[One stage combined endoscopic and per-oral buccal fat pad approach for large oro-antral-fistula closure with secondary chronic maxillary sinusitis].

There are numerous surgical approaches for oro-antral-fistula (OAF) closure. Secondary sinus disease is still considered by many experts a relative contra indication for primary closure. To describe a single-stage combined endoscopic sinus surgery and per-oral buccal fat pad (BFP) flap approach for large OAF causing chronic maxillary sinusitis. The records of all the patients with OAF and chronic manifestations of secondary rhinosinusitis that were treated between 2010 and 2013 in our tertiary care medical center were reviewed. The exclusion criteria were: OAF 5 mm, resolved sino-nasal disease, OAF secondary to malignancy, recurrent fistula, medical history that included radiotherapy to the maxillary bone and age <18 years. Each procedure was performed by a team consisting of a rhinologist and a maxillofacial surgeon. The surgical approach included an endoscopic middle antrostomy with maxillary sinus drainage, and a per-oral BFP regional flap for OAF closure. Total OAF closure, complications and need for revision surgeries. Forty-five patients that underwent OAF closure together with sinus surgery using a combined endoscopic sinus surgery (ESS) and BFP flap approach met the inclusion criteria. There were 28 males and 17 females with a mean ± SD age of 53.5 ± 14.9 years (range 22-80 years). The presenting signs and symptoms included purulent rhinorrhea (n = 22, 48.9%), foreign body in sinus (n = 10, 22.2%) nasal congestion (n = 7, 15.5%), halitosis (n = 6, 13.3%) and pain (n = 5, 12.2%). Surgical complications included local pain (n = 2, 4.4%), persistent rhinitis (n = 2, 4.4%) and synechia (n = 1, 2.2%). One patient required revision surgery due, to an unresolved OAF. The OAF of all the other 44 patients (97.8%) was closed after the first procedure and the paranasal sinuses on the treated side were completely recovered. The mean follow-up time for the group was 7.6 ± 4.3 months (7-21 months), and no untoward sequelae or recurrence were reported. Combined, one step, endoscopic Maxillary sinus drainage together with per-oral BFP flap approach is an efficacious surgical approach for safe closure of OAFs that are complicated with secondary chronic maxillary sinusitis.

Advanced stage adenoid cystic carcinoma of the sinonasal cavity and skull base: a retrospective 20-year analysis.

The purpose was to describe the presentation, treatment, and outcomes of skull base invasive sinonasal adenoid cystic carcinoma (SNACC). A retrospective cohort study was performed of all consecutive patients aged >18 years at the time of presentation, who were diagnosed as having primary SNACC with skull base invasion, at a single tertiary referral center between 2002-2022. Eighteen patients were enrolled (11 female, 7 male; mean ± standard deviation age at initial presentation 55 ± 14 years). Nasal obstruction was the most prevalent sign/symptom, followed by facial numbness, facial swelling, epistaxis and facial pain. The most common tumor epicenter was the maxillary sinus, followed by nasal cavity and ethmoidal sinuses. Middle fossa was invaded in 13 cases and anterior fossa in eight. Orbital invasion was evident in eight patients. Positive surgical margins were identified macroscopically in five patients and were not associated with worse overall survival (OS) (P = 0.356) or disease-specific survival (DSS) (P = 0.732). Perineural invasion was associated with reduced OS (P = 0.037) and DSS (P = 0.044). SNACC is a slowly progressing, rare entity that is usually at an advanced stage at diagnosis. Orbit and skull base invasion is common, necessitating destructive surgery with frequent free flap reconstruction. Perineural invasion is common and associated with reduced overall survival.

Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research priorities for mucocutaneous bleeding disorders.

