patients with diabetes, mellitus between 1977 and 1983. All patients were followed for an average of 36 months to determine if they subsequently showed progression of diabetic retinopathy. Divided into groups according to the type of procedure and IOL received, they were compared for age, sex, duration of diabetes, treatment required for the diabetes, intraoperative complications, and follow-up period. Patients who had intracapsular cataract extractions with anterior chamber IOLs were three times as likely to show proliferative retinopathy as those who had extracapsular cataract extractions with posterior chamber IOLs. Insulin-dependent patients were three to four times more likely to show progression to proliferation than noninsulin dependent patients. We conclude that, while some procedures are riskier for the diabetic eye, extracapsular lens extraction with implantation of a posterior chamber lens does not imply an increased risk of development of proliferative retinopathy.

The lacrimal drainage system is a very important functional and anatomic assembly in the orbit and midface. For surgeons who intend to become involved in its repair or reconstruction, it is mandatory to understand the full range of anatomic, physiologic, and diagnostic considerations prior to embarking upon a surgical course. Proper eyelid function depends upon the integrity of its constituent parts, including the margin, tarsus, muscle, and globe apposition. The lacrimal pump mechanism is produced by proper eyelid function and structure, and must be adequately assessed. The puncta and canaliculi are delicate structures and must be manipulated with care and gentleness. The lacrimal sac is a static structure that serves as a collecting sphere but also may be forced to evacuate its contents into the nasolacrimal duct by the "squeezing" action of the investing tendons. Proper tendon position must be maintained after surgery or trauma to facilitate this action. The nasolacrimal sac may be damaged after facial fractures or blocked from intranasal conditions. If the blockage cannot be relieved, it must be bypassed by performing a dacryocystorhinostomy. The use of long-term, indwelling silicone intubation catheters greatly facilitates the successful reconstruction of the lacrimal drainage system. Proper attention to all of these points will be appreciated by the patient.

Before performing a blepharoplasty, the surgeon must completely evaluate the patient to ascertain the proper diagnosis and indication for surgery and to identify any potentially complicating factors. The anatomy and physiology of the eyelids and lacrimal system must be understood in detail. A complete ophthalmologic examination should be performed to document preoperative decreased visual acuity or limited visual fields. The prevention of complications and the satisfaction of the patient are the goals of the blepharoplasty procedure. These require accurate assessment, proper preoperative diagnosis, and meticulous surgical technique.

Dacryocystorhinostomy is used in the effective treatment of epiphora secondary to obstruction of the lacrimal drainage system. Common causes of obstruction include canalicular disruption, lacrimal sac fibrosis, and external and internal nasal trauma. Most techniques of dacryocystorhinostomy attempt to suture the lacrimal sac mucosa to the nasal mucosa. At best this is technically difficult, and the mucosa frequently tears. A technique is presented using an anteriorly based lacrimal sac pedicle flap sutured to the periosteum of the anterior lacrimal crest. The sutured flap is quite strong, and the procedure is technically simpler than others. A brief description of the causes of lacrimal obstruction is given. The Jones primary and secondary dye tests for lacrimal system patency are reviewed.

Traumatic arteriovenous malformations (AVM) represent an abnormal communication between arteries and veins and are usually complex. They occur most commonly in the extremities and are noted most often in military casualties. In the literature there are approximately 25 cases of traumatic AVM of the facial region which are angiographically documented. To these are added five documented cases from this paper, one which was proven at surgery, and one which was suspected from classical signs and symptoms but not diagnosed. The trauma leading to the AVM may be: penetrating, blunt, postsurgical, or inflammatory. A swelling of the face, pulsatile tinnitus, throbbing headache and bleeding comprise the main presenting symptoms. A bruit and thrill are usually present. Doppler ultrasonography and selective arteriography will provide the essential diagnostic information. Embolization therapy may be a helpful preoperative adjunct or may be the total therapy if surgery cannot be performed. Proper identification of the feeder vessels, surgical control of these vessels, total excision of the AVM with functional and cosmetic reconstruction of the tissue defect remain the basic principles of therapy.

Diagnosis and surgical treatment of a male patient with severe facial lacerations involving the lacrimal duct, parotid duct, and buccal branch of facial nerve are presented. Careful wound care and localization of severed nerves and ducts, and repair under microscope are emphasized.

