Biweekly administration of docetaxel and carboplatin for advanced or recurrent endometrial and ovarian carcinomas.

OBJECTIVE: To examine efficacy and safety of biweekly administration of docetaxel and carboplatin for advanced or recurrent en- dometrial and ovarian carcinomas. MATERIAL AND METHODS: The recommended doses were determined in the phase I study. In the phase II feasibility study, the primary end-point was safety, and the secondary end-point was response rate and progression-free survival (PFS). RESULTS: The recommended doses of docetaxel and carboplatin were determined to be 45 mg/n(2) and AUC 3.0, respectively, in phase I study. In phase II feasibility study, no treatment-related death was observed. Most non-hematotoxicity cases were mild or moderate. Grade 4 neutropenia was confirmed in 13 patients (31.0%), whereas all cases showed tolerability with 2.6 days delay of anticancer drugs administration in both groups. Response rate was 55.0% in the ovarian carcinoma group, and average PFS was 8.7 months. In the endometrial carcinoma group, response rate was 50.0% and average PFS was 32.0 months. CONCLUSION: The present results showed that biweekly administration of docetaxel and carboplatin for advanced and recurrent endometrial and ovarian carcinomas results in acceptable side effects, response rate, and PFS.

Antigenic stimulation with cytochrome P450 2J expressed in mouse hepatocellular carcinoma cells regulates host anti-tumour immunity.

Cytochrome P450 2J subfamily (CYP2J) enzymes expressed in mouse hepatocellular carcinoma (HCC) cells were identified as an antigen recognized by specific CD4(+) T cells and the structure of its T cell epitope was determined by proteomics-based exploration. The major histocompatibility complex (MHC) class II binding peptides were isolated from I-A(k)/peptide complex of dendritic cells (DCs) loaded or unloaded with MIH-2 mouse HCC cells. MHC class II-binding peptides found in MIH-2-loaded DCs but not in unloaded DCs were determined by tandem mass spectrometric analysis. The peptide, consisting of amino acid 276-290 (DFIDAFLKEMTKYPE) of mouse CYP2J enzymes, was identified as an antigenic peptide presented in the context of MHC class II. Preventive treatment of mice with CYP2J peptide stimulated interferon (IFN)-gamma production of splenocytes and suppressed the growth of implanted CYP2J-positive MIH-2 cells but not CYP2J-negative murine bladder tumour cells. However, continuous treatment of MIH-2-bearing mice with CYP2J peptide significantly suppressed IFN-gamma production of splenocytes and accelerated the growth of implanted MIH-2 tumours in vivo. Increased frequencies of CD4(+)forkhead box P3 regulatory T cells and CD11b(+)Gr-1(+) myeloid suppressor cells were observed in splenocytes from the continuously immunized mice. These results indicate that antigenecity of CYP2J isoforms expressed in HCC cells activate host anti-tumour immunity at an initial stage of HCC, but suppress host anti-tumour immunity with excessive antigenic stimulation at an advanced stage.

Donor site morbidity after vascularized fibula free flap: gait analysis during prolonged walk conditions.

The aim of this study was to determine the effect of vascularized fibula free flap (VFFF) harvest on gait variables during the six-minute walk test (6MWT). Eleven patients who had undergone VFFF harvest and 11 healthy peers participated in this case-control study. The main evaluation consisted of the collection of gait variables using the GAITRite system during three periods of the 6MWT: beginning (0-1min), middle (2:30-3:30min), and end (5-6min). The 6MWT was significantly shorter in the VFFF group than in the reference group (-31%, P<0.001). Most gait variables differed significantly between the groups for each period (P-value range 0.04-0.0004), including toe in/out on the operated side (P-value range 0.005-0.01). The increase in toe in/out on the operated side suggests a functional modification caused by an imbalance of the agonist-antagonist muscles. On comparison of the different periods, gait velocity decreased between the beginning and middle periods and increased between the middle and end periods in both groups. However, a significantly lower velocity between the beginning and end periods was found only for the VFFF group (P=0.026), suggesting an alteration in physical management. In conclusion, these results suggest that VFFF harvesting could alter gait and joint integrity.