BACKGROUND: Excessive or abnormal mucocutaneous bleeding (MCB) may impact all aspects of the physical and psychosocial wellbeing of those who live with it (PWMCB). The evidence base for the optimal diagnosis and management of disorders such as inherited platelet disorders, hereditary hemorrhagic telangiectasia (HHT), hypermobility spectrum disorders (HSD), Ehlers-Danlos syndromes (EDS), and von Willebrand disease (VWD) remains thin with enormous potential for targeted research. RESEARCH DESIGN AND METHODS: National Hemophilia Foundation and American Thrombosis and Hemostasis Network initiated the development of a National Research Blueprint for Inherited Bleeding Disorders with extensive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them. They recruited multidisciplinary expert working groups (WG) to distill community-identified priorities into concrete research questions and score their feasibility, impact, and risk. RESULTS: WG2 detailed 38 high priority research questions concerning the biology of MCB, VWD, inherited qualitative platelet function defects, HDS/EDS, HHT, bleeding disorder of unknown cause, novel therapeutics, and aging. CONCLUSIONS: Improving our understanding of the basic biology of MCB, large cohort longitudinal natural history studies, collaboration, and creative approaches to novel therapeutics will be important in maximizing the benefit of future research for the entire MCB community.

More people experience mucocutaneous bleeding (MCB), affecting tissues like skin and gums, than have hemophilia A or B. MCB is not understood as well as hemophilia. Common types of MCB include nosebleeds, bleeding gums, heavy menstrual bleeding, and digestive tract bleeding. Mucocutaneous inherited bleeding disorders include inherited platelet disorders, hereditary hemorrhagic telangiectasia (HHT), hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS), von Willebrand Disease (VWD), and others. Diagnosing and treating MCB is complicated and sometimes medical providers dismiss the bleeding that patients report when they cannot find a medical explanation for it. Many people with mucocutaneous bleeding (PWMCB) do not receive the care they need; for example, women with VWD live with symptoms for, on average, 16 years before they are diagnosed in the US. This struggle to obtain care has important negative impacts on patients' physical and psychological health and their quality-of-life. The National Hemophilia Foundation (NHF), a large US bleeding disorders patient advocacy organization, set out to develop a National Research Blueprint for Inherited Bleeding Disorders focused on community priorities. They brought together a group of patients, providers, and researchers with MCB expertise to identify the research that would most improve the lives of PWMCB through targeted and accessible diagnostics and therapies. We report in this paper that research is needed to better understand the biology of MCB and to define the mechanisms of disease in these disorders. We also describe high priority research questions for each of the main disorders, novel therapeutics, and aging.

Quality of life after mandibulectomy: the impact of the resected subsite.

The purpose of this study was to identify the factors that impact the quality of life (QOL) scores of patients undergoing mandibulectomy. All patients with a diagnosis of an oral cavity neoplasm involving the mandible who underwent a mandibulectomy between January 1, 2000 and December 31, 2015 and completed a University of Washington QOL questionnaire (UW-QOL) were included in the study. Fifty-eight patients fulfilled all inclusion criteria and completed the UW-QOL questionnaire. Forty patients (69%) underwent a segmental mandibulectomy and 18 patients underwent a marginal mandibulectomy. Forty-eight patients (82.7%) had a free flap reconstruction. There was no significant difference in the QOL scores between patients who underwent a marginal or a segmental mandibulectomy. In contrast, patients who underwent symphysial resection reported significantly worse scores in various domains compared to patients with body or ramus segmental mandibulectomy. Patients who underwent a segmental mandibulectomy that included the symphysis had worse outcomes in chewing, recreation, health-related and social QOL domains compared to those whose mandibulectomy did not include the symphysis.

Regional isolated limb perfusion of melanoma intransit metastases using mechlorethamine (nitrogen mustard).

