Caregiver-reported physical health status of children and young people with fetal alcohol spectrum disorder.

While fetal alcohol spectrum disorder (FASD) has primarily been thought of as a neurodevelopmental condition, research is beginning to highlight its 'whole-body' implications. Accordingly, the current study sought to provide a snapshot of potential health issues. Caregivers of children (median age of 12 years) with an FASD diagnosis were invited to participate in an online survey. Information relating to sample demographics, FASD status of the child and health outcomes were collected. The prevalence of health conditions reported in the FASD sample was compared against national prevalence data. Multiple linear regression utilising a stepwise approach was used to investigate potential predictors of the number of diagnosed health conditions. Survey data were from an international cohort (n = 197), with the majority of respondents based in Australia (40.2%) or the United States (27.7%). The most commonly reported diagnosed health conditions were eye conditions (44.7%), asthma (34.5%), heart conditions (34.0%) and skin conditions (27.4%). Binomial testing indicated the proportion of children diagnosed with these disorders was generally higher in the current FASD population, compared to national prevalence data. Indicators of metabolic dysfunction including diabetes and obesity were not significantly different compared to national prevalence data. Age of FASD diagnosis, existence of comorbid mental health conditions and the primary caregiver being in paid work were identified as being associated with the prevalence of diagnosed health conditions. Overall, the study has provided an up-to-date snapshot of health problems reported in a sample of children with FASD, confirming their increased risk of adverse health outcomes.

Effect of ischemic preconditioning and postconditioning on liver regeneration in prepubertal rats.

BACKGROUND: Liver regeneration has great importance for transplantation, especially in children; however, it has not been studied sufficiently in development animals. Ischemia-reperfusion injury is a problem, and strategies such as ischemic preconditioning and postconditioning are not well defined regarding regeneration. OBJECTIVE: This study sought to evaluate liver regeneration with modulation by ischemic preconditioning and postconditioning in prepubertal rats subjected to total ischemia and reperfusion. METHODS: Thirty-five 5-week-old female Wistar rats were divided into groups of 7 animals each: control group (SHAM), 70% hepatectomy (HEP), total ischemia 30 minutes before hepatectomy (IR), ischemic preconditioning 10/10 minutes before ischemia (PRE), and two 30/30-second ischemic postconditioning cycles after ischemia and hepatectomy (POS). All animals were subjected to 24-hour reperfusion. Aspartate aminotransferase and alanine aminotransferase activity were measured to evaluate liver damage, and histological analysis, proliferating cell nuclear antigen (PCNA) and regenerated mass liver were used to evaluate liver regeneration. Statistical analyses were performed using ANOVA and Kruskal-Wallis test. RESULTS: Alanine aminotransferase and aspartate aminotransferase levels were significantly lower in conditioned groups than in the IR group. Regarding mitotic index, IR > control group and HEP (P < .05), PRE and POS were not significantly different from IR, and POS > HEP (P < .05). PCNA analysis showed that IR > HEP (P < .01), PRE < IR (P < .01), and no significant differences were observed between POS and IR groups. No significant differences in regenerated mass liver were observed between conditioned groups and HEP. CONCLUSIONS: Ischemic postconditioning prevented ischemic injury, promoted greater liver regeneration, and should be further investigated as an alternative better than ischemic preconditioning.

HIDA scan ejection fraction does not predict sphincter of Oddi hypertension or clinical outcome in patients with suspected chronic acalculous cholecystitis.

