Δ9-THC as a discriminative stimulus in rats and pigeons: Generalization to THC metabolites and SP-111

In a drug discrimination paradigm pigeons and rats were trained with an operant procedure to discriminate between the presence and absence of the effects of ⁹-THC (1.0 and 3.0 mg/kg, injected IM 90 min and I.P. 30 min before the start of the session). Once trained, various THC metabolites as well as a water-soluble derivative of THC (SP-111), were substituted for ⁹-THC to test for generalization to the training drug. Generalization to ⁹-THC occurred with the 11-hydroxy metabolites and the potency order was 11-OH-⁹-THC >11-OH-⁸-THC ⁹-THC. Among the other metabolites tested (8-OH-⁹-THC, 8, 11-di-OH-⁹-THC, 8-OH-⁹-THC, 8, 11-di-OH-⁹-THC), it was only 11-di-OH-⁹-THC that completely substituted for ⁹-THC in pigeons, albeit at very high dose levels (rats were not tested with these metabolites). SP-111 generalized to ⁹-THC in both species. However, the onset of action of SP-111 was slower than that for ⁹-THC, especially in pigeons. These studies show the importance of obtaining complete dose-effect determinations over time when assessing structure-activity relationships with drug-discrimination procedures.A brief account of the results, which are summarized in Neuropharmacology 18:1023–1024, 1979), was presented at the British Association for Psychopharmacology Summer Conference, July 15–17, Birmingham, England, 1979     

A unique case of three autografts for acute myelogenous leukaemia with subsequent long term survival in second remission

We report here a patient with acute mycloid leukaemia who relapsed 20 months after undergoing a double autograft procedure in first remission. He was reinduced and subsequently underwent a third autologous bone marrow transplantation in second remission using bone marrow harvested in second remission and a Busulphan and Cyclophosphamide conditioning regimen. Although the engraftment was very slow, he has remained in second remission for 34+ months. This case demonstrates that durable disease-free survival can be attained by a second preparative therapy, even in second remission, for patients relapsed after autologous bone marrow transplantation.     

In situ demonstration of T cell subsets in atrophic parapsoriasis

It has been demonstrated recently in mycosis fungoides and lichen planus that T lymphocyte subsets may be identified in cutaneous lymphocytic infiltrates using the immunoperoxidase technic in conjunction with monoclonal antibodies produced by the technic of Kohler and Milstein. This communication describes the application of this technic to cutaneous lymphoid infiltrates of parapsoriasis in which T cell predominance has been demonstrated previously. The lymphoid infiltrates of six patients with atrophic parapsoriasis were examined by the indirect immunoperoxidase technic using monoclonal antibodies (from two commercial sources) directed against "helper" and "suppressor" T cell subsets. Both "helper" and "suppressor" cells (as defined by a positive reaction with monoclonal antibodies) could be identified in cutaneous infiltrates. "Helper" cells predominated, but in varying degrees among patients. The relevance of these findings in relation to the possible development of clinical mycosis fungoides from atrophic parapsoriasis is discussed. In addition, factors causing difficulty in the consistent identification of cell subtypes are discussed. These factors suggest that in the present state of imperfection, difficulty will be experienced in using this technic for the accurate quantification of percentages of lymphocyte subsets in tissue sections.U     

Effects of chronic Δ9-tetrahyrocannabinol administration on schedule-controlled behavior of pigeons: Cross-tolerance to pentobarbital and barbital

Pigeons responding under a variable-interval (VI) 75-s schedule of food presentation were used to study cross-tolerance from ⁹-tetrahyrocannabinol (⁹-THC) to pentobarbital and barbital. After initial dose-effect functions for pentobarbital and barbital were determined, the birds received ⁹-THC injections for 6 weeks. This chronic administration regimen resulted in a greater than 100-fold tolerance to ⁹-THC. Redetermination of the pentobarbital and barbital dose-effect functions during the chronic ⁹-THC regimen revealed statistically significant shifts to the right for the pentobarbital (0.191 log unit) and barbital (0.078 log unit) dose-effect curves. All six birds showed tolerance to pentobarbital, while four of the six showed tolerance to barbital. Blood barbital levels before and after chronic ⁹-THC administration did not differ significantly. Tolerance to ⁹-THC was more prolonged and of much greater magnitude than the cross-tolerance to pentobarbital or barbital. The results demonstrate that cross-tolerance can develop from ⁹-THC to a barbiturate that normally undergoes little metabolism.     

