Rewarming from immersion hypothermia: a comparison of three techniques

Analysis of measurements from the tali of 21 individual fossil primates from Africa shows that the specimens fall into five clearly defined groups. Accordingly, these specimens have been included as groups along with extant species in a subsequent canonical analysis thus allowing the fossils to play their part in the determination of the canonical separations. The results of this procedure show that the five fossil groups lie in a part of the canonical space not occupied by any extant African primate. Their positions are between the envelope of Asiatic apes (Hylobates and Pongo) and the envelope of African forms near the edge which contains Pan and Papio. One fossil group is so similar to Hylobates that its talus may have functioned in locomotion in a parallel manner. Others lie near to Pongo in directions proceeding towards Pan and Papio and it is possible that this similarity may indicate remnants of morphological adaptation for climbing in these fossils. At the same time, however, individual specimens are closer to one or another of the extant groups and this considerable spread suggests that the locomotor adaptations as evidenced by talar morphology, of the primate fauna in Africa, may have been very different from those of the present day. This would not the inconsistent with the different habitats, floras and non-primate faunas that may have characterized the East African scene at these earlier times. Particular fossils from Olduvai and Kromdraai that are supposed to be australopithecine and therefore bipeds, are confirmed (Oxnard, '72; Lisowski et al., '74) as being totally different from man in their talar morphology and essentially rather similar to the majority of the other fossil tali examined.     

Production of satiety with small intraduodenal infusions in the rat.

9 male Sprague-Dawley rats equipped with chronic intragastric and intraduodenal catheters received small infusions of various solutions through 1 catheter during spontaneous meals. Regardless of which compartment or which solution was infused, the Ss maintained a constant daily nutrient intake. However, all hypertonic solutions reduced mean meal size and increased the frequency of feeding when injected intraduodenally, while only nutritive solutions reduced mean meal size when infused intragastrically. Water ingestion varied with the effective osmotic pressure of the injected solutions, but there were no differences in water ingestion as a function of the compartment infused. Data suggest both the presence of a duodenal satiety mechanism and the validity of interpreting the meal patterns of vagotomized Ss eating a liquid diet as resulting from the rapid emptying of the diet into the duodenum. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Donor lymphocyte infusions

Donor lymphocyte infusions for treatment of relapse after allogeneic bone marrow or stem cell transplantation is being used with increasing frequency. Study of this form of adoptive immunotherapy will shed light on different aspects of cell-mediated cytotoxicity such as antigen presentation, processing, immune recognition, lymphocyte subsets involved, and mechanism of cell death. Donor lymphocyte infusions are extremely effective for cytogenetic relapses or chronic-phase relapses of chronic myelogenous leukemia, but are less effective in acute leukemias or other disorders. Donor lymphocyte infusions are associated with a significant risk of morbidity and mortality due to graft-versus-host disease and pancytopenia. Lower cell doses, earlier infusions, and selective depletion of CD8+ lymphocytes have been proposed as methods of diminishing these toxicities. Current research is focusing on methods of making donor lymphocyte infusions more effective in the nonchronic myelogenous leukemia setting, and decreasing their toxicity without losing their clinical efficacy in the treatment of relapsed chronic myelogenous leukemia.     

Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions

We have previously shown that eating disorders are a compulsive behaviour disease, characterized by frequent recall of anorexic thoughts. Evidence suggests that memory is a neocortical neuronal network, excitation of which involves the hippocampus, with recall occurring by re-excitement of the same specific network. Excitement of the hippocampus by glutamate-NMDA receptors, leading to long-term potentiation (LTP), can be blocked by ketamine. Continuous block of LTP prevents new memory formation but does not affect previous memories. Opioid antagonists prevent loss of consciousness with ketamine but do not prevent the block of LTP. We used infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily nalmefene as opioid antagonist to treat 15 patients with a long history of eating disorder, all of whom were chronic and resistant to several other forms of treatment. Nine (responders) showed prolonged remission when treated with two to nine ketamine infusions at intervals of 5 days to 3 weeks. Clinical response was associated with a significant decrease in Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients (non-responders) the score was: before ketamine, 42.8 +/- 3.7; after ketamine, 44.8 +/- 3.1. There was no significant response to at least five ketamine treatments, perhaps because the compulsive drive was re-established too soon after the infusion, or because the dose of opioid antagonist, nalmefene, was too low.     