BACKGROUND: Hepatobiliary iminodiacetic scan with ejection fraction (HIDA EF) is used to evaluate chronic acalculous cholecystitis (CAC). A presumed etiology of CAC is sphincter of Oddi hypertension (SOH). In this study, we evaluated the value of HIDA EF to predict patient response to laparoscopic cholecystectomy and to identify SOH. METHODS: A prospective study of 93 patients with biliary pain but without gallstones (CAC) who underwent preoperative HIDA EF was conducted. At laparoscopic cholecystectomy, transcystic antegrade biliary manometry was performed to determine the SO pressure. Patients were evaluated postoperatively for response to cholecystectomy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. The outcomes were compared with the clinical impression. RESULTS: Of the 93 patients with both HIDA EF and SOP measurements, 50 had abnormal EF (< 35%); of these, 29 had SOH (SO pressure > or = 40 mmHg). Of the 43 patients with normal HIDA EF, 30 had SOH. The sensitivity was 49%, specificity 38%, PPV 58%, and NPV 30%. Eighty-six of the 93 patients returned for follow-up evaluation. Follow-up ranged from 0 to 99 months, with a mean of 26.4 months. Overall, 73 patients (85%) improved. Of the 46 with abnormal HIDA EF, 42 (91%) improved. Of the 40 patients with normal HIDA EF, 31 (77.5%) improved. The sensitivity was 57.7%, specificity 69.2%, PPV 91.3%, and NPV 22.5%. CONCLUSION: Although the PPV of abnormal HIDA EF is high, it is not much better than the clinical impression. The sensitivity and specificity are marginal. The NPV is poor. Based on the review of these 93 patients, HIDA EF is not reliable for identifying CAC. We recommend that patients with normal HIDA EF have additional testing or consultation before ruling out CAC. HIDA EF does not predict SOH.

Mechanisms of Bacillus subtilis spore resistance to and killing by aqueous ozone.

AIMS: To determine the mechanisms of Bacillus subtilis spore killing by and resistance to aqueous ozone. METHODS AND RESULTS: Killing of B. subtilis spores by aqueous ozone was not due to damage to the spore's DNA, as wild-type spores were not mutagenized by ozone and wild-type and recA spores exhibited very similar ozone sensitivity. Spores (termed alpha-beta-) lacking the two major DNA protective alpha/beta-type small, acid-soluble spore proteins exhibited decreased ozone resistance but were also not mutagenized by ozone, and alpha-beta- and alpha-beta-recA spores exhibited identical ozone sensitivity. Killing of spores by ozone was greatly increased if spores were chemically decoated or carried a mutation in a gene encoding a protein essential for assembly of the spore coat. Ozone killing did not cause release of the spore core's large depot of dipicolinic acid (DPA), but these killed spores released all of their DPA after a subsequent normally sublethal heat treatment and also released DPA much more readily when germinated in dodecylamine than did untreated spores. However, ozone-killed spores did not germinate with either nutrients or Ca(2+)-DPA and could not be recovered by lysozyme treatment. CONCLUSIONS: Ozone does not kill spores by DNA damage, and the major factor in spore resistance to this agent appears to be the spore coat. Spore killing by ozone seems to render the spores defective in germination, perhaps because of damage to the spore's inner membrane. SIGNIFICANCE AND IMPACT OF THE STUDY: These results provide information on the mechanisms of spore killing by and resistance to ozone.

Mechanisms of killing of Bacillus subtilis spores by Decon and Oxone, two general decontaminants for biological agents.

AIMS: To determine the mechanisms of Bacillus subtilis spore killing by and resistance to the general biological decontamination agents, Decon and Oxone. METHODS AND RESULTS: Spores of B. subtilis treated with Decon or Oxone did not accumulate DNA damage and were not mutagenized. Spore killing by these agents was increased if spores were decoated. Spores prepared at higher temperatures were more resistant to these agents, consistent with a major role for spore coats in this resistance. Neither Decon nor Oxone released the spore core's depot of dipicolinic acid (DPA), but Decon- and Oxone-treated spores more readily released DPA upon a subsequent normally sublethal heat treatment. Decon- and Oxone-killed spores initiated germination with dodecylamine more rapidly than untreated spores, but could not complete germination triggered by nutrients or Ca(2+)-DPA and did not degrade their peptidoglycan cortex. However, lysozyme treatment did not recover these spores. CONCLUSIONS: Decon and Oxone do not kill B. subtilis spores by DNA damage, and a major factor in spore resistance to these agents is the spore coat. Spore killing by both agents renders spores defective in germination, possibly because of damage to the inner membrane of spore. SIGNIFICANCE AND IMPACT OF STUDY: These results provide information on the mechanisms of the killing of bacterial spores by Decon and Oxone.

Mechanisms of killing of Bacillus subtilis spores by hypochlorite and chlorine dioxide.

