Classifying chronic myelomonocytic leukemia.
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Biomedical subjects
Publications and source records attributed to P Cook.
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PURPOSE: To test the equivalence of three versus four cycles of bleomycin, etoposide, and cisplatin (BEP) and of the 5-day schedule versus 3 days per cycle in good-prognosis germ cell cancer. PATIENTS AND METHODS: The study was designed as a 2 x 2 factorial trial. The aim was to rule out a 5% decrease in the 2-year progression-free survival (PFS) rate. The study included the assessment of patient quality of life. A cycle of BEP consisted of etoposide 500 mg/m(2), administered at either 100 mg/m(2) days 1 through 5 or 165 mg/m(2) days 1 through 3, cisplatin 100 mg/m(2), administered at either 20 mg/m(2) days 1 through 5 or 50 mg/m(2) days 1 and 2. Bleomycin 30 mg was administered on days 1, 8, and 15 during cycles 1 through 3. The randomization procedure allowed some investigators to participate only in the comparison of three versus four cycles. RESULTS: From March 1995 until April 1998, 812 patients were randomly assigned to receive three or four cycles: of these, 681 were also randomly assigned to the 5-day or the 3-day schedule. Histology, marker values, and disease extent are well balanced in the treatment arms of the two comparisons. The projected 2-year PFS is 90.4% on three cycles and 89.4% on four cycles. The difference in PFS between three and four cycles is -1.0% (80% confidence limit [CL], -3.8%, +1.8%). Equivalence for three versus four cycles is claimed because both the upper and lower bounds of the 80% CL are less than 5%. In the 5- versus 3-day comparison, the projected 2-year PFS is 88.8% and 89.7%, respectively (difference, -0.9%, (80% CL, -4.1%, +2.2%). Hence, equivalence is claimed in this comparison also. Frequencies of hematologic and nonhematologic toxicities were essentially similar. Quality of life was maintained better in patients receiving three cycles; no differences were detected between 3 and 5 days of treatment. CONCLUSION: We conclude that three cycles of BEP, with etoposide at 500 mg/m(2), is sufficient therapy in good-prognosis germ cell cancer and that the administration of the chemotherapy in 3 days has no detrimental effect on the effectiveness of the BEP regimen.
A case of leukemia cutis (LC) of monocytic lineage in a patient with myelodysplastic syndrome (MDS) is presented. Cutaneous infiltrates were recognized concurrent with diagnosis of refractory anemia (RA) with monocytosis. Skin infiltrates subsequently spontaneously regressed although MDS progressed with increasing monocytosis, anemia, and thrombocytopenia. Death occurred 6 months after diagnosis with evolution of acute monoblastic leukemia complicated by sepsis. This case supports previous observations of poor prognosis associated with leukemia cutis. LC associated with MDS is reviewed including the role of monocytes.
Different electrodes and stimulus protocols commonly used for electroretinography in rodent eyes were compared for convenience of use, degree of damage to corneal epithelium, and for magnitude of amplitude, reproducibility, left versus right eye accuracy, and reliability of recorded parameters of the flash electroretinogram (ERG). Adult C57BL/6 pigmented mice and albino Wistar rats were used to determine scotopic ERGs in response to Ganzfeld or strobe-light stimulation and light-adapted (photopic) ERGs recorded from both eyes at the same time. Test-retest data were used for statistical analyses to compare a monopolar gold-wire contact lens electrode (CLE), a cotton-wick silver-silver chloride electrode (CSCE), a DTL fiber electrode (DTLE), and a circular stainless steel wire electrode (SSE). Corneas were evaluated for abrasion after ERG recordings using fluorescein staining and also for the time taken, ease of insertion, and re-insertions required for the different electrodes. Compared to CSCE, DTLE, and SSE, the ERG potentials recorded by CLE had significantly larger scotopic amplitudes and oscillatory potentials under strobe or Ganzfeld stimulation and for light-adapted ERG b-wave amplitudes in both mice and rats. In analyzing test-retest data of scotopic ERG a-wave and b-wave amplitudes, the intraclass correlation coefficient showed the best agreement for the CLE (range 0.61-0.94) compared to the SSE (0.13-0.77), DTLE (0.02-0.69), and CSCE (0.12-0.51). In mice and rats, logistic regression analyses revealed significant correlations for amplitudes of most scotopic ERG parameters between contralateral eyes obtained with CLE and for some ERG components recorded by SSE. When comparing ERG amplitudes for stimulation by strobe or Ganzfeld, the difference was least with the CLE compared to DTLE, CSCE, or SSE. The time taken to insert the four different electrodes was greatest for the CLE in both mice and rats. The extent of corneal abrasion resulting from electrode use in mice was largest for the SSE followed by the CLE. However, in rats there was almost no corneal damage after ERG recordings with the CLE. Because of the stability of eye contact, the CLE allows ERGs to be determined over a longer recording session. Recording of scotopic and photopic (light-adapted) ERGs in rodents with monopolar gold-wire contact lens electrodes provides greater amplitudes and higher reproducibility when compared to other commonly used corneal electrodes. These electrodes are significantly better overall than others that were evaluated and should be considered for a standard protocol to monitor retinal function in rodent eyes.