The correlation of TERT expression with c-myc expression in cervical cancer.

Recently putative catalytic telomerase subunit was identified as telomerase reverse transcriptase (TERT). Several reports showed that TERT expression correlated with telomerase activity. It has also been found that c-myc can induce telomerase activation through TERT expression. We examined expression of TERT and c-myc and their correlation in cervical cancers by reverse transcription-polymerase chain reaction (RT-PCR). It was found that TERT and c-myc expression was observed mostly in malignancies and expression of c-myc was concordant for positivity and negativity with TERT. These results support recent studies that c-myc expression is closely associated with TERT and telomerase activity. c-myc up-regulation may play an important role in activation of TERT and telomerase.

Expression and activity of matrix metalloproteinase 2 and 9 in human trophoblasts.

Indiscriminate invasion upon the endometrium by normal trophoblasts is strictly regulated unlike that by choriocarcinoma cells. In this study, we focused on the activity of matrix metalloproteinase (MMP)-2 and MMP-9 as parameters of invasion in normal human placenta. In situ hybridization (ISH), immunohistochemical staining (IH) and film in situ zymography (FIZ) were performed to identify cells having MMP-2 or MMP-9 expression and activity. Purified cytotrophoblasts (CTs) were used to examine the expression and activity of MMP-2 and MMP-9, and their invasive ability. In first trimester placental tissue, the MMP-2 expression was observed in extravillous trophoblasts (EVTs), and MMP-9 mainly in villous cytotrophoblasts (VCTs). FIZ revealed marked gelatinase activity in the EVTs which MMP-2 expression was observed in. In full-term placental tissue, the MMP-2 expressions was observed in the EVTs similar to that in first trimester, whereas the gelatinase activity in these cells was decreased or completely lost. Using purified CTs, the gelatinase activity was marked in early CTs, but not term CTs. Invasive ability of early CTs was inhibited by tissue inhibitor of metalloproteinase (TIMP)-2 and MMP-2 antibody in a dose dependent manner. These suggests that the invasive ability of trophoblasts may be regulated by the enzyme activity of gelatinases, especially MMP-2.

Angular homeostasis. V: Some issues in genetics, ontogeny, and evolution.

We discuss a provisional model that deals with aspects of normal control of the direction in which cells grow; hence, the organization of structure. The interacting issues of genetics, ontogeny, and phylogeny in relationship to normal development and its defects are addressed. Our main goal is to define a model with a small and sufficient set of conditions that would make it possible to undertake statistically efficient genetic studies of certain congenital defects. But to do so in plausible and heuristic terms, one must address two classical questions: 1) How is the genome translated (or sometimes mistranslated) into a phenotype that is clinically conspicuous and that can be the object of genetic selection, and hence of evolution? 2) Granted that evolution of species occurs in small, rare steps, what is the path that calls for the smallest number of mutations through which ontogenesis could have developed, the intermediate stages being conserved because of actual phenotypic advantage?

Angular homeostasis: VI. Threshold processes with bivariate liabilities.

The general structure of the threshold model of multifactorial determination is discussed. It is supposed that in place of a single liability (in Falconer's sense) there are two separate liabilities; and whether or not the pathological trait is present depends on a non-additive interaction between the liabilities, so that the region has curved boundaries. The genetics of ontogeny of a process involving spatial orientation (e.g., cardiac ontogeny) is used as a substantive illustration. Genetic analysis of the trait (as contrasted with the liabilities) yields results that on the one hand may seem quite counterintuitive, yet on the other hand they correspond to the kind of bizarre patterns encountered in quasi-empirical genetic counseling for cleft palate or neural tube defect. The impact of refinement of phenotype made possible by non-invasive methods is sketched. This model can be generalized to any number of liabilities, independent or not.

Angular homeostasis II: Pursuit of a moving target in a plane and some implications for cardiac teratology.

