Postoperative Health-Related Quality of Life of Cervical Cancer Patients - A Comparison between the Wertheim-Meigs Operation and Total Mesometrial Resection (TMMR).

Introduction: The present study compares for the first time the standard therapy for cervical cancer in FIGO-stages IB-IIB, radical hysterectomy according to the Wertheim-Meigs operation, with the newly developed, nerve-sparing surgical technique, total mesometrial resection (TMMR) with regard to postoperative, health-related quality of life. Method: In the framework of a multicentre, retrospective cohort study a total of 110 cervical cancer patients were interviewed once by means of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the cervical cancer module (EORTC QLQ-CX24). The influence of the surgical method was investigated by analysis of covariance under control of age and the time elapsed between treatment and interview. Results: An influence of the therapeutic method was demonstrated in the EORTC scales physical function (p = 0.047), role function (p = 0.016), fatigue (p = 0.028), pain (p = 0.018), shortness of breath (p = 0.034), lack of appetite (p = 0.006) and diarrhoea (p = 0.012) in favour of the 74 women treated by TMMR. With regard to cognitive, emotional and social functioning as well as cervical cancer-specific symptoms, no significant differences between the therapy groups were found. Conclusion: The findings presented in this study suggest a superiority of TMMR in comparison to the previously employed radical hysterectomy according to Wertheim-Meigs with regard to the postoperative quality of life, especially in the fields of physical activity and fatigue. This needs to be validated in the course of prospective, multicentre studies. In addition, it must be clarified as to what extent the found effects are, in particular, due to the omission of an additional radiotherapy.

[Recruitment for general practice - relationship between practice-based curriculum and career choice]. / Gewinnung hausärztlichen Nachwuchses - Zusammenhang zwischen praxisorientierter Lehre und Karriereentscheidung.

BACKGROUND: Demographic change and recruitment problems in general practice are increasingly threatening an adequate primary care workforce in many countries. Medical schools play an important role in attracting young physicians to this field. The influence of the general practice curriculum on the career choice of graduates has not yet been sufficiently investigated. METHODS: The present study combines continuously collected data of medical students concerning the participation in miscellaneous general practice courses with data of a later graduate survey. RESULTS: Response rate was 64.2%. Although only 4.7% of the participants preferred a career in general practice at study entry, this specialty was, at 12.3%, the second most frequent career choice. Among the future general practitioners, only 18.5% had initially planned this career. The future general practitioners took part significantly more frequently in all facultative general practice courses. They reported more frequently to have met role models in general practice and to have gained experience in rural areas. Future general practitioners would more often prefer to work in rural areas in the future. CONCLUSIONS: Overall, the present results indicate that a broad and practice-oriented general practice curriculum has the potential to attract medical students to the specialty.

Short-range to long-range charge-transfer excitations in the zincbacteriochlorin-bacteriochlorin complex: a Bethe-Salpeter study.

We study, using the Bethe-Salpeter formalism, the singlet excitation energies of the zincbacteriochlorin-bacteriochlorin dyad, a paradigmatic photosynthetic complex. In great contrast with standard time-dependent density functional theory calculations with (semi)local kernels, charge transfer excitations are correctly located above the intramolecular Q-band transitions found to be in excellent agreement with experiment. Further, the asymptotic Coulomb behavior towards the true quasiparticle gap for charge transfer excitations at long distance is correctly reproduced, showing that the present scheme allows us to study with the same accuracy intramolecular and charge transfer excitations at various spatial ranges and screening environments without any adjustable parameter.

Effect of pharmacological manipulations of neuropeptide Y and corticotropin-releasing factor neurotransmission on incubation of conditioned fear.

