Effect of leukocyte antibodies on the fate in vivo of indium-111- labeled granulocytes

The effect of different leukocyte antibodies on the fate in vivo of granulocytes is not known. Thus, the optimum in vitro serologic tests to determine a safe and effective granulocyte transfusion or to diagnose immune destruction of granulocytes in other clinical situations have not been identified. We have studied the effect of granulocyte agglutinating (GA), granulocytotoxic (GC), and lymphocytotoxic (LC) antibodies on the intravascular recovery and half- life (t 1/2) and the extravascular localization of Indium-111- granulocytes in 50 patients. GA antibodies caused reduced granulocyte recovery and t 1/2 in three of three non-neutropenic patients (one with anti-NB1), increased sequestration of cells in the liver, and failure of granulocytes to localize at sites of infection in two of two patients (one with anti-NA1). In contrast, GC antibodies in five patients and LC antibodies in one patient did not cause reduced intravascular recovery or t 1/2 of granulocytes. In nine patients with GC and six patients with LC antibodies, incompatible granulocytes localized at known sites of infection. It appears that GA, but not GC nor LC, antibodies alter the fate in vivo of granulocytes.     

Physiology: Sperm numbers and distribution within the human Fallopian tube around ovulation

This study aimed to determine the number and distribution ofspermatozoa within the human Fallopian tubes around ovulation.Parous women, undergoing total abdominal hysterectomy for menorrhagia,were inseminated with either partner's semen (3/10) or donorsemen (7/10). Approximately 18 h later both Fallopian tubeswere ligatured into ampullary, isthmic and intramural regions.These were removed and assessed for sperm content by flushing,scanning electron microscopy (SEM) or homogenization. A medianof 251 spermatozoa were recovered (range, 79–1386). Thenumber of spermatozoa within each tube was not significantlydifferent. The ovulatory ampulla contained a significantly (P 0.01) larger percentage of spermatozoa than the non-ovulatoryampulla. The number of motile spermatozoa inseminated was notsignificantly correlated to the number of spermatozoa recovered,but a trend was identified. The time between the onset of theluteinizing hormone surge and hysterectomy was significantlycorrelated (P 0.01) to the number of spermatozoa within theintramural regions, but not to the tubal sperm distribution.Spermatozoa were not observed, by SEM, bound to the tubal epithelium.These data suggest that, after artificial insemination at least,sperm access to the human Fallopian tube may be controlled,but that ovulation does not affect the redistribution of spermatozoabetween tubal regions and that the isthmus does not appear toact specifically as a sperm reservoir.     

Lymphocyte subpopulations,interleukin-2 and interleukin-2 receptor expression in childhood nephrotic syndrome

Abnormal T lymphocyte function and reduced interleukin-2 (IL-2) production have been implicated in the pathogenesis of the nephrotic syndrome (NS). We investigated: (1) lymphocyte subpopulations and expression of IL-2 receptor (IL-2R) on T cells using two-colour flow cytometry, (2) serum IL-2 and (3) the soluble component of IL-2R (sIL-2R) in serum, using enzyme-linked immunosorbent assay, in 38 children with NS. All children, except those in remission, had marked proteinuria. They were divided into groups according to renal pathology: (1) steroid-sensitive NS (SSNS) not receiving prednisolone therapy, (2) SSNS on prednisolone, (3) focal segmental glomerulosclerosis (FSGS), (4) SSNS in remission and not receiving prednisolone therapy, (5) congenital NS (CNS). Results were compared with 26 age-matched controls. Total T lymphocytes (CD3) were reduced in groups 1 and 2; CD4 count was reduced in groups 1–4; CD8 count increased in groups 2 and 3; CD8 and CD19 (B lymphocytes) were significantly reduced in group 5. Increased IL-2R expression (CD25) on CD4 lymphocytes was noted in groups 1, 2 and 3 implying activation of these cells. In patients with SSNS, increased serum sIL-2R was recorded during relapse (1,273±497 U/l vs. 913±401 U/l in remission,P<0.005) but free serum IL-2 was not detectable at any stage. The specific alterations in lymphocyte subpopulations in SSNS and FSGS would imply an involvement of the immune system distinct from that in CNS.     

