Charles Edward Smith: Coccidioidomycologist and public health leader.

Although Charles Edward Smith did not discover coccidioidomycosis, he defined the disease through his infatigueable studies of the epidemiology, clinical findings, and immunology of this infection. He became its preeminent authority. He also had an important role in the development of public health, and for the last 16 years of his life he was the Dean of the School of Public Health at the University of California at Berkeley, where he was a revered and energetic leader.

The Discovery of Q Fever and Its Cause.

An outbreak of a febrile illness among workers in a slaughterhouse in Brisbane, Australia led E.H. Derrick to discover a new infection, which he labeled Q fever. Almost simultaneously, investigators in Montana discovered a new organism in ticks that caused fever in guinea pigs. Eventually, investigators found that the Q fever and tick microbes were identical. Outbreaks of Q fever occurred in laboratories, and epidemics of it affected both Axis and Allied troops in Europe during World War II, but it was only afterwards that an explanation emerged about what the major reservoir of the organism was and how infection was most commonly transmitted to animals and humans.

Distinct cortical responses evoked by electrical stimulation of the thalamic ventral intermediate nucleus and of the subthalamic nucleus.

OBJECTIVE: To investigate the spatial and temporal pattern of cortical responses evoked by deep brain stimulation (DBS) of the subthalamic nucleus (STN) and ventral intermediate nucleus of the thalamus (VIM). METHODS: We investigated 7 patients suffering from Essential tremor (ET) and 7 patients with Parkinson's Disease (PD) following the implantation of DBS electrodes (VIM for ET patients, STN for PD patients). Magnetoencephalography (MEG) was used to record cortical responses evoked by electric stimuli that were applied via the DBS electrode in trains of 5 Hz. Dipole fitting was applied to reconstruct the origin of evoked responses. RESULTS: Both VIM and STN DBS led to short latency cortical responses at about 1 ms. The pattern of medium and long latency cortical responses following VIM DBS consisted of peaks at 13, 40, 77, and 116 ms. The associated equivalent dipoles were localized within the central sulcus, 3 patients showed an additional response in the cerebellum at 56 ms. STN DBS evoked cortical responses peaking at 4 ms, 11 ms, and 27 ms, respectively. While most dipoles were localized in the pre- or postcentral gyrus, the distribution was less homogenous compared to VIM stimulation and partially included prefrontal brain areas. CONCLUSION: MEG enables localization of cortical responses evoked by DBS of the VIM and the STN, especially in the sensorimotor cortex. Short latency responses of 1 ms suggest cortical modulation which bypasses synaptic transmission, i.e. antidromic activation of corticofugal fiber pathways.

Paul Beeson (1908-2006), Distinguished Physician.

Paul Bruce Beeson (1908-2006) was a preeminent academic physician in both the United States and Great Britain. He attended medical school at McGill University in Canada and then trained at the University of Pennsylvania and Harvard University. During his career, he was Chairman of the Departments of Medicine at Emory University and at Yale University and then became Nuffield Professor at Oxford University. He ended his career at the Veterans Administration in Seattle as a Distinguished Physician. He was a skilled administrator and an excellent and admired clinician. He was also a productive scientist, who discovered interleukin-1, studied the pathogenesis of urinary tract infections and endocarditis, and delineated the causes of prolonged fever of unknown origin.

From Squirrels to Biological Weapons: The Early History of Tularemia.

After George McCoy accidentally discovered a new infection in 1911 while investigating bubonic plague in squirrels, he transmitted the disease to experimental animals and isolated the causative organism. He called it Bacterium tularense, after Tulare County, California. In 1919, Edward Francis determined that an infection called "deer-fly fever" was the same disease, naming it "tularemia." He demonstrated that it occurred in wild rabbits and inadvertently showed that it was highly infectious, for he and all his laboratory assistants contracted the illness. This characteristic led to studies of its potential as a biological weapon, including involuntary human experimentation by Japan among civilian, political and military prisoners, and its probable use in warfare during World War II. Later, in the United States, voluntary human experimentation occurred in the 1950s-1960s with penitentiary inmates and non-combatant soldiers. Soviet Union scientists allegedly developed a vaccine-resistant strain, which they tested as a biological weapon in 1982-1983.

Parkinsonian rest tremor can be detected accurately based on neuronal oscillations recorded from the subthalamic nucleus.

OBJECTIVE: To investigate the possibility of tremor detection based on deep brain activity. METHODS: We re-analyzed recordings of local field potentials (LFPs) from the subthalamic nucleus in 10 PD patients (12 body sides) with spontaneously fluctuating rest tremor. Power in several frequency bands was estimated and used as input to Hidden Markov Models (HMMs) which classified short data segments as either tremor-free rest or rest tremor. HMMs were compared to direct threshold application to individual power features. RESULTS: Applying a threshold directly to band-limited power was insufficient for tremor detection (mean area under the curve [AUC] of receiver operating characteristic: 0.64, STD: 0.19). Multi-feature HMMs, in contrast, allowed for accurate detection (mean AUC: 0.82, STD: 0.15), using four power features obtained from a single contact pair. Within-patient training yielded better accuracy than across-patient training (0.84vs. 0.78, p=0.03), yet tremor could often be detected accurately with either approach. High frequency oscillations (>200Hz) were the best performing individual feature. CONCLUSIONS: LFP-based markers of tremor are robust enough to allow for accurate tremor detection in short data segments, provided that appropriate statistical models are used. SIGNIFICANCE: LFP-based markers of tremor could be useful control signals for closed-loop deep brain stimulation.

