Two new Cu(ii) and La(iii) 2D coordination polymers, synthesis and in situ structural analysis by X-ray diffraction.

Two new coordination polymers were synthesized solvothermally using 4,4'-dimethoxy-3,3'-biphenyldicarboxylic acid (H2dmbpdc), and di- and trivalent metal salts (Cu(NO3)2·2.5H2O and La(NO3)3·6H2O). Their structures were determined by single-crystal X-ray diffraction analysis, and their thermal stability was evaluated by thermogravimetric analysis. The copper compound Cu(dmbpdc)(DMF; N,N-dimethylformamide), CPO-71-Cu, is based on the well known copper acetate paddlewheel secondary building unit. The asymmetric unit comprises one copper cation with one DMF molecule and one linker molecule coordinated. The lanthanum compound La2(dmbpdc)3(DMF)(H2O)3, CPO-72-La, is formed from a dimer of nine-coordinate, edge sharing lanthanum cations. To this dimer, three water molecules and one DMF molecule are coordinated in an ordered fashion. In addition, the asymmetric unit contains three crystallographically unique linker molecules. Both CPO-71-Cu and CPO-72-La form two-dimensional layered structures, and topological analyses reveal sql topologies with point symbol 4(4)·6(2) and vertex symbol 4·4·4·4·6(2)·6(2). The thermal behavior of CPO-71-Cu was investigated in an in situ structural analysis by variable temperature powder- and single-crystal X-ray diffraction.

Factors influencing the reliability of oral contraceptives.

BACKGROUND: The reliability of oral contraceptives (OC) is high but several known factors can potentially induce failures. The dose of estrogen (EE) has been reduced through the years. Interaction with concomitant use of other medicine is wellknown and gastroenteritis can reduce the uptake of EE. To further characterize and quantify these factors we have performed this study. METHODS: Among patients admitted for legal abortion we selected those who had taken OC (only combined preparations; gestagen-only preparations were excluded) according to the prescription but nevertheless became pregnant. Various parameters were noted. RESULTS: Among 8058 women 70 women were found. Twenty-nine used three-phased and 25 used low-dose OC while the rest used high-dose, two-phased or unknown OC (four, five and seven patients respectively). Five patients used other medicine concurrently (salbutamol, astemizol, mianserin, chlorcyclizin, paradryl, carbamazepin, lithium, chlorprotoxin and imipramin). Sixteen patients had symptoms of gastroenteritis at the time of conception. Forty-nine patients had failure without any known influencing factors. There was no significant difference between the various OC used by the patients compared to sales of them in Denmark. About two-thirds of the patients wanted to continue with OC as future prevention. CONCLUSIONS: Failure of OC is a rare event but can occur in case of concurrent gastroenteritis or use of other medicine but in many cases, however, no definite cause can be determined. The EE-content of the various OC was not found to have any influence. Although OC-failure had occurred two-thirds of the patients wanted to continue the use of OC.

PIP: The factors associated with unplanned pregnancies among oral contraceptive (OC) users were investigated in the 8058 women admitted to University Hospital (Copenhagen, Denmark) during 1986-91 for induced abortion. 70 (0.87%) of these women had been consistent OC users; women with a history of missing 1 or more days of pill use and users of gestagen-only pills were excluded. The largest subgroup (41.4%) of these women used triphasic OCs; 35.7% used a low-dose OC and the remainder took high-dose, two-phased, or unknown preparations. Concomitant use of one or more other drugs (spray saline, astemizol, mianserin, chlorcyclizin, paradryl, carbamazepin, lithium, chlorprotixen, and imipramine was reported by 5 women (7%) who experienced OC failure; 4 of these women were using a triphasic OC. At the time of conception, 16 women (30%) had symptoms of gastroenteritis (vomiting and/or diarrhea) and had self-medicated with an unknown preparation. No risk factor could be identified in the remaining 49 women (70%). 2/3 of women who became pregnant while taking OCs returned to this method after abortion. There was no association between the annual sales of various OCs during the study period and the incidence of OC failure. These findings confirm the contributions of concurrent gastroenteritis and drug interactions to OC failure but suggest these are rare occurrences.

