Falls and functional impairments in cancer survivors with chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study.

PURPOSE: This study was conducted in order to characterize the prevalence of falls and functional impairments (FIs) and their association with chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors. METHODS: We analyzed baseline assessments from a phase III RCT in cancer survivors with self-reported CIPN scores of >4 out of 10. Patients completed the EORTC QLQ-CIPN-20 for neuropathy and reported falls in the previous 3 months. FIs were defined using the Activities of Daily Living subsection of the Vulnerable Elder's Scale. Associations of baseline characteristics and CIPN with falls and FIs were examined using logistic regression. RESULTS: Of 421 patients, 11.9 % experienced recent falls and 26.6 % reported FIs. Motor neuropathy was the only factor associated with falls (OR = 1.127, p = 0.01). Factors associated with FIs included non-white race (OR = 0.335 white relative to non-white, 0.781, p = 0.01) and greater motor neuropathy scores (OR = 1.262, p < 0.0001). CONCLUSION: CIPN, primarily motor, is associated with falls and FIs. Future prospective research should investigate the ability of motor neuropathy severity to predict falls.

Successes and challenges of latent TB screening and treatment in a high-prevalence US region.

BACKGROUND: South Texas has higher TB disease incidence than much of the United States. We evaluated a multi-site South Texas interferon-gamma release assay (IGRA)-based testing and latent TB infection (LTBI) treatment program targeting high-risk populations.METHODS: Number of IGRA tests, test results, LTBI confirmation, and treatment outcomes were collected over 2.5 years. Sixteen semi-structured patient interviews and 10 site-based focus groups were conducted with providers, nurses, and administrators. Grounded theory identified themes associated with successful outcomes.RESULTS: Of 9,050 IGRA tests, 687 (8%) were positive; 340 (49%) confirmed as LTBI; 191 initiated LTBI treatment; and 130 (68% of initiators) completed treatment. Patient barriers to treatment completion included lack of knowledge, misconceptions, and treatment toxicities. Clinic staff concurred that toxicity was a barrier to treatment and requiring new processes with limited resources were implementation barriers.CONCLUSIONS: Over 9,000 patients were screened with a high prevalence of IGRA positivity, but confirming LTBI, initiating, and completing treatment were challenging. Qualitative evaluation supports low literacy patient education on LTBI and toxicities and expanded support for process implementation and provider training. These findings highlight challenges at all levels of the LTBI care cascade and provide patient, staff, and provider perspectives on implementation of these programs.

The efficacy of calcitriol therapy in the management of bone loss and fractures: a qualitative review.

UNLABELLED: Osteoporosis, a skeletal disorder characterized by a reduction in bone strength, increases fracture risk. Primary osteoporosis is usually a result of reduced bone mineral density as a consequence of natural aging. Secondary osteoporosis is usually a result of a disease, such as cystic fibrosis, or medical treatment, such as corticosteroids or cancer treatment. INTRODUCTION: Currently, ten million Americans are osteoporotic and an additional 34 million have the precursor condition, osteopenia. Osteoporosis leads to 1.5 million fractures and 500,000 hospitalizations annually. Osteoporosis-related fractures increase mortality and reduce quality of life. Calcitriol, the active form of vitamin D, regulates intestinal calcium absorption, among other actions. During the past four decades, many clinical trials investigating the effect of calcitriol on bone loss have been performed. METHODS: We conducted a systematic qualitative review of clinical trials that assessed calcitriol for the treatment of osteoporosis and bone loss. In these clinical trials, calcitriol was used as a monotherapy and in combination with other therapeutic bone agents. RESULTS AND CONCLUSION: Studies using calcitriol monotherapy, although not conclusive, found that calcitriol slowed the rate of bone loss in a variety of populations. Calcitriol in combination with other therapeutic bone agents was shown to have additional bone-preserving effects when compared to the use of therapeutic bone agents alone. A common side-effect of calcitriol therapy was hypercalcemia and hypercalciuria, but the degree of hypercalcemia was mild. Recent research found that intermittent dosing can reduce hypercalcemia rates. Calcitriol, alone or in combination with other agents, should be considered for the therapy of osteoporosis.

