A reappraisal of the stereoselective metabolism of nicotine to nicotine-1'-N-oxide

1. The cis and trans 1'-N-oxide metabolites of (2'R)-(+)-nicotine have the absolute configuration (1'S; 2'R) and (1'R; 2'R), respectively, and not the reverse as previously published. 2. Reinterpretation of metabolic data in the light of this reassignment reveals that N-oxidation of nicotine leads preferentially to the (1'R)-N-oxide, with little dependence on the configuration of the 2'-centre. 3. It is proposed that (2'S)-(-)-nicotine and (2'R)-(+)-nicotine bind to the same enzymic site by two distinct modes of binding; each of these modes involves the more basic centre (in this case the pyrrolidine ring) as the governing binding moiety.     

Some aspects of the relationship between body weight and sexual behaviour with particular reference to massive obesity and anorexia nervosa

There is some evidence for the existence of a precise weight/fat threshold for puberty. Following puberty, body weight and shape take on important new psycho-social significances for both males and females. Adolescent females usually strive to reduce their 'fatness' even it is not excessive from a biological standpoint. Super-obesity and anorexia nervosa are two human disorders of weight and fatness, more common in women, and importantly related to disturbances of sexual behavior, metabolic, social and experiential. These latter aspects sometimes at least reflect the presence of several factors which have contributed to the development of the disorders. Anorexia nervosa in particular reflects the adaptive psychosocial needs of the person concerned. Attention to this aspect during treatment will often allow the patient to tolerate the major weight gain required for recovery, thereby at the same time providing a paradigm for aspects of the pubertal process which can then be studied. The results of some such investigations together with related studies of the super-obese are reported here.     

Diagnosis and management of colovesical fistulas

Diagnosis and management may present difficult problems in patients with colovesical fistulas. Symptoms in the urinary tract are most common, and cystoscopy, and cystography are the most valuable diagnostic procedures. It may not always be possible to demonstrate the fistula by diagnostic tests, and a high index of suspicion should be maintained in patients with inflammatory or neoplastic disease of the rectosigmoid area or bladder with recurrent cystitis. Definitive treatment should include resection of the fistula and diseased segment of the intestine. Both one stage and multistage procedures have their place in the treatment of this condition. There are specific criteria for success for a one stage procedure.     

Upper extremity replantation: current concepts and patient selection

Dramatic advances in replantation and microsurgery have somewhat altered the criteria we use in selecting patients to be candidates for upper extremity replantation surgery. We suggest that contraindications for such replantation are: presence of associated life-threatening injuries; serious anesthetic risk; preexisting medical or psychiatric problems; previous injury or disease of the amputated part; warm ischemic time greater than 6-8 hours for extremities or greater than 10-12 hours for digits; and single-digit amputations (except thumb, for grasp). Replantation is feasible when: amputated part is properly preserved; injury type is sharp amputation, mild to moderate crush, or selected avulsion, and amputation is proximal to the DIP joint. Careful preservation of the amputated part, not in dry ice, is mandatory. On an individual basis, the decision to attempt replantation rests on the prediction that the patient may have better function with such surgery than with a prosthesis.     

Design approach to low-cost process control

The design of a control package for industrial use on small-scale processes is discussed. A modular system is described, made up of intelligent satellite and peripheral controllers plus various cards to provide communication with the industrial plant itself. The design is intended for operators who have little or no experience of computing. It is based on a language called paracode, an interpretive language structured to provide a number of control sequences which can run independently of each other or in parallel. Two applications of the design—a clean-in-place system and a beer-fermentation controller—are used as illustrations.     

Bilateral femoral neck fractures as a complication of myelography

This paper discusses two cases of bilateral subcapital fracture of the proximal femur as a complication of myelography with Conray 60. The literature is reviewed.     

Software to compute and conduct sequential Bayesian phase I or II dose-ranging clinical trials with stopping rules

The aim of dose-ranging phase I (resp. phase II) clinical trials is to rapidly identify the maximum tolerated dose (MTD) (resp., minimal effective dose (MED)) of a new drug or combination. For the conduct and analysis of such trials, Bayesian approaches such as the Continual Reassessment Method (CRM) have been proposed, based on a sequential design and analysis up to a completed fixed sample size. To optimize sample sizes, Zohar and Chevret have proposed stopping rules (Stat. Med. 20 (2001) 2827), the computation of which is not provided by available softwares. We present in this paper a user-friendly software for the design and analysis of these Bayesian Phase I (resp. phase II) dose-ranging Clinical Trials (BPCT). It allows to carry out the CRM with stopping rules or not, from the planning of the trial, with choice of model parameterization based on its operating characteristics, up to the sequential conduct and analysis of the trial, with estimation at stopping of the MTD (resp. MED) of the new drug or combination.