Renal impairment as a complication of uterine fibroids: a retrospective hospital-based study.

Leiomyomas can cause obstructive renal impairment and renal failure. This was a retrospective study of women with renal impairment seen at the University of the West Indies Hospital, Jamaica, between 2000 and 2004, looking at aetiology and severity (group 1). We also evaluated patients, in the same hospital, with fibroids who had ultrasonography during a later period (2006-2011), comparing those who had hydronephrosis and those without (group 2). In group 1, 274 women were coded as renal impairment. Case notes for 160 patients (59%) were analysed. Uterine fibroids accounted for 13/160 (8.1%) of cases. Comparing cases with and without fibroids, none of those with fibroids were over 50 years old compared with 59.3% of the others, OR 0.02 (CI 0.00-0.35) p = 0.0001. Hospital data for renal failure showed that most mean values were significantly better for those with fibroids. Urea, 8.59 mmol/l (SD 9.89) vs 17.00 mmol/l (SD 13.41) p = 0.003; Creatinine 300.15 µmol/l (SD490.92) vs 424.05 µmol/l (SD553.29) p = 0.022 and Creatinine clearance 73.21 ml/min (SD 38.92) vs 44.25 ml/min (SD 49.71) p = 0.017. However, mean potassium values were similar, 4.52 mmol/l (SD 0.61) vs 4.85 mmol/l (SD1.03) p = 0.2. In group 2, there were 216 patients and we found 31 (14.35%) patients at ultrasonography with hydronephrosis from fibroids. These patients had significantly larger uteri than those without hydronephrosis but renal function was similar, with only urea values significantly worse. Leiomyomas can cause renal impairment, however the prognosis appears good.

Bone mineral density in Jamaican black women after hysterectomy and bilateral oophorectomy: an observational study.

OBJECTIVE: To see if black Jamaican postmenopausal women who had hysterectomy were at increased risk of osteoporosis. To assess the risk of osteoporosis in hysterectomized Jamaican postmenopausal patients. METHOD: We reviewed 809 women (403 hysterectomized and 406 controls) for cardiovascular disease risk. We did a demographic history and examination looking at blood pressure, waist hip ratio and body mass index and investigations done included fasting blood glucose and total and high density lipoprotein (HDL) cholesterol. We also measured bone density at the heel in all women using the Achilles ultrasound bone densitometer looking at T-score and Z-score. RESULTS: There was a significant association of hysterectomy status and bone mineral density (BMD) status with a smaller than expected proportion of women with osteoporosis in the hysterectomy group (χ2 = 18.4; p = 0.001). The mean T-score was significantly higher in the hysterectomized women, adjusting for age, waist circumference and sociodemographic factors. The relationship between the various predictors and BMD was explored by stepwise regression modelling. The factors that were significantly related to low BMD were hysterectomy status, age, waist circumference and being employed. CONCLUSION: Hysterectomy was not found to be a significant risk factor for osteoporosis. The osteoporosis risk among menopausal women in Jamaica appears to be due to other risk factors which probably existed prior to the operation.

VimA-dependent modulation of acetyl coenzyme A levels and lipid A biosynthesis can alter virulence in Porphyromonas gingivalis.

