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Dry tree floating platforms for deepwater offshore developments are typically Spars and Tension Leg Platforms (TLPs). All production semisubmersibles in operation support only wet tree systems because the hull motions are not sufficiently small to allow the use of riser tensioning systems which connect vertical production risers from the subsea wells directly to the topsides. The wet tree semisubmersible designs can potentially be improved for dry tree applications with reduced heave motions. The advantages of dry tree semisubmersibles for deepwater development are presented in this paper with focus on the hull global performance and the cost benefits. This paper presents a dry tree semisubmersible design with low heave motion and reduced vortex-induced-motion (VIM), hence named Heave and VIM Suppressed (HVS) semisubmersible. A case study of the HVS semisubmersible is performed for the dry tree application to support a relatively small topsides payload of 7,000 MT and five top tensioned risers (TTRs) in benign South East Asian environment. Through numerical simulations using Computational Fluid Dynamics (CFD) and conventional motion analysis based on potential flow theory, the hull global performance and maximum riser tensioner stroke range are provided. The stability analysis results for intact and damaged conditions are presented. The constructability and stability in pre-service conditions are briefly discussed to address the practical application of this hull with respect to cost effectiveness. The results demonstrate technical readiness of this hull design by showing its ability in supporting dry tree systems with field proven riser tensioners and its superior stability for drilling operations. The application of this dry tree semisubmersible is technically feasible today in mild-to-moderate environmental conditions and thus it is an attractive option for new deepwater development with potential cost benefits.

Riminophenazines were specifically developed as drugs active against Mycobacterium tuberculosis but extensive research over several decades has shown that these compounds are also active against many other mycobacterial infections, particularly those caused by Mycobacterium leprae and the Mycobacterium avium complex (MAC). Clofazimine, the lead compound in this series, is included in the regimens that are approved by the WHO for the treatment of leprosy and has contributed significantly to the control of that disease, particularly that caused by dapsone-resistant bacteria. Despite early problems, clofazimine has shown clinical efficacy in tuberculosis, in particular that caused by multiple drug resistant strains. Clofazimine does not induce resistance and also inhibits emergence of resistance to isoniazid in M. tuberculosis. The efficacy of clofazimine against MAC is more varied and the availability of better drugs has limited its use. Newer riminophenazines, such as B746 and B4157, not only showed increased anti-mycobacterial activity but also produced less skin pigmentation, which is the main drawback of this group of compounds. The most important virtues of riminophenazines, such as intracellular accumulation in mononuclear phagocytic cells, anti-inflammatory activity, a low incidence of drug resistance and slow metabolic elimination, make them attractive candidates for the treatment of mycobacterial infections. It is essential, however, to investigate the newer analogues clinically, while continuing the pursuit of alternate candidates that demonstrate higher anti-mycobacterial activity and lower rates of skin pigmentation.

A rapid and sensitive HPLC method is described for the analysis of synthetic phenazines, including clofazimine, from a variety of biological samples. Phenazines were extracted from serum, tissue and fat using a mixture of dichloromethane and sodium hydroxide. The drugs were then quantified on a reversed-phase C18 column using a mobile phase consisting of 594 ml of water, 400 ml of tetrahydrofuran, 6 ml of concentrated acetic acid and 0.471 g of hexanesulfonic acid. In this mobile phase, each phenazine tested had its own retention time. This allowed one phenazine to be used as an internal standard for the analysis of other phenazines. The method was validated for clofazimine [3-(4-chloroanilino)-10-(4-chlorophenyl)-2,10-dihydro-2-(isopro pylimino) phenazine] and B4090 [7-chloro-3-(4-chloranilino)-10-(4-chlorophenyl)-2, 10-dihydro-2-(2,2,6,6-tetramethylpiperid-4-ylimino)phenazine ] (VI) and shown to be accurate and precise across a broad concentration range from 0.01 to 50 micrograms/g (microgram/ml). Extraction was 100% for each agent across this range. This system was used to measure clofazimine and VI levels following their administration to rats. The pharmacokinetic profile of VI was different to that of clofazimine, with high tissue concentrations but lower fat levels.

