Risk of cervical intra-epithelial neoplasia and invasive cancer of the cervix in DES daughters.

OBJECTIVE: Women exposed to diethylstilbestrol in utero (DES) have an increased risk of clear cell adenocarcinoma (CCA) of the vagina and cervix, while their risk of non-CCA invasive cervical cancer is still unclear. METHODS: We studied the risk of pre-cancerous (CIN) lesions and non-CCA invasive cervical cancer in a prospective cohort of 12,182 women with self-reported DES exposure followed from 2000 till 2008. We took screening behavior carefully into account. Incidence was obtained through linkage with the Netherlands Nationwide Pathology database (PALGA). General population data were also derived from PALGA. RESULTS: The incidence of CIN1 was increased (Standardized Incidence Ratio (SIR)=2.8, 95% Confidence Interval (CI)=2.3 to 3.4), but no increased risk was observed for CIN2+ (CIN2, CIN3 or invasive cancer) compared to the screened general population (SIR=1.1, 95% CI=0.95 to1.4). Women with DES-related malformations had increased risks of both CIN1 and CIN2+ (SIR=4.1, 95%CI=3.0 to 5.3 and SIR=1.5, 95%CI=1.1 to 2.0, respectively). For CIN2+, this risk increase was largely restricted to women with malformations who were more intensively screened. CONCLUSIONS: An increased risk of CIN1 among DES daughters was observed, especially in women with DES-related malformations, probably mainly due to screening. The risk of CIN2+ (including cancer) was not increased. However, among DES daughters with DES-related malformations a true small risk increase for non-CCA cervical cancer cannot be excluded.

Deep brain stimulation of the subthalamic nucleus facilitates coordination of hand preshaping in Parkinson's disease.

Several studies have found that Parkinson's disease (PD) disrupts the organization of complex motor sequences regardless of the influence of parkinsonian medications. A clear candidate for the neural bases of such deficits, which we term "coordinative," is the failure to integrate propioceptive and visual information by cortico-striatal circuits in a timed fashion. Recent reports, however, have indicated that deep-brain stimulation of the subthalamic nucleus (STN DBS) may result in an improvement in coordinative deficits beyond the amelioration of "intensive deficits" such as bradykinesia and scaling errors. The present study examined the spatio-temporal organization underlying the shaping of the hand during reaching to grasp objects differing in shape. Six PD patients ON and OFF their STN DBS when OFF their concomitant medications and six age-matched controls participated in this study. STN DBS improved the coordination involved in preshaping the hand while grasping. We discuss these results in light of our earlier work with PD patients on and off dopamine replacement therapy.

[Settlement effected for damages for victims of diethylstilbestrol (DES)]. / Regeling voor schadevergoeding aan slachtoffers van di-ethylstilbestrol (des) een feit.

In 2007 the Dutch DESFonds (DES Fund) starts payment to victims of exposure to diethylstilbestrol in a collective settlement. This is unique in the world because the arrangement covers the entire range of DES-related disorders and individual persons do not have to start an expensive and emotionally taxing legal procedure with uncertain outcome, which would last several years. Individuals can now be compensated based on medical evidence of DES exposure and the presence of a DES-related disorder covered by the settlement. In close collaboration with the DES Centre (an association of DES victims) a careful procedure was followed before this settlement was realised. The Dutch Expert Committee on DES-related Health Effects first reviewed the literature for evidence and established a list of disorders with a causal association with DES. For each DES-related disorder covered by the settlement, the appropriate compensation was determined by the attributive risk and the severity of the disease. The settlement is the result of close collaboration between all parties involved.

Use of misoprostol in first and second trimester abortion: a review.