The presence of galactorrhea and/or hyperprolactinemia in patients with the primary empty sella syndrome (PESS) has been proposed to be of hypothalamic etiology. To further elucidate this possible mechanism, sequential testing of 19 subjects with PESS with 500 micrograms thyrotropin-releasing hormone (TRH), followed by the injection of 0.7 mg/kg chlorpromazine (CPZ) 150 minutes later, was compared with results obtained in 6 patients with idiopathic galactorrhea (IG) and 3 normal adult women in the early follicular phase of the menstrual cycle. The thyroid-stimulating hormone and prolactin (PRL) response to TRH was similar in all three groups. The mean maximal increase of serum PRL following CPZ, however, was 16.1 +/- 18.5 ng/ml (standard deviation) in the PESS group, whereas the mean maximal PRL response was 68.6 +/- 40.9 ng/ml in subjects with IG and 67.7 +/- 48.1 ng/ml in the seven normal women. The impaired responsiveness of CPZ in the PESS group was significant (P less than 0.05) when compared with the normal CPZ response in the other two groups. The results of this study suggest that patients with PESS may have hypothalamic dysfunction, and that sequential testing of subjects with TRH and CPZ may be of value in differentiating patients with PESS from those with IG.

From 1973 to 1980, 727 patients with facial fractures received formal ophthalmologic consultation. The series included 174 mandible fractures, 29 nasal fractures, 436 midfacial fractures, and 88 frontal fractures. Of these, a total of 67% sustained some degree of ocular injuries. Seventy-nine percent of the eye injuries were categorized as temporary, 18% were serious, and 3% were blinding. Of the mandibular fractures, 29% had ocular injuries, 59% nasal fractures, 59% midfacial fractures, and 89% frontal fractures.

This study has indicated that numerous benefits accrue from remounting dentures to correct occlusion and recontouring the tissue side of the bases at the time of insertion. This appears to be due to the changes in contour of the denture bases after the stone casts have been removed from them and indicates that a significant change in the occlusal relationship occurs during the deflasking procedure. Since adjustments and postinsertion complaints were materially decreased by early remounting and alteration, patients should benefit from such procedures by receiving restorations that may decrease the rate of bone resorption, be more comfortable, and tend to be effective for a longer period of time. The dentist should consequently be more satisfied knowing that he has done everything possible to provide quality dentistry to his patients.

Blunt and penetrating trauma to the nasoethmoid complex can present a challenge to reconstruction by the facial trauma surgeon. Both functional and cosmetic problems exist with these injuries and both must be considered in the surgical plan. Adequate preoperative physical examination and roentgenologic evaluation, coupled with a thorough ophthalmologic consultation, are required for complete knowledge of the extent of the damage. The surgical repair of nasoethmoid fractures involving the medial canthal tendon and lacrimal drainage system should be repaired primarily. A medial blow-out fracture of the orbit is uncommon but should be considered in all cases of severe nasoethmoid complex fractures.

A group of six patients with non-infected synovial effusions requiring diagnostic or therapeutic aspiration, were given a short oral course of 'Septrin' (two tablets bd for two doses, each tablet containing 80 mg of trimethoprim plus 400 mg of sulphamethoxazole). Serum and synovial fluid (SF) were sampled frequently following antibiotic administration. It was found that concentrations of trimethoprim in SF approached serum levels after a short lag time (about 3 h) and thereafter approximated to the serum levels, whereas sulphamethoxazole did not as readily penetrate into SF. With the regimens used MIC levels for trimethoprim were achieved in SF, which suggests that this drug could be usefully prescribed in normal doses for the treatment of septic arthritis due to bacterial infection.

In many clinical situations, the standard for evaluating extraocular muscle (EOM) size, particularly in thyroid ophthalmopathy, has been use of the computerized tomography (CT) scanner. The impression is generally reported as "enlarged or normal EOMs." If the report of "normal EOM" on CT scan weighs heavily against the diagnosis of thyroid eye disease, how does this qualitative assessment compare with the diagnostic modality of ultrasound? The technique of standardized A-scan measurement of extraocular muscles has been extremely accurate. In this paper, standardized A-scan measurements and CT scan estimates of EOMs are compared in a series of ten patients with a clinical diagnosis of Graves' disease. Three of ten patients displayed enlarged EOMs by CT interpretations; seven of ten patients were categorized as consistent with Graves' disease by correlation with current ultrasonographic criteria for muscle enlargement, asymmetry, and high irregularity of tissue reflectivity.

Full-thickness eyelid defects, as a result of trauma, continue to present a dilemma to the reconstructive surgeon. The authors present a technique of utilizing a temporalis fascia graft to hammock and support a nasal septal cartilage graft as part of reconstruction of the lower eyelid and the lateral canthus after traumatic avulsion. The static suspension afforded by the fascia helps produce proper apposition of the lower eyelid to the globe and provides lateral canthal support. This tissue implant is well tolerated in the eyelid and is readily available in the ophthalmic surgical field.

