Regional fat loss from the thigh in obese women after adrenergic modulation

Beta-adrenergic stimulation and alpha 2-adrenergic inhibition increase lipolysis from fat cells. Twenty-eight obese women were placed on a calorie-restricted diet and one of five treatments was applied to one thigh three to five times per week for four weeks: (1) isoproterenol injections; (2) cream containing colforsin (forskolin), aminophylline, and yohimbine; (3) yohimbine cream; (4) colforsin cream; or (5) aminophylline cream. The opposite thigh was treated with a placebo (injection or cream). The treated thighs lost significantly more girth after treatment, both by injection and by cream. No adverse reactions were attributable to either the cream or the injections. It is concluded that local fat reduction from the thigh can be safely accomplished.     

The effect of haemorrhage on venous return and regional blood flow in the anaesthetized cat

1. In cats under pentobarbitone anaesthesia, a venous long-circuit technique was used to measure the blood flows in the superior vena cava and the hepatic, renal and iliac segments of the inferior vena cava. The sum of these flows gave the venous return (minus coronary and bronchial flows).2. In these preparations, the mean venous return was 130 ml./kg. Of this 28% came from the superior vena cava and 37% from the hepatic, 23% from the renal and 12% from the iliac segments of the inferior vena cava.3. After haemorrhage, the flows from all the venae cavae segments decreased. The quantitative changes varied with the particular cat, the degree and duration of the haemorrhage and whether the animal had been subjected to a previous haemorrhage.4. The proportion of the reduced venous return draining from the superior vena cava and the hepatic segment increased, that draining from the renal and iliac segments decreased. Vasoconstriction occurred in all vascular beds, but was greatest in the kidney and hind limbs. Thus the blood flow through the head and liver was partially maintained at the expense of that through the kidneys and hind limbs.5. Autoregulation of blood flow in the kidneys was usually seen immediately after the first removal of blood but with the onset of renal vasoconstriction it was reduced or abolished for the remainder of the experiment.     

The effects of adrenaline and noradrenaline on venous return and regional blood flows in the anaesthetized cat with special reference to intestinal blood flow

1. In cats, a venous long-circuit technique was used to measure the blood flows in the superior vena cava and the hepatic, renal and iliac segments of the inferior vena cava. The sum of these flows gave the venous return (minus coronary and bronchial flows). In further experiments using an electromagnetic flowmeter, flow in the portal vein and in the superior mesenteric and coeliac arteries was measured.2. Approximately two-thirds of the hepatic blood flow is derived from the portal vein.3. After block of conduction in the cervical region of the spinal cord, the proportions of the venous return coming from each region during the control periods were not significantly altered although the arterial pressure and total venous return were decreased.4. Intravenous infusions of adrenaline caused an increase in venous return which was associated with a marked increase in hepatic blood flow. The increase in hepatic blood flow was due to an increase in flow in the superior mesenteric artery and portal vein. Flow in the coeliac artery remained unchanged. This response was unaffected by block of the cervical region of the spinal cord and by atropine or pentolinium.5. Intravenous infusions of noradrenaline caused little change in venous return or regional blood flows. Small increases in superior mesenteric artery flow were occasionally seen and on cessation of the infusion a large but brief increase occurred. These facts suggest that noradrenaline has a similar action to adrenaline but this is masked by concomitant vasoconstriction.     

Pharmaceutical cost savings of treating obesity with weight loss medications

OBJECTIVE: To evaluate, in compliant patients, the pharmaceutical costs of treating obesity with fenfluramine/mazindol, fenfluramine/phentermine, caffeine/ephedrine, or mazindol relative to the pharmaceutical costs of treating obesity-related comorbid conditions and reducing cardiovascular risk. METHODS AND PROCEDURES: Subjects were between 18 and 60 years of age with a BMI of >30 kg/m2. Pharmaceutical costs were evaluated in 73 of 220 subjects taking medications for diabetes, hyperlipidemia, or hypertension before and after treatment using fenfluramine with mazindol or phentermine. The pharmaceutical cost of weight loss, cardiac risk reduction, and low-density lipoprotein (LDL) cholesterol reduction was calculated for fenfluramine with mazindol or phentermine, caffeine with ephedrine, or mazindol alone, and compared to approved lipid-lowering medications. RESULTS: Losses of 6% to 10% of initial body weight reduced pharmacy costs $122.64/month for insulin treated diabetes, $42.92/month for sulfonylurea-treated diabetes, $61.07/month for hyperlipidemia treated with medication, and $0.20/month for hypertension treated with medication. Blood pressure and laboratory evidence of insulin resistance improved in all medication groups. Caffeine/ephedrine was most cost-effective of the three treatments in reducing weight, cardiac risk, and LDL cholesterol. DISCUSSION: Obesity medications produced a substantial weight loss in compliant patients and resulted in a net pharmaceutical cost savings compared to treating obesity related comorbid conditions.     

