Managing sore throat: a literature review. I. Making the diagnosis.

OBJECTIVE: To assess the justification for the routine use of investigations in the diagnosis of bacterial causes of sore throat. DATA SOURCES: The literature from 1945 to 1990 was systematically screened to identify studies that addressed diagnosis of bacterial infection and the efficacy of antibiotics in sore throat, using the key-words "pharyngitis" and "tonsillitis". RESULTS: Difficulties were identified with clinical methods and investigations that identify streptococcal infections. The practice of throat-swab culture--the "gold standard"--appears to have developed as a strategy to protect patients from acute rheumatic fever. However, this method may be limited in its usefulness for protection against acute rheumatic fever because: (i) in many cases in which the streptococcus is isolated from symptomatic patients there is no serological evidence of infection; (ii) there are very high asymptomatic carrier rates of the streptococcus; (iii) even after adequate treatment with penicillin there are high bacteriological failure rates; and (iv) those organisms that can be isolated from the mucosal surface are a poor representation of organisms lying deep in the tissues. Evaluation of other diagnostic techniques such as Gram's stain and rapid antigen testing, as well as decision analysis, has also been hampered by the difficulties encountered with use of this inadequate gold standard. CONCLUSION: There is little indication from the literature that any routine system of identifying bacterial causes of sore throat is helpful to the clinician.     

Evaluation of a training program to improve clinical competencies of pharmacists serving skilled nursing facilities

Forty-eight pharmacists from the New York area were selected for specialized training in consultant clinical services to skilled nursing home facilities. A skills curriculum was developed, and the pharmacists participated in 15 training sessions which included lectures by nationally recognized experts, audiovisual presentations, and on-site clinical workshops. Evaluations were based upon clinical preprogram v. clinical postprogram testing, comparisons with clinical pharmacy experts, and attitudinal pre- and postprogram testing. It was found that the training course did improve the skills of the trainees but they still performed at a level below recognized clinical pharmacy experts. Future programs should stress fewer topics, but in more detail, and should focus upon monitoring techniques, laboratory results, and more on-site experiences.     

Beneficial effect of verapamil added to chronic ACE inhibitor treatment on renal function in hypertensive elderly patients

This study analysed the effect of low doses ofverapamil added to chronic treatment withangiotensin-converting enzyme (ACE) inhibitors onblood pressure and serum creatinine levels in eightelderly hypertensive patients who had a steadyincrease of serum creatinine while on ACE inhibitors.The study was performed in eight elderly hypertensivesubjects, five men and three women (mean age 70 ±2 years; systolic blood pressure 173 ± 4 mmHg; diastolic blood pressure 99 ± 1 mm Hg) andserum creatinine of 1.60 ± 0.27 mg/dl beforetreatment. During an average of 25 weeks, ACEinhibitors significantly reduced both systolic anddiastolic blood pressures, but serum creatinine levelswere increased over basal levels (0,68 ± 0,20 mg/dl, p < 0.05). During an average of 10 weeks,the addition of verapamil did not decrease bloodpressure further, but serum creatinine levels werereduced to baseline. Our study suggests that theaddition of verapamil to ACE inhibitors can reverseACE-induced increase in creatinine levels in elderlyhypertensive patients in whom this side effect isobserved. This revised version was published online in August 2006 with corrections to the Cover Date.     

CD34+ cells from acute myeloid leukemia, myelodysplastic syndromes, and normal bone marrow display different apoptosis and drug resistance-associated phenotypes.