We recently developed a procedure to study fear incubation in which rats given 100 tone-shock pairings over 10 days show low fear 2 days after conditioned fear training and high fear after 30 or 60 days. Here, we studied the role of the stress-related peptides, neuropeptide Y (NPY) and corticotropin-releasing factor (CRF), in fear incubation. We gave rats either 10 or 100 30-s tone-0.5-s footshock pairings over 1 day (short training) or 10 days (long training) and then assessed tone-cue-induced conditioned suppression of lever responding 2 days after short training or 2 days and 1 month after long training. Prior to testing, we injected NPY (5-10 microg, i.c.v.), the NPY Y1 receptor antagonist BIBO3304 (20-40 microg, i.c.v.), the NPY Y2 receptor antagonist BIIE0246 (2.5-5 mg/kg s.c.), the non-selective CRF receptor antagonist D-Phe CRF(12-41) (10 microg, i.c.v.), or the CRF1 receptor antagonist MTIP (10-20 mg/kg s.c.). Conditioned suppression after long training was higher after 1 month than after 2 days (fear incubation); conditioned suppression was robustly expressed 2 days after short training (non-incubated fear). Both incubated and non-incubated fear responses were attenuated by NPY. In contrast, D-Phe CRF(12-41), MTIP, BIBO3304, or BIIE0246 had no effect on conditioned fear at the different time points. Results confirm previous work on the potent effect of exogenous NPY administration on conditioned fear, but the negative results with BIBO3304 and BIIE0246 question whether endogenous NPY contributes to incubated (or non-incubated) fear. Results also suggest that CRF receptors are not involved in cue-induced fear in the conditioned suppression procedure.

A proposed semantic framework for diabetes education content management, customisation and delivery within the M2DM project.

M2DM (multi access services for telematic management of diabetes mellitus, ) is an EU-funded telemedicine project that aims at increasing the quality of diabetes care by improving communication between patients and caregivers. As part of this project, we have undertaken the initial work of describing the necessary requirements (framework) of an advanced educational component for M2DM in accordance with the latest Semantic Web concepts. This paper describes our proposed semantic framework for educational content management, customisation and delivery. A big internet challenge today is to find and push situation and user-specific quality knowledge to users based on their actual individual needs, circumstances and profiles at any given time. We believe that the semantic framework presented in this paper could be a good step towards meeting this challenge. Benefits for users, both developers and end users, of adopting such framework are also discussed. The ideas discussed in this paper could be easily adapted to other similar services besides M2DM and to different health topics besides diabetes mellitus.

A computer system for interpreting blood glucose data.

This paper presents an overview on the design and implementation of a computer system for the interpretation of home monitoring data of diabetic patients. The comprehensive methodology covers the major information processing steps leading from raw data to a concise summary of what has happened between two subsequent visits. It includes techniques for summarising and interpreting data, checking for inconsistency, identifying and diagnosing metabolic problems and learning from patient data. Data interpretation focuses on extracting trend patterns and classifying/clustering daily blood glucose (BG) profiles. The software helps clinicians to explore data recorded before the main meals and bedtime, and to identify problems in the patient's metabolic control which should be addressed either by educating the patient and/or adjusting the current management regimen.

Epidermal growth factor receptor-targeted immunophotodiagnosis and photoimmunotherapy of oral precancer in vivo.

Immunophotodiagnosis uses a fluorescence-labeled monoclonal antibody (MAb) that recognizes a tumor-associated antigen to image the fluorescence emitted from the fluorophore-bound MAb that has localized in the tissue. It may be used to diagnose malignant or precancerous lesions, to delineate the margins for tumor resection, or as a feedback mechanism to assess response to treatment. In oral precancer, the epidermal growth factor receptor (EGFR) is overexpressed and could be used as a marker for early detection or as a target for therapy. The goal of this study was to test an anti-EGFR MAb (C225) coupled to either the near-infrared fluorescent dye N,N'-di-carboxypentyl-indodicarbocyanine-5,5'-disulfonic acid for detection or a photochemically active dye (chlorin(e6)) for therapy of early premalignancy in the hamster cheek pouch carcinogenesis model. Fluorescence levels in the carcinogen-treated tissue correlated with the histological stage of the lesions when the C225-N,N'-di-carboxypentyl-indodicarbocyanine-5,5'-disulfonic acid conjugate was used but did not do so with the irrelevant conjugates. Discrete areas of clinically normal mucosa with high fluorescence (hot spots) were subsequently shown by histology to contain dysplastic areas. The best contrast between normal and carcinogen-treated cheek pouches was found at 4-8 days after injection. To test the potential of immunophotodiagnosis as a feedback modality for therapeutic intervention, experiments were conducted with the same MAb conjugated to chlorin(e6) followed by illumination to reduce expression of the EGFR by a photodynamic effect. Subsequent immunophotodiagnosis showed that this treatment led to a significant reduction in fluorescence in the carcinogen-treated cheek pouch compared with nonilluminated areas. This difference between illuminated and dark areas was not seen in the normal cheek pouch. Taken together, the results demonstrate the potential for development of immunophotodiagnosis as a diagnostic tool and as a method of monitoring response to therapy and that the EGFR may be an appropriate target in head and neck cancer.

