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This review will apply a multidisciplinary approach to GI symptoms with attention to symptom assessment (instruments and qualitative aspects), differential diagnosis, and recent findings relevant to management of symptoms and underlying diseases. We conclude that further development of supportive interventions for GI symptoms for both patient and caregivers has the potential to reduce distress from GI symptoms, and anticipate better symptom control with advances in scientific knowledge and improvement of the evidence base., (Published by Elsevier Inc.)

Phenylthiosemicarbazones (PTSCs) are proton-coupled anion transporters with pH-switchable behaviour known to be regulated by an imine protonation equilibrium. Previously, chloride/nitrate exchange by PTSCs was found to be inactive at pH 7.2 due to locking of the thiourea anion binding site by an intramolecular hydrogen bond, and switched ON upon imine protonation at pH 4.5. The rate-determining process of the pH switch, however, was not examined. We here develop a new series of PTSCs and demonstrate their conformational behaviour by X-ray crystallographic analysis and pH-switchable anion transport properties by liposomal assays. We report the surprising finding that the protonated PTSCs are extremely selective for halides over oxyanions in membrane transport. Owing to the high chloride over nitrate selectivity, the pH-dependent chloride/nitrate exchange of PTSCs originates from the rate-limiting nitrate transport process being inhibited at neutral pH., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Context: Although gastric cancer is one of the most common tumors worldwide, there is little knowledge about symptom clusters and quality of life (QoL) in this population., Objectives: The objectives were to identify the symptom clusters in gastric cancer patients receiving chemotherapy, and explore their effects on QoL., Methods: Gastric cancer patients receiving chemotherapy were recruited. Data were collected using the Memorial Symptom Assessment Scale Short Form, the Functional Assessment of Cancer Therapy-Gastric and the self-designed General Information Evaluation Form. The symptom clusters were extracted through the exploratory factor analysis. The influencing factors of symptom clusters and their effects on QoL were identified using multiple linear regression analysis., Results: A total of 322 participants were enrolled from three medical centers. Five factors were identified in this exploratory factor analysis based on symptom prevalence, namely fatigue related symptom cluster, epithelial symptom cluster, neurologic symptom cluster, malnutrition related symptom cluster and psychological symptom cluster (χ 2  = 31.470, P < 0.05). The affecting factors across symptom clusters and QoL subscales were relatively stable, but also different. Generally, fatigue related symptom cluster, malnutrition related symptom cluster and psychological symptom cluster demonstrated significantly negative effects on all aspects of QoL except social well being., Conclusion: Five symptom clusters were identified in gastric cancer patients receiving chemotherapy in mainland China. The symptom clusters negatively contributed to the variance in all aspects of QoL except social well being. Further studies should examine interventions for symptom clusters, their influencing factors, and their effects on improving QoL., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. All rights reserved.)

