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Objectives:According to the literature, voice rest following phonosurgery, as recommended in clinical practice, varies between 3 and 7 days. However, up until now, no randomized trials have been published comparing voice rest of short versus long duration.Methods:This is an ongoing prospective randomized study, comparing strict voice rest of 5 versus 10 days on the voice following phonosurgery. Thirty-one elective patients operated on for benign laryngeal lesions were randomized. They completed pre- and postoperative assessments, including perceptual voice quality (Grade, Roughness, Breathiness, Asthenia, Strain, Instability scale), Voice Handicap Index total score, and voice analysis with both acoustic and aerodynamic measurements. Additional factors such as smoking, vocal abuse, reflux, and preoperative speech therapy were also taken into account.Results:Sixteen patients were randomized to follow 5 days’ voice rest and 15 patients were randomized to 10 days’ voice rest. Statistical analysis showed no significant differences in pre- or postoperative measurements between the 2 groups. However, multilinear regression analysis for the effect of voice rest duration on postoperative values showed a significant improvement in maximum phonation time (MPT) with 10 days’ voice rest.Conclusions:Preliminary results show a benefit of prolonged voice rest (10 days’ duration) on MPT.

Excess visceral adiposity induces chronic subclinical inflammation resulting in the metabolic syndrome. Whether excess visceral adiposity impacts posttraumatic inflammatory profiles more is unknown. We hypothesized that obese patients (body mass index >30 kg/m2) with higher visceral to subcutaneous adipose tissue distribution would have increased inflammatory outcomes.

As part of a clinical trial investigating the level of nicotine replacement with different doses of transdermal therapy for smoking cessation, peak and trough serum nicotine and plasma cotinine concentrations were measured in 70 subjects while they were actively smoking (baseline) and daily for 6 consecutive inpatient days while they were receiving transdermal nicotine. Subjects were randomly assigned to a daily 24‐hour patch delivering a transdermal nicotine dose of 0, 11, 22, or 44 mg and stratified by self‐reported smoking rate as either light (10–15 cigarettes per day), moderate (16–30 cigarettes per day), or heavy (>30 cigarettes per day). Steady‐state concentrations of nicotine and cotinine were attained in 1 and 3 days, respectively, at all doses and were independent of baseline smoking rate. Mean percentage replacement of nicotine was calculated by dividing steady‐state peak nicotine or cotinine concentrations by their respective baseline concentrations. Significant underreplacement occurred in subjects receiving the 11 mg/day patch regardless of baseline smoking rate. Underreplacement also occurred in moderate and heavy smokers receiving 22 mg/day and in light smokers at this same dose. Complete replacement occurred only in subjects receiving the 44 mg/day patch. These results have several implications for transdermal nicotine therapy. First, with the higher nicotine and cotinine levels observed with heavier smoking, it is inherent that one size does not fit all, and there is a need to consider more individualization of dosage for nicotine patch therapy. Second, there is substantial underreplacement with the 22 mg/day dose in moderate to heavy smokers and in some light smokers. Third, even with twice the usual dose (i.e., 44 mg/day), there was no accumulation of either nicotine or cotinine. Plasma cotinine levels after achievement of steady state (i.e., after 3 days of patch therapy) can be collected at any time and used to calculate percent replacement using baseline levels.

As part of a clinical trial investigating the level of nicotine replacement with different doses of transdermal therapy for smoking cessation, urine excretion rates of nicotine and cotinine were measured in 70 subjects while they were actively smoking (baseline) and for 6 consecutive inpatient days while they were receiving transdermal nicotine therapy. Subjects were stratified according to baseline smoking rate as light (10–15 cigarettes per day), moderate (16–30 cigarettes per day), or heavy (>30 cigarettes per day) smokers and randomly assigned to a daily 24‐hour patch delivering a transdermal nicotine dose of 0, 11, 22, or 44 mg. Steady‐state excretion rates of nicotine and cotinine were attained in 2 and 3 days, respectively, at all doses and were independent of smoking rate. Percentage replacement of nicotine was calculated by dividing steady‐state nicotine or cotinine excretion rates by their respective baseline excretion rates. Significant underreplacement occurred with the 11‐mg/day dose, particularly in moderate and heavy smokers (<50%). At a dose of 22 mg/day, nicotine replacement was still <100% in the majority of subjects. Only at a dose of 44 mg/day did mean replacement exceed 100% regardless of baseline smoking rate.