The Porphyromonas gingivalis VimA protein has multifunctional properties that can modulate several of its major virulence factors. To further characterize VimA, P. gingivalis FLL406 carrying an additional vimA gene and a vimA-defective mutant in a different P. gingivalis genetic background were evaluated. The vimA-defective mutant (FLL451) in the P. gingivalis ATCC 33277 genetic background showed a phenotype similar to that of the vimA-defective mutant (FLL92) in the P. gingivalis W83 genetic background. In contrast to the wild type, gingipain activity was increased in P. gingivalis FLL406, a vimA chimeric strain. P. gingivalis FLL451 had a five times higher biofilm-forming capacity than the parent strain. HeLa cells incubated with P. gingivalis FLL92 showed a decrease in invasion, in contrast to P. gingivalis FLL451 and FLL406, which showed increases of 30 and 40%, respectively. VimA mediated coenzyme A (CoA) transfer to isoleucine and reduced branched-chain amino acid metabolism. The lipid A content and associated proteins were altered in the vimA-defective mutants. The VimA chimera interacted with several proteins which were found to have an LXXTG motif, similar to the sorting motif of gram-positive organisms. All the proteins had an N-terminal signal sequence with a putative sorting signal of L(P/T/S)X(T/N/D)G and two unique signatures of EXGXTX and HISXXGXG, in addition to a polar tail. Taken together, these observations further confirm the multifunctional role of VimA in modulating virulence possibly through its involvement in acetyl-CoA transfer and lipid A synthesis and possibly by protein sorting.

Filifactor alocis has virulence attributes that can enhance its persistence under oxidative stress conditions and mediate invasion of epithelial cells by porphyromonas gingivalis.

Filifactor alocis, a Gram-positive anaerobic rod, is one of the most abundant bacteria identified in the periodontal pockets of periodontitis patients. There is a gap in our understanding of its pathogenicity and ability to interact with other periodontal pathogens. To evaluate the virulence potential of F. alocis and its ability to interact with Porphyromonas gingivalis W83, several clinical isolates of F. alocis were characterized. F. alocis showed nongingipain protease and sialidase activities. In silico analysis revealed the molecular relatedness of several virulence factors from F. alocis and P. gingivalis. In contrast to P. gingivalis, F. alocis was relatively resistant to oxidative stress and its growth was stimulated under those conditions. Biofilm formation was significantly increased in coculture. There was an increase in adherence and invasion of epithelial cells in coculture compared with P. gingivalis or F. alocis monocultures. In those epithelial cells, endocytic vesicle-mediated internalization was observed only during coculture. The F. alocis clinical isolate had an increased invasive capacity in coculture with P. gingivalis compared to the ATCC 35896 strain. In addition, there was variation in the proteomes of the clinical isolates compared to the ATCC 35896 strain. Hypothetical proteins and those known to be important virulence factors in other bacteria were identified. These results indicate that F. alocis has virulence properties that may enhance its ability to survive and persist in the periodontal pocket and may play an important role in infection-induced periodontal disease.

Filifactor alocis: Recent Insights and Advances.

Filifactor alocis, a fastidious Gram-positive obligate anaerobic bacterium, is a newly appreciated member of the periodontal community that is now proposed to be a diagnostic indicator of periodontal disease. Its pathogenic characteristics are highlighted by its ability to survive in the oxidative stress-rich environment of the periodontal pocket and to significantly alter the microbial community dynamics by forming biofilms and interacting with several oral bacteria. Here, we describe the current understanding of F. alocis virulence attributes, such as its comparative resistance to oxidative stress, production of unique proteases and collagenases that can cause structural damage to host cells, and dysregulation of the immune system, which enable this bacterium to colonize, survive, and outcompete other traditional pathogens in the inflammatory environment of the periodontal pocket. Furthermore, we explore the recent advancements and future directions for F. alocis research, including the potential mechanisms for oxidative stress resistance and our evolving understanding of the interactions and mechanisms of bacterial survival inside neutrophils. We also discuss the current genetic tools and challenges involved in manipulating the F. alocis genome for the functional characterization of the putative virulence genes. Collectively, this information will expedite F. alocis research and should lead to the identification of prime targets for the development of novel therapeutics to aid in the control and prevention of periodontal disease.

regT can modulate gingipain activity and response to oxidative stress in Porphyromonas gingivalis.