Clofazimine (CFM), a riminophenazine drug, is primarily used in therapy for leprosy and Mycobacterium avium infections. With an objective of identifying drugs active against Mycobacterium tuberculosis, including those with multi-drug resistance, we investigated CFM and nine of its chemical analogues. Among these, B746 and B4101 had better activity than CFM against six drug-susceptible and nine single/multiple drug-resistant M. tuberculosis strains. B746 also showed slightly better activity than CFM against intracellular M. tuberculosis in J774A.1 macrophages and was comparable to CFM in its in vivo activity against experimental tuberculosis in C57BL/6 mice. Interestingly, it caused less pigmentation in internal organs.

Clofazimine (CFM), a riminophenazine drug, is primarily used in therapy for leprosy and Mycobacterium avium infections. With an objective of identifying drugs active against Mycobacterium tuberculosis, including those with multi-drug resistance, we investigated CFM and nine of its chemical analogues. Among these, B746 and B4101 had better activity than CFM against six drug-susceptible and nine single/multiple drug-resistant M. tuberculosis strains. B746 also showed slightly better activity than CFM against intracellular M. tuberculosis in J774A.1 macrophages and was comparable to CFM in its in vivo activity against experimental tuberculosis in C57BL/6 mice. Interestingly, it caused less pigmentation in internal organs.

ac voltammograms were recorded for gold in different strong acids both in the absence and presence of various oxidants and reductants. Two incipient hydrous oxide species were assumed to be involved: a similar conclusion was reached earlier for gold in base. The first was a cationic Au(I) species that is stable to quite low potentials; the reversible potential for formation of this species is too low to be of interest in most electrocatalytic reactions in acid. However, this lower oxide is apparently an inhibitor of S 2 O 2− 8 reduction. The second product, formed by oxidation of low coverage Au adatoms, can exist in two different forms: analogous behaviour was again noted earlier for this metal in base. The Au(III) products were observed to mediate oxidations, and inhibit reductions, of different species at two distinct potentials, one at ca 0.8 V( rhe ) and the other at ca 1.0 V( rhe ). The latter conclusions were supported by dc investigation of the same processes.

The stability of hydrous oxide films grown on platinum in both acid and base was investigated as a function of holding potential in solutions of different pH. In contrast to similar films grown on gold —whose behaviour was described earlier—the stability of the bulk of the hydrous oxide deposits on platinum was not very dependent on solution pH. This was attributed to a rather facile rearrangement, in the case of platinum, of the initially anionic oxide species to a virtually neutral state. However, there was invariably a minor component in these deposits that was difficult to reduce in base; this probably involves an outer layer of oxide material (the latter being in contact with the aqueous phase) which retained its hyperextended, anionic form. Reduction of the bulk hydrous oxide in base showed a marked degree of inhibition in the region of 0 V(RHE); the effect seemed to be related to the presence of weakly bound hydrogen on the platinum surface. The hydrous oxide growth process on platinum showed a marked dependence on electrode history—this is a topic for further investigation.

Evidence is presented to illustrate the important role of hydrous oxide in noble metal electrocatalysis. It was demonstrated, for instance, that in the case of gold in acid the onset/termination potential, under potential sweep conditions, for hydrazine oxidation and persulfate or iodate reduction occurred at the end of the hydrous oxide reduction peak (recorded for a thick film growth grown by potential multicycling); there was also a maximum in the faradaic ac response for gold in acid in the same region. Both gold and platinum were investigated in acid and base electrolytes. In some cases a range of potential, rather than a discrete value, was found to be involved, different species react with (or are inhibited by) different types (or coverages) of these submonolayer species. In some, possibly electrocatalytically nondemanding, reduction reactions the hydrous oxide seemed to have little effect.

In 1921 there was little provision for the care of the pregnant woman in Northern Ireland where there were only two hospitals staffed by specialist obstetricians. The mortality statistics reflected this, the province having the highest maternal mortality and the second highest infant mortality rates in the United Kingdom. There was little progress until the establishment of the National Health Service in 1948. Within a short time, excellent hospital specialist and domiciliary midwifery services were developed. Scientific advances, mainly during the 1970's, led to further expansion of the specialist service and the disappearance of the general practitioner service. These advances have again been reflected in the statistics. The maternal mortality is now zero and the perinatal mortality 8 per 1,000 births.