Forty-two patients with intransit metastases of melanoma in a limb were treated by isolated regional perfusion chemotherapy using mechlorethamine (nitrogen mustard). Group 1 (n = 12) underwent treatment at low dose, less than 0.35 mg/kg, or low temperature, less than 38 degrees C. Group 2 (n = 30) received higher doses, 0.35 to 0.6 mg/kg, plus heat at 38 degrees C to 41 degrees C. No patient had evidence of disease outside the limb at the time of perfusion. The median follow-up time was 48 months (range, 1 to 9 years). Of the 42 patients, 29 had measurable lesions that responded as follows: group 1, complete response (CR) in two of ten and partial response (PR) in none; group 2, CR in six of 19 and PR in six of 19. The combined CR and PR rate of 12 of 19 in group 2 was significantly higher than that of group 1 (P less than .05). CR lasted only 2 months in the two patients of group 1, but persisted in the six patients of Group 2, four of whom are still alive free of disease at 16, 21, 33, and 40 months. Relapse-free control of disease in the limb was achieved in 36% of the patients in group 2 at 24 months, compared with 0% in group 1 (P less than .05). An overall survival of 74% at 48 months was observed in group 2, significantly higher than that of 64% for group 1 (P less than .05). The status of the regional lymph nodes (RLN) and the number of metastases did not affect tumor response. However, 77% of RLN-negative patients survived 48 months, in contrast to only 38% of RLN-positive patients (P less than .05). One patient died postoperatively of myocardial infarction. No serious systemic toxicity developed. Two patients who underwent repeat salvage perfusions developed a reversible peripheral neuropathy in the limb. Limb function was good after treatment, and dramatically improved in patients who had advanced satellitosis that responded to treatment. These results suggest that heated limb perfusion using mechlorethamine at an adequate dose can offer long-term control of intransit metastases in approximately one third of these patients, with preservation of good limb function and possible prolongation of survival.

Basal glucagon replacement in chronic glucagon deficiency increases insulin resistance.

To evaluate the role of glucagon in insulin-mediated glucose metabolism, we studied four men and four women, ranging in age from 30-73 yr (mean +/- SEM, 54 +/- 5) who had undergone complete pancreatic resection for cancer or chronic pancreatitis 16-58 mo previously. The patients had undetectable C-peptide levels and established lack of biologically active 3500 mol wt glucagon. Euglycemic insulin clamp studies were performed with a 40 mU X m-2 X min-1 insulin infusion in the basal, post-absorptive, insulin-withdrawn state, before and during the last 3 h of a 72-h glucagon replacement-dose infusion (1.25 ng X kg-1 X min-1). In four patients, hepatic glucose production was determined by a primed-constant infusion of 3-[3H]glucose. Monocyte insulin-binding studies, pre- and postglucagon, were performed in all patients. The 72-h glucagon infusion, resulting in mean plasma glucagon levels of 124 +/- 7 pg/ml, caused a significant rise in the mean plasma glucose level (249 +/- 8 versus 170 +/- 13 mg/dl preglucagon) and a sixfold increase in mean 24-h glucose excretion. Both with and without glucagon, euglycemic hyperinsulinemia achieved identical and complete suppression of hepatic glucose production. The mean glucose utilization rate (4.70 +/- 0.36 mg X kg-1 X min-1 preglucagon) was significantly decreased by glucagon replacement (3.83 +/- 0.31 mg X kg-1 X min-1, P less than 0.02). Mean glucose clearance was also diminished with glucagon (4.49 +/- 0.32 versus 5.73 +/- 0.45 ml X kg-1 X min-1 preglucagon, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluating cholesterol screening. The importance of controlling for regression to the mean.

OBJECTIVES: To determine the overall impact of a voluntary cholesterol screening program and to assess the importance of controlling for regression to the mean when evaluating the impact on higher-risk subgroups. DESIGN: Longitudinal study comparing baseline survey and cholesterol results with those obtained 17 months later, with adjustment for regression to the mean. SETTING: Participants were seen at three sites: an academic teaching hospital, an intermediate-care hospital, and a suburban community center. PARTICIPANTS: One thousand fifty-three participants were enrolled in a voluntary cholesterol screening program. MEASUREMENTS/MAIN RESULTS: Of 1053 study enrollees, 785 (75%) completed a follow-up questionnaire and 656 (62%) returned for follow-up cholesterol tests. Among all participants at high risk, measured cholesterol levels were 0.66 mmol/L (25.5 mg/dL) lower at follow-up, but 58% of this apparent change (0.38 mmol/L [14.7 mg/dL]) was attributable to the statistical phenomenon of regression to the mean. Among all participants at increased (both high and moderate) risk, after controlling for regression to the mean, reductions in cholesterol levels were significant for those younger than 60 years (-0.28 mmol/L [-10.8 mg/dL]; 95% confidence interval, -0.43 to -0.13; n = 390) but not for those 60 years or older (+0.007 mmol/L [+0.3 mg/dL]; 95% confidence interval, -0.16 to +0.17; n = 266). CONCLUSIONS: For subjects found at high risk in a cholesterol screening program, more than half of the apparent beneficial change in cholesterol level is attributable to regression to the mean. For participants older than 60 years, no clear benefit of cholesterol screening was documented.

