Impact of atrial arrhythmias on outcome in adults with congenital heart disease.

BACKGROUND: Adults with congenital heart disease (ACHD) are affected by atrial arrhythmias (AA). To elucidate the impact of AA on prognosis, we aimed to determine the impact of AA on death, heart failure and stroke in ACHD patients in a prospective nationwide clinical registry. METHODS: All patients aged ≥18years included in the CONCOR registry per October 1st 2015 were analysed. Prior AA was defined as atrial fibrillation, atrial flutter or unspecified AA before inclusion in CONCOR and new-onset AA as a first documented AA during follow-up. The outcomes were death, first stroke and first admission for heart failure (HF). RESULTS: The study cohort comprised 14,224 patients (baseline median age 33.6 [IQR 23-47], male 49.5%, AA n=1501, complex defect 10.3%, repaired defect 58.9%). Median follow-up was 6.5years [IQR 3-10]. Adjusting for age, sex, repair status and defect severity, patients with prior AA had higher mortality and more HF admissions, but no increased risk of stroke compared to those without AA (HR=2.11; 95% CI=1.79-2.49; p<0.001, HR=4.06; 95% CI=2.66-6.19; p<0.001 and HR=1.09; 95% CI=0.71-1.68; p=0.698, respectively). New-onset AA during follow-up was significantly associated with stroke (HR=2.04; 95% CI=1.05-3.96; p=0.036). CONCLUSIONS: ACHD patients with prior AA have a 2-fold increased risk of death and a 4-fold increased risk of heart failure, but no increased risk for stroke compared to those without AA. Defect severity and age appear to be more important risk factors for stroke than prior AA. Stroke risk is increased only after conversion of new onset AA.

Detection and imaging of atmospheric radio flashes from cosmic ray air showers.

The nature of ultrahigh-energy cosmic rays (UHECRs) at energies >10(20) eV remains a mystery. They are likely to be of extragalactic origin, but should be absorbed within approximately 50 Mpc through interactions with the cosmic microwave background. As there are no sufficiently powerful accelerators within this distance from the Galaxy, explanations for UHECRs range from unusual astrophysical sources to exotic string physics. Also unclear is whether UHECRs consist of protons, heavy nuclei, neutrinos or gamma-rays. To resolve these questions, larger detectors with higher duty cycles and which combine multiple detection techniques are needed. Radio emission from UHECRs, on the other hand, is unaffected by attenuation, has a high duty cycle, gives calorimetric measurements and provides high directional accuracy. Here we report the detection of radio flashes from cosmic-ray air showers using low-cost digital radio receivers. We show that the radiation can be understood in terms of the geosynchrotron effect. Our results show that it should be possible to determine the nature and composition of UHECRs with combined radio and particle detectors, and to detect the ultrahigh-energy neutrinos expected from flavour mixing.

Peptide YY release after colectomy in slow transit constipation.

BACKGROUND: The gut hormone peptide YY is abundant in the colonic mucosa. Circulating PYY inhibits gastrointestinal motility and decreases food intake. The aim was to determine whether colectomy decreases PYY release in patients with slow transit constipation. METHODS: Plasma PYY concentrations were measured in 10 patients with slow transit constipation before and 3-24 months after total abdominal colectomy with ileorectal anastomosis, and in 8 healthy controls. A liquid meal was infused intraduodenally to stimulate PYY release. RESULTS: Postprandial PYY significantly (P < 0.05) increased from a basal value of 15.6 +/- 1.8 pM to a peak of 71.2 +/- 11.6 pM after colectomy. Basal and postprandial plasma PYY concentrations were not significantly different from the results before surgery. Fasting, but not postprandial, plasma peptide YY after colectomy was significantly higher than that in healthy volunteers, 10.9 +/- 0.9 pM. CONCLUSION: Despite removal of a major source of PYY-secreting cells, colectomy with ileorectal anastomosis does not induce major impairment of PYY release in slow transit constipation.

Evaluation of 239 cases of perinatal death using a fundamental classification system.