The intra- and extracellular activities of 5 novel tetramethylpiperidine (TMP)-substituted phenazines against Mycobacterium tuberculosis H37Rv (ATCC 27294) were determined and compared with those of clofazimine and rifampicin. Two of these agents, together with clofazimine, were also tested for their activities against drug-resistant strains of M. tuberculosis. Three of the TMP-substituted phenazine compounds were significantly more active than clofazimine against M. tuberculosis, including multidrug-resistant clinical strains of this microbial pathogen, demonstrating a lack of cross-resistance between the riminophenazines and standard anti-tuberculous drugs. Using M. tuberculosis-infected monocyte-derived macrophages, all of the TMP-substituted phenazines were found to possess intracellular activity which was superior to that of both clofazimine and rifampicin. In this model of intracellular bioactivity, the experimental compounds inhibited bacterial growth at concentrations which were approximately 10-fold lower than the corresponding minimal inhibitory concentration values obtained using conventional in vitro sensitivity testing procedures. These results demonstrate that the novel TMP phenazines are active against multidrug-resistant M. tuberculosis strains, and particularly effective intracellularly.

In our efforts to develop new drugs for the treatment of tuberculosis, especially that caused by multidrug-resistant strains, we investigated clofazimine (CFM) and two of its analogs, B4154 and B4157, for their antituberculosis activities. Twenty M. tuberculosis strains were tested, including 16 drug-resistant strains (strains resistant to one or more antituberculosis drugs), for their susceptibilities to these three agents. All of the strains were found to be susceptible to B4154 and B4157, and one strain showed moderate resistance to CFM. The MICs of B4154, B4157, and CFM at which 90% of strains were inhibited were 0.25, 0.12, and < or = 1.0 microgram/ml, respectively. The intracellular activities of CFM and B4157 were superior to that of B4154. The chemotherapeutic activities of the three compounds were evaluated in C57BL/6 mice. At a dose of 20 mg/kg of body weight, the activity of CFM was slightly superior to that of B4157; however, both compounds prevented mortality and caused a significant reduction in the numbers of CFU in the lungs and spleens. The animals treated with B4157 showed less pigmentation than animals treated with CFM. The chemotherapeutic activity of CFM was comparable to those of rifampin and isoniazid. Complete susceptibility of multidrug-resistant strains to CFM and B4157 and the therapeutic efficacies of these compounds against mouse tuberculosis make these drugs attractive agents for the treatment of drug-resistant tuberculosis.

Hepatocarcinogenesis is deterministic in transgenic mice expressing in the liver gene construct Alb-DS4 that encodes autocrine growth factor IgEGF (D Stern et al. (1987), Science 235: 321-324), causing their death within 7.1 months. Hepatic expression of construct AAT-myc encoding murine c-myc causes liver cancer in 44% of the mice at 14.8 months. Cooperation of these genes was evident in CD2F1 transgenics bearing Alb-DS4 plus AAT-myc, in which accelerated hepatocellular carcinoma (HCC) formation caused death of all mice within 4.4 months. Alb-DS4 also cooperates with the Hcs locus, which in C3H/HeJ mice mediates high susceptibility to spontaneous hepatocarcinogenesis, causing accelerated formation of HCC to which mice succumbed at 5.1 months. Thus, genes that predispose to HCC formation cooperate in transgenic mice and their interaction is a key to understand mechanisms that cause liver cancer.

(1995). The Pharmacology, Metabolism, and Chemistry of Clofazimine. Drug Metabolism Reviews: Vol. 27, No. 4, pp. 591-614.

The successful development of a methanol/air fuel cell requires optimum performance of the air/ oxygen cathode at about 0.8 V vs RHE. Ideally the operating potential should be even more positive but oxygen gas reduction on platinum (the best electrocatalyst for this reaction to date at low pH) is generally severely inhibited above 0.8 V. It was demonstrated that in the region of interest the performance of platinum dispersed on carbon prepared by a thermal reduction technique was much superior to that of a similar material in which the platinum was dispersed on carbon by a wet chemical procedure. With the latter material the surface is apparently too reactive: surface platinum atoms of quite low lattice coordination number spontaneously oxidize to yield incipient hydrous oxide species that inhibit the oxygen gas reduction process to potentials below about 0.6 V vs RHE, at which point this oxide is unstable with regard to reduction. The superior performance of the slightly sintered material may be attributed to the lower tendency of the slightly less reactive surface to spontaneously form the inhibiting oxide.