Recombinant VimA protein can interact with the gingipains and several other proteins that may play a role in its biogenesis in Porphyromonas gingivalis. In silico analysis of PG2096, a hypothetical protein that was shown to interact with VimA, suggests that it may have environmental stress resistance properties. To further evaluate the role(s) of PG2096, the predicted open reading frame was PCR amplified from P. gingivalis W83 and insertionally inactivated using the ermF-ermAM antibiotic-resistance cassette. One randomly chosen PG2096-defective mutant created by allelic exchange and designated FLL205 was further characterized. Under normal growth conditions at 37 °C, Arg-X and Lys-X gingipain activities in FLL205 were reduced by approximately 35 % and 21 %, respectively, compared to the wild-type strain. However, during prolonged growth at an elevated temperature of 42 °C, Arg-X activity was increased by more than 40 % in FLL205 in comparison to the wild-type strain. In addition, the PG2096-defective mutant was more resistant to oxidative stress when treated with 0.25 mM hydrogen peroxide. Taken together these results suggest that the PG2096 gene, designated regT (regulator of gingipain activity at elevated temperatures), may be involved in regulating gingipain activity at elevated temperatures and be important in oxidative stress resistance in P. gingivalis.

Cardiovascular disease risk factors in menopausal Jamaican black women after hysterectomy and bilateral oophorectomy: an observational study.

OBJECTIVE: To determine differences in prevalence of cardiovascular risks and diseases in black Jamaican postmenopausal women who had hysterectomy (hysgroup) compared with those without (control). METHOD: Eight hundred and nine (809) women (hysterectomized (HYSGRP) = 403; non-hysterectomized (controls) = 406) were enrolled. Sociodemographic information and lifestyle history, measured blood pressure, waist hip ratio, body mass index, fasting blood glucose, total and HDL cholesterol were obtained. RESULTS: Of the 809 women, complete cardiovascular risk data were available in 341 controls and 328 in the HYSGRP group. There was no difference in mean age, blood pressure and body mass indices between the subjects excluded and the subjects in the data analytical sample. A significantly lower proportion of women in the control group exercised, attained post-secondary education and were of higher parity. Systolic (mean diference with 95% CI; 6 (3, 9) mmHg and diastolic (3 (1, 5) mmHg) blood pressure were lower in the HYSGRP compared with controls but total cholesterol (0.2 (0.07 to 0.4) mmol/L was greater HDL cholesterol was not different between both groups 1.3 mmol/L (SD 0.3) vs 1.3 mmol/L [SD 0.4] (p = 0.8435). There was no difference in the prevalence of diabetes, hypertension and high waist-hip ratio in hysterectomized women compared with controls adjusting for hormone replacement therapy usage, cigarette smoking, exercise and educational status. Within the HYSGRP there was also no diference in cardiovascular disease or risk in women who had bilateral oophorectomy compared with women who had at least an ovary preserved at time of operation. CONCLUSION: Hysterectomy was not associated with an increased risk of cardiovascular disease. This must be taken cautiously since data did not allow for analysis on duration of menopause.

The arterial blood gas algorithm: Proposal of a systematic approach to analysis of acid-base disorders. / El algoritmo de la gasometría arterial: propuesta de un enfoque sistemático para el análisis de los trastornos del equilibrio ácido-base.

Abnormalities in the acid-base balance are common clinical problems and can have deleterious effects on cellular function and be a clue to various disorders. Therefore, it is important for the clinician to make a precise diagnosis of the acid-base disorder(s) present for a proper treatment. Three approaches have been proposed to evaluate acid-base disorders: a bicarbonate-centric approach; the Stewart approach, and the base excess approach. Although the latter two have many adherents, we will only discuss the bicarbonate-centric approach. This approach is simpler to utilize at the bedside, has a physiological evaluation of the acid-base disorder, presents an easily understandable approach to assess severity, and provides a more solid foundation for the development of effective therapies. Therefore, the following discussion will be limited to an examination of this approach. In this case-centric review, important new concepts will be introduced first; their benefits and limitations discussed; and then their utilization to analyze actual cases will be shown. A systematic approach algorithm that incorporates these new concepts has been generated and will be highlighted.

Venous thromboembolism in Jamaican women: experience in a university hospital in Kingston.