The use of misoprostol in medical termination of first and second term pregnancies and cervical priming in surgically induced termination of pregnancies has been studied extensively. A survey is given on the available literature (MEDLINE to May 1998) on the usage as a single medication or in combination with mifepristone or methotrexate. A review is given on literature concerning side effects and complications. Misoprostol is a most promising, cheap, and effective agent, which does not need cool storage like other prostaglandins. The use of misoprostol as an abortifacient has, however, not been supported by the manufacturer. This leads to the situation (similar to mifepristone/RU 486) that it is used and researched, but probably will not be officially approved for this specific indication.

Salmonella enteritidis in an endometriotic ovarian cyst.

Isolated Salmonella infections are rare. In view of the rarity, we present a case of a 16-year-old patient with an endometriotic ovarian cyst where Salmonella enteritidis was isolated from aspirated material from the cyst. We include a review of the world literature on ovarian Salmonella infection from 1966 to June 1996.

A prospective randomized study comparing amoxycillin/clavulanate with cefuroxime plus metronidazole for perioperative prophylaxis in gynaecological surgery.

A prospective, randomized, open study was performed in 199 patients at the Leyenburg Hospital comparing amoxycillin/clavulanate (AMX/CL) with cefuroxime plus metronidazole (CR/MN) in the prophylaxis of infection following gynaecological surgery. AMX/CL was given as a single dose of 2200 mg i.v. at the start of the operation. CR/MN, 750/500 mg i.v. was administered 3 times within 24 h, beginning at the start of the operation. The study group consisted of patients undergoing either a vaginal hysterectomy, a vaginal hysterectomy with cysto/rectocele repair or a secondary caesarean section. There were no statistically significant differences in demographic characteristics, duration of surgery or anaesthetic method between the two groups. Postoperatively, 10.6% of patients developed a urinary tract infection, and febrile temperatures were found in 9.0% of patients. There were no statistically significant differences between the two treatment groups. Other complications were found in less than 1% of the study population, equally distributed between the two regimens. In this study there was a low overall percentage of infection after gynaecological surgery. AMX/CL was as effective as CR/MN as a perioperative prophylactic treatment and has the dual advantage of a single dose and lower cost.

A comparison of pefloxacin/metronidazole and doxycycline/metronidazole in the treatment of laparoscopically confirmed acute pelvic inflammatory disease.

A double-blind, randomised study was conducted to compare the efficacy and safety of a combination of pefloxacin and metronidazole versus doxycycline and metronidazole in patients with pelvic inflammatory disease (PID). The clinical diagnosis had to be confirmed by laparoscopy before patients were included. Of the 74 patients who fulfilled the clinical criteria for PID, laparoscopy confirmed the diagnosis in only 40 patients (54%). The microorganism most frequently found as causative pathogen was Chlamydia trachomatis. Both treatment groups showed a good response to the study-medication. At discharge 9 patients in the pefloxacin group (45%) were cured and 10 patients (50%) had improved. In the doxycycline group 7 patients (35%) were cured and 10 patients (50%) had improved. Obviously pefloxacin/metronidazole and doxycycline/metronidazole are equally effective in the treatment of PID.

[Acute fatty degeneration of the liver in pregnancy]. / Acute leververvetting in de zwangerschap.

Acute fatty liver of pregnancy is considered an uncommon disorder that may complicate the third trimester of pregnancy, with high fetal and maternal mortality rates. However, in recent years it has become clear that the course of the disorder can be less fulminant than previously believed. The diagnosis is also made more frequently. The case histories of three patients are described followed by a review of the clinical and diagnostic features. It is concluded that with all women showing symptoms of malaise, nausea, vomiting and upper abdominal pain in the third trimester of pregnancy liver enzymes should be measured. If evidence of liver dysfunction is found, acute fatty liver of pregnancy should be considered in the differential diagnosis. Only early recognition and prompt treatment will improve both fetal and maternal survival.

Should the Cytobrush be used in routine screening for cervical pathology?