We related serum nicotine and cotinine levels while subjects were smoking their usual numbers of cigarettes to levels while wearing a nicotine patch under carefully controlled, smoke-free conditions in a clinical research center. Twenty-four volunteers who needed intensive treatment for severe nicotine dependence were admitted to the clinical research center and were treated with a 22 mg transdermal nicotine patch each day and an intensive smoking-cessation program. Serum nicotine and cotinine levels, withdrawal symptoms, and hours and quality of sleep were noted. The steady-state serum nicotine and cotinine levels produced with the nicotine patch were lower than those observed when the subjects were smoking. Mean nicotine and cotinine levels were inversely related to mean withdrawal scores for the first 6 days. A fixed dose of transdermal nicotine will not be effective for all smokers. Individualization of therapy should be based on objective biologic measures such as serum cotinine and subjective assessment of withdrawal relief.Clinical Pharmacology and Therapeutics (1993) 54, 98–106; doi:10.1038/clpt.1993.117

Ulcerative colitis is predominantly a disease of nonsmokers, and transdermal nicotine is therapeutic but often results in adverse reactions. Colonic administration of nicotine tartrate as a liquid enema could decrease systemic nicotine absorption and adverse reactions. The purpose of the current study was to determine the bioavailability and pharmacokinetic parameters of nicotine after administration by hydrophilic liquid enema (acidic and basic), hydrophobic liquid enema (acidic and basic), and by oral and intravenous routes. Thirty healthy volunteers received 45 μg nicotine base/kg (as nicotine tartrate) in one of five formulations (each n = 6): hydrophilic acidic liquid enema, hydrophilic basic liquid enema, hydrophobic acidic liquid enema, hydrophobic basic liquid enema, and oral solution. All participants also received 15 μg nicotine base/kg (as nicotine tartrate) intravenously during a separate study period. Serum concentrations of nicotine were determined by gas chromatography with mass spectrometry. The mean (± SD) bioavailabilities of nicotine after administration in the liquid enema formulations (hydrophilic acidic 17 ± 18%, hydrophilic basic 16 ± 16%, hydrophobic acidic 25 ± 17%, hydrophobic basic 15 ± 12%) were similar to the bioavailability of nicotine after administration by oral solution (20 ± 25%). The bioavailabilities of nicotine for all five nonintravenous formulations were significantly less than for intravenous nicotine (100%). Serum concentrations of nicotine did not predict adverse reactions. Nicotine tartrate administered as either a liquid enema or as an oral solution had low bioavailability and was well tolerated. The therapeutic potential of nicotine tartrate liquid enemas, which can potentially limit toxicity by local (colonic) delivery of high doses of nicotine should be investigated in patients with left‐sided ulcerative colitis.

Background/Aims:Uncontrolled studies suggest that cyclosporine administered as an enema may be of benefit for left-sided ulcerative colitis and safer than intravenous or oral administration. The efficacy and safety of cyclosporine enemas for left-sided ulcerative colitis in a placebo-controlled trial was assessed. Methods:Steroid and mesalamine enemas were withdrawn before the study. Forty patients were assigned to 1 of 4 strata: no concomitant therapy, oral steroids, oral salicylates, or oral steroids and salicylates. After stratification, patients were randomized to nightly treatment with 350 mg cyclosporine (n = 20) or placebo (n = 20) enemas. Clinical response was determined at baseline and 4 weeks by endoscopy, physician assessment, and a patient diary of daily symptoms. Trough blood cyclosporine levels were measured by high-performance liquid chromatography. Results:At 4 weeks, 8 of 20 patients (40%) who received cyclosporine showed clinical improvement compared with 9 of 20 patients (45%) who received placebo. One patient receiving cyclosporine had reversible neutropenia attributable to sulfasalazine, and another patient receiving cyclosporine was unable to tolerate the enema vehicle. No other toxicity was noted during the trial. Blood cyclosporine levels were detectable in only two patients. Conclusions:Cyclosporine enemas administered in a dosage of 350 mg/day for 4 weeks are not efficacious in mildly to moderately active left-sided ulcerative colitis.