OBJECTIVE: To review cases of venous thromboembolism (VTE) at UHWI from 1999-2004, to identify methods of diagnosis, risk factors and to evaluate differences between survivors and fatalities. METHODS: Patients coded with the diagnosis of thromboembolism at the University Hospital of the West Indies (UHWI) from 1999-2004 were identified. The medical records were reviewed to determine the prevalence of thromboembolism and possible variables associated with this diagnosis. In addition, variables associated with fatality were examined by evaluating cases diagnosed at autopsy RESULTS: There were 959 patients coded for thromboembolism between 1999-2004 at UHWI. Of these, 657 (68.5%) were females and 302 were males (31.5%). During that period, 65,657 women and 40,826 men were admitted to hospital with prevalence rates for thromboembolism of 1% in women and 0.7% in men. Of the 657 females, 520 case notes were located (case identification 80%). Of this, 435 were analysed as confirmed thromboembolism. The median age was 51 years with a range of 2-95 years. Common associations were obesity, 53.5%; age over 50 years, 52.5%; hypertension, 44.7%; immobilisation, 36.3%; cardiac disease, 26%; diabetes, 19.4%; fibroids, 16.3%; surgery, 15.8% and cancer 14%. Recurrent venous thromboembolism occurred in 12.8% and 15.8 % of women (66) died, diagnosed with PE at post-mortem. Using logistic regression analysis, leading risk factors in fatalities compared to survivors were hypertension and increased age. Obesity and surgery were significantly more likely in survivors. CONCLUSION: Venous thromboembolism was common in this cohort of women and avoidance of risk factors and institution of prophylaxis in high risk women is important to decrease morbidity and mortality.

Poverty eradication and decreased human papilloma virus related cancer of the penis and vulva in Jamaica.

Human papilloma virus causes genital cancers. Decreases in cervical cancer have been reported to be due to comprehensive screening programmes difficult to replicate in poorer countries. HPV cancer may be related to poverty. In Jamaica, we have seen decreases in cancer of the penis and vulva and there has also been a decrease in poverty. The decrease cannot be attributed to screening. We believe elimination of poverty has decreased HPV persistence and decreased cancer rates.

Role of extracytoplasmic function sigma factor PG1660 (RpoE) in the oxidative stress resistance regulatory network of Porphyromonas gingivalis.

In Porphyromonas gingivalis, the protein PG1660, composed of 174 amino acids, is annotated as an extracytoplasmic function (ECF) sigma factor (RpoE homologue-σ24). Because PG1660 can modulate several virulence factors and responds to environmental signals in P. gingivalis, its genetic properties were evaluated. PG1660 is co-transcribed with its downstream gene PG1659, and the transcription start site was identified as adenine residue 54-nucleotides upstream of the ATG translation start codon. In addition to binding its own promoter, using the purified rPG1660 and RNAP core enzyme from Escherichia coli with the PG1660 promoter DNA as template, the function of PG1660 as a sigma factor was demonstrated in an in vitro transcription assay. Transcriptome analyses of a P. gingivalis PG1660-defective isogenic mutant revealed that under oxidative stress conditions 176 genes including genes involved in secondary metabolism were downregulated more than two-fold compared with the parental strain. The rPG1660 protein also showed the ability to bind to the promoters of the highly downregulated genes in the PG1660-deficient mutant. As the ECF sigma factor PG0162 has a 29% identity with PG1660 and can modulate its expression, the cross-talk between their regulatory networks was explored. The expression profile of the PG0162PG1660-deficient mutant (P. gingivalis FLL356) revealed that the type IX secretion system genes and several virulence genes were downregulated under hydrogen peroxide stress conditions. Taken together, we have confirmed that PG1660 can function as a sigma factor, and plays an important regulatory role in the oxidative stress and virulence regulatory network of P. gingivalis.

Filifactor alocis collagenase can modulate apoptosis of normal oral keratinocytes.