OBJECTIVE: To classify 239 cases of perinatal death in a newly introduced classification system for underlying causes of perinatal death. DESIGN: Prospective, descriptive. SETTING: Dutch healthcare region Delft-Westland-Oostland (DWO). MATERIALS AND METHODS: In 10 years (1983-1992), all cases of perinatal death with a birthweight above 500 g (n=239) were included into the study. We used a classification model based upon the underlying cause of death using simple principles of obstetrical and neonatal pathology. A team consisting of a gynaecologist, neonatologist and pathologist classified all cases of perinatal death into seven groups to determine the "most-probable" cause of death. RESULTS: Birth trauma was seen in two cases (0.8%). Infections were seen in 16 cases (6.8%). Acute/subacute placental pathology in 77 cases (32.2%) and chronic placental pathology in 50 cases (21%). Bloodtype antagonism was seen in two cases (0.8%). Lethal congenital malformations in 55 cases (23%). Complications of pre-viable delivery in 20 cases (8.4%). Unclassifiable were 17 cases (7%): two cases could not be classified despite thorough investigation (1%) and 15 cases were lost for follow-up (6%). CONCLUSIONS: Classification of perinatal death causes by using our fundamental classification system gives insight in the possible underlying causes of death. The results of such a classification can be used as guidelines for preventive measures in the future.

Fundamental classification of perinatal death. Validation of a new classification system of perinatal death.

OBJECTIVE: To validate a newly introduced classification system for the registration of perinatal mortality. DESIGN: Descriptive. SETTING: Dutch Healthcare region Delft-Westland-Oostland (DWO). MATERIAL AND METHODS: In a 10-years period (1983-1992), all cases of perinatal death with a birthweight above 500 g (n=239) were included into the study. Six assessors: four gynaecologists and two paediatricians were asked to classify all cases using a classification model proposed by the authors. This model is based on the underlying cause of death using simple principles of obstetrical and neonatal pathology: birth trauma, infection, placenta or cord pathology, pathology of immune tolerance of mother and fetus, congenital malformation of the fetus and complications of a pre-viable delivery. Therefore, we used the term fundamental classification. The six assessors worked independently of each other in classifying all cases of perinatal death, were not involved in the original development of the system and were unaware of the results of the classification of their colleagues. Agreement beyond chance between assessors was calculated using kappa's coefficient for multiple observers and multiple test results. RESULTS: Overall kappa was 0.70 (95% confidence interval (C.I.) 0.68-0.72). Reproducibility was poor for the categories trauma and unclassifiable, fair for the categories infections and placental/cord pathology, and very good to excellent for the categories maternal immune system pathology, congenital malformations and complications of prematurity. CONCLUSIONS: The proposed system showed a good level of agreement and appeared to be simply applicable. It offers a good insight in the underlying cause of death with the possibility for recognising preventive factors in future pregnancies and will enable (inter)national comparisons in causes of perinatal death. A reliable uniform registration of perinatal death based on the underlying causes should be the basis for improvement of the quality of perinatal care.

Therapeutic immune reconstitution in HIV-1-infected children is independent of their age and pretreatment immune status.

OBJECTIVE: To evaluate long-term immune reconstitution of children treated with highly active antiretroviral therapy (HAART). METHODS: The long-term immunological response to HAART was studied in 71 HIV-1-infected children (aged 1 month to 18 years) in two prospective, open, uncontrolled national multicentre studies. Blood samples were taken before and after HAART was initiated, with a follow-up of 96 weeks, and peripheral CD4 and CD8 T cells plus naive and memory subsets were identified in whole blood samples. Relative cell counts were calculated in relation to the median of the age-specific reference. RESULTS: The absolute CD4 cell count and percentage and the CD4 cell count as a percentage of normal increased significantly (P < 0.001) to medians of 939 x 106 cells/l (range, 10-3520), 32% (range, 1-50) and 84% (range, 1-161), respectively, after 48 weeks. This increase was predominantly owing to naive CD4 T cells. There was a correlation between the increase of absolute naive CD4 T cell counts and age. However, when CD4 T cell restoration was studied as percentage of normal values, the inverse correlation between the increase of naive CD4 T cell count and age was not observed. In addition, no difference in immunological reconstitution was observed at any time point between virological responders and non-responders. CONCLUSIONS: Normalization of the CD4 cell counts in children treated with HAART is independent of age, indicating that children of all age groups can meet their CD4 T cell production demands. In general, it appears that children restore their CD4 T cell counts better and more rapidly than adults, even in a late stage of HIV-1 infection.