Context: Comprehensive symptom assessment is crucial for symptom management. The Memorial Symptom Assessment Scale-Short Form (MSAS-SF) has been validated for symptom assessment in cancer patients, but there is no simplified Chinese version., Objectives: To present the validation procedures and results for the simplified Chinese version of the Memorial Symptom Assessment Scale-Short Form (MSAS-SF-SC) among cancer patients in mainland China., Methods: The MSAS-SF was translated and culturally adapted into simplified Chinese. About 359 cancer patients completed the MSAS-SF-SC, the Chinese Functional Assessment of Cancer Therapy-General, the Chinese Brief Fatigue Inventory, the Chinese Hospital Anxiety and Depression Scale, and the Chinese Medical Outcomes Study Social Support Survey. Reliability was assessed by internal consistency and test-retest coefficients. Convergent and divergent validity were analyzed by Pearson's correlation coefficients between MSAS-SF-SC subscales and the other instruments. Known-groups validity used Eastern Cooperative Oncology Group-Performance Status, hemoglobin level, and primary site., Results: The MSAS-SF-SC was reliable with Cronbach's alpha coefficients for subscales ranging from 0.782 to 0.874 and test-retest coefficients ranging from 0.819 to 0.872. MSAS-SF-SC subscales correlated with corresponding Chinese Functional Assessment of Cancer Therapy-General subscales (-0.557 to -0.680; P < 0.001), Chinese Brief Fatigue Inventory (0.620; P < 0.001), and Chinese Hospital Anxiety and Depression Scale (0.663; P < 0.001) indicating convergent validity. MSAS-SF-SC subscales showed low or no correlations with the Chinese Medical Outcomes Study Social Support Survey (-0.146 to -0.165; P < 0.01), indicating divergent validity. MSAS-SF-SC subscales showed appropriate differences by Eastern Cooperative Oncology Group-Performance Status, hemoglobin level, and primary site., Conclusion: The MSAS-SF-SC demonstrated good psychometric properties and is culturally adapted. The instrument could be a valuable tool for Chinese health care professionals and researchers., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Context: Symptoms of patients with cancer need to be evaluated with a standard instrument. The Memorial Symptom Assessment Scale-Short Form (MSAS-SF) is a symptom assessment tool that has been validated in many languages., Objectives: The aim of the present study was to validate the Korean-version Memorial Symptom Assessment Scale-Short Form (MSAS-SF) in patients with gynecologic cancer., Methods: We translated the MSAS-SF into Korean, and 175 gynecologic cancer inpatients completed the MSAS-SF, Functional Assessment Cancer Therapy-General (FACT-G), and gathered demographic and clinical data and Karnofsky Performance Status (KPS). Reliability was assessed for internal consistency with Cronbach's alpha coefficient. Pearson's correlation coefficient was calculated between the MSAS-SF and FACT-G subscales for convergent validity. T-test analysis was used to compare differences in MSAS-SF subscales by cancer stage and KPS for discriminant validity., Results: The Cronbach's alpha coefficients for the MSAS-SF subscales ranged from 0.80 to 0.91. The Korean-version MSAS-SF subscales showed convergent validity with FACT-G subscales. The correlation coefficients were -0.640 (P < 0.001) and -0.628 (P < 0.001) for global distress index and total MSAS score with FACT-G total score. The scores of MSAS-SF subscales showed appropriate differences by cancer stage and KPS., Conclusion: The Korean-version MSAS-SF is a valid tool for the reliable assessment of patients with gynecologic cancer in Korea., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Context: Physicians overestimate survival in patients with advanced cancer. Patient-reported outcomes could provide another way to estimate survival. We previously reported four prognostic groups based on Karnofsky Performance Status, Functional Assessment of Cancer Therapy physical well-being subscale, and Memorial Symptom Assessment Scale-Short Form physical symptom distress subscale scores., Objectives: To determine the validity of these four prognostic groups., Methods: We performed prospective surveys. Data from a total of 880 Veterans Affairs Medical Center patients, 417 in the First Cohort and 463 in the Validation Cohort, were analyzed. Both inpatients and outpatients were prospectively recruited in Institutional Review Board-approved studies from August 1999 to September 2009. Survival was measured from the date of entry until death or December 1, 2009. Patients completed self-assessments with the Functional Assessment of Cancer Therapy and Memorial Symptom Assessment Scale-Short Form. Analysis of variance was used to test differences between groups in continuous variables; a generalized Wilcoxon test was used for differences between groups for survival., Results: The average age in the Validation Cohort was 66.5 years and 98% were men. The majority of patients had metastatic cancer (90%), with lung (28%) and prostate (26%) cancers being predominant. The median Karnofsky Performance Status was 70. Median survival was 33, 46.5, 124, and 209.5 days for the four prognostic groups (P < 0.0001, all pair-wise comparisons P < 0.02)., Conclusion: The four prognostic groups remained distinct in the prospective cohort. Small differences in patient-reported physical well-being can halve survival estimates. Patient-reported outcomes can correct for physician overestimate of prognosis. This study provides a way to use patient-reported outcomes for prognosis in patients with advanced cancer, with important implications for assessment., (Published by Elsevier Inc.)

