Physical functioning and risk for sleep disorders in US adults: results from the National Health and Nutrition Examination Survey 2005-2014.

OBJECTIVES: Sleep disorders (SDs), particularly problems with falling asleep or daytime sleepiness, have negative impact on health and longevity. Sleep deprivation is also associated with a decline in physical functioning (PF) that mediates the ability to perform activities of daily living. But it remains unknown if deterioration in PF can predict the risk of having a SD. Therefore, the purpose of the present study is to assess the risk of SD associated with PF status in the US adult population. STUDY DESIGN: Cross-sectional study design with data from the National Health and Nutrition Examination Survey from year 2005 to year 2014. METHODS: PF limitation is assessed by reported difficulty in performing 10 tasks selected from PF questionnaire. SD is identified by subjective description of presence of doctor diagnosed SD. Also, five categories of comorbidities that caused difficulty in carrying out these tasks were created. RESULTS: The adults with self-reported PF limitation have 41% higher odds of having a SD (odds ratio [OR] = 1.41, 95% confidence interval [CI] = 1.22-1.59). Moreover, participants having cognitive problems and cardiovascular and pulmonary disorders as secondary conditions that cause difficulty in PF have 145% and 28% higher odds (OR = 2.45 and 1.28; 95% CI = 2.01-3.01 and 1.08-1.53, respectively) of having a SD. Also, females have a 27% lower odds of having a SD than males (OR = 0.73, 95% CI = 0.63-0.83). CONCLUSION: Risk for SD is associated with increasing level of functional disability. We advocate the importance of engagement in physical activities to prevent or delay the onset of SD.

Patterns and risk factors for locoregional failures after mastectomy for breast cancer: an International Breast Cancer Study Group report.

BACKGROUND: Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT). PATIENTS AND METHODS: Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years. RESULTS: Ten-year cumulative incidence for chest wall recurrence of >15% was seen in patients aged <40 years (16.1%), with ≥4 positive nodes (16.5%) or 0-7 uninvolved nodes (15.1%); for supraclavicular failures >10%: ≥4 positive nodes (10.2%); for axillary failures of >5%: aged <40 years (5.1%), unknown primary tumor size (5.2%), 0-7 uninvolved nodes (5.2%). In patients with 1-3 positive nodes, 10-year cumulative incidence for chest wall recurrence of >15% were age <40, peritumoral vessel invasion or 0-7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site. CONCLUSION: PMRT to the chest wall and supraclavicular fossa is supported in patients with ≥4 positive nodes. With 1-3 positive nodes, chest wall PMRT may be considered in patients aged <40 years, with 0-7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla.

Ecological Aspects of Amphibian Metamorphosis: Nonnormal distributions of competitive ability reflect selection for facultative metamorphosis.

A synthetic theory of the ecology of amphibian metamorphosis is founded on the observation that the large variation in length of larval period and body size at metamorphosis typical of a particular species of amphibian cannot be directly explained by differences in dates of hatching or egg sizes. It is proposed that as development proceeds, variation in exponential growth coefficients causes a trend from a normal distribution to a skewed distribution of body sizes. The degree of skewing increases and the median of the distribution decreases with increasing initial densities of populations. The relative advantages of the largest members of a cohort may arise from a variety of mechanisms including the production of growth inhibitors, interference competition, and size-selective feeding behavior. These mechanisms result in a nonnormal distribution of competitive ability, a possible source of the density-dependent competition coefficient found in systems with many species (1). In our model the ranges of body sizes and dates of metamorphosis are determined by a minimum body size that must be obtained and a maximum body size that will not be exceeded at metamorphosis. Between these two size thresholds the endocrinological initiation of metamorphosis is expected to be related to the recent growth history of the individual larva. Species that exploit uncertain environments will have a wide range of possible sizes at metamorphosis. Species exploiting relatively certain environments will have a narrower range. The evolution of neoteny and direct development logically follow from the application of these ideas to the ecological context of the evolution of amphibian life histories. Species that live in constant aquatic habitats surrounded by hostile environments (desert ponds, caves, high-altitude lakes) may evolve permanent larvae genetically incapable of metamorphosis. Other populations may evolve a facultative metamorphosis such that populations are a mixture of neotenes and terrestrial adults. Direct development results from selection to escape the competition, predation, and environmental uncertainty characteristic of some aquatic habitats and is usually accompanied by parental care. The relation between our ecological model and the physiological mechanisms that initiate metamorphosis can only be suggested and it remains an open problem for developmental biologists.

