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Biomedical subjects

K Yuen

Publications and source records attributed to K Yuen.

At least 37 records · Page 2Linked to original sources

Radioenhancement by cisplatin with accelerated fractionated radiotherapy in a human tumour xenograft.

The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tumours were exposed to twice-daily 2-Gy fractions, applied 6 h apart over 2 weeks, 5 days a week, alone or combined with cisplatin given at maximally tolerated doses in three different schedules: (1) i.p. as a single bolus (SB) or (2) i.p. as a daily bolus at 30 min before the first daily radiation fraction or (3) s.c. as a continuous infusion through a mini-osmotic pump over 13 days, commencing 24 h prior to the first daily radiation fraction. The end point for the study was tumour growth delay (TGD), calculated as the difference between the delay in regrowth to 200% of the initial tumour size in treated versus control mice. SB cisplatin plus radiation showed only an additive effect on TGD, whereas daily-bolus and continuous-infusion cisplatin demonstrated a greater than additive effect when combined with accelerated fractionated radiation in this human tumour model. Cisplatin appears to be especially beneficial as a radiation enhancer when given throughout the course of radiation.

Animals↗

Evaluation of facial palsy by moiré topography index.

We investigated the usefulness of moiré topography for evaluating facial nerve function in 51 patients with facial palsy and 10 normal volunteers. This method visualizes the shape of objects in three dimensions. We devised three moiré indexes as a simple method of quantifying the severity of facial palsy: the nasolabial groove moiré index, the oral angle moiré index, and the inner canthus moiré index. We compared the results obtained by the moiré indexes with findings obtained using the House-Brackmann grading system and found that they were highly correlated. These three moiré indexes included all the standard factors of the House-Brackmann grading system, allowing us to develop the total moiré index.

Adolescent↗

Palliative care in a multicultural society: perceptions of health care professionals.

This study assesses the perceived competence of 191 Australian palliative care professionals in delivering crosscultural care. The relationship between the perceived competence levels of professionals and their experience and training is examined. Strategies to improve crosscultural palliative care, as suggested by palliative care providers, are also presented. Information about perceived competence and the kinds of difficulties encountered in crosscultural palliative care interactions form the basis of suggested guidelines for proposed education programmes. The results of this study suggest that specific education, rather than individual experience of crosscultural interactions, which may not always be positive, is needed to improve the competence of palliative care professionals. Education, therefore, is the key to the provision of culturally appropriate care to patients and their families from all cultural backgrounds.

Adult↗

Bilateral congenital cholesteatoma.

We report a case of bilateral congenital cholesteatoma in a 6-year-old boy. Cholesteatoma was present in both ears around the tympanic isthmus (the only open passage from the tympanic cavity to the attic), extending to behind the horizontal portion of the facial nerve. This patient underwent a total of three canal wall up operations on each side to remove the cholesteatoma completely and improve hearing. This case fulfills the criteria proposed by Derlacki and Clemis in 1965. Bilateral congenital cholesteatoma is a rare condition, but the incidence of congenital cholesteatoma in children has increased recently for the following reasons: Reassessment of the criteria, the introduction of computed tomography, and increased awareness of congenital cholesteatoma. When operating on patients with bilateral cholesteatoma, the best method for preservation of hearing should be chosen. We discuss these problems in the present report.

Cartilage↗

Coexistence of central diabetes insipidus and salt wasting: the difficulties in diagnosis, changes in natremia, and treatment.

Both central diabetes insipidus (DI) and a high rate of excretion of sodium (Na) and chloride (Cl) contributed to the development of polyuria and dysnatremia in two patients during the acute postoperative period after neurosurgery. To minimize difficulties in diagnosis and projections for therapy, two available (but not often used) clinical tools were helpful. First, the osmole excretion rate early on revealed the co-existence of central DI and an osmotic diuresis. The osmoles excreted were largely Na salts; after antidiuretic hormone acted, this electrolyte diuresis caused the urine flow rate to be much higher than otherwise anticipated. Interestingly, part of this saline diuresis occurred when the extracellular fluid volume was contracted. The tool to explain the basis for the dysnatremias was a tonicity balance. Hypernatremia, which developed before treatment of central DI, was primarily a result of a positive balance for Na rather than a large negative balance for water. Moreover, hyponatremia that developed once antidiuretic hormone acted was primarily a result of a negative balance for Na; the urine volume was large and its Na concentration was hypertonic. To prevent a further decline in the plasma Na concentration, either the Na concentration in the urine should be decreased by provision of urea or a loop diuretic while replacing all unwanted water and electrolyte losses; alternatively, the fluid infused should have a similar Na concentration and volume as the urine (infuse hypertonic saline).