Prognosis of vulvar dysplasia and carcinoma in situ with special reference to histology and types of human papillomavirus (HPV).

Sixty-one women with vulvar dysplasia or carcinoma in situ were treated with local laser excision of the initial lesion and of the recurrences, and followed at intervals of from 3 increasing to 12 months. Recurrences were observed in 16 (26%) patients. No case of invasive carcinoma was seen. Patients with recurrences were significantly younger than those without (P < 0.02, median age 42.5 and 54 years, respectively). The resection borders were significantly more often involved in the initial lesions in the group with recurrences (36%) than in the group without (9%) (P < 0.014). All lesions were classified according to the WHO (mild, moderate, severe dysplasia or carcinoma in situ) and Toki et al. (1991) (warty, basaloid, combined warty/basaloid or mixed (warty, basaloid and simple). No pure types of Toki (1991) could be demonstrated. There were no differences regarding recurrences in any of these groups. HPV DNA was detected in the initial lesions by PCR in 50/56 (89%) (44 with HPV type 16 and 6 with HPV type 33) and by ISH in 23/61 (38%). The same type of HPV could be demonstrated in all first recurrences except in two, where HPV types 33 was shown in specimens harboring HPV type 16 in the initial lesions. In one of these cases, HPV type 16 could again be demonstrated in the second and final recurrence. In no specimen was more than one type of HPV detected. The results indicate that the most important parameter in predicting the recurrence of vulvar dysplasia or carcinoma in situ is the involvement of the resection borders. The location of the lesion, the degree and type of dysplasia, and the type of HPV seem to play a minor role. Local excision and subsequent intensive control with removal of any visible new lesion probably prevents development of vulvar invasive carcinoma.

Female urethral diverticulum. Clinical aspects and a presentation of 15 cases.

OBJECTIVE: Fifteen patients with female urethral diverticulum (FUD) were referred during nine years. In order to point out the symptomatology and findings and to evaluate the treatment we have reviewed these patients. METHODS: A retrospective analysis of 15 women treated with transvaginal diverticulectomy. The technique is described. RESULTS: The median age was 54 years. All the patients had symptoms of lower urinary tract disorder. The time from the first appearance of symptoms to referral was median 2 years (range, 4 days 30 years). Seventy-five percent of the cases had a pronounced tenderness. In 14 patients a suburethral mass could be found. Purulent material could be expressed in twelve cases. Three patients with symptoms for more than 10 years were characterized by stress incontinence and frequency and recurrent cystitis. No single diagnostic test proved to be specific for FUD. In eight patients (53%) the indication for operation was based only on symptomatology and the presence of a suburethral mass. CONCLUSION: Diverticulum of the urethra is to be suspected in women with unexplained lower urinary tract symptoms. We recommend a collaboration of the two specialties: Gynaecology and Urology.

Human papillomaviruses and multifocal genital neoplasia.

In 143 patients with vulvar carcinoma (76 cases) or vulvar intraepithelial neoplasia (VIN III, 67 cases), cervical cancer or cervical intraepithelial neoplasia CIN III lesions developed in 39 patients (27%) at some time during their life. In patients with classic keratinizing squamous cell carcinoma (KSC) of the vulva, cervical neoplasia developed in only one of 51 (2%), whereas the frequency was 10 of 25 (40%) in patients with vulvar carcinoma of the basaloid or warty type and 28 of 67 (42%) in patients with VIN III lesions. The original, paraffin-embedded surgical specimens were examined by polymerase chain reaction and type-specific molecular hybridization for human papillomavirus (HPV) DNA of the types 6, 11, 16, 18, and 33. DNA of the oncogenic types HPV 16 or HPV 33 was found in 4% of the KSCs, in 84% of the basaloid or warty carcinomas, in 90% of VIN III lesions, and in 89% of the cervical lesions. The same HPV type was found in both lesions in 81% of the patients with double primary tumors. The results support the concept that VIN III and a subgroup of vulvar carcinomas are HPV-related lesions, that they are frequently associated with another HPV-related genital primary tumor, and that these multiprimary tumors are secondary to an HPV infection involving the entire genital tract.

