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Additional file 1:. Grown in Wales Prenatal Participant Questionnaire

The quartz-tube method for the combustion of organic samples before the determination of sulphur1 has been improved. A new catalyst—ceria on alumina—has been produced which is as active as the previous vanadium oxide catalyst, and has the advantage of being unaffected by chlorine. The absorption train has also been much improved. These modifications are described in Part I. A rapid volumetric method, using disodium dihydrogen ethylenediaminetetra-acetate, for the determination of low concentrations of sulphate ion is described in Part II. This method has been shown to give results of the same order of accuracy as those obtained by the standard gravimetric procedure.

The bending of flat sheet metal materials using a laser process is not new to the metals industry. However, refining the process to the point where an angle bend can be predicted is significant when developing prototypes of small and large components. The methods and process developed to perform this task are presented, and key elements to maintain consistency and repeatability of the process are identified. A 50-Watt CO2 Desktop laser system provided the appropriate controls necessary to create the specific shapes. The forming tests were performed on CRES (302) with thickness varying from 0.26 mm to 0.64 mm. The variations of beam divergence, feed rate, laser power, and pulses per inch were evaluated, and the effects of these laser variables are presented. Material preparation techniques are also described since it was determined that the surface condition and the methods of edge preparation had significant effects on the overall results of forming. Compound radius bends were performed by calculating the effects of simple bends in conjunction with multiple passes. The data collected from the experiments were compiled and a section on the analysis of these data is also presented. This program was a joint effort in cooperation with the American Welding Society under contract with the Defense Advanced Research Projects Agency (DARPA). The initial development work was funded by DARPA through the Flexible Laser Automated Intelligent Research (FLAIR) program and the remaining work performed on the task was funded internally by High Tech Images and Tactical Technical Solutions, Inc. A synopsis of the laser forming process development and applications of the laser forming process are given.The bending of flat sheet metal materials using a laser process is not new to the metals industry. However, refining the process to the point where an angle bend can be predicted is significant when developing prototypes of small and large components. The methods and process developed to perform this task are presented, and key elements to maintain consistency and repeatability of the process are identified. A 50-Watt CO2 Desktop laser system provided the appropriate controls necessary to create the specific shapes. The forming tests were performed on CRES (302) with thickness varying from 0.26 mm to 0.64 mm. The variations of beam divergence, feed rate, laser power, and pulses per inch were evaluated, and the effects of these laser variables are presented. Material preparation techniques are also described since it was determined that the surface condition and the methods of edge preparation had significant effects on the overall results of forming. Compound radius bends were performed by calculating the...

Temperature and blood flow studies were performed in the upper limbs of six patients with reflex sympathetic dystrophy (RSD), nine patients with repetitive strain injury (RSI) and 12 control subjects using thermography, laser Doppler flowmetry, infrared photoplethysmography and venous occlusion strain gauge plethysmography. The contralateral responses of the symptomatic and asymptomatic limbs were examined after being subjected, separately, to mild cold stress (20°C for 1 min). Altered thermoregulation and haemodynamics were evident in RSD. Though the pattern of response to contralateral cold challenge is similar to normal in RSI, vasodilatation and reduced vasomotion appears to be characteristic in this condition. Such changes may assist in distinguishing between RSD and RSI from other causes of chronic upper limb pain.

The disposition of metronidazole in cervical mucus and serum after single and repeated oral doses (400 mg) was investigated in six healthy female subjects. Metronidazole reached higher concentrations in serum than cervical mucus after both single and repeated oral doses. Metronidazole concentrations in both cervical mucus and serum were high enough to be trichomonicidal and bactericidal. After oral administration, metronidazole concentrations in cervical mucus are due to diffusion rather than ion trapping.

Concentrations of an acidic drug, ibuprofen, in cervical mucus and serum have been measured by HPLC after oral administration in six healthy volunteers. After an 800 mg single dose of ibuprofen, the concentration reached in cervical mucus was less than 4% of that in serum. It is postulated that because ibuprofen is an acidic drug which is not subject to ‘ion-trapping’ in the acidic environment of cervical mucus, it is not concentrated in this secretion.

Pentoxifylline was tested in three raising concentrations (0.7 mM/l, 1.5 mM/l, 3.6 mM/l) on human sperm cells in vitro. On 143 samples, we examined drug effect on motile sperm concentration, grade of their motility, acrosome reaction and membrane status. Obtained results show improvement in motile sperm concentration, as well as in the grade of progression in the majority of samples. Spermatozoa membranes as well as occurrence of the acrosomal reaction were not affected by penoxifylline.