Ocular deposition of copper associated with multiple myeloma.

PURPOSE: To report a case of hypercupremia with deposits in both eyes on the Descemet's membrane, surface of the iris, and lens capsule associated with multiple myeloma. METHOD: Case report. RESULTS: A 64-year-old white woman had metallic deposits in both eyes on the central Descemet's membrane, surface of the iris, and the anterior and posterior lens capsule. A systemic examination revealed an elevated serum copper, normal serum ceruloplasmin, and an increased level of total protein and IgG kappa gammaglobulin. Based on these results, she was diagnosed with multiple myeloma. CONCLUSIONS: Copper deposits on the Descemet's membrane, surface of the iris, and lens capsule may be the first sign of multiple myeloma.

Infection of human monocyte-derived macrophages with Chlamydia trachomatis induces apoptosis of T cells: a potential mechanism for persistent infection.

Viruses can escape T-cell surveillance by infecting macrophages and thereby induce apoptosis of noninfected T cells. This ability had not been demonstrated for bacteria. We investigated whether infection of macrophages with the important human pathogen Chlamydia trachomatis can induce T-cell apoptosis. Because Chlamydia-Mycoplasma coinfection is a frequent event, the ability of Mycoplasma fermentans-infected macrophages to induce T-cell apoptosis was also studied. Infected macrophages were cocultivated with autologous T cells in different activation states. Propidium iodide-based fluorescence-activated cell sorter analysis demonstrated that macrophages infected with viable chlamydiae induced T-cell death. Apoptosis was identified as the mode of death induction by using a terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay. Induction of T-cell death was macrophage dependent. Incubation of T cells with infectious chlamydiae in the absence of macrophages did not lead to T-cell apoptosis. UV irradiation of chlamydiae diminished the ability to induce death. T-cell death was induced by a cell-free supernatant of infected macrophages. Not only phytohemagglutinin-preactivated T cells but also non-mitogen-preactivated T cells were susceptible to C. trachomatis-induced apoptosis. In contrast, M. fermentans infection of macrophages did not induce T-cell death. Coinfection had no additional effect. In summary, intracellular chlamydial infection of macrophages can induce T-cell apoptosis. Apoptosis induction by chlamydiae possibly explains how persistently infected macrophages escape T-cell surveillance and why the Chlamydia-specific T-cell response is diminished during persistent chlamydial infection.

Topical tetracaine with bandage soft contact lens pain control after photorefractive keratectomy.