To successfully colonize host cells, pathogenic bacteria must circumvent the host's structural barrier such as the collagen-rich extracellular matrix (ECM), as a preliminary step to invasion and colonization of the periodontal tissue. Filifactor alocis possesses a putative Peptidase U32 family protein (HMPREF0389_00504) with collagenase activity that may play a significant role in colonization of host tissue during periodontitis by breaking down collagen into peptides and disruption of the host cell. Domain architecture of the HMPREF0389_00504 protein predicted the presence of a characteristic PrtC-like collagenase domain, and a peptidase domain. Our study demonstrated that the recombinant F. alocis peptidase U32 protein (designated PrtFAC) can interact with, and degrade, type I collagen, heat-denatured collagen and gelatin in a calcium-dependent manner. PrtFAC decreased viability and induced apoptosis of normal oral keratinocytes (NOKs) in a time and dose-dependent manner. Transcriptome analysis of NOK cells treated with PrtFAC showed an upregulation of the genes encoding human pro-apoptotic proteins: Apoptotic peptidase activating factor 1 (Apaf1) cytochrome C, as well as caspase 3 and caspase 9, suggesting the involvement of the mitochondrial apoptotic pathway. There was a significant increase in caspase 3/7 activity in NOK cells treated with PrtFAC. Taken together, these findings suggest that F. alocis PrtFAC protein may play a role in the virulence and pathogenesis of F. alocis.

Studies of the extracytoplasmic function sigma factor PG0162 in Porphyromonas gingivalis.

PG0162, annotated as an extracytoplasmic function (ECF) sigma factor in Porphyromonas gingivalis, is composed of 193 amino acids. As previously reported, the PG0162-deficient mutant, P. gingivalis FLL350 showed significant reduction in gingipain activity compared with the parental strain. Because this ECF sigma factor could be involved in the virulence regulation in P. gingivalis, its genetic properties were further characterized. A 5'-RACE analysis showed that the start of transcription of the PG0162 gene occurred from a guanine (G) residue 69 nucleotides upstream of the ATG translation initiation codon. The function of PG0162 as a sigma factor was confirmed in a run-off in vitro transcription assay using the purified rPG0162 and RNAP core enzyme from Escherichia coli with the PG0162 promoter as template. As an appropriate PG0162 inducing environmental signal is unknown, a strain overexpressing the PG0162 gene designated P. gingivalis FLL391 was created. Compared with the wild-type strain, transcriptome analysis of P. gingivalis FLL391 showed that approximately 24% of the genome displayed altered gene expression (260 upregulated genes; 286 downregulated genes). Two other ECF sigma factors (PG0985 and PG1660) were upregulated more than two-fold. The autoregulation of PG0162 was confirmed with the binding of the rPG0162 protein to the PG0162 promoter in electrophoretic mobility shift assay. In addition, the rPG0162 protein also showed the ability to bind to the promoter region of two genes (PG0521 and PG1167) that were most upregulated in P. gingivalis FLL391. Taken together, our data suggest that PG0162 is a sigma factor that may play an important role in the virulence regulatory network in P. gingivalis.

A putative TetR regulator is involved in nitric oxide stress resistance in Porphyromonas gingivalis.

To survive in the periodontal pocket, Porphyromonas gingivalis, the main causative agent of periodontal disease, must overcome oxidative and nitric oxide (NO) stress. Previously, we reported that, in the presence of NO comparable to stress conditions, the transcriptome of P. gingivalis was differentially expressed, and genes belonging to the PG1178-81 cluster were significantly upregulated. To further evaluate their role(s) in NO stress resistance, these genes were inactivated by allelic exchange mutagenesis. Isogenic mutants P. gingivalis FLL460 (ΔPG1181::ermF) and FLL461 (ΔPG1178-81::ermF) were black-pigmented, with gingipain and hemolytic activities comparable to that of the wild-type strain. Whereas the recovery of these isogenic mutants from NO stress was comparable to the wild-type, there was increased sensitivity to hydrogen peroxide-induced stress. RNA-Seq analysis under conditions of NO stress showed that approximately 5 and 8% of the genome was modulated in P. gingivalis FLL460 and FLL461, respectively. The PG1178-81 gene cluster was shown to be part of the same transcriptional unit and is inducible in response to NO stress. In the presence of NO, PG1181, a putative transcriptional regulator, was shown to bind to its own promoter region and that of several other NO responsive genes including PG0214 an extracytoplasmic function σ factor, PG0893 and PG1236. Taken together, the data suggest that PG1181 is a NO responsive transcriptional regulator that may play an important role in the NO stress resistance regulatory network in P. gingivalis.

