Long term patient-reported benefit from ptosis surgery.

PURPOSE: To assess the long term impact of ptosis surgery on health-related quality-of-life using the Glasgow Benefit Inventory (GBI) patient-reported outcome measure. PATIENTS AND METHODS: A retrospective case note review was carried out on all patients who had undergone ptosis surgery (6 November 2008 to 5 December 2010) by one surgeon at Royal Bournemouth Hospital. Patient demographics, surgical technique, and complications were recorded. The GBI questionnaire data was obtained by telephone interview. RESULTS: A total of 62 ptosis operations (33 right, 29 left, of which 18 were bilateral) on 44 patients; 20 male, 24 female were included. Median age 77 years (range: 17-95 years). One wound dehiscence occurred, but no redo ptosis procedures were required. GBI data was obtained on 32 patients (45 ptosis procedures) at a mean follow-up period of 42.8 months postoperatively (range 31-67 months). The mean total GBI score for ptosis surgery was +21.36 (range 0-58.33; 95% confidence interval: 17.28-25.43, P<0.05). CONCLUSION: Patients derived a highly significant benefit to their health-related quality-of-life from ptosis surgery measured by the GBI that was maintained for up to 5 years.

The pharmacokinetics of oral fleroxacin and ciprofloxacin in plasma and sputum during acute and chronic dosing.

AIMS: To examine the pharmacokinetics of ciprofloxacin and fleroxacin in plasma and sputum of patients with an acute exacerbation of chronic bronchitis or bronchiectasis following the first dose and again during the third day of treatment. METHODS: Twelve patients, aged >35 years, with acute infective exacerbation of bronchitis or bronchiectasis were allocated randomly to treatment with either fleroxacin 400 mg daily or ciprofloxacin 500 mg twice daily in an open, parallel group design. Plasma and sputum were collected during the first and third days of treatment. The time course of concentrations in sputum was modelled assuming that it acted as a negligibly small compartment of distribution. RESULTS: The mean sputum to plasma ratios of both ciprofloxacin and fleroxacin were approximately 1 on both days 1 and 3. Peak concentrations of ciprofloxacin in sputum were achieved 1.6 (95% CI on mean difference 0.8-2.3) and 1.2 (0.4-1.9) h later than in plasma on day 1 and day 3, respectively (mean difference +/- 95% confidence interval). For fleroxacin, the corresponding delay in time to peak concentrations was less marked and not significant. Fleroxacin accumulated in plasma (accumulation index 1.52+/-0.07) and sputum (accumulation index 1.79+/-0.39) from day 1 to day 3. Accumulation did not occur for ciprofloxacin because the dose interval (12 h) was considerable longer than its half life (3-4 h). CONCLUSIONS: The sputum to plasma ratio of ciprofloxacin and fleroxacin is approximately 1. The time to peak concentrations of ciprofloxacin in sputum is slightly delayed compared with plasma. Fleroxacin accumulates over time in both plasma and sputum consistent with its longer half-life.

Paroxetine in human milk.

AIMS: The primary aims of the study were to estimate the exposure of infants to paroxetine via breast milk and to determine the maternal milk:plasma ratio (M/P) of paroxetine. Secondary aims were to compare single point and area under the curve (AUC) estimates of M/P, to assess variability of M/P in fore and hind milk, and to compare the observed M/P with that predicted by a model. METHODS: Two studies were performed. In one study, six nursing mothers who were being treated with paroxetine were studied over a 24 h dose interval at steady-state. The total amount of paroxetine in the milk was measured, which represented the 'dose' to the infant. The M/PAUC was calculated and compared with a predicted value. In the second study, four nursing mothers who were being treated with paroxetine, were studied at steady-state, around a normal infant feeding time. A single plasma sample and a prefeed milk sample were taken approximately 3 h after the morning dose of paroxetine, and a postfeed milk sample taken around 1 h later. The dose received by the infant was estimated from the average milk concentrations of the pre and postfeed samples using standard assumptions, and M/P calculated directly. Plasma concentrations of paroxetine were measured in 8 of the 10 infants in the two studies. RESULTS: The mean dose of paroxetine received by the infants in the first study was 1.13% (range 0.5-1.7) of the weight adjusted maternal dose. The mean M/PAUC was 0.39 (range 0.32-0.51). The predicted M/P was 0.22. The mean dose of paroxetine received by the infants in the second study was 1.25% (range 0.38-2.24) of the weight adjusted maternal dose. The mean M/P was 0.96 (range 0.31-3.33) and did not differ between fore and hind milk. The drug was not detected in the plasma of seven of the infants studied and was detected but not quantifiable (<4 microg l-1 ) in one infant. No adverse effects were observed in any of the infants. CONCLUSIONS: Measured M/P and estimated infant dose were similar in the two studies, although the range was wider for the single point study. Paroxetine can be considered 'safe' during breast feeding because the dose transferred to the infant is well below the recommended safety limit of 10% of the weight adjusted maternal dose, concentrations in the infants were generally undetectable, and no adverse effects were reported.

