Search

OBJECTIVE: Intramuscular injections may be painful. Some of this pain may be caused by the infiltration of medication into the muscle, separate from the pain of skin puncture. We hypothesized that topical application of lidocaine/prilocaine (EMLA) cream would reduce the pain of intramuscular infiltration. METHODS: A double-blinded, placebo-controlled study was performed in 40 adult volunteers to compare the pain of needle puncture and of infiltration of saline into the deltoid muscle after application of EMLA cream or placebo. Each subject served as his or her own control. Pain scores were obtained by using a 100 mm visual analog scale (VAS). RESULTS: Pain associated with needle puncture was significantly reduced by EMLA cream as compared with placebo (median VAS score, 7.5 vs 19.5; p = 0.0043), as was pain associated with intramuscular infiltration (median VAS score, 2.5 vs 11; p <0.00005). CONCLUSIONS: Our results suggest that further clinical studies of EMLA cream for modifying perceived pain from intramuscular injection in children are warranted. (J Pediatr 1996;129:718-21)

Cells disseminated from primary epithelial tumors into peripheral blood, called circulating tumor cells (CTCs), can be monitored to assess metastases and to provide a surrogate marker of treatment response. Here, we demonstrate how the flexible micro spring array (FMSA)device—a novel microfluidic device that enriches CTCs by two physical parameters: size and deformability—could be used in the rational development of treatment intervention and as a method to study the fundamental biology of CTCs. Cancer cells of different origins were spiked into healthy samples of donor blood to mimic blood samples of metastatic cancer patients. This spiked human blood was filtered using the FMSA device, and the recovered cells were successfully expanded in vitro and in a novel in vivo system. A series of experiments were performed to characterize these cells and to investigate the effect of chemotherapy on the resulting cultures. As few as 20 colon cancer cells in 7.5 mL blood could be isolated with the FMSA device, expanded both in vitro and in vivo and used at 25 cells per well to obtain significant and reliable chemosensitivity data. We also show that isolating a low number of viable patient CTCs and maintaining them in culture for a few weeks is possible. The isolation of viable cancer cells from human blood using the FMSA device provides a novel and realistic means for studying the biology of viable CTCs and for testing drug efficacy on these rare cells—a hypothesis that can be tested in future clinical trials.

Breast cancer is a highly osteotropic neoplasm, and as many as 75% of patients with metastatic disease will have involvement of the bony skeleton. On radiologic examination, these metastases are predominantly osteolytic but can be osteoblastic or mixed. The mechanisms by which metastases are formed are complex, involving many steps that include angiogenesis, invasion, and proliferation in the bone microenvironment. Tumor cells in the bone microenvironment produce a large number of cytokines that stimulate osteoclastic activity. Increased osteoclastic activity, in turn, leads to production of a variety of lymphokines and growth factors that can increase tumor cell proliferation. Thus, a cytokine network is established, which results in an imbalance of the processes of bone formation and bone resorption. As tumor burden in bone increases, osteoclast-mediated bone resorption is accelerated, resulting in loss of bone strength, fractures, pain, and other morbidities. Tumor cells metastatic to bone can also secrete growth factors, leading to increased osteoblastic activity. Osteoblasts lay down an excess of new bone that is structurally weak. There is considerable crosstalk between osteoclasts, osteoblasts, macrophages, and other cellular elements within the bone environment. The increasing understanding of the biology of bone metastases has opened the door to improved management of this important clinical problem. Current treatment strategies include approaches to reduce tumor burden and developing treatments that directly inhibit osteoclast function. The bisphosphonates are a class of drugs that inhibit osteoclast recruitment and function. Several highly potent bisphosphonates are now available for clinical use and represent an important adjunct in the management of bone metastases from breast cancer, multiple myeloma, and several other types of malignancies. Some newer therapeutic approaches include agents designed to inhibit the osteoclast-osteoblast signaling interactions or alter processes of adhesion and invasion.

ABSTRACTAcyclovir cream has been available for the treatment of herpes labialis in numerous countries outside the United States for over a decade. Evidence for its efficacy comes from a few small clinical trials conducted in the 1980s. To examine more comprehensively the efficacy and safety of this formulation, we conducted two independent, identical, parallel, randomized, double-blind, vehicle-controlled, large-scale multicenter clinical trials. Healthy adults with a history of frequent herpes labialis were recruited from the general population, screened for eligibility, randomized equally to 5% acyclovir cream or vehicle control, given study medication, and told to self-initiate treatment five times daily for 4 days beginning within 1 h of the onset of a recurrent episode. The number of patients who treated a lesion was 686 in study 1 and 699 in study 2. In study 1, the mean duration of episodes was 4.3 days for patients treated with acyclovir cream and 4.8 days for those treated with the vehicle control (hazards ratio [HR] = 1.23; 95% confidence interval [CI], 1.06 to 1.44; P= 0.007). In study 2, the mean duration of episodes was 4.6 days for patients treated with acyclovir cream and 5.2 days for those treated with the vehicle control (HR = 1.24; 95% CI, 1.06 to 1.44; P= 0.006). Efficacy was apparent whether therapy was initiated “early” (prodrome or erythema lesion stage) or “late” (papule or vesicle stage). There was a statistically significant reduction in the duration of lesion pain in both studies. Acyclovir cream did not prevent the development of classical lesions (progression to vesicles, ulcers, and/or crusts). Adverse events were mild and infrequent.