Plasma bupivacaine concentrations associated with continuous extradural infusions in babies

The biological role of diadenosine oligophosphates (DAOP) remains obscure in spite of numerous attempts to solve this enigma. It is known that Ap3A contrary to Ap4A accumulates in human cultured cells treated with interferons (IFNs) alpha or gamma. Since IFNs are considered as antiproliferative regulators, we assumed that different cell status may be associated with varying intracellular levels of DAOP. Promyelocytic human cell line HL60 induced by phorbol ester (TPA) to differentiate to macrophage-like cells in culture exhibits a profound loss of proliferative potential. Here we have shown a 4-5-fold increase in Ap3A concentration in HL60 cells induced by TPA, similar to the effect of IFN, while the Ap4A concentration remained unchanged. On the contrary, in cells undergoing apoptosis induced by VP16, a topoisomerase II inhibitor, the Ap3A concentration considerably decreased, while the Ap4A concentration increased. These findings combined with earlier results suggest an involvement of the Ap3A/Ap4A ratio in signal transduction pathways controlling the cell status.     

Intravenous long term infusions of the rat without anesthesia

The lumbar-spine radiographs of 67 patients with idiopathic chondrocalcinosis articularis were reviewed for disc calcification and other changes. Calcification was present in 21 (31%) of the patients, seen most frequently at the L 2-3 disc space. The 21 patients as a group were significantly older than the 46 patients without disc calcification, and also had a much higher incidence of chondrocalcinosis in peripheral joints. There was no association with back pain or spinal stiffness. The 21 patients with disc calcification included six patients with a destructive peripheral arthropathy, and three of them had destructive changes affecting the lumbar spine. Three patients with a destructive peripheral arthropathy were also included in the group without disc calcification, and one of these had a destructive arthritis of the lumbar spine. For comparison, there was a 55% incidence of spinal chondrocalcinosis in nine patients with primary hyperparathyroidism and peripheral joint chondrocalcinosis, and a 6% incidence in 100 anteroposterior lumbar spine radiograph 'controls', taken before intravenous urography, although in this latter group the changes were minimal and confined to the margin of a single disc in each case.     

Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer

PURPOSE: To evaluate the efficacy and toxicity of paclitaxel administered as a 1-hour infusion on weekly basis, without interruption, to patients with metastatic breast cancer who had received prior therapy. PATIENTS AND METHODS: Thirty patients with metastatic breast cancer received sustained weekly paclitaxel therapy at an initial dose of 100 mg/m2 until disease progression. Prior therapy included adjuvant only (n=17), metastatic only (n=7), or both (n=6). Eighteen patients had received prior anthracycline therapy, 12 of whom had demonstrated progression of disease within 12 months of it. All patients were assessable for efficacy; 29 patients were assessable for toxicity. Pharmacokinetic studies of paclitaxel were also performed. RESULTS: A total of 469 weekly paclitaxel infusions were administered to 30 patients (median, 14 infusions/patient). The median delivered dose-intensity was 91 mg/m2/wk (range, 80 to 108). The overall response rate was 53% (95% confidence interval [CI], 34% to 72%), with 10% complete responses (CRs) and 43% partial responses (PRs). Median response duration was 7.5 months (range, 2 to 11+). Responses were observed in nine of 18 (50%) patients with prior anthracycline therapy, including six of 12 (50%) with disease progression on anthracycline within 1 year (three of four within 6 months). Therapy was well tolerated and remarkable for a lack of overall and cumulative myelosuppression. Grade 3/4 neutropenia occurred in four patients; febrile neutropenia was not observed. Peripheral neuropathy prohibited dose escalation above 100 mg/m2, and grade 3 neuropathy was observed in two of 21 patients at < or = 100 mg/m2. CONCLUSION: Weekly paclitaxel therapy is active and well tolerated in patients with metastatic breast cancer. Weekly therapy should be considered as a current clinical option for these patients and should be incorporated into future comparative clinical trials.     