Multicentre analysis of treatment planning information: Technical requirements,possible applications and a proposal

Digital data from 3‐D treatment planning computers is generally used for patient planning and then never considered again. However, such data contains enormous quantities of information regarding patient geometries, tissue outlining, treatment approaches and dose distributions. Were such data accessible from planning systems from multiple manufacturers, there would be substantial opportunities for undertaking quality assurance of radiotherapy clinical trials, prospective assessment of trial outcomes and basic treatment planning research and development. The technicalities of data exchange between planning systems are outlined, and previous attempts at producing systems capable of viewing and/or manipulating imaging and radiotherapy digital data reviewed. Development of a software system for enhancing the quality of Australasian clinical trials is proposed.     

A prospective trial of short‐fractionation radiotherapy for the palliation of liver metastases

The purpose of this study was to prospectively examine the effectiveness and tolerability of a simple radiotherapy technique for the palliation of symptomatic liver metastases. Twenty‐eight patients with symptomatic liver metastases were enrolled from seven centres, and received targeted (partial or whole) liver irradiation consisting of 10 Gy in two fractions over 2 days. Symptoms at baseline were hepatic pain (27 patients), abdominal distension (19), night sweats (12), nausea (18) and vomiting (eight). Twenty‐two patients (76%) had failed previous treatment with chemotherapy, hormonal therapy and/or high‐dose steroids. Symptoms and potential toxicities were prospectively assessed at the time of treatment, then 2, 6 and 10 weeks later. Individual symptom response rates were 53?66% at 2 weeks. Partial or complete global symptomatic responses were noted in 15 patients (54%) overall. The treatment was well tolerated with two patients (7%) experiencing grade 3 toxicity (one vomiting and one diarrhoea); however, four patients reported temporary worsening of pain shortly after treatment. This simple and well‐tolerated treatment achieves useful palliation.     

A Correlational Test of the Relationship Between Posttraumatic Growth,Religion, and Cognitive Processing

The present study examined the degree to which event related rumination, a quest orientation to religion, and religious involvement is related to posttraumatic growth. Fifty-four young adults, selected based on prescreening for experience of a traumatic event, completed a measure of event related ruminations, the Quest Scale, an index of religious participation, and the Posttraumatic Growth Inventory. The three subscales of the Quest Scale, the two groups of rumination items (soon after event/within past two weeks), and the index of religious participation were entered in a standard multiple regression with the total score of the Posttraumatic Growth Inventory as the dependent variable. The degree of rumination soon after the event and the degree of openness to religious change were significantly related to Posttraumatic Growth. Congruent with theoretical predictions, more rumination soon after the event, and greater openness to religious change were related to more posttraumatic growth. Present findings offer some confirmation of theoretical predictions, and also offer clear direction for further research on the relationships of religion, rumination, and posttraumatic growth.     