A model of cardiac ontogenesis is analyzed. It is cast in terms of the geometry of the pursuit of a linearly moving target by the growth of a chain of cells in the same plane, the pursuer, which at each step adjusts its direction of growth towards the current position of the target. The endpoint is the fusion between them, which can occur in 2 modes: either by the leading cell of the pursuer catching up with the target (pursuer-mediated fusion, or PMF) or by the target running into the preformed side of the pursuer (target-mediated fusion, or TMF). The causal specifications are the step size, the speed of the pursuer, the speed of the target, the restoration constant, and the initial direction of the pursuer; the outcome variables are the number of steps to fusion and the mode of fusion. The pattern of behavior is complicated, being more-or-less regular over large tracts of values, interspersed with abrupt, threshold-like changes that may generate a dichotomous pattern of inheritance despite a continuous gradation of genetic or other causes. The temporary abolition of the correction process (a change introduced to simulate the pattern of the effect of a teratogen) may delay fusion and suggest how a septum may fail to fuse, the ductus arteriosus to close, or an endocardial cushion to form. But the model also predicts that under certain plausible conditions, the "teratogen" would speed up fusion and hence perhaps offset a genetic predisposition to a congenital defect.

Mutation and transcription analyses of the p63 gene in cervical carcinoma.

Genetic mutation of p53, which monitors DNA damage and operates cellular checkpoints, is a major factor in the development of human malignancies. A novel gene p63/p73L/p51, encoding a protein with significant homology to p53 and p73, was recently identified at 3q27-9. To investigate the penetration of p63 in cervical carcinogenesis, mutation and transcription analyses of p63 were performed in cervical carcinoma. A certain isotype of p63 called TAp63gamma encodes the acidic N-terminus and possesses a short C-terminus. Using reverse transcriptase-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis for TAp63gamma, one mutation was found in the cervical carcinoma cell line SKG-I. However, no mutations causing amino acid substitutions or frameshifts were found in 54 cases examined for TAp63gamma, which is thought to be a tumor suppressor gene. While cervical carcinomas tended to yield a positive signal in the RT-PCR reaction designed to amplify transcripts encoding the acidic N-terminus, normal cervix and cervical intraepithelial neoplasia (CIN) did not express this transcript. These data suggest that the p63 gene does not play an essential role as a tumor suppressor gene, but expression of TAp63gamma may be speculatively associated with tumor growth in cervical carcinogenesis.

Doxapram hydrochloride in the treatment of acute exacerbation of chronic respiratory failure. A patient with four episodes treated without use of a respirator.

A 51-year-old woman with chronic respiratory failure (status after tuberculosis) was given an infusion of doxapram hydrochloride (1 to 2 mg/kg of body weight per hour) for four episodes of acute exacerbation of her condition. Treatment with the drug prevented worsening of hypercapnia in the four episodes, when administration of 24 percent oxygen had occasioned rises in the arterial carbon dioxide tension of 23, 10, 9, and 7 mm Hg.

Breathing during sleep with mild hypoxia.

To investigate ventilatory response to mild hypoxia during non-rapid-eye-movement sleep, we administered approximately 16% O2 (which corresponds to concentrations found in commercial high altitude air craft) to 12 normal subjects by using a Venturi mask, which did not alter the breathing pattern during this study. Under mild hypoxia, inspiratory minute ventilation during sleep showed an initial rapid increase (P less than 0.001) but then declined significantly (P less than 0.001) and stabilized. Stable levels differed among individuals and, compared with those measured before hypoxia, were significantly lower in some subjects, higher in one, and essentially unchanged in the others. The initial rapid increase in minute ventilation after mild hypoxia during sleep correlated with the respective values of hypoxic ventilatory response during the awake state (P less than 0.01), but the final lowered levels did not. We conclude that the ventilatory response after mild hypoxia during sleep is biphasic and hypoxic depression exerts considerable influence on ventilation under mild hypoxia during sleep. So we should take hypoxic depression into consideration to evaluate the response to hypoxia during sleep.

Fixed drug eruption. Expression of epidermal keratinocyte intercellular adhesion molecule-1 (ICAM-1).

