PubMed Health⌕ Search

Biomedical subjects

L P Kok

Publications and source records attributed to L P Kok.

At least 19 recordsLinked to original sources

Legal issues in the treatment of a violent manic patient in a non-gazetted setting: a case report.

INTRODUCTION: Psychiatrists in non-gazetted treatment settings, like psychiatric wards in restructured general hospitals and private hospitals, face a major problem when psychiatric patients who require admission are either not competent or refuse to consent to admission and treatment, although they are clearly in need of such inpatient management. Admission to the state mental hospital is often refused by their relatives for a number of reasons, like the stigma attached to admission to such a hospital, and the fear that future employment prospects might be affected. CLINICAL PICTURE: Mr X, a manic, violent patient, had no insight into his disorder and refused admission and treatment for his manic episode. He was the head of a large corporation, and his relatives were apprehensive he would make decisions that could jeopardize the company. TREATMENT: He refused oral medication, could not tolerate parenteral haloperidol and had lithium nephrotoxicity. Inpatient electroconvulsive therapy had to be administered, after which he responded satisfactorily. CONCLUSION: The legal implications in this case, like consent for treatment and admission, and ethical issues, are discussed.

Aged↗

Koilocytosis and squamous (pre)neoplasia as detected in population-based cervical screening: practice and theory.

INTRODUCTION: Koilocytosis (cavitation of the cytoplasm due to active HPV infection) can be detected in the screening process for cervical carcinoma. OBJECTIVE: To report the practice of detection of koilocytosis and (pre)neoplasia in population screening and to exploit the collected data to propose an explanation for the relationship between HPV infection and nuclear precancerous changes. STUDY DESIGN: Centrally collected and stored (SBBW, Leiden, the Netherlands) data from all smears of six regional pathology laboratories (1995-2002), coded according to KOPAC (the national cervical smear coding system; S1: normal thru S9: invasive carcinoma) were accessed. Prevalences per 100,000 smears were calculated for koilocytosis and for squamous abnormalities after stratification for country of origin of screenees. The relative risk (RR) for the ethnic (age) groups was computed by dividing the prevalence of the relevant ethnic (age) group by the prevalence of all women. RESULTS: Surinamese women featured the highest prevalence of koilocytosis and of all squamous abnormalities. Moroccan women the lowest. The RR for koilocytosis was highest at 30 years (1.84) and lowest at 60 (0.26). RR dependence on age of S5-S9 lesions was similar. Compared to nonkoilocytotic smears, koilocytosis was 104 times more frequent in the 1,500 S4 smears, 36x more frequent in the 6,700 S2-S3 smears, and 24x more frequent in the 1,740 S5-S9 smears. In all three categories this difference is statistically significant. CONCLUSION: High prevalences for both koilocytosis and for preneoplasia were detected in Surinamese immigrants, however, it still does not exclude HPV infection as a confounder linked to sexual lifestyle. The presence of koilocytosis in cervical smears may serve to identify patients with an increased risk for cervical cancer and perhaps warrant more intensive surveillance than what is provided through five-yearly screening.

Adult↗

[No major difference between population screening for cervical carcinoma at the present screening interval of 5 years and the former interval of 3 years].

