Closed to reason: time for accountability for the International Narcotic Control Board

For more than two decades, the International Narcotic Control Board (INCB) has tried to stop harm reduction and its HIV prevention programs. This posture is based on a fundamental misunderstanding of their responsibilities and of drug addiction itself – i.e. as a public health and clinical care matter made criminal by decree. A recent focal point for the Board's action has been rejecting the use of supervised injection facilities to reduce morbidity and mortality of drug injectors. They single out individual countries and attempt to bully them into rejecting such programs under the banner of the United Nations (falsely) and in the name of international treaties. Their unrelenting and unjustified badgering of signatories to the international treaties that established the INCB is not only unjustified; it is an affront to one of the core purposes of the Board itself: to ensure adequate medical supplies and safe use of controlled substances. The INCB's ill-conceived obsession with intravenousaddiction as a crime flies in the face of the medical view and policies of the World Health Organization and the universally endorsed principles of the General Assembly of the United Nations.     

Semirigid and malleable penile implants

Unless complications such as infection, erosion, or excessive bleeding develop and unless an inordinate number of malpractice suits ensue, I believe that the outpatient setting for implantation of a penile prosthesis will become increasingly utilized. As emphasized at the beginning of this article, the essential basis for success is thorough evaluation of the candidates for implantation, detailed and documented informed consent, and the elimination as outpatient candidates of poor-risk patients such as certain insulin-dependent diabetics. Patients who are good surgical and postsurgical risks are totally acceptable for outpatient operation. The cost to the patient and insurance carriers is drastically reduced. There is every reason to believe that, in the hands of the highly qualified surgeon, this type of intervention is safe, reliable, and cost-effective.     

Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.     

Inhibitory effects of AH 21-132 in guinea-pig isolated ileum and taenia caeci.

1. AH 21-132 is being investigated as a potential chemotherapeutic agent for bronchial asthma. The present experiments were designed to determine whether AH 21-132 shares the activity of theophylline as an antagonist at adenosine A1 receptors and to assess its potency as a relaxant in intestinal smooth muscle. 2. In the transmurally-stimulated guinea-pig ileum, theophylline (1 mM), but not AH 21-132 (1 and 10 microM), antagonized twitch depression induced by adenosine. Higher concentrations (100 microM and 1 mM) of AH 21-132 themselves had a depressant effect. Neither theophylline (1 mM) nor AH 21-132 (1 and 10 microM) antagonized twitch depression induced by noradrenaline. 3. AH 21-132 (100 microM and 1 mM) depressed maximum contractions of ileum induced by both acetylcholine (ACh) and histamine. 4. In ileum treated with hyoscine (1 microM), AH 21-132 (greater than 10 microM) caused a concentration-dependent depression of the log concentration-effect curve for potassium chloride. 5. Simultaneous extracellular electrophysiological and mechanical recording from taenia caeci showed that AH 21-132 (100 microM-1 mM) inhibited spontaneous tension waves and their associated bursts of electrical spike activity. 6. Intracellular electrophysiological recording from taenia caeci showed that the mechano-inhibitory effect of 1 mM AH 21-132 was accompanied by abolition of spontaneous spike activity. Following spike abolition, the membrane potential assumed a value very close to that observed during periods of electrical quiescence prior to drug exposure. 7. AH 21-132 inhibited the activity of cyclic AMP-dependent and cyclic GMP-dependent phosphodiesterases derived from homogenates of ileal smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.      

To stay or not to stay: are fears about shorter postnatal hospital stays justified?

Common concerns raised during a Ministerial Review of Birthing Services in Victoria, Australia about the potential detrimental effects of shorter hospital stays after birth were examined in a study of women's actual experiences of and opinions about their hospital stays. Just under one in four women left hospital within five days of the birth, with the greater majority staying five days or more. Satisfaction with length of stay was high in the sample, with 82% of women feeling their stay had been about right, 11% feeling it had been too long and only 7% of women feeling their stay had been too short. A number of the concerns about the consequences of shorter lengths of stay were not borne out. Women who left hospital earlier than the traditional 5-7 day stay were not less likely to breast feed, nor were they more likely to be depressed 8-9 months after the birth. They were also much more likely to feel confident about looking after their baby when they went home than women who stayed five days or more. Implications for further research and for policy development concerning length of stay are considered.     

Cryptococcosis of the anterior segment in acquired immune deficiency syndrome.

Cryptococcosis is a rare form of human ocular infection, usually occurring in immunocompromised patients. Unilateral or bilateral posterior segment involvement is the rule. The authors describe a unique case of intraocular cryptococcosis presenting as an iris inflammatory mass in a patient with acquired immune deficiency syndrome. Diagnosis was established by anterior chamber paracentesis and confirmed by histopathologic examination of the enucleated eye.