Adult↗

[The efficacy of neoadjuvant chemotherapy and morphological classification of invasive bladder cancer according to chemoresponse].

BACKGROUND: We investigated the propriety of neoadjuvant chemotherapy and the possibility of bladder preservation based on clinical and pathological responses in invasive bladder cancer. METHOD: Nineteen cases of invasive bladder cancer which had been subjected to two courses of neoadjuvant chemotherapy followed by radical cystectomy were analyzed. RESULTS: The overall response rate was 79% (5/19), and 7 cases (37%) had a pathological complete response (pCR). Many cases showed degeneration or necrosis of cancer cells and infiltration of lymphocytes around the original cancer sites. Foamy macrophage or fibrous change was observed in high response cases. Thickening of the bladder wall were found after chemotherapy in such cases, which led to over-staging of the CT scan. We divided invasive bladder cancers into four different types based on gross tumor appearance and histology from TUR biopsy specimen: Type 1 which has an nodularly elevating pedunculated structure: Type 2A which has an elevating nonpedunculated structure with partly papillary component and no lymph vessel invasion: Type 2B which has an elevating nonpedunculated structure with partly papillary component and marked lymph vessel invasion: and Type 3 which has a nonelevating diffuse invasive structure with CIS lesion. The therapeutic effect was greater than grade 2 in 7 cases out of 8 (88%) Type 1, 2 cases out of 3 (67%) Type 2A, no case out of 6 (0%) type 2B, and 1 case out of 2 (50%) type 3. CONCLUSION: This classification will indicate the appropriate preoperative treatment for invasive bladder cancer, and will be useful when formulating criteria for bladder preservation. In particular, Type 1 or Type 2A is chemosensitive and may be considered for bladder preservation.

Adult↗

Pharmacokinetics and pharmacodynamics of prolonged oral etoposide in women with metastatic breast cancer.

The pharmacokinetics and pharmacodynamics of prolonged oral etoposide chemotherapy were investigated in 15 women with metastatic breast cancer who received oral etoposide 100 mg as a single daily dose for up to 15 days. There was considerable interpatient variability in the day 1 pharmacokinetic parameters: area under the plasma concentration time curve (AUC) (0-24 h) 1.95 +/- 0.87 mg/ml per min (mean +/- SD), apparent oral clearance 60.9 +/- 21.7 ml/min per 1.73 m2, peak plasma concentration 5.6 +/- 2.5 micrograms/ml, time to peak concentration 73 +/- 35 min and half-life 220 +/- 83 min. However, intrapatient variability in systemic exposure to etoposide was much less with repeated doses. The intrapatient coefficient of variation (CV) of AUC for day 8 relative to day 1 was 20% and for day 15 relative to day 1 was 15%, compared to the day 1 interpatient CV of 45%. Neutropenia was the principal toxicity. Day 1 pharmacokinetic parameters were related to the percentage decrease in absolute neutrophil count using the sigmoidal Emax equation. A good fit was found between day 1 AUC and neutrophil toxicity (R2 = 0.77). All patients who had a day 1 AUC > 2.0 mg/ml per min had WHO grade III or IV neutropenia. The predictive performance of the models for neutrophil toxicity was better for AUC (percentage mean predictive error 5%, percentage root mean square error 18.1%) than apparent oral clearance, peak plasma concentration, or daily dose (mg/m2). A limited sampling strategy was developed to predict AUC using a linear regression model incorporating a patient effect. Data sets were divided into training and test sets. The AUC could be estimated using a model utilizing plasma etoposide concentration at only two time points, 4 h and 6 h after oral dosing (R2 = 98.9%). The equation AUCpr = -0.376 + 0.631 x C4h + 0.336 x C6h was validated on the test set with a relative mean predictive error of -0.88% and relative root mean square error of 6.4%. These results suggest monitoring of AUC to predict subsequent myelosuppression as a strategy for future trials with oral etoposide.

Administration, Oral↗

Changing patterns of susceptibilities of blood, urinary and respiratory pathogens in Hong Kong.