OBJECTIVE: To assess the effect of extending the screening interval from 3 to 5 years on the detection of premalignant changes and invasive cervical carcinoma in the restructured population screening programme. DESIGN: Retrospective follow-up study. METHOD: The results were collected of the 1st round (1996-2000; 277, 377 women) and a part of the 2nd round (2001; 49,622 women; screening interval: 5 years) of the screening programme in Region West, the Netherlands. Histoscores for cervical intraepithelial neoplasia (CIN) 3 and squamous cell carcinoma (n/100 women investigated) and the hit count (sum of the histoscores for CIN 3, adenocarcinoma in situ and (micro)invasive cervical carcinoma) were calculated. Data of women with adenocarcinoma in situ and endocervical (adeno)carcinoma were recorded separately. The results of the 1st and 2nd round of the current screening programme (commenced in 1996) were compared with those of the historical screening programme that commenced in 1976 (screening interval: 3 years). RESULTS: From the 1st to the 2nd round of the historical screening programme that commenced in 1976, the histoscores for CIN 3 (3.33, 1.88) and squamous cell carcinoma (0.53, 0.19) and the hit count (3.92, 2.15) all diminished significantly. The current restructured programme, which commenced in 1996, showed low starting values for all three parameters, comparable to those in the 2nd round of the 1976 programme; a further reduction (0.16, 0.08; p < 0.01) was seen only in the histoscore for squamous cell carcinoma. In both rounds of both programmes, the histoscores for adenocarcinoma in situ (0.02, 0.02, 0.05, 0.04, respectively) and endocervical adenocarcinoma (0.04, 0.06, 0.05, 0.04) remained stable. CONCLUSION: In the current cervical carcinoma screening programme, with a screening interval of 5 years, the hit count of serious abnormalities remained constant while the incidence of squamous cell carcinoma decreased; this is in contrast to the historical screening programme (commenced in 1976), when both the hit count and the histoscore for CIN 3 diminished significantly. There were indications that cervical screening has no beneficial effect on the prevention of cervical adenocarcinoma.

Carcinoma↗

Mental disorders and public safety of the community at large--does the Tarasoff principle apply in Singapore?

The Tarasoff Principle is a legal ruling arising out of the Tarasoff case in California, in which 2 therapists were found by a court to be negligent for not warning an intended victim of a threat to her by their mentally disordered patient, and she was subsequently killed. The 2 therapists were deemed to have an obligation to protect an intended victim of a patient who presented a serious danger of violence. The question is whether this would apply under Singapore law, and whether an act of disclosure to protect a victim would be a breach of confidentiality and the doctor-patient relationship.

Humans↗

How to improve cytologic screening for endocervical adenocarcinoma?

AIM: A retrospective study was undertaken to investigate how to improve the diagnosis of endocervical adenocarcinoma in screening programs. MATERIAL AND METHODS: The study group consisted of 29 slides of women diagnosed with cancer but who had negative smears. The slides were subdivided in 12 smears taken less than one year before diagnosis by histology and 17 smears taken between one and 10 years prior to diagnosis. A hundred smears of healthy women were used for comparison. All smears were studied macroscopically after which both groups of smears were scanned by the Neural Network Scanner (NNS). Differences between groups were studied for statistical significance using Pearson's Chi-squared test. FINDINGS: The macroscopic parameter of these smears found to be present most frequently was a heavy admixture of blood. The presence of blood (lysed or not) in the smears was equally consistently highlighted by the NNS. Statistical significance of the association of this parameter, with the presence of cancer, was demonstrated. CONCLUSION: The awareness of blood as a background feature of adenocarcinoma of the cervix will help to select cases needing special attention. These difficult bloody smears, studied by light microscopy and by NNS images can also be selected for additional MiB-1 staining. With this approach, blood in smears, otherwise frequently leading to a compromise of classification, can become a blessing in disguise. The diagnosis of endocervical adenocarcinoma in screening smears will therefore be improved.

Adenocarcinoma↗

Less medical intervention after sharp demarcation of Grade 1-2 cervical intraepithelial neoplasia smears by neural network screening.

