Cryptococcus Infection in an Immunocompetent Patient.

Cryptococcal meningitis is a fungal infection of the CNS, generally thought of as an opportunistic infection in those with T-cell immunodeficiencies including AIDS (usually with a CD4 count of less than 100), chronic steroid use, hematological malignancies, and transplant recipients. It can have irreversible CNS morbidity, including vision loss, intracranial hypertension, and cognitive decline. Diagnosis depends on cerebrospinal fluid (CSF) analysis, in which cultures and cryptococcal antigen are most sensitive. CSF PCR can also be done. Most patients have disseminated disease, and blood cultures are also positive. Outcomes remain guarded, with a poor prognosis (morbidity and high mortality) among survivors. This article presents a case of cryptococcal meningitis in an immunocompetent individual, where absolutely no identifiable risk factor was present.

A Rare Case of Pyriform Sinus Fistula in an Adult.

The pyriform sinus fistula is very rare in adults, and it can present as recurrent deep neck space infection and abscess formation. The fistula results due to failure of obliteration of the third and fourth pharyngeal pouches. The diagnosis is often challenging, even with standard imaging techniques. We present a case of a patient who developed recurrent neck space infection and abscess formation. She was found to have a pyriform sinus fistula with fluoroscopy esophagram, although it was not seen with a standard contrast-enhanced computed tomography scan of the neck.

Pleural and Pericardial Infection Due to Cutibacterium acnes in a Splenectomized Patient: A Case Report of an Underreported Systemic Infection.

Infectious pericarditis does not always present with all the classic findings. Some of the traditional signs of fever, pleuritic chest pain, and frictional rub may be missing. This presents a diagnostic challenge, thus clinical suspicion is important. The most common cause of infectious pericarditis is viral. However, bacterial pericarditis may occur with severe complications such as constrictive pericarditis, pericardial effusion, cardiac tamponade, left ventricular pseudoaneurysm, and aortic mycotic aneurysm. The purpose of this presentation is to increase awareness of Cutibacterium acnes (C. acnes) as a cause of bacterial pericarditis. This case report highlights C. acnes as a prevalent cause of both pleural and pericardial infections. The diagnosis can be challenging, considering that this bacterium is difficult to isolate, slow growing, and causes indolent illness. Prolonged incubation time may be required. In addition to the more traditional causes of bacterial pericarditis, namely Staphylococcus and Streptococcus species, C acnes appears to play an important role. It should not be considered a contaminant as it may require further investigation.

Asthma in the geriatric population.

Asthma is associated with significant morbidity and mortality in the geriatric population. Despite the rising incidence of asthma in people >65 years of age, the diagnosis is frequently missed in this population. Factors that contribute to this include respiratory changes caused by aging, immunosenescence, lack of symptoms, polypharmacy, clinician unawareness, and lack of evidence-based guidelines for diagnosis and management that target this population. This literature review addresses the current state of research in this area. Age-related changes influence the pathophysiology and role of allergy in elderly asthmatic patients. Specific obstacles encountered in caring for these patients are discussed. Asthma in the elderly and younger population are compared. We conclude with a broad set of goals to guide future management driven by a multidiscipline approach.

Alzheimer's disease and immunotherapy.

Alzheimer's disease (AD) is a growing health care epidemic. It is the most common cause of dementia and its incidence is rising. Age, which influences the oxidative and inflammatory states of the brain, is the most important risk factor. Currently there is no disease modifying treatments available for this irreversible, progressive debilitating disease. Immunotherapy represents an emerging, potentially disease modifying strategy aimed at reducing the pathological lesions of AD and facilitating cognitive improvement. Many clinical trials are currently underway. This literature review highlights current knowledge regarding the physiology of aging and how it relates to the pathogenesis of AD. In addition, immunotherapy is discussed in the context of its mechanism, current studies and future goals.

A review on the role of quinones in renal disorders.