Recent studies suggest that cyclosporine may be an alternative to colectomy in children with severe ulcerative colitis who fail traditional therapy with bowel rest and high-dose corticosteroids. We report the clinical course of two such children. Patient I received oral cyclosporine at 15 mg/kg/day for 1 week followed by 8 mg/kg/day for 6 weeks. Clinical remission occurred within 5 days and has been sustained for 24 weeks after azathioprine was substituted for cyclosporine. Patient 2 received oral cyclosporine at 7–8 mg/kg/day for 7 days after which colectomy was performed due to lack of clinical improvement. Blood cyclosporine levels for patient 1 ranged from 95 to 406 ng/ml and for patient 2 from 36 to 65 ng/ml. Sigmoid colonic tissue cyclosporine concentrations for patients 1 and 2 were 10,058 and 3,205 ng/g, respectively. The patient who responded had significantly higher blood and colonic tissue cyclosporine concentrations than the patient who did not respond. Further studies with larger numbers of patients are needed to determine if there is a correlation between blood and colonic tissue cyclosporine concentrations and clinical response.

A rat testes tubule tissue receptor assay was utilized to study the kinetics of combination of the hormone-specific β subunit of human follicle-stimulating hormone (hFSH) with the α subunits of hFSH, human luteinizing hormone (hLH), bovine luteinizing hormone (bLH), and human chorionic gonadotropin (hCG). In this competitive protein-binding assay, 125I-hFSH is the radioligand and FSH activity is measured by the ability of the test substance to inhibit uptake of the radioligand by the rat testes tubule receptors. Rate data for combination of subunits were analyzed for quality of fit to first or second order integrated rate equations by nonlinear regression analysis. The time course for the appearance of FSH activity upon incubation of the various subunit combinations was neither clearly first or second order, although each simple mechanism could be fitted to the experimental data. We conclude that at least one kinetically distinguishable state follows formation of the initial α/β subunit complex and that this complex has a binding affinity for its receptors in rat testes tubules which is much less than those of subsequent states. Hybrid molecules of bLH-α/hFSH-β, hLH-α/hFSH-β, and hCG-α/hFSH-β were formed at differing rates, but each was more rapid than the combination always gous hFSH-α/hFSH-β pair. Maximum combination always occurred by 1440 min of incubation. Hybrid molecules formed after this time were tested for FSH activity by the in vitrorat testes tubule receptor assay and results compared with FSH activity as measured by a classical in vivobioassay. The in vitroactivity of hFSH-α/hFSH-β, hLH-α/hFSH-β and hCG-α/hFSH-β hybrid molecules was from 2 to 4 times greater than their activity as measured in vivo. The in vitroactivity of these hybrids was similar to that of intact hFSH, but the activity of the hybrid molecules in vivowas less than that of intact hFSH. Of particular interest were the properties of the hybrid molecule formed between bLH-α/hFSH-β. This combinant had an in vitroactivity which was 2.8 times greater than that of purified hFSH. The activity of the bLH-α/hFSH-β hybrid as measured by the in vivobioassay, however, was only 0.14 times the activity of purified hFSH. The ratio of activity in vitroto in vivofor this artificial FSH molecule was 19.8. It is suggested that the bLH-α/hFSH-β hybrid has a greater affinity than native hFSH for receptors in rat testes tubules, but that expression of in vivobiological activity is depressed probably because of factors related to its more rapid clearance from the circulation.