Examining the blurred boundaries between medical and recreational cannabis – results from an international study of small-scale cannabis cultivators

Aim: To compare characteristics of recreational vs. medical growers in a sample of small-scale cannabis cultivators from 12 countries.

Methods: Six thousand eight hundred ninety six respondents who took part in an online survey were divided into three groups as: those who reported growing for recreational use, those cultivating for medical purposes who also reported use of other illegal drugs, and those who reported cultivation for medical use and didn’t use other illegal substances. The groups were compared using multinomial logistic regression.

Findings: In comparison to recreational growers, the two groups of medical growers included more females, consumed cannabis more frequently, and were more likely to cite health-related motivations for growing. The medical growers without other illicit drug use shared some of the same features with the medical growers with illicit drug use, but in comparison to both other groups, they were older, used less alcohol and tobacco, and were less likely to be involved in illicit activities other than drug crimes.

Conclusions: Findings suggest that claims of medical use are not simply an attempt to justify personal cannabis consumption, but do at least partly reflect a genuine belief in medical benefit. However, those growing cannabis for medical reasons form a heterogeneous group of people.     

Synthesis and pharmacology of new psychoactive substance 5F‐CUMYL‐P7AICA,a scaffold‐ hopping analog of synthetic cannabinoid receptor agonists 5F‐CUMYL‐PICA and 5F‐CUMYL‐PINACA

Synthetic cannabinoid receptor agonists (SCRAs) are a dynamic class of new psychoactive substances (NPS), with novel chemotypes emerging each year. Following the putative detection of 5F‐CUMYL‐P7AICA in Australia in 2016, the scaffold‐hopping SCRAs 5F‐CUMYL‐PICA, 5F‐CUMYL‐PINACA, and 5F‐CUMYL‐P7AICA were synthesized and characterized by nuclear magnetic resonance (NMR) spectroscopy, gas chromatography–mass spectrometry (GC–MS), and liquid chromatography–quadrupole time‐of‐flight–MS (LC–QTOF–MS). Since little is known of the pharmacology of 7‐azaindole SCRAs like 5F‐CUMYL‐P7AICA, the binding affinities and functional activities of all compounds at cannabinoid type 1 and type 2 receptors (CB₁ and CB₂, respectively) were assessed using tritiated radioligand competition experiments and fluorescence‐based plate reader membrane potential assays. Despite CB₁ binding affinities differing by over two orders of magnitude (K_i = 2.95–174 nM), all compounds were potent and efficacious CB₁ agonists (EC₅₀ = 0.43–4.7 nM), with consistent rank order for binding and functional activity (5F‐CUMYL‐PINACA >5F‐CUMYL‐PICA >5F‐CUMYL‐P7AICA). Additionally, 5F‐CUMYL‐P7AICA was found to exert potent cannabimimetic effects in mice, inducing hypothermia (6°C, 3 mg/kg) through a CB₁‐dependent mechanism.     

Validity of medication-based co-morbidity indices in the Australian elderly population

Objectives: To determine the validity of two medication-based co-morbidity indices, the Medicines Disease Burden Index (MDBI) and Rx-Risk-V in the Australian elderly population.
Methods: In Phase I, the sensitivity and specificity of both indices were determined in 767 respondents from wave 6 of the Australian Longitudinal Study of Ageing (ALSA). Medication-defined index disease categories were compared to self-reported medical conditions. Correlation with self-rated health was examined and Cox proportional hazards models were used to assess the predictive validity for mortality. Phase II verified the predictive ability of Rx-Risk-V in a sample of 213,191 veterans from Australian Department of Veterans' Affairs (DVA) database.
Results: MDBI and Rx-Risk-V scores could be calculated for 28% and 73% of the ALSA sample respectively. Both indices had high specificities and low to moderate sensitivities compared to self-reported medical conditions. Total weighted scores were significantly related to self-rated health (p<0.001). Both indices were predictive of mortality (Hazard Ratio (HR) =3.690 (95% CI 2.264-6.015) for MDBI and HR 1.079 (95% CI 1.045-1.114) for Rx-Risk-V. The predictive validity for mortality of Rx-Risk-V was confirmed using DVA data (HR= 1.090, 95% CI 1.088-1.092).
Conclusions: Medication-based co-morbidity indices Rx-Risk-V and MDBI are valid measures of co-morbidity. However, Rx-Risk-V detects more comorbidity in the Australian elderly population and is likely to be a more suitable index to use in administrative datasets, particularly where studies include large numbers of outpatients.     