Introduction: Despite recent therapeutic advances, lung cancer is a difficult disease to manage. This study assessed clinicians' perceptions of care difficulty, quality of life (QOL), and symptom reports for their lung cancer patients compared with their patients with breast, prostate, and colon cancer., Methods: This report focused on secondary analyses from the Eastern Cooperative Oncology Group (ECOG) Symptom Outcomes and Practice Patterns (SOAPP) study (E2Z02); outcome measures included clinician ratings of 3106 solid tumor patients. Univariate analyses focused on patterns of disease-specific perceptions; multivariable analyses examined whether disease-specific differences persisted after covariate inclusion., Results: In univariate comparisons, clinicians rated lung cancer patients as more difficult to treat than other solid tumor patients, with poorer QOL and higher symptom reports. After covariates were adjusted, the odds of clinicians perceiving lower QOL for their lung cancer patients were 3.6 times larger than for patients with other solid tumors (odds ratio = 3.6 [95% confidence interval, 2.0-6.6]; p < 0.0001). In addition, the odds of clinicians perceiving weight difficulties for their lung cancer patients were 3.2 times larger (odds ratio = 3.2 [95% confidence interval, 1.7-6.0]; p = 0.0004). No other outcome showed significant differences between lung versus other cancers in multivariable models., Conclusion: Clinicians were more pessimistic about the well-being of their lung cancer patients compared with patients with other solid tumors. Differences remained for clinician perceptions of patient QOL and weight difficulty, even after controlling for such variables as stage, performance status, and patient-reported outcomes. These continuing disparities suggest possible perception bias. More research is needed to confirm this disparity and explore the underpinnings.

Cervical cancer is the second most common female cancer worldwide. The ability to quantify physiological and morphological changes in the cervix is not only useful in the diagnosis of cervical precancers but also important in aiding the design of cost-effective detection systems for use in developing countries that lack well-established screening and diagnostic programs. We assessed the capability of a diffuse reflectance spectroscopy technique to identify contrasts in optical biomarkers that vary with different grades of cervical intraepithelial neoplasia (CIN) from normal cervical tissues. The technology consists of an optical probe and an instrument (with broadband light source, dispersive element, and detector), and a Monte Carlo algorithm to extract optical biomarker contributions including total hemoglobin (Hb) concentration, Hb saturation, and reduced scattering coefficient from the measured spectra. Among 38 patients and 89 sites examined, 46 squamous normal sites, 18 CIN 1, and 15 CIN 2(+) sites were included in the analysis. Total Hb was statistically higher in CIN 2(+) (18.3 +/- 3.6 microM, mean +/- SE) compared with normal (9.58 +/- 1.91 microM) and CIN 1 (12.8 +/- 2.6 microM), whereas scattering was significantly reduced in CIN 1 (8.3 +/- 0.8 cm(-1)) and CIN 2(+) (8.6 +/- 1.0 cm(-1)) compared with normal (10.2 +/- 1.1 cm(-1)). Hemoglobin saturation was not significantly altered in CIN 2(+) compared with normal and CIN 1. The difference in total Hb is likely because of stromal angiogenesis, whereas decreased scattering can be attributed to breakdown of collagen network in the cervical stroma.