In 632 women visiting a family planning clinic, paired cervical smears were taken using a wooden spatula and a Cytobrush. Of the spatula smears 7.8% were unreliable with too little or scanty material to allow a cytologic diagnosis (class 0); 17.7% of spatula smears were inadequate, lacking endocervical cells. Combined spatula/Cytobrush cytology reduced these figures significantly; 4.3% unreliable smears and 3.2% inadequate specimens. Seventy-three (11.6%) of the smears revealed some abnormality, in most cases Papanicolaou class IIIA, suggestive of mild dysplasia. In 10 cases, dysplastic cells were found only in the Cytobrush cytology. It is concluded that the Cytobrush adds to the improvement of smear quality and the accuracy of routine cervical cytology obtained by relatively inexperienced smear takers.

Immunohistologic evidence for the malignant potential of congenital melanocytic nevi.

Monoclonal antibodies (MoAbs) against six well-defined progression-associated melanoma antigens (PAMAs) and a MoAb against the nuclear proliferation-associated antigen Ki67 were used for an immunoperoxidase study on 44 biopsies from 36 congenital melanocytic nevi (CMN). Twenty-nine common acquired nevi and 16 metastasizing primary melanomas were studied as controls. Two CMN of the series were giant CMN (greater than 20 cm), one of which later progressed to metastasizing melanoma. Of the remaining 34 CMN, four were histologically associated with a malignant melanoma. DNA flow cytometry was performed on adjacent cryostat sections of 37 biopsies from 28 CMN without melanoma. PAMAs were found expressed in CMN in the following frequencies: A-1-43: 36%; P358: 27%; PAL-M1: 20%; HLA-DR: 9%; Muc 18: 2%; A-10-33: 0%. No PAMAs were present in only 15 biopsies (34%). One single PAMA was found in 20 lesions (45%), and two or more PAMAs in nine lesions (21%). In all four CMN histologically associated with melanoma, and also in one biopsy from the giant CMN which later progressed to melanoma, at least two PAMAs were expressed. The latter biopsy was the only CMN in which the proliferation-associated antigen could be demonstrated. Only this biopsy and a single biopsy of the other giant CMN showed aneuploidy. We found expression of single PAMAs and co-expression of PAMAs in CMN in higher frequency than in common acquired melanocytic nevi. Co-expression of PAMAs was a feature of metastasizing primary melanomas. We conclude that co-expression of two or more PAMAs in a CMN might indicate its malignant potential, because this was found in all CMN proven to have progressed to malignant melanoma.

Performance of the Cytobrush in patients at risk for cervical pathology: does it add anything to the wooden spatula?

In 130 high-risk patients for cervical pathology paired smears were obtained with a wooden spatula and a Cytobrush. The Cytobrush was useful in lowering the amount of inadequate smears (2 vs 22%, p less than or equal to 0.01), and detected more abnormal cytology in combination with the spatula compared to the spatula smear alone (27 vs 35%, p less than or equal to 0.05). In 6 cases, adequate false-negative spatula smears, containing endocervical cells, were corrected by the Cytobrush. It is concluded that the Cytobrush is useful in lowering the amount of inadequate smears and false-negative cytology, while there is little evidence of false-positive cytology. The use of the wooden spatula/Cytobrush-combination is recommended in high risk populations.

Efficacy of screening for cervical squamous and adenocarcinoma. The Dutch experience.

The nationwide screening program for cervical carcinoma in The Netherlands was unique in that all women between the age of 35 and 55 years were individually invited to undergo a cervical spatula smear. The total rate of positive histologic findings in six regions of the country was 3.9 per thousand, and decreased in the second screening after 3 years with 48% of patients. Further analysis of the change in rates of the separate histologic subgroups in six regions revealed: Severe dysplasia showed no change in rates. The rates of carcinoma in situ and invasive squamous cell carcinoma were influenced clearly by the screening. The preinvasive stages of adenocarcinoma of the cervix were underdiagnosed in the first screening, and there was no decrease in the score of invasive adenocarcinoma. The rates in the six regions differed significantly and were dependent on the degree of urbanization. Cervical screening using the Ayre spatula is not effective for detecting cervical adenocarcinomas.