Residential traffic exposure and pregnancy-related outcomes: a prospective birth cohort study

Background  

The effects of ambient air pollution on pregnancy outcomes are under debate. Previous studies have used different air pollution exposure assessment methods. The considerable traffic-related intra-urban spatial variation needs to be considered in exposure assessment. Residential proximity to traffic is a proxy for traffic-related exposures that takes into account within-city contrasts.     

Characterization of lymphadenopathy by magnetic resonance relaxation times: preliminary results

The purpose of this study was to evaluate the ability of magnetic resonance (MR) to enable characterization of disease within lymph nodes and differentiation between benign and malignant lymph nodes. Ninety-three patients were examined. Normal and malignant lymph nodes were excised from seven patients, and the T1 and T2 relaxation times were analyzed in vitro using spectroscopy. In 86 patients, T1 and T2 relaxation times of the lymph nodes were determined from MR images. Spectroscopic analysis revealed an increase in the T1 and T2 values of nodes involved by neoplasm compared with uninvolved nodes in an individual case. Comparison of measurements from 28 lymph nodes analyzed in vitro using spectroscopy showed an overlap of the T1 and T2 values between normal and malignant lymph nodes. T2 relaxation times and relative spin density values were greater for acute inflammatory nodes than for nodes involved by granulomatous diseases (tuberculosis and sarcoidosis) or nodes replaced by lymphoma or metastasis. Changes in T1 relaxation values were not specific. The measurements of T1 and T2 relaxation times and relative spin density showed an overlap between nonspecific lymphadenopathy, nodes involved by granulomatous diseases, and malignant nodes. Differentiation between these various nonacute types of enlarged lymph nodes could not be achieved using current MR parameters.     

MR cisternography and myelography with Gd-DTPA in monkeys

To enhance the contrast between cerebrospinal fluid (CSF), brain, spinal cord, and surrounding meninges and bone on magnetic resonance (MR) images, as well as to study CSF flow, gadolinium-DTPA was injected in the subarachnoid space of eight monkeys. Six doses of progressively higher concentrations (from .125 mmol to 250 mmol) were injected every 30-40 minutes. Images of head and spine were obtained at .26 T or .5 T in sagittal and axial planes, using both spin-echo and inversion-recovery sequences in 13 imaging experiments. Marked, consistent changes of signal intensity in the CSF cavities were observed following the injections. These changes were dose related and occurred at different times in the areas close to the injection site versus those distant, a disparity that obviously was related to CSF flow. Gd-DTPA cisternography and myelography may be valuable in MR imaging of central nervous system disease, such as tumors adjacent to the CSF cavities, abnormal CSF collections (e.g., arachnoidal cysts), CSF rhinorrhea and otorrhea, syringohydromyelia, and studies of hydrocephalus and CSF flow dynamics.     

Induction of photoallergy in guinea-pigs by injection of photoallergen-protein conjugates

Photoconjugates were prepared by ultraviolet irradiation of guinea-pig albumin (GPA) with the photoallergens tetrachlorosalicylanilide (T4CS) and fentichlor. Injections of T4CS-GPA induced photoallergy to T4CS in 11 of 12 guinea-pigs whereas injections of fentichlor-GPA induced photoallergy in 5 of 12 guinea-pigs. Thus the fentichlor-GPA photoconjugate, which contained a molar ratio of hapten to protein 3 times higher than the corresponding T4CS conjugate, produced a significantly lower response. The results demonstrate the importance of protein conjugate formation in the induction of photoallergy, i.e. the role of carrier protein in contact sensitivity. The high potency of the T4CS-GPA photoconjugate in inducing photoallergy suggests that albumin may have a special role as a carrier protein in T4CS photoallergy.