Transforming growth factor-alpha in human implantation trophoblast: immunohistochemical evidence for autocrine/paracrine function.

Epidermal growth factor (EGF) and its receptor (EGF-R) have been demonstrated in human implantation sites. Transforming growth factor-alpha (TGF-alpha), a protein with extensive sequence homology to EGF and with equal affinity for the EGF-R, was localized immunohistochemically in early intrauterine and ectopic pregnancies. Within the same experiments, TGF-alpha immunostaining was more intense in ectopic than intrauterine pregnancies. In both groups, TGF-alpha immunostaining was moderate to intense in the syncytiotrophoblast (ST), light to moderate in the cytotrophoblast (CT), and moderate to intense in intermediate trophoblast (IT). In ST, TGF-alpha immunostaining localized to the cytoplasm and plasma membranes, including microvilli. No nuclear associated TGF-alpha was noted in ST. In CT, differential TGF-alpha immunostaining was noted between the villous and nonvillous CT. Villous CT demonstrated light to absent cytoplasmic TGF-alpha immunostaining with intense nuclear staining. In contrast, nonvillous CT revealed moderate to intense cytoplasmic staining without demonstrable nuclear staining. These results demonstrate the presence of immunoreactive TGF-alpha in all forms of trophoblast. The known presence of the EGF-R suggests an autocrine/paracrine role for TGF-alpha during human implantation.

Interleukin-6 differentially stimulates haptoglobin production by peritoneal and endometriotic cells in vitro: a model for endometrial-peritoneal interaction in endometriosis.

Based on our previous observation that peritoneal endometriotic (PE) lesions synthesize in vivo substantially more haptoglobin (Hp) than related eutopic tissues, we hypothesized that this increase in Hp production was due to endometrial-peritoneal interactions. As interleukin-6 (IL-6) stimulates Hp in other tissues and is produced by endometrial cells, we tested our hypothesis by evaluating the effects of IL-6 on Hp production by PE cells, normal peritoneal (P) cells, and eutopic endometrial cells from women with (UE-E) and without endometriosis (UE-C) using semiquantitative RT-PCR and enzyme-linked immunoabsorbent assay. Endogenous production of IL-6 was also assessed. Treatment with human recombinant IL-6 and dexamethasone significantly increased Hp production by P or PE cells in a dose- and time-dependent manner (P < 0.05). Hp messenger ribonucleic acid was not detected in UE-E and UE-C cells in the absence or presence of IL-6 and dexamethasone. PE and UE-E cells expressed significantly more IL-6 messenger ribonucleic acid than P and UE-C cells (P < 0.05). Moreover, UE-E cells secreted 6 times more IL-6 protein than UE-C cells (P < 0.05). These findings support our hypothesis and suggest a novel endometrial-peritoneal interaction whereby locally synthesized IL-6 and Hp may participate in the establishment and persistence of peritoneal endometriosis.

Immunohistochemical localization of transforming growth factor-alpha in human endometrium, decidua, and trophoblast.