Differential modulation of STN-cortical and cortico-muscular coherence by movement and levodopa in Parkinson's disease.

Previous research suggests that oscillatory coupling between cortex, basal ganglia and muscles plays an important role in motor behavior. Furthermore, there is evidence that oscillatory coupling is altered in patients with movement disorders such as Parkinson's disease (PD). In this study, we performed simultaneous magnetoencephalography (MEG), local field potential (LFP) and electromyogram (EMG) recordings in PD patients selected for therapeutic subthalamic nucleus (STN) stimulation. Patients were recorded (i) after withdrawal of anti-parkinsonian medication (OFF) and (ii) after levodopa administration (ON). We analyzed STN-cortical and cortico-muscular coherence during static forearm contraction and repetitive hand movement in order to evaluate modulations of coherence by movement and medication. Based on previous results from studies investigating resting state coherence in PD patients, we selected primary motor cortex (M1) and superior temporal gyrus (STG) as regions of interest. We found beta coherence between M1 and STN to be suppressed by administration of levodopa. M1-muscular coherence was strongly reduced in the alpha and beta band during repetitive movement compared to static contraction, but was unaffected by administration of levodopa. Strong STG-STN but not STG-muscular coherence could be observed in the alpha band. Coherence with STG was modulated neither by movement nor by medication. Finally, we found both M1-STN and M1-muscular beta coherence to be negatively correlated with UPDRS akinesia and rigidity sub-scores in the OFF state. The present study provides new insights into the functional roles of STN-cortical and cortico-muscular coherence and their relationship to PD symptoms. The results indicate that STN-cortical and cortico-muscular coupling are correlated, but can be modulated independently. Moreover, they show differences in their frequency-specific topography. We conclude that they represent partly independent sub-loops within the motor system. Given their negative correlation with akinesia, neither can be considered "antikinetic".

Reinvestigating 2,5-di(pyridin-2-yl)pyrazine ruthenium complexes: selective deuteration and Raman spectroscopy as tools to probe ground and excited-state electronic structure in homo- and heterobimetallic complexes.

The mono- (1) and dinuclear (2) ruthenium(II) bis(2,2'-bipyridine) complexes of 2,5-di(pyridin-2-yl)pyrazine (2,5-dpp), for which the UV/Vis absorption and emission as well as electrochemical properties have been described earlier, are reinvestigated here by resonance, surface enhanced and transient resonance Raman spectroscopy together with selective deuteration to determine the location of the lowest lying excited metal to ligand charge transfer ((3)MLCT) states. The ground state absorption spectrum of both the mono- and dinuclear complexes are characterised by resonance Raman spectroscopy. The effect of deuteration on emission lifetimes together with the absence of characteristic bipy anion radical modes in the transient Raman spectra for both the mono- and dinuclear complexes bridged by the 2,5-dpp ligand confirms that the excited state is 2,5-dpp based; however DFT calculations and the effect of deuteration on emission lifetimes indicate that the bipy based MLCT states contribute to excited state deactivation. Resonance Raman and surface enhanced Raman spectroscopic (SERS) data for 1 and 2 are compared with that of the heterobimetallic complexes [Ru(bipy)(2)(2,5-dpp)PdCl(2)](2+)3 and [Ru(bipy)(2)(2,5-dpp)PtCl(2)](2+)4. The SERS data for 1 indicates that a heterobimetallic Ru-Au complex forms in situ upon addition of 1 to a gold colloid.

Distinct oscillatory STN-cortical loops revealed by simultaneous MEG and local field potential recordings in patients with Parkinson's disease.

Neuronal oscillations are assumed to play a pivotal role in the pathophysiology of Parkinson's disease (PD). Neurons in the subthalamic nucleus (STN) generate oscillations which are coupled to rhythmic population activity both in other basal ganglia nuclei and cortical areas. In order to localize these cortical areas, we recorded local field potentials (LFPs) and magnetoencephalography (MEG) simultaneously in PD patients undergoing surgery for deep brain stimulation (DBS). Patients were withdrawn from antiparkinsonian medication and recorded at rest. We scanned the entire brain for oscillations coherent with LFPs recorded from the STN with a frequency domain beamformer. Coherent activity in the low (12-20 Hz) and high (20-35 Hz) beta range was found in the ipsilateral sensorimotor and the premotor cortex. Coherence in the alpha range (7-12 Hz) was observed at various locations in the ipsilateral temporal lobe. In a subset of subjects, the superior temporal gyrus consistently showed coherent alpha oscillations. Our findings provide new insights into patterns of frequency-specific functional connectivity between basal ganglia and cortex and suggest that simultaneous inter-regional interactions may be segregated in the frequency domain. Furthermore, they demonstrate that simultaneous MEG-LFP recordings are a powerful tool to study interactions between brain areas in PD patients undergoing surgery for DBS.