Measurement of albumin and low molecular weight proteins in the urine of newborn infants using a cotton wool ball collection method

Objective : The aim of this study was to investigate the inter-relationship between urinary excretion of alpha-1-microglobulin (AIM), retinol-binding protein (RBP) and albumin in term and premature neonates, with urine collected into cotton wool balls and extracted by a novel method. Subjects and methods : Sixty-four infants were studied on the first day of life; 26 had been born at term (37–42 weeks gestation) and 38 prematurely (24–28 weeks n = 16, 29–36 weeks n = 22). Urine collected into cotton wool balls was analysed following a new detergent extraction method, which resulted in a recovery rate of 94–107% for albumin, AIM, RBP and creatinine. Results : Urinary protein excretion, expressed as a ratio to urinary creatinine, decreased significantly with increasing gestational age (24–28 weeks, 29–36 weeks, 37–42 weeks: albuminxreatinine ratio mg/mmol mean 96.9, 31.7, 19.3; AIM: creatinine ratio mg/mmol mean 99.3, 37.0, 7.8; RBP: creatinine ratio mg/mmol mean 16.2, 3.8, and <0.01, below the limit of detection, respectively). When results were corrected for birthweight, this gestation-associated effect was still present for A1M and RBP, but not for albumin. In premature infants there was a significant positive correlation between AIM: creatinine ratio and RBP: creatinine ratio ( r = 0.85), and also between albumin and both AIM and RBP ( r = 0.82 and 0.77). Conclusion : Increased excretion of AIM, RBP and albumin at earlier gestational ages is probably due to proximal tubular immaturity, although tubular damage and also glomerular dysfunction cannot be excluded as possible explanations.     

Delayed umbilical cord clamping in preterm infants: A feasibility study

Objectives: To assess: (i) the size of placental transfusion following a 30 s delay in cord clamping following vaginal and Caesarean births; and (ii) the feasibility of delaying cord clamping in the labour ward and particularly in the operating theatre.
Methods: Fourty-six infants born at 26–33 weeks gestation were randomized to having the umbilical cord clamped either immediately or 30 s after birth. The venous haematocrit was measured at 1 and at 4 h of age.
Results: There were trends towards higher mean haematocrits in the infants following delayed clamping, but these were not significant either at 1 h (55±7.7 vs 52.9±7) or at 4 h of age (55±7 vs 52.5±7). The trends were more marked in the infants born by Caesarean section, and in those born at 26–29 weeks gestation.
Conclusions: A 30 s delay in cord clamping is feasible at both vaginal and Caesarean births, but does not lead to the predicted difference in infant haematocrit. Although physiological studies suggest that a placental transfusion of 15–20 mL/kg occurs within 30 s of delivery, these data suggest that future trials should either delay cord clamping for more than 30 s, or should alter the position of the infant in relation to the uterus in order to facilitate the transfusion. Delayed cord clamping is feasible at Caesarean section.     

Incidence of apnoea and bradycardia in preterm infants following DTPw and Hib immunization: A prospective study

Objective: To evaluate the incidence and severity of apnoea and bradycardia in hospitalized preterm infants following immunization at 2 months of age, and identify risk factors.
Methodology: A prospective study of 98 preterm infants, of gestational age 24–31 weeks, immunized at approximately 2 months post natal age with diphtheria-tetanus-whole cell pertussis vaccine (DTP_w) in the neonatal intensive care unit (NICU) at King George V Hospital Sydney. Half the infants also received Haemophilus influenzae type b conjugate vaccine (Hib) simultaneously. All infants were monitored for apnoea and bradycardia in the 24 h periods pre- and post immunization.
Results: Only one infant had apnoea and/or bradycardia pre-immunization compared with 17 post immunization. For 12 infants these events were brief, self-limiting and not associated with desaturations (oxygen saturation <90%). However, for five infants (30%) these events were associated with oxygen desaturation and two of these infants required supplemental oxygen. The group that had apnoea and/or bradycardia and the group that did not were not significantly different in terms of gestational age, birth weight and other variables. Infants who received Hib together with DTP_w were less likely to have apnoea and/or bradycardia than those given DTP_w alone.
Conclusion: When considering immunization for preterm infants, the benefits of early immunization must be balanced against the risk of apnoea and bradycardia. We recommend that the cardio-respiratory function of hospitalized infants born at less than 31 weeks gestation be monitored for 48 h post immunization.