There are very few symptom assessment instruments in Chinese. We present the validity and reliability of the Memorial Symptom Assessment Scale Short Form (MSAS-SF) and the Condensed Form MSAS (CMSAS) in Chinese cancer patients. The Chinese version of the 32-item MSAS-SF, a self-report measure for assessing symptom distress and frequency in cancer patients, was administered to 256 Chinese patients with colorectal cancer at a clinical oncology outpatient unit. Highly prevalent symptoms included worrying (59%), dry mouth (54%), lack of energy (54%), feeling sad (48%), feeling irritable (48%), and pain (41%). Both the MSAS-SF and CMSAS demonstrated good validity and reliability. For the MSAS-SF subscales, Cronbach alphas ranged from 0.84 to 0.91, and for CMSAS subscales, from 0.79 to 0.87. Moderate-to-high correlations of MSAS-SF and CMSAS subscales with appropriate European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 subscales (0.42-0.71, Ps<0.001) indicated acceptable convergent validity. Low correlations with the Rosenberg Self-Esteem and Optimism Scale (0.22, P<0.001) indicated divergent validity. MSAS subscales varied as expected with other Chinese scales--the Chinese Health Questionnaire (CHQ) and the Life Orientation Scale. Construct validity of both MSAS versions was demonstrated by effective differentiation between clinically distinct patient groups (Karnofsky scores <80% vs. > or =80% [P<0.001]; no active treatment vs. active treatment [P<0.002-0.034]; CHQ-12 scores < or =4 vs. CHQ-12 scores >4 [P<0.001]). The Number of Symptoms subscale correlated appropriately with the EORTC QLQ-C30 function (-0.46 to -0.60, P<0.001) and symptom scales (0.31-0.64, P<0.001). The average time to complete the MSAS-SF was six minutes. The Chinese versions of the MSAS-SF and CMSAS are valid and practical measures. Further validation is needed for Chinese patients with other cancer types and with other symptom instruments.

Although bone metastasis to the acetabulum can cause significant disability from pain and immobility, little has been written about the diagnosis and management of a pathologic acetabular fracture. We present three patients with metastatic acetabular fractures and discuss an approach to evaluation and management. When a high index of suspicion of fracture exists, further radiographic workup is warranted. Management requires a multidisciplinary approach. Factors such as age, associated comorbidities, natural history of the underlying primary cancer, general health status, prognosis, acetabular fracture characteristics, and quality of bone should be considered. We briefly discuss the options available to nonoperative candidates.

Veteran patients possess distinctive characteristics such as a higher mortality rate, lower socioeconomic status and poorer health status. We report the prevalence and predictors of unmet needs and examine the association between unmet needs and quality of life (QOL). Two hundred ninety-six male cancer patients who presented with distressing symptom(s) completed the following instruments: a 14-item multidimensional unmet needs questionnaire, Functional Assessment of Cancer Therapy (FACT-G), Memorial Symptom Assessment Scale-Short Form (MSAS-SF) and other validated measurements of function, depression, health and social support. Multiple linear regression models were used to identify independent predictors of each unmet needs domain and of total unmet needs. The relationships between total unmet needs, QOL and multidimensional variables were also explored. The median number of total unmet needs was three, and the most frequently reported unmet needs areas were physical (80.0%), activities of daily living (53.3%), nutrition (46.1%) and emotional (32.5%). Different predictors of each unmet needs domain were identified. Younger age was associated with a higher risk of unmet needs in physical, economic and medical domains. Higher psychological symptom distress was associated with more unmet needs in the emotional/social, economic and medical domains. Physical symptom distress, extent of disease and health measure were only significant in the physical unmet needs domain. The depression, psychological and physical symptom distress scores, confident and affective social support scores, total unmet needs and age independently predicted FACT-G total QOL score (R(2)=63%, P < 0.00001). Patients with higher psychological, physical symptom distress and depression scores, younger age, lower functional status and metastatic disease were more likely to report more unmet needs. The total number of unmet needs was predictive of QOL. The unmet needs and QOL outcomes model was developed but needs further validation.

The natural variation of Mg and Ca stable isotopes of carbonates has been determined in carbonate skeletons of perforate foraminifera and reef coral together with Mg/Ca ratios to assess the influence of biomineralisation processes. The results for coral aragonite suggest its formation, in terms of stable isotope behaviour, approximates to inorganic precipitation from a seawater reservoir. In contrast, results for foraminifera calcite suggest a marked biological control on Mg isotope ratios presumably related to its low Mg content compared with seawater. The bearing of these observations on the use of Mg and Ca isotopes as proxies in paleoceanography is considered., (Copyright 2004 Elsevier Inc.)