A rapid method for measuring nicotine concentration in serum and urine is described. Deuterated nicotine is used as an internal standard. Nicotine and deuterated nicotine are extracted using a copolymeric-bonded phase silica column. The extract is analysed by gas chromatography coupled with mass spectrometry (GC/MS) operating in selected ion monitoring mode. The method has a lower limit of detection of approximately 2 μg/L and is linear to at least 2000 μg/L. Within-run percentage coefficients of variation (% CV) are < 4 in both assays over a nicotine concentration range of 10–2000 μg/L. Between-run %CV in the serum assay are 5.4, 5.2, 4.8 and 5.9, respectively, at nicotine concentrations of 10, 15, 25, and 50 μg/L. Between-run %CV in the urine assay are 5.9, 4.5, 2.7 and 5.2, respectively, at nicotine concentrations of 100, 250, 500, and 2000 μg/L. The absolute recovery of nicotine is 61±+6% (mean±SD) over the range of 10–250 μg/L. The assay has been used to measure serum nicotine concentrations and 24-h urinary excretion of nicotine to monitor the extent of replacement in subjects receiving transdermal nicotine therapy for smoking cessation.

No abstract available for this article.

In 1906, Bordet and Gengou1 succeeded in cultivating Bacillus pertussis from cases of whooping cough. Since their pioneer discoveries, isolated reports of a few cases each have been published, but in this country routine cultures in cases of whooping cough have had little vogue.The work of Meyer, Chievitz2 and their co-workers at the Danish Serum Institute has demonstrated conclusively the value of bacteriologic methods in the diagnosis of this disease, and their studies, now extending over a number of years, have been too little appreciated in the United States. In a report covering 1,106 cases they were able to isolate the causative organism in 970, a percentage of 87.7 isolations. Dividing these cases into groups according to the stage of the disease at the time cultures were taken, their success may be tabulated as shown in table 1.In the United States, reports on the bacteriology of the

It has been fifteen years since Dam1 announced the discovery of vitamin K and described its antihemorrhagic properties. In the past two years we have seen proof of the valuable properties of this newcomer to the family of vitamins in two important clinical fields, namely the hemorrhagic state associated with obstructive jaundice and the hemorrhagic diathesis of the newborn. The rapid development in the chemical synthesis of vitamin K stands out as a landmark of accomplishment in the field of biologic chemistry.In March 1939 we2 recorded the cases of two newborn infants both with marked prothrombin deficiency. In one infant there was in addition unnatural bleeding. To each of these infants natural vitamin K concentrate was administered orally, and within the short interval of two hours the prothrombin deficiency appeared to have been corrected and bleeding in the one instance promptly was controlled. On the basis of

Presents the minutes of the New Piles Committee meetings held between April and July 1944. Members of the committee; Views of the committee on breeder reactors; Factor that led to the design and construction of the materials test reactor in the late 1940s.

On account of lack of employment after the South African War, quite a number of miners from the Transvaal returned to England. Many of these were broken down in health. Their cases were studied by Thomas Oliver,1 who emphasized the fact that dyspnea was the chief symptom. He noted, too, that most of these men died under 40 and urged that steps be taken to avert the loss of so many lives in the mining industry. His urgent plea was not futile. British medical literature affords striking evidence of the thoroughness with which the situation has been handled.In America the health hazards of metal miners have not received the attention accorded other dangerous trades. According to Lanza2 the life expectancy of a metal miner, from the time he commences hard rock mining and including one year of disability immediately preceding his death, is but 9.6 years.Lanza

The article reviews the exhibition "BP Spotlight: Hockney's Double Portraits," faturing several works by painter David Hockney on display at Tate Britain.