[Gastrointestinal surgery and gastroenterology. XI. Stomas and stoma surgery]. / Gastro-intestinale chirurgie en gastro-enterologie. XI. Stomata en stomachirurgie.

Stomas are an essential part of gastrointestinal surgery. Indications for stoma construction are faecal diversion from a distal diseased bowel segment, prevention of an intestinal anastomosis in intra-abdominal sepsis, and faecal incontinence. Pre- and postoperative counselling and nursing care is essential for a good functional outcome. Following stoma construction, complications such as dermatitis, retraction, prolapse, stenosis and parastomal hernia occur in 30-60% of cases. Thirty percent of stomas need surgical re-intervention in the first 10 years. For diversion of a distal anastomosis, construction of a loop-ileostomy is preferred to a loop-colostomy. Closure of a temporary stoma should not be done within eight weeks of construction. Preoperative evaluation of the distal segment is mandatory. Stoma closure involves an intra-abdominal anastomosis with all its associated complications. The incidence of complications after stoma closure is about 10%.

Effects of rectal mobilization and lateral ligaments division on colonic and anorectal function.

PURPOSE: Colonic and anorectal function are altered after posterior rectopexy. The aim of this randomized, prospective study was to evaluate the effects of rectal mobilization and division of the lateral ligaments on colonic and anorectal function. METHODS: Posterior rectopexy was performed in 18 patients with complete rectal prolapse. Anal manometry and measurement of rectal compliance, total and segmental colonic transit time, constipation score, and defecation frequency were performed preoperatively and three months postoperatively. Ligaments were divided in ten patients. RESULTS: Mean preoperative total transit time was similar between the two patient groups and doubled postoperatively (P = 0.03). Mean postoperative segmental transit time increased by a factor of 1.7 in segments I (ascending colon) and II (descending colon) and by a factor of 2.3 in segment III (rectosigmoid). The same pattern was found in both groups. Mean resting pressure decreased after division of the lateral ligaments and increased after preservation. Mean rectal compliance decreased after division of the ligaments and increased when they were preserved. Mean postoperative constipation score differed little from the preoperative score. Mean defecation frequency was decreased in the group with the ligaments preserved and increased in the group with the ligaments divided. None of the effects of rectal mobilization or division of the lateral ligaments on anorectal function reached statistical significance. CONCLUSION: Rectal mobilization had a statistically significant effect on colonic function. Total and segmental colonic transit times doubled. The effects on anorectal function were not significant. Division of the lateral ligaments did not significantly influence postoperative functional outcome.

Cumulative risk of developing polyps or malignancy at the ileal pouch-anal anastomosis in patients with familial adenomatous polyposis.

Restorative proctocolectomy with an ileal pouch-anal anastomosis is performed in an increasing number of patients with familial adenomatous polyposis (FAP). Two techniques are currently used to construct an ileal pouch-anal anastomosis: (1) a double-stapled anastomosis between the pouch and the anal canal and (2) mucosectomy with a hand-sewn ileoanal anastomosis at the dentate line. Although this procedure is thought to abolish the risk of colorectal adenoma, an increasing number of case reports have been published concerning the development of adenoma at the anastomotic site. The purpose of this study was to evaluate the overall cumulative risk of developing adenomatous polyps after ileal pouch-anal anastomosis and to compare the cumulative risk after either anastomotic technique. A total of 126 consecutive FAP patients undergoing a restorative proctocolectomy were identified from polyposis registries in The Netherlands, Denmark, Italy, Germany, and New York. Life-table analysis was used to calculate the cumulative risk of developing polyps in 97 patients with at least 1 year of endoscopic follow-up (median 66 months, range 12 to 188 months). A double-stapled anastomosis was used in 35 patients, whereas in 62 patients a hand-sewn anastomosis with a mucosectomy was performed. In 13 patients polyps developed at the anastomotic site, four with severe and four with moderate dysplasia. None of the patients developed a carcinoma at the anastomotic site. The cumulative risk of developing a polyp at the anastomotic site was 8% (95% confidence interval 2% to 14%) at 3.5 years and 18% (95% confidence interval 8% to 28%) at 7 years, respectively. The risk of developing a polyp at the anastomotic site within 7 years was 31% for patients with a double-stapled vs. 10% for patients with a hand-sewn anastomosis with mucosectomy (P = 0.03 [log-rank test]). Because FAP patients undergoing a restorative proctocolectomy with either a double-stapled or hand-sewn anastomosis have a substantial risk of developing adenomatous polyps at the anastomotic site, lifelong endoscopic surveillance is mandatory in both groups.