Transforming growth factor-alpha (TGF-alpha) was localized immunohistochemically in human proliferative and secretory endometrium, decidua, and trophoblast from first, second, and third trimester pregnancies. In proliferative endometrium, TGF-alpha immunostaining was moderate to intense and localized predominantly to stromal cells, whereas glandular staining was absent to light. After ovulation, TGF-alpha staining was light within the stroma, but moderate to intense around spiral arterioles. Moderate to intense staining was also detected in glandular and surface epithelium in secretory endometrium, with no staining noted in subnuclear vacuoles. In hypersecretory endometrium, staining was predominantly epithelial. In decidua, TGF-alpha was detected in intermediate trophoblast and on the surface epithelium. In first trimester trophoblast, TGF-alpha was detected in both cytotrophoblast (CT) and syncytiotrophoblast. Cytoplasmic staining was light in CT and moderate to intense in ST, with particular staining of plasma membranes. Intense TGF-alpha staining of nuclear membranes in CT was noted. TGF-alpha staining was light to absent in second and absent in third trimester trophoblast. This study demonstrates immunoreactive TGF-alpha in tissues known to be responsive to epidermal growth factor, and also demonstrates the presence of immunoreactive TGF-alpha associated with nuclear membranes. Thus, TGF-alpha may play an autocrine/paracrine role in endometrial development and trophoblast function.

Immunohistochemical localization of transforming growth factor-beta in human implantation sites.

Transforming growth factor-beta (TGF beta), a protein known to antagonize many of the functions of the epidermal growth factor-receptor system, was localized immunohistochemically in unruptured ectopic pregnancies (EP) removed by salpingectomy (n = 8), uterine decidua from EP (n = 4), and decidua and trophoblast from electively terminated first trimester pregnancies (ETP; n = 8). Two rabbit polyclonal antisera that recognize both TGF beta 1 and beta 2 were used. Immunostaining for TGF beta was identified in all three forms of trophoblast, cytotrophoblasts, intermediate trophoblasts, and syncytiotrophoblasts, which were differentiated histologically and immunohistochemically. Moderate cytoplasmic immunostaining was found in villous cytotrophoblasts in both EP and ETP. Nonvillous (anchoring) cytotrophoblasts in these same tissues demonstrated moderate immunostaining adjacent to the villous and light immunostaining distal to the villous. In intermediate trophoblasts, moderate to intense immunostaining was seen in EP and ETP. Syncytiotrophoblasts demonstrated moderate cytoplasmic immunostaining in EP and ETP as well as moderate to intense staining of plasma membranes and microvilli. Nuclear staining was not evident in any form of trophoblast. TGF beta immunostaining was demonstrated in both glands and stroma of decidua from both EP and ETP; however, staining was more intense in decidua from ETP. With the known presence of TGF beta receptors and mRNA in placenta, these results suggest an autocrine/paracrine role for TGF beta regulation of endometrial-trophoblast function during human implantation.

Thermogenic and nitrogen response to submaximal exercise in parenterally repleted normal man.

To determine whole-body energy and nitrogen responses to submaximal exercise during repletion levels of intravenous feeding (IVF), five normal male volunteers were hospitalized and underwent serial changes in nutritional intake consisting of weight-maintaining oral feeding (4 d), starvation (10 d), and weight-increasing parenteral feeding (10 d). Twelve-hour aliquots for urinary nitrogen, creatinine, and 3-methylhistidine were collected during the final 36 h of oral feeding and IVF. During these experimental periods, indirect calorimetry was utilized to determine resting oxygen consumption and that occurring during a 1-h period of submaximal (40% of maximal) upright, bicycle exercise. Despite differences in the route of nutrient delivery, oxygen uptake during a fixed rate of exercise (75 W) was similar during oral (16.7 +/- 0.4 mL X kg-1 X min-1) and IVF (14.7 +/- 1.0 mL X kg-1 X min-1). When compared with basal urinary losses, submaximal exercise resulted in diminished nitrogen (p less than 0.01, oral) and 3-methylhistidine (p less than 0.05, oral; p less than 0.01, IVF) excretion during a 12-h post-exercise recovery period.

Asterixis following metrizamide myelography.

Two patients seen after lumbar myelography with metrizamide demonstrated transient confusion and asterixis. Metabolic etiologies were excluded. To our knowledge, these are the first reported cases of asterixis following myelography with metrizamide.

Effects of heparin and cardiac catheterization on serum lipoprotein and triglyceride levels.