The incidence and antimicrobial susceptibility of organisms isolated from blood, urine and respiratory specimens at a teaching hospital in Hong Kong were studied retrospectively from 1986-1993. The incidence of Gram-positive bacteraemia, particularly coagulase-negative staphylococci (CNS), increased significantly from 33.6 to 47.3% (P < 0.001) while that of Gram-negative bacteraemia fell from 60.0 to 47.0% (P < 0.001). Among blood isolates, methicillin resistance of CNS increased from 17.0 to 58.0% (P < 0.001) and cefuroxime resistance of Enterobacter spp. increased from 21.0 to over 50% (P < 0.01). Among urinary isolates, cefuroxime resistance of Klebsiella spp. (11.0 to 24.0%, P < 0.001) and Enterobacter spp. (32.0 to 75.0%, P < 0.001) increased. Nalidixic acid resistance among Gram-negative urinary isolates, except Proteus mirabilis, rose by three- to sixfold. For Streptococcus pneumoniae, isolated from the respiratory tract, penicillin resistance increased dramatically (2 to 18%, P < 0.001). For respiratory isolates of Haemophilus influenzae, ampicillin resistance increased from 17.0 to 29.0% (P < 0.001). These data are useful in guiding empirical treatment of nosocomial infections.

Bacteremia↗

Superficial siderosis of the central nervous system: a case with an unruptured intracranial aneurysm.

We present a case of superficial siderosis (SS) of the central nervous system (CNS) with an unruptured intracranial aneurysm to illustrate that the commonly encountered unexplainable progressive sensorineural hearing loss (SNHL) can be an important sign for the early awareness of this rare disorder. The literature on SS is reviewed and the pathogenesis of SS is discussed.

Central Nervous System Diseases↗

Observation of head-shaking nystagmus with an infrared Frenzel's glass.

It has been reported that a head-shaking test is very useful in clinical practice. To observe head-shaking nystagmus (HSN) a Frenzel's glass and electronystagmography (ENG) have been used. Although observation with Frenzel's glass is a simple method, it tends to suppress after shaking nystagmus, as gazing is not completely eliminated with Frenzel's glass. An electronystagmogram in darkness can eliminate gazing completely, but it requires much trouble in routine use. We therefore tried to use Frenzel's glass with an infrared CCD camera. We observed highly provoked HSN like ENG in darkness and were able to use it without difficulty. We recognized the second phase in several cases with only an infrared Frenzel's glass and the rotatory component of the nystagmus. This method is more convenient and valuable for clinical use than ENG and Frenzel's glass.

Dizziness↗

Palliative care in the home. The GP/home hospice team.

The family doctor has always had a significant role in caring for terminally ill patients. Giving support to patients in their last few weeks or hours of life can be an emotionally demanding, clinically frustrating, time-consuming task. The advent of home palliative care services has given patients, families and doctors access to a home hospice team that can provide invaluable support.

Family Practice↗

Analysis of factors influencing the efficacy of pooled platelet transfusions.

The results of 839 platelet transfusions in 115 patients were studied to establish the relative importance of 10 clinical factors in determining the efficacy of pooled donor transfusions. Efficacy was measured by the one hour corrected increment in platelet count. The number of transfusions available for study from individual patients varied widely from 1 to 37. Two methods of analysis are presented. The first makes assumptions about the correlation between transfusions within patients, and the variation between patients. The second is based on a repeated sampling procedure whereby unbiased estimates of the parameters of interest are obtained from random samples containing only one transfusion per patient.

Bias↗

The definition of refractoriness to platelet transfusions.

The relationship between the 1 and 20 h post-transfusion platelet count and three parameters used to define refractory transfusions, namely the corrected increment (CI), platelet increment (PI), and percentage platelet recovery (%REC), was studied in 437 non-HLA matched platelet transfusions given to 102 patients with bone marrow failure. The percentage agreement between common definitions of refractoriness was calculated based on these parameters. As the maintenance of platelet counts above 20 x 10(9)/l is a relevant clinical goal for platelet support, the values of the CI, PI and %REC, which best corresponded to 1- and 20-h post-transfusion counts of 20 x 10(9)/l, were identified. A 1-h post-transfusion CI < 3 (PI < 7 x 10(9)/l or % REC < 8%) corresponded to clinically unsuccessful transfusions with a 1-h platelet count < 20 x 10(9)/l. A 1-h CI > or = 5.5 (PI > or = 12 x 10(9)/l or %REC > or = 14%) corresponded to clinically successful transfusions with a 20-h post-transfusion count of > or = 20 x 10/l. These data tie together the end points reported in the literature for defining refractory transfusions.

Blood Platelets↗

Factors influencing 20-hour increments after platelet transfusion.