Intraocular lens implantation was performed as part of a residency training program over a period of two years. Both residents and faculty performed surgery, using anterior chamber angle-fixated (Tennant-Choyce) and iris-fixated (Worst Medallion) lenses. Data with at least three months of follow-up were collected on 148 patients. Of these, visual acuity of 20/40 or better was achieved in 65% (68% of resident cases, 61% of faculty cases). Cystoid macular edema was the most common complication (13% of all cases) occurring nearly twice as often in resident cases. Based on the above, the authors conclude that it is justified to continue a program of lens implantation in a training environment.

Blunt and penetrating trauma to the orbital region can have a devastating effect both functionally and cosmetically for the orbit. Penetrating injuries to the orbit should be suspected whenever there is a history of trauma to the regions of the eyelids. Meticulous inspection of the eyelids and globe should be undertaken, and if there is any suspicion of a foreign body retained within the orbital soft tissues, then a CT scan should be obtained. It is possible that the foreign body is not opaque, and exploration of the soft tissues may be indicated. Blow-out fractures of the orbit should be explored and repaired when the evidence clearly indicates that a blow-out is present. This includes the clinical presence of diplopia, evidence of muscle entrapment with forced duction testing, and CT scan showing orbital wall fracture with explosion of the orbital contents into the paranasal sinuses. If these signs or symptoms are equivocable, then a waiting period of 10 to 14 days is indicated to rule out the presence of a nerve palsy, which should improve. However, a CT scan showing a large blow-out defect of the orbit should be repaired regardless of the clinical signs at the time because of the late sequelae of enophthalmos and hypophthalmos. It is very difficult to secondarily repair an orbit that is contracted owing to loss of volume from an orbital blow-out fracture. Procedures of this sort involve the reintroduction of autogenous fat into the orbital contents and are very difficult technically. Although orbital fractures should not be routinely explored, each should be viewed with its own merit and an aggressive approach developed if there is clinical evidence of a blow-out fracture.

Ocular and adnexal injuries frequently occur during blunt facial trauma but the actual incidence and visual consequence of these injuries have not been heretofore established in any large series. Our review of 1,436 cases of maxillofacial trauma presenting from 1973-1980 outlines the types of fractures, associated specific ocular injuries, and their visual significance. Fifty-one percent (727) of these patients received complete ophthalmologic examination and 67% of these sustained ocular injuries. Seventy-nine percent of the eye injuries were categorized as temporary, 18% were serious, and 3% were blinding. The positive yield for eye injuries approached or exceeded 60% in nasal, midface, and frontal fractures. These data provide concrete evidence for placing high priority on ophthalmologic consultation in all cases of maxillofacial trauma.

Fifty-five unpremedicated outpatients scheduled for cataract surgery were randomly allocated to receive either a fixed dose of nalbuphine and methohexitone or fentanyl and diazepam administered in a dose adjusted to produce the required sedative effect. Statistical analysis revealed no difference between groups with regard to immediate side effects, intra-ocular pressure or postoperative nausea or vomiting. Recovery time from administration of the sedative until compliance with simple commands was significantly longer in the nalbuphine/morphine group (89 vs 196 seconds) but this was not felt to be of clinical importance. This combination was better in terms of sedation at the time of insertion of the nerve blocks, lack of recall of insertion of the nerve block, incidence of intra-operative complications, surgeon's assessment of operating conditions and patient acceptability. This fixed dose by weight drug combination for intravenous sedation should be applied widely.

The lacrimal drainage system is both an anatomic and a physiologic system. Anatomic abnormalities may be a result of congenital defects, infection, trauma, or tumors. The physiologic action of the eyelids, if altered, will affect the tear flow as well as disturb the lacrimal pump. Physiologic and anatomic abnormalities may be defined using the Schirmer, basic secretion, Jones I and II dye, and fluorescein dye disappearance tests. Once the correct diagnosis has been made, the appropriate surgical procedures restore the system's integrity. Punctal abnormalities and eyelid malpositions require surgical correction. Canalicular lacerations should be primarily repaired. Lacrimal sac obstruction is treated with a dacryocystorhinostomy and canalicular intubation. Placement of a Jones tube is required for obstruction of the upper collecting system.

Six patients with non-infected synovial effusions, associated either with inflammatory or degenerative arthropathy and requiring diagnostic or therapeutic aspiration, were given a short course of 400 mg metronidazole (Flagyl) 8-hourly for 3 doses. Serum and synovial fluid (SF) were sampled frequently during this time, and assayed for metronidazole by a specific high pressure liquid-chromatographic method. It was found that concentrations of metronidazole in SF reached those in serum after a short time-lag, and thereafter approximated to the serum concentration. With this regimen, metronidazole concentrations were readily achieved in synovial fluid, above the minimum inhibitory concentrations for most susceptible anaerobes. These results indicate that the drug freely enters the synovial fluid and suggests that metronidazole would prove effective in the treatment of septic arthritis due to anaerobic bacteria.