PURPOSE: A major disadvantage of photorefractive keratectomy (PRK) is pain and discomfort in the first three postoperative days. We tried to assess the efficacy and safety to the cornea of a limited amount of topical tetracaine given to patients for use when needed to manage severe pain. METHODS: Sixty-nine eyes of 49 patients who underwent PRK between June 21, 1996 and June 15, 1998 by a single surgeon were prospectively included. Approximately 10 drops of commercial, non-preserved 0.5% tetracaine were given to patients to use when needed to control severe pain. A bandage soft contact lens was applied. Patients were examined at 1 and 3 days after surgery, at which time corneal re-epithelization was assessed and the number of tetracaine drops used was noted. No systemic analgesic or topical non-steroidal anti-inflammatory was prescribed. RESULTS: All eyes healed within 3 days. The mean number of drops of tetracaine used was 2.3 drops over 3 days, although in 33 eyes (48%) the patient did not use any tetracaine. There was no correlation between the attempted correction in diopters and the number of drops used. No significant difference was found in the number of drops used in the second eye of patients who had both eyes treated. CONCLUSIONS: Limited use of topical anesthetics is an effective and safe analgesic option after PRK. Use of tetracaine in this protocol did not prolong the time to re-epithelialization. Giving only a limited amount of tetracaine to patients prevents abuse and toxicity to the cornea while managing severe pain.

Suture loop to aid in ganciclovir implant removal.

BACKGROUND: The ganciclovir implant (Vitrasert; Bausch & Lomb Inc, Claremont, Calif) has been a useful device in the management of cytomegalovirus retinitis. Seven months after placement, implant exchange is often considered. However, removal may be difficult and may result in vitreous hemorrhage or intraocular dislocation. OBJECTIVE: To describe a suture loop attached to the implant strut and left in the sub-Tenon space to aid in implant removal. METHODS: Twenty-five eyes of 17 patients received a ganciclovir implant with an 8-0 nylon suture loop left beneath the Tenon capsule and underwent at least 6 months of follow-up. Two of these eyes subsequently had a similarly modified ganciclovir implant placed at a separate site (inferonasally) with at least 6 additional months of follow-up. Six eyes of 3 patients had the implant removed as part of an exchange and underwent at least 4 months of follow-up. RESULTS: In the 25 eyes, there were no cases of endophthalmitis, wound leak, suture exposure, or other complications. At implant removal in the 6 eyes previously mentioned, the loop was used for traction on the implant and aided in localization of the implant strut. In these 6 eyes, there were no cases of retinal or choroidal detachment, visually significant vitreous hemorrhage, implant dislocation, or other complications. CONCLUSION: A sub-Tenon capsule suture loop is well tolerated and can assist in ganciclovir implant removal.

Refractive astigmatism after oblique clear corneal phacoemulsification cataract incision.

PURPOSE: To determine the astigmatic effect of a supero-oblique clear corneal phacoemulsification cataract incision. SETTING: A university-based general ophthalmology practice. METHODS: All eyes having supero-oblique phacoemulsification cataract surgery using the right hand of a single surgeon between April 17, 1997, and July 24, 1997, were prospectively included. There were 52 eyes of 52 consecutive patients. Manifest refraction was performed preoperatively and 1, 3, and at least 6 months postoperatively. A Fourier method of vector analysis was used. RESULTS: Mean refractive error (Fourier corrected) for all eyes and all ages preoperatively was -1.422 + 0.085 x 35.85. At 6 months, it was -0.620 + 0.190 x 14.2. There was little difference between right and left eyes. Patients older than 80 years had greater induced astigmatism. CONCLUSION: This study provides evidence that making a supero-oblique clear corneal phacoemulsification incision while sitting in the more natural superior position does not induce a clinically important amount of oblique astigmatism.

Optical imaging technology in minimally invasive surgery. Current status and future directions.

Optical engineering and imaging technology have played a major role in the evolving field of minimally invasive surgery (MIS) by making it possible to visualize the manipulation of tissue at remote internal sites. We assess and review the optical imaging technology used during a variety of MIS procedures from an engineering perspective. The field of MIS is evolving rapidly. Optic-based technologies have the potential to further improve diagnostic capabilities of MIS. Optical imaging technologies and instrument designs are discussed in relation to their current and future use in MIS procedures. Technical limitations in imaging technology are described, along with potential solutions. We review the current status and future role of optical imaging technology in MIS. In the future, synergistic benefits from engineering, imaging technology, and MIS are likely to improve diagnostic ability and patient care.

Reproducibility of corneal flap thickness in LASIK.