Management of low-grade CIN: follow-up or treatment?

OBJECTIVE: To examine whether low-grade cervical dysplasia carries a higher risk of progression when associated with the cancer-related human papillomavirus types 16, 18, 31 or 33. STUDY DESIGN: Retrospective, with PCR-based HPV diagnosis on the original cervical biopsies from 71 patients with CIN I and II. CIN III developed in 34 lesions, and 37 showed complete regression during non-invasive follow-up. RESULTS: Progression occurred in 15/41 CIN I and in 19/30 CIN II lesions (P = 0.03). HPV DNA was detected in 43 specimens. CIN III developed in 25% of HPV-negative lesions, in 48% of HPV-positive CIN I lesions, and in 77% of HPV-positive CIN II lesions. CONCLUSION: Low-grade lesions are at higher risk of progression when associated with HPV types 16, 18, 31 or 33 (P = 0.002). HPV diagnosis can be useful in the triage of patients with low-grade CIN.

Human papillomavirus (HPV) in vulvar dysplasia and carcinoma in situ.

Surgical specimens from 62 patients with vulvar dysplasia and carcinoma in situ were morphologically investigated. Lesions were classified according to WHO (mild, moderate, severe dysplasia and carcinoma in situ) and according to Toki et al. (1991) (warty, basaloid, combined warty/basaloid or basaloid/warty types or mixed (warty, basaloid and simple) forms). Following the WHO classification, moderate dysplasia was shown in 4 cases, severe dysplasia in 47 and carcinoma in situ in 11 cases. Pure warty type was shown in 2 cases (both biopsy specimens). One case revealed pure simple dysplasia whereas no case of pure basaloid type was found. Various combinations of warty and basaloid types were shown in 52 cases and mixed forms in 7 cases. The results indicate that pure forms of warty and basaloid types probably do not exist. HPV DNA was detected by PCR in 51/58 cases (88%) (45 with HPV type 16 and 6 with HPV type 33) evenly distributed in all age groups and in all types of lesions (WHO and Toki et al. 1991). By ISH HPV was detected in 24/62 cases (39%) (21 with HPV type 16/18 and 3 with HPV type 31/33), nearly always in warty areas. All these cases were positive for the same virus type by PCR. No case revealed more than one type of HPV. HPV type 6, 11, 18, and 31 were not detected by PCR. The results indicate a correlation between HPV type 16 and 33 and dysplasia/carcinoma in situ in the vulva.

Vulvar intraepithelial neoplasia III: a viral disease of undetermined progressive potential.

Seventy-three patients with vulvar intraepithelial neoplasia (VIN) grade III were followed for a median of 5 years after primary treatment. Thirty women also had a diagnosis of cervical neoplasia. During the follow-up 26 patients (36%) had one or more vulvar recurrences. Recurrences were seen significantly more often in the patients who also had cervical neoplasia, indicating a common etiology. Microinvasive carcinoma developed in 12 patients, 3 of whom later developed frankly invasive vulvar cancer. The original, paraffin-embedded vulvar specimens were examined by the polymerase chain reaction for human papillomavirus DNA of the types HPV 6, 11, 16, 18, and 33. HPV types 16 and 33 were found in 90% of the VIN lesions. It is concluded that VIN III is an HPV-related disease in all or almost all cases, and that a generalized genital HPV infection may be a factor in the development of multicentric genital neoplasia. No association was observed between the specific HPV type and the risk of recurrent vulvar disease, cervical neoplasia, or malignant progression.

Vulvar squamous cell carcinoma and papillomaviruses: indications for two different etiologies.