BackgroundThe Breathe Better group (BBG) has been running from Marie Curie Hospice Bradford (MCHB) since 2008. It aims to reduce dyspnoea, improve quality of life and mastery of illness for patients with end stage COPD. It uses four methods: education, exercise, pharmacological management and individual consultations. We aimed to ascertain the impact of the BBG.MethodA retrospective longitudinal study was performed on patients referred between August 2010 and June 2013. Data were collected on shuttle walk distance, mastery, Hospital Anxiety and Depression Scores (HADS), advance care planning (ACP), and mortality. Outcomes were analysed using a paired t-test.ResultsData from 56 patients was analysed. Mean shuttle walk distance increased by an average of 10.8m which was statistically significant (p = 0.05). Total HADS score improved by 2 points. 65% of patients had an ACP after the group, compared with 24% prior to commencement. 76% patients died with two years of the group. Place of death (below) demonstrates an increase in rates of hospice death when compared with regional and national COPD data.Place of Death (n = 45)Care home11%Home7%Hospital38%Hospice31%Not recorded13%DiscussionResults suggest that BBG improves shuttle walk distance and recording of ACP which appears to influence place of death. Missing data means conclusions are based on a small sample size. Improved data recording is a local priority in order to render future evaluations more meaningful.ImplicationsOther hospices may wish to consider pilot schemes especially as often this patient group are unable to access current NHS schemes such as Pulmonary Rehabilitation due to their poor health. A larger study with a control group of patients who did not attend will allow more accurate evaluation.

BackgroundThe Breathe Better group (BBG) has been running in the hospice in 2008. It aims to reduce dyspnoea, improve quality of life and mastery of illness for patients with end stage COPD using four methods: education, exercise, pharmacological management and individual consultations. We aimed to ascertain the short and long-term impact of the BBG.MethodA retrospective longitudinal study was performed on patients referred between 2010 and 2013. Data were collected on shuttle walk distance, mastery, Hospital Anxiety and Depression Scores (HADS), advance care planning (ACP), and mortality. Outcomes were analysed using a paired t-test.ResultsData from 56 patients was analysed. Mean shuttle walk distance increased by an average of 10.8 m which was statistically significant (p = 0.05). Total HADS score improved by 2 points. 65% of patients had an ACP after the group, compared with 24% prior to commencement. 76% patients died with 2 years. Place of death was as follows: (n = 45) Care home 11%, Home 7%, Hospital 38%, Hospice 31%, Not recorded 13%. There was a significantly increased rate of hospice death compared to regional and national COPD data and a proportionate reduction in hospital deaths.DiscussionResults suggest that BBG improved shuttle walk distance and recording of future health decisions and may influence place of death.ImplicationsBBG improved patients’ exercise tolerance and ACP. From a public health perspective, the success of BBG suggests other hospices may wish to consider pilot schemes. A larger study with a defined control group (patients choosing not to attend) will allow more accurate comparison. Improved record-keeping is required to enhance data accuracy and reduce missing data.ReferencesChin C, Booth S.Managing breathlessness: a palliative care approach. Postgrad Med J2016Purdy S.Avoiding hospital admissions: What does the evidence say. London: The King’s Fund; 2010Spathis A, Booth S. End of life care in chronic obstructive pulmonary disease: in search of a good death. Int J Chron Obstruct Pulmon Dis2008;3(1):11–29

Brem and Zeiler,1 in 1911, successfully used ipecac by rectum and through the appendix after appendicostomy in several cases of amebic dysentery that had not yielded to other methods of treatment. This method does not seem to have come into any general use. We have been using a similar method for about five years, although, up until recently, we were ignorant of Brem and Zeiler's work. Our number of cases has been somewhat limited, and it is only in the past year that we have been able to test this method to our satisfaction. Our method of procedure is to put 60 or even 120 grains of powdered ipecac into about 24 ounces of water; this is kept hot for an hour, but not allowed to boil. After washing out the bowel with warm water, this whole preparation, without filtering, is given slowly by rectum to be retained as

In March 1931, as already reported,1 a man aged 51 acutely ill with hemophilia was treated by venesection. In forty-eight hours he was almost free from symptoms. For long intervals he had been completely incapacitated because of joint symptoms occurring with the hemophilia. After this the patient, on the onset of symptoms, would come in for venesection on an average of about once every six weeks. From 400 to 500 cc. of blood was removed each time. The last venesection done by us was on June 23, 1939, when he was apparently in good physical condition except for nervousness and marked apprehension of death. He had been in rather good condition as a whole during the many years that we had been bleeding him, except for some discomfort in one knee. The x-ray film of this knee showed small cystic looking areas in the patella and lower femur.He