Associations between adult and childhood secondhand smoke exposures and fecundity and fetal loss among women who visited a cancer hospital.

BACKGROUND: A large percentage of the population continues to be exposed to secondhand smoke (SHS). Although studies have consistently linked active smoking to various pregnancy outcomes, results from the few studies examining SHS exposure and pregnancy difficulties have been inconsistent. METHODS: Approximately 4800 women who presented to Roswell Park Cancer Institute between 1982 and 1998 and reported being pregnant at least once were queried about their childhood and adult exposures to SHS using a standardised questionnaire. Women were asked to report on selected prenatal pregnancy outcomes (fetal loss and difficulty becoming pregnant). RESULTS: Approximately 11.3% of women reported difficulty becoming pregnant, while 32% reported a fetal loss or 12.4% reported multiple fetal losses. 40% reported any prenatal pregnancy difficulty (fetal loss and/or difficulty becoming pregnant). SHS exposures from their parents were associated with difficulty becoming pregnant (OR = 1.27, 95% CI 1.03 to 1.56) and lasting >1 year (OR = 1.34, 95% CI 1.12 to 1.60). Exposure to SHS in both at home during childhood and at the time of survey completion was also associated with fetal loss (OR = 1.39, 95% CI 1.17 to 1.66) and multiple fetal losses (OR = 1.62, 95% CI 1.25 to 2.11). Increasing current daily hours of SHS exposure as an adult was related to the occurrence of both multiple fetal loss and reduced fecundity (p(trend) < 0.05). CONCLUSIONS: Reports of exposures to SHS during childhood and as an adult were associated with increased odds for prenatal pregnancy difficulties. These findings underscore the public health perspective that all people, especially women in their reproductive years, should be fully protected from tobacco smoke.

Prevalence and correlates of anticipatory nausea and vomiting in chemotherapy patients.

Forty-seven of 225 (21%) consecutive cancer patients were found to experience nausea and/or vomiting prior to a chemotherapy treatment. Multivariate examination of demographic and clinical characteristics showed patients with anticipatory side effects to report more severe posttreatment emesis, to report their most severe posttreatment nausea as occurring later after treatment, and to be more likely to be taking cisplatin than patients without anticipatory side effects. Seventy percent of the patients with anticipatory nausea and/or vomiting attributed the side effects to a psychologic etiology.

Clinical characteristics associated with the development of anticipatory nausea and vomiting in cancer patients undergoing chemotherapy treatment.

Approximately one in four patients experiences nausea and/or vomiting in anticipation of a chemotherapy treatment by the time of their fourth treatment cycle. Anticipatory nausea and vomiting is a prevalent problem of clinical significance in the total management of chemotherapy side effects. While refractory to standard antiemetic treatment, anticipatory nausea and vomiting has been successfully treated with behavioral approaches such as systemic desensitization. The present study was designed to identify the characteristics of patients at high risk for developing anticipatory side effects. Early identification of cancer patients prone to developing anticipatory side effects could lead to preventive measures. One hundred seventy-six consecutive ambulatory patients with histologically confirmed cancer who were being treated at three geographically separate hospitals of the University of Rochester Cancer Center were studied at the time of their fourth chemotherapy treatment. Patients found to experience anticipatory nausea and vomiting were significantly more likely (P less than .001) to have four or more of the following characteristics than patients who did not report anticipatory side effects: (1) less than 50 years of age; (2) the experience of nausea and/or vomiting after their last chemotherapy treatment; (3) a description of nausea after the last treatment as "moderate, severe, or intolerable"; (4) a description of vomiting after the last treatment as "moderate, severe, or intolerable"; (5) the reporting of the side effect "warm or hot all over" after their last treatment; (6) a susceptibility to motion sickness; (7) the experience of "sweating after their last treatment"; (8) and the experience of "generalized weakness after their last chemotherapy treatment." Results support a view that anticipatory side effects are conditioned and point to practical interventions for their clinical control.