The roles of RgpB and Kgp in late onset gingipain activity in the vimA-defective mutant of Porphyromonas gingivalis W83.

Previous studies have shown that VimA, an acetyltransferase, can modulate gingipain biogenesis in Porphyromonas gingivalis. Inactivation of the vimA gene resulted in isogenic mutants that showed a late onset of gingipain activity that only occurred during the stationary growth phase. To further elucidate the role and contribution of the gingipains in this VimA-dependent process, isogenic mutants defective in the gingipain genes in the vimA-deficient genetic background were evaluated. In contrast with the wild-type strain, RgpB and Kgp gingipain activities were absent in exponential phase in the ∆rgpA::tetQ-vimA::ermF mutant. However, these activities increased to 31 and 53%, respectively, of that of the wild-type during stationary phase. In the ∆rgpA::cat-∆kgp::tetQ-vimA::ermF mutant, the RgpB protein was observed in the extracellular fraction but no activity was present even at the stationary growth phase. There was no gingipain activity observed in the ∆rgpB::cat-∆kgp::tetQ-vimA::ermF mutant whereas Kgp activity in ∆rgpA::cat-∆rgpB::tetQ-vimA::ermF mutant was 24% of the wild-type at late stationary phase. In contrast to RgpA, the glycosylation profile of the RgpB catalytic domain from both W83 and P. gingivalis FLL92 (vimA::ermF) showed similarity. Taken together, the results suggest multiple gingipain activation pathways in P. gingivalis. Whereas the maturation pathways for RgpA and RgpB are different, the late-onset gingipain activity in the vimA-defective mutant was due to activation/maturation of RgpB and Kgp. Moreover, unlike RgpA, which is VimA-dependent, the maturation/activation pathways for RgpB and Kgp are interdependent in the absence VimA.

Metabolome variations in the Porphyromonas gingivalis vimA mutant during hydrogen peroxide-induced oxidative stress.

The adaptability and survival of Porphyromonas gingivalis in the oxidative microenvironment of the periodontal pocket are indispensable for survival and virulence, and are modulated by multiple systems. Among the various genes involved in P. gingivalis oxidative stress resistance, vimA gene is a part of the 6.15-kb locus. To elucidate the role of a P. gingivalis vimA-defective mutant in oxidative stress resistance, we used a global approach to assess the transcriptional profile, to study the unique metabolome variations affecting survival and virulence in an environment typical of the periodontal pocket. A multilayered protection strategy against oxidative stress was noted in P. gingivalis FLL92 with upregulation of detoxifying genes. The duration of oxidative stress was shown to differentially modulate transcription with 94 (87%) genes upregulated twofold during 10 min and 55 (83.3%) in 15 min. Most of the upregulated genes (55%), fell in the hypothetical/unknown/unassigned functional class. Metabolome variation showed reduction in fumarate and formaldehyde, hence resorting to alternative energy generation and maintenance of a reduced metabolic state. There was upregulation of transposases, genes encoding for the metal ion binding protein transport and secretion system.

Accelerated alveolar bone loss in mice lacking interleukin-10.