Pain and pain management in newborn infants: a survey of physicians and nurses

BACKGROUND: Despite an increased awareness among clinicians regarding pain and pain management for infants undergoing surgery, pain associated with procedures performed outside the operating room may not be adequately managed. PURPOSE: To examine the beliefs and self-described behavior of physicians and nurses regarding the management of procedural pain in newborn infants. METHODS: A survey was distributed to 467 clinicians (nurses and physicians) working in 11 level II and 4 level III nurseries in a large metropolitan area. Respondents were asked to rate the painfulness of 12 common bedside nursery procedures and how often pharmacologic and nonpharmacologic (comfort) measures are currently used and should be used for those procedures. Demographic data were also collected. RESULTS: Surveys were completed by 374 clinicians (80% response rate). Physicians and nurses believe infants feel as much pain as adults and that 9 of the 12 listed procedures are moderately to very painful. Neither pharmacologic nor comfort measures are believed to be used frequently, even for the most painful procedures. Physicians and nurses believe both pharmacologic and comfort measures should be used more frequently, but nurses believe comfort measures should be used more frequently than do physicians. Beliefs about infant pain and procedural pain were related to pain management preferences. Physicians' but not nurses' ratings were associated with significant personal pain. CONCLUSIONS: Despite their beliefs that infants experience significant procedure-related pain, clinicians believe pain management for infants remains below optimal levels. Barriers to more consistent and effective pain management need to be identified and surmounted.     

Bacterial and mammalian DNA alkyltransferases sensitize Escherichia coli to the lethal and mutagenic effects of dibromoalkanes

Here we confirm and extend our previous studies demonstrating that the mutagenic potency of 1,2-dibromoethane (DBE) and dibromomethane (DBM) is markedly enhanced (not prevented) in bacteria expressing the O6- alkylguanine-DNA alkyltransferase (ATase) encoded by the Escherichia coli ogt gene. We demonstrate that, in close parallel with mutagenesis, the Ogt ATase sensitizes the bacteria to the lethal effects of these carcinogens, suggesting that one or more of the potentially mutagenic lesions induced by DBE and DBM in the presence of Ogt has additional lethal capacity. We further demonstrate that the sensitization to both lethality and mutagenesis by DBE and DBM is a property shared by other DNA alkyltransferases. This objective was accomplished by quantifying the induction of mutations and lethal events in ogt- ada- E. coli expressing an exogenous bacterial or mammalian ATase from a multicopy plasmid. Mammalian recombinant ATases enhanced the lethal and mutagenic actions of DBE and suppressed the lack of sensitivity of the vector- transformed bacteria to DBM. In most cases the order of effectiveness of the ATases ranked: murine > human > Ogt > rat. Further comparisons included the full-length Ada ATase from E. coli and a truncated Ada version (T-ada) that retains the O6-methylguanine binding domain of the protein. The full-length Ada ATase was effective in enhancing the lethality but not the mutagenicity induced by DBE and DBM. The T-ada ATase provided less sensitization than Ada to lethality by DBE, but of the three bacterial ATases T-ada yielded the highest sensitization to mutagenesis by this compound. T-ada and Ada ATases were in general less effective than the mammalian versions, with the exception of the rat recombinant ATase. The effectiveness of the different mammalian and bacterial ATases in promoting the deleterious actions of dibromoalkanes was compared with the effectiveness of these proteins in suppressing the lethal and mutagenic effects induced by N-nitroso-N-methylurea. The ability to sensitize E. coli to the lethal and mutagenic effects of DBE and DBM seems restricted to DNA alkyltransferase, since overexpression of thioredoxin (Trx) or glutaredoxin (Grx1) in ogt- ada- cells showed no effect, in spite of the reported potential of bioactive dihaloethane- derived species to alkylate Trx.      

New horizons in the understanding of the causes and management of diabetic foot disease: report from the 2017 Diabetes UK Annual Professional Conference Symposium

Diabetes‐related foot disease remains a common problem. For wounds, classic teaching recommends the treatment of any infection, offloading the wound and ensuring a good blood supply, as well as ensuring that the other modifiable risk factors are addressed and optimized. There remain, however, several questions about these and other aspects of the care of diabetes‐related foot disease. Some of these questions are addressed in the present report; in particular, the impact of newer technologies in the identification of any organisms present in a wound, as well as the use of novel approaches to treat infections. The use of new remote sensing technology to identify people at risk of developing foot ulceration is also considered, in an attempt to allow early intervention and prevention of foot ulcers. The psychological impact of foot disease is often overlooked, but with an increasing number of publications on the subject, the cause‐and‐effect role that psychology plays in foot disease, such as ulcers and Charcot neuroarthropathy, is considered. Finally, because of heterogeneity in diabetic foot studies, comparing results is difficult. A recently published document focusing on ensuring a standardized way of reporting foot disease trials is discussed.