Impaired release of peptide YY in patients with proctocolectomy and ileal pouch-anal anastomosis.

BACKGROUND: Peptide YY (PYY) is a gut hormone produced by endocrine cells in the distal small bowel, colon, and rectum. PYY inhibits upper gastrointestinal secretory and motor functions. The aim of this study was to determine whether basal and postprandial plasma PYY levels in patients with proctocolectomy and ileal pouch-anal anastomosis (IPAA) are reduced and to determine the relationship between plasma PYY and plasma cholecystokinin (CCK) levels. METHODS: Plasma concentrations of PYY and CCK were measured before and after ingestion of a standardized breakfast in 14 IPAA patients and in 12 healthy control subjects. RESULTS: Basal PYY was slightly lower in the IPAA patients than in the controls (8.3 +/- 0.3 versus 9.3 +/- 1.1 pM; not significant). Ingestion of the meal induced a small but significant increase of PYY to a maximum of 10.9 +/- 0.9 pM in patients. Integrated postprandial PYY was markedly reduced in patients when compared with the controls (1725 +/- 66 pM*180min versus 3194 +/- 480 pM*180 min; P < 0.005). Plasma PYY concentrations were inversely correlated with plasma CCK concentrations in the 2nd and 3rd h after the meal (r = -0.86; P = 0.0001). CONCLUSION: PYY release in response to meal ingestion is markedly reduced but not completely absent in patients with proctocolectomy and ileal pouch-anal anastomosis. The inverse relationship between circulating PYY and CCK in the late postprandial phase is compatible with a negative feedback regulation of CCK release by endogenous PYY.

Detection and typing of human papillomavirus in cervical carcinomas in Russian women: a prognostic study.

BACKGROUND: The correlation between human papillomavirus (HPV) infection and tumor prognosis in 159 Russian women with cervical carcinoma was investigated. The presence of various HPV types was correlated with the histologic parameters of the carcinomas and with their immunoreactivity with antibodies to p53, Ki-67-Ag, and bcl-2. METHODS: Formalin fixed, paraffin embedded tissue specimens representing 159 cases of International Federation of Gynecology and Obstetrics Stage I and II were used. HPV DNA was detected by polymerase chain reaction (PCR) using a general primer set that targets the L1 region and synthesizes a product of only 65 base pairs. The HPV types were determined by direct sequencing and compared with known HPV types. RESULTS: All 159 carcinomas were positive for HPV. HPV 16 (64.8%) was most frequently found, followed by HPV 18 (10.7%) and HPV 45 (8.2%). In 6 patients (3.8%), HPV types could not been further classified, and these cases were therefore categorized as HPV X. Although a trend was noted toward poorer prognosis for women with carcinomas harboring HPV types 16, 18, and 45 than for patients with carcinomas harboring HPV types 31, 33, 35, 52, 56, 58, and 68, the differences were not statistically significant. The prevalence of adenocarcinoma and adenosquamous carcinoma was higher among HPV 18 positive patients than among patients with the other known HPV types (P=0.0002). CONCLUSIONS: The rate of HPV positivity in these 159 cervical carcinomas was 100%. These findings challenge the assumption that HPV negative cervical carcinomas exist. This high rate might be attributed to the use of a new broad-spectrum HPV PCR test. HPV typing in cervical carcinoma was not significantly related to clinical outcome. HPV 18 was significantly more frequently found in adenocarcinoma and adenosquamous carcinoma. The possibility of classifying HPV 45 as an oncogenic high risk type should be considered.

[Perinatal mortality in Delft and surrounds, 1983-1992: further reduction is possible by targeting lethal congenital abnormalities and placental insufficiency]. / Perinatale sterfte in Delft en omstreken, 1983-1992: verdere reductie mogelijk door gerichte aandacht voor letale congenitale afwijkingen en placenta-insufficiëntie.