AIMS: To determine the mechanisms of Bacillus subtilis spore killing by hypochlorite and chlorine dioxide, and its resistance against them. METHODS AND RESULTS: Spores of B. subtilis treated with hypochlorite or chlorine dioxide did not accumulate damage to their DNA, as spores with or without the two major DNA protective alpha/beta-type small, acid soluble spore proteins exhibited similar sensitivity to these chemicals; these agents also did not cause spore mutagenesis and their efficacy in spore killing was not increased by the absence of a major DNA repair pathway. Spore killing by these two chemicals was greatly increased if spores were first chemically decoated or if spores carried a mutation in a gene encoding a protein essential for assembly of many spore coat proteins. Spores prepared at a higher temperature were also much more resistant to these agents. Neither hypochlorite nor chlorine dioxide treatment caused release of the spore core's large depot of dipicolinic acid (DPA), but hypochlorite- and chlorine dioxide-treated spores much more readily released DPA upon a subsequent normally sub-lethal heat treatment than did untreated spores. Hypochlorite-killed spores could not initiate the germination process with either nutrients or a 1 : 1 chelate of Ca2+-DPA, and these spores could not be recovered by lysozyme treatment. Chlorine dioxide-treated spores also did not germinate with Ca2+-DPA and could not be recovered by lysozyme treatment, but did germinate with nutrients. However, while germinated chlorine dioxide-killed spores released DPA and degraded their peptidoglycan cortex, they did not initiate metabolism and many of these germinated spores were dead as determined by a viability stain that discriminates live cells from dead ones on the basis of their permeability properties. CONCLUSIONS: Hypochlorite and chlorine dioxide do not kill B. subtilis spores by DNA damage, and a major factor in spore resistance to these agents appears to be the spore coat. Spore killing by hypochlorite appears to render spores defective in germination, possibly because of severe damage to the spore's inner membrane. While chlorine dioxide-killed spores can undergo the initial steps in spore germination, these germinated spores can go no further in this process probably because of some type of membrane damage. SIGNIFICANCE AND IMPACT OF THE STUDY: These results provide information on the mechanisms of the killing of bacterial spores by hypochlorite and chlorine dioxide.

Vaginal paravaginal repair: one-year outcomes.

OBJECTIVE: This study was carried out to determine the efficacy and safety of the vaginal approach to paravaginal repair of symptomatic paravaginal defect cystocele. METHODS: This study is an observational case series of 100 consecutive women, referred from December 1996 to August 2000, with symptomatic grade II to IV paravaginal defect cystocele. Preoperative and postoperative pelvic evaluations were performed with the Baden-Walker halfway system. The same surgeon performed all repairs. Fourteen patients had prior anterior repairs, and 530 concomitant procedures were performed. The vaginal approach consisted of a thorough entry from the vesicovaginal space under the inferior pubic ramus into the retropubic space, widely exposing the area of the arcus tendineus. A repair was done bilaterally in 95 patients and unilaterally in 5. Between 1 and 6 Gore-tex CV-0 sutures (W. L. Gore and Associates, Inc, Elkton, Md) were placed widely around the arcus tendineus on either side and fixed to appropriate locations on the bladder fascia and anterior vaginal walls. Tying these sutures resulted in dramatic elevation of the lateral superior sulci. Patients were followed up for 1 to 36 months, with a mean of 10.6 months. Criteria for objective cure were defined as the lateral sulci of the anterior vaginal walls being at grade 0 and firmly apposed to the lateral pelvic sidewalls. RESULTS: Of the 100 patients, 34 had grade II, 54 had grade III, and 12 had grade IV paravaginal defect cystocele. Patients were followed up postoperatively for 1 to 36 months: 84 for more than 6 weeks and 55 for 1 year or longer. Our objective cure rate was 98%. Two asymptomatic patients had a unilateral grade I or a bilateral grade II paravaginal defect cystocele. A recurrent midline cystocele occurred in 22 patients between 3 and 11 months after the operation. Twenty-one patients were asymptomatic and one was symptomatic. Twenty-one patients had grade I-II cystocele and one had grade III cystocele. There were 3 major intraoperative hemorrhagic complications; one of the operations was converted to an anterior colporrhaphy. There were a total of 21 major and 14 minor inpatient complications. Twenty-five subsequent complications included various urinary symptoms in 14 patients, long-term lower extremity neuropathy in 2, bloody discharge from intravaginal sutures in 3, absent coital sensation in 1, and recurrent pelvic organ prolapse in 5, all of which included grade III enterocele between 3 and 25 months. CONCLUSIONS: The vaginal approach to the correction of paravaginal defect cystocele is highly effective in our population at a mean of 11 months after the operation. Frequent complications do occur but are largely manageable.