Transmission dynamics of the amphibian ranavirus Ambystoma tigrinum virus.

Transmission is central to pathogen fitness and strongly influences the impact of pathogens on host populations. Particularly important to transmission dynamics is the distinction between direct transmission requiring close physical contact (e.g. bumping, fighting, or coughing) and indirect transmission from environmental sources such as contaminated substrates. We present data from 4 experiments addressing the form, routes, and timing of transmission of Ambystoma tigrinum virus (ATV) among tiger salamanders Ambystoma tigrinum nebulosum. Our data suggest that ATV is efficiently transmitted by direct interactions between live animals (bumping, biting and cannibalism) as well as by necrophagy and indirectly via water and fomites. Determining which form of transmission is most important in nature is essential for understanding transmission at the population level. Our experiments also revealed an important temporal aspect of infectiousness: larval salamanders become infectious soon after exposure to ATV and their propensity to infect others increases with time. These results begin to clarify the mechanisms and dynamics of ATV transmission and lead to key questions that need to be addressed in future research.

Immunolymphoscintigraphy for the detection of lymph node metastases from breast cancer.

The presence of metastases in the regional lymph nodes is the major prognostic factor in breast cancer in the absence of overt distant metastases and is also an important indicator of the need for adjuvant therapy in "early" breast cancer. Currently, the accurate assessment of axillary lymph node status requires axillary dissection which has an associated morbidity. An alternative method of identifying patients who are "node positive" has been developed by means of immunolymphoscintigraphy with s.c. administered radioiodinated monoclonal antibody. The 131I-labeled anti-breast cancer antibody (RCC-1; 400 micrograms) and cold iodine-labeled "blocking" antibody (Ly-2.1; 2 mg which is nonreactive with breast cancer) were injected s.c. into both arms and scintigraphy images were obtained 16-18 h after the injection, using the axilla contralateral to the side of the breast cancer as the control. Studies were reported as positive (and therefore indicative of lymph node metastases) if the amount of background-subtracted radioactive count in the axilla of interest exceeded the normal side by a radio equal to or greater than 1.5:1.0 as assessed by computer analysis. In 38 of 40 patients the findings on scintigraphy were correlated with operative and histopathological findings on the axillary dissection specimen or cytological findings of fine needle aspiration of axillary lymph nodes. In a prospective study of 26 patients, the method is more sensitive (86%) and specific (92%) than preoperative clinical assessment (57% sensitivity, 58% specificity) in the detection of axillary lymph node metastases; and by combining both modalities of assessment, there was an improvement in the sensitivity (100%) but a deterioration in the specificity (50%). There was no significant complication from this essentially outpatient procedure and only 1 of 40 patients developed a human anti-mouse antibody response. This novel and safe method of imaging may become a most useful adjunct in the surgical management of breast cancer.

Multicycle high-dose chemotherapy and filgrastim-mobilized peripheral-blood progenitor cells in women with high-risk stage II or III breast cancer: five-year follow-up.

PURPOSE: To determine the safety and efficacy of multiple cycles of dose-intensive, nonablative chemotherapy in women with poor-prognosis breast cancer. PATIENTS AND METHODS: Women with stage II breast cancer and 10 or more involved nodes or four or more involved nodes and estrogen receptor-negative tumors and women with stage III disease received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2, with progenitor cell and filgrastim support every 28 days (n = 79) or 21 days (n = 20). Patients were reviewed at least twice yearly thereafter. Twenty-six patients had bone marrow and apheresis collections assessed for the presence of micrometastatic tumor cells. RESULTS: Ninety-nine women (median age, 43 years; range, 24 to 60 years) were treated. Ninety-two completed all three cycles of chemotherapy. The major toxicity was severe, reversible myelosuppression that was more prolonged with successive cycles, and this did not differ between patients given treatment every 28 days and those treated every 21 days. Febrile neutropenia occurred in 176 (61%) of 287 cycles. Severe mucositis (grade 3 or 4) occurred in 23% of cycles but tended to be short-lived and was reversible. The cardiac ejection fraction fell by a median of 4% during treatment, and three patients developed evidence of cardiac failure after chemotherapy. Two patients (2%) died of acute toxicity. Three of 26 patients had evidence of circulating micrometastatic tumor cells. The actuarial distant disease-free and overall survival rates at 60-month follow-up were 64% (95% confidence interval [CI], 53% to 75%) and 67% (95% CI, 56% to 78%), respectively. CONCLUSION: Multiple cycles of dose-intensive, nonablative chemotherapy is a feasible and safe approach. Disease control and survival are similar to those in other studies of myeloablative chemotherapy in poor-prognosis breast cancer. The regimen is being evaluated in a randomized trial of the International Breast Cancer Study Group.