OBJECTIVE: To establish the distribution of perinatal mortality over the various levels of obstetrical care, taking into account the various causes of perinatal mortality. DESIGN: Prospective, descriptive. METHODS: Data were collected on all parturitions of women living in the region Delft-Westland-Oostland (DWO), the Netherlands, during the period 1983-1992, regardless of the ultimate setting of the parturition. A prospective regional registration system for perinatal mortality in the region was matched with the registration by the Central Statistics Office (CBS). With anonymous linking, duplicatures could be excluded. The causes of death were assessed by a gynaecologist, a paediatrician and a child pathologist. It was determined for all cases of perinatal mortality whether the antenatal care had been under the final responsibility of a midwife or a general practitioner (primary care), either at home or in the outpatient clinic, or under the final responsibility of a gynaecologist (secondary care). RESULTS: In the decade studied, 28,983 children were born in the DWO region; 51% under primary care management. The actual perinatal mortality of the region was calculated as amounting to at least 247 cases (0.85%). In 26% (n = 64) of these, the childbirth was managed under primary care responsibility, in 43% (n = 106) after risk selection from primary to secondary care, in 14% (n = 34) under the exclusive responsibility of secondary care and in 17% (n = 43) after risk selection from secondary to tertiary care. The most frequent causes of death were progressive placental insufficiency and lethal congenital anomalies. CONCLUSIONS: The results show that further decrease of perinatal mortality may be achieved by risk selection (in primary care) with regard to lethal congenital anomalies and acute or progressive placental abnormalities. The perinatal mortality is so low (0.85%) that further medicalization of childbirth may be expected to contribute only little to a further decrease of the perinatal mortality figures.

Relationship between human papillomavirus type 16 in the cervix and intraepithelial neoplasia.

OBJECTIVE: To evaluate a temporal relationship between the presence of cervical human papilloma virus (HPV) type 16 and the risk of developing cervical intraepithelial neoplasia (CIN). METHODS: Fifty-four women with HPV 16 polymerase chain reaction (PCR)-positive tests were selected from the gynecologic outpatient clinic of the Reinier de Graaf Hospital, Delft, The Netherlands. At least three successive PCR tests were performed in each woman at intervals of 6 months. The PCR HPV 16 assay was performed in conjunction with cervical smear, and colposcopy and biopsy, if indicated. Women with at least three consecutive positive PCR tests were defined as having persistent HPV 16 infections. Women with one positive test followed by two negative tests were defined as having transient infections. Subdivided into two groups, 25 women had persistent infections and 29 had transient infections. RESULTS: In significantly more women in the persistent group compared with the transient group, CIN developed (11 of 25 versus six of 29, P = .036). Lesions in women with persistent HPV 16 infection were more severe (six of 11 were CIN III versus one of six P = .041). CONCLUSION: Persistent infection with HPV 16 is associated with a higher risk of developing CIN, which is often high-grade.

Contribution of congenital malformations to perinatal mortality. A 10 years prospective regional study in The Netherlands.

OBJECTIVE: : To determine the precise contribution of congenital malformations to perinatal mortality in a region. DESIGN: Prospective, descriptive. SETTING: Region, Delft-Westland-Oostland (DWO) in the Netherlands. MATERIAL AND METHODS: The registration was based on data concerning all deliveries of women domiciled in the health region DWO of the Netherlands. The incidence and contribution of congenital malformations to perinatal death was evaluated by a team consisting of a gynaecologist. a paediatrician and a paediatric pathologist. Malformations were classified as lethal or nonlethal and recorded separately for stillbirth (from 28 weeks gestation) and liveborn infants with 7-day follow-up. RESULTS: In 10 years (1993-1992) 28983 children were born in the region DWO. The perinatal mortality was calculated as 247 cases (0.85%). The overall incidence of congenital malformations in the perinatal death-group was 33%. Lethal congenital malformations were found in 51% of the cases in the stillbirth-group and 70% of the cases in the neonatal death-group. Congenital malformations of the central nervous system are mostly lethal in the stillbirth-group (45%). Cardiovascular- and pulmonary-defects were more prominent in the neonatal period (27% and 33% respectively of the neonatal deaths). Uro-genital and minor malformations (miscellaneous) are more often seen in perinatal deaths without being a contributor to the cause of death. CONCLUSIONS: As most congenital malformations are multifactorial in origin, it is in the understanding and control of such conditions that efforts and resources should now be turned. Through a detailed postmortem fetal and placental examination and clinical-pathological correlations lethal congenital malformations were found in 51% in stillbirths (mainly central nervous system) and 70% in neonates (mainly cardiovascular and pulmonary defects).