1. The perception of UVA light (320 < lambda < 400 nm) by domestic fowl may be an adaptation to naturally lit habitats and may still be functional in farmed varieties, although not utilised owing to the absence of these wavelengths in commercial house lighting. One function may be the mediation of sexually related signalling or communication. 2. In experiment 1, two groups of 41 adult broiler breeders (four cockerels, 37 hens) were kept under conventional fluorescent light, with or without fluorescent UVA supplementation amounting to 16.9% of the total spectral power output of the luminaires. Each light environment was approximately iso-illuminant as perceived by the birds. The two groups were exposed to the light environments alternately for five 2-day periods in a cross-over design. Mating behaviour, production measures and time budgets were recorded on the second day of each period. 3. A UVA-enriched environment increased the number of attempted matings (1.27 vs 0.99 matings/cockerel.h) and locomotion (5.3 vs 3.7 min/bird.hour). 4. In a second experiment, 10 hens were allowed to choose between four cockerels lit under different power levels of UVA (1.6%, 14.6%, 43.5%, 57.5% of the total spectral power output of the luminaires) in a four-armed maze. Again, each light environment was approximately iso-illuminant as perceived by the birds. Each hen was allowed to make one choice per day over four days, with the position of the cockerels and the UVA levels interchanged each day. This schedule was repeated with the same hens for two other groups of four cockerels. 5. At a distance of no less than 60 cm from the cockerel, the hens spent most time inspecting whichever cockerel was lit by 1.6% or 14.6% UVA (1.33 vs 1.37 vs 1.22 vs 1.16 log seconds/hen.choice, respectively for increasing UVA level). Similarly, when allowed to approach closer to the cockerels, the hens spent most time in the arm which contained a cockerel lit by 14.6% UVA light, (1.62 vs 1.88 vs 1.69 vs 1.51 log s/hen.choice, respectively for increasing UVA level). 6. UVA is clearly implicated in the transmission of sexual signals or communication which may have implications for the welfare and production of broiler breeders.
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BACKGROUND: This study aimed to assess the face, content, and construct validity and the internal reliability of a tool for assessing the generic needs of patients with cancer (the Supportive Care Needs Survey). METHODS: A total of 1,492 consecutive patients attending the surgical, radiation, or medical oncology departments of 9 cancer treatment centers in New South Wales, Australia, were asked to participate. Of the 1,370 eligible patients, 1,354 (99%) consented to participate and 888 (65%) completed the survey. Eligible consenting patients were given a Supportive Care Needs Survey to complete at home and return by mail within 7 days. RESULTS: In the assessment of construct validity, the principal components method of factor analysis identified 5 factors with eigenvalues greater than 1, which together accounted for 64% of the total variance (patients' needs in the domains of psychologic, health system and information, physical and daily living, patient care and support, and sexuality). Face and content validity were found to be high following pilot tests and tests of reading ease. Internal reliability coefficients (Cronbach alpha) of all 5 factor-based scales were found to be substantial, ranging from 0.87 to 0.97. CONCLUSIONS: These findings suggest that the Supportive Care Needs Survey provides a reliable and valid index of the global needs of oncology patients. The standardized and widespread application of this instrument is recommended following further refinement and evaluation.
BACKGROUND: The aim of this study was to determine the prevalence and predictors of the perceived unmet needs of cancer patients undergoing treatment for their disease at public treatment centers. METHODS: A total of 1,492 consecutive patients attending the surgical, radiation, or medical oncology departments of 9 major public cancer treatment centers in New South Wales, Australia, were asked to participate. Of the 1,370 eligible patients, 1,354 (99%) consented to participate and 888 (65%) returned completed surveys. Eligible consenting patients were given a Supportive Care Needs Survey to complete at home and return by mail within 7 days. RESULTS: Patients' perceived needs were assessed across the following five areas: psychologic, health system and information, physical and daily living, patient care and support, and sexuality. Patients' perceived needs were highest in the psychologic, health system and information, and physical and daily living domains. Logistic regression modeling revealed subgroups of patients with different types of needs. The significant predictors of reporting some unmet need for help varied according to the domain examined. CONCLUSIONS: This statewide study shows that cancer patients experience high levels of unmet needs across the range of domains examined. The study provides information that may be valuable in identifying areas where interventions could be tested and evaluated in an attempt to address the unmet needs of people living with cancer.