BACKGROUND: Neural network technology has been used for the daily screening of cervical smears in The Netherlands since 1992. The authors believe this method might have the potential to demarcate diagnoses of Grade 1-2 cervical intraepithelial neoplasia (CIN 1-2). METHODS: Of 133,196 women who were screened between 1992-1995, there were 2236 CIN 1-2 smears; 1128 of which were detected by means of neural network screening (NNS) (n = 83,404 women) and 1108 of which were diagnosed by conventional screening (n = 49,792 women). Cytologic and clinical outcomes (first cytologic or histologic follow-up diagnosis) were retrieved for all the women in the study population (n = 1920). Stratification based on clinical outcome resulted in the cases being grouped as overdiagnosed, concordant, or underdiagnosed. The smears were performed by general practitioners, whereas the biopsies were obtained by gynecologists. RESULTS: The prevalence rate for CIN 1-2 was 1.15% (95% confidence interval [95% CI], 1.08-1.23%) for NNS and 1.92% (95% CI, 1.80-2.04%) for conventional diagnosis (P < 0.001). Concordance with histology was significantly higher for NNS (53.9%; 95% CI, 50.7-57.0%) compared with conventional screening (29.2%; 95% CI, 26.4-32.2%). In addition, overdiagnosis was significantly lower for cases diagnosed by NNS (39.4%; 95% CI, 36.3-42.4%) compared with cases diagnosed by conventional screening (62.4%; 95% CI, 59.3-65.5%). CONCLUSIONS: Neural network-based screening can lead to fewer women being burdened unnecessarily with a cytologic diagnosis of CIN 1-2 by resulting in a sharp demarcation in these diagnoses and a corresponding reduction in unnecessary medical interventions. [See editorial on pages 171-172, this issue.]

Cytogenetic Analysis↗

Boon's disease: hemorrhagic cystitis in conjunction with massive exfoliation of degenerated urothelial cells (apoptosis?) during intercontinental flights in an otherwise healthy person.

Hemorrhagic cystitis is a well-defined clinical emergency, usually occurring in the course of treatment with toxic agents such as cyclophosphamide. We present a case of hemorrhagic cystitis in an otherwise completely healthy female. The three documented attacks were severe and started during intercontinental flights. This type of hemorrhagic cystitis as a disease proved to be a boon, treatable by drinking large amounts of water, and was diagnosed by and in Dr. Boon; thus was the appellation Boon's disease coined. Cellular changes in the urine specimen taken after onset of the disease indicated massive exfoliation of degenerated urothelial cells with morphological features suggestive of apoptosis. It seems likely that this process can be initiated by any event which is associated with compromise of vitality of the urinary bladder lining, such as may occur in hypovolemia. This type of hemorrhagic cystitis is most probably not uncommon in susceptible individuals during intercontinental flights.

Aircraft↗

Presence of proliferating (MiB-1-positive) cells in cervical smears of women infected with HIV is associated with clinical outcome: a study of Brazilian women.

The hypothesis tested was that there is an association between the presence of proliferating (MiB-1-positive) cervical cells and clinical outcome of women infected with human immunodeficiency virus (HIV). Female partners (attending the Gynecology Outpatients Clinic of the University Hospital of Rio Grande, Brazil) of known HIV-positive (HIV+) men were used for this pilot study. Among these women, 25 were also HIV+. Papanicolaou smears of these 25 HIV+ women and of 44 HIV- women were graded as negative, CIN I, CIN II, or CIN III, using neural network screening. MiB-1 grading and HPV identification were also performed. The immune status of patients was determined using the current Centers for Disease Control classification. In agreement with the scientific literature, in these Brazilian women both CIN and HPV were associated with HIV. In the HIV+ women, the immune status tends to correlate with MiB-1 grading. Also, in the one case in whom progression from CIN I to invasive cervical carcinoma was observed, the smear contained many MiB-1-positive cells. Staining cervical smears of HIV+ women is a simple procedure to get an indication of clinical outcome of the patient.

Adult↗

Neural network-based screening (NNS) in cervical cytology: no need for the light microscope?

Neural network-based screening (NNS) of cervical smears can be performed as a so-called "hybrid screening method," in which parts of the cases are additionally studied by light microscope, and it can also be used as "pure" NNS, in which the cytological diagnosis is based only on the digital images, generated by the NNS system. A random enriched sample of 985 cases, in a previous study diagnosed by hybrid NNS, was drawn to be screened by pure NNS. This study population comprised 192 women with (pre)neoplasia of the cervix, and 793 negative cases. With pure NNS, more cases were recognized as severely abnormal; with hybrid NNS, more cases were cytologically diagnosed as low-grade. For a threshold value > or = HSIL (high-grade squamous intraepithelial lesions), the areas under the receiver operating characteristic (ROC) curves (AUC) were 81% (95% CI, 75-88%) for pure NNS vs. 78% (95% CI, 75-81%) for hybrid NNS. For low-grade squamous intraepithelial lesions (LSIL), the AUC was significantly higher for hybrid NNS (81%; 95% CI, 77-85%) than for pure NNS (75%; 95% CI, 70-80%). Pure NNS provides optimized prediction of HSIL cases or negative outcome. For the detection of LSIL, light microscopy has additional value.