Small bowel obstruction after total or subtotal colectomy: a 10-year retrospective review.

BACKGROUND: The aim of this retrospective study was to determine the cumulative incidence of adhesive small bowel obstruction (SBO) after total or subtotal colectomy and to investigate the site of the obstructive adhesions in the abdominal cavity. METHODS: The records of 234 patients who underwent colectomy from 1985 to 1994 were reviewed for SBO, potential risk factors for SBO, and the site of adhesions causing obstruction. Mean follow-up, which was complete in 215 patients, was 63 months. RESULTS: SBO occurred in 56 patients (24 per cent) of whom 42 (18 per cent) had adhesive obstruction. The risk of SBO due to adhesions within 1 year was 11 per cent, increasing to 30 per cent 10 years after colectomy. With univariate analysis no risk factor for adhesive SBO, including previous laparotomies, septic complications and omental resection, was identified. The most common site of obstructing adhesions was the pelvis (ten of 28 patients). CONCLUSION: The incidence of SBO after colectomy is high. Colectomy may be a suitable model for studies of adhesion prevention.

[Measurement of colon transit time useful in the evaluation of functional constipation]. / Meting van colonpassagetijd nuttig bij de evaluatie van functionele obstipatie.

OBJECTIVE: To determine the colon transit time (CTT) in patients complaining of functional constipation and the correlation between abnormal transit times and the types of constipation and of the symptoms. DESIGN: Retrospective, descriptive. SETTING: Department of Surgery, University Hospital, Nijmegen, the Netherlands. METHOD: The signs and symptoms of 112 patients with infrequent or difficult defaecation, 93 (83%) of them women, with a median age of 42 years (range: 16-72), were recorded by means of a questionnaire. After ingestion of radiopaque markers per day for 10 days, an abdominal survey X-ray was made on day 11. The numbers of markers in the X-ray and per segment (right and left hemicolon and rectosigmoid) were counted; the CTT in hours was calculated by multiplying this number by 2.4. Slowness was defined as more than 45 h for the total CTT and as more than 15 h for the segmental CTT. RESULTS: The total CTT was normal in 33 patients (29%) and prolonged in 79 (71%). The CTT was prolonged only in the rectosigmoid in 14 patients with a normal CTT (42%) and in 50 patients with a prolonged total CTT (63%). Of the patients with a normal total CTT, 13 (39%) had a normal segmental CTT. No statistically significant correlation could be demonstrated between the presence of any symptom and a prolonged CTT. CONCLUSION: Functional constipation may be associated with a normal CTT. Disorders of colonic motility and of rectal evacuation could be distinguished by measuring the total and the segmental colonic transit times.

Pelvic floor procedures produce no consistent changes in anatomy or physiology.

PURPOSE: Postanal repair was designed to restore both anatomy and function of the anal canal in neurogenic fecal incontinence. In most series, the degree of continence is improved in fewer than 50 percent of patients. Adding anterior levatorplasty and sphincter plication (total pelvic floor repair) is claimed to improve functional results. We performed a randomized trial comparing postanal and total pelvic floor repair for neurogenic incontinence. METHOD: Twenty female patients were studied. All had Type D incontinence (Parks and Browning). Anal manometry, defecography, and grading of the degree of continence were repeated 12 weeks after surgery to assess changes in clinical, manometric, and radiologic parameters. Statistical analysis was done using Wilcoxon's signed-rank test and Wilcoxon's two-sample test. RESULTS: Continence improved in eight patients. Differences among clinical, manometric, and radiologic data were not statistically significant. CONCLUSION: Pelvic floor repair procedures produce no consistent changes in anatomy or physiology. Clinical improvement is caused by creation of a local stenosis or by the placebo effect rather than by improvement of muscle function.

Influence of Parks' anal retractor on anal sphincter pressures.