1. The trans-membrane migration ratio (TMMR) technique is a simple method for quantitating and comparing the effect of drugs on sperm motility. 2. The ultrafilter membrane (Nucleopore) used allows mixing between the solutions on either side resulting in 21-fold dilution of a drug initially mixed with semen. 3. The concentration of drug originally mixed with semen does not remain constant over the incubation time. 4. The phosphate buffer saline (PBS) in the lower chamber should be replaced by PBS containing the same concentration of drug as in the upper chamber so that a homogenous system is established throughout the incubation. 5. Reports of previous studies using this technique may have underestimated the effect of drugs on sperm motility.

Lithium is a widely prescribed drug used for the treatment of bipolar affective illness. Previous reports on its effects on sperm motility and male fertility are conflicting. The effect of lithium on human sperm motility was examined in vitro using the modified transmembrane migration method. This technique takes account of the dilution of lithium that occurs during the incubation. Lithium inhibits human sperm motility in vitro in concentrations comparable with those reported to be achieved in semen after oral administration.

SummaryTwenty-three hospital in-patients with severe lower respiratory tract infections were treated with cefuroxime sodium. The drug was given intramuscularly in a dose of either 750 mg or 1000 mg at 8-hourly intervals for 5 days. Of the 21 patients who could be assessed, the response to treatment was highly satisfactory and there were no treatment failures. Eight patients had failed to respond to a course of oral antibiotics before being seen. Most of the patients were elderly and all were very ill. The sputum became mucoid in all but 1 patient. There was no change in tests of liver or renal function. Cefuroxime appears to be an effective and well-tolerated drug for the treatment of patients with severe chest infections.

Measurements of the back central optical radius in the course of 336 hours of hydration of lathe cut corneal lenses disclosed changes in curvature which were more rapid and of greater magnitude than those previously reported for poly (methyl methacrylate) lenses.

Six healthy women participated in a study of the concentrations of propranolol achieved in plasma after insertion of the drug into the vagina. In four of the women the concentrations were also determined after administration by mouth. The area under the concentration curve for propranolol administered per vaginam was significantly greater than that after oral administration. There were small significant reduction in systolic blood pressure, pulse rate, and forced expiratory volume in one second after vaginal administration but these did not cause any symptomatic side effects. The tolerability of the vagina to drugs and the safety of this form of treatment remain to be determined. Probably further studies of the contraceptive effects of propranolol should be conducted with the dextro isomer of the drug.

Thirteen hypertensive patients entered a double-blind crossover trial of guanethidine and oxprenolol in combination. In nine patients who completed the trial there was an additive effect on blood pressure, but the combination had a smaller effect on heart rate than was expected from the individual effects, and side effects were not increased. During treatment with oxprenolol the plasma potassium concentration rose from 3.6 mmol (mEq)/1 to 3.9 mmol (mEq)/1. No correlation was found between the plasma oxprenolol concentration and changes in blood pressure or response to injected isoprenaline, but measurements of plasma oxprenolol concentrations were of value in determining compliance with the protocol.

The effort to develop vaginal contraceptives began in the distant past and is still underway today. 1000 years ago, South American Indians inserted into the vagina bark strips impregnated with quinine. In medieval times women used vaginal inserts of cloth soaked in honey or vinegar. Quinine pessaries were introduced into Europe in the late 1800s, and in the early 1900s investigators began to study the effects of various chemicals on sperm motility. Following World War II, surfactant spermicides which disrupt the sperm membrane were developed and marketed. Many of these preparations contained nonoxynol-9. Currently, the D-isomer of propranolol is being examined as a spermicidal contraceptive, and several bacteriocides, e.g., benzalkonium and chlorhexidine, are being developed as spermicides which reduce the penetrability of cervical mucus. Other chemicals being investigated act by inhibiting the acrosome reaction. Advantages of vaginal contraceptives are that they are inexpensive, reversible, and relatively safe and easy to use. Generally they require no medical intervention or supervision. In addition, spermicides may kill or inhibit the growth of organisms responsible for sexually transmitted diseases. Disadvantages of spermicides are that they are generally less effective than many other methods, some interfere with sexual spontaneity, they may cause local irritations, and some women find them messy to use. Recently, concerns were expressed about the possible teratogenic effects of sperimicides. Most of these concerns proved to be unfounded. Given the many new avenues of research, the major disadvantage of sperimicides, i.e., their high failure rates, may be minimized in the near future.