The pathogenic mechanism of preferential localization to certain skin sites of fixed drug eruption lesions has remained unknown. Skin biopsy specimens were obtained from four patients with fixed drug eruptions at various time points after final exposure to the causative drug and were studied immunohistologically using monoclonal antibodies to intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1, and HLA-DR. The expression of ICAM-1 by keratinocytes was confined exactly to the involved epidermis. In contrast, the expression of HLA-DR by keratinocytes was observed not only in the involved epidermis but also in the uninvolved epidermis, although to a lesser extent. In general, the intensity of expression of ICAM-1 by keratinocytes correlated well with the degree of epidermal invasion of lymphocytes but not with the degree of dermal lymphocytic infiltration. Interestingly, in fixed drug eruption lesions, basal keratinocytes still showed intense reactivity for ICAM-1 6 to 10 days after final exposure to the causative drug, at which time the expression of HLA-DR was already down-modulated. Such a strong dissociation between the expression of ICAM-1 and HLA-DR on lesional keratinocytes was never observed at any time in the normal skin of control patients challenged with dinitrochlorobenzene. These results suggest that localized misregulated expression of ICAM-1 by the keratinocytes may be one factor that explains the preferential site-specificity characteristic of fixed drug eruptions.

Changes in the arterial PCO2 during a single night's sleep in patients with obstructive sleep apnea.

To investigate the relationship between hypercapnia during sleep and its influence on the PaCO2 during the morning after sleep in patients with obstructive sleep apnea syndrome (OSAS), the transcutaneous PCO2 (PtcCO2) was measured throughout the night, and the arterial blood gases (ABG) were also measured while awake before and after polysomnography in 30 OSAS patients with (n=13, hypercapnic group: HC) and without (n=17, normocapnic group: NC) hypercapnia. Significant differences were observed in the body mass index (p=0.03), the difference between the highest PtcCO2 during sleep and the PtcCO2 during awake before sleep (D-PtcCO2), (HC: 11.l+/-1.7 mmHg; NC: 6.3+/-0.5 mmHg; p=0.0057) and the lowest SaO2 during sleep (p=0.0007). In the HC, the PaCO2 on the morning after sleep (50.0+/-0.14 mmHg) was significantly increased (p=0.0029) compared with the PaCO2 on the night before sleep (47.4+/-1.1 mmHg). In the NC, this phenomenon was not observed. Severe hypercapnia (high D-PtcCO2) during a single night's sleep has a significant effect on the waking PaCO2 immediately following sleep in the HC.

Relationship between dyspnea in daily life and psycho-physiologic state in patients with chronic obstructive pulmonary disease during long-term domiciliary oxygen therapy.

We examined the relationships among dyspnea ratings in daily life, the physiologic state, and anxiety and depression of fifty-two patients with chronic obstructive disease (COPD) during long-term domiciliary oxygen therapy (LTOT). Clinical ratings of dyspnea were assessed by the visual-analog scale (VAS) during eight types of basic behavior in indoor daily life. Analysis of the physiologic state included forced expiratory volume in 1 second (FEV1.0), and arterial blood gas (PaO2, PaCO2) at rest while breathing room air. The hospital anxiety and depression (HAD) scale, which consists of 14 questions, was used to assess the degree of anxiety (HAD-A) and depression (HAD-D). The mean age of the patients was 69.5 +/- 10.8 year (SD), and the duration of LTOT was 944 +/- 739 days. The mean values were 0.77 +/- 0.45 L for FEV1.0, 57.7 +/- 7.4 Torr for PaO2, and 47.4 +/- 8.1 Torr for PaCO2. FEV1.0 was correlated with PaCO2(r = -0.548, p < 0.0001), but it was not correlated with PaO2. High correlation was noted between HAD-A and HAD-D (r = 0.693, P < 0.0001), whereas correlation was not noted between HAD and the physiologic state. VAS was significantly correlated with FEV1.0 (r = 0.320, p < 0.05), as well as with HAD-A (r = 0.358, p < 0.01) and HAD-D (r = 0.444, p < 0.01). Dyspnea ratings were found to be influenced by anxiety and the depression state, and also by the degree of flow limitation in patients with COPD during LTOT. In contrast, the physiologic state scarcely influenced the anxiety and depression state. Thus, psychotherapy may play an important role in the reduction of dyspnea sensation, which is an important determinant of quality of life.