Adjuvant treatment of high-risk breast cancer using multicycle high-dose chemotherapy and filgrastim-mobilized peripheral blood progenitor cells.

Women with primary breast cancer associated with extensive axillary node involvement or large primary tumors have a very poor prognosis despite treatment with standard-dose adjuvant chemotherapy. In an attempt to improve the outlook of these patients, we investigated the safety and feasibility of delivering three cycles of high-dose epirubicin and cyclophosphamide supported with filgrastim-mobilized peripheral blood progenitor cells (PBPC). Fifteen previously untreated women, median age 50 (range, 30-58) years, with poor prognosis early stage breast cancer received filgrastim (12 microgram/kg daily for 6 days) prior to chemotherapy to mobilize progenitor cells. Patients were then given three cycles of epirubicin (200 mg/m2) and cyclophosphamide (4 g/m2) at planned 28-day intervals, each followed by infusion of one third of the PBPC collected and daily administration of filgrastim (5 microgram/kg s.c.). Three leukaphereses collected a median of 114.9 (range, 22.7-273.5) x 10(4) granulocyte-macrophage-colony-forming cells/kg body weight. Hemopoietic recovery was rapid after each cycle, and there was no correlation between the rate of recovery and the number of granulocyte-macrophage-colony-forming cells infused. There was a small but significant progressive delay in recovery from hematological and nonhematological toxicities across the three cycles. Left ventricular ejection fraction fell to below 50% in eight (53%) patients, but none developed congestive cardiac failure. Two patients did not complete three cycles because of insufficient PBPC for a third cycle (n = 1) and 2-mercaptoethane sodium sulfonate- related drug reaction during the second cycle (n = 1). There were no deaths during the study or during the follow-up period (median, 70 weeks; range, 50-85 weeks), and no late toxicities occurred. Therefore, we concluded that the delivery of multiple cycles of nonmyeloablative, dose-intensive chemotherapy supported by PBPC and filgrastim is safe, and may be widely applicable to a variety of common chemosensitive cancers with a poor prognosis. The efficacy of three cycles of high-dose epirubicin and cyclophosphamide is to be compared with standard-dose chemotherapy in a randomized trial in patients with high-risk, operable stage II and III breast cancer.

Transient compulsive foraging behavior associated with crack cocaine use.

Compulsive foraging behavior associated with use of crack cocaine involves compulsively searching the environment for possibly misplaced pieces of crack. Of 41 crack cocaine addicts evaluated, 33 (80.5%) reported at least some compulsive foraging associated with use of crack; 21 (51.2%) reported such behavior as always associated with crack use. The mean length of time spent in compulsive foraging was 90 minutes. Cocaine-induced foraging may represent a drug-induced model of a type of compulsive behavior.

Assessment of protein nutrition in surgical patients--the value of anthropometrics.

In order to evaluate the reliability of anthropometry in assessing protein stores we have compared, in 10 normal adults and 82 surgical patients with varying degrees of weight loss, measurements of weight/height, arm circumference, arm muscle circumference, and arm muscle area with direct measurements of body nitrogen using in vivo neutron activation analysis. Anthropometry is reliable for the assessment of protein nutrition in groups of patients (for 100 patients 95% confidence limits are +/- 30 g nitrogen) but the magnitude of variance shown makes it inappropriate for assessing the individual as a single measurement (95% confidence limits are +/- 300 g nitrogen). Repeat measurements were made after 2 weeks on 35 patients and there was no correlation between changes in body nitrogen and changes in the anthropometric measurements. Anthropometry is not reliable in following changes in body nitrogen in individual patients over short periods of time.

Plasma proteins in patients receiving intravenous amino acids or intravenous hyperalimentation after major surgery.