Sixteen patients with moderately severe essential hypertension completed a double-blind crossover trial with four treatment periods each lasting for six weeks. They received in random order, placebo; tienilic acid 250 mg/day; propranolol 80 mg b.d.; and tienilic acid 250 mg/day and propranolol 80 mg b.d. in combination. Mean blood pressure in the lying position was 169/98 mmHg on placebo, 157/94 mmHg on tienilic acid, 159/90 mmHg on propranolol and 142/86 mmHg on the combination of tienilic acid and propranolol. The effects of tienilic acid and propranolol on blood pressure were additive and there was no evidence of any interaction. The onset of the hypotensive effect of tienilic acid was gradual while the effect of propranolol was maximal within 2 weeks of the start of treatment. Tienilic acid produced a significant reduction in serum urate from 0.33 mmol/l to 0.18 mmol/l. The combination of tienilic acid and propranolol in the doses used in the trial was effective and acceptable in the reduction of raised blood pressure.

Fifteen episodes of encephalopathy have been studied in 13 renal transplant recipients. All episodes of encephalopathy occurred during an acute rejection crisis. Clinical and biochemical features were recorded during rejection crises associated with encephalopathy and in an equal number of uncomplicated rejection episodes in the same patients. Encephalopathy was related to the severity of the rejection crisis and not to other features such as blood pressure, fever, steroid therapy or plasma electrolytes. The definition of the syndrome of rejection encephalopathy and its relation to the severity of the rejection has important therapeutic implications. Steroid therapy should not be withdrawn or reduced because of acute neurological features. Control of hypertension, fluid overload and electrolyte imbalance, in addition to treatment of the rejection episode, are necessary to reverse the encephalopathy. The prognosis of this syndrome is excellent with no long-term sequelae.

Hypoxia is well known to cause an increase in brain anaerobic glycolysis. Ornithine alpha ketoglutarate (OAKG) given to six dogs was shown to attenuate these metabolic disturbances caused by hypoxia. Brain oxygen utilization was higher after ornithine alpha ketoglutarate during hypoxia than during a period of hypoxia alone. It is suggested that the clinical usefulness of OAKG should be explored in those situations where there is cerebral hypoxia or ischemia.

Spermicides have long been used for vaginal contraception. Quinine was the prototype membrane-active drug used as a vaginal spermicide. Subsequently, propranolol, in both racemic and D-isomeric forms, has been shown to be a powerful inhibitor of sperm motility. The transmembrane migration ratio method was used to quantify the effects of various drugs with membrane stabilizing activity such as propranolol on sperm motility in vitro. Preliminary data from a clinical trial suggests that propranolol tablets used as a vaginal spermicide produce a pregnancy rate of between 3-4/100 women-years in a fertile population. Propranolol is extensively absorbed from the vagina since systolic blood pressure fell below baseline values and plasma concentrations were higher after vaginal administration than after oral administration. Pulse rates also declined. The clinical implications of these studies are discussed.

Propranolol inhibits sperm motility and has been considered as a spermicide contraceptive. In view of the inhibitory effects of D-propranolol on sperm flagellar activity, we have investigated its effect on motility and growth of two human flagellate, protozoan parasites. D-propranolol had a dose-dependant inhibitory effect on motility of Giardia lamblia and Trichomonas vaginalis with ED50s of 0.38 and 0.66 mmol/l respectively, D-propranolol also inhibited growth of both parasites with ED50s of 0.18 and 0.23 mmol/l for Giardia and Trichomonas respectively. D-propranolol, unlike DL-propranolol is devoid of the unwanted effects of beta-blockade, and thus may be a useful antiprotozoal drug particularly after vaginal placement when it is concentrated in vaginal mucus.

Summary Fifteen hypertensive patients entered a single-blind study to examine the effects of metoprolol (100 mg twice daily) on fasting plasma lipids. In 12 patients who completed the study, non-esterified fatty acid concentrations fell, but cholesterol and triglyceride levels were unchanged after 12 weeks' treatment. These results conflict with earlier reports of the effect of metoprolol on plasma triglyceride concentrations.

1 The effect of intravenous injections of labetalol at doses of 1 and 2 mg/kg was studied in 15 patients with severe hypertension inadequately controlled by beta-adrenoreceptor-blocking drugs. 2 At a dose of 1 mg/kg there was a slight but statistically insignificant reduction in blood pressure. When 2 mg/kg was given there was a prolonged (6 h) significant reduction in lying blood pressure. At both dose levels there was a small initial increase in pulse rate but forced peak flow was not affected. 3 Side-effects were limited to transient postural hypotension and a feeling of warmth. 4 It is concluded that intravenous labetalol at a dose of 2 mg/kg is safe and effective in rapidly reducing blood pressure in patients already receiving beta-adrenoreceptor-blocking drugs.

The potencies of caffeine, theophylline, lysine-theophylline and 3-isobutyl-1-methylxanthine (IBMX) in stimulating sperm motility have been compared, and we have found IBMX to be significantly more potent than the other three compounds, which did not exhibit significant differences in potency from each other.