Myelodysplastic syndromes and acute myeloid leukemia (AML) are heterogeneous disorders in which conflicting results in apoptosis and multidrug resistance (MDR) have been reported. We have evaluated by multiparameter flow cytometry the expression of apoptosis- (APO2.7, bcl-2, and bax) and MDR-related proteins [P-glycoprotein (P-gp), multidrug resistance protein (MRP), and lung resistance protein (LRP)] specifically on bone marrow (BM) CD34+ cells, and their major CD32-/dim and CD32+ subsets, in de novo AML (n=90), high-risk myelodysplastic syndrome (n=9), and low-risk myelodysplastic syndrome (n=21) patients at diagnosis, and compared with normal BM CD34+ cells (n=6). CD34+ myeloid cells from AML and high-risk myelodysplastic syndrome patients displayed higher expression of bcl-2 (P <0.0001) and lower reactivity for APO2.7 (P=0.002) compared with low-risk myelodysplastic syndrome and normal controls. Similar results applied to the two predefined CD34+ myeloid cell subsets. No significant differences were found in the expression of P-gp, MRP, and LRP between low-risk myelodysplastic syndrome patients and normal BM, but decreased expression of MRP (P <0.03) in AML and high-risk myelodysplastic syndromes and P-gp (P=0.008) in high-risk myelodysplastic syndromes were detected. Hierarchical clustering analysis showed that low-risk myelodysplastic syndrome patients were clustered next to normal BM samples, whereas high-risk myelodysplastic syndromes were clustered together and mixed with the de novo AML patients. In summary, increased resistance to chemotherapy of CD34+ cells from both AML and high-risk myelodysplastic syndromes would be explained more appropriately in terms of an increased antiapoptotic phenotype rather than a MDR phenotype. In low-risk myelodysplastic syndromes abnormally high apoptotic rates would be restricted to the CD34- cell compartments.     

Continuous care in the cancer patient: palliative care in the 21<Superscript>st</Superscript> century

Continuous care for the cancer patient is an open concept that is not only applicable only to the terminal stage. Such a simplification could generate inequities of therapy and discrimination. Historically, oncology services have been structured as networks dispensing chemotherapy and radiotherapy rather than services dedicated to the integrated care of the cancer patient. This situation has changed in a continuous and progressive manner over the past few years, as reflected in the latest Spanish Libro Blanco de Oncología. We are still far from reaching the optimum level of integrated care, possibly because we have not, as yet, achieved services that are structured and appropriate for the care-needs of the patient and, perhaps, to the lack of the necessary personnel. We must always make sure that cancer patients receive the best possible treatment, irrespective of whet-her the disease is in relapse. Oncologists must not “give up”, indicating that, in addition to using the most effective anticancer treatments available, they should deploy their best knowledge and experience to control the symptoms of cancer while providing psycho-social help to the patient and family. This is best conducted with a communication that is adjusted to the changing needs of the patient over the longterm clinical process, and should be provided by a multidisciplinary team, according to the needs of the patient and the family. Within a program of integrated care, it is possible to coordinate the existing care structures without creating parallel health networks so as to cover the needs of the greatest number of cancer patients in advanced stage of the disease.     

Importance of uniform heparin coating on biopolymers

Cardiopulmonary surgeries need connectors for extracorporeal circulation. The patient's blood in contact with the tube surfaces modifies its plasmatic proteins, promotes platelet aggregation, and activates the complement system, unleashing thrombus formation. Thus, it becomes necessary for an anticoagulant to keep the circuit free from these events. Heparin is the anticoagulant used even after reports about its disadvantages. Platelet adherence seems to be very dependent on the quality from the surfaces that can promote cellular proliferation, aggregation, and thrombosis. In this study, we compare the quality of the heparin-coated and uncoated surfaces. We used a blood cell culture and scanning electron microscopy (SEM) to visualize the platelet aggregation. It was concluded that there are groove areas that permit platelet adherence, and if they are not coated totally by the heparin, aggregation still occurs although in lower scale than on the uncoated tubes.     

Hippocampal dopamine receptors modulate the motor activation and the increase in dopamine levels in the rat nucleus accumbens evoked by chemical stimulation of the ventral hippocampus.