Quinones are electron and proton carriers that play a primary role in the aerobic metabolism of virtually every cell in nature. Most physiological quinones are benzoquinones. They undergo highly regulated redox reactions in the mitochondria, Golgi apparatus, plasma membrane and endoplasmic reticulum. Important consequences of these electron transfer reactions are the production of and protection against reactive oxygen species (ROS). Quinones have been extensively studied for both their cytotoxic as well as cellular protective properties and they have been particularly useful in rational drug design. The role of quinones in medicine is explored in this literature review with a particular focus on renal diseases. Due to their high basal metabolism and detoxification role, the kidneys are particularly sensitive to oxidative stress. Regardless of the underlying etiology, ROS plays an important role in both acute kidney injury (AKI) and chronic kidney diseases (CKD). Depending on the oxidative state of the kidney, quinones can be nephrotoxoic or nephro-protective. Many factors play a role in the interaction between quinones and the kidney and the consequences of this are just beginning to be explored.

Bacterial biofilms and chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a highly prevalent disease in the adult and pediatric population. It causes significant burden and the management is considered one of the most costly public health conditions. Comorbidities include asthma, aspirin sensitivity, and nasal polyposis. Staphylococcus aureus biofilms and exotoxins that act as superantigens have been implicated to play an important pathological role in the incidence, maintenance, and ongoing burden of CRS. A better understanding of the interplay between bacterial factors, host factors, and the environment will facilitate better management of this disease. This literature review focuses on these factors and highlights current research in this field.

Tuberculous empyema presenting as a persistent chest wall mass: case report.

Empyema necessitatis is an empyema that spreads outside of the pleural space involving the chest wall. Tuberculosis is the most common cause. It occurs in both immunocompetent and immunocompromised patients. Due to the long latency period and the paucity of symptoms, diagnosis can be challenging. Clinicians must have a high awareness of this disease, especially in patients from endemic regions. The disease is treatable with surgical and medical interventions. Failure to diagnose can lead to grave consequences for both the individual patient and public health. This is particularly true in endemic regions where controlling the spread of TB is challenging. We report a rare presentation of pulmonary tuberculosis in an otherwise healthy 72-year-old USA immigrant from Thailand. He presented with a painless, chronic chest wall swelling with minimal systemic symptoms. Imaging revealed empyema necessitatis. Histopathology could not give a definitive diagnosis because the tissue was too necrotic. Despite negative acid-fast staining, sputum cultures were positive for tuberculosis. The case presentation is followed by a brief review of the current relevant literature. This case highlights the importance of clinical suspicion and increased awareness for this silent but serious infection.

Primary cerebral echinococcosis presenting as long-standing generalized weakness.

Echinococcosis is an infectious disease that can remain dormant for years. The most common sites of infection are liver and lungs. Primary cerebral disease is very rare. Here we report on an unusual case of echinococcosis, where the only identifiable lesion was a slowly growing intracranial hydatid cyst. No lesions on the liver identified. The patient is a United States immigrant from rural South India with a chief complaint of progressive weakness and aphasia. Further analysis revealed an interesting association between the clinical, anatomical and hematological findings over time. We conclude that hydatid cyst disease should be considered in patients from endemic areas with long-standing neurological symptoms.

Permanent pacemaker-associated actinomycetemcomitans endocarditis: A case report.

Aggregatibacter actinomycetemcomitans is a Gram-negative bacillus, member of the HACEK group of bacteria, and it is a very rare cause of endocarditis. It is also an extremely rare cause of device-associated infection of the heart. We describe the case of a 25 year-old man who presented with pacemaker-associated endocarditis due to Aggregatibacter actinomycetemcomitans and also discuss the implications and treatment of this organism.

Slow dissociation of a charged ligand: analysis of the primary quinone Q(A) site of photosynthetic bacterial reaction centers.