Temporal bone histopathology in trisomy 22.

Trisomy 22 has multiple physical anomalies, and aural malformations are commonly associated with trisomy 22. However, there has been only one report describing the temporal bone histopathology in trisomy 22. Our case is the second reported temporal bone histopathology of trisomy 22. Aural anomalies in this case were less serious than those earlier described, though showing Mondini dysplasia of the bony and membranous labyrinth. Deafness in patients with trisomy 22 may manifest sensorineural, conductive or mixed hearing losses, and/or vestibular dysfunction of varying degrees, according to the site and severity of aural anomalies.

Nodular cutaneous lupus mucinosis: report of a case and review of previously reported cases.

A wide variety of cutaneous manifestations of lupus erythematosus have been reported. Among them, papulonodular eruptions produced by dermal mucin deposition have been recognized as nodular cutaneous lupus mucinosis (NCLM), and many cases have been reported in Japan. A 21-year-old woman with systemic lupus erythematosus (SLE) showed papulonodular eruptions on her back. A skin specimen from the nodule revealed mucin deposition (hyaluronic acid) in the dermis. NCLM should be recognized as a clinical form associated with SLE. The pathogenesis of the mucin deposition in NCLM is still uncertain.

[Incidence proportion estimation, prevalence and effective visiting nurse care of pressure ulcers].

PURPOSE: The purpose of this study are as follows: 1. To determine incidence proportion estimations and prevalence of pressure ulcers in home care settings. 2. To clarify the effective nursing care for prevention and treatments of pressure ulcers at visiting nursing service stations. 3. To show whether demographic characteristics are factors in pressure ulcer development. METHODS: This research is a part of the series of studies on prevalence of pressure ulcers in 934 visiting nursing service stations on October 1995 in Japan. This was followed in November 1, 1996 to October 31, 1997, by another investigation for incidence proportion estimation and prevalence of pressure ulcers and their relationship to nursing care facilities, in which questionnaires were mailed to 620 facilities that participated in the first research. Responses from 294 (47.4%) facilities and 1,208 subjects were received. We analyzed the responses from 215 facilities (73.1%) and 864 subjects to the two types of questionnaires. RESULTS: Prevalence of pressure ulcers was found to be 8.0% (95% CI: 7.5-8.6) on July 1, 1997 and incidence proportion estimation was 3.7% (95% CI: 3.3-4.1) from November 1, 1996 to October 31, 1997 for the 10,750 clients in 215 facilities. The number of prescriptions for turning of client sleep position (p = 0.044), and having a standard care assessment procedure (p = 0.015) were significantly higher for no-present pressure ulcer than in facilities with under 5% having present pressure ulcers and facilities with over 5% having present pressure ulcers. Subtracting the prevalence point in 1997 from 1995, the utilization of a primary nursing care plan (p = 0.021), and the number of part-time nurses (p = 0.008) were significantly higher in the groups that had a decrease or no-change compared to the increased groups. 45.6% of the ulcers identified were situated on the sacrum/buttocks and 39.4% of the ulcers were grade 2. The mean total score on the Braden Scale was 12.7. A score of 18 may be considered as the cut-off point in home care settings. DISCUSSION: Prevalence of pressure ulcers was found to be 8.0% and incidence proportion estimation was 3.7%. The present findings concerning incidence proportion estimation and prevalence of pressure ulcers and the practice of nursing care in visiting nursing service stations suggests possibility for improving outcomes for clients with pressure ulcers and for those at risk factors of developing them.

[A review of methodology on community health nursing diagnosis].