Difference between the measured and ordered dose of catecholamine infusions

OBJECTIVE: To measure the actual concentrations of dopamine, dobutamine, and epinephrine in infusates prepared for patients, and to compare these concentrations with those of the dopamine HCl, dobutamine, and epinephrine HCl infusates that had been prescribed to evaluate drug preparation accuracy. DESIGN: Prospective, unblind study. SETTING: Pediatric intensive care unit in a tertiary-care teaching hospital. PARTICIPANTS: All dopamine, dobutamine, and epinephrine infusions ordered for patients during the 2-month study period were eligible for inclusion in the study. MEASUREMENTS: Daily samples of dopamine, dobutamine, and epinephrine infusates that were prepared for 41 pediatric patients were obtained; the infusate catecholamine concentration was measured by HPLC and compared with the ordered concentration. The concentration than was multiplied by the rate of infusion to determine the catecholamine dose. MAIN RESULTS: There were significant differences between the measured doses of dopamine, dobutamine, and epinephrine and the dopamine HCl, dobutamine, and epinephrine HCl doses (p = 0.0001, p = 0.039, and p = 0.0009, respectively) that had been ordered because of preparation inaccuracies. Failure to account for the HCl salt in the stock drug accounted for some, but not all, of the inaccuracy of the dopamine HCl and epinephrine HCl infusates. There was a wide interday variability in the measured catecholamine dosage in patients receiving the same dose for 3 days or more. CONCLUSIONS: There are daily fluctuations in the preparation of dopamine, dobutamine, and epinephrine infusates that could alter the amount of drug actually delivered to critically ill patients and potentially contribute to their hemodynamic instability.     

Effects of isoproterenol infusions on heart rate variability in patients with panic disorder

Some evidence suggests that patients with panic disorder have a decreased cardiac vagal and a relatively higher sympathetic activity. In this study, spectral analysis of the time series of heart rate before and after isoproterenol infusions was used to study heart rate variability in six panic disorder patients and 11 normal control subjects. These preliminary data reveal a significant increase of sympathovagal ratios only in the patient group after isoproterenol administration. The findings suggest a relative increase in cardiac sympathetic and a relative decrease in cardiac vagal function in patients with panic disorder during isoproterenol infusions.     

Treatment of relapse after allogeneic BMT with donor leukocyte infusions in 16 patients

Sixteen patients with relapse after allogeneic BMT were treated with donor leukocyte infusions (DLI) from the original donor. The diagnoses at relapse were: CML in chronic phase (CP) (two patients), CML in accelerated phase (AP) (four patients), AML (four patients), MDS (one patient), ALL (four patients) and relapse of Hodgkin's disease (one patient). The patients received a mean of 5.2 x 10(8) leukocytes/kg with a range of 1.4-12.3 x 10(8) leukocytes/kg. Six patients obtained complete remission (CR), one with CML in CP, three with CML in AP, one MDS and one ALL. Partial remission (PR) was seen in three patients, one patient with CML in AP, one with AML and one with Hodgkin's disease. Seven patients had no response (NR) to the infusions, including one patient with CML in CP transplanted with a syngeneic donor. Four patients developed marrow hypoplasia after DLI (three CR and one PR) and two patients (ALL with CR and MDS with CR) were hypoplastic at relapse and marrow hypoplasia continued after DLI. GVHD occurred without GVL, but GVL only occurred in one patient with absence of GVHD. Eleven patients died of leukemia, six patients are alive. Three patients with CML are in CR 12, 12 and 32 months after DLI and one patient with ALL is in CR 15 months after DLI.     

Digoxin bioavailability: formulations and rates of infusions

22 patients with atheromatous narrowing of the left coronary trunk underwent surgery between 1969 and 1974. Most of these patients had severe and incapacitating angina pectoris. The clinical features are readily explained by the size of the diffuse anatomical lesions, which are to be found on the left coronary trunk as well as on the three coronary vessels themselves. This series has not confirmed the serious risk of surgery in such cases, as there were no operative deaths. Secondary mortality was low (9%), and the 20 survivors (average length of follow-up: 26 months) were mostly (18/20) in an excellent condition functionally. These facts have lead us to advise surgery whenever possible.     

The effect of prenatal fructose infusions upon metabolic condition of the newborn

Changes of total blood sugars, glucose, fructose, lactate, pyruvate, acid-base balance and free fatty acids were followed in 15 healthy newborns whose mothers received fructose infusions during labour. The results were compared with 20 control newborns and with 10 newborns after prenatal glucose infusions. The levels of total blood sugars during 24 h after infusions remained higher after fructose than in 2 other groups. The values of lactate and pyruvate increased, but the lactate/pyruvate ratio remained unchanged. The free fatty acids were lower than in the control group. Results show that fructose is not a suitable source of energy for the human fetus even under normal conditions.     