The vulvectomy specimens of 78 patients with vulvar squamous cell carcinoma were reviewed and examined for human papillomavirus (HPV) types 6, 11, 16, 18, and 33 by the polymerase chain reaction technique. The tumors were classified as keratinizing squamous cell carcinoma (KSC), as warty carcinoma (WC), and as basaloid carcinoma (BC). DNA of HPV types 16 and 33 was found in 2/51 KSC, in 12/17 WC, and in 10/10 BC. HPV types 6, 11, and 18 were not detected. Patients with WC and BC were younger, and 78% had VIN III lesions adjacent to the carcinoma. Patients with KSC were older and had a high incidence of dystrophic lesions, including lichen sclerosus, adjacent to the tumor. None of the KSC showed adjacent VIN III. In conclusion, vulvar carcinoma segregates into two categories, of which KSC seems to be the classic type, only rarely associated with HPV infection, and mostly affecting older women; WC and BC constitute an HPV-related subgroup of tumors occurring in younger patients and are associated with VIN III lesions from which they may emerge.

The value of CA 125 measurement before second-look laparotomy in patients with ovarian carcinoma.

Serum CA 125 levels were evaluated in 71 patients undergoing second-look laparotomy for primary epithelial ovarian cancer. With a cut-off limit of 35 U/ml, 17 of 45 patients with residual disease (38%) were CA 125-positive. All of 26 patients with pathological complete response were marker-negative. Second-look laparotomy may be avoided in a select group of patients with elevated CA 125 values.

Cervical koilocytosis and high risk HPV types: the benefit of laser vaporization.

Forty-six patients with biopsy-proven cervical koilocytosis, which in 19 cases was associated with CIN I, were randomized to treatment by cervical laser vaporization or to follow-up without therapy. The polymerase chain reaction was used to examine the paraffin-embedded cervical biopsies for human papillomavirus (HPV) types 6, 11, 16, 18 and 33 by polymerase chain reaction and molecular hybridization technique. Twenty biopsies contained HPV DNA, in 17 cases of the putatively oncogenic types HPV 16 and HPV 18. During a mean follow-up of 28 months, the lesions resolved in 37 women, 5 women had progression to CIN III lesions, and 4 women had persisting disease. Lesions not harboring any of the 5 HPV types showed a high spontaneous regression rate of 88%, which was not improved by the laser therapy. In the HPV-positive lesions, resolution occurred in only 29% of untreated lesions, but in 92% of those treated by laser. The difference is significant (P = 0.007). It is concluded that in patients with cervical koilocytosis, the HPV diagnosis could be of practical value in identifying patients who might benefit from treatment.

CO2 laser vaporization in the treatment of cervical human papillomavirus infection in women with abnormal Papanicolaou smears.

In a randomized study, we have evaluated the treatment of cervical human papillomavirus (HPV) lesions by CO2 laser vaporization. Fifty patients with abnormal Papanicolaou smears and histological evidence of cervical HPV infection associated or not with cervical intraepithelial neoplasia (CIN) grade I were randomized to either a treatment or a control group. The cervical swabs were obtained every 3 months in both groups and examined for HPV type 16 DNA by the polymerase chain reaction. After a follow-up period of 12 months no significant differences were found between the laser treatment and the control groups in relation to the disappearance of the abnormal Papanicolaou smear. Two patients in the treatment group and 3 in the control group had a conization because of development of CIN I or aggravation of the concomitant CIN found at the initial visit. The percentage of women who demonstrated HPV in their cervical smears at 12 months' follow-up was identical in the two groups, supporting the hypothesis that HPV is a persistent infection during which the virus is widespread in the vaginal epithelium.

CA-125, placental alkaline phosphatase and tissue polypeptide antigen as preoperative serum markers in ovarian carcinoma.