Eleven plasma proteins were compared for each of three groups of 10 closely matched patients before and 15 days after rectal excision who were receiving an addition to oral diets the following parenteral solutions by central venous catheter: 1) no hyperalimentation, 2) hypertonic glucose plus amino acids, or 3) amino acids alone. Plasma transferrin, prealbumin, and retinol-binding protein were normal before surgery in all but seven patients. Postoperatively, concentrations were decreased, but were restored to normal after full hyperalimentation whereas they were significantly less and lower than normal in controls and patients receiving amino acids. Acute phase proteins were higher than normal before surgery and also 15 days later. Lower values in patients receiving hyperalimentation were mainly due to hydration compared with higher values in the other groups caused by the higher incidence of sepsis. It is concluded that full hyperalimentation after major surgery restores "visceral" proteins more rapidly than by infusion of amino acids alone and is associated with fewer clinical complications.

A randomised study to compare the effect of the luteinising hormone releasing hormone (LHRH) analogue goserelin with or without tamoxifen in pre- and perimenopausal patients with advanced breast cancer.

The use of goserelin with or without tamoxifen was investigated in a randomised multicentre study involving 318 pre- and perimenopausal advanced breast cancer patients. With a median follow-up of 93 weeks, 31% of goserelin-treated patients had objective responses (UICC criteria) compared with 38% of goserelin plus tamoxifen-treated patients (P = 0.24). There was a modest benefit in favour of combination therapy in time to progression (P = 0.03) but not in survival (P = 0.25). Median follow-up for survival was 117.5 weeks. Median times for disease progression and survival were 23 and 127 weeks in the goserelin alone group and 28 and 140 weeks in the combination group, respectively. In 115 patients with skeletal metastases only, significant differences in favour of combination therapy were seen in response rate, time to progression and survival. Both treatments were well tolerated and no additional safety issues were associated with combination therapy.

Vascular myxolipoma ("angiomyxolipoma") of the spermatic cord.

We report a case of vascular myxolipoma of the spermatic cord occurring in a 32-year-old man. Clinically, the lesion was mobile and tender. Pathologically, the tumor was encapsulated and rubbery with a beige-yellow gelatinous cut surface. Microscopically, the lesion consisted of adipose tissue with extensive areas of myxoid change and an abundance of thin and thick-walled blood vessels. We consider this tumor a vascular type of myxolipoma and propose the term angiomyxolipoma. The lesion should be distinguished from liposarcoma and aggressive angiomyxoma, which have malignant or aggressive clinical course.

Absence of serum prostate-specific antigen and loss of tissue immunoreactive prostatic markers in advanced prostatic adenocarcinoma after hormonal therapy: a report of two cases.

We report two cases of advanced prostatic adenocarcinoma (PA) showing complete loss of three tissue immunoreactive prostatic markers, ie, prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and Leu-7 (CD57), with absence of elevated serum PSA level, despite tumor progression after hormonal therapy with or without radiotherapy. The pretreatment serum PAP in the first case and serum PAP and PSA in the second case were elevated. In both cases, the prostatic adenocarcinoma in the initial transurethral resection specimens showed positive immunoreactivity with three prostatic markers. After treatment, in both cases, the serum PSA were undetectable, and tumor cell immunostaining for three prostatic markers was negative. In addition, the posttreatment tumors in both cases showed increased number of tumor cells with neuroendocrine differentiation in comparison those in the pretreatment tumors. Although early PA without elevated serum level of PSA is common, advanced PA with absence of elevated serum PSA, associated with presence of tissue immunoreactive prostatic markers are rare. This is the first report of advanced prostatic adenocarcinomas showing loss of tumor cell prostate-specific markers with absence of elevated serum PSA level after hormonal therapy despite tumor progression.

Strongyloidiasis in immunosuppressed patients.

An increasing number of severe, even fatal cases of strongyloidiasis in patients on immunosuppressive drugs are being reported. During a 26 month period, three severe cases of Strongyloides stercoralis infestation were diagnosed in patients who were on steroid therapy. These cases are of special interest because of the following factors. Firstly, all the patients lived in a nonendemic metropolitan area. Secondly, a single stool specimen from one patient contained several distinct developmental stages of the parasite's life cycle. This finding appears to be unique considering the fact that the patient had not been administered a purgative or anthelminthic. Lastly, a surviving renal transplant patient continues to have persistent strongyloidiasis despite repeated Mintezol (thiabendazole) therapy.

Glucose, fat, and protein kinetics in patients with primary and secondary hyperparathyroidism.

