Hypogonadism in men receiving methadone and buprenorphine maintenance treatment.

The aim of this study was to determine the prevalence and investigate the aetiology of hypogonadism in men on methadone or buprenorphine maintenance treatment (MMT, BMT). 103 men (mean age 37.6 +/- 7.9) on MMT (n = 84) or BMT (n = 19) were evaluated using hormone assays, body mass index (BMI), serological, biochemical, demographic and substance use measures. Overall 54% of men (methadone 65%; buprenorphine 28%) had total testosterone (TT) <12.0 nm; 34% (methadone 39%; buprenorphine 11%) had TT <8.0 nm. Both methadone- and buprenorphine-treated men had lower free testosterone, luteinising hormone and estradiol than age-matched reference groups. Methadone-treated men had lower TT than buprenorphine-treated men and reference groups. Prolactin did not differ between methadone, buprenorphine groups, and reference groups. Primary testicular failure was an uncommon cause of hypogonadism. Yearly percentage fall in TT by age across the patient group was 2.3%, more than twice that expected normally. There were no associations between TT and opioid dose, cannabis, alcohol and tobacco consumption, or chronic hepatitis C viraemia. On multiple regression higher TT was associated with higher alanine aminotransferase and lower TT with higher BMI. Men on MMT have high prevalence of hypogonadotrophic hypogonadism. The extent of hormonal changes associated with buprenorphine needs to be explored further in larger studies. Men receiving long term opioid replacement treatment, especially methadone treatment, should be screened for hypogonadism. Wide interindividual differences in methadone metabolism and tolerance may in a cross-sectional study obscure a methadone dose relationship to testosterone in individuals. Future studies of hypogonadism in opioid-treated men should examine the potential benefits of dose reduction, choice of opioid medication, weight loss, and androgen replacement.

The impact of bispectral index monitoring on sedation administration in mechanically ventilated patients.

The aim of this prospective randomised controlled trial was to assess the effectiveness of the Bispectral Index (BIS) monitor in supporting clinical sedation management decisions in mechanically ventilated intensive care unit patients. Fifty adult mechanically ventilated surgical and general intensive care unit patients receiving sedative infusions of morphine and midazolam were randomly allocated to receive BIS monitoring (n=25) or standard sedation management (n=25). In the BIS group, sedation was titrated to maintain a BIS value of greater than 70. In the standard management group, sedative needs were titrated based on subjective assessment and clinical signs. There was no statistically significant difference in the amount of sedation administered (morphine P = 0.67 and midazolam P = 0.85). However, there was a statistically significant difference in sedation administration over time. Patients in the BIS group received increasing amounts of sedation over time whilst those in the control group received decreasing amounts of sedation over time. The same inverse relationship existed for both sedative agents (morphine P = 0.005, midazolam P = 0.03). Duration of mechanical ventilation was comparable in the two groups. We conclude that the use of BIS monitoring did not reduce the amount of sedation used, the length of mechanical ventilation time or the length of ICU stay.

Blinded evaluation of DNA extraction and genotyping of stained Cryptosporidium on glass slides.

AIMS: A blinded trial was performed on Cryptosporidium genotyping using polymerase chain reaction (PCR)/restriction fragment length polymorphism analysis of the Cryptosporidium oocyst wall protein (COWP) gene between DNA extracted from oocyst suspensions as compared with DNA from fixed and stained faecal smears on glass microscope slides. METHODS AND RESULTS: Sixty-five faecal smears on slides were stained by one of three different methods comprising 50 positives and 15 negatives as determined by the observation of Cryptosporidium oocysts by microscopy. The expected result in terms of detection and the COWP genotype detected was achieved using DNA extracted from 94% of the slides tested. CONCLUSIONS: This study shows that DNA, which can be amplified by PCR, is present in stained smears on glass microscope slides. SIGNIFICANCE AND IMPACT OF THE STUDY: The method may be useful for molecular epidemiological studies on a range of gastrointestinal pathogens where samples are collected from locations remote from the testing laboratory.

Aluminium beverage cans as a dietary source of aluminium.

OBJECTIVE: To examine the possibility that aluminium beverage cans contribute to the dietary level of aluminium. METHOD: The aluminium content of a variety of beverages from aluminium cans and glass containers was measured. RESULTS: The contents of 106 aluminium cans and bottles representing 52 different beverages all had a higher aluminium content than Newcastle tap water at 1.4 mumol/L, ranging as high as 385 mumol/L. Non-cola soft drinks averaged 33.4 mumol/L from cans and 5.6 mumol/L from bottles. Cola drinks averaged 24.4 mumol/L from cans and 8.9 mumol/L from bottles, whereas beer in cans or bottles averaged about 6 mumol/L. CONCLUSIONS: In general, the aluminium content of beverages from aluminium cans was higher than that from glass containers, and it rose with decreasing pH. Within a given category there was a wide variation in aluminium content. If the speculative link between aluminium intake and Alzheimer's disease is established then beverages from aluminium cans, particularly soft drinks, may be a risk factor.

Uptake and destruction of 125I-CSF-1 by peritoneal exudate macrophages.