When antibiotics are unnecessary.

Dermatologists can decrease unnecessary use of antimicrobial agents by avoiding them in situations wherein good evidence indicates that they are ineffective. Controlled trials indicate that antimicrobial agents are unhelpful in treating cutaneous abscesses, inflamed epidermal cysts, uninfected atopic eczema, and cutaneous ulcers caused by venous insufficiency or diabetes in the absence of significant contiguous soft-tissue inflammation. Prophylactic antibiotics are rarely appropriate for routine dermatologic surgery and are not indicated for patients who have prosthetic joints or vascular grafts. They are recommended only for a small group of patients who have abnormal cardiac valves, and then only with surgery involving clearly infected skin or soft-tissue. Topical antibiotics are no better than white petrolatum in covering sutured wounds, and with moist occlusive dressings, no ointment is necessary.

Benjamin Franklin and medicine.

Benjamin Franklin, called Dr. Franklin after receiving an honorary degree in 1759 for his contributions to understanding electricity, was not formally trained as a physician. Nevertheless, he had numerous interests in medicine, including experimentation, shrewd observations about health and disease in himself and others, civic activities, and inventions of medical devices. These achievements show his capacity for detailed, perceptive insights; his fastidiousness in recording his observations; and his thoughtful analyses of scientific phenomena and human conduct. In medicine, perhaps uniquely in his life, his major interests intersected: scientific pursuits, civic activities, amused scrutiny of human behavior, and the desire to improve the lot of his fellow man.

Antibiotics for common respiratory tract infections in adults.

A thorough review of the published information indicates that antibiotics rarely benefit acute bronchitis, exacerbations of asthma and chronic bronchitis, acute pharyngitis, and acute sinusitis, although they are commonly prescribed for these illnesses. Rather than prescribing them for these conditions, practitioners should explain to their patients that antibiotics, which have numerous adverse effects, will not hasten resolution of their symptoms, which will often respond to other medications. Most patients will accept this approach if the clinician addresses their concerns, shows a personal interest in them, discusses the expected course of the ailment, and explains the treatment.

Do bacteria cause exacerbations of COPD?

Exacerbations of COPD, which include combinations of dyspnea, cough, wheezing, increased sputum production (and a change in its color to green or yellow), are common. The role of bacterial infection in causing these episodes and the value of antibiotic therapy for them are debated. An assessment of the microbiological studies indicates that conventional bacterial respiratory pathogens, such as Streptococcus pneumoniae and Haemophilus influenzae, are absent in about 50% of attacks. The frequency of isolating these organisms, which often colonize the bronchi of patients in stable condition, does not seem to increase during exacerbations, and their density typically remains unchanged. Serologic studies generally fail to show rises in antibody titers to H influenzae; the only report available demonstrates none to Haemophilus parainfluenzae; and the sole investigation of S pneumoniae is inconclusive. Trials with vaccines against S pneumoniae and H influenzae show no clear benefit in reducing exacerbations. The histologic findings of bronchial biopsies and cytologic studies of sputum show predominantly increased eosinophils, rather than neutrophils, contrary to what is expected with bacterial infections. The randomized, placebo-controlled trials generally show no benefit for antibiotics, but most have studied few patients. A meta-analysis of these demonstrated no clinically significant advantage to antimicrobial therapy. The largest trials suggest that antibiotics confer no advantage for mild episodes; with more severe attacks, in which patients should receive systemic corticosteroids, the addition of antimicrobial therapy is probably not helpful.

Antimicrobial prophylaxis in dermatology.

Few circumstances in dermatology warrant antimicrobial prophylaxis. In cutaneous surgery postoperative infections are too infrequent and insufficiently severe to justify preventive antibiotics, except rarely. Petrolatum is as effective as, and cheaper than, topical antibiotic ointment to cover surgical wounds. In patients with numerous staphylococcal skin infections, oral clindamycin 150 mg every day for 3 months safely reduces further episodes. For recurrent cellulitis, oral penicillin or erythromycin 250 mg twice daily or monthly intramuscular benzathine penicillin decreases subsequent attacks. In patients with frequent episodes of genital or labial herpes simplex an antiviral agent such as valacyclovir 500 mg to 1 g every day is effective as a suppressant.

Pustular tinea pedis.

Pustules are uncommon in tinea pedis and may suggest a bacterial infection. We describe a patient with large pustules on his feet that contained hyphae on Gram's stain of the pus and on a potassium hydroxide preparation of the pustule roof. Cultures were negative for bacteria, but grew Trichophyton rubrum.