A randomized clinical trial of alprazolam versus progressive muscle relaxation in cancer patients with anxiety and depressive symptoms.

A randomized nonblinded study was performed in three cancer centers to test over a 10-day period the efficacy of (1) a triazolobenzodiazepine, alprazolam, 0.5 mg three times a day and (2) use of a behavioral technique in which patients were trained in progressive muscle relaxation at an initial session with a behavioral psychologist and then asked to listen at home to an audiotape of the session three times a day. Of 147 cancer patients who met entry levels of distress and completed the study, uncontrolled for site or disease stage, 70 were randomized to drug, 77 to relaxation. Four measures of anxiety and depression were used: Covi, Raskin, Affects Balance, and Symptoms Checklist-90 (SCL-90). Results showed that both treatment arms resulted in significant (P less than .001) decrease in observer and patient-reported anxious and depressed mood symptoms. Although both treatment arms were effective, patients receiving the drug showed a slightly more rapid decrease in anxiety and greater reduction of depressive symptoms. These findings confirm efficacy of both alprazolam and relaxation to reduce cancer-related anxiety and depression. As safe, inexpensive, and effective interventions, physicians should consider their use in cancer patients experiencing anxiety and depressive symptoms.

Informed consent for investigational chemotherapy: patients' and physicians' perceptions.

One hundred forty-four patients and 68 physicians at three cancer centers were studied for their perceptions of the consent procedure, in which they participated one to three weeks earlier, for chemotherapy by one of 65 investigational protocols. Patients recalled the procedure positively and relied heavily on physician's advice. They felt most physicians wanted them to accept; 29% felt their participation in the decision was not encouraged. Primary reasons for accepting were trust in the physician, belief the treatment would help, and fear the disease (viewed as highly serious) would get worse without it. Nearly a fourth did not recall the information given that treatment was investigational. The consent form played no role in decision-making for 69%. Physicians believed therapeutic benefits would exceed potential problems for most patients; they viewed 41% of the patients as less than eager for details of treatment, a third as avoiding the seriousness of the discussion, and a third as passive in decision-making. The perceptual set of both parties places inadvertent constraint on patients' autonomy in decision making.

Predictors of mortality in the immunocompromised patient with pulmonary infiltrates.

To determine predictors of mortality in immunocompromised patients with pulmonary infiltrates, we reviewed the records of all such patients admitted to two community teaching hospitals who underwent a lung biopsy over a ten-year period. We examined the consequences of advancing age, primary disease, fever, neutropenia, immunosuppressive corticosteroid therapy, previous lung radiation, roentgenographic pattern, result of lung biopsy, room air arterial oxygen pressure (Pao2), early mechanical ventilation, and the presence of a comorbid disease on eventual outcome. We identified 104 episodes in 99 patients. Sixty-seven (64%) survived and 37 died. By both discriminant analysis and logistic regression statistical methods, mechanical ventilation, the initial room air Pao2, and corticosteroid therapy were the dominant independent variables, in that order, to significantly predict mortality. No patient survived who simultaneously had a room air Pao2 less than or equal to 50 mm Hg, was on corticosteroids, and was mechanically ventilated. Eighty-three percent of survivors had either none or, at most, one of these three variables present. We conclude that hypoxia, immunosuppression by corticosteroids, and the necessity for mechanical ventilation within 72 hours of hospitalization indicate a poor prognosis in the immunocompromised patient with pulmonary infiltrates who has undergone a lung biopsy.

Who keeps the first outpatient appointment?

The authors studied 1,106 consecutive patients who called for an initial outpatient appointment at a medical center department of psychiatry during a one-year period. The 759 (68.6%) patients who kept their initial scheduled appointment differed from the 347 (31.4%) who did not in age, previous psychiatric treatment, source of referral, chief complaint, and number of days they waited for an appointment. A telephone follow-up conducted with almost 30% of those who did not keep their initial appointment revealed that of those contacted, 26 (25%) sought other routes for psychiatric help and 23 (22%) made a subsequent contact at the facility studied.