Measurement of total phospholipids in urine of patients treated with gentamicin.

AIMS: The excretion of phospholipids in urine may be a marker of the early renal toxicity of the aminoglycoside antibiotics. Urinary phospholipids are formed in myeloid bodies which develop in the lysosomes of proximal tubules during treatment with the aminoglycosides, and overflow into the urine. METHODS: Published assays were modified in order to measure the total phospholipid concentrations in human urine. Phospholipids were extracted from freeze-dried urine samples, digested in concentrated sulphuric acid, and the inorganic phosphorus content determined by complexing with ammonium molybdate and measuring the absorbance at 820 nm. Ten septicaemic patients treated with gentamicin for 5-7 days had significantly higher urine phospholipid concentrations than 10 healthy untreated control subjects (P < 0.0001). There was a negative linear relationship between phospholipid excretion and creatinine clearance (r2 = 0.71). RESULTS: In 34 patients with acute pyelonephritis, increased phospholipid concentrations were observed prior to treatment compared with healthy controls (P < 0.001) and did not alter during treatment with gentamicin. However, the phospholipid concentrations decreased significantly after treatment was completed (P < 0.03). CONCLUSIONS: These studies suggest that urinary phospholipids may indicate early aminoglycoside toxicity but with poor specificity, as many of the infections being treated may themselves be associated with phospholipiduria.

Simple method for the quantitation of mycophenolic acid in human plasma.

A simple and rapid isocratic reversed-phase high-performance liquid chromatographic method using UV detection was developed for the quantitation of mycophenolic acid (MPA) in human plasma. The assay was sufficiently robust to allow the analysis of up to 100 samples in a single analytical run.

Oxygen saturation of patients recovering from electroconvulsive therapy.

Oxygen saturation was measured by pulse oximetry in 33 psychiatric patients breathing air during recovery from 60 episodes of electroconvulsive therapy. Desaturation to less than 90% occurred in 17% of patients. Oxygen saturation values in recovery were significantly lower than pre-operative saturations (p = 0.0014 using ANOVA), with a significant difference (p = 0.001) for up to 5 min in recovery.

Comparative effects of ciprofloxacin and lomefloxacin on the oxidative metabolism of theophylline.

Nine healthy male volunteers were studied to assess the interaction between theophylline and ciprofloxacin and to assess whether a similar interaction occurred with lomefloxacin, using a randomised, crossover design. Subjects received theophylline 125 mg 8 hourly with and without lomefloxacin 400 mg 12 hourly or ciprofloxacin 500 mg 12 hourly for 7 days. Ciprofloxacin treatment lowered total theophylline clearance by 27%, owing to a decreased clearance via 1-, 3-demethylation and 8-hydroxylation. Lomefloxacin treatment did not alter theophylline clearance. Ciprofloxacin, at usual clinical doses, could cause a clinically significant interaction when co-administered with theophylline.

Propofol: clinical strategies for preventing the pain of injection.

Eight modes of administration of propofol were assessed in order to minimise the pain of injection. An intravenous bolus injection in the antecubital fossa was the only approach that caused no pain. When administered intravenously in the dorsum of the hand the pain score and the number of patients who experienced pain was reduced significantly by mixing the agent with lignocaine when compared with a bolus injection. Slowing the speed of injection caused the greatest discomfort. An indirect biochemical mechanism for the pain is proposed.

The effect of fentanyl on propofol requirements for day case anaesthesia.

Fifty women of ASA grade 1 or 2 scheduled to undergo minor gynaecological procedures were allocated randomly to two groups. Group A received fentanyl 100 micrograms intravenously before induction; group B received no sedative or analgesic drugs. Anaesthesia was induced with propofol intravenously and maintained using 67% nitrous oxide in oxygen with incremental doses of propofol. Induction time and dose were significantly less and mean arterial pressure decreased significantly lower in Group A. These differences were, however, small and the ranges of values were large. The incidence of side effects and subjective assessment of quality of anaesthesia were similar in both groups. Fentanyl did not confer any practical advantage when used with propofol in the techniques described above.

Respiratory depression after morphine in the elderly. A comparison with younger subjects.

The effects of intravenous morphine (10 mg/70 kg) on the ventilatory response to CO2 were studied in two groups of subjects, young (18-29 years) and old (66-85 years), prior to elective surgery. In both groups morphine caused a significant depression of respiration as judged by a reduction in the slope of the CO2 response curve, a reduction in the calculated ventilation at an end tidal CO2 tension of 7.3 kPa, a rise in resting end tidal CO2 and a rise in the CO2 threshold. There were no significant differences between the two groups in the changes produced by the drug, suggesting that acute respiratory depression after a single intravenous injection of morphine is similar in old and young people.

