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1.
Thorax ; 72(6): 576-578, 2017 06.
Article in English | MEDLINE | ID: mdl-28404809

ABSTRACT

The Heimlich manoeuvre is a well-known intervention for the management of choking due to foreign body airway occlusion, but the evidence base for guidance on this topic is limited and guidelines differ. We measured pressures during abdominal thrusts in healthy volunteers. The angle at which thrusts were performed (upthrust vs circumferential) did not affect intrathoracic pressure. Self-administered abdominal thrusts produced similar pressures to those performed by another person. Chair thrusts, where the subject pushed their upper abdomen against a chair back, produced higher pressures than other manoeuvres. Both approaches should be included in basic life support teaching.


Subject(s)
Airway Obstruction/therapy , Foreign Bodies/therapy , Heimlich Maneuver/methods , Aged , Air Pressure , Food , Humans , Male , Middle Aged , Thorax/physiopathology
4.
Endocr Relat Cancer ; 22(4): R219-33, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26113607

ABSTRACT

The year 2015 marks the 50th anniversary since the discovery of the anticancer potential of cisplatin and it remains just as useful now as it did back then, especially for the treatment of some endocrine-related cancers like ovarian and testicular carcinomas. Since its discovery, five other platin drugs have received approval in various countries. While several new platin drugs are in preclinical development, in the last decade only two new platin drugs have entered clinical trials, LA-12 and dicycloplatin, reflecting a shift in research focus from new drug design to improved formulations of already approved platin drugs. These formulations include their encapsulation with macrocycles to slow and prevent their degradation by proteins and peptides; their attachment to nanoparticles to passively target solid tumours through the enhanced permeability and retention effect and their coordination to important nutrients, proteins, antibodies and aptamers for active tumour targeting. These formulation methods have all shown potential but none have yet yielded a new marketable medicine containing a platin drug. The reasons for this are problems of consistent drug loading, controlling the location and timing of drug release and the inherent toxicity of some of the drug delivery vehicles. In addition to drug delivery, functional genomics is now playing an increasing role in predicting patients' responses to platin chemotherapy and their likelihood of experiencing severe side effects.


Subject(s)
Antineoplastic Agents/therapeutic use , Organoplatinum Compounds/therapeutic use , Antineoplastic Agents/administration & dosage , Carboplatin/administration & dosage , Carboplatin/therapeutic use , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Drug Delivery Systems , Humans , Organoplatinum Compounds/administration & dosage
5.
J Vis Exp ; (87)2014 May 28.
Article in English | MEDLINE | ID: mdl-24893964

ABSTRACT

Amide coupling reactions can be used to synthesize bispyridine-based ligands for use as bridging linkers in multinuclear platinum anticancer drugs. Isonicotinic acid, or its derivatives, are coupled to variable length diaminoalkane chains under an inert atmosphere in anhydrous DMF or DMSO with the use of a weak base, triethylamine, and a coupling agent, 1-propylphosphonic anhydride. The products precipitate from solution upon formation or can be precipitated by the addition of water. If desired, the ligands can be further purified by recrystallization from hot water. Dinuclear platinum complex synthesis using the bispyridine ligands is done in hot water using transplatin. The most informative of the chemical characterization techniques to determine the structure and gross purity of both the bispyridine ligands and the final platinum complexes is (1)H NMR with particular analysis of the aromatic region of the spectra (7-9 ppm). The platinum complexes have potential application as anticancer agents and the synthesis method can be modified to produce trinuclear and other multinuclear complexes with different hydrogen bonding functionality in the bridging ligand.


Subject(s)
Amides/chemistry , Antineoplastic Agents/chemical synthesis , Coordination Complexes/chemical synthesis , Organoplatinum Compounds/chemical synthesis , Pyridines/chemical synthesis , Amines/chemistry , Isonicotinic Acids/chemistry , Ligands
6.
PLoS One ; 9(1): e85361, 2014.
Article in English | MEDLINE | ID: mdl-24454850

ABSTRACT

The macrocycle family of molecules called cucurbit[n]urils are potential drug delivery vehicles as they are able to form host-guest complexes with many different classes of drugs. This study aimed to examine the utility of Cucurbit[6]uril (CB[6]) in topical cream-based formulations for either localised treatment or for transdermal delivery. Cucurbit[6]uril was formulated into both buffered cream aqueous- and oily cream-based dosage forms. The solid state interaction of CB[6] with other excipients was studied by differential scanning calorimetry and the macrocycle's transdermal permeability was determined using rat skin. Significant solid state interactions were observed between CB[6] and the other dosage form excipients. At concentrations up to 32% w/w the buffered aqueous cream maintained its normal consistency and could be effectively applied to skin, but the oily cream was too stiff and is not suitable as a dosage form. Cucurbit[6]uril does not permeate through skin; as such, the results imply that cucurbituril-based topical creams may potentially only have applications for localised skin treatment and not for transdermal drug delivery.


Subject(s)
Bridged-Ring Compounds/administration & dosage , Dosage Forms , Imidazoles/administration & dosage , Pharmaceutical Vehicles , Administration, Topical , Bridged-Ring Compounds/chemistry , Calorimetry, Differential Scanning , Drug Delivery Systems , Fluorescence , Imidazoles/chemistry , Skin Absorption , Thermogravimetry
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