Blood samples were drawn before laparotomy in 42 cases of benign, 17 cases of borderline, and 53 cases of malignant epithelial ovarian neoplasms. The concentrations of CA-125, tissue polypeptide antigen, and placental alkaline phosphatase (PLAP) were determined. No significant difference was found between the levels of CA-125 and TPA. No significant correlation was seen between tumour type and these two markers; however, both were significantly correlated to tumour malignancy and clinical stage, and CA-125 was also correlated to tumour grade. No correlation was found between PLAP and the other markers or any of the above-mentioned parameters. If at least one of two or three markers was requested to be positive, a moderate increase in the 'detection rate' of malignant tumours was found. However, the rate of positive benign samples increased to as much as 41%. Requesting at least two markers out of two or three to be positive certainly reduced the number of 'false-positive' benign tumours, but the sensitivity for malignant tumours was reduced concomitantly to levels where marker determinations would be of little use. The study demonstrated a possible, but limited role for preoperative determinations of the markers. A combination of two or three markers was not superior to single markers. The results indicate that neither of these markers will be of significant value in a screening context.

[Pelvic floor reconstruction with a Prolene net in enterocele]. / Baekkenbundsrekonstruktion ved enterocele med Prolene-net.

Nine women, all of whom were multiparae with large symptom-producing enteroceles and all of whom had been submitted to operation by other methods without permanent effect, were submitted to total pelvic floor reconstruction with non-absorbable mesh. No complications of this intervention were observed and the discomfort due to enterocele disappeared in all of the patients during the follow-up period which averaged 11 months (range 1-24 months). The method is recommended in the treatment of large enteroceles where other forms of surgical treatment have failed.

CO2-laser vaporization of human papillomavirus (HPV)-induced abnormal cervical smears. A simple and effective solution to a recurrent clinical problem.

Fifty women with human papillomavirus (HPV)-induced abnormal cervical smears were randomly allocated to either CO2-laser vaporization or routine control. The success rate at the 6 months check was 100% after laser treatment compared to that of 72% in the control group (p less than 0.05). Although longer follow-up is needed to fully establish the efficacy of the treatment, the method seems appropriate to this large group of women at risk of developing cervical intraepithelial neoplasia.

Diagnostic value of an abnormal smear in non-pregnant women. Evaluation of positive smear from the surface of the portio obtained by the cottonswab method or by the dry wooden Ayre spatula and the relevance of positive smear from the endocervix and/or from the surface of the portio.

During a 3-4 year period, 324 women with a positive smear were registered consecutively and prospectively and divided into two groups according to the design of the investigation. In one group the smear was taken with an Ayre spatula and in the other group with a cotton swab. The purpose of this investigation has been to make a comparison between the endocervical smear and the smear taken from the surface of the portio and at the same time between the samples taken with a dry wooden Ayre spatula and with a cotton swab. No differences were found. The cytological findings have been registered and correlated both with the histological findings by colposcopically directed punch-biopsies and endocervical curettings and with the final histological diagnosis obtained by punch-biopsy, conization or hysterectomy.

CA 125, placental alkaline phosphatase, and tissue polypeptide antigen in the monitoring of ovarian carcinoma. A comparative study of three different tumor markers.

Three different tumor markers, placental alkaline phosphatase (PLAP), tissue polypeptide antigen (TPA), and cancer antigen 125 (CA 125), were measured in serum samples obtained during chemotherapy in 57 ovarian carcinoma patients. At the start of chemotherapy, 37, 63, and 77% had elevated serum values of PLAP, TPA, and CA 125, respectively. During chemotherapy, changing PLAP serum levels reflected disease regression and, later, progression in only 2 patients. TPA serum levels reflected the disease course in 15 patients and CA 125 in 28 patients. Rising CA 125 values predicted disease progression in 12 patients for a median of 2 months. At second-look laparotomy, all 11 patients with pathological complete response were marker negative. In the remaining 46 patients with residual or progressive disease, 27, 50, and 61% had elevated serum levels of PLAP, TPA, and CA 125, respectively. None of the markers reflected microscopic disease or pure carcinomatosis. For management decisions, CA 125 was clearly the most useful of the markers. In this study no further information was gained from the other two markers.

A randomized study of sequential versus alternating combination chemotherapy in advanced ovarian carcinoma.