PURPOSE: To develop a systematic method and model for community health nursing diagnosis to be used in teaching and in community practices. METHOD: From searching the databases of Medline (from Jan. 1966 to May 1997) and the Japana Centra Revuo Medicina (from Jan. 1987 to Jan. 1997), literature on community diagnosis, community health nursing, diagnosis, assessment and analysis were classified into keywords, purposes, subjects, health problems and methods. RESULTS: 1. As an explanation of the process of nursing diagnosis the community-as-partner model (Anderson and McFarlane; 1995) is useful for understanding the target community and the use of the community health nursing diagnosis process. 2. The methodology of the community health nursing diagnosis is based on three strategies of public health diagnosis. The method of interview surveys was strengthened by incorporating the ethnographic method. 3. Several case studies in the partnership between communities and universities in USA were introduced. CONCLUSION: Changes in community health policy require that public health nurses develop specialized and comprehensive practices in their communities. The authors presented the model of the community health nursing diagnosis process and proposed a partnership between communities and universities. The construction of community health nursing diagnosis process in this paper is based on the public health diagnosis framework consisting of three strategies, to which analysis of existing data, a social survey utilized in epidemiological community diagnosis, and free interviewing from ethnographic methods are incorporated. Developing this systematic diagnosis process of facilitates the search for potential or actual community health problems or concerns, the practice of applying data from surveys and the discussion of concrete strategies toward problem solving. It is useful for educational and research processes and in practice in the community.

A descriptive analysis of the upper limb patterns during gait in individuals with cerebral palsy.

Patients with cerebral palsy (CP) are characterized by a large diversity of gait deviations; thus, lower limb movements during gait have been well-analyzed in the literature. However, the question of upper limb movements and, more particularly, arm movements during gait has received less attention for CP patients as a function of the disease type (Hemiplegic, HE or Diplegic, DI). Thus, the aim of this study was to investigate upper limb movements for a large group of CP patients; we used a retrospective search, including upper limb kinematic parameters and 92 CP patients (42 females and 50 males, mean±standard deviation (SD); age: 15.2±6.7 years). The diagnoses consisted of 48 HE and 44 DI. A control group of 15 subjects (7 females and 8 males, age: 18.4±8.4 years) was included in the study to provide normal gait data. For the DI patients and CG, 88 arms and 30 arms were analyzed, respectively. For the HE patients, 48 affected arms and 48 non-affected arms were analyzed. The kinematic parameters selected and analyzed were shoulder elevation angles; elbow flexion angles; thorax tilt and obliquity angles; hand vertical and anterior-posterior movements; and arm angles. Several gait parameters were also analyzed, such as the gait profile score (GPS) and normalized speed. Statistical analyses were performed to compare CG with the affected and non-affected upper limbs of HE patients and with the two upper limbs of DI patients. The results show that HE and DI patients adopt abnormal upper limb movements. However, DI patients have greater shoulder, elbow, thorax and arm angle movements compared with HE patients. However, HE patients adopt different movements between their affected and non-affected arms. Thus, the patients used their upper limbs to optimize their gait more where gait deviations were more important. These observations confirm that the upper limbs must be integrated into rehabilitation programs to improve inter-limb coordination.

Associations between gait and clinical parameters in patients with severe knee osteoarthritis: a multiple correspondence analysis.

BACKGROUND: Given the complexity of the gait of patients with knee osteoarthritis, a multiple correspondence analysis may be helpful to optimise the extraction of relevant gait and clinical information. Therefore, the aims of this study are to identify the main associations with clinical and gait biomechanical parameters and to evaluate whether there are more specific knee osteoarthritis groups with different gait profiles. METHODS: Ninety patients with severe knee osteoarthritis and twenty-six healthy individuals participated in this study. Pain and function were assessed with the WOMAC Index; knee joint deformity was assessed by the hip-knee-ankle angle on full-limb radiography; and full body gait analysis was performed with a motion analysis system and force plates. FINDINGS: Using multiple correspondence analysis, two categories of gait parameters that best explain the gait variance of patients with knee osteoarthritis were highlighted. The forward displacement category is composed of the parameters speed, stride length, hip flexion and knee flexion. The frontal category is composed of the parameters thorax obliquity and knee adductor moments. Moreover, based on these parameters, four distinct gait profiles were identified: two gait profiles were associated with knee varus deformities, increased thorax obliquity and different forward displacements, while two gait profiles were associated with valgus deformities and different forward displacements. INTERPRETATION: These gait parameters can be used to simplify the characterisation of the gait of the knee osteoarthritis population. Patients in varus profiles increase thorax obliquity on the stance limb and may reduce forward displacement. Patients in valgus profiles, however, only reduce forward displacement.