J. E. M., a white man aged 51, was admitted to the Jefferson Hospital in March 1931, acutely ill with hemophilia. He presented signs and symptoms pointing to the presence of hemorrhage in the meninges, pleural cavities and abdominal viscera. There was bleeding from the genito-urinary tract, and there were also many large areas of subcutaneous hemorrhages.After several days the patient was worse and in what seemed a hopeless condition; feeling that possibly these hemorrhagic crises were an effort of nature for relief, my associates and I1 tried venesection. The results were surprising. Though the patient had been in a comatose condition, forty-eight hours after the venesection he was clear mentally and seemed in good shape physically. Since that time, a period of seven years, he has been constantly under the care of one of us (A. B. G.) and has had venesection done, with the removal of

We have had the opportunity of studying a patient with hemophilia who came under our observation in an acutely ill condition. For reasons given later, this patient was treated by venesection with most gratifying results. REPORT OF CASE J. E. M., a man, aged 51, referred by Dr. A. B. Graybeal of Marion, Va., was admitted to the Jefferson Hospital, March 27, 1931. Two weeks before admission he began to have a pain in the right lower part of the chest, which was worse on motion and deep breathing. For six days he had had a severe lower abdominal pain and had passed bloody urine several times. The pain was so severe as to require morphine for relief. Three days before admission he became very restless, noisy and delirious at times. He does not remember coming to the hospital or anything that happened for several days thereafter.He gave a

In fixing blood-slides by heat, one finds that the results of the copperplate method are so inconstant that it is difficult to get a good specimen unless one keeps in constant practice. There is no way of determining the exact amount of heat used or of keeping the heat regular. I have devised the following simple apparatus for office and laboratory use:As shown in the illustration, an ordinary laboratory standard supports an iron dish, C, resting on an asbestos plate, under which is a gas burner. This iron dish is easily made by screwing a two-inch nipple into a pipe cap. This dish is filled with petrolatum, into which is sunk a small, thin copper cup so that the end sticks out as shown at B. This cup is just large enough to admit with ease the glass slide. In the petrolatum is sunk the bulb of a thermometer, A.

This instrument consists merely of the barrel of a medicine dropper fitted air tight, by means of a perforated stopper, into the barrel of a pointed glass urethral syringe as shown in illustration.The tubing on a fountain syringe is cut near the bag and the apparatus is inserted between the cut ends. The liquid can be seen as it drops from the glass tip to the bottom of the air space in the syringe barrel. A small stopcock is put in the rubber tubing between the apparatus and the rubber bag. One may readily adjust the stopcock so as to get a steady stream or only a few drops each minute. A small catheter is attached to the rubber tubing and inserted into the rectum as is usually done.This apparatus has the advantage over the old style of partially grasping the tube with an artery clamp because after

EARTHQUAKE phenomena are extremely rare in this highly favoured part of the world; but we had a very decided shake near the close of the year 1882. It occurred last night (Sunday, December 31) at about five minutes past ten o'clock, Halifax time, as nearly as can be determined at present. My observation was made at Lucyfield, ten miles north from the city of Halifax; the house stands on a rounded bill formed of unaltered drift, overlying slate rock, and at an elevation of about 350 feet above sea-level.

YOUR correspondent at p. 385, vol. xxx., may be informed that in this part of the world wasps enter dwellings by the open windows in summer-time, and hunt house-flies unmercifully, leaving the dead flies in hundreds on the floors, ready to be swept into a dustpan. This occurs only in the country, and where wasps' nests are near by. Westwood quotes from St. John's “Letters to an American Farmer” that: “The Americans, aware of their (wasps') service in destroying flies, sometimes suspend a hornets' nest in their parlours” (Introduction to “Modern Classification of Insects,” ii. p. 246, foot-note).