Interleukin-10 regulates pro-inflammatory cytokines, including those implicated in alveolar bone resorption. We hypothesized that lack of interleukin-10 leads to increased alveolar bone resorption. Male interleukin-10(-/-) mice, on 129/SvEv and C57BL/6J background, were compared with age-, sex-, and strain-matched interleukin-10(+/+) controls for alveolar bone loss. Immunoblotting was used for analysis of serum reactivity against bacteria associated with colitis and periodontitis. Interleukin-10(-/-) mice had significantly greater alveolar bone loss than interleukin-10(+/+) mice (p = 0.006). The 30-40% greater alveolar bone loss in interleukin-10(-/-) mice was evident in both strains, with C57BL/6J interleukin-10(-/-) mice exhibiting the most bone loss. Immunoblotting revealed distinct interleukin-10(-/-) serum reactivity against Bacteroides vulgatus, B. fragilis, Prevotella intermedia, and, to a lesser extent, against B. forsythus. The results of the present study suggest that lack of interleukin-10 leads to accelerated alveolar bone loss.

Protease-active extracellular protein preparations from Porphyromonas gingivalis W83 induce N-cadherin proteolysis, loss of cell adhesion, and apoptosis in human epithelial cells.

BACKGROUND: The protease-induced cytotoxicity of P. gingivalis may partly result from alteration of the extracellular matrix and/or surface receptors that mediate interaction between the host cells and their matrix. While P. gingivalis-induced degradation of E-cadherin has been documented, there is no information on the effects of P. gingivalis proteases on other members of this family of cell adhesion proteins. METHODS: Human epithelial KB cells were exposed to protease-active extracellular protein preparations from isogenic mutants of P. gingivalis. Quantification of apoptosis was performed by visualization of nuclei stained with 4,6'-diamidino-2-phenylindole. Alteration of cell adhesion proteins was examined by immunoblotting of cell lysates using monoclonal antibodies to those proteins. RESULTS: Treated cells exhibited loss of cell adhesion properties with apoptotic cell death subsequently observed. These effects correlated with the different levels of cysteine-dependent proteolytic activities of the isogenic mutants tested. Cleavage of N-cadherin was observed in immunoblots of lysates from detached cells. There was a direct correlation between the kinetics of N-cadherin cleavage and loss of cell adhesion properties. Loss of cell adhesion, as well as N-cadherin cleavage, could be inhibited by preincubation of P. gingivalis protease active extracellular protein preparations with the cysteine protease inhibitor TLCK. In control experiments, the cleavage of N-cadherin was detected after treatment of KB cells with trypsin but not after cell dissociation by a non-enzymatic method. CONCLUSIONS: These results suggest that extracellular proteases from P. gingivalis can induce degradation of N-cadherin, which could have implications for the pathogenicity of this bacterium.

Successful pregnancies in patients with antiphospholipid syndrome treated with low-dose aspirin.

Four patients with bad obstetrical histories and with positive lupus anticoagulant tests were treated with low-dose aspirin, prednisone or heparin. They had pre-term deliveries of live babies who all survived.

Ovarian hyperstimulation syndrome associated with clomiphene citrate.

Ovarian hyperstimulation is a recognized complication of ovulation induction with gonadotrophins. The syndrome is becoming more common as the number of women undergoing in-vitro fertilization increases. It is rarely seen in conjunction with clomiphene citrate usage. This case report is of moderate to severe ovarian hyperstimulation in a patient who was treated with clomiphene citrate because of infertility secondary to anovulation. She presented with amenorrhoea for five weeks, lower abdominal pain and a positive urinary human chorionic gonadotrophin (hCG) test. Pelvic ultrasonography was suggestive of a possible ectopic pregnancy with a differential diagnosis of a ruptured ovarian cyst. Diagnostic laparoscopy was done followed by laparotomy. Oophorectomy was performed because the ovary was thought to be complex with solid areas. However, conservative management with avoidance of laparotomy is the recommendation in confirmed cases of ovarian hyperstimulation but this requires a high level of suspicion in patients who have ovulation induction.