Expression of heat shock proteins in mouse skin during wound healing.

Wound healing conditions generate a stressful environment for the cells involved in the regeneration process and are therefore postulated to influence the expression of heat shock proteins (Hsps). We have examined the expression of four Hsps (Hsp27, Hsp60, Hsp70 and Hsp90) and a keratin (keratin 6) by immunohistochemistry during cutaneous wound repair from Day 1 to Day 21 after wounding in the mouse. Hsps were constitutively expressed in normal mouse epidermis and their patterns of expression were modified during the healing process. The changes were not directly linked to the time course of the healing process but rather were dependent on the location of cells in the regenerating epidermis. In the thickened epidermis, Hsp60 was induced in basal and low suprabasal cells, Hsp70 showed a reduced expression, and Hsp90 and Hsp27 preserved a suprabasal pattern with an induction in basal and low suprabasal cells. All Hsps had a uniform pattern of expression in the migrating epithelial tongue. These observations suggest that the expression of Hsps in the neoepidermis is related to the proliferation, the migration, and the differentiation states of keratinocytes within the wound.

Latrogenesis imperfecta--a new pediatric problem.

In this medical age which relies heavily on electronic and technologic advances, the physician is often willing to place unwarranted confidence in laboratory data regarding his patients. In those unusual situations in which the patient is not directly examined, e.g., prospective screening or prenatal diagnosis, treatment errors can be made. These acts of commissions are initiated by interpretation of laboratory data and can result in detrimental effects to the patient. The term iatrogenesis imperfecta has been designated to describe this situation.

Moped injuries in children.

Moped injuries are an important cause of traffic-related injuries in children. An attempt was made to define the epidemiology as well as the nature and severity of injuries sustained in 88 moped-related accidents. Bicycle injuries among children (579) were used as a control. The patients with moped injuries were younger than expected (mean 12.8 years with a minimum legal driving age of 14 years in the study area). Among 26 hospital admissions due to moped accidents, there were 11 admissions to the intensive care unit, demonstrating the severe nature of the injuries. Fifty percent of the patients had orthopaedic injuries and 46% had neurologic injuries. These injuries resulted in an average length of hospitalization of 8.5 days (intensive care unit admissions lasted an average of 14.6 days). Recommendations are made to aid pediatricians in the counseling of patients and parents.

Interaction of maternal and neonatal obesity.

Maternal weight and height before pregnancy and weight gain during pregnancy were recorded for each of 109 mothers who were delivered of normal infants after gestations of 37 to 43 weeks. Infant parameters obtained included gestational age, birth weight, bilateral mid-arm circumference, and eight skin fold thickness measurements. The eight skin fold thicknesses were summed (SSFT) for each infant. Infants with SSFTs greater than 40 mm (N = 8) for the group were classified as "fatter" infants. All of the fatter infants were large for gestational age (LGA), but accounted for only one third of the LGA infants in the study. Birth weight, length, and cross-sectional mid-arm fat area were significantly increased in the fatter LGA group when compared to other LGA infants. Cross-sectional mid-arm muscle area was not significantly different for the fatter LGA infants compared to the other LGA group. Mothers were defined as obese or nonobese according to pregnant weight for height. Obese mothers had infants with significantly increased SSFTs when compared with infants of nonobese mothers. Mulitple regression analysis showed that both prepregnant weight for height and weight gain during pregnancy were associated with increased subcutaneous fat in the neonate. Weight gain during pregnancy was associated with increased neonatal fatness and length, while prepregnant weight for height was associated with neonatal fatness independent of neonatal length.

Atypical Menkes steely hair disease.

Menkes steely hair disease (MSHD) is a rare disorder which typically results in severe mental retardation and death in early childhood. A 21-month-old boy with an atypical milder form was presented by Procopis et al. [1981]. A second child with the atypical form is presented here who has survived to age 9 years and is doing well clinically.