Results of efficacy study with diclofenac/orphenadrine infusions in patients with musculoskeletal diseases and functional disorders

During a post-marketing surveillance study, 641 patients (age range 18 to 86 years) with painful rheumatic diseases, mostly of vertebral etiology, were given ready-for-use infusions containing a combination of the non-steroid antiphlogistic agent diclofenac (75 mg) and the muscle relaxing agent orphenadrine (30 mg) parenterally for 7 days. The goal of the study was to investigate efficacy, tolerability, and acceptance of this intravenous therapy in wide use in physicians' practices. At the end of treatment, the global evaluation resulted in a score of 1.6 on a scale of 1 (very good) to 4 (insufficient). The tolerability score was 1.3 and the acceptability score was 1.5. Only 20 patients (3.1%) had adverse effects, most of which were of gastrointestinal nature. The medication proved appropriate for use in the treatment of painful spine syndromes, inflammatory osteoarthritis, painful osteoporosis, post-operative conditions, and extra-articular rheumatism and could represent a first step towards multi-factorial therapeutic management of these diseases.     

Long-term intravenous hydroxyurea infusions in patients with advanced cancer. A phase I trial

BACKGROUND: Hydroxyurea is an S-phase specific drug. Constant exposure of tumor cells with a low S-phase fraction to the agent may result in improved cell kill. Because of its short half-life, a continuous intravenous infusion may result in better tumor exposure than intake by mouth. The goal of this trial was to find the longest tolerable duration of a continued intravenous infusion of hydroxyurea (HU) given at escalating doses. METHODS: Eligible patients had histologically confirmed cancer without effective alternate therapy, normal blood counts, liver and kidney function. After giving informed consent, the infusion began via a permanent indwelling catheter utilizing a portable pump. Dose levels (in g/m2/d) were 0.5 for level I, 1.0 for level II, 1.66 for level III, and 2.5 for level IV. RESULTS: Fourteen patients were entered. Five were men. Median age was 56 years of age (range: 32-67), median performance status 1 (range: 0-2). Diagnoses were as follows: colorectal cancer, seven; unknown primary site, three; breast cancer, two; melanoma, one; and adenoid-cystic carcinoma, one. Nine patients were pretreated with chemotherapy. Three patients were entered per dose level, except on level I, were five were entered. The mean duration of infusion was 12 weeks on level I, 5 weeks on II, 3 on III, 1 on IV. Toxicity included leukopenia below 2.0 K/mm3 in one patient each on levels III and IV, thrombocytopenia below 100 K/mm3 in one patient each on levels II and IV, and stomatitis in three patients (one on level II and two on IV). This toxicity was dose limiting. One patient on level III, with an unknown primary, had an objective response. HU levels were measured by a modification of the Fabricius-Rajewsky method. Mean plasma levels in micrograms per milliliter (SEM) were as follows: level I, 3.6 (0.23); level II, 5.1 (0.57); level III, 10.1 (1.55); and level IV, 16.7 (one point). Fetal hemoglobin rose two-fold and five-fold in two patients on level I after 9 and 16 weeks on therapy, respectively. CONCLUSIONS: HU as a continuous intravenous infusion is well tolerated; the maximum duration of therapy is related inversely with the dose given. No major antitumor activity was seen. The greatest interest in the drug rests in its future use as a modulator and radiation potentiator. The increase in hemoglobin F was of interest and may be important in the treatment of sickle cell disease.     

Use and misuse of albumin infusions in neonatal care

During the neonatal period, albumin infusions are administered in response to a variety of clinical scenarios. Review of currently available literature, however, demonstrates that crystalloid rather than colloid infusions should be used both to treat hypovolaemic hypotension and as the replacement fluid in a dilutional exchange. The role of an albumin infusion in "treating" metabolic acidosis needs further evaluation, but the practice of giving albumin to correct "asymptomatic" hypoalbuminaemia or at resuscitation should be discouraged. CONCLUSION: The neonatologist would be well advised, when reaching for an albumin infusion, to reflect that there may be a safer, certainly cheaper and equally effective alternative.