Porphyromonas gingivalis has been implicated in the onset and progression of periodontitis and the availability of hemin for in vitro growth has been associated with virulence of the bacterium in animal models. We report here the cloning and sequence analysis of a P. gingivalis TonB-linked outer membrane receptor gene tlr. This gene was previously identified as a TonB-linked adhesin gene tla and shown to be essential for growth at low concentrations of hemin. The tlr gene is immediately downstream of four open reading frames (htrABCD) that encode a putative ATP binding cassette transport system with sequence similarlity to heme transport systems of other bacteria. Analysis of P. gingivalis W50 mRNA revealed that the htrABCD genes are cotranscribed similar to hemin transport genes of other bacteria.
Hepatitis B virus (HBV) drug resistance to lamivudine is always accompanied by mutations in the viral polymerase gene at position 550, termed group 1 (M550V with L526M) or group 2 (M550I) mutations. The latter mutation has not been associated with famciclovir resistance. Thus, the addition of famciclovir to lamivudine therapy in persons with group 2 lamivudine resistance may lead to virus suppression. The effect of lamivudine/famciclovir combination therapy on HBV infection was monitored in 5 lamivudine-resistant patients by quantitative polymerase chain reaction and polymerase gene sequencing of serum virus. No patients treated with combination therapy had a decline in HBV load >1 log10. Continual evolution of the viral polymerase was detected in association with virologic resistance to both drugs. Cloning experiments identified the preexistence of these multidrug-resistant virus variants as minority species prior to addition of famciclovir therapy. HBV resistance to lamivudine monotherapy is associated with a complex mixture of variants that limit the efficacy of second-line nucleoside-analogue therapy. First-line potent combination therapy may reduce the emergence of HBV drug resistance.
To compare corneal electrodes commonly used in rodent eyes for repeat and left versus right eye accuracy and variability to record the flash electroretinogram (ERG). Animals studied were eight C57BL/6 mice and eight rats of the Wistar strain. Scotopic ERGs were recorded from eyes of dark-adapted anesthetized rodents to compare a custom-made gold-wire contact lens electrode (CLE), a cotton-wick silver-silver chloride electrode (SCLE), and a coiled stainless steel wire electrode (SSE). Compared to SCLE and SSE. the potentials recorded by CLE are characterized by significantly larger ERG amplitudes and oscillatory potentials in both rats and mice (p <0.0001). In analyzing test-retest data comparing the three different electrodes the coefficient of variation was smaller (range, 10.3-15.5%) and the interclass correlation coefficient (0.77-0.93) showed a better agreement for the CLE. Recording scotopic ERGs with custom-made gold-wire contact lens electrodes records large amplitudes and shows a good reproducibility and reliability to monitor retinal function in rodent eyes.
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A prospective study was undertaken to investigate the relationship between various measured pre-treatment parameters and the reduction in overjet achieved when using a twin block functional appliance. Forty-three subjects were fitted with a twin block functional appliance, and a number of pre-treatment clinical and radiographic morphological features were recorded. The functional appliance wear was monitored for 6 months and any individual who did not co-operate with wear was excluded from the subsequent analysis. Multiple regression analysis with stepwise inclusion was used to relate the percentage reduction in overjet achieved by functional appliance wear to any of the pre-treatment parameters. The data from 22 individuals was included in the final analysis. The overbite and SNB angle were the most strongly related variables to percentage reduction in overjet. These were then used to construct a predictive equation for the expected percentage reduction in overjet: Percentage reduction in overjet in 6 months = 132 + 4.9x1 - 1.4x2, where x1 = overbite and x2 = SNB. The pre-treatment overbite was, in isolation, the most influential feature in predicting the percentage of overjet reduction.