BACKGROUND: The purpose of the microkeratome in laser assisted in situ keratomileusis (LASIK) is to create a corneal flap of desired thickness, thus exposing the stroma. The accuracy and repeatability of intended flap thickness with the current microkeratome system has not been documented. The purpose of this study was to determine the precision and consistency of creating a corneal flap thickness of 160 microns with the Moria LSK-One microkeratome (distributed by Microtech, Inc., Doylestown, PA). PATIENTS AND METHODS: The records of 93 eyes from 67 patients who underwent LASIK were reviewed. The central corneal thickness was measured at baseline. The microkeratome using a "130" footplate was used to create an intended flap 160 microns thick, and the corneal thickness was then remeasured. RESULTS: The mean flap thickness for both eyes combined was 159 microns (S.D. = 28). There was no significant correlation between pre-flap corneal thickness or average K and the corneal flap thickness. CONCLUSION: This study provides evidence that the Moria LSK-One microkeratome creates reproducible LASIK flaps consistently near the intended 160 microns corneal flap thickness. This knowledge enables the surgeon to make a corneal flap with great confidence in the thickness of the excision. In addition, this study provides a clinical, in vivo model for testing corneal flap thickness.

Diagnosis of bladder carcinoma using protoporphyrin IX fluorescence induced by 5-aminolaevulinic acid.

OBJECTIVE: To report the results of a clinical study investigating the diagnosis of malignant and dysplastic bladder lesions by protoporphyrin IX (PPIX) fluorescence and to compare them with those from earlier studies. PATIENTS AND METHODS: The study included 55 patients with suspected bladder carcinoma (at initial diagnosis or at tumour follow-up visits); 130 bladder biopsies from 49 patients were classified by pathological analysis. All patients received an intravesical instillation of 50 mL of a 3% 5-aminolaevulinic acid (ALA) solution a mean of 135 min before cystoscopy, which was then performed under white and blue light. Malignant/dysplastic lesions showing red fluorescence under blue-light excitation were noted and the increase in detection rate calculated. RESULTS: There were 63 benign and 67 malignant/dysplastic areas biopsied; 10 malignant/dysplastic lesions (four transitional cell carcinoma, two carcinoma in situ, four dysplasia) were not detected during routine white-light cystoscopy but were identified under blue light. Fluorescence cystoscopy improved the overall diagnosis of malignant/dysplastic bladder lesions by 18% over standard white-light cystoscopy. The improvement was greater for dysplastic lesions and carcinoma in situ (50%). However, the improvement over standard cystoscopy was less than that found by other groups. CONCLUSION: The ALA-based fluorescence detection system significantly enhanced the diagnosis of malignant/dysplastic bladder lesions. However, determining the optimum drug exposure time requires further investigation using well-characterized instrumentation and study protocols, which would then allow comparison of the results from different groups.

Surgical repair of retinal detachment secondary to cytomegalovirus retinitis.

BACKGROUND AND OBJECTIVE: This study was conducted to determine preoperative predictors of postoperative visual acuity in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis and retinal detachment. PATIENTS AND METHODS: The study design was a retrospective chart review of 38 eyes in 33 patients with AIDS and CMV retinitis who had retinal reattachment surgery by pars plana vitrectomy with the use of silicone oil tamponade. Factors considered included: preoperative visual acuity, macular attachment status and CMV activity at the time of surgery, and length of time from diagnosis of retinal detachment to surgical repair. RESULTS: Retinal reattachment was achieved in 37 of 38 eyes. Mean interval from surgery to best corrected visual acuity (VA) was 9 weeks. The mean best corrected post-op VA was 20/70. Approximately half of the patients died within 7 months of the surgery. There was good correlation between preoperative VA and best attained postoperative VA (Spearman's: r = 0.5139, P = 0.001). The interval from retinal detachment to surgery, and best attained postoperative VA did not correlate (Spearman's: r = 0.2339, P=0.158). The lack of macular CMV retinitis correlated well with postoperative VA (P = 0.0066, Wilcoxon rank-sum test). CONCLUSIONS: Preoperative visual acuity and macular attachment status correlates with better postoperative visual acuity results, whereas early surgical repair of retinal detachment does not.