Mersilene mesh sling: short- and long-term clinical and urodynamic outcomes.

OBJECTIVE: We sought to determine the long-term efficacy, safety, and urodynamic effects of the Mersilene mesh suburethral sling in treating complicated forms of genuine stress incontinence. STUDY DESIGN: Two hundred women diagnosed with genuine stress incontinence, complicated by recurrence, intrinsic sphincter deficiency, or chronically increased intraabdominal pressure underwent a suburethral mesh sling procedure (Mersilene; Ethicon Inc, Somerville, NJ). They were monitored with yearly clinical examinations plus short- and long-term postoperative urodynamic evaluations; statistical analysis was carried out by use of the Friedman 2-way analysis by rank, Fischer-Freeman-Halton exact testing, analysis of variance for repeated measures, Wilcoxon, exact Mann-Whitney U test, and Bonferroni paired t test. Of 176 patients who were 5 months or more postop, 127 (72%) had preoperative and short-term postoperative urodynamic evaluations (range 5 to 23 months, mean 12.6 months). Fifty-two of 117 women who were more than 19 months postop (44%) completed preoperative and long-term postoperative urodynamic evaluations at a mean of 63 months (range 20 to 107). One hundred thirty-six of 176 patients (77%) who were more than 4 months postop had a short- and/or long- term postoperative urodynamic evaluation (range 5 to 107 months, mean 30 months). RESULTS: Objective cure rate by stress test was 93% (126 of 136 patients) at a mean of 30 months follow-up. The long-term objective cure rate was 94% (49 of 52). Subjectively, the short- and long-term cure rates were 95.3% and 90.4%, respectively. The cotton swab angle deflection decreased by a mean of 54 degrees at 1 year and 50 degrees at 5 years. Of the 10 failures, the mean preoperative cotton swab straining angle was 19.6 degrees, with 6 being < 30 degrees. Nineteen patients had a negative preoperative cotton swab angle test result (mean straining angle 15 degrees before operation, -6 degrees after operation) and a long-term cure rate of 67%. The objective cure rate in patients with positive cotton swab angle results monitored long term (mean 62 months) was 100% (41 of 41). The postvoid residual increased by a mean of 25 mL short term and 10 mL long term. Thirty-eight patients (19%) had a total of 43 complications. Seven patients (3.5%) had long-term retention. De novo detrusor instability occurred in 12 patients (8.8%), although it was cured in 6 (4.4%). Eight patients (4%) had vaginal or inguinal sling erosion and were healed after revision. Delayed healing at the vaginal sling site responded completely to estrogen cream in two (1%) patients. Five women had treatable vaginal stenosis, 5 had a local inguinal collection/infection unrelated to the mesh, and 3 required a 2-unit transfusion of packed red blood cells. One patient each had an entrapped nerve released, a cystotomy repaired, or experienced thigh numbness or groin pain. CONCLUSIONS: The suburethral Mersilene mesh sling has a very high long-term objective and subjective cure rate in the treatment of complicated forms of genuine stress incontinence. Frequent complications do occur but are remediable. The 33% failure rate among patients with a preoperative negative cotton swab angle test result and the very low cotton swab straining angle among the 7% who had sling failures further confirms the widely held belief that sling urethropexy in the absence of hypermobility lacks efficacy.

Ultrastructure of substance P-immunoreactive terminals and their relation to vascular smooth muscle cells of rat small mesenteric arteries.