Reaction centers (RCs) are integral membrane proteins that undergo a series of electron transfer reactions during the process of photosynthesis. In the Q(A) site of RCs from Rhodobacter sphaeroides, ubiquinone-10 is reduced, by a single electron transfer, to its semiquinone. The neutral quinone and anionic semiquinone have similar affinities, which is required for correct in situ reaction thermodynamics. A previous study showed that despite similar affinities, anionic quinones associate and dissociate from the Q(A) site at rates ≈10(4) times slower than neutral quinones indicating that anionic quinones encounter larger binding barriers (Madeo, J.; Gunner, M. R. Modeling binding kinetics at the Q(A) site in bacterial reaction centers. Biochemistry 2005, 44, 10994-11004). The present study investigates these barriers computationally, using steered molecular dynamics (SMD) to model the unbinding of neutral ground state ubiquinone (UQ) and its reduced anionic semiquinone (SQ(-)) from the Q(A) site. In agreement with experiment, the SMD unbinding barrier for SQ(-) is larger than for UQ. Multi Conformational Continuum Electrostatics (MCCE), used here to calculate the binding energy, shows that SQ(-) and UQ have comparable affinities. In the Q(A) site, there are stronger binding interactions for SQ(-) compared to UQ, especially electrostatic attraction to a bound non-heme Fe(2+). These interactions compensate for the higher SQ(-) desolvation penalty, allowing both redox states to have similar affinities. These additional interactions also increase the dissociation barrier for SQ(-) relative to UQ. Thus, the slower SQ(-) dissociation rate is a direct physical consequence of the additional binding interactions required to achieve a Q(A) site affinity similar to that of UQ. By a similar mechanism, the slower association rate is caused by stronger interactions between SQ(-) and the polar solvent. Thus, stronger interactions for both the unbound and bound states of charged and highly polar ligands can slow their binding kinetics without a conformational gate. Implications of this for other systems are discussed.

Modification of quinone electrochemistry by the proteins in the biological electron transfer chains: examples from photosynthetic reaction centers.

Quinones such as ubiquinone are the lipid soluble electron and proton carriers in the membranes of mitochondria, chloroplasts and oxygenic bacteria. Quinones undergo controlled redox reactions bound to specific sites in integral membrane proteins such as the cytochrome bc(1) oxidoreductase. The quinone reactions in bacterial photosynthesis are amongst the best characterized, presenting a model to understand how proteins modulate cofactor chemistry. The free energy of ubiquinone redox reactions in aqueous solution and in the Q(A) and Q(B) sites of the bacterial photosynthetic reaction centers (RCs) are compared. In the primary Q(A) site ubiquinone is reduced only to the anionic semiquinone (Q(*-)) while in the secondary Q(B) site the product is the doubly reduced, doubly protonated quinol (QH(2)). The ways in which the protein modifies the relative energy of each reduced and protonated intermediate are described. For example, the protein stabilizes Q(*-) while destabilizing Q(=) relative to aqueous solution through electrostatic interactions. In addition, kinetic and thermodynamic mechanisms for stabilizing the intermediate semiquinones are compared. Evidence for the protein sequestering anionic compounds by slowing both on and off rates as well as by binding the anion more tightly is reviewed.

Modeling binding kinetics at the Q(A) site in bacterial reaction centers.

Bacterial reaction centers (RCs) catalyze a series of electron-transfer reactions reducing a neutral quinone to a bound, anionic semiquinone. The dissociation constants and association rates of 13 tailless neutral and anionic benzo- and naphthoquinones for the Q(A) site were measured and compared. The K(d) values for these quinones range from 0.08 to 90 microM. For the eight neutral quinones, including duroquinone (DQ) and 2,3-dimethoxy-5-methyl-1,4-benzoquinone (UQ(0)), the quinone concentration and solvent viscosity dependence of the association rate indicate a second-order rate-determining step. The association rate constants (k(on)) range from 10(5) to 10(7) M(-)(1) s(-)(1). Association and dissociation rate constants were determined at pH values above the hydroxyl pK(a) for five hydroxyl naphthoquinones. These negatively charged compounds are competitive inhibitors for the Q(A) site. While the neutral quinones reach equilibrium in milliseconds, anionic hydroxyl quinones with similar K(d) values take minutes to bind or dissociate. These slow rates are independent of ionic strength, solvent viscosity, and quinone concentration, indicating a first-order rate-limiting step. The anionic semiquinone, formed by forward electron transfer at the Q(A) site, also dissociates slowly. It is not possible to measure the association rate of the unstable semiquinone. However, as the protein creates kinetic barriers for binding and releasing anionic hydroxyl quinones without greatly increasing the affinity relative to neutral quinones, it is suggested that the Q(A) site may do the same for anionic semiquinone. Thus, the slow semiquinone dissociation may not indicate significant thermodynamic stabilization of the reduced species in the Q(A) site.