Twenty-five compounds structurally related to clofazimine were tested for their ability to inhibit the growth of Mycobacterium leprae using the kinetic method of drug evaluation in the mouse foot pad model of leprosy. Seven of the phenazine derivatives displayed anti-M. leprae activity comparable to that of clofazimine when administered at a concentration of 0.01% (w/w) in the diet. Three of the compounds, B746, B4087, and B4101, were active when administered at 0.001% in the diet. At a dietary concentration of 0.0001%, B4087 and B4101 were slightly more active than clofazimine, while B746 was less active. In the kinetic method of drug evaluation, greater anti-M. leprae activity of phenazine derivatives was generally associated with greater pigmentation of abdominal fat. Of the compounds which did not cause pigmentation when fed at a concentration of 0.01% in the diet B4090 was the most active. This compound also inhibits the growth of a clofazimine-resistant M. smegmatis strain.

A case of autoimmune oophoritis is reported. A 41-year-old woman had a total abdominal hysterectomy and bilateral salpingo-oophorectomy for menorrhagia, polymenorrhoea and cystic ovaries. The diagnosis of autoimmune oophoritis was not suspected clinically, and was an unexpected histological finding in the ovaries. The gross and histological appearances of this rare condition are described, and the lymphoid infiltrate characterised by immunocytochemistry. Recognition of this condition by pathologists is important, as there is an associated risk of developing other autoimmune disease, even some years later, necessitating close patient follow-up. In this case serum auto-antibodies to adrenal cortex were detected, indicating a subsequent risk of Addison's disease.

Evidence is presented to illustrate the important role of hydrous oxide in noble metal electrocatalysis. It was demonstrated, for instance, that in the case of gold in acid the onset/termination potential, under potential sweep conditions, for hydrazine oxidation and persulfate or iodate reduction occurred at the end of the hydrous oxide reduction peak (recorded for a thick film growth grown by potential multicycling); there was also a maximum in the faradaic ac response for gold in acid in the same region. Both gold and platinum were investigated in acid and base electrolytes. In some cases a range of potential, rather than a discrete value, was found to be involved, different species react with (or are inhibited by) different types (or coverages) of these submonolayer species. In some, possibly electrocatalytically nondemanding, reduction reactions the hydrous oxide seemed to have little effect.

Clofazimine analogues active against a strain of Mycobacterium smegmatis 607 made resistant to the antileprosy agent have been synthesized. Activity (i.e., less than or equal to 2 micrograms/mL causing complete inhibition of growth) requires that there be a basic nitrogen in the "rimino" side chain and that the spacer distance between this nitrogen and the imino nitrogen be at least three carbon atoms. The nitrogen may be primary, secondary, or tertiary and may be part of an open chain or enclosed in a ring compound. Provided that the criteria of basicity and spacer distance are satisfied, all are active in vitro against both the sensitive and resistant strains. Substitution elsewhere in the molecule had little effect on the activity. The compounds have been shown to have growth inhibitory activity against human-derived Mycobacterium leprae in murine macrophages in culture.

A case of extra uterine pregnancy with a surviving mother and baby is reported. from a review of the literature it is obvious that:—

SummarySummaryThirty-seven patients with recurrent stress incontinence despite previous surgery, underwent the gauze-hammock sling operation. Seven patients had pre-operative urodynamic assessment. Three yean after surgery 28 patients (76 per cent) were cured. In nine cases the operation failed. Three of the nine needed removal of the sling, and two others had detrusor instability on postoperative urodynamic studies. Age, weight, and parity were not related to surgical outcome. The gauze-hammock operation is an effective treatment for recurrent stress incontinence. The success rate could possibly be improved further by pre-operative urodynamic assessment.

The action of ethanolic potassium cyanide on certain 2- benzylidene- coumaran - 3-ones gives the corresponding flovones

Hydrogenations de dihydro-1,2 imidazo [4,5-b] phenazines en aryl-10 arylamino-3 dihydro-2,10 phenazinone-2 imines

Derivatives of pyridazine and benzodiazines have been found to possess growth inhibitory properties against HeLa cells in vitro and experimental tumours in mice.