Clinical application of DNA analysis in a family with OTC deficiency.

We describe the clinical application of DNA restriction fragment analysis to the genetic evaluation of a family with a child deficient in ornithine transcarbamylase (OTC). The results of protein loading studies and the interpretation of the DNA haplotype profiles for the human OTC gene are reported. DNA restriction fragment analysis may be a reliable technique for the prenatal diagnosis of OTC deficiency and identification of obligate carriers of this gene.

Evaluation for Hsp70 as a biomarker of effect of pollutants on the earthworm Lumbricus terrestris.

Induction of heat shock proteins (Hsps) is often associated with a cellular response to a harmful stress or to adverse life conditions. The main aims of the present study were (1) to assess if stress-induced Hsp70 could be used to monitor exposure of the earthworm species Lumbricus terrestris to various soil pollutants, (2) to assess the specificity of pollutants in their tissue targeting and in Hsp70 induction, and (3) to evaluate if dose-response relationships could be established and if the stress-response observed was specific. The midgut/intestinal tissues of L. terrestris are shown to express an inducible member of the Hsp70 family after heat shock treatment in vitro and exposures to different soil toxicants in vivo (re: artificial soil). Short-term (24-72 hours) and long-term (14-16 days) exposures to the chemical standards chloroacetamide and pentachlorophenol and to heavy metals (Pb++, Cd++, Cu++, and Hg++) also affected the earthworms, and Hsp70 was induced in their midgut/intestinal tissues. After a 3-day exposure to heavy metals, the level of Hsp70 induction in the midgut/intestinal tissues appears to correlate well with the reported in vivo and in vitro toxicity data. Comparatively, in proximal and midbody wall muscle tissues of animals exposed to the heavy metals, a decrease in expression of Hsp70 was sometimes detected. Thus Hsp analysis by Western blot in L. terrestris tissues and particularly in the midgut/intestine proved to be a suitable and sensitive assay for adverse effects in earthworms and showed a good level of reproducibility despite some individual variations. The use of pristine/nonexposed animals transposed into contaminated environments as in the present study should therefore be of high ecological relevance. Induction of Hsp70 in earthworms should represent not only a good wide-spectrum biomarker of exposure but also a biomarker of effect since known toxicants altered gene expression in tissues of these animals, as contrasted with a simple accumulation of Hsp. Hence, the detection of Hsp70 in earthworms can constitute an early-warning marker for the presence of potentially deleterious agents in soils, with L. terrestris in particular and earthworms in general acting as potential sentinel animal species.

Expression of recombinant human glucose-dependent insulinotropic polypeptide in Escherichia coli by sequence-specific proteolysis of a protein A fusion protein.

Glucose-dependent insulinotropic polypeptide (GIP) is a forty-two amino acid hormone that stimulates the secretion of insulin from the pancreatic B-cells in the presence of elevated glucose concentrations. The human GIP gene with the human A alpha-fibrinopeptide sequence was synthesized and linked to the Staphylococcus aureus protein A gene in the vector pRIT2T. This plasmid was expressed in Escherichia coli, and the resulting fusion protein consisted of three domains: protein A for ease of purification, fibrinopeptide sequence for thrombin cleavage and human GIP. The GIP was subsequently cleaved from the fusion protein with alpha-thrombin. The identity of the recombinant human GIP was confirmed by SDS-PAGE, ELISA, HPLC and amino-terminal amino acid sequence analysis. This recombinant product was shown to have comparable insulinotropic activity to porcine GIP in the isolated perfused pancreas.

MPTP produces a mosaic-like pattern of terminal degeneration in the caudate nucleus of dog.

This paper describes the spatial pattern of terminal degeneration in the caudate nucleus and putamen of the dog following an injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Marked inhomogeneities in the filed of terminal degeneration were found in the head of the caudate nucleus, which are reminiscent of the fundamental patch/matrix organization of the striatum. Using MPTP as a selective lesioning method, our results provide further evidence that the dopaminergic, nigrostriatal projection has a heterogeneous organization.