Thyrotropin-releasing hormone (TRH) injected into the retrotrapezoid nucleus (RTN) of anesthetized rats produces a large, prolonged stimulation of ventilatory output (C. L. Cream, A. Li, and E. E. Nattie. J. Appl. Physiol.83: 792–799, 1997). Here we inject or dialyze TRH into the RTN of conscious rats. In 6 of 17 injections (200 nl, 3.1 ± 1.7 mM), ventilation (V˙e) increased 31% by 10 min, with recovery by 60 min. With dialysis, each animal of one group (n= 5) received, in random order, 10 mM TRH, 10 mM TRHOH (a metabolite of TRH), and artificial cerebrospinal fluid (aCSF); each animal of a second group (n= 5) received aCSF and 1 mM TRH. TRHOH and aCSF had no sustained effects. TRH (1 mM) increasedV˙e(32%,P< 0.02, by 10 min, with recovery by 60 min), O2consumption (V˙o2; 19%,P< 0.03), and body (rectal) temperature (Tre; 0.5°C,P< 0.09). TRH (10 mM) increasedV˙e(78%,P< 0.01, by 10 min, with no recovery at 60 min), V˙o2(48%, P< 0.01), and Tre(1.0°C,P< 0.01). TRH also induced arousal. The tissue volume affected in dialysis, estimated by spread of dialyzed fluorescein (332.3 mol wt, mol wt of TRH = 362.4), was 1,580 ± 256 nl for 10 mM (n= 5) and 590 ± 128 nl for 1 mM (n= 5). We conclude that1) the RTN is involved in the integration ofV˙e,V˙o2, Tre, and arousal and2) TRH may establish the responsiveness of RTN neurons.

Julia Cream describes the prevalence and common symptoms of dementia, and discusses the challenges facing society in caring for an increasingly ageing population. In an era of tight budgets and shrinking resources, she suggests ways to focus care on those most in need of it.

Attention has recently been focused on the use of ISD behavioral data for specifying aircrew training requirements. However, behavioral data are not sufficient for the actual specification of design of equipment, which frequently represents the major dollar investment for training programs. The paper presents a methodology for designing training equipment. This methodology in some ways goes beyond the collection of behavioral data, and in other ways ayoids the weaknesses of the behavioral data approach. The emphasis is on ensuring that device fidelity requirements are specifically correlated with training requirements. Four critical areas are addressed: (1) acquisition of behavioral data; (2) determination of training capabilities; (3) performance measurement; and (4) special requirements for crew coordination training.

Cream, Carlos L., Aihua Li, and Eugene E. Nattie. RTN TRH causes prolonged respiratory stimulation. J. Appl. Physiol.83(3): 792–799, 1997.—We injected thyrotropin-releasing hormone (TRH; 10 nl; 0.25, 0.5, 1.0, or 10 mM), its inactive free acid form (TRHOH; 1 mM), or a metabolite with low TRH-receptor binding affinity, histidine-proline diketopiperazine (cHP; 1 mM), into the retrotrapezoid nucleus of anesthetized rats. Injection location was verified by anatomic analysis. Lower doses (0.25–0.5 mM) significantly increased both the product of integrated phrenic amplitude and frequency (∫Phr ⋅ f) and f for 20–30 min compared with artificial cerebrospinal fluid control injections. Higher doses (1.0–10 mM) produced greater and long-lasting stimulation of ∫Phr ⋅ f,∫Phr, and f and of blood pressure. This stimulation reached values 150% of baseline and durations of 270 min after a single injection. TRHOH (1 mM ) or cHP (1 mM) had no effect on∫Phr but increased f, as did 1 mM TRH. We conclude that TRH has a very powerful stimulatory effect in the retrotrapezoid nucleus region on ∫Phr ⋅ f, with the ∫Phr response seemingly specific for TRH receptors. Similar responses of f to TRHOH and cHP suggest it may be nonspecific.

A description is provided of a research study being conducted by the United States Air Force with participation by representatives from the Army and Navy. The basic objectives of this study are to define, collect, analyze and present data, findings and conclusions relevant to the use, effectiveness and cost of aircrew training devices. Study philosophy, approach, difficulties and current status are discussed.

The article presents an overview of some of the most common and accepted quality management tools from the Australian Wine Research Institute Analytical Service laboratory. The Analytical Service facilitates the transfer of research outcomes into practical applications and services to the benefit of Australian grapegrowers and winemakers. Having the right quality management system in place has a positive impact on the overall business results.

Olaparib was first FDA approved for use in women with advanced ovarian cancer and germline BRCA mutations. Based on the results of subsequent research, the use of this drug has been expanded to patients with metastatic breast cancer with germline BRCA mutation. With the use of a relatively new medication and a larger patient population eligible for therapy, monitoring for novel adverse events associated with therapy is important. This case represents a patient with metastatic breast cancer and germline BRCA2 mutation who developed erythema nodosum after initiation of therapy with olaparib capsules. Her characteristic rash appeared shortly after starting olaparib and recurred after restarting olaparib an additional two times. She was treated with short courses of prednisone therapy with or without holding olaparib with resolution of her rash. The patient was later restarted on olaparib capsules 200 mg twice daily, and she more recently has been maintained on olaparib tablets 300 mg twice daily. On both regimens, the patient experienced only attenuated episodes of erythema nodosum that have not required cessation of therapy or steroid therapy.

Thirty-five patients with cutaneous vasculitis were studied. Sixteen had raised serum levels of cryoglobulins. In all but one the cryoglobulin was an immune complex. Eleven patients had anticomplementary sera and five had a low serum IgM. Clinically, the cryoglobulinaemic patients were not readily distinguishable from the non-cryoglobulinaemic in that cold sensitivity occurred in only six of sixteen patients with cryoglobulins. Peripheral neuropathy and lesions in the upper respiratory tract were confined to those with cryoglobulinaemia. An immunopathological classification for the purpuric vasculitides is suggested.