Very rapid amplification of DNA by PCR in small volumes can be continuously monitored by the detection of the binding of probes with a rapid cycler with built-in fluorometric detection. Primers were designed to amplify approximately 100 bp of the polymerase gene of hepatitis B virus (HBV) spanning codon 550, where mutations associated with resistance to lamivudine invariably occur. Four hybridization probes were synthesized: one was 3' labelled with fluorescein and hybridized upstream of codon 550. The others were 5' labelled with Cy5 and 3' labelled with biotin and spanned codon 550. The Cy5-labelled oligonucleotides contained either wild-type (ATG) or mutant (GTG or ATT) sequences. A Cy5-labelled probe and either the fluorescein-labelled probe or Sybr Green 1 (a compound that fluoresces when bound to double-stranded DNA) were included in each PCR. After completion of the amplification by using a LightCycler (Idaho Technology), the temperature at which the Cy5 probe melted from the product was determined in a melt program that took ca. 3 min. Pre- and posttreatment samples from eight patients (five chronic and three transplant) who failed lamivudine treatment were amplified, and the presence of mutations in codon 550 was determined by ABI sequencing and by using the LightCycler; in some cases PCR products were also cloned, and multiple clones were sequenced. Concordant results were obtained in all cases. We found the LightCycler to be better at resolving the sequences of genomic mixtures; for example, two samples showed a sequence at codon 550 of (A/G)T(G/T), which was found by fluorimetry to be mixtures of GTG and ATT but no ATG, and this finding was confirmed by the sequencing of clones. However, this approach was not more sensitive than population sequencing for the detection of the presence of mixtures. Overall, this pilot study has demonstrated an approach that could be an extremely rapid and economical method for the detection of lamivudine resistance-associated mutations in HBV.
The aim of the study was to investigate the effect of epidural analgesia on blood pressure, duration of the second stage and mode of delivery. In a prospective controlled study carried out in a district general hospital, 122 parturients made up the study population; 81 had epidural blocks and 41 had other forms of analgesia during labour. Data were collated using questionnaires within 48 hours of delivery: 58/81 (71.6%) of those who chose epidural were primigravidae compared with 14/41 (34%) in the non-epidural group (p < 0.001). During labour, minimum diastolic blood pressure was significantly lower in the epidural group: 65.8 versus 72.4 mmHg (p = 0.003). Mean duration of the second stage of labour was significantly longer in the epidural group: 108.3 versus 41.6 minutes (p < 0.0001); 28/81 (34.6%) of the epidural group had operative vaginal deliveries compared with 6/41 (14.6%) of the non-epidural group (p = 0.0004). Epidural analgesia provides an effective form of pain relief in labour, which has a particularly strong appeal to primigravidae. It has a hypotensive effect which can be put to beneficial effect in hypertensive disease of pregnancy, but is significantly associated with a lengthened second stage of labour, resulting in an increased operative vaginal delivery rate.
This report describes nucleotide sequence analysis of part of the polymerase gene of hepatitis B virus (HBV) during the development of lamivudine-resistant HBV in five patients who received lamivudine treatment in conjunction with liver transplantation. Samples from patients were analysed before, during and after drug treatment in conjunction with serum HBV quantification by PCR. Lamivudine resistance was found to be associated with L526M and M550V changes in two patients and M550I change in three patients. Other changes associated with lamivudine resistance in some patients were V509I, A546V, S565A and A568T. The effects on HBV surface antigen are also described. Some patients were subsequently treated with famciclovir and/or ganciclovir with variable outcomes. In two out of three patients who stopped lamivudine treatment, reversion (partial or complete) to wild-type virus was observed after about 5 months. In contrast, a complex mixture of mutant viruses emerged in a third patient who stopped lamivudine treatment.
BACKGROUND: Laparoscopy in patients with intra-abdominal malignancy remains controversial. This study evaluates the incidence of tumor recurrence at the port site after laparoscopy in patients with intra-abdominal malignancy. METHODS: The medical records of all patients with nongynecologic malignancies who underwent laparoscopic procedures between May 1, 1990, and June 30, 1996, at the University of Texas M.D. Anderson Cancer Center were reviewed. Data on extent of tumor, histologic findings, primary location, procedures performed, and complications were recorded. RESULTS: During this time, 533 patients with known intra-abdominal malignancies underwent laparoscopy. Mean follow-up time was 13.2 +/- 0.5 months (range 1 to 71 months; median 10.6 months). Four recurrences at the port site were identified (0.8%). Three of these patients had advanced intra-abdominal disease at the time of laparoscopy; 1 patient without advanced disease at the time of laparoscopy had a recurrence at the port site as the only site of recurrent disease (0.19%). The incidence of port site recurrences among patients with advanced intra-abdominal disease at the time of laparoscopy (3/71) was significantly greater than the risk of development of a recurrence at the port site among patients without advanced intra-abdominal disease at the time of laparoscopy (1/462; P < .0003, by chi-square analysis). CONCLUSION: Recurrence at the port site is very rare. When implantation at the port site does occur, it is most commonly associated with advanced intra-abdominal disease.