The concept of using either alternating or sequential combination chemotherapy with non-cross-resistant combinations was tested in a randomized trial including 301 previously untreated patients with advanced epithelial ovarian carcinoma. The sequential schedule consisted of CAF (cyclophosphamide, doxorubicin, 5-fluorouracil) followed by PH (cisplatin, hexamethylmelamine) in nonresponders, CAF- greater than PH (n = 157), and the alternating regimen consisted of CAF/PH (n = 144). With a median observation time of 54 months, no statistically significant differences were found between the pathologically complete response (PCR) rates of 17% and 16%, respectively, nor were there any statistical differences in median disease-free survival for PCR patients (CAF- greater than PH 34+ months and CAF/PH 26+ months), in overall survival (28 and 24 months, respectively), or in time to treatment failure (10 and 11 months). The overall estimated cure rate was 13%. An equal degree of myelosuppression was seen with the two regimens, whereas neuro- and nephrotoxicity were more pronounced when PH was given sequentially to CAF than with the alternating schedule. We conclude that the sequential and the alternated use of doxorubicin- and platinum-based regimens yield equivalent results and that other approaches should be investigated to improve treatment effects.

Intestinal obstruction in patients with advanced carcinoma of the ovaries treated with combination chemotherapy.

An analysis of incidence, risk factors and treatment results of intestinal obstruction caused by carcinoma of the ovaries was performed in 310 consecutive patients with carcinoma of the ovaries, The International Federation of Gynecology and Obstetrics stage IIB to IV, treated with combination chemotherapy. With a median observation time of 46 months, the incidence was 14 per cent and the cumulated risk was estimated to be 26 per cent at five years after treatment was begun. Risk factors were stages IIIB and IV, residual primary tumor size greater than 2 centimeters and presence of intestinal carcinomatosis at primary laparotomy. There was no difference in the survival time between 16 conservatively treated patients and 25 surgically treated patients (a median of 30 and 68 days, respectively, p greater than 0.30). The complication risk of surgical treatment was high (64 per cent), and surgical benefit--defined as survival greater than 60 days with total palliation of intestinal symptoms--was achieved in only 32 per cent.

A randomized study of single agent vs combination chemotherapy in FIGO stages IIB, III and IV ovarian adenocarcinoma.

From 1977 until 1980, 179 patients with newly diagnosed FIGO stages IIB, III or IV ovarian adenocarcinoma were randomized in a two-armed clinical trial: dihydroxybusulfan (B) 600 mg/m2 p.o. for 4-6 weeks q 12 weeks or cyclophosphamide (C) 150 mg/m2 p.o. for 7 days q 4 weeks vs a combination of cyclophosphamide 400 mg/m2 i.v., doxorubicin 30 mg/m2 and 5-fluorouracil 400 mg/m2 i.v., days 1 and 8 q 4 weeks (CAF). In addition, stage IIB patients were randomised to +/- pelvic irradiation. The patients were stratified according to anatomic stage. The treatment groups were comparable with respect to performance status, age and histology. Twenty-three patients were excluded because of protocol violation, leaving 156 patients evaluable for survival with an observation period of 3-6 yr. Twenty patients were in stage IIB, while the remaining 136 patients were classified as stages III and IV. No statistically significant difference was found in survival or response between the two single agents. The overall median response rate (single drug: 27%; CAF: 47%) and the median response duration (single drug: 5 months; CAF: 10 months) were significantly superior for the CAF group compared to the single agent group. No statistical difference in median survival was observed between single-drug treatment (12 months) and CAF (14 months), despite the fact that responders lived significantly longer than nonresponders (17 vs 10 months). In stage IIB patients receiving chemotherapy no benefit of pelvic irradiation was found. Thirty patients (19%) underwent second-look laparotomy, with 15 (50%) being completely free of disease. So far only one patient (7%) has relapsed. Two additional patients, who had microscopic disease removed at second-look laparotomy, seem to have been rescued by this procedure.