This study determined whether heparin administration and procedures involving heparin significantly affect lipid measurement. Serum lipid and lipoprotein analyses (total cholesterol, triglycerides, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, apolipoprotein B, and apolipoprotein A-I) were performed at baseline and at several time points after (1) intravenous heparin or placebo in 6 healthy volunteers (group 1), (2) cardiac catheterization with heparin in 26 patients (group 2), and (3) peripheral angiography without heparin in 11 patients (group 3). In group 1, after heparinization, triglycerides decreased 50 +/- 12 mg/dl (-57%, p < 0.001 vs baseline and placebo) at 60 minutes. No changes were observed in other lipid or lipoprotein fractions. After cardiac catheterization (group 2), however, decreases were observed not only in triglycerides (58 +/- 26 mg/dl [-40%]), but also in total cholesterol (28 +/- 12 mg/dl [-14%]), LDL cholesterol (19 +/- 22 mg/dl [-15%]), apolipoprotein B (13 +/- 9 mg/dl [-14%]), and apolipoprotein A-I (21 +/- 14 mg/dl [-17%]) (p < 0.001 vs baseline for all), and HDL cholesterol (4 +/- 7 mg/dl [-3%], p = 0.07). With the exception of triglycerides, these values remained significantly decreased for > or = 24 hours. The change in HDL was variable: Whereas most patients had a decrease (n = 24), 2 patients had a dramatic increase (> 100%) after administration of heparin. Similar decreases in total cholesterol, LDL cholesterol, and apolipoproteins B and A-I were observed in group 3 undergoing peripheral angiography without heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of lactate dehydrogenase and lactate dehydrogenase isoenzymes for diagnosis of acute myocardial infarction.

The usefulness of lactate dehydrogenase (LD) and LD isoenzymes in the diagnosis of acute myocardial infarction (AMI) is controversial. The present study reviewed 507 consecutive patients in whom creatine kinase, creatine kinase isoenzymes, LD and LD isoenzymes were ordered over a 1-month period. Of these, 249 had an insufficient number of serial enzyme determinations to establish a laboratory diagnosis of AMI. After excluding an additional 11 patients for other reasons, 247 patients remained for analysis. Of these, only 2 (0.8%) had myocardial infarction by standard clinical criteria with normal creatine kinase and creatine kinase-MB but elevated LD and abnormal LD isoenzymes. Seven patients (7 of 247, 2.8%) had false-positive LD isoenzymes. Thus, the routine use of LD and LD isoenzymes was of no use in most patients (96%) and led to the incorrect diagnosis of AMI more than 3 times as often as it helped with a correct diagnosis. Total 1-month charges for all the LD and LD isoenzymes obtained equalled +42,450. Therefore, it appears that LD and LD isoenzymes are not routinely useful in the diagnosis of AMI and may result in considerable unnecessary expense. It is suggested that LD and LD isoenzymes be ordered only under suspicion of late presentation (greater than 48 hours) of AMI.

Effects of two types of fish oil supplements on serum lipids and plasma phospholipid fatty acids in coronary artery disease.

Fish oil has consistently been shown to lower triglyceride levels, but its effects on low-density lipoprotein (LDL) cholesterol remain controversial. The current study compares the long-term effects of 2 different fish oil preparations (ethyl ester and triglyceride) versus olive oil in patients with coronary artery disease. Eighty-nine subjects were randomly assigned to receive capsules containing 6 g/day (triglyceride group) or 7 g/day (ethyl ester group) of n-3 fatty acids, or capsules containing 12 g/day of olive oil for 6 months. Mean triglyceride levels decreased by 28% in the ester and 32% in the triglyceride fish oil groups (p less than 0.05 for both). LDL cholesterol levels increased by 3% (difference not significant) in the ester and 12% (p less than 0.05) in the triglyceride fish oil groups; in hypertriglyceridemic subjects the increase was 23% (p less than 0.01) and 14% (difference not significant), respectively. Plasma phospholipid fatty acid analysis showed a fivefold increase in eicosapentaenoic acid levels in both fish oil groups (p less than 0.001), and a long-term decrease in arachidonic acid levels (p less than 0.001). Achieved eicosapentaenoic acid level correlated with the degree of increase in LDL cholesterol (r = 0.38, p less than 0.05). These data suggest that fish oil administration is associated with an increase in LDL cholesterol levels in a diverse group of patients with coronary artery disease; this change appears to be correlated with n-3 fatty acid absorption. The impact of this increase in LDL is unknown, but should be considered as potentially adverse.