The 20-hour posttransfusion platelet count determines transfusion policy for patients requiring platelet support, and yet factors influencing the 20-hour count have been poorly defined. The clinical factors influencing both the 1- and 20-hour corrected count increment (CCI), were studied in 623 human leukocyte antigen (HLA)-unmatched platelet transfusions in 108 patients. The 1- and 20-hour CCIs were highly correlated (r = 0.67, p less than 0.001). On average, the 20-hour CCI was 64 percent of the 1-hour CCI. Multiple linear regression analyses identified splenectomy, bone marrow transplantation, disseminated intravascular coagulation, administration of amphotericin B, palpable spleen, and HLA antibody grade as the major factors influencing the 20-hour posttransfusion CCI. Platelet-specific antibodies, number of concurrent antibiotics, clinical bleeding, and temperature did not significantly influence the 20-hour posttransfusion CCI. The 1-hour CCI was the only significant factor influencing the 20-hour CCI in a regression model containing the 1-hour CCI and the above factors. Thus, the same clinical factors exert a major influence on the CCI at both 1 and 20 hours after platelet transfusion, with no evidence that any factor has more influence at 20 hours after transfusion than at 1 hour.

Blood Platelets↗

Etoposide, carboplatin, cyclophosphamide and vincristine in previously untreated patients with small-cell lung cancer.

The efficacy and toxicity of 120 mg/m2 etoposide and 100 mg/m2 carboplatin given i.v. daily x 3 together with 750 mg/m2 cyclophosphamide and 1.4 mg/m2 vincristine given i.v. on day 1 (ECCO) in a regimen given every 28 days for 6 courses was assessed in 90 (40 limited stage, 50 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to limited-stage patients without progression after 3 courses of chemotherapy. Cranial irradiation with 30 Gy in 10 fractions was given to all patients attaining a complete response (CR). Objective responses were seen in 83% [CR, 60%; partial response (PR), 23%] of patients with limited and 76% (CR, 22%; PR, 54%) of those with extensive disease. The median relapse-free survival for objective responders with limited disease was 13.4 months, with a median of 8.0 months for extensive-stage patients. The median relapse-free survival for patients achieving a CR was 13.4 months, with a median of 7.8 months for those undergoing a PR. The median survival was 13.3 months for patients with limited disease, with a median of 9.6 months for those with extensive disease. The median survival following a CR was 18.2 months, with a median survival of 9.9 months for those showing a PR. The combination was well tolerated, with either no nausea or nausea only (WHO grade 0 or 1) in 56% of patients and minimal mucositis, renal toxicity, neurotoxicity or ototoxicity. Neutropenia measuring less than 1.0 x 10(9) WBC/l (WHO grade 3 or 4) was seen in 74% of patients, with two deaths due to infection occurring during neutropenia. Thrombocytopenia of less than 50 x 10(9) platelets/l (WHO grade 3 or 4) occurred in 24% of patients. ECCO is a new, active, well-tolerated program for previously untreated patients with small-cell lung cancer.

Adult↗

A randomized trial of cisplatin versus cisplatin plus methotrexate in advanced cancer of the urothelial tract.

One hundred eight patients with recurrent or metastatic transitional cell carcinoma of the urothelial tract were randomized to receive cisplatin (C) 80 mg/m2 on day 1 every 4 weeks, or methotrexate (M) 50 mg/m2 on days 1 and 15 plus C 80 mg/m2 on day 2 every 4 weeks (C + M). Fifty-three eligible patients were randomized to C + M and 55 to C. In the C + M arm, 45% of patients responded (complete response [CR], 9%) and 31% (CR, 9%) in the C arm (P = .18). In the C arm, 20 patients failing or relapsing after C received M. Two patients responded, and four with progressive disease (PD) and one with a previous partial response (PR) showed no change. The median survival was 8.7 months (C + M arm) and 7.2 months (C arm), P = .7. Relapse-free survival was not significantly different, but C + M was associated with a significantly increased time to disease progression (median, 5.0 months, v 2.8 months for C arm). The response of untreated patients (37%) was not different from those with prior treatment (39%). On the C + M arm, 92% of patients and 96% of patients on the C arm received 85% or more of the scheduled C dose. Significantly more grade 3 or 4 hematological toxicity (27% v 2%; P = .01) and mucositis (20% v 0%; P = .0005) occurred in patients on the C + M arm. Although the initial response rates seen on the combination arm look superior, and the time to disease progression is increased, these effects have not translated into a clinically important increase in the duration of survival and were associated with increased toxicity.

Adult↗