Cervix Uteri↗

Analysis of three-dimensional architecture in Feulgen-stained fine-needle liver aspirates, using confocal scanning laser microscopy.

Early and accurate diagnosis of hepatocellular carcinoma in liver nodules using fine-needle aspiration biopsy can still pose difficulties, particularly in cirrhotic nodules containing dysplastic hepatocytes. Loss of architectural clues, which may aid diagnosis, can be overcome by using confocal scanning laser microscopic examination of tissue fragments in smears without the need for further processing of slides. The basic fuchsin of the Feulgen method resulted in excellent confocal images without the need for further processing of the smears. Clear morphological differences in three-dimensional reconstructions of optically sectioned tissue fragments were demonstrated in normal, hyperplastic, and malignant smears as an aid to diagnosis.

Biopsy, Needle↗

Neural network-based digitized cell image diagnosis of bladder wash cytology.

In this pilot study, we tested whether it is possible to apply neural network-based diagnostics on bladder washings to detect urothelial cell carcinoma of the bladder. Eighty-five bladder wash (BW) samples were chosen at random from our own database. Cystoscopy, histology, and follow-up data concerning tumor recurrence were available. Each slide was scanned by the neural network-based digitized cell image system. The neural network-based diagnosis (NNBD) was based on 128 digitized cell images provided by the system. The light microscopic diagnosis (LMD) was rendered by an experienced cytopathologist using the same terminology, i.e., negative, low-grade tumor, and high-grade tumor. Finally, an automatic QUANTICYT analysis was performed on the same material, with as classification low, intermediate, and high risk. The sensitivity for diagnosing a histologically confirmed tumor was for NNBD 92%, for LMD 50%, and for QUANTICYT 69%. For the three methods, receiver operating characteristic (ROC) curves were made for the thresholds low grade/intermediate risk and high grade/high risk. For the prediction of a positive cystoscopy, the highest area under the curve (AUC) was found for NNBD, being 0.71. The AUC for LMD was 0.58. QUANTICYT analysis had the highest AUC value (0.62) for predicting tumor recurrence after a negative cystoscopy, with a lower value for NNBD (0.50). These findings indicate that neural network-based diagnosis of bladder washing samples is highly promising.

Area Under Curve↗

4D confocal microscopy for visualisation of bone remodelling.

Until recently it was very time consuming and difficult to make three-dimensional (3D) images of newly formed bone. With the advent of confocal technologies and increased computer power, 3D imaging is greatly facilitated. In this paper we demonstrate that enhanced confocal visualisation of newly formed bone is possible when bone is labelled in vivo sequentially with two osteotropic markers (xylenol orange and tetracycline). Computer-assisted reconstruction of the confocal optical sections was achieved through the use of the CONVEX Application Visualisation System (AVS). The computerised image data provides the researcher with ample flexibility in displaying the results. It was found that CSLM combined with AVS is excellent for visualising the remodelling process in three and four dimensions, in which the fourth dimension is time. With this approach visualised bone remodelling has become possible in a manner not easily achieved by other techniques.

Animals↗

Insomnia in the community.

This study is the first to document the prevalence of insomnia in Malays and Chinese in a Singapore community. The overall rate of insomnia was low at 15.3% with females and Malays at higher risk. Patients with insomnia had significantly higher sleep latency, awakenings at night, as well as a report of not feeling fresh throughout the day. There was an association between insomnia patients with increased stress levels, especially at home, and a higher rate of co-morbid minor psychiatric disorder. However, most patients do not seek medical help, and even less resort to sleeping pills.

Adolescent↗

Confocal microscopy of false-negative breast aspirates.