A number of studies have shown that chemical stimulation (using N-methyl-D-aspartate (NMDA) infusions) or electrical stimulation of the ventral hippocampus (VH) elicits locomotor activation and sustained increases in nucleus accumbens (NAc) dopamine (DA) levels in rodents. How DA neurotransmission in NAc is involved in these effects has also been well established. However, the modulatory role of the DA receptors located in VH is not yet fully understood. The purpose of this study was to characterize the role played by VH D1 and D2 subtype receptors in both the locomotor activation and NAc DA increases induced by NMDA stimulation of the VH. This was assessed by studying how retrodialysis application of NMDA (50 mM, 10 min) affects motor activity and NAc DA levels during simultaneous retrodialysis administration of the D1/D5 receptor antagonist SCH 23390 (100 and 250 microM, 60 min) or the D2 receptor antagonist raclopride (100 and 250 microM, 60 min). SCH 23390 attenuated or completely abolished NMDA-evoked locomotor activation and the concurrent increase in NAc DA levels. On the other hand, raclopride was initially able to attenuate the effects of VH NMDA stimulation. However, in the last phase of the experiments, animals showed an important increase in clonic seizure activity with a simultaneous and dramatic increase in NAc DA levels. Our results show that the NMDA receptor-mediated effects in the VH require both D1 and, probably, D2 receptors and suggest that DA in VH strongly modulates the excitatory outputs from this brain area.     

Localization of NADPH diaphorase/nitric oxide synthase and choline acetyltransferase in the spinal cord of the frog, Rana perezi

The localization of nitrergic cells and fibers and cholinergic cells has been analyzed in the spinal cord of the anuran amphibian Rana perezi. Histochemistry for nicotinamide adenine dinucleotide phosphate-diaphorase and nitric oxide synthase immunohistochemistry revealed a concurrent pattern of labeled structures. A large population of nitrergic spinal neurons was found from the level of the obex to the filum terminale. They are abundant in the dorsal horn and intermediate gray matter, but also occur in territories of the ventral horn and, only occasionally, in somatic motoneurons. Numerous nitrergic fibers were present in the spinal white matter, particularly in the dorsal and dorsolateral funiculi. A special arrangement of nitrergic axons is present in Lissauer's tract, where a collateral system is formed. Cholinergic cells, revealed by choline acetyltransferase immunohistochemistry, were observed throughout the spinal cord. The somatic motoneurons were the most conspicuously immunoreactive cells. A large population of cholinergic cells forms a discontinuous column in the intermediate gray, from the third spinal segment to lumbar segments. These cells were organized in a medially located or intercalated cell group, and a laterally located intermediolateral group. Numerous scattered cholinergic cells were present in the central zone of the ventral horn and were absent in the dorsal horn. Double-labeling experiments revealed a high degree of codistribution of nitrergic and cholinergic cells, mainly in the intermediate gray, but colocalization of both markers in the same neurons was not found. This result contrasts with the situation found in mammals and raises the question of whether coexpression of both substances was acquired in spinal cord neurons through evolution only in amniotes or, even, only in mammals.     

Death and neuroprotection of retinal ganglion cells after different types of injury

In adult Sprague-Dawley rats, retinal ganglion cell survival was investigated after intraorbital optic nerve section and after transient ischemia of the retina induced by elevation of the intraocular pressure or by selective ligature of the ophthalmic vessels. The thickness of the inner nuclear and inner plexiform layers was also assessed after transient periods (120 min) of retinal ischemia induced by selective ligature of the ophthalmic vessels. In addition, we have also investigated the neuroprotective effects of different substances in these paradigms. The intraocular injection of brain-derived neurotrophic factor increased RGC survival after retinal ischemia induced by elevation of the intraocular pressure or by selective ligature of the ophthalmic vessels. The caspase-inhibitor Z-DEVD increased retinal ganglion cell survival after optic nerve section and also after 90 min of retinal ischemia induced by selective ligature of the ophthalmic vessels. The peptide Bcl-2 did not increase retinal ganglion cell survival after optic nerve section but increased retinal ganglion cell survival after 60 or 90 min of retinal ischemia induced by selective ligature of the ophthalmic vessels. Finally, BDNF, nifedipine, naloxone and bcl-2 prevented in part the decrease in thickness of the inner nuclear layer and inner plexiform layer induced by selective ligature of the ophthalmic vessels. Our results suggest that retinal ganglion cell loss induced by different types of injury, may be prevented by substances with neuroprotective effects, by altering steps of the cascade of events leading to cell death.