PURPOSE: The effects of the Parks' anal retractor on anal sphincter function were studied in a prospective, randomized trial. A closed hemorrhoidectomy was performed intra-anally in 20 patients using the Parks' anal retractor; in 20 other patients, the procedure was done perineally without the use of a retractor. METHODS: Anal manometry was performed before and at 6 and 12 weeks after hemorrhoidectomy. RESULTS: Mean squeeze pressure decreased by 4 percent whether or not a retractor was used. Mean resting pressure decreased by 23 percent after use of Parks' anal retractor (P = 0.01) compared with 8 percent when it was not used (P > 0,05). CONCLUSIONS: The internal anal sphincter is easily damaged with the use of the Parks' anal retractor. When possible, its use should be avoided to obtain better manometric and functional results.

Progressing imbalance between proliferation and apoptosis with increasing severity of cervical intraepithelial neoplasia.

The equilibrium between cell proliferation and protection against apoptosis was studied immunohistochemically using monoclonal antibodies against Ki-67-Ag and bcl-2, respectively, in consecutive sections from normal and metaplastic cervical epithelia and cervical intraepithelial neoplasia (CIN) lesions and cervical carcinomas. A high percentage of Ki-67-Ag positive cells was seen in the parabasal cells of normal ectocervical and mature squamous metaplastic epithelium, although the basal cells were virtually negative. In preneoplastic lesions, however, the basal cells showed high proliferative activity and an increasing frequency of Ki-67-Ag positive cells was observed in the higher epithelial layers with increasing severity of CIN. In squamous cell carcinomas, variable numbers of Ki-67-Ag positive cells were observed and in adenocarcinomas expression increased with the degree of anaplasia. bcl-2 expression was observed only in the basal cells of normal endo- and ectocervix including reserve cells. With increasing severity of CIN, staining intensity and number of bcl-2 positive cells gradually increased. Five of eight squamous cell carcinomas were variably positive. All five adenocarcinomas showed extensive bcl-2 expression. Increased expression of both Ki-67-Ag and bcl-2 with increasing severity of CIN indicates an increasing imbalance between cell proliferation and protection from apoptosis. It is therefore proposed that an increasing proliferative fraction combined with a higher number of cells protected from apoptotic cell death contributes to progression of CIN. This phenotype may identify premalignant lesions with the potential to transform to cervical cancer.

[Discrepancy between results of registration of perinatal cause of death by the CBS (Central Bureau of Statistics) and by personal studies in the Delft-Westland-Oostland region]. / Discrepantie tussen resultaten van registratie van perinatale doodsoorzaken door CBS en door eigen onderzoek in de regio Delft-Westland-Oostland.

OBJECTIVE: To determine the reliability of the Dutch registration of causes of perinatal death by the Centraal Bureau voor de Statistiek (CBS, Central Statistics Office). DESIGN: Prospective, descriptive. SETTING: Region Delft-Westland-Oostland, the Netherlands. MATERIAL AND METHODS: The registration was based on data concerning all deliveries of women domiciled in the region, irrespective of the ultimate place of delivery, during 1983-1992. By linking, in retrospect, a prospective regional registration system for perinatal mortality within the region anonymously to the CBS registration, the reliability of the latter registration with regard to the causes of death was determined. To establish the causes of death, all available data were judged by a team consisting of a gynaecologist, a paediatrician and a paediatric pathologist. The diagnoses were classified with the aid of the International Classification of Diseases 9 (ICD-9). RESULTS: In 10 years, 28983 children were born in the region. Over this period, the CBS recorded 227 cases of perinatal mortality. The actual perinatal mortality was calculated as at least 247 cases. In 32% of the cases of stillbirth, the cause of death was not known at the CBS. Of the 82 cases in which the CBS had recorded a diagnosis, the causes of death were in agreement with those found in the regional study in 46%. Of the first-week mortality, the diagnosis was unknown at the CBS in one case and of the remaining 76 cases, the registration of the cause of death was the same in 68% of the cases. CONCLUSIONS: Registration of the causes of death regarding perinatal mortality and particularly stillbirth by the CBS shows gaps, mostly due to incorrect reporting of the cause of death by the treating physician or autopsist, due to the fact that at the time of notification the morbid-anatomical diagnosis and/or laboratory data were not complete. For the study of the backgrounds of perinatal mortality the current CBS registration of causes of death appears unsuitable.