Association of HLA and autoantibody in transfused sickle cell disease patients.

This study evaluates autoantibody production in sickle cell disease patients and determines whether genes in the major histocompatibility complex are associated with autoantibody responses. Rheumatoid factor was significantly increased for both male and female patients and was less prevalent in highly transfused patients. Significant increases were also detected in the incidences of antinuclear antibody for females and antismooth muscle antibody for males. Low incidence of antinuclear antibody was significantly associated with HLA-DR3. Significant associations were also found between the incidence of antinuclear antibody and both HLA-A28 and B15.

Sedation and cerebral angiography. The effects of pentazocine and midazolam on arterial carbon dioxide tension.

A study of the effects of sedation on arterial blood gases in patients undergoing cerebral angiography was performed. Twenty-one patients received pentazocine (30 mg) and midazolam (5-22.5 mg) and arterial carbon dioxide and oxygen tensions were measured from radial artery samples before and during the procedure. A statistically significant rise in arterial carbon dioxide tension was demonstrated. It is suggested that this may cause a rise in intracranial pressure by increasing cerebral blood flow in a group of patients in whom there is a high incidence of raised intracranial pressure. The clinical significance of this increase in arterial carbon dioxide tension is discussed.

Anti-nuclear antibodies in murine alloantisera are not necessarily related to antibodies to murine leukemia viruses.

Murine alloantisera often contain antinuclear antibodies. Frequently, these sera also have antibodies to murine leukemia viruses. In order to evaluate the relationship of these activities several alloantisera were tested for the presence of antinuclear and antiviral antibodies. The results of this study show that there is neither quantitative nor qualitative correlation between antinuclear and antiviral antibodies.

Handedness incidence in a population of black university students.

A modified version of the Edinburgh Handedness Inventory was used to assess degrees of left-, mixed-, and right-handedness in USA and Caribbean black university students. The distributional pattern of handedness in men and women was significantly different, largely due to a higher incidence of left- and mixed-handed men. Sinistral incidence in men of this population was significantly higher than that reported in some other studies on Anglo-Saxon populations.

Acebutolol and oral surgery: plasma levels following a single oral dose.

Twenty eight patients were randomly allocated into treatment or placebo groups. The treatment group received a single 400 mg oral dose of acebutolol, the placebo group an identical inert prepation. A blood sample from each patient was subsequently analysed for plasma concentrations of acebutolol and diacetolol, and the electrocardiogram was continuously monitored for changes of rate and rhythm. The plasma concentrations of acebutolol and diacetolol were all above the previously reported minimum levels for effective dysrhythmia control and the nine patients in whom irregularities of rhythm occurred were all in the placebo group. One patient in the treatment group, who was 58 years old, required intravenous injection of atropine for bradycardia and hypotension after induction of anaesthesia. It is suggested that in patients with small body weights and in those patients over 50 years of age the predmedication dose of acebutolol should be reduced to 200 mg.

Antinuclear factors in murine alloantisera.

We have demonstrated that anti-Thy 1.1 and certain of H-2 alloantisera contain an antinuclear factor (ANF) detected by fluorescent antimouse IgG. The incidence of ANF positive antisera that we report may actually be an underestimate. ANF is present in sera not only from our laboratory but also from other sources; thus ANF is not an artifact of our laboratory. ANF is not identical to alloantibody, and the ANF appears to be of an autoimmune nature. A variety of environmental and genetic factors may influence the appearance of ANF in anti-H-2 sera, but we believe that the consistent detection of ANF in sera directed against H-2.31,34 or against H-2.4 suggest that some specific aspect of immune stimulation by these H-2 antigens, and likely by other H-2 antigenic specifications, induces the appearance of ANF. It is not known whether it is these K and D antigens or other determinants associated with the H-2 complex that may actually provide the immune stimulation for ANF induction. The particular mechanisms that may be operating to induce ANF cannot be determined at present. We are continuing with experiments to define what parameters influence the appearance of ANF in alloantisera.

Qualitative and quantitative evaluation of indirect immunofluorescent H-2 stain on tissue sections.

We have utilized H-2 specific antisera from congenic resistant donor recipient combinations to localize H-2 antigens in tissue sections using the indirect immunofluorescent technique. H-2 specific immunofluorescence is observed in spleen, kidney, and liver sections: however, especially with liver sections, there are cases in which the expected specific stain is weak or absent. In addition to microscopic evaluation by eye, we have employed a microscope attached photometer; recordings from this instrument differentiate positive from control stained spleen sections.