The binding and uptake of the colony-stimulating factor CSF-1 by peritoneal exudate macrophages (PEM) from lipopolysaccharide insensitive C3H/HeJ mice was examined at 2 degrees C, and at 37 degrees C. At 2 degrees C, 125I-CSF-1 was bound irreversibly to the cell surface. At 37 degrees C, 90% of the cell surface associated 125I-CSF-1 was rapidly internalized and subsequently degraded and the remaining 10% dissociated as intact 125I-CSF-1. Thus classical equilibrium or steady state methods could not be used to quantitatively analyze ligand-cell interactions at either temperature, and alternative approaches were developed. At 2 degrees C, the equilibrium constant (Kd less than or equal to 10(-13) M) was derived from estimates of the rate constants for the binding (kon congruent to 8 x 10(5) M-1 s-1) and dissociation (koff less than or equal to 2 x 10(-7) s-1) reactions. At 37 degrees C, the processes of dissociation and internalization of bound ligand were kinetically competitive, and the data was formally treated as a system of competing first order reactions, yielding first order rate constants for dissociation, koff = 0.7 min-1 (t1/2 = 10 min) and internalization, kin = 0.07 min-1 (t 1/2 = 1 min). Approximately 15 min after internalization, low-molecular weight 125I-labeled degradation products began to appear in the medium. Release of this degraded 125I-CSF-1 was kinetically first order over three half-lives (Kd = 4.3 x 10(-2) min-1, t1/2 = 16 min). Thus CSF-1 binds to a single class of receptors on PEM, is internalized with a single rate limiting step, and is rapidly destroyed without segregation into more slowly degrading intracellular compartments.

Motion processing in peripheral vision: reaction time and perceived velocity.

Reaction times to motion onset were measured as a function of eccentricity of presentation. These were compared with measurements of perceived speed at various eccentricities. For slowly moving targets, both dependent measures changed substantially with eccentricity: RT increased and perceived speed declined. For more rapidly moving targets, both dependent measures were unchanged by eccentricity. These results may be related to the difference between retinotopic distribution of neural mechanisms responsive to low rates of temporal modulation and the retinotopic distribution of neural mechanisms responsive to higher rates of temporal modulation.

Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy.

CSF-1 is a hemopoietic growth factor that specifically causes the proliferation and differentiation of mononuclear phagocytic cells. Receptors for CSF-1 occur exclusively on cells of the mononuclear phagocytic series (precursor leads to monoblast leads to promonocyte leads to monocyte leads to macrophage). Studies of the actions of CSF-1 on freshly explanted macrophages have been complicated by contamination of the primary cell isolates with CSF-1-producing cells and by the heterogeneity of the proliferative responses of individual macrophages. A method is described for the production of a highly purified and homogeneous population of adherent bone marrow-derived macrophages (BMMs) that are devoid of CSF-1-producing cells. The method may also be used to obtain nonadherent precursors of the mononuclear phagocytic series. Studies of CSF-1 action and degradation in cultures of BMMs have revealed several new findings. First, CSF-1 is required for both the survival (without proliferation) and the proliferation of BMMs. Second, CSF-1 is degraded by BMMs in a concentration-dependent manner, over the range of concentrations that stimulates both cell survival and proliferation. Third, the rate of CSF-1 degradation is saturable (or approximately 7 X 10(4) molecules per cell per hour) at CSF-1 concentrations that cause maximum proliferation (or approximately 0.4 nM). Under these conditions, BMMs are greatly enlarged and contain numerous phase-lucent vacuoles. Thus macrophages specifically require CSF-1 for both survival and proliferation, yet selectively and rapidly degrade it. This apparent dichotomy may have important implications for the role of CSF-1 in macrophage homeostasis in vivo.

Synchronous combined transvaginal-transvesical repair of vesicovaginal fistulas.

Nine cases of vesicovaginal fistula which followed hysterectomy, with or without radiotherapy, are presented. The repair by the above-mentioned technique eventually led to successful closure in all cases. A strong argument can now be advanced that this is the technique of choice in the large, high postoperative type of vesicovaginal fistula which is now the common type of fistula seen in affluent countries.

Rapid measurement of contrast-sensitivity functions.

We have developed a reliable and valid procedure for determining a person's contrast sensitivity function in approximately 6 min. This rapid procedure, which resembles that used in the Bekesy sweep-frequency audiometer, has potential as a clinical tool for diagnostic assessment.

Moving visual phantoms: a new contour completion effect.

Moving contours surrounding an empty region make phantoms appear to move through the empty region. The phantoms are contours, dimmer than the inducing contours but of the same pattern, color, speed, and direction of movement. The phantoms originate in the brain and may be related to completion effects most often seen with visual pathology.

Visual temporal order: a new illusion.

Brief visutal stimuli presented in rapid sequience, one to the left and one to the right, appear to occur left first, then right, regardless of the actual order of presentation. This illutsion persists under conditions of forced-choice testing and does not vary with presemitation to the same or opposite retinal hemifields, A series of experiments suggests that this illutsion may be the product of an internal mechanism that scans visual inputs in a left-to-right order.