Even when using a novel optimized FNA-21 for breast fine-needle aspiration biopsy, our series of 163 breast lesions with consecutive histology, including 110 carcinomas, contained eight cancer cases with a negative cytologic diagnosis. Two consisted exclusively of thick, undiagnosable epithelial fragments and were devoid of detached malignant cells on which the proper diagnosis could have been made. Optical sectioning of the original smears by the confocal microscope allowed us to reclaim from these epithelial fragments the diagnostic abnormal chromatin patterns, even in the air-dried smears. In the thin optical sections the cancerous tubular or cribriform growing pattern was visualized. The high spatial resolution of the confocal microscope can be further exploited with the application visualization system (AVS). The AVS three-dimensional reconstructions allow us to see the surface of these malignant cells in a detail approaching that of scanning electron microscopy. Furthermore, the internal aspects of the malignant nuclei can be visualized with these techniques.

Biopsy, Needle↗

Semiautomatic PAPNET analysis of proliferating (MiB-1-positive) cells in cervical cytology and histology.

With the event of microwave-antigen retrieval it has become possible to detect proliferating cells (staining positive for MiB-1) in cervical smears containing epithelial fragments and in paraffin sections containing cancerous cervical epithelium. The PAPNET system, using neural network computing, is able to collect from the slides epithelial fragments with positive-staining nuclei. The nuclei in epithelial fragments are semiautomatically quantitated using the PAPNET-digitized images. The parameter PPN (proportion-positive nuclei), in which the nuclear area of the positive nuclei is taken into account, prove to be superior to the proliferation index for distinguishing moderate dysplasia from carcinoma in situ. In repair cells, all four quantitative parameters are close to those of moderate dysplasias, indicating that this method is unfit for distinguishing these two entities. However, we show that MiB-1 staining is valuable for the analysis of "false-negative" and "false-positive" smears, and for quantifying proliferation in sections of carcinoma in situ.

Antigens, Nuclear↗

N-[18F]-fluoroalkylation of noraporphines: microwave versus thermal treatment.

A comparable study of microwave versus thermal heating is described for the N-[18F]-fluoroalkylation of noraporphines. As compared to thermal treatment, different products were obtained during microwave treatment. Thermal treatment resulted in the loss of the protection of the catechol functionality of the noraporphines (O-deacylation), whereas during microwave treatment N-[18F]-fluoroalkylation was observed. The results described in this report might suggest that the influence of microwaves on chemical transformations is not exclusively thermal.

Alkylation↗

A controlled double-blind trial of moclobemide and imipramine in the treatment of depression.

The aim of this study is to compare the antidepressant efficacy and side effects of moclobemide with imipramine (a standard antidepressant). Moclobemide is a reversible inhibitor of monoamine-oxidase-A (RIMA) with selectivity for the MAO type A isoenzyme. Thirty-two patients who met DSM-3R criteria for major depressive episode or dysthymia were randomly assigned to receive either moclobemide or imipramine in a double-blind prospective study. The results indicated no difference in antidepressive efficacy between the two drugs, but imipramine had more anticholinergic side-effects. Neither drug had significant effects on pulse rate, blood pressure, weight changes or blood chemistry. These results were confirmed by previous studies.

Adult↗

Ultrarapid vacuum-microwave histoprocessing.

A novel histoprocessing method for paraffin sections is presented in which the combination of vacuum and microwave exposure is the key element. By exploiting the decrease in boiling temperature under vacuum, the liquid molecules in the tissues have been successfully extracted and exchanged at relatively low temperatures during each of the steps from dehydration, clearing, and impregnation. In this vacuum-microwave method, an extremely short time suffices for the preparation of optimal-quality paraffin blocks. No xylene (but isopropanol instead) was used as the intermediate solvent. Thirty biopsies (thickness 2-4 mm) can be processed in 40 min. In addition, this approach can be used to produce large sections of giant blocks (4 x 6 x 1 cm3) which can be easily cut on a routine microtome due to the optimal paraffin impregnation. These giant blocks do not shrink during this vacuum-microwave histoprocessing.

Biopsy↗