Mesenteric arteries of the rat are surrounded by a plexus of primary afferent nerve terminals which contain both substance P (SP) and calcitonin gene-related peptide (CGRP). The ultrastructural arrangement of the innervation was studied in second-order branches of the rat mesenteric artery using immunohistochemical labelling with antibodies against SP. The structure and distribution of SP-immunoreactive (SP+) and SP-negative (SP-, i.e., virtually all noradrenergic) axons and their terminals within the adventitia of the artery have been determined. Sixteen percent of axons and 22% of varicosities in the perivascular plexus were SP+. Most of the SP+ varicosities lay between 0.4 and 2 microm from the smooth muscle cells, whereas most SP- varicosities lay much closer to the vessel (i.e., <1 microm). SP+ varicosities typically contained the same number and size of small synaptic vesicles and mitochondria as SP- varicosities, but there were more large dense-cored vesicles in the SP+ varicosities. Unlike SP- varicosities, the peptidergic varicosities did not show clustering of synaptic vesicles toward one part of the axon membrane, and none of them formed junctions with the smooth muscle cells. Close relationships between SP+ and SP- varicosities lacked any detectable structural specialization. The arrangement of SP+ (primary afferent) terminals and their association with vascular smooth muscle cells indicates that peptide released from afferent terminals must diffuse further than noradrenaline from sympathetic terminals to reach the vascular smooth muscle.

Extended angiotensin converting enzyme inhibition changes the innervation of renal glomerular afferent arterioles.

Chronic inhibition of the angiotensin I converting enzyme (ACE) with enalapril, results in a phenotypic change of the medial cells of renal afferent arterioles from contractile smooth muscle cells to renin containing epithelioid cells. In normal animals, the density of the innervation of the juxtaglomerular renin containing epithelioid cells is much lower compared to the contractile cells. The effector tissues are known to play an important role in determining the pattern and density of their innervation. In this study, we tested the hypothesis that the density of the innervation of the afferent arteriole smooth muscle cells decreases when they change their phenotype from contractile to renin containing epithelioid cells. The results show that the density of the innervation had significantly increased and the association of the terminals with the smooth muscle cells had changed. There were significantly more varicosities around renal afferent arterioles from rabbits treated with enalapril (10 microg/kg/h) for 6 weeks (mean +/- SEM = 634 +/- 175 x 10(3)/mm2 vessel surface, cf. 329 +/- 69 x 10(3)/mm2 vessel surface in untreated rabbits, P = 0.05), with the number of neuroeffector junctions remaining the same (124 +/- 14 and 164 +/- 32 x 10(3)/mm2 vessel surface) and significantly more non-contacting varicosities (i.e. lying > 100 nm from the medial cells) (74 +/- 5% and 25 +/- 7%, respectively; P = 0.003). Thus, there was no reduction in the innervation of afferent arterioles in which the smooth muscle cells had changed phenotype in response to enalapril treatment as hypothesised. Instead, it would appear that proliferation of the innervation had occurred, with the formation of additional varicosities but these varicosities failed to form neuromuscular junctions. This study has identified a form of neural plasticity in the kidney that has not previously been described.

Cumulus cell dispersal from murine oocytes by an epididymal guanidinobenzoatase.

Guanidinobenzoatase (GB), a serine proteinase with a molecular weight of 71,000, is found both free in the epididymal fluids of the mouse and bound to the sperm surface. Microgram quantities of the enzyme, purified from epididymal fluid, will completely disperse follicle cells from freshly ovulated oocytes after 15 min of incubation. Purified GB exhibits no hyaluronidase activity as determined by the acid albumin assay. The ability of GB to disperse follicle cells is blocked by a proteinase inhibitor endogenous to the male reproductive tract. The inhibitor has no effect on bovine testicular hyaluronidase. Although the function of GB has not been defined, the observations presented here indicate that it may play a role in cumulus matrix penetration during fertilization.

Characterization of the guanidinobenzoatase in the epididymal fluids of the mouse.

Guanidinobenzoatase (GB), a proteolytic enzyme found in the epididymal fluids of mice, was purified to apparent homogeneity by molecular sieving and affinity chromatography. It has a molecular mass of 71 kDa and its enzymatic activity is heat labile and sensitive to EGTA. Its kinetic parameters (K(m) of 6.66 microM and a Vmax of 4.38 nmol/min/mg) were determined using 4-methylumbelliferyl-p-guanidinobenzoate (MUGB) as the substrate. GB activity is concentrated in the cauda epididymal region of the genital tract. Heat-solubilized whole zonae, biologically active ZP3, and several serine proteinase inhibitors, including a proteinase inhibitor endogenous to the male genital tract, effectively block the ability of GB to hydrolyze MUGB. Pretreating cumulus-free, zonae intact oocytes with purified GB reduces, in a concentration-dependent manner, the number of sperm able to bind to the zonae. The function of the soluble enzyme is not known. Its ability to bind both trypsin inhibitors and ZP3 suggests a possible role in gamete recognition.