We performed a series of isotopic studies in 16 normal volunteers, four patients with secondary hyperparathyroidism (SHPT), and in nine patients with primary hyperparathyroidism (PHPT). Using the primed constant infusion of stable and radioisotopes, we have determined glucose, glycerol, free fatty acids, and urea kinetics, as well as glucose oxidation. Measurements were performed both in the basal state and during glucose infusion (4 mg/kg body weight/min). Compared with normal volunteers, PHPT patients are intolerant of glucose because of a limited suppression of endogenous glucose turnover during glucose infusion (34% versus 96% suppression). In addition, the plasma cortisol level increased in the PHPT patients during glucose infusion. Glucose oxidation and fat kinetics in both PHPT patients and volunteers were similar, but the rate of net protein loss was significantly greater in the PHPT patients than in the volunteers (2.1 +/- 0.5 versus 1.4 +/- 0.2 gm/kg/day). Rates of VO2 in the PHPT patients and volunteers were similar, but the value in the SHPT patients was higher (120 +/- 9 versus 142 +/- 20 mumol/kg/min for PHPT and SHPT patients, respectively). The SHPT patients had significantly increased rates of glucose turnover, glucose clearance, and glycerol turnover, compared with the other two groups, as well as an increased reliance on glucose for energy. We conclude from these studies that (1) SHPT patients are catabolic and have increased rates of glucose and fat turnover; (2) PHPT patients have limited suppression of endogenous glucose turnover after glucose infusion compared with volunteers and higher rates of net protein loss; (3) fat metabolism and glucose utilization are unimpaired in PHPT patients; and (4) these alterations in metabolism and hormonal response to glucose infusion suggest that some of the symptoms seen in these patients may have a metabolic-hormonal basis.

Left-sided colectomy with retroileal colorectal anastomosis.

Following resection of the sigmoid and descending colon for cancer or extensive diverticular disease, it may be impossible to make a colorectal anastomosis due to inadequate length of the residual transverse colon. To correct this problem, the remaining transverse colon may be pulled into the pelvis by making a "window" in the terminal part of the ileal mesentery. From January 1966 to January 1975, 302 resections of the descending colon with colorectal anastomoses were performed by one of the authors (R.B.T.) for upper sigmoid cancer and extensive diverticulitis at the Cleveland Clinic. Eleven patients (4%) had retroileal colorectal anastomoses. The retroileal apprach is a technical aid when performing an extensive left-sided colectomy and/or when there is insufficient length of residual transverse colon to make a tension-free colorectal anastomosis.

"Ghost" forms of Giardia lamblia cysts initially misdiagnosed as Isospora.

Because of their distinctive morphology the cysts of Giardia lamblia usually are not mistaken for cysts or eggs of other intestinal parasites. At a hospital laboratory in Kentucky a case of giardiasis was encountered in which the initial fecal examination revealed only degenerated cysts of Giardia which were mistaken for the oocysts of Isospora at the one-sporoblast stage.

Toward further reducing wound infections in cardiac operations.

BACKGROUND: Serious wound infections such as mediastinitis still occur at a rate of 0.8% to 2.0%, according to the most recently published cardiac operative series. METHODS: Data from careful surveillance for infection have been collected prospectively during a 4.5-year period on 1,717 patients who underwent cardiac operations performed under direct ultraviolet C radiation. RESULTS: The rate for mediastinitis was 0.23%, and for deep incisional infection without mediastinitis, 0.12%; these rates are significantly lower than those for eight of nine of the most recently published cardiac series. When our infection rates were stratified using the National Nosocomial Infection Surveillance risk index, they were also significantly lower in the most important risk categories than the corresponding stratified rates collected from the participating hospitals of the Centers for Disease Control and Prevention National Nosocomial Infection Surveillance system. CONCLUSIONS: Though we lack the proof that only a large, randomized study might provide, certainly, one possible explanation for our lower wound infection rate was the use of bactericidal ultraviolet C radiation during operation. This is a simple and effective means of minimizing operating room airborne bacteria as one possible source of these infections.

Experience with lyophilized human dura for treatment of Peyronie disease.

Peyronie disease was treated by excision of the plaque and patch grafting with lyophilized human dura in 17 patients. Results were satisfactory as far as correction of penile curvature was concerned, but the incidence of impotence and glans hypoesthesia was disappointing. Less complex operations such as the Nesbit procedure may be a better choice of treatment for the surgical management of Peyronie disease.

Corporeal septal necrosis secondary to penile cylinder aneurysmal dilatation.

A case report of necrosis of the corporeal septum secondary to aneurysmal dilatation of a penile prosthesis cylinder is presented. Recommendations are made for surgical management.