Compartmental models for glycaemic prediction and decision-support in clinical diabetes care: promise and reality.

This paper reviews and critically appraises the application of compartmental models for generating glycaemic predictions and offering clinical decision support in diabetes care. Comparisons are made with alternative algorithmic-based approaches. Unresolved issues raised for model-based techniques include the relative lack of input data necessary for generating reasonable blood glucose predictions, and the high level of uncertainty associated with such predictions which limits their use as guides for therapeutic insulin-dosage adjustments. It is concluded that compartmental model-based approaches, while not offering much benefit for clinical/therapeutic application, will have a role to play as research tools and for educational use. By contrast it is proposed that algorithmic-based approaches, especially in conjunction with telemedicine and Internet applications, are likely to see growing use for day-to-day therapeutic decision support. Randomised controlled clinical trials however will be required, together with other evaluation efforts, before algorithmic-based approaches-like any other clinical technique-can be widely adopted into routine medical practice.

Autofluorescence guided biopsy for the early diagnosis of bladder carcinoma.

PURPOSE: We validate the usefulness of laser-induced autofluorescence for the detection of bladder carcinoma. MATERIALS AND METHODS: We obtained and analyzed fluorescence spectra from 75 patients in whom bladder cancer was suspected. Tissue fluorescence was excited by a nitrogen laser using a quartz optical fiber placed in gentle contact with the area of interest. The laser-induced autofluorescence spectrum was recorded using an intensified optical multichannel analyzer system. Spectra were corrected for the spectral response of the optical system, and the ratios of laser-induced autofluorescence intensities (I) at 385 and 455 nm. (I385/I455) were determined. We had previously established this ratio as a diagnostic algorithm. We included only suspicious bladder lesions (erythematous, edematous, raised and so forth) that were difficult to diagnose by cystoscopy as well as areas from which random biopsies were obtained. The fluorescence ratio algorithm was applied to 130 bladder areas. RESULTS: Of the 130 biopsies obtained during routine cystoscopy 107 (82%) were nonmalignant by histological classification. In contrast, because laser-induced autofluorescence effectively guides biopsies towards malignant lesions, only 30 biopsies (72% fewer) would have been obtained from nonmalignant tissue if the fluorescence ratio that identifies 95% of malignant lesions (95th percentile) had been selected as the decision criterion during standard cystoscopy. CONCLUSIONS: By guiding the surgeon to suspicious lesions that are most likely to be malignant, laser-induced autofluorescence substantially decreases the number of biopsies obtained from nonmalignant tissue during cystoscopy to diagnose bladder carcinoma.

Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA.

OBJECTIVE: To provide recommendations for the treatment of acquired immunodeficiency syndrome-related cytomegalovirus (CMV) end-organ diseases, including retinitis, colitis, pneumonitis, and neurologic diseases. PARTICIPANTS: A 17-member panel of physicians with expertise in clinical and virological research and inpatient care in the field of CMV diseases. EVIDENCE: Available clinical and virological study results. Recommendations are rated according to the quality and strength of available evidence. Recommendations were limited to the treatment of CMV diseases; prophylaxis recommendations are not included. PROCESS: The panel was convened in February 1997 and met regularly through November 1997. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. CONCLUSIONS: Although the epidemiological features of CMV diseases are changing in the setting of potent, combination antiretroviral therapy, continued attention must be paid to CMV diseases in patients infected with the human immunodeficiency virus to prevent irreversible endorgan dysfunction. The initial and maintenance treatment of CMV retinitis must be individualized based on the characteristics of the lesions, including location and extent, specific patient factors, and characteristics of available therapies among others. Management of relapse or refractory retinitis must be likewise individualized. Ophthalmologic screening for patients at high risk for retinitis or who have a prior diagnosis of extraretinal disease is recommended. Recommendations for gastrointestinal, pulmonary, and neurologic manifestations are included.