Ovarian Burkitt lymphoma: pelvic pain in a woman with AIDS.

BACKGROUND: Non-Hodgkin lymphomas, a common AIDS-defining manifestation of human immunodeficiency virus (HIV), are aggressive, advanced at diagnosis, and tend to involve extranodal sites. Burkitt lymphoma comprises approximately 20% of AIDS-related non-Hodgkin lymphomas. Sites frequently affected by the disease include the central nervous system, bone marrow, gastrointestinal tract, and mucocutaneous tissue. Gonadal involvement is less common; reports of testicular lymphomas in adult males with AIDS have been sporadic. Ovarian involvement in AIDS-related lymphoma is exceedingly rare and usually involves pediatric patients. CASE: We report an unusual case in which disseminated Burkitt lymphoma presented as pelvic pain in a 32-year-old woman with AIDS. At laparoscopy, the ovaries were unremarkable in appearance but at the upper limits of normal size. However, extreme friability of the left ovary led to hemorrhage and oophorectomy. Pathologic evaluation of the ovary resulted in the diagnosis of Burkitt lymphoma. CONCLUSION: With improved survival because of antiretroviral therapy, the incidence of AIDS-related lymphomas is expected to rise. Lymphoma should be considered in the differential diagnosis of women with AIDS with perplexing abdominal or pelvic symptoms.

Conservative management of incidental cystotomy at laparoscopy. A report of two cases.

BACKGROUND: In the last 20 years the technique of operative laparoscopy has rapidly evolved, so the majority of gynecologic procedures can now be performed endoscopically. However, laparoscopy is still a relatively new technique, and we have much to learn about its associated complications and their management. In the English-language literature there are 15 reported cases of bladder perforation associated with laparoscopy, and 4 of them occurred with insertion of the primary trocar. CASES: Two cases are described in which incidental cystotomy occurred with primary trocar insertion during laparoscopy for infertility and chronic pelvic pain. Both patients were treated successfully with Foley catheterization. CONCLUSION: To our knowledge, nothing was written earlier about conservative management of incidental cystotomy occurring at the time of primary laparoscopic trocar insertion. This paper reports two such cases.

Proportions and structure of contacting and non-contacting varicosities in the perivascular plexus of the rat tail artery.

Most sympathetic postganglionic noradrenergic varicosities of the perivascular plexus of small muscular arteries in laboratory mammals make contact with the outer smooth muscle cells of the media at neuromuscular junctions. These neurovascular junctions have most of the characteristics of those in skeletal muscle. In the rat tail artery, which bears a particularly dense perivascular plexus, many studies indicate that both purinergic and noradrenergic mechanisms underlie neurally mediated vasoconstriction. We have examined the relationship of large axonal varicosities to the smooth muscle surface of proximal parts of this vessel using three-dimensional reconstructions from serial thin sections photographed in the electron microscope. Unlike in small arterioles, less than 50% of the large photographed in the electron microscope. Unlike in small arterioles, less than 50% of the large varicosities lying within 1 micron of the outer surface of this artery were found to make neuromuscular junctions. In some non-contacting varicosities, accumulations of synaptic vesicles were aggregated toward axonal membrane which was bare of Schwann cell toward the vessel surface. Prejunctional membrane specializations were detected at 20% of contacting and 12% of non-contacting varicosities. All of the latter lay close (< 350nm) to the smooth muscle. These anatomical data suggest that, in the rat tail artery, transmitter release by exocytosis may occur from both types of varicosity.

A practical approach to perimenopausal and postmenopausal urinary incontinence.

This article provides a logical approach to the evaluation and management of urinary incontinence in the perimenopausal and postmenopausal woman. The impact of the climacteric on normal anatomy and physiology of the female continence mechanism is addressed. Primary office evaluation and guidelines for referrals are provided. The surgical and nonsurgical treatments of incontinence are discussed with illustrative cases.

Hematometra complicating conization with radiologic correlation. A case report.

We report hematometra as a rare complication of cervical stenosis after a cone biopsy. Ultrasound and magnetic resonance imaging were very helpful in determining the diagnosis in conjunction with a physical examination.