Reducing adult phlebotomy blood loss with the use of pediatric-sized blood collection tubes.

The feasibility of collecting smaller blood volumes during phlebotomy for diagnostic laboratory testing was evaluated by substituting pediatric-size for adult-size blood collection tubes. The volume of blood drawn with the use of pediatric-size tubes from 41 patients in an intensive care unit (120.2 mL total; 32.2 mL/day) was 46.8% lower than in that of a control population for which adult-size tubes were used (226.1 mL total; 55.6 mL/day). Sufficient blood was available for performance of all laboratory tests ordered at the time of the phlebotomy. Although substituting pediatric-size tubes does not address the problem of excessive use of laboratory tests, smaller tubes may reduce the severity of phlebotomy-induced anemia in adults without compromising laboratory test procedures.

Morphine ingestion: genetic control in mice.

C57BL/6J mice will drink large amounts of, and display a highly positive preference for, morphine sulfate when it is dissolved in an aqueous solution of sodium saccharin. In identical test situations DBA/2J mice will drink very little of, and display a strong avoidance toward, the morphine-saccharin solution. This clear separation between morphine-accepting and morphine-rejecting animals within a single species combined with a quick and simple method of inducing high levels of morphine ingestion could facilitate the discovery of causal factors in opiate addiction.

Cancer cachexia and the rate of whole body lipolysis in man.

While malnutrition attending cancer cachexia may be associated with variable losses of body fat, lipid metabolism has been only minimally studied. To clarify potential aberrations of lipid metabolism in weight losing cancer patients, the whole body rate of lipolysis was determined in 9 cancer patients in the postabsorptive state and compared to that in 5 normal subjects. A primed-three stage infusion of glycerol was used to measure plasma glycerol clearance and turnover. A positive correlation between glycerol turnover and plasma concentration was demonstrated in both cancer patients (r = 0.72) and in normal subjects (r = 0.81). Glycerol turnover rate in cancer patients (2.05 +/- 0.14 mumol X kg-1 X min-1) was not different from that in normals (2.31 +/- 0.50); while glycerol clearance in cancer patients (1.72 +/- 0.13 L/min) was significantly lower (P less than 0.025) by 32% than that in normals. This study demonstrates that the whole body lipolytic rate in cancer patients is not different from healthy normals. As a consequence, the loss of body fat in patients with cancer cachexia may be due to a reduced rate of lipogenesis rather than augmented lipolysis as is observed in nonmalignant malnutrition, starvation, or injury.

Orotic acid excretion during starvation and refeeding in normal men.

The effects of acute food deprivation and subsequent refeeding on urinary orotic acid excretion were examined in nine healthy adult male subjects. During inpatient metabolic ward conditions, the volunteers were fed a nutritionally complete, pyrimidine- and purine-free diet for three days and subsequently underwent a ten-day fast followed by a ten-day period of refeeding by total parenteral nutrition. Mean daily excretion of 4.33 +/- 0.23 mg (2.77 +/- 0.12 mg/g creatinine) of orotic acid during the enterally fed state was significantly reduced (mean 46 +/- 5%) in all subjects during starvation. This reduction in the excretion of orotic acid during starvation is more likely related to a lowered rate of production and utilization. The starvation adaptation of orotate excretion occurred more rapidly than did the decrease in urinary nitrogen loss. All subjects showed an increase (mean 48 +/- 14%) in the excretion of orotic acid during the first day of refeeding which continued throughout the refeeding phase. A significant positive correlation was shown between the daily orotic acid excretion and nitrogen intake (r = 0.98) or protein balance (r = 0.83). The response to refeeding of acutely malnourished normal male is an increase in orotic acid excretion with a decrease in whole body protein catabolism.