The purpose of this study was to identify independent predictors of clinically significant fatigue based upon a multidimensional model. A total of 180 cancer patients completed the Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Fatigue (FACT-F), Memorial Symptom Assessment Scale Short Form (MSAS-SF), and the Zung Self-Rating Depression Scale (SDS). Additional data included Karnofsky Performance Status (KPS) score, laboratory tests, and demographic information. The BFI usual fatigue severity > or =3/10 was defined as clinically significant fatigue. Possible independent variables were identified from a biopsychosocial model of fatigue. Fisher's exact test was used to univariately assess the association of each variable with clinically significant fatigue. Multiple logistic regression analyses were used to identify independent predictors of fatigue within each dimension, and then across dimensions. Fatigue was present in 113 (62%) patients, and 80 (44.4%) patients had usual fatigue > or =3/10. The unidimensional independent predictors were use of analgesics (situation dimension); hemoglobin and serum sodium (biomedical dimension); feeling drowsy, dyspnea, pain and lack of appetite (physical symptom dimension); and feeling sad and feeling irritable (psychological symptom dimension). In a multidimensional model, dyspnea, pain, lack of appetite, feeling drowsy, feeling sad, and feeling irritable predicted fatigue independently with good calibration (Hosmer Lemeshow Chi Square=5.73, P=0.68) and discrimination (area under the receiver operating characteristic curve=0.88). Physical and psychological symptoms predict fatigue independently in the multidimensional model, and superseded laboratory data. These findings support a symptom-oriented approach to assessment of cancer-related fatigue.

To document quality-of-life (QOL), symptom distress and Karnofsky Performance Status (KPS) over time, 67 advanced cancer patients completed the Functional Assessment of Cancer Therapy (FACT-G) and Memorial Symptom Assessment Scale - Short Form (MSAS-SF) from the time of determination of no active anti-cancer treatment to death at 3-6 week intervals. The KPS was determined at each time point. Statistical analyses with mixed effects models were performed to examine the association between changes in QOL, symptom distress and KPS at selected time points in the advanced cancer trajectory. Median survival for the population was 115 days, and a median of 5 interviews was completed per patient. Slow steady changes in KPS, MSAS-SF and FACT-G QOL parameters started 6 months prior to death, with accelerated decline in the last 2 to 3 months and dramatic increase in psychological symptoms during the last month. Different domains changed at different rates at different selected time points. The correlation between changes in KPS, FACT-G parameters and MSAS-SF subscales at enrollment and near death suggests that when patients were stable, changes in KPS correlated significantly with changes in sum FACT-G QOL and physical well being, and with changes in the MSAS-SF subscales. However, when patients were near death, changes in KPS did not correlate with any other changes, and only emotional well being reflected changes in physical and psychological symptom distress. The sequence of changes, and how determinants of symptom distress and QOL change over time, may help clinicians assess the prognosis of terminally ill patients and plan appropriate interventions.

We measured pain outcomes in a cohort of patients with cancer pain in a general hematology/oncology setting at a Veterans Administration Medical center (VA). The outcomes included pain relief, pain severity, changes in pain severity, interference scores, symptom distress, quality of life (QOL), and satisfaction. Seventy-four (74) consecutive patients with worst cancer-related pain equal to or greater than 4/10 were recruited. Cancer pain diagnoses were made and the cancer pain management guidelines of the United States Agency for Health Care Policy and Research were followed. Patients were followed weekly using the Brief Pain Inventory (BPI), medication diary, satisfaction questionnaire, visual analogue quality of life scale (VASQOL) and record of side effects for 3 weeks. The Functional Assessment of Cancer Therapy (FACT-G) and Memorial Symptom Assessment Scale Short Form (MSAS-SF) were used at initial and final interviews. The mean initial worst pain severity was 8.3 (range 4-10) and mean pain relief was 40% (range 0-100). By week 1, the majority of patients achieved pain relief of >/=80%, with a corresponding decrease in worst pain severity and pain interference scores. Pain continued to decrease over three weeks. At week 3, there was a significant improvement in the MSAS-SF psychological symptom distress subscale (P = 0.02). The average number of opioid-related side effects was 5 and remained steady over time. Most patients felt "quite a bit" or "very much" satisfied at all weeks. There was a significant improvement in VASQOL (P < 0.005) and in FACTG SUMQOL scores (P = 0.007). This experience demonstrates that cancer pain management can result in measurable and significant changes in pain relief, pain severity, pain interference scores, psychological symptom distress, and QOL scores.

The purpose of this study was to develop a Cancer Pain Prognostic Scale (CPPS) which could predict the likelihood of pain relief within 2 weeks for cancer patients with moderate to severe pain. Seventy-four (74) consecutive patients who presented with cancer-related pain were managed in accordance with the guidelines for pain management developed by the United States Agency for Health Care Policy and Research (AHCPR). Patients were followed weekly using the Brief Pain Inventory (BPI), and medications were recorded weekly for 3 weeks. Baseline scores from the Functional Assessment of Cancer Therapy (FACT-G), Mental Health Inventory (MHI), Karnofsky Performance Status (KPS), and Memorial Symptom Assessment Scale Short Form (MSAS-SF) at initial interview served as explanatory variables in a logistic regression model. Pain relief > or = 80% at the end of weeks 1 and 2 were used as outcomes in this model. From this analysis, we developed a predictive formula, the CPPS, which includes the worst pain severity, FACT-G emotional well being, daily opioid dose, and pain characteristics. The rule yields a numerical score that ranges from 0-17. Higher scores correspond to a higher probability of good pain relief. The CPPS has the potential to rapidly identify patients with poor pain prognosis. It can be used as a research tool to characterize pain in cancer patients.

To examine the relationship between different cancer pain management outcomes over time, 74 patients with the worst cancer related pain rated as four or greater on an 11-point numeric scale were followed weekly with the Brief Pain Inventory (BPI), and the satisfaction questionnaire and global visual analogue scale quality of life (VASQOL) for 3 weeks. Univariate and multivariate regression analyses were performed at weekly time points. The analyses indicated that pain outcomes can be categorized into separate QOL and satisfaction paths linked by the worst pain severity. In the QOL path, the worst pain severity predicted a pain interference score, which consistently predicted VASQOL. For the satisfaction path, independent predictors were pain relief at Week 1, and worst pain severity and changes in worst pain severity at Week 2. No variables predicted satisfaction at Week 3. The data suggest that satisfaction and quality of life may be independent outcomes of pain management. The timing of assessment may itself be important.

Patients with unresectable pancreatic cancer often suffer severe pain. Various techniques are available for pain control. We present a patient with pancreatic cancer who underwent unilateral video-assisted thoracoscopic sympathectomy-splanchnicectomy and had complete pain relief. This minimally invasive procedure offers promise in carefully selected patients with severe pain from pancreatic cancer and other conditions which are not amenable to conventional interventions.

Bone marrow (BM) fibrosis may occur in myeloproliferative diseases, lymphoma, myelodysplastic syndrome, myeloma, and infectious diseases. In this study, the role of substance P (SP), a peptide with pleiotropic functions, was examined. Some of its functions-angiogenesis, fibroblast proliferation, and stimulation of BM progenitors-are amenable to inducing BM fibrosis. Indeed, a significant increase was found in SP-immunoreactivity (SP-IR) in the sera of patients with BM fibrosis (n = 44) compared with the sera of patients with hematologic disorders and no histologic evidence of fibrosis (n = 46) (140 +/-12 vs 18 +/-3; P <.01). Immunoprecipitation of sera SP indicated that this peptide exists in the form of a complex with other molecule(s). It was, therefore, hypothesized that SP might be complexed with NK-1, its natural receptor, or with a molecule homologous to NK-1. To address this, 3 cDNA libraries were screened that were constructed from pooled BM stroma or mononuclear cells with an NK-1 cDNA probe. A partial clone (clone 1) was retrieved that was 97% homologous to the ED-A region of fibronectin (FN). Furthermore, sequence analyses indicated that clone 1 shared significant homology with exon 5 of NK-1. Immunoprecipitation and Western blot analysis indicated co-migration of SP and FN in 27 of 31 patients with BM fibrosis. Computer-assisted molecular modeling suggested that similar secondary structural features between FN and NK-1 and the relative electrostatic charge might explain a complex formed between FN (negative) and SP (positive). This study suggests that SP may be implicated in the pathophysiology of myelofibrosis, though its role would have to be substantiated in future research. (Blood. 2001;97:3025-3031)

Phantom limb pain is a common sequela of amputation. Studies suggest that over time, there is a decrease in frequency and intensity of phantom pain. Persistently increased phantom pain has been seen in benign lesions affecting the peripheral and central nervous system. We present a 74-year-old woman who had a left above-knee amputation for leiomyosarcoma of the foot 24 years previously. She had been free of disease and ambulated independently until 1 month before hospitalization, when she noted increasing pain in her phantom foot. At the time of admission, she had developed increasing low back pain and was diagnosed with adenocarcinoma of unknown primary. Work-up confirmed involvement of the L4 vertebral body with epidural and paraspinal disease. We believe this is the first reported case of worsening phantom limb pain resulting from a spinal metastasis. We review the literature on the potential implications of increased phantom pain.

Rapidly progressive pain, or "crescendo" pain, can be a difficult management problem. A cancer patient is presented who experienced crescendo neuropathic pain due to progressive pelvic disease. This patient reported significant pain relief with the administration of intravenous phenytoin. The case illustrates the type of therapeutic approach that may be considered for crescendo pain and highlights a potential role for intravenous phenytoin in the management of patients with crescendo cancer-related neuropathic pain.

Fetal hemoglobin (HbF) levels vary widely among individuals with sickle cell anemia (SS). Previous studies have suggested that HbF levels in SS individuals with alpha-thalassemia (two or three functional alpha-globin genes) are lower than HbF levels in SS individuals with four normal alpha-globin genes. Using immunocytochemical techniques, we studied F cell production as measured by % F reticulocytes, the amount of HbF per F cell, and the preferential survival of F cells versus non-F cells in 51 subjects with four alpha genes, 32 subjects with three alpha genes, and 18 subjects with two alpha genes. Comparison between alpha-globin gene groups was performed for the total sample as well as for a subset of 82 individuals who had replicate samples and a further subset of 39 age-matched individuals. %HbF levels were 6.8, 4.9, and 4.5 percent for the total four-, three-, and two-alpha-globin-gene groups, respectively. The percentage of F reticulocytes, percentage HbF per F cell, and the enrichment ratio (% F cell/% F reticulocytes) did not change significantly with alpha-globin gene number. Moreover, no correlation existed between alpha-globin gene number and the absolute number of F cells in any group studied. However, there was a strong inverse correlation (r = -0.407, P = .0001) between non-F cell levels (1.7 +/- 2, 2.2 +/- 5, 3.0 +/- 1.0 X 10(12)/L) and decreasing alpha-globin gene number. These data suggest that falling HbF levels among SS individuals with lessened numbers of alpha-globin genes reflect prolonged survival of non-F cells and are not due to intrinsic differences in F cell production or in the amount of HbF per F cell. The improved survival of non-F cells in SS alpha